# Four-electron reduction of CO2: from formaldehyde and acetal synthesis to complex transformations

Sarah Desmons, Julien Bonin, Marc Robert, Sébastien Bontemps

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Sarah Desmons, Julien Bonin, Marc Robert, Sébastien Bontemps. Four-electron reduction of CO2: from formaldehyde and acetal synthesis to complex transformations. Chemical Science, 2024, 15 (37), pp.15023-15086. 10.1039/d4sc02888k. hal-04693877

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Submitted on 11 Sep 2024

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Cite this: DOI: 10.1039/d4sc02888k

# Four-electron reduction of CO₂: from formaldehyde and acetal synthesis to complex transformations

Sarah Desmons,†ª Julien Bonin,ªbc Marc Robert ID *bcd and Sébastien Bontemps ID *a

The expansive and dynamic field of the CO₂ Reduction Reaction (CO₂RR) seeks to harness CO₂ as a sustainable carbon source or energy carrier. While significant progress has been made in two, six, and eight-electron reductions of CO₂, the four-electron reduction remains understudied. This review fills this gap, comprehensively exploring CO₂ reduction into formaldehyde (HCHO) or acetal-type compounds (EOCH₂OE, with E = [Si], [B], [Zr], [U], [Y], [Nb], [Ta] or -R) using various CO₂RR systems. These encompass (photo)electro-, bio-, and thermal reduction processes with diverse reductants. Formaldehyde, a versatile C₁ product, is challenging to synthesize and isolate from the CO₂RR. The review also discusses acetal compounds, emphasizing their significance as pathways to formaldehyde with distinct reactivity. Providing an overview of the state of four-electron CO₂ reduction, this review highlights achievements, challenges, and the potential of the produced compounds – formaldehyde and acetals – as sustainable sources for valuable product synthesis, including chiral compounds.

Received 30th April 2024
Accepted 2nd August 2024

DOI: 10.1039/d4sc02888k

rsc.li/chemical-science

## 1. Introduction

Research in CO₂ transformations conducted by the Carbon Capture and Utilization (CCU) community is driven by both fundamental and applicative motivations. On the fundamental side, the goal is to find the keys to transform this thermodynamically and kinetically stable molecule. On the practical side, there is a desire to emulate nature by using CO₂ either as a synthetic building block or as an energy carrier. These objectives gain urgency due to the increasing concentration of atmospheric CO₂ and the inevitable depletion of fossil

<figure><img src="image_3.png" /><figcaption>Sarah Desmons</figcaption></figure>

Sarah Desmons is currently a postdoctoral researcher in the Laboratory of Inorganic Synthesis and Catalysis (LSCI) at École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland. She obtained her PhD in Chemistry and Biochemistry for the chemo-enzymatic conversion of CO₂ into carbohydrates from the Laboratoire de Chimie de Coordination (LCC) and the Toulouse Biotechnology Institute (TBI) in Toulouse, France.

Her current research focuses on the enantioselective production of chiral amines via tailored bio-catalyzed hydroamination reactions.

<figure><img src="image_4.png" /><figcaption>Julien Bonin</figcaption></figure>

chemistry, redox catalysis and CO₂ reduction.

Julien Bonin received his PhD in molecular physical chemistry from the Université Paris-Sud 11 in 2005. He then joined the Radiation Laboratory at the University of Notre Dame as a Postdoctoral Research Associate for one year. From 2006 to 2024, he has been an Associate, then a Full Professor of Chemistry at the Université Paris Cité, and he has now joined Sorbonne Université. His current research interests are related to photo-

<figure><img src="image_5.png" /></figure>

<footnote>ªLCC-CNRS, Université de Toulouse, CNRS, 205 route de Narbonne, 31077 Toulouse Cedex 04, France. E-mail: sebastien.bontemps@lcc-tenhouse.fr</footnote>

<footnote>ᵇLaboratoire d'Electrochimie Moléculaire, Université Paris Cité, CNRS, F-75013, Paris, France. E-mail: julien.bonin@sorbonne-universite.fr; marc.robert@sorbonne-universite.fr</footnote>

<footnote>ᶜInstitut Parisien de Chimie Moléculaire, Sorbonne Université, CNRS, F-75005, Paris, France</footnote>

<footnote n="4">⁴Institut Universitaire de France (IUF), F-75005, Paris, France</footnote>

<footnote>† Present address: Laboratory of Inorganic Synthesis and Catalysis, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), EPFL-ISIC-LSCI, BCH 3305, Lausanne, CH 1015 Switzerland.</footnote>
<figure><img src="image_6.png" /></figure>

resources. Given its significance and broad scope, the field of CO₂ transformation has been extensively covered in numerous reviews and books. Early reviews¹ and comprehensive perspectives² provide authoritative insights. Other reviews focus specifically on the use of CO₂ as an energy carrier³ or as a synthetic reagent.⁴ From an applied perspective, the importance of Life Cycle Assessment (LCA)⁵ has been considered to evaluate the industrial potential of various processes.⁶ From a thermodynamic standpoint, this expansive field can be categorized into reactions involving a redox event at the carbon atom of CO₂ (CO₂ Reduction Reaction: CO₂RR) or those that do not.⁴ᵃ Motivations for the CO₂RR include using CO₂ as an energy carrier, as energy is formally stored during CO₂ reduction, and as a sustainable source of carbon. In the CO₂RR, comprehensive reviews have focused on the type of reduction used, whether it involves thermal reduction with dihydrogen,⁷ hydroboranes,⁸ or hydrosilanes,⁹ (photo)electro reduction¹⁰ or bio-catalysed reduction.¹¹ Other reviews explore the homogeneous¹² or heterogeneous¹³ nature of the catalytic system.

Within the CO₂RR, the level of reduction of CO₂ is arguably the most important parameter to consider. Since the carbon atom of CO₂ is fully oxidized (+IV), it can be reduced by as much as 8e⁻ giving rise to four possible even reduction states shown (Scheme 1). The +II, 0, -II and -IV carbon atom oxidation states can be reached by electroreduction or hydrogenation of CO₂. The corresponding C₁ reduction products are represented in Scheme 1(a): CO¹⁴ and HCOOH¹⁵ (2e⁻), HCHO and ROCH₂OR (4e⁻), CH₃OH¹⁵ᵃ,¹⁶ (6e⁻) and CH₄ (ref. 17) (8e⁻). As shown in Scheme 1(b), the same oxidation states are reached with hydroelementation (E-H) reactions. Using mostly hydroborane (E = BR₂) and hydrosilane (E = SiR₃), HCOOE (2e⁻), EOCH₂OE and HCHO (4e⁻), CH₃OE (6e⁻) and CH₄ (8e⁻) have indeed been reported. Although it does not correspond to a formal hydroelementation, the catalytic formation of CO (2e⁻) was reported with hydroborane¹⁸ and with diborane.¹⁹ The 4e⁻ reduction products of CO₂ – namely formaldehyde and acetal compounds

– occupy a distinct position compared to other C1 reduction products (Scheme 1c). The reasons for this are explained below.

## 1.1. Why reducing CO₂ by 4e⁻ to formaldehyde?

In the context of an increasing demand for complex transformations of CO₂ beyond the simple C₁ building blocks mentioned earlier²⁰,²¹ and the desire for long-term CO₂ storage, formaldehyde offers unparalleled potential in terms of reactivity and versatility.²² More than 30 million tons of formaldehyde are produced and used annually by the chemical industry. This commodity compound is typically synthesized from the partial oxidation of methanol under energy-demanding conditions, representing over 35% of the total methanol transformation.²²ᵃ,²³ A mild and sustainable synthesis of formaldehyde from CO₂ would thus represent a significant advancement for the chemical industry. Most industrial applications use formaldehyde as a reticulating agent in condensation reactions leading to various C-N, C-O, C-S, and C-C bonds.

Furthermore, formaldehyde serves as a precursor to more complex molecules, including chiral ones,²⁴ being a C₁ and a Cₙ source in aldol²⁵ and formose reactions,²⁶ notably. These transformations are beyond the reach of other CO₂ reduction products.

However, there is still no selective and sustainable synthesis of formaldehyde from CO₂. This can be attributed to two major issues: (i) the 4e⁻ reduction stage requires any catalytic system to overcome the energy barriers for both the 2 and 4e⁻ reduction steps while preventing the 6e⁻ reduction, and (ii) the detection of formaldehyde (HCHO) is challenging due to its intrinsic instability, limiting further development and optimization. Depending on the reaction media (pH, solvent, co-substrates), formaldehyde can polymerize, precipitate, or react with other chemicals present in the mixture, making its characterization difficult. Several detection methods have been used, such as optical methods, chemical derivatization for HPLC and GC analysis, or chemical conversion for colorimetric method analysis (established by Nash in the 1950s).²⁷ Recently,

<figure><img src="image_7.png" /><figcaption>Marc Robert</figcaption></figure>

Long time Professor at Université Paris Cité, Marc Robert is now Professor at Sorbonne Université and a Senior member (Innovation Chair) of the Institut Universitaire de France (IUF). His work is dedicated to electrochemical and photochemical approaches of electron-transfer processes and the catalytic activation of small molecules (CO₂, N₂), in an effort to solve contemporary energy challenges. He is an International

Advisory Board member at Angewandte Chemie International Edition, ChemSusChem (Wiley), Artificial Photosynthesis and ACS Electrochemistry (ACS).

<figure><img src="image_8.png" /><figcaption>Sébastien Bontemps</figcaption></figure>

Sébastien Bontemps has received his PhD in 2006 from the University Paul Sabatier in Toulouse and carried out post-doctoral stays at the University of Chicago and McGill University. Since 2009, he has been a CNRS researcher in LCC-CNRS in Toulouse developing research studies directed at CO₂ transformations, boron and hydride chemistry and at the synthesis of new first row metal complexes.
<figure><img src="image_9.png" /></figure>

<figure><img src="image_10.png" /><figcaption>**Scheme 1** C₁ products generated from CO₂ reduction by (a) hydrogenation or electroreduction or (b) hydroelementation reactions. (c) Formaldehyde and acetal compounds as the products of four-electron reduction of CO₂ covered in the present review.</figcaption></figure>

a new and simple method for trapping and quantifying formaldehyde in aqueous solutions by ¹H NMR was designed, otherwise allowing for isotope labelling experiments and thus unambiguous demonstration that the HCHO production arises from CO₂ reduction.²⁸

## 1.2. Why reducing CO₂ by 4e⁻ to acetal compounds?

The formation of acetal (EOCH₂OE) from hydroelementation of CO₂ is an important process linked to formaldehyde, because

(i) Some of these acetal compounds were shown to quantitatively release formaldehyde, offering an efficient and selective access to it under particularly mild conditions and with isotope labelling proving the origin of formaldehyde. The generated formaldehyde was subsequently used as C₁ and also Cₙ sources,²⁹ and notably in the first enantioselective transformation of CO₂ into a C₄ carbohydrate,³⁰ representing the highest level of complexity obtained from CO₂ at that time.³¹

(ii) Beyond the release of formaldehyde, acetal compounds were also involved in transformations related to but distinct

from formaldehyde, notably when used as a Cₙ source. Interestingly, in one case, boryl moieties remained on the product, demonstrating a difference in reactivity compared to formaldehyde.³² This finding should open opportunities to use the boryl or silyl functional groups as an integral part of new compounds as opposed to a waste moiety.

(iii) Finally, mild conditions and organic solvents used in hydroelementation enable *in situ* NMR monitoring leading to easier proofs of the origin of the acetal or formaldehyde by isotopic labelling experiments.

## 1.3. Objective and organization of the review

We aim at presenting the challenges and mechanistic considerations associated with formaldehyde³³ and acetal synthesis from CO₂ (Scheme 2a), as well as highlighting the reactions in which these reduction products have been involved (Scheme 2b). This review is organized by the type of reduction system: Hydrosilylation (Section 2), Hydroboration (Section 3), Other hydroelementation reactions (Section 4), Hydrogenation

<figure><img src="image_11.png" /><figcaption>**Scheme 2** General scheme presenting the current review: (a) synthesis of formaldehyde or acetal compounds from CO₂RR and (b) utilisation of formaldehyde and acetal as C₁ and Cₙ sources.</figcaption></figure>
(Section 5), Electroreduction (Section 6), Photo(electro)reduction (Section 7), and Bio-catalysed reduction (Section 8). In each section, the reduction and subsequent transformations of the $4e^-$ reduction products are presented, with special attention drawn to the mechanisms involved.

## 2. Hydrosilylation

Hydrosilylation of multiple C=C, C=O and C=N bonds has been intensely investigated, fuelling applications in the silicon industry as well as in synthetic chemistry, in asymmetric reductions in particular.³⁴ Hydrosilylation of CO₂ involves the addition of a Si-H bond to the C=O bond, transferring the hydride to the carbon atom and forming a Si-O bond. This reaction is favoured kinetically and thermodynamically by the polarity of the Si-H bond (electronegativity (E. N.) of H = 2.2, Si = 1.9) and the formation of a strong Si-O bond (>500 kJ mol⁻¹),³⁵ respectively. As a consequence, CO₂ hydrosilylation usually operates under mild conditions of temperature and pressure.

CO₂ hydrosilylation was first reported in 1981 with Ru- and Pd-based catalysts, independently.³⁶ In both cases, the reduction process led to formoxysilane ($2e^-$ reduction product). Hydrosilylation beyond the $2e^-$ reduction stage was hypothesized in these two initial reports based on the observation of bis(silyl) ether ($R_3SiOSiR_3$) and of a small amount of formaldehyde (<4% yield) with the Ru-based catalyst.³⁶b In 1989, an Ir-based catalyst enabled unambiguous observation of the hydrosilylation of CO₂ beyond the $2e^-$ reduction stage. In this pioneering study, it was remarkable that the 2, 4 and $6e^-$ reduction products – formoxysilane, bis(silyl)acetal (BSA) and methoxysilane, respectively – were subsequently observed.³⁷ Finally, the first report of CO₂ hydrosilylation into methane was published in 2006 by Matsuo and Kawaguchi with a $[Zr]/B(C_6F_5)_3$ catalytic system.³⁸

Since these initial reports, the reduction of CO₂ by $4e^-$ with hydrosilane witnessed a growing attention. The present section aims to cover in detail (i) the formation of BSA and formaldehyde in part 2.1, (ii) the mechanisms accounting for their generation in part 2.2, (iii) the proposed origin of the selectivity toward BSA in part 2.3, and (iv) their use as reactive intermediates in reductive functionalization reactions leading to more complex products in part 2.4 (Scheme 3).

### 2.1. Hydrosilylation of CO₂ into bis(silyl)acetals (BSAs) and formaldehyde

2.1.1. Description of BSA 1 to BSA 11. Bis(silyl)acetals (BSAs) are obtained from the double hydrosilylation of one

molecule of CO₂. They feature an acetal core with two stabilizing silyl moieties attached to both oxygen atoms. Reported BSAs are depicted in Scheme 4 and their NMR characterizations are given in Table 1. Currently, eleven BSAs (BSA 1–11) have been reported in the literature. BSA 1–6 have been generated from tertiary silanes $HSiMe_3$, $HSiEt_3$, $HSiPh_3$, $HSiMe_2Et$, $HSiPh_2Me$ and $HSiPhMe_2$, respectively, in excellent NMR yields (79 to 99%) regardless of the nature of silane substituents (trialkyl, triaryl or mixed silanes). Among them, only BSA 2 and 3 were isolated with best yields of 94 and 95% with C4 and C17, respectively. The utilization of secondary and primary silanes led to the formation of BSA 7–10. None of them was isolated. BSA 10a was characterized from a quasi-stoichiometric control experiment between a Co-formate complex and phenylsilane.⁴² The use of only three equivalents of silane enabled the characterization of BSA 10a as the sole (silyl)acetal, in contrast to the observation of several BSA signals under the catalytic conditions. The presence of more than one hydride as reductive entities on the silicon atom with primary or secondary silanes indeed leads to the observation of multiple (silyl)acetal signals. This was clearly exemplified by Eisenberg *et al.* when using the dialkylsilanes, $Me_2SiH_2$ and $Et_2SiH_2$ (BSA 7–8, respectively).³⁷ In both cases, three ¹³C and ¹H NMR signals characteristic of BSA were observed. Despite the ill-defined nature of the acetal mixture, the characteristic NMR chemical shifts and the absence of other signals in this area enable not only the detection but also the quantification of the (silyl)acetal entities. As shown in Table 1, a narrow range of methylene chemical shifts was observed in ¹H NMR (4.96 to 5.80 ppm) and in ¹³C NMR (83 to 85.7 ppm) with $J_{CH}$ coupling constants between 161.5 and 164.4 Hz. In addition, conclusive labelling studies were reported with ¹³CO₂.²⁹Si NMR data are restricted to BSA 2, 4–6, and 11 with chemical shifts of 18.3, 17.7, -2.74, 6.99 and 24.0 ppm, respectively.

Most of the characterized BSA features tertiary silane moieties (BSA 1–6 and BSA 11). Three of them were isolated (BSA 2, 3 and 11) and the latter two were characterized by XRD. The higher stability of (silyl)acetals featuring tertiary silyl moieties is discussed in the mechanism section, Section 2.2. Catalysts were necessary to generate BSA but for BSA 11, which was derived from the hydrosilylation of CO₂ by an aluminum complex featuring two hydrosilane pendent moieties. BSA 11 was generated as a minor product in 24% yield and features an acetal fragment stabilized by the Lewis acidic alane moiety.⁴³

2.1.2. Catalytic systems. Selective (C1–C25) and non-selective (C26–C36) catalytic systems leading to the formation of BSA 1–10 are described separately below. We consider

<figure><img src="image_12.png" /><figcaption>Scheme 3 General scheme of Section 2: CO₂ hydrosilylation.</figcaption></figure>

<figure><img src="image_13.png" /></figure>
<figure><img src="image_14.png" /></figure>

<figure><img src="image_15.png" /><figcaption>Scheme 4 Synthesis of BSA 1–11. The yields indicated are the best reported yields.</figcaption></figure>

<table><caption>Table 1 NMR characterization of BSA 1–11</caption><thead><tr><th rowspan="2">BSA</th><th rowspan="2">Solvent</th><th colspan="4"><sup>13</sup>C(CH<sub>2</sub>)</th><th rowspan="2">Ref.</th></tr><tr><th>δ (ppm)</th><th><sup>1</sup>J<sub>CH</sub> (Hz)</th><th>δ<sub>H</sub>(CH<sub>2</sub>) (ppm)</th><th>δ<sub>Si</sub> (ppm)</th></tr></thead><tbody><tr><td>1</td><td>C<sub>6</sub>D<sub>6</sub></td><td>—</td><td>164</td><td>5.03</td><td>—</td><td>37</td></tr><tr><td>2 <sup>a</sup></td><td>C<sub>6</sub>D<sub>6</sub></td><td>84.6</td><td>—</td><td>5.03</td><td>18.3</td><td>39</td></tr><tr><td rowspan="2">3 <sup>a</sup></td><td>C<sub>4</sub>D<sub>5</sub>Br</td><td>85.5</td><td>—</td><td>5.55</td><td>—</td><td>38</td></tr><tr><td>C<sub>6</sub>D<sub>6</sub></td><td>85.7</td><td>164.4</td><td>5.45</td><td>—</td><td>38</td></tr><tr><td>4</td><td>C<sub>6</sub>D<sub>6</sub></td><td>84.0</td><td>—</td><td>5.02</td><td>17.72</td><td>40</td></tr><tr><td>5</td><td>C<sub>6</sub>D<sub>6</sub></td><td>84.9</td><td>—</td><td>5.21</td><td>-2.74</td><td>40</td></tr><tr><td>6</td><td>C<sub>6</sub>D<sub>6</sub></td><td>84.5</td><td>—</td><td>5.06</td><td>6.99</td><td>40</td></tr><tr><td rowspan="3">7</td><td rowspan="3">C<sub>6</sub>D<sub>6</sub></td><td>85.4</td><td rowspan="3">164</td><td>5.02</td><td rowspan="3">—</td><td rowspan="3">37</td></tr><tr><td>84.5</td><td>5.08</td></tr><tr><td>83.8</td><td>5.12</td></tr><tr><td>8</td><td>—</td><td>—</td><td>—</td><td>—</td><td>—</td><td>37</td></tr><tr><td>9</td><td>CD<sub>3</sub>CN</td><td>83</td><td>—</td><td>5.8</td><td>—</td><td>41</td></tr><tr><td>10</td><td>C<sub>6</sub>D<sub>6</sub></td><td>85.6</td><td>—</td><td>—</td><td>—</td><td>42</td></tr><tr><td>11 <sup>a</sup></td><td>C<sub>6</sub>D<sub>6</sub></td><td>87.6</td><td>—</td><td>5.04</td><td>24.0</td><td>43</td></tr><tr><td></td><td></td><td></td><td></td><td>5.18</td><td></td><td></td></tr></tbody></table>

a system selective when it affords BSA as the major product even if at a low conversion rate of silane. Catalysts C1–C25 are depicted in Fig. 1. The specific mode of action of these catalysts indicated with a colour code in Fig. 1 (bottom right) are discussed in detail in the mechanism section, Section 2.2.

Table 2 gathers the catalytic performances (turnover number – TON, turnover frequency – TOF, yield) of catalysts C1–25. Key features are the mild conditions in terms of temperature (ranging from 25 to 80 °C) and CO₂ pressure (from stoichio-metric quantities to 6 atm). We have selected the conditions affording the best performances in terms of TON, TOF and/or yield for each catalytic system. TOFs are not given at the initial rate because such data were available only for C5 (Table 2). All BSA derivatives were obtained selectively with the exception of BSA 1, 7 and 8. Most of the TON values are in between 10 and 89. The catalysts C1, C8, C11, C12, C17 and C25 afford high TONs of 203, 395, 285, 620, 178 and 670, respectively. Only catalysts C4 and C8 led to exceptionally high TON values of 3400 and 1200, respectively. Moreover, C8 and C25 led to maximum TOFs of 55.8 and 52 h⁻¹, respectively, while all the other catalysts led to TOFs between 0.1 and 10.4 h⁻¹.

In addition to TON and TOF, yields are important to assess the selectivity of a given system. This is particularly important when the synthesized BSA is intended to be used as an intermediate in one-pot transformation (see reductive functionalization, Section 2.4). Most of the catalysts afforded BSA in yields higher than 73%. BSA 2 was notably isolated from C8-catalyzed CO₂ hydrosilylation on the NMR scale, while larger scales of BSA 2 (570 mg, 2.1 mmol) and BSA 3 (2.67 g, 4.7 mmol) were isolated with C4- and C17-catalyzed reactions, in 94 and 95% yield respectively. This preparative scale notably facilitated the utilization of BSA 3 in subsequent transformations (see reductive

<footnote><sup>a</sup> Isolated.</footnote>
<figure><img src="image_16.png" /><figcaption>Fig. 1 Catalysts C1–C25 leading to the selective formation of BSA.</figcaption></figure>

functionalization, Section 2.4). The yields for hydrosilylation of CO₂ are given based on the hydrosilane and not on the CO₂ conversion in the vast majority of the cases. This is due to the

difficulty in controlling the amount and conversion of CO₂ as a gas with ¹³C NMR titration and to the fact that silane is considered to be the most expensive reactant. Yields based on
<table><caption>Table 2 Catalytic performances of the selective catalysts C1–C25 for the synthesis of BSA 2–6, 9 and 10</caption><thead><tr><th>BSA</th><th>Catalyst</th><th>TON<sup>a</sup></th><th>TOF (h<sup>-1</sup>)</th><th>Yield<sup>b</sup> (%)</th><th>P<sub>CO<sub>2</sub></sub><sup>f</sup></th><th>T (°C)</th><th>Time (h)</th><th>[Cat] (%)</th><th>Ref.</th></tr></thead><tbody><tr><td rowspan="10">2</td><td>C1</td><td>203</td><td>1.2</td><td>82</td><td>1</td><td>25</td><td>165</td><td>0.9</td><td>38</td></tr><tr><td>C2</td><td>89</td><td>5.9</td><td>87</td><td>5</td><td>80</td><td>15</td><td>1</td><td>44</td></tr><tr><td>C3</td><td>95</td><td>7.3</td><td>89</td><td>5</td><td>80</td><td>13</td><td>1</td><td></td></tr><tr><td>C4</td><td>1000</td><td>10.4</td><td>94<sup>e</sup></td><td>4</td><td>65</td><td>96</td><td>0.1</td><td>45</td></tr><tr><td></td><td>3400</td><td>n.d</td><td>94<sup>e</sup></td><td>4</td><td>65</td><td>n.d</td><td>0.02</td><td></td></tr><tr><td>C5a</td><td>25</td><td>6.2/11<sup>c</sup></td><td>99</td><td>5</td><td>80</td><td>4</td><td>4</td><td>40</td></tr><tr><td></td><td>49</td><td>1.5/8.6<sup>c</sup></td><td>80</td><td>5</td><td>80</td><td>32</td><td>2</td><td></td></tr><tr><td>C5b</td><td>25</td><td>0.51/&lt;0.01<sup>c</sup></td><td>89</td><td>5</td><td>80</td><td>48</td><td>4</td><td></td></tr><tr><td>C5c</td><td>25</td><td>0.34/0.00<sup>c</sup></td><td>&gt;99</td><td>5</td><td>80</td><td>72</td><td>4</td><td></td></tr><tr><td>C6</td><td>n.d</td><td>n.d</td><td>91</td><td>1</td><td>50</td><td>24</td><td>10</td><td>46</td></tr><tr><td>C7</td><td>n.d</td><td>n.d</td><td>54</td><td>1</td><td>50</td><td>41</td><td>10</td><td></td></tr><tr><td>C8</td><td>1200</td><td>55.8</td><td>60<sup>d</sup></td><td>4</td><td>70</td><td>21.5</td><td>0.05</td><td>39</td></tr><tr><td></td><td>910</td><td>26.8</td><td>91<sup>d</sup></td><td>4</td><td>70</td><td>34</td><td>0.1</td><td></td></tr><tr><td></td><td>C9</td><td>20</td><td>0.8</td><td>82</td><td>3</td><td>60</td><td>24</td><td>5</td><td>47</td></tr><tr><td></td><td>C10</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td>C11</td><td>395</td><td>6.6</td><td>76</td><td>1</td><td>22</td><td>60</td><td>0.24</td><td>48</td></tr><tr><td></td><td>C12</td><td>285</td><td>5.9</td><td>55</td><td>1</td><td>22</td><td>48</td><td>0.24</td><td></td></tr><tr><td></td><td>C13</td><td>9</td><td>0.69</td><td>60</td><td>6</td><td>80</td><td>13</td><td>1.5</td><td>49</td></tr><tr><td></td><td>C22</td><td>57</td><td>57.3</td><td>86</td><td>4</td><td>50</td><td>1</td><td>1.5</td><td>50</td></tr><tr><td></td><td>C24</td><td>17</td><td>0.3</td><td>85</td><td>2</td><td>60</td><td>58</td><td>10</td><td>51</td></tr><tr><td></td><td>C25</td><td>99</td><td>99</td><td>99</td><td>5</td><td>25</td><td>1</td><td>1</td><td>52</td></tr><tr><td rowspan="7">3</td><td>C1</td><td>50</td><td>0.13</td><td>64</td><td>1</td><td>25</td><td>384</td><td>2</td><td>38</td></tr><tr><td>C14</td><td>36</td><td>2</td><td>100</td><td>1</td><td>23</td><td>22.7</td><td>2.5</td><td>53</td></tr><tr><td>C15</td><td>12</td><td>0.1</td><td>n.d</td><td>1</td><td>25</td><td>120</td><td>2:10</td><td>54</td></tr><tr><td>C16</td><td>83</td><td>1.2</td><td>n.d</td><td>1</td><td>25</td><td>69</td><td>0.5:2.5</td><td></td></tr><tr><td>C17</td><td>178</td><td>2.5</td><td>n.d</td><td>1</td><td>25</td><td>72</td><td>0.5:2.5</td><td>29a</td></tr><tr><td></td><td>n.d</td><td>n.d</td><td>95<sup>e</sup></td><td>1</td><td>25</td><td>672</td><td>1</td><td></td></tr><tr><td>C25</td><td>670</td><td>52</td><td>67</td><td>5</td><td>80</td><td>13</td><td>1</td><td>52</td></tr><tr><td rowspan="2">4</td><td>C5a</td><td>31</td><td>0.57/7.8<sup>c</sup></td><td>64</td><td>5</td><td>80</td><td>55</td><td>2</td><td>40</td></tr><tr><td></td><td>25</td><td>2.3/12<sup>c</sup></td><td>90</td><td>5</td><td>80</td><td>11</td><td>4</td><td></td></tr><tr><td rowspan="2">5</td><td>C5a</td><td>17</td><td>0.23/3.9<sup>c</sup></td><td>24</td><td>5</td><td>80</td><td>73</td><td>2</td><td>40</td></tr><tr><td></td><td>25</td><td>0.69/12<sup>c</sup></td><td>79</td><td>5</td><td>80</td><td>36</td><td>4</td><td></td></tr><tr><td rowspan="2">6</td><td>C8</td><td>620</td><td>16.5</td><td>62<sup>d</sup></td><td>4</td><td>70</td><td>37.5</td><td>0.1</td><td>40</td></tr><tr><td></td><td>137</td><td>18.3</td><td>82<sup>d</sup></td><td>4</td><td>70</td><td>7.5</td><td>0.6</td><td></td></tr><tr><td rowspan="3">9<sup>g</sup></td><td>C5a</td><td>32</td><td>0.44/6.2<sup>c</sup></td><td>55</td><td>5</td><td>80</td><td>73</td><td>2</td><td>40</td></tr><tr><td></td><td>24</td><td>0.32/9.5<sup>c</sup></td><td>79</td><td>5</td><td>80</td><td>75</td><td>4</td><td></td></tr><tr><td></td><td>121</td><td>40</td><td>78</td><td>4</td><td>70</td><td>3</td><td>0.6</td><td>39</td></tr><tr><td rowspan="4">10<sup>h</sup></td><td>C8</td><td>3.5</td><td>0.07</td><td>31</td><td>6</td><td>80</td><td>48</td><td>1</td><td>49</td></tr><tr><td>C13</td><td>40<sup>i</sup></td><td>1.7<sup>i</sup></td><td>40<sup>i</sup></td><td>1 mmol</td><td>25</td><td>24</td><td>1</td><td>55</td></tr><tr><td>C19</td><td>5.6</td><td>1.4</td><td>7</td><td>5</td><td>25</td><td>4</td><td>1.25</td><td>56</td></tr><tr><td>C18</td><td>32/126<sup>i</sup></td><td>1.2/4.8<sup>i</sup></td><td>63</td><td>0.4 mmol</td><td>25</td><td>26</td><td>2</td><td>42</td></tr></tbody></table>

CO₂ conversion are nonetheless significant because (i) it allows for more complete description of a given catalytic system by reporting its performances based on both reactants and (ii) silane is not necessarily the most expensive substrate, notably when isotopically labelled CO₂ is used. Performance data based on CO₂ conversion are particularly important when ¹¹CO₂ and ¹⁴CO₂ are used for radiochemistry.⁵⁷

Compounds C26,⁵⁸ C27,³⁷ C28,⁵⁹ C29,⁶⁰ C30,⁶¹ C31,⁴¹ C32,⁶² C33,⁴⁹ C34,⁴⁹ C35,⁶³ and C36,⁶⁴ were shown to catalyse the hydrosilylation of CO₂ affording BSA as a minor product (Fig. 2). Most of these systems were optimized for the generation of methoxysilane and/or methane and not for BSA. The observation of BSA as intermediates in many cases confirms that (silyl)

acetals are very often on the reaction pathway to the 6 and 8e⁻ reduction products in hydrosilylation processes.

**2.1.3. Formaldehyde.** The observation of formaldehyde from CO₂ hydrosilylation was only reported at 100 °C with Ru(Cl)₂(PPh₃)₃ as the catalyst in 1981 (Scheme 5).³⁶b It was however observed in less than 4% yield and detailed experimental data are lacking to know if free formaldehyde was observed by a direct or indirect method after derivatization. Based on current knowledge, one can wonder if the detected formaldehyde may result from BSA evolution, although the authors explicitly indicated that no experimental proofs were found for BSA generation.

More recently, BSA was utilized as an intermediate to selectively access formaldehyde (Scheme 6). The air stable **BSA 3**

<figure><img src="image_17.png" /></figure>

<footnote><sup>a</sup> TON = silane converted/catalyst loading unless otherwise stated. <sup>b</sup> *In situ* yield unless otherwise stated. <sup>c</sup> Initial rate measured after 1 hour. <sup>d</sup> No other product detected. <sup>e</sup> Isolated yield. <sup>f</sup> atm unless otherwise stated. <sup>g</sup> 2 eq. vs. CO₂. <sup>h</sup> 4 eq. vs. CO₂. <sup>i</sup> Based on hydrosilane and on CO₂ conversion.</footnote>

<footnote><sup>j</sup> Based on CO₂ conversion.</footnote>
<figure><img src="image_18.png" /><figcaption>Fig. 2 Unselective catalytic systems C26–C36 and hydrosilane employed.</figcaption></figure>

<figure><img src="image_19.png" /><figcaption>Scheme 5 Early observation of formaldehyde from CO₂ hydrosilylation.</figcaption></figure>

<figure><img src="image_20.png" /><figcaption>Scheme 6 Quantitative generation of formaldehyde from BSA 2 and 3.</figcaption></figure>
featuring triphenylsilyl groups was shown to quantitatively deliver formaldehyde in DMSO/H₂O at 100 °C or in the presence of H₂SO₄ at room temperature.²⁹ᵃ Alternatively, CsF promoted the generation of formaldehyde at room temperature, presumably *via* the breaking of the Si–O bond after fluoride attack on the silicon centre.

In another study, **BSA 2** featuring triethylsilyl moieties was shown to quantitatively release formaldehyde in the form of trioxane within 1 h in the presence of 5 mol% of B(C₆F₅)₃ as the catalyst at room temperature.⁶³ Conversely, **BSA 3** did not release formaldehyde in the presence of 22 mol% of B(C₆F₅)₃ in 10 days at room temperature.²⁹ᵃ These contrasting reactivities between **BSA 2** and **BSA 3** highlight the influence of the silyl fragment on the reactivity of the BSA.

## 2.2. Mechanistic considerations

The 4e⁻ reduction of CO₂ into bis(silyl)acetal (BSA) or formaldehyde by hydrosilane takes place along two steps: (i) the 2e⁻ reduction of CO₂ into either formoxysilane or metal formate (Scheme 7, step (i)), followed by (ii) the hydrosilylation of the intermediate into the corresponding 4e⁻ reduction products (Scheme 7, step (ii)). The elementary reactions accounting for step (i) have been already investigated both experimentally and theoretically in reviews focusing on CO₂ hydrosilylation.⁹ We will focus here on the less investigated second reduction step leading to the 4e⁻ reduction products. A thorough evaluation of

the different mechanisms showed that the role of the catalyst is to activate either the hydrosilane or the formoxysilane, along different activation modes depending on the nature of the catalyst which are described hereafter for the catalysts C1–36. A summary of the different activation modes is given in Section 2.2.7 with a general scheme, Scheme 13.

2.2.1. **Activation of the hydrosilane by a Lewis base.** The N-Heterocyclic Carbene (NHC) C31 has been shown to catalyse the hydrosilylation of CO₂ into methoxysilane with the observation of BSA as an intermediate.⁴¹ DFT investigations have suggested that the NHC activates the hydrosilane to trigger a hydride transfer to the formoxysilane and the generation of the BSA (Scheme 8).⁶⁵ The calculated transition state (TS1) of the rate determining step involves three key components: C31 acting as the LB activator, Ph₂SiH₂ as the reductant and finally the formoxysilane intermediate. A subsequent – almost barrier less – step regenerates the catalyst C31 along with the BSA release. Although not yet proven, the action mode of C20,⁵⁶ C30⁶¹ and C32⁶² may be similar to that of C31 because of their high Lewis basicity. Theoretical investigations on the hydrosilylation of CO₂ catalysed by the perrhenate anion C30 also support such views with a similar activation pathway of the hydrosilane for the first reduction step to formoxysilane.

2.2.2. **Activation of the hydrosilane by a Lewis acid.** Hydrosilanes are typically activated by strong Lewis acids promoting the transfer of a silylium "Si⁺" moiety. The cationic

<figure><img src="image_21.png" /><figcaption>**Scheme 7** Two mechanistic pathways for the 4e⁻ reduction of CO₂ by hydrosilanes.</figcaption></figure>

<figure><img src="image_22.png" /><figcaption>**Scheme 8** Schematic view of the computed transition state (TS1) of the Lewis basic activation of hydrosilane by catalyst C31.</figcaption></figure>

<figure><img src="image_23.png" /></figure>
Ir-based complex C14 and B(C6F5)3 are two prototypical compounds known to catalyse the activation of hydrosilanes in various transformations.⁶⁶ In such Lewis acid-catalysed gener- ation of BSA, combined cationic TM-based complexes and B(C6F5)3 were proposed to catalyse hydrosilylation either of a silylformate or of a metal formate as illustrated in Scheme 9a and b, respectively.

2.2.2.1. *Silyl formate intermediate.* Scheme 9a describes the mechanism associated with a Lewis acidic system promoting the silylium “Si⁺” transfer to *silyl formate* species. Such a reaction occurred in an SN₂-type activation going through the transition state **TS1a**. The resulting intermediate is then involved in a second elementary step through the transition state in which the hydride abstracted by the Lewis acid (H-LA) is transferred to the carbon atom of the carbonyl function to form the corre- sponding BSA derivative while regenerating the Lewis acid. Such a mechanism was computed for C14,⁵³,⁶⁷ C26,⁵⁸,⁶⁸ and C35.⁶³

In the cases of C14 and C26, **TS1a** was found to be higher in energy than **TS2a**, while the reverse was found with C35. The catalysts C1, C11–13, C15–17, C24–25, C28 and C36 are proposed to follow a similar pathway. The catalysts C18, C33 and C34 could also follow a similar pathway but the observed induction period points toward a more complex process.

2.2.2.2. *Metal formate intermediate.* Scheme 9b describes the mechanism associated with the Lewis acidic system promoting the silylium “Si⁺” transfer to metal formate species. In the cases of C2, C3 and C8, the second reduction step indeed occurred at a metal formate intermediate. The mechanism involving C8 has been investigated by DFT (Scheme 9b).⁶⁹ Both **TS1b** and **TS2b** are similar to **TS1a** and **TS2a** respectively (Scheme 9a). The acetal obtained after these two first steps is a metal silyl acetal. After a second activation of the hydrosilane by B(C6F5)3, this metal silyl acetal intermediate is converted into the corre- sponding BSA derivative along with the regeneration of the

<figure><img src="image_24.png" /></figure>

<figure><img src="image_25.png" /><figcaption>**Scheme 9** Calculated Lewis acid activation of (a) silylformate or (b) metal formate intermediates. Only TS are shown for the sake of simplicity, and the movement of the electrons is schematically shown with arrows.</figcaption></figure>
<figure><img src="image_26.png" /></figure>

<figure><img src="image_27.png" /><figcaption>Fig. 3 Complexes resulting from the heterolytic splitting of hydrosilane prior to CO₂ hydrosilylation.</figcaption></figure>

active catalyst. An alternative pathway involving TS2'b was also calculated to be iso-energetic.⁶⁹

### 2.2.3. Heterolytic cleavage of the hydrosilane by bifunctional activation.
While the catalytic systems C4–5 ⁴⁰,⁴⁵ and C9 ⁴⁷ are structurally different systems, the proposed mechanism of activation is similar: heterolytic cleavage of the hydrosilane prior to the reduction of the formoxysilane (Fig. 3, left). To support this assumption, catalysts C4–5 and C9 were shown to heterolytically cleave hydrosilanes to afford the three species **Int-C4**,⁴⁵ **Int-C5** ⁷⁰) and **C10** (Fig. 3).⁴⁷ In addition, **C10** was isolated and used as a catalyst in place of C9, showing similar catalytic activity toward CO₂ hydrosilylation to that of C9. These compounds are proposed to transfer both silylum and hydride moieties to the formoxysilane intermediate to form the corresponding BSA derivative. Based on previous results concerning the hydrosilylation of other substrates, Oestreich *et al.* proposed the initial transfer of the silylum moiety followed by hydride transfer in a two elementary step mechanism with **Int-C5**.⁴⁰ Such a two-step pathway would be very similar to the calculated pathway for the Lewis acid activation of hydrosilane described above.

### 2.2.4. Homolytic cleavage of the hydrosilane by a radical initiator.
Mn(CO)₅Br complex C22 was shown to catalyse the hydrosilylation of CO₂ into **BSA 2** with triethylsilane.⁵⁰ C22 was proposed to generate a radical complex upon loss of a bromine atom which would then activate triethylsilane in a homolytic manner (Scheme 10). Although no mechanism for the second step was proposed, following the logic of the first reduction step suggests that addition of the silyl radical to the silylformate could take place, followed by hydrogen transfer from a Mn hydride species.

### 2.2.5. Activation of the formoxysilane by a metal-hydride moiety.
As shown in Scheme 11, formoxysilane may be activated by metal hydride species by its formal addition into the M–H bond, leading to a metal(silyl)acetal which will then release the corresponding BSA. Catalytic systems C18, C21, C27 and C29 are proposed to follow this pathway. Detailed pathways were calculated with C29 ⁶⁰ and C21.⁷¹ The in-depth theoretical investigation on catalyst C21 points toward the insertion of the formoxysilane into the Co–H bond leading to the formation of a metal silyl acetal intermediate.⁷¹ Following this addition, the metal centre is able to activate the hydrosilane *via* an oxidative addition leading to the transfer of the silyl ligand to produce BSA. Moreover, calculations enabled comparison of the three distinct catalytic cycles leading to the formoxysilane, the BSA and the methoxysilane products. The authors compared the

<figure><img src="image_28.png" /><figcaption>Scheme 11 Computed pathway for the hydrosilylation of formoxysilane to BSA with M–H catalyst C29 and C21.</figcaption></figure>

<figure><img src="image_29.png" /><figcaption>Scheme 10 Proposed mechanism for the radical activation of Et₃SiH by C22 based on experimental results.</figcaption></figure>
<figure><img src="image_30.png" /></figure>

energy gap values δE between the most stable intermediate and the highest transition state for each cycle. The smaller value (24.2 kcal mol⁻¹) found for the formation of the formoxysilane compared to the values for the BSA (28.9 kcal mol⁻¹) and the methoxysilane (29.9 kcal mol⁻¹) explain why formoxysilane could be obtained selectively. The small difference between the δE of BSA vs. δE of methoxysilane explains the difficulty in selectively generating BSA in these systems. These calculations reproduced the experimental selectivity obtained under different reaction conditions of temperature and pressure. We hypothesize that the catalytic system C19 followed this pathway as well, based on the assumption that the combination of the bidentate ligand (i.e., 1,10-phenanthroline) and Zn(OAc)₂ would generate a Zn-H moiety in the presence of a hydrosilane under catalytic conditions.

### 2.2.6. Activation of the formate by a borohydride.
Catalyst systems C6 and C7 are the only borohydride compounds reported so far to catalyse the hydrosilylation of CO₂ into BSA.⁴⁶ No theoretical investigations were conducted. Based on experimental findings, the proposed mechanism involves the insertion of CO₂ into two B-H bonds of borohydride catalyst leading to a dianionic acetal intermediate (Scheme 12). This assumption is based on the observed reactivity of C7 with CO₂ and bromobenzoic acid as the CO₂ surrogate. The reactivity of C7

toward CO₂ was indeed immediate but led to an insoluble material difficult to analyse. However, the reactivity toward bromobenzoic acid led to the reaction of the two borohydride fragments with two equivalents of the carbonyl part. While no further insights were gathered with theoretical investigations for these specific systems, the ability of borohydride to insert CO₂ was observed previously in various studies.⁷² An alternative BR₃/SiR₃ exchange after each borohydride addition may also be at play and would avoid any charge build-up.

### 2.2.7. Summary of the activation modes of hydrosilane or formoxysilane.
Most of the catalytic systems activate the hydrosilane reductant either *via* (i) Lewis base (LB), (ii) Lewis acid (LA), (iii) heterolytic splitting of the Si-H bond in a bifunctional manner or (iv) homolytic cleavage by a radical initiator. The Lewis acid activation is at play in the majority of the examples. In fewer cases, the silyl- or boryl-formate intermediates are activated by (v) a metal or (vi) a borohydride species. The different activation modes are summarized in Scheme 13.

## 2.3. Origin of the selectivity for BSA

The control or simply the understanding of the selectivity for bis(silyl)acetal (BSA) is a challenge. In this section we describe some of the main parameters which have been shown to favour

<figure><img src="image_31.png" /><figcaption>Scheme 12 Proposed mechanism for C6 and C7 catalytic systems based on experimental results.</figcaption></figure>

<figure><img src="image_32.png" /><figcaption>Scheme 13 Activation modes of hydrosilane or formoxysilane leading to (silyl) acetal BSA (LB = Lewis base, LA = Lewis acid).</figcaption></figure>
BSA accumulation either upon thermodynamic stabilization or by disfavouring further reduction to methoxysilane or methane.

**2.3.1. Thermodynamic and kinetic stabilization of BSA by the nature of the silyl groups.** Although no specific study was conducted on the role of the silyl group in the stabilization of BSA, two theoretical investigations provided some reactivity trends. These calculations suggested that BSA evolves to formaldehyde *via* TS1, and the formaldehyde is then further reduced to methoxysilane and/or methane (Scheme 14). This process was calculated in two independent studies with phenylsilyl groups (SiH₂Ph) to be thermodynamically favoured by -9.1 and -5.0 kcal mol⁻¹, with an activation barrier of 25.1 and 26.7 kcal mol⁻¹.⁶⁵,⁷³ When the same transformation was calculated with triethylsilyl (SiEt₃) groups, the reaction was then thermodynamically disfavoured by +1.7 kcal mol⁻¹ with a barrier of 37.6 kcal mol⁻¹.⁶³ It thus appears that SiEt₃ groups bring both kinetic (>10 kcal mol⁻¹) and thermodynamic (about 8 kcal mol⁻¹) stability compared to phenylsilyl moieties. Although care must be taken while comparing different theoretical studies, these investigations point toward a higher stability of a BSA featuring tertiary silyl moieties as compared to BSA featuring primary silyl moieties. This corroborates the predominance of tertiary silanes for the selective generation of **BSA 1–6**, and **11**. Moreover, some catalysts were shown to favour BSA when tertiary silanes were employed, but methoxysilane and methane when secondary and primary silanes were

employed. This is the case for example with C1 and C15–17, while most of the other selective catalysts have not been tested with primary or secondary silanes. Finally, every isolated BSA featured trisubstituted silyl groups (BSA 2, 3 and 11).

**2.3.2. Sequestration of B(C₆F₅)₃.** The origin of selectivity for BSA of the catalytic systems C4 and C8 employing B(C₆F₅)₃ is proposed to be the result of the formation of a Lewis pair between B(C₆F₅)₃ and an oxygen atom present on the complex. This so-called sequestration of B(C₆F₅)₃ during the process is proposed to prevent further reduction.³⁹,⁴⁵,⁶⁹ B(C₆F₅)₃ has indeed been shown to favour further reduction to methoxysilane or methane. Two modes of action were calculated (Scheme 15, paths a and b). In path a, B(C₆F₅)₃ catalyses the transformation of BSA into formaldehyde *via* TS1. This result was obtained within the same study presented just above with **BSA 2** featuring triethylsilyl moieties.⁶³ The B(C₆F₅)₃-catalyzed reaction was calculated to be 10 kcal mol⁻¹ lower in energy compared to the uncatalyzed transformation. Moreover, the reaction was probed experimentally: while **BSA 2** was stable for a day in solution, it was transformed into formaldehyde within 1 h in the presence of 5% of B(C₆F₅)₃. The second mode of activation b occurs *via* an SN₂-type activation of the hydrosilane by the Lewis acid B(C₆F₅)₃ leading to silylum transfer (TS2) and finally hydride (TS3) transfer to form methoxysilane (Scheme 15, path b). These transformations were calculated in the cases of C14 (ref. 67) and C26.⁶⁸ In accordance with this mechanism proposal, various

<figure><img src="image_33.png" /><figcaption>**Scheme 14** Computational findings regarding the capability of BSA to liberate HCHO based on the type of silyl moiety.</figcaption></figure>

<figure><img src="image_34.png" /><figcaption>**Scheme 15** Computed B(C₆F₅)₃-catalyzed conversion of BSA into formaldehyde or methoxysilane.</figcaption></figure>
<figure><img src="image_35.png" /></figure>

<figure><img src="image_36.png" /><figcaption>**Scheme 16** Calculated pathway for the generation of formaldehyde from formoxysilane with the Ir-based catalytic system C14.</figcaption></figure>

selective systems reported further reduction when an additional catalytic amount of B(C₆F₅)₃ was added to the system. This was notably the case for C4, C8 and C15–17.

**2.3.3. Stoichiometry.** In most of the CO₂ hydrosilylation reactions reported, an excess of CO₂ gas was employed. In order to influence the level of reduction of the hydrosilylation reaction, 2 and 4 equivalents of CO₂ vs. silane were used with catalytic systems C18 and C19, respectively. Under such stoichiometric or quasi-stoichiometric conditions, it was possible to observe the formation of BSA in 40 and 63% yields for C18 and C19, respectively. The importance of the stoichiometry conditions was proven for C18 since a larger ratio of CO₂ gave rise to formoxysilane whereas a larger amount of silane led to methoxysilane.

**2.3.4. Hydrosilylation of CO₂ to formaldehyde without the intermediary of BSA.** While formaldehyde was experimentally shown to be obtained from BSA with further insights from calculations, its generation without the intermediary of BSA remains an open question. Besides its experimental observation early on in less than 4%, there is only one theoretical investigation reporting such generation with the Ir-based catalytic system C14.⁶⁷ As depicted in Scheme 16, the cationic [Ir]-hydride complex was calculated to promote silylum transfer to the OSiR₃ moiety of the formoxysilane intermediate in TS1, ultimately leading to formaldehyde via TS2. However, the same calculation showed that the silylum transfer to the oxygen atom of the carbonyl leading to BSA was favoured explaining why formaldehyde was not observed experimentally during the reaction.

## 2.4. Bis(silyl)acetal as an intermediate in reductive functionalization of CO₂

The reductive functionalization of CO₂ refers to the reduction of CO₂ combined with the functionalization of the reduced product with a co-reactant. The term was first employed in the case of the hydrosilylation of CO₂ into formoxysilane, accepted with amines to afford formamide, formamidine or methylamine derivatives.²⁰c,⁷⁴ An early reaction of this type can

be traced back to a report on the preparation of formamide from CO₂ reduction in the presence of amine in 1988.⁷⁵ In this case, the reductant was not hydrosilane but dihydrogen. Although unexpected, the first reductive functionalization of CO₂ via the generation of a bis(silyl)acetal (BSA) intermediate was reported in a study devoted to the use of cationic Al-based species for catalysing the hydrosilylation of CO₂ to methane.⁷⁶ In the course of the reaction, the formation of deuterated diphenylmethane 1 featuring a bridged-methylene moiety was observed (Scheme 17). Experimental proofs showed that transiently generated BSA reacted with the deuterated solvent via electrophilic catalysis by the cationic Al-based compound to afford compound 1 via compound 2.

Following this preliminary report, subsequent studies reported the use of BSA as a key intermediate for the generation of more complex products in the presence of various co-reactants. Such strategies considerably enlarged the scope of compounds obtained from CO₂ in using BSA as a source of methylene for the formation of C-N, C-C, C-S and C-O bonds.

### 2.4.1. Reductive functionalization of CO₂ via a transient BSA intermediate

**2.4.1.1. TBD/PhSiH₃: a pioneering reduction system in reductive functionalization. Formation of C-N and C-C bonds.** The first system describing a reductive functionalization of CO₂ with

<figure><img src="image_37.png" /><figcaption>**Scheme 17** First example of reductive functionalization of CO₂ into product 1, involving a BSA intermediate and compound 2.</figcaption></figure>
<figure><img src="image_38.png" /></figure>

hydrosilane with the intermediary of BSA was reported in 2015 (Scheme 18).⁷⁷ It included the use of TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene) which catalysed the hydrosilylation of CO₂ with phenylsilane into the corresponding BSA, although it was never directly observed or characterized. Besides TBD, other Lewis basic catalysts including 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), Verkade's base and NHC (IPr and IrBu) were tested to catalyse the reduction step. Slightly lower yields of the final products were obtained. Various co-substrates featuring N-H (Scheme 18a) or C-H functionalities (Scheme 18b) acted as functionalizing agents in intercepting the transiently formed BSA leading to the formation of methylene-bridged “N-CH₂-N” and “C-CH₂-C” moieties. In total, 19 cyclic or acyclic symmetrical aminal products 3 were generated selectively with yields ranging from 14 to 99% (larger than 70% in most cases, Scheme 18a). In addition, 5 dissymmetric aminal products 4 were also generated using two different amines with yields ranging from 62 to 94% (Scheme 18a). For the synthesis of these dissymmetric aminal compounds, a key factor was to employ two amines featuring different nucleophilicities, enabling the most nucleophilic amine to first react with BSA, which affords an intermediate aminosilylacetal. Subsequently, the second (less nucleophilic) amine reacts with the aminosilylacetal intermediate yielding the corresponding aminal compound. Replacing the amine co-reactant with 2 equivalents of the nucleophilic malonate compound led to the unique formation of two C-C bonds in 58% yield (compound 5, Scheme 18b).

2.4.1.2. *Extension of the scope with the TBD/PhSiH₃ reduction system.* The TDB/PhSiH₃ system was proven to be reliable and versatile to insert one or two methylene units in complex structures. To do so, 10–20 mol% of TBD was used at temperatures ranging from 100 to 120 °C and reaction times from 6 to 30 h (Scheme 19). Indolepyrrolidine derivatives were engaged as co-reactants leading to cyclisation reactions with the formation

of C-CH₂ and N-CH₂ bonds. A second enantioselective reduction step of the pyrrolidine ring afforded spiro-indolepyrrolidine products 6 (Scheme 19), and 17 different compounds have been obtained in good to very good yields (55–92%).⁷⁸ Reductive functionalization with amine was then used to incorporate two methylene units from the hydrosilylation of CO₂ (Scheme 19, compounds 7).⁷³ Key features of these transformations include the use of (i) a primary amine leading to the generation of an imine intermediate and (ii) a Lewis acid-catalysed cyclization reaction with various enaminones. The scope of the reaction was evaluated with 32 identified examples of tetrahydropyrimidine compounds with isolated yields (based on the enaminone) ranging from 50 to 99% (in most cases larger than 80%). The mechanism for the formation of compounds 7 was also investigated by DFT (Scheme 20). TBD was calculated to catalyse the hydrosilylation of CO₂ into **BSA 10** followed by the liberation of formaldehyde. The imine is then generated from the condensation of the primary amine with formaldehyde (step i). Controlled experiment proved that a stable imine can be formed when a bulky bis(diisopropyl)aniline is used. The enaminone nucleophilically adds to the intermediate imine *via* a Lewis acid/TBD-catalysed reaction (step ii) leading to an aza-diene compound after phenylamine elimination (step iii). The Diels–alder reaction between the aza-diene intermediate and a second equivalent of *in situ* generated imine finally furnishes the tetrahydropyrimidine 7 (step iv). This elegant strategy employing a primary amine as a first functionalization step transformation was further used to generate enaminones (Scheme 19, compounds 8, 22 examples, 43–94%) and 1,4-dihydropyridines (Scheme 19, compounds 9, 9 examples, 71–95%).⁷⁹

2.4.1.3. *Development of new catalysts.* Besides the utilization of TBD as a catalyst, two other catalytic systems were employed for reductive functionalization with hydrosilanes. The

<figure><img src="image_39.png" /><figcaption>**Scheme 18** First selective reductive functionalization of CO₂ *via* the generation of a BSA intermediate leading to the formation of (a) C-N and (b) C-C bonds.</figcaption></figure>
<figure><img src="image_40.png" /><figcaption>Scheme 19 Extension of the product scope upon reductive functionalization of CO₂ with hydrosilanes.</figcaption></figure>

combination of [CpFe(CO)₂]₂ and P(nBu)₃ was shown to catalyse the hydrosilylation of CO₂ with phenylsilane in the presence of tryptamine derivatives to afford a variety of tetrahydro-β-carbolines and other nitrogen-containing heterocycles 10 after 36 h at 60 °C (Scheme 21).⁸⁰ In total, 19 heterocycles were obtained in yields ranging from 50 to 94%. The [CpFe(CO)₂]₂/P(nBu)₃ system is proposed to catalyse the hydrosilylation of CO₂ into BSA which is then involved in a Pictet–Spengler-type cyclization. Other Fe-based precursors did not afford any conversion, while diphenylsilane or other tertiary phosphine afforded the expected compounds although in lower yields. Another report described the use of a phosphorus ylide to intercept the

reduction intermediate *via* a Wittig reaction (Scheme 21, compounds 11).⁸¹

If the first tests were conducted with the TBD/PhSiH₃ system in acetonitrile, optimization conditions revealed the beneficial role of an inorganic base and notably of sodium *tert*-butoxide (NaOtBu) in DMF in catalysing the hydrosilylation of CO₂ with PMHS (polymethylhydrosiloxane) – a waste of the silicone industry. This process led to the synthesis of 20 olefins in yields ranging from 30 to 85%. Ionic liquids²²⁴ and covalent organic frameworks⁸³ were also employed as catalysts in a similar synthesis of aminal by CO₂ reductive functionalization.
<figure><img src="image_41.png" /><figcaption>**Scheme 20** Proposed mechanism for the synthesis of tetrahydropyrimidine 7.</figcaption></figure>

**2.4.2. Reductive functionalization of CO₂ via an isolated BSA intermediate (BSA 3).** In contrast to the previous examples in which BSA was not isolated or observed, **BSA 3** could be isolated before being involved in subsequent transformations.²⁹ª Such a process avoids compatibility issues between the reduction and the functionalization steps since they are performed independently. Using the Mg-based catalytic system **C17**, **BSA 3**, featuring triphenylsilyl groups, was isolated in high yield on a 3 g scale (95% yield, Table 2). As presented in Section 2.1.3, **BSA 3** was found to quantitatively release formaldehyde either in DMSO at 100 °C, in the presence of CsF at room temperature or under acidic conditions (H₂SO₄) at room

temperature (Scheme 6). Under these conditions, **BSA 3** was then engaged in further transformations (Scheme 22).

In the presence of diol or di-thiol substrates under acidic conditions, the cyclic compounds **12** were generated in good yields forming CH₂-O (69% yield) and CH₂-S bonds (51% yield), respectively. The reaction with hydrazine proved to be efficient to generate a CH₂=N bond (compound **13**, 62% yield), while reactions with molecules comprising primary amine and thiol or secondary amine function led to benzimidazole and benzothiazole compounds **14** (95 and 57% yields), respectively. Finally, the reaction with ammonia afforded hexamethylene tetra-amine **15** in 77% yield. In addition, C–C bonds were also generated (i) with malonate leading to 5,5-dimethylcyclohexane-1,3-dione compound **16** (89% yield), (ii) through a Wittig reaction leading to the acrylate compounds **17** (80 and 87% yields) and finally (iii) through a Pictet–Spengler-type cyclization reaction leading to compound **18** (82% yield). It must be noted that ¹³C-labelled **BSA 3** could also be efficiently generated and isolated from the catalytic hydrosilylation of ¹³CO₂ and was used as a dry source of ¹³C-labeled HCHO.

**2.4.3. Conclusion on the reductive functionalization of CO₂.** Reductive functionalization of CO₂ with hydrosilanes led to the synthesis of a very broad range of various products in which the intermediate BSA was used as a methylene source to form C–N, C–O, C–S and even C–C bonds. In these reactions, BSA is generated either transiently when PhSiH₃ is the reductant – although not observed – or isolated when Ph₃SiH is the reductant.

**2.5. Conclusion and perspectives**

In conclusion, the four-electron reduction of CO₂ with hydrosilane is noteworthy for several reasons. Firstly, it distinguishes itself with a considerable number and variety of selective

<figure><img src="image_42.png" /><figcaption>**Scheme 21** New catalysts for reductive functionalization with hydrosilanes.</figcaption></figure>
<figure><img src="image_43.png" /></figure>

catalytic systems (C1-24), primarily based on the combination of transition metal-based complexes and B(C₆F₅)₃. Comprehensive experimental and theoretical studies have revealed five distinct activation modes, elucidating the 2 to 4 electron reduction stage. Despite the highest reported TON of 3400 and TOF of 10.4 h⁻¹, there is room for further enhancements. Secondly, it stands out due to the diverse array of characterized and isolated bis(silyl)acetal (BSA) compounds, with a current total of 11 reported. These isolated BSAs were predominantly obtained from tertiary silanes, demonstrating high selectivity (79 to 99% yields) under mild conditions. Finally, the process is notable for numerous transformations involving BSA in reducing functionalization, ranging from simple condensation to multi-step reactions with co-reactants. Interestingly, when primary silanes were employed, BSA formation was never observed, likely due to its high reactivity. In contrast, tertiary silanes led to the isolation of BSA before engaging in subsequent functionalization through formaldehyde release.

Perspectives in the field of 4e⁻ CO₂ hydrosilylation could involve rationalizing the stability of the generated bis(silyl) acetal (BSA) based on the choice of hydrosilane. Generating BSAs with intermediate stability holds particular interest, offering potential for expanding the reactivity scope of BSA compounds. A significant breakthrough would be utilizing BSAs as a Cₙ source for producing high-value added products, an area yet to be explored compared to their borylated counterparts discussed in the next section. However, the primary challenge remains the treatment of the siloxane by-product produced during CO₂ hydrosilylation, currently considered as waste. Exploring potential uses for these siloxane moieties or designing a regeneration system for the sustainable recycling of hydrosilane presents a promising avenue for further research.

### 3. Hydroboration

In the realm of hydroelementation reactions, hydroboration holds an important and specific place. Since the discovery of hydroboration of olefins,⁸⁴ this reaction has been largely developed for the reduction of unsaturated bonds.⁸⁵,⁸⁶ Beyond reduction, the formal addition of B-H bonds is used as a privileged access to organoboron compounds which are then used as reagents in coupling reactions.⁸⁶ Hydroboration of CO₂ involves the addition of a B-H bond to the C=O bond, transferring the hydride to the carbon atom and forming a B-O bond. It is favoured both kinetically and thermodynamically by the polarity of the B-H bond (E. N. of H = 2.2, B = 2.0) and the strength of the formed B-O bond (BDE(B-O) >500 kJ mol⁻¹),⁸⁷ respectively. As a consequence, CO₂ hydroboration reactions, like CO₂ hydro-silylation ones, operate under much milder conditions – usually room temperature and 1 atm of CO₂ – than CO₂ hydrogenation.⁸⁸ However, it is noticeable that the catalytic systems used for the hydroboration or the hydrosilylation of CO₂ are different in most cases.

The first catalytic hydroboration of CO₂ was reported in 2010 with a Ni-based catalytic system and was shown to afford the 6e⁻ reduction product, methoxyborane, readily hydrolysed to methanol.⁸⁸ While the 2e⁻ reduction product – formoxyborane – was observed, no 4e⁻ reduction product was detected, although formaldehyde was proposed as an elusive intermediate.⁸⁸,⁸⁹ The Ni-based pincer system used as the catalyst remains one of the most efficient catalyst of CO₂ hydroboration into methoxyborane with TOF and TON of 495 and 495 h⁻¹, respectively. It is worth noticing that an earlier report described the use of borane in the reduction of CO₂. However, it was not a hydroboration reaction, but the reduction of CO₂ into CO by B₂pin₂ and a (NHC)Cu-based catalyst.¹⁹b It was only in 2012 and 2014 that

<figure><img src="image_44.png" /><figcaption>Scheme 22 Products obtained from the functionalization of HCHO released from BSA 3.</figcaption></figure>
<figure><img src="image_45.png" /></figure>

<figure><img src="image_46.png" /><figcaption>Scheme 23 General scheme for Section 3: CO₂ hydroboration.</figcaption></figure>

bis(boryl)acetal (BBA)⁹⁰ and formaldehyde⁹¹ were respectively characterized from the hydroboration of CO₂, although not in a selective manner. Later on, the efficient and selective generation of BBA derivatives was reported using different hydroboranes as reductants. These transformations (Scheme 23, step a) will be presented in the first part 3.1 and the mechanism will be discussed in part 3.2. Finally, the use of these 4e⁻ reduced products as reactants in further transformations (Scheme 23, step b) will be described in part 3.3 and a general conclusion will be drawn in part 3.4.

### 3.1. Hydroboration of CO₂ into bis(boryl)acetals (BBAs) and formaldehyde

In total, 7 BBA derivatives have been synthesized by the hydroboration of CO₂.⁹² BBA 1–4 were obtained from the hydroboration of CO₂ (Scheme 24) catalysed by compounds C36–C45 (selective catalysts, Fig. 4) and C46–C63 (unselective catalysts, Fig. 4). BBA 5–7 were obtained in the absence of a catalytic system (Scheme 25). BBA 2 and 4 were shown to be key intermediates leading to formaldehyde in high yields. These transformations are described hereafter.

#### 3.1.1. Catalytic hydroboration of CO₂ into BBA 1–4 catalysed by C36–C63.
BBA 1, featuring pinacolboryl moieties (Scheme 24), was the first BBA reported in the literature in 2012. It was characterized *in situ* as a minor product with Ru-based catalysts C46–C47 bearing a tricyclohexylphosphine (PCy₃) ligand.⁹⁰ Its selective generation was reported with C38 albeit with a low yield of 30%.⁹³ It was only in 2017 that the use of 0.2% of the Ni hydride catalyst C36 led to its selective generation at room temperature, with high *in situ* yields of 84% and 97% after reaction times of 1 h and 4 h, respectively.⁹⁴ Such high selectivity enabled the isolation of BBA 1 by precipitation in 71% yield. This currently remains the only example in which BBA 1 was isolated. Under optimized reaction conditions, benzene was the solvent of choice. While cyclohexane gave a similar result, the use of THF induced a net decrease (30% yield). C43⁹⁵ (15 min at room temperature with 2% of the Ni-based precatalyst) and C44⁹⁶ (2 h at 90 °C with 1% of the Mo-based catalyst) were shown to afford BBA 1 as the major product. It must be noted that BBA 1 was observed as a minor product in hydroboration reactions catalysed by compounds C46–C47,⁹⁰ C48–C50,⁹⁴,⁹⁷ C51,⁹⁸ and C54–C61.⁹⁹,¹⁰⁰

<figure><img src="image_47.png" /><figcaption>Scheme 24 Catalytic generation of BBA 1–4 with C36–C63 catalysts.</figcaption></figure>
<figure><img src="image_48.png" /></figure>

<figure><img src="image_49.png" /><figcaption>b) Other catalysts (BBA as minor product)</figcaption></figure>

<figure><img src="image_50.png" /><figcaption>Fig. 4 Catalysts C36–C63 for the generation of BBA 1–7 and formaldehyde: (a) selective catalysts C36–C45 and (b) unselective catalysts C46–C63.</figcaption></figure>

BBA 2 was reported for the first time in 2014 in CO₂ hydro-
boration catalysed by the nitrogen-based Lewis base TBD
(C45).¹⁰¹ This study focused on the reduction of CO₂ to the
methoxyborane compound with various metal-free catalysts and
hydroboranes. Using 9-BBN and 2.5 mol% of catalyst C45, BBA 2
was detected as the major intermediate after 1 h (85% ratio)
before decaying, leading to the final methoxyborane compound.
The selective generation of BBA 2 and yield quantification
(instead of ratio) were then described with C37–C39.

In 2015, the well-defined iron dihydride bis-diphosphine
catalyst C38 was used at room temperature and under 1 atm
of CO₂ to afford BBA 2 in 85% yield (TOF = 109 h⁻¹) with
a catalyst loading of 1 mol%.⁹³ The importance of the THF

solvent was identified since such selectivity was not observed
with benzene or toluene. Moreover, a high TOF of 516 h⁻¹ was
measured upon increasing the temperature to 60 °C with the
generation of **BBA 2** in 86% yield in only 10 min. In 2016, the
well-defined [Co]- and [Cu]-precatalysts **C41** and **C42** were
shown to generate **BBA 2** as the major product after 24 h at room
temperature and 60 °C, respectively.¹⁰² Beyond these selective
systems, catalysts **C46–C47**,⁹⁰ **C52–C53**,¹⁰³ **C60–C61**¹⁰⁴ and **C62–
C63**¹⁰⁵ were also reported to catalyze the generation of **BBA 2** as
a minor product under mild conditions. **BBA 3** has only been
partially characterized once as a minor compound, despite
numerous studies using HBCat for CO₂ hydroboration. This is
in marked contrast with the selective generation of **BBA 1** and
<figure><img src="image_51.png" /></figure>

<figure><img src="image_52.png" /><figcaption>Scheme 25 Catalyst free generation of BBA 5–7.</figcaption></figure>

BBA 2, and might be explained by the ability of HBCat to readily reduce CO₂ to the methoxyborane stage (*vide infra* in mechanistic consideration).

In this context, **BBA 3** was characterized *in situ* as a minor intermediate, during methoxyborane preparation with catalyst C37.⁹⁷ Following the reaction, a minor signal was observed by ¹H NMR in the characteristic area of acetals. Its broadness suggested the reversible formation of **BBA 3**. This assumption was confirmed by its sharpening at -35 °C leading to the first characterization of the acetal moiety of **BBA 3**. When ¹³CO₂ was used, this acetal signal appeared as a doublet, which finally disappeared upon further reduction to the methoxyborane product. **BBA 4** was obtained from the CO₂ hydroboration with HBMes₂ catalysed by the iron hydride catalyst C38 with an *in situ* yield of 75%.³⁰ This BBA exhibits higher stability as compared to **BBA 1–3**, as shown by an isolated yield of 69% and its characterization by X-ray diffraction analysis.³⁰ Moreover, **BBA 4** featuring a ¹³C-labelled methylene fragment was also isolated in similar yield from ¹³CO₂ hydroboration. The stability of **BBA 4** was used to perform enzymatic transformations (*vide infra*). It is noteworthy that catalyst C38 is able to catalyse the selective generation of three BBA derivatives, namely, **BBA 1**, **2** and **4**.

The performances of catalysts C36–C42 for the selective generation of **BBA 1–2** and **BBA 4** are reported in Table 3. The performances of catalysts C43–C45 are not indicated because

only the ratio between the detected products were measured and not the quantitative yields. The performances of catalysts C46–C63 are not given since **BBA 1–3** were only observed as minor compounds. Among the seven selective catalytic systems (C36–C42), one can notice that all of them are transition metal (TM)-based catalysts and five based on 3d-TM (C36–C39, C41). The active centre is a metal hydride fragment either present in the initial catalyst or presumably generated *in situ* during the reaction with the hydroborane. The best performances in terms of TON and TOF were obtained with C37 (487 and 122 h⁻¹) and C38 (85, 109 h⁻¹ at room temperature and 86, 516 h⁻¹ at 60 °C) for the generation of **BBA 1** and **BBA 2**, respectively. The best yields were obtained with catalysts C36 (97% yield) and C38 (86% yield) for the generation of **BBA 1** and **2**, respectively. The selectivity is an important factor to be considered when the generated BBA is further engaged in additional reactions (see Section 3.3). If a catalytic system exhibits high TON and TOF but poor selectivity, the presence of other products or of the remaining hydroborane may be detrimental for the subsequent reactions.

3.1.2. **Catalyst-free generation of BBA 5–8.** Currently, three BBA derivatives, **BBA 5–7**, have been obtained without any catalyst (Scheme 25). **BBA 5** features two different aryl substituents on each boryl moiety, 2,4,5-Me₃C₆H₂ and o-NMe₂-C₆H₄ groups (Scheme 25). It resulted from the reaction of the ambiphilic ortho amino-borane compound 19 with H₂ and CO₂ (72 h,
<table><caption>**Table 3** Catalytic performances of the selective formation of BBA 1, 2 and 4 with catalysts C36–C42</caption><thead><tr><th>BBA</th><th>Catalyst</th><th>TON</th><th>TOF (h<sup>-1</sup>)</th><th>Yield<sup>a</sup> (%)</th><th>P<sub>CO<sub>2</sub></sub> (atm)</th><th>T (°C)</th><th>Time<sup>b</sup></th><th>Cat loading (%)</th><th>Ref.</th></tr></thead><tbody><tr><td rowspan="3">1</td><td>C36</td><td>487</td><td>122</td><td>97<br>71<sup>c</sup></td><td>1</td><td>rt</td><td>4</td><td>0.2</td><td>94</td></tr><tr><td>C37</td><td>690</td><td>173</td><td>69</td><td>1</td><td>rt</td><td>4</td><td>0.1</td><td>97</td></tr><tr><td>C38</td><td>6</td><td>1.2</td><td>30</td><td>1</td><td>25</td><td>5</td><td>5</td><td>93</td></tr><tr><td rowspan="7">2</td><td>C38</td><td>85</td><td>109</td><td>85</td><td>1</td><td>rt</td><td>47 min</td><td>1</td><td>93</td></tr><tr><td>C39</td><td>86</td><td>516</td><td>86</td><td>1</td><td>60</td><td>10 min</td><td>1</td><td>97</td></tr><tr><td>C40</td><td>32</td><td>2</td><td>64</td><td>1</td><td>rt</td><td>16</td><td>1</td><td>97</td></tr><tr><td>C41</td><td>15</td><td>3.8</td><td>75</td><td>1</td><td>rt</td><td>4</td><td>5</td><td>106</td></tr><tr><td>C42</td><td>25</td><td>1</td><td>38</td><td>1</td><td>60</td><td>24</td><td>1.5</td><td>102</td></tr><tr><td>C43</td><td>53</td><td>2</td><td>79</td><td>1</td><td>rt</td><td>24</td><td>1.5</td><td>102</td></tr><tr><td>C44</td><td>75</td><td>75</td><td>75<br>69<sup>c</sup></td><td>1</td><td>25</td><td>1</td><td>1</td><td>30</td></tr></tbody></table>

<sup>a</sup> In situ yield unless otherwise stated. <sup>b</sup> Hour unless otherwise stated. <sup>c</sup> Isolated yield.

room temperature). **BBA 5** was isolated in 60% yield as a monocystal suitable for the first X-ray diffraction analysis of a BBA. DFT investigations suggested that $H_2$ led to the protobeborylation of compound **19** giving rise to a monohydroborane compound (not observed) which would formally doubly add to $CO_2$ and generate **BBA 5**. **BBA 6** is a dissymmetric BBA featuring one diboryl and one BBN moieties (Scheme 25).¹⁰⁷ It is the only dissymmetric BBA reported to date and was obtained in two consecutive steps. Compound **20**, so-called diborane (4), was proposed to be nucleophilic enough to readily transfer a hydride to $CO_2$ affording a formoxyborane intermediate, which was characterized in situ in a mixture of compounds in 70% yield. In a second step, 9-BBN reduced the formoxy fragment to afford **BBA 6** within 5 h with an in situ NMR yield of 80% (56% overall yield). **BBA 7** features boryl units bearing two different substituents at the boron atom, a perfluoroaryl group (1,3,5-tris(trifluoromethyl)phenyl) and an alkyl phosphine group (2-dimesitylphosphino-ethyl, Scheme 25).¹⁰⁸ It was readily synthesized in 5 h at 60 °C and isolated in 54% yield from the in situ generated phosphino-hydroborane dimer **21**. **BBA 7** was characterized by XRD analysis.

**3.1.3. Summary of the generation of BBA 1–7.** In total, seven BBA derivatives resulting from $CO_2$ hydroboration have

been characterized so far in the literature since the first report in 2012. **BBA 1–4** were obtained using commercially available pinacolborane (HBPin), 9-borabicyclo[3.3.1]nonane (9-BBN) and catecholborane (HBCat) and the non-commercially available dimesitylborane (HBMe$_2$), respectively (Scheme 24). It is worth mentioning that the commercially available hydroborane $BH_3$ led to the reduction of $CO_2$ to the methoxyborane stage.¹⁰⁴,¹⁰⁹ To our knowledge, detection of a corresponding BBA was never reported. NMR analysis was used as a key tool to characterize these species that are often difficult to isolate. The methylene moiety was indeed easily characterized by ¹H and ¹³C NMR in a narrow range of chemical shifts: 4.90 < δ¹H < 5.72 and 81.9 < δ¹³C < 91.3 (Table 4). Moreover, ¹³C-labelled control experiments with ¹³CO$_2$ allowed confirmation of the origin of the carbon atom in the product. Boron chemical shift is not characteristic of BBA since the boron atom substituents have a strong impact. They also influence the stability of BBA as observed in the case of BSA derivatives. This general feature is illustrated in BBA compounds by (i) the rather ease of generating **BBA 1** and **2** as opposed to **BBA 3**, (ii) the stability of **BBA 4**, 5 and 7 which could be isolated and crystallized while **BBA 2** was never isolated and (iii) the possibility to generate BBA in the absence of a catalyst in the cases of **BBA 5–7**.

<table><caption>**Table 4** Selected NMR chemical shifts for BBA 1–7</caption><thead><tr><th>BBA</th><th>Isolated</th><th>XRD</th><th>Solvent</th><th>δ<sup>13</sup>C(CH<sub>2</sub>)</th><th>δ<sup>1</sup>H(CH<sub>2</sub>)</th><th>δ<sup>11</sup>B</th><th>Ref.</th></tr></thead><tbody><tr><td rowspan="2">1</td><td rowspan="2">Yes</td><td rowspan="2">No</td><td rowspan="2">C<sub>6</sub>D<sub>6</sub></td><td>85.7</td><td>5.51</td><td>22.8</td><td>94</td></tr><tr><td>85.4</td><td>5.49</td><td>—</td><td>90</td></tr><tr><td rowspan="2">2</td><td rowspan="2">No</td><td rowspan="2">No</td><td rowspan="2">THF-d<sub>8</sub></td><td rowspan="2">87.0</td><td><sup>1</sup>J<sub>HC</sub> = 167.2 Hz</td><td rowspan="2">58.6 (ref. 100c)</td><td rowspan="2">93</td></tr><tr><td>5.54</td><td>165.2 Hz</td></tr><tr><td>3</td><td>No</td><td>No</td><td>C<sub>6</sub>D<sub>6</sub></td><td>81.9</td><td>5.27</td><td>n.d</td><td>97</td></tr><tr><td>4</td><td>Yes</td><td>Yes</td><td>THF-d<sub>8</sub></td><td>89.6</td><td>5.49</td><td>48.5</td><td>30</td></tr><tr><td>5</td><td>Yes</td><td>Yes</td><td>C<sub>6</sub>D<sub>6</sub></td><td>90.9</td><td>5.72</td><td>46.1</td><td>110</td></tr><tr><td rowspan="3">6</td><td rowspan="3">No</td><td rowspan="3">No</td><td rowspan="3">CD<sub>2</sub>Cl<sub>2</sub></td><td rowspan="3">91.3</td><td rowspan="3">5.20</td><td>-5.4</td><td>107</td></tr><tr><td>6.8</td><td></td></tr><tr><td>55.5</td><td></td></tr><tr><td>7</td><td>Yes</td><td>Yes</td><td>C<sub>6</sub>D<sub>6</sub></td><td>88.5</td><td>4.90</td><td>51.0</td><td>32</td></tr></tbody></table>
<figure><img src="image_53.png" /><figcaption>Scheme 26 Synthesis of BBA 8 by the phosphoborylation of CO₂.</figcaption></figure>

**3.1.4. Miscellaneous BBA 8.** BBA 8 is an additional bis(boryl)acetal that is not presented with the other BBAs because it does not result from a double hydroboration of CO₂ but rather from formal double phosphoborylation (Scheme 26).¹¹¹ This compound features a central acetal core that is substituted by two diphenylphosphino substituents. The reactivity of a series of phosphinoborane compounds (R₂PBR₂) toward CO₂ led to a single insertion (compound 22) and then ultimately to the formation of diphosphaurea compound 23. BBA 8 was shown experimentally, with support from theoretical calculation, to be an intermediate and was synthesized and crystallized enabling its XRD analysis at low temperature. However, its instability precluded any further characterization in solution.

**3.1.5. Hydroboration of CO₂ into formaldehyde.** The direct observation of free formaldehyde from the hydroboration reaction has been described only once, in 2014, with the ruthenium catalyst C46 featuring two tricyclopentylphosphine (PCyp₃) ligands and HBpin as the reductant (Scheme 27a).⁹¹ Under optimized conditions, HBpin was consumed in 30 min at room temperature with 10 mol% catalyst loading. Formaldehyde was observed as the major reduction product (ratio of 22%) along with other borylated products including BBA 1 and

methoxyborane (CH₃OBPin). Labelling experiments using ¹³CO₂ confirmed the generation of free formaldehyde with its characteristic resonances in ¹H and ¹³C NMR spectra (8.74 and 193.0 ppm, respectively in C₆D₆). In order to drive the selectivity toward formaldehyde, 2,6-bis(diisopropyl)aniline was added in the reaction mixture before CO₂ pressurization. The related imine resulting from the condensation reaction between formaldehyde and the aniline was generated after 1 h at room temperature in 74% and 85% yields based on CO₂ and aniline, respectively (Scheme 27b). Upon hydrolysis of the generated imine, a formalin solution was obtained.

Observation of formaldehyde from CO₂ hydroboration was also mentioned in two other studies.⁹⁵,¹¹² In both cases, it appears to result from the evolution of **BBA 1**. Using the selective formation of BBA as a tool to access formaldehyde was further developed recently. **BBA 2** and **BBA 4** were selectively generated with catalyst C38, and subsequently hydrolysed with 10 equivalents of D₂O. This led to their complete hydrolysis into formaldehyde at room temperature within 30 min and less than 2 h for **BBA 2** and **BBA 4**, respectively (Scheme 28). The generated formaldehyde was then further transformed in organo-²⁹b or enzymatic³⁰-catalyzed reactions (see Section 3.3). It is remarkable that **BBA 2** and **BBA 4** were stable enough to be

<figure><img src="image_54.png" /><figcaption>Scheme 27 Hydroboration of CO₂ into formaldehyde: (a) generation and (b) selective trapping of HCHO.</figcaption></figure>

<figure><img src="image_55.png" /></figure>
<figure><img src="image_56.png" /></figure>

<figure><img src="image_57.png" /><figcaption>Scheme 28 Generation of formaldehyde from BBA 2 and BBA 4 hydrolysis.</figcaption></figure>

generated selectively – and even isolated in the case of **BBA 4** – and yet efficiently released formaldehyde under mild hydrolytic conditions.

## 3.2. Mechanistic considerations

This section is dedicated to mechanistic considerations for the formation of bis(boryl)acetal (BBA) or formaldehyde. It is divided into three parts: (i) metal-hydride catalysis (C36–C44, C46–C51), (ii) organic catalysis (C45, C52–C63) and (iii) uncatalyzed generation of **BBA 5–7**.

### 3.2.1. Metal hydride catalysis.
The catalysts C36–C44 and C46–C51 feature a metal hydride moiety or are believed to generate such a function upon reaction with the hydroborane (C41–C43). This hydride is proposed to be the key species of the catalytic process leading to BBA. As shown in Scheme 29, the elementary steps accounting for the 2e⁻ reduction of CO₂ are the insertion of CO₂ into the M–H bond leading to the formate complex 24, followed by a σ-bond metathesis with the hydroborane leading to formoxyborane 25. We will not describe further this 2e⁻ reduction of CO₂ since it was reviewed elsewhere.⁸ Our discussion will rather concentrate on the ensuing reduction step leading to BBA and formaldehyde. At present, theoretical⁸⁹,¹¹³ and experimental⁹⁰,⁹¹,⁹⁷,¹¹²,¹¹⁴ studies are converging on the central role of metal boryl acetal compound 26, which is proposed to result from the reaction of 25 with M–H (step a, Scheme 29). The corresponding transition state (TSa, Scheme 29) is characterized by a hydride attack on the electrophilic carbon atom of 25, as proposed by several DFT calculations on Ni,⁸⁹,¹¹⁵ Ru,¹¹³ Fe,¹¹³a Os¹¹³a and Mn¹¹⁶ systems. The concomitant M–O interaction is often calculated to occur but does not seem mandatory. The likely involvement of

a formoxyborane species 25 as an intermediate to the 4e⁻ and 6e⁻ stages was experimentally asserted when a formoxyborane featuring a pinacolboryl moiety was shown to give similar rate and product distribution to that in CO₂ hydroboration with catalyst C46.¹¹²

Numerous experimental proofs demonstrated that formate complex 24 obtained from CO₂ insertion into M–H bond could be used in hydroboration reactions.⁸a,⁹⁰,⁹¹ However, although the metal boryl acetal species 26 has been calculated to be central for the 4e⁻ reduction of CO₂, identification and or isolation of these species are still lacking. The aluminum compound 27 is the only metal boryl acetal compound characterized without ambiguity (Scheme 29).¹¹⁴ It was obtained from the subsequent reaction of the corresponding [Al]–H with CO₂ and then with 9-BBN and 27 was fully analysed by NMR and X-ray diffraction (XRD) studies. It is noticeable that only 9-BBN gave access to this metal boryl acetal structure. Analogous structures could indeed neither be observed with HBpin because of the lack of reactivity nor with HBCat or BH₃ because of subsequent reduction processes. It is also important to notice that like boron, aluminium is a group 13 element and that despite mimicking important steps of CO₂ hydroboration, neither the starting Al hydride complex nor complex 27 catalyses the CO₂ hydroboration reaction because the initial Al–H species is not regenerated under the reaction conditions. Step a' (Scheme 29) is an alternative step to generate 26 from the direct hydroboration of the formate complex 24. To the best of our knowledge, it has not been reported in DFT investigations but we believe that it should not be discarded ipso facto. Compound 26 is a key intermediate because it serves as a bifurcation point either toward BBA (Scheme 30, step b) or

<figure><img src="image_58.png" /><figcaption>Scheme 29 Calculated elementary steps (a and a') leading to the generation of the elusive intermediate 26 and structure of the only metal boryl acetal (27) so far characterized.</figcaption></figure>
<figure><img src="image_59.png" /><figcaption>Scheme 30 Calculated elementary steps (b, c, c', d) and transition states (TSb, TSc-1 and TSc-2) from metallic borylacetal.</figcaption></figure>

<figure><img src="image_60.png" /></figure>

formaldehyde (Scheme 30, step c). BBA is formed from the
hydroboration of the metallic acetal intermediate **26**. **TSb**
represents the type of transition state calculated to account for
this step. It formally corresponds to an M–O metathesis. Step c
illustrates the route leading to formaldehyde and the boryl ether
**28** which eventually leads to the 6e⁻ reduction hydroboration
product **29** through step d. This last step was experimentally
identified with the Ru–H complex **C46** that was shown to
catalyse the hydroboration of formaldehyde into methoxybor-
ane with HBpin. The first transition state **TSc-1** does not involve
HBR₂ and is simply a rearrangement of the metal boryl acetal
**26**. The aliphatic chain rearranges to enable the interaction of
the second oxygen atom with the metal centre. This reorgani-
zation weakens the M–O bond of the first oxygen atom and the
O–CH₂ bond of the second oxygen atom. This leads to the
release of formaldehyde and the formation of an M–OBR₂
intermediate which is subsequently hydroborated to regenerate
the metal hydride and affords the ether compound **28** *via* **TSc-2**.

The factors influencing the selectivity have been explored in
a thorough study involving the use of various hydride pincers of
Ni- and Pd-based catalysts and three different hydroboranes,
namely, HBpin, HBCat and 9-BBN.⁹⁷ The origin of the selectivity
between the 2e⁻ and 4e⁻ reduction products was proposed to be
dependent on the relative rate of reaction between the metal
hydride fragment (M–H) and either (i) CO₂ to afford the for-
moxyborane 25 (k₁) or (ii) the formoxyborane intermediate 25 to
afford the metal boryl acetal 26 (k₂) (Scheme 29). It was indeed
shown that a lower pressure of CO₂ led to a higher selectivity
toward the 4e⁻ reduction product presumably by disfavouring
k₁. It was also proposed that k₂ could be favoured by (i)
increasing the concentration of the hydroborane, (ii) decreasing
the steric hindrance of the boryl unit, (iii) increasing its elec-
trophilicity and (iv) using a Lewis acid to co-activate the
formoxyborane.

The origin of the selectivity between the 4e⁻ and the 6e⁻ reduction products appears to be the preference between the formation of BBA and the formation of formaldehyde, since the latter readily leads to further reduction. However, the factors influencing the preference toward BBA or formaldehyde remain to be disclosed. In addition, the formation of BBA was shown to

be reversible which eventually led to the final generation of the
more stable methoxyborane in various systems.⁹⁰,⁹⁷ This feature
explains the key role that the boryl moieties may play in the
kinetic and/or thermodynamic stabilization of the correspond-
ing BBA. Step c' is an alternative path generating formaldehyde
directly from BBA (Scheme 30). Such evolution has not been
proposed as a plausible path for M–H catalysis but for organic
catalysis (*vide infra*).⁹⁶,⁹⁸ The direct generation of a methoxybor-
ane compound 29 from the metal boryl acetal 26 has not been
identified so far.

**3.2.2. Organic catalysis.** As shown in the first section, compounds C45 (TBD) and C52–63 are able to catalyse the hydroboration of CO₂ without any metal centre. The metal ions in compounds C55 and C57 are not believed to be the active catalytic centres. The suggested mechanism with C55 and C57 indeed follows a similar pathway to that with C54 and C56, as it involves the anionic carbon moiety as the active catalytic centre. This was based on the theoretical investigations conducted on the Ru-based system C55 and is depicted in Scheme 31(a).⁸²,¹¹⁷

The carbanion located on the backbone of the ligand of the
complex was found to react both with HBPin and CO₂ to
produce the catalytic species **30**. Compound **30** was proposed to
activate the formoxyborane intermediate **25** and HBPin
concomitantly through **TS1** to afford **BBA 1**. The regenerated
catalyst **30** could then be involved in the transformation of **BBA**
**1** into formaldehyde *via* an 8-membered-ring (**TS2**). In this
reaction, formaldehyde was not experimentally observed but
was proposed to be a transient intermediate *en route* to the
observed methoxyborane structure. The ambiphilic phosphine
borane **31** was shown to catalyse CO₂ hydroboration into
methoxyborane with different hydroboranes (HBCat, HBPin, 9-
BBN and BH₃) (Scheme 31b).¹¹⁸ Although no free formaldehyde
nor BBA was observed, a pathway, similar on various aspects to
the previous one (Scheme 31a), was proposed. Theoretical
investigations notably concluded on the co-activation of HBPin
and formoxyborane (TS, Scheme 31b) to afford **BBA 1**. **BBA 1**
then evolves to formaldehyde which ultimately reacts with
compound **31** to form the formaldehyde adduct **32**. Interest-
ingly, labelling experiments proved that the formaldehyde
moiety of compound **32** was not reduced further to afford the
<figure><img src="image_61.png" /><figcaption>Scheme 31 Calculated elementary steps for the 4e⁻ reduction mechanism of CO₂ with (a) C55 (energies indicated in parenthesis are ΔG values in kcal mol⁻¹) and (b) compound 31.</figcaption></figure>

methoxyborane.¹⁰⁹ª Instead, the adduct **32** acts as a more effective catalyst in the hydroboration of CO₂ into methoxyborane with the various boranes tested. This feature is responsible for an observed induction period, which was also noticed (i) in the CO₂ hydroboration reactions with catalyst C52 leading to the generation of C53,¹⁰³,¹¹⁹ (ii) in the hydroboration of CO₂ with PtBu₃ in which a formaldehyde derived intermediate (compound **36**, Scheme 33) was also observed,¹²⁰ and (iii) when using catalyst C60 leading to C61 which was proven to be a more active catalyst.¹⁰⁴ The similar pathway identified in these two studies implies (i) the reduction of CO₂ into formoxyborane as the 2e⁻ reduction intermediates are observed with metal

hydride catalysts and (ii) the subsequent generation of BBA (Scheme 32, step a) and then formaldehyde (Scheme 32, step b) before further reduction to the 6e⁻ reduction product.¹²¹ This latter feature stands in contrast with the metal hydride systems in which BBA and formaldehyde are not generated along the same pathway (Scheme 30). This common pathway remains to be confirmed by further studies on additional organo-catalysed systems. Generalizing such a mechanism remains highly hypothetical because of (i) the very small number of reported theoretical investigations, (ii) the large variety of organic catalysts C45 and C52–C63 and (iii) the difficulty to study very reactive intermediates experimentally. A general trend is the

<figure><img src="image_62.png" /><figcaption>Scheme 32 Elementary steps a and b for the reduction of formoxyborane **25** to methoxyborane **29** calculated with compound **32**.</figcaption></figure>
ability of these main group organic catalysts to co-activate
several substrates and/or intermediates (CO₂, hydroborane,
formoxyborane). This feature highlights the powerful synergy
observed between moderately reactive centres (moderate Lewis
acid and Lewis base fragments) for the transformation of very
stable molecules such as carbon dioxide.

**3.2.3. Uncatalyzed hydroboration for the generation of BBA**
5-7. No DFT investigations have been performed to rationalize
the catalyst-free generation of **BBA** 5-7. At first glance, the
presence of a pendent N- or P-based Lewis base on the boryl unit
in all three cases is a striking feature. Based on the ability of
main group organic compounds to catalyse CO₂ hydroboration,
one could assume that the pendent Lewis base plays a role
either in the intramolecular B–H activation or in an intermo-
lecular CO₂ anchoring/activation.⁴³ Another role could lie in the
stabilization of the formed BBA, even though no interaction of
the pendant Lewis base was detected in the XRD analyses of **BBA**
4, 5 and 7. Finally, the uncatalyzed addition of the hydroborane
21 to CO₂ affording **BBA** 7 is surprising if one considers the
hydride transfer as being the first elementary step for such
transformation. Indeed, the presence of a perfluoroaryl
substituent on the boron atom certainly decreases the hydricity
of the B–H bond.¹²² With this reactive trend in mind, one would
assume that the B–H bond hydricity in compound 21 is lower
than the one in HBPiN, HBcat and 9-BBN which were proved
unreactive toward CO₂ in the absence of a catalyst. That the
empty p orbital at the boron atom might be at play in the first
elementary step is worth considering at least in the latter case.

**3.3. Use of formaldehyde and bis(boryl)acetal as C<sub>1</sub> and C<sub>n</sub> sources**

The known high reactivity of formaldehyde was first evidenced
in four side reactions involving CO₂ reduction. In these reac-
tions, *in situ* generated formaldehyde reacted with other prod-
ucts or catalysts present in solution (Scheme 33a).

The formation of compounds 32 ¹⁰⁹a,¹¹⁸ and C53 ¹⁰³ was
postulated from calculation to arise from the reaction between
transiently generated formaldehyde and the ambiphilic
compounds 31 and 33, respectively. Compounds 34 ⁹⁰,¹¹²,¹²³ and
35 ⁹¹ were shown experimentally to arise from the reaction of
formaldehyde with 25 and 29, respectively, which was
confirmed by labelling experiments. BBA compounds were also
shown to readily react under mild conditions. We believe that
the characterization of compound 36 was the first observation
of such BBA reactivity (Scheme 33b).¹²⁰ Although the authors did
not elaborate on the mechanism of its formation, we propose
that 36 could be formed from the reaction of **BBA 2** with the
phosphine used as the catalyst, on the basis of a similar reaction
later observed between **BBA 2** and an NHC leading to compound
48 (Scheme 37) analogous to compound **36**. These examples
showed that BBA intermediates or formaldehyde is prone to
react. Such “undesired” yet attractive reactivities may pave the
way to more controlled transformations. Along this idea, we
present hereafter different examples using BBA or formalde-
dehyde in subsequent reactions either (i) as a C₁ source for the
formation of C–O, C–N, C–P and C–C bonds, or (ii) as a Cₙ

<figure><img src="image_63.png" /></figure>

<figure><img src="image_64.png" /><figcaption>Scheme 33 Side reactions obtained with *in situ* generated HCHO (a) and BBA 2 (b).</figcaption></figure>

source in oligomerization reactions leading to the formation of
carbon chains and the synthesis of chiral carbon centres.

**3.3.1. BBA as a C<sub>1</sub> source in the formation of H<sub>2</sub>C–O, H<sub>2</sub>C–N and H<sub>2</sub>C–P bonds.** BBA 2 was the first BBA involved in reductive functionalization.⁹³,¹²⁴ Although BBA 2 has never been isolated so far, its selective and efficient generation in 85% yield after 47 min at room temperature from ¹²CO₂ and ¹³CO₂ hydroboration enabled probing of its reactivity toward various E–H substrates (E = RO or R₂N, Scheme 34).⁹³ Its reaction with methanol and (diisopropyl)aniline led to the characterization of the hemiacetal compound 37 (89% yield, <5 min) and imine 38 (83% yield, 20 min), respectively. These short reaction times and high yields were the first evidence that BBA 2 could indeed be used as a formaldehyde surrogate leading to the transfer of a methylene fragment for the formation of H₂C–O and H₂C=N bonds. The reactivity was further extended to the generation of the hemiaminal 39 (67% yield, 1 h) and both cyclic and acyclic aminal compounds 40 (77% yield, 3 h) and 41 (84% yield, 1 h), respectively. Finally, the reaction with ammonia afforded the cage compound hexamethylenetetramine 15 in 84% yield after 16 h. In the latter example, it is remarkable that the six fully deoxygenated carbon atoms are issued from BBA 2 and thus from CO₂. BBA 1 was also used as a source of methylene in

<figure><img src="image_65.png" /></figure>
<figure><img src="image_66.png" /><figcaption>Scheme 34 Formation of CH₂-N, CH₂=N and CH₂-O bonds from BBA 2: generation of compounds 15, 37–41.</figcaption></figure>

reductive functionalization reactions (Scheme 35).⁹⁴ Being selectively generated (71% isolated yield), its reactivity was explored first with (diisopropyl)aniline giving rise to the corresponding imine 38 (86% yield, 24 h). It is interesting to note that similar yields were obtained starting from both **BBA 1** and **BBA 2** (i.e., 83% and 86% yields, respectively) but with longer reaction time with **BBA 1** (24 h) than with **BBA 2** (20 min). The reaction with phenylmethylamine afforded the aminal 42 (79% yield, 24 h). Finally, the reaction with diphenylphosphine gave rise to a single product assigned to compound 43. Subsequent reaction with phenylamine led to the isolation of compound 44 (78% yield, 48 h) featuring for the first time a C–P bond.

**3.3.2. CO₂ as a C₁ source in the formation of C–C bonds.**
The formation of C–C bonds from CO₂ reduction is of high interest, yet challenging. Such a process was first described with the condensation reaction between **BBA 2** and 2 equivalents of a substituted phenol derivative, leading to the generation of the methylene-bridged compound 45 (46% yield, 36 h, 120 °C, Scheme 36). **BBA 2** was also used in a Wittig reaction, producing styrene 46 (72% yield, 5 h, room temperature). These two examples showed that the formation of C–C and C≡C bonds could be successfully achieved from CO₂.⁹³

**3.3.3. BBA as a Cₙ source: oligomerization of BBA and formaldehyde.** The conversion of CO₂ into Cₙ compounds by the construction of a carbon chain is an appealing process because of the higher complexity and diversity of the Cₙ products as compared to the C₁ products. However, this reaction is highly challenging in terms of conditions, selectivity and scope of products.³b,²¹a–c In particular, no asymmetric carbon atom was generated from CO₂. So far, the 4e⁻ reduction of CO₂ by hydrogenation, hydrosilylation and hydroboration aimed at employing CO₂ exclusively as a C₁ source. While the difficulties encountered in controlling the 4e⁻ reduction processes may have been the main reason for this, the long-known possibilities of oligomerizing formaldehyde – the so-called formose reaction – were strongly calling for using CO₂ 4e⁻ reduction products as a Cₙ source.¹²⁵ This was first accomplished upon reacting **BBA 2**, generated *in situ* from CO₂ hydroboration, with N-heterocyclic carbene (NHC, Scheme 37).³² Ender's NHC carbene 47 is a classical organo-catalyst able to catalyse the formation of C–C bonds of carbonyl compounds and notably the oligomerization of formaldehyde.¹²⁶ Its stoichiometric reactivity with **BBA 2** was first probed, leading to the formation and isolation of compound 48 (40% yield, 3 h, 10 °C) (Scheme 37). This reaction resulted from the formal isomerization of **BBA 2** triggered by the addition of the NHC on the electrophilic methylene moiety of

<figure><img src="image_67.png" /><figcaption>Scheme 35 Generation of CH₂-N and CH₂-P bonds from BBA 1.</figcaption></figure>

<figure><img src="image_68.png" /><figcaption>Scheme 36 Generation of C–C and C≡C bonds from BBA 2.</figcaption></figure>
<figure><img src="image_69.png" /></figure>

<figure><img src="image_70.png" /><figcaption>Scheme 37 Homocoupling of BBA 2 resulting in the formation of compounds 49 and 50.</figcaption></figure>

BBA 2 via an SN₂ type mechanism, as proposed by DFT investigations.³² This reaction illustrated that a Lewis base can promote the migration of an O-BR₂ fragment onto the other Lewis acid moiety of a BBA molecule, which is reminiscent of the generation of compound 36 from the reaction of BBA 2 with tertiary phosphines (Scheme 33b). The intermediate 48 was shown to further react with CO₂ to form compound 49 (50% yield, 1 h, 60 °C), which was notably characterized by X-ray diffraction analysis. This compound was obtained from the loss of a borinic acid moiety (R₂BOH), possibly generating a transient original O-borylated Breslow intermediate which was then able to trap a CO₂ molecule in a bifunctional manner.¹²⁷

Compound 49 features a new C–C bond between two carbon atoms arising from two CO₂ molecules. In this reaction, the new

C–C bond was formed thanks to the nucleophilic character of the carbon atom linked to the NHC. This Umpolung process – classical of organocatalyzed C–C bond formation with such a carbene – was further used to generate compound 50 from the homocoupling of three BBA 2 molecules in the presence of 33 mol% of NHC, generating a chain of three carbon atoms (C¹, C², C³) arising from three CO₂ molecules. It must be pointed out that two of the three carbon atoms (C², C³) of the chain are asymmetric carbons and were generated with a high diastereoecontrol, thanks to the presence of the boryl moiety. DFT investigations were conducted to get insights on the elementary steps accounting for these transformations,³² which stand as the first reported example of the generation of asymmetric carbon centres from CO₂. In the process leading to 50, it should

<figure><img src="image_71.png" /><figcaption>Scheme 38 Chemo- and enzyme-catalysed oligomerization of BBA 2 and 4.</figcaption></figure>
be noticed that formaldehyde is never released from **BBA 2**. The oligomerization reaction involves BBA without the intermediary of formaldehyde, as shown from the presence of boryl moieties in the final product **50**. The possibility that formaldehyde could be released from BBA – in the same vein as what was explored with **BSA 3** – before its engagement in the oligomerization process, was recently explored with **BBA 2** and **BBA 4** (Scheme 38). Despite its powerful nature, the formose reaction remains a challenging reaction due to the difficulty in controlling both the length of the carbon chain and the chirality of the generated carbohydrates.<sup>26,126,128</sup>

As presented earlier, **BBA 2** was shown to quantitatively release formaldehyde after 1 h at room temperature in the presence of 10 equivalents of D<sub>2</sub>O. Optimization of both the hydrolysis and the formose steps led to the synthesis of the C<sub>2</sub> carbohydrate glycolaldehyde 51 in 62% yield after 30 min at 80 °C using 2.5 mol% of NHC 47 as the catalyst (Scheme 37).<sup>29b</sup> Glycolaldehyde was further engaged in one-pot reactions leading to the formation of compound 52 (37% isolated yield) *via* a Petasis–Borono–Mannich reaction or to the formation of the C<sub>4</sub> carbohydrates erythrose (53, 40% yield) and threose (54, 24% yield) generated from Zn(pro)-catalysed dimerization reactions (pro = proline).

In a parallel study, **BBA 4** was identified as a promising candidate to conduct enzymatic transformations.<sup>30</sup> Its isolation, in contrast to **BBA 2**, was seen as an important feature toward this aim. If it was stable enough for isolation, **BBA 4** was nonetheless shown to readily release formaldehyde upon hydrolysis under relatively similar conditions to those with **BBA 2**. Enzymatic transformations were then thought about in order to control the length of the generated carbon chain and the chirality of the product. While formaldehyde is usually responsible for enzyme inhibition and even denaturation,<sup>129</sup> D-fructose-6-phosphate aldolase (FSA) and formolase (FLS) were shown to catalyse aldolization and formose transformations of formaldehyde, respectively.<sup>24,130</sup> These enzymes were thus selected to perform the transformation of formaldehyde released from **BBA 4**. The enzymatic transformations were conducted at 30 °C for 48 h in a triethanolamine (TEA) buffered solution (25 mM, pH 7.0 with 1 mM MgSO<sub>4</sub> and 0.1 mM thiamine pyrophosphate (TPP)) with THF. The presence of 10% THF was found optimal to ensure the solubility of **BBA 4**, while limiting the detrimental effect of this organic solvent on FLS and FSA activities (Scheme 38).<sup>30</sup> Under these conditions, **BBA 4** was oligomerized by FLS into dihydroxyacetone (55) in 86% yield. **BBA 4** was then reacted with commercial dihydroxyacetone in the presence of the mono-mutant FSA A129S<sup>131</sup> to afford the corresponding C<sub>4</sub> carbohydrate, L-erythrulose (56) in 53% yield with a perfect enantiocontrolled aldol reaction. In this case, one carbon atom of the carbon chain arose from **BBA 4**. Following recently reported cascade reactions with formaldehyde,<sup>132</sup> these two enzymes were then combined in a one-pot cascade reaction to achieve the transformation of **BBA 4** into L-erythrulose 57 in 35% yield. All four carbon atoms of the carbohydrate arose from CO<sub>2</sub>, including the chiral one. This reaction corresponds to the first cell-free enantioselective transformation of CO<sub>2</sub>.

### 3.4. Conclusion and perspectives

In conclusion, the 4e<sup>-</sup> hydroboration of CO<sub>2</sub> stands out for several reasons: (i) the uncatalyzed formation of three bis(boryl) acetal (BBA) compounds derived from specific hydroboranes; (ii) the highest reported turnover frequency (TOF) at 516 h<sup>-1</sup> among hydroelementation reactions; (iii) the reactive nature of BBA at room temperature, facilitating condensation reactions or formaldehyde release; (iv) the utilization of BBA as a C<sub>n</sub> source with or without formaldehyde release, wherein the reaction without formaldehyde release results in the formation of an O-borylated C<sub>3</sub> compound; (v) the use of BBA in the pioneering enantioselective generation of a carbon centre from CO<sub>2</sub>.<sup>30-32</sup> This significant breakthrough was achieved through formaldehyde release and subsequent enzymatic cascade reactions.

As perspectives in CO<sub>2</sub> hydroboration, the primary challenge lies in the stoichiometric utilization of hydroborane and thus the stoichiometric amount of borinic acid (R<sub>2</sub>BOH) generated as a co-product following the hydrolysis of BBA compounds. Since there is currently no sustainable process for regenerating hydroborane from this co-product, CO<sub>2</sub> hydroboration is scarcely applicable unless the product synthesized from BBA holds a very high value. For example, carbohydrates, particularly rare and non-natural ones, are of significant interest to the pharmaceutical industry. Their synthesis from CO<sub>2</sub>, especially with isotope labelling, could be an avenue worth exploring for generating chiral complex C<sub>n</sub> products from CO<sub>2</sub>. On the other hand, the prospect of generating O-borylated C<sub>n</sub> products could open new avenues to retain boryl moieties in CO<sub>2</sub> transformation products, instead of treating them as waste after B–O bond hydrolysis. This would allow for further functionalization of the generated compounds. To achieve these objectives, future efforts could focus on exploring a broader variety of hydroboranes with diverse properties. Such a range of hydroboranes could lead to the formation of a diverse array of BBA compounds with varying stability and reactivity, suitable for various applications. Additionally, other CO<sub>2</sub> hydroelementation reactions, beyond hydrosilylation and hydroboration, may provide an even greater variety of acetal compounds with unique properties. Specific CO<sub>2</sub> hydroelementation reactions involving early transition-metal hydride species are discussed in the subsequent section of this review.

## 4. Other hydroelementation reactions

The CO<sub>2</sub> hydroelementation involving metal hydrides and phosphines has seen limited development. We have compiled these results in this concise standalone section, separated from the broader and more extensive sections.

### 4.1. Hydroelementation with actinide, early TM and rare earth metal hydride species to acetal complexes

Hydride complexes of U, Zr, Ta, Nb and Y were shown to react with CO<sub>2</sub> under mild conditions to afford the bi-metallic acetal or methylene diolate complexes shown in Scheme 39. The reaction of the U(iv) hydride complex (Cp')<sub>3</sub>U(H) (Cp' =
<figure><img src="image_72.png" /><figcaption>Scheme 39 Generation of BZrA 1, BTaA 1, BTaA 2 and BNbA 1.</figcaption></figure>

$C_5H_4(SiMe_3)$) with 1 atm $CO_2$ led to the expected formoxy
uranium $(Cp')_3U(OCHO)$. However, when only 0.5 equiv. of $CO_2$
was introduced in an NMR tube, the bis(uranyl)acetal complex
**(BUA)** was generated.¹³¹ This complex was also isolated by
crystallization from the stoichiometric reaction of $(Cp')_3U(OCHO)$
with $(Cp')_3U(H)$ in 75% yield after 4 h at 70 °C. The
methylene fragment was characterized at 73.83 ppm in ¹H NMR

due to the proximity with the paramagnetic uranium centre.
The reaction of the Schwartz's reagent, $Cp_2Zr(H)Cl$, was inves-
tigated with $^{13}CO_2$.¹³⁴ A frozen THF-$d_8$ solution of the Zr
complex was prepared and reaction with $^{13}CO_2$ was investigated
at an early stage. After initiating the reaction by a gentle shaking
of the frozen solution, the acetal **BZrA 1** could be observed by ¹H
NMR analysis for only 10 min. To further characterize the acetal
<figure><img src="image_73.png" /></figure>

<figure><img src="image_74.png" /></figure>

Steps i) + ii): $\Delta G^{\circ} = -19.0$ 42.8

Step ii): $\Delta G^{\ddagger} = 23.6$ 62.7

<caption>Scheme 40 DFT investigations for the formation of metallic acetal upon reaction of [Ni]-H and [Zr]-H hydrides with CO₂ (free enthalpies in kcal mol⁻¹).</caption>

species, ¹H and ¹³C{¹H} NMR analyses were conducted at 235 K.<sup>134b</sup> The methylene signal appeared at $\delta^{1}$H = 5.36 ppm and $\delta^{13}$C = 101.2 ppm. Low temperature diffusion ordered NMR spectroscopy (DOSY) confirmed the dimeric nature of **BZrA 1** in solution.<sup>134a</sup> The reduction of CO₂ was also investigated with Ta-H and Nb-H complexes. The acetal complexes **BTaA 1**, **BTaA 2** and **BNbA 1** were isolated and characterized, notably by XRD in the case of the two former ones (Scheme 39).<sup>135</sup> Two diastereoisomers with diastereotopic methylene protons, the *rac* and *meso* forms, were observed for **BTaA 1** and **BNbA 1**, being the result of a C₂ and C₅ symmetry, respectively. The [Ta]- and [Nb]- based hydride complexes featured a peculiar aziridine-metallacycle which was shown to generate a 5-membered cycle leading to **BTaA 2**. Another Ta acetal complex **BTaA 3** was later reported from the reaction of a dinuclear Ta tetrahydride complex with 0.9 equivalent of CO₂ at low temperature.<sup>134</sup> The methylene signal was characterized in solution at $\delta^{1}$H = 6.11 ppm and $\delta^{13}$C = 110.6 ppm and the complex was structurally characterized by X-ray diffraction analysis. Finally, a tetranuclear yttrium tetrahydride complex was also shown to readily react with 1 atm of CO₂ to afford **BYA** featuring two methenediolate bridge fragments maintaining the tetranuclear

structure. The complex was analysed in the solid state by X-ray diffraction and in solution by NMR (CH₂ fragment: $\delta^{1}$H = 6.27 ppm and $\delta^{13}$C = 94.3 ppm).<sup>137</sup>

The methylene signal of these acetal products appeared at a lower field in ¹H NMR (6.11 ppm < $\delta^{1}$H < 7.33 ppm) as compared to BBA, BSA and **BZrA 1** structures while the ¹³C{¹H} NMR chemical shifts of the early-TM acetals are in a slightly lower field area as compared to the ones obtained from BBA and BSA derivatives (101.2 ppm < $\delta^{13}$C < 103.5 ppm).

DFT investigations<sup>89</sup> were conducted to compare the reactivity of CO₂ toward the Schwartz's reagent [Zr]-H complexes<sup>134</sup> vs. [Ni]-H complexes used as catalysts in CO₂ hydroboration,<sup>88</sup> regarding the formation of the corresponding metallic acetal species (Scheme 40). This study disclosed a rare comparison between the reactivities of early and late TM complexes toward CO₂.<sup>138</sup> The formation of the acetal from two equivalents of [M]-H and CO₂ (steps (i) + (ii), Scheme 36) is exergonic with $\Delta G^{\circ} = -19.0$ kcal mol⁻¹ for the Zr complex, while it is endergonic for the Ni analogue by +42.8 kcal mol⁻¹. Replacing the bulky 'Bu group of the pincer system on Ni led to a more accessible, yet still endergonic reaction by +26.9 kcal mol⁻¹. The thermodynamic barriers ($\Delta G^{\ddagger}$) for step (ii) were calculated to equal 23.6 and 62.7 kcal mol⁻¹ for the Zr-H and Ni-H, respectively. These calculations explained why the bis-nickel acetal was never observed in contrast to the Zr analogue.<sup>89</sup>

## 4.2. Hydroelementation to formaldehyde and reductive functionalization

While the formation of **BZrA 1** is favourable as shown in experiments and upon DFT calculations, it is not stable at room temperature, in contrast to **BTaA 1**, **BTaA 2** and **BNbA 1**. The reaction of group IV elements toward CO₂ has been studied for a long time, with an early report in the 1970s.<sup>139</sup> Using Schwartz's reagent as the reductant, CO₂ was readily reduced to formaldehyde at room temperature (Scheme 41).<sup>139a,b</sup> Besides the formation of a [ZrOZr] complex, the proof for the formation of formaldehyde was obtained by *in situ* condensation with 5,5-

<figure><img src="image_75.png" /><figcaption>Scheme 41 Condensation of a cyclohexanedione with formaldehyde generated from CO₂ hydrozirconation.</figcaption></figure>
<figure><img src="image_76.png" /></figure>

dimethylcyclohexane-1,3-dione to afford the corresponding maledone compound **16** which displays a methylene-bridged structure. This study reported the actual first example of reductive CO₂ functionalization.¹³⁹a,¹⁴⁰

### 4.3. Hydrophosphination

CO₂ hydrophosphination was reported to afford the corresponding formate compound.¹⁴¹ Despite similar electronegativity values for P and H atoms, 1,3,2-diazaphospholene (NHP-H) exhibits zwitterionic properties¹⁴² leading to the 2e⁻ reduction of CO₂ into a phosphorus formate moiety in high yield (93% isolated yield). However, no further reduction to the 4, 6 or 8e⁻ reduction levels was evidenced. One can imagine that further structural modification would be necessary to achieve further reduction.

### 4.4. Conclusion

In conclusion, the 4e⁻ hydroelementation with early TM presented in this section stands out by the fact that (i) only four examples were reported so far; (ii) formaldehyde is spontaneously released at low temperature from BZrA 1; and (iii) the insertion of CO₂ into the early TM hydride bond is uncatalyzed.

As perspectives, hydroelementation of CO₂ to the 4e⁻ reduction level might offer a wide range of reactivity via the modification of the coordination sphere of the metal fragment.

## 5. Hydrogenation

The hydrogenation of CO₂ into HCOOH, HCHO, CH₃OH and CH₄ are reactions of utmost importance in the actual momentum of producing green H₂ from water electrolysis.¹³f,¹⁵a,¹⁶a,¹⁴³ As opposed to hydroelementation, hydrogenation of CO₂ is a 100% atom economical reaction making CO₂ perfectly fitted to store energy and/or to afford key C₁ building blocks for the chemical industry. As a consequence, these transformations have been intensively investigated but for

formaldehyde synthesis. There are indeed currently only five catalytic systems, including heterogeneous and homogeneous processes, which have reported the generation and detection of formaldehyde in CO₂ hydrogenation (Scheme 42a). These systems are presented in Section 5.1. Three of these examples generated formaldehyde as the major product and none disclosed its isolation. Reasons are because of (i) the disfavoured thermodynamic parameters in gas and in liquid phases, (ii) the highly reactive nature of formaldehyde and (iii) its volatility as a gas under atmospheric conditions.

To circumvent such hurdles, the hydrogenation reaction conducted in the presence of alcohol as the solvent and co-reactant led to the stabilization of the 4e⁻ reduction stage in the form of acetals (Scheme 42b) as described in Section 5.2, which is in line with the formation of BSA and BBA presented in the previous sections. The specific roles of H₂ and alcohol are thoroughly explained in the mechanism described in Section 5.2.3.

### 5.1. Hydrogenation of CO₂ into formaldehyde

Catalysts **C64–C68** were reported to generate formaldehyde from CO₂ hydrogenation (Scheme 43). The catalytic conditions and performances are presented in Table 5. It is worth mentioning that the origin of the detected HCHO was not confirmed with ¹³CO₂ labelling experiments in any of these cases.

**C65**,¹⁴⁵ **C67**¹⁴⁷ and **C68**¹⁴⁸ gave rise to the generation of formaldehyde as the major product. **C64**¹⁴⁴ is the only reported molecular homogeneous system and operates in liquid media similarly to **C67** and **C68**, while **C65** and **C66**¹⁴⁶ operate in the gas phase. Reaction temperatures range between 40 and 200 °C, while the total gas pressure (P<sub>CO₂</sub> + P<sub>H₂</sub>) ranges between 4 and 70 atm. The positive impact of a high P<sub>H₂</sub>/P<sub>CO₂</sub> ratio on the selectivity toward HCHO formation is a common feature observed for **C64**, **C65** and **C67**. It can also be noticed that both selective systems, **C65** and **C67**, relied on a Pt-based catalyst system. The small number of catalytic systems and their disparities preclude

<figure><img src="image_77.png" /><figcaption>Scheme 42 CO₂ hydrogenation into 4e⁻ reduction products: (a) formaldehyde (Section 5.1) and (b) acetals (Section 5.2).</figcaption></figure>

<figure><img src="image_78.png" /><figcaption>Scheme 43 CO₂ hydrogenation into formaldehyde catalysed by C64–C68.</figcaption></figure>
<figure><img src="image_79.png" /></figure>

<table><caption>**Table 5** Properties of reported systems for CO₂ hydrogenation into formaldehyde catalysed by C64–C68</caption><thead><tr><th></th><th>K[Ru(EDTA-H)Cl]·H₂O</th><th>Pt-Cu/SiO₂</th><th>Ni-Co NPs</th><th>Pt-Ni and Pt-Cu/Al₂O₃</th><th>Ru/LDH</th></tr></thead><tbody><tr><td>Catalytic systems</td><td>C64<sup>144</sup></td><td>C65<sup>145</sup></td><td>C66<sup>146</sup></td><td>C67<sup>147</sup></td><td>C68<sup>148</sup></td></tr><tr><td>Performances</td><td>Rate = 2.79 × 10<sup>-2</sup> M h<sup>-1</sup></td><td>5.22 × 10<sup>-3</sup> M g<sub>cat</sub><sup>-1</sup> h<sup>-1</sup></td><td>CO₂ conv. = 0.24%<br>HCHO ratio = 30%</td><td>0.41 × 10<sup>-5</sup> M g<sub>cat</sub><sup>-1</sup> h<sup>-1</sup></td><td>0.037 M g<sub>cat</sub><sup>-1</sup> h<sup>-1</sup></td></tr><tr><td>T (°C)</td><td>40</td><td>150</td><td>200</td><td>25</td><td>50</td></tr><tr><td>P<sub>CO₂</sub> (atm)</td><td>17</td><td>0.3</td><td>1</td><td>4</td><td>10</td></tr><tr><td>P<sub>H₂</sub> (atm)</td><td>17</td><td>5.7</td><td>3</td><td>66</td><td>10</td></tr><tr><td>Medium</td><td>H₂O</td><td>CO₂ gas</td><td>CO₂ gas</td><td>CH₃OH</td><td>H₂O</td></tr><tr><td>HCHO as the major product?</td><td>No</td><td>Yes</td><td>No</td><td>Yes</td><td>Yes</td></tr></tbody></table>

further general considerations. C64–C68 systems are described separately hereafter in a chronological order.

The first report of formaldehyde generation dates back to 1989 with the use of the homogeneous Ru-based catalyst C64.¹⁴⁴ The reaction was performed in water at 40 °C with a total gas pressure ($P_{CO₂} + P_{H₂}$) of 34 atm. Under these catalytic conditions, CO₂ hydrogenation led to the generation of HCOOH and HCHO which then decomposed into CO and H₂O. The generation of CO was monitored by GC analysis while formation of HCOOH and HCHO was followed spectrophotometrically upon reaction with Nash's reagent.¹⁴⁹ Kinetic investigation showed that the decrease of $P_{CO₂}$ while keeping $P_{H₂}$ constant led to a rate increase in HCHO formation. The initial rate of formation of formaldehyde was measured at $2.79 × 10^{-2}$ M h⁻¹ using 1 mmol of catalyst loading with an estimated activation energy of 8.3 kcal mol⁻¹. The rate of formation of formaldehyde was found to be lower than its rate of decomposition, explaining the lack of formaldehyde build-up within the system. In addition, the rate of formation of formic acid was always higher than that of formaldehyde explaining the favoured selectivity towards formic acid. In 2001, an impregnated Pt/Cu (ratio = 0.03) on SiO₂ surface (C65) was shown to afford formaldehyde and methanol with a total gas pressure ($P_{CO₂} + P_{H₂}$) of 6 atm in the gas phase.¹⁴⁵ The reaction was monitored by temperature programmed surface reaction spectroscopy indicating an optimum temperature of 150 °C for the formation of formaldehyde. While methanol was favoured at a $P_{H₂}/P_{CO₂}$ ratio of 3, the selectivity was reversed when this ratio was increased to 20. At this ratio, the rate of formation reached $0.12 g_{cat}^{-1}$ h⁻¹ for methanol and $5.22 × 10^{-3} g_{cat}^{-1}$ h⁻¹ for formaldehyde, respectively. In the absence of Pt, the analogous Cu-based catalyst afforded only methanol. The importance of Pt in the formation of formaldehyde was attributed to the known ability of Pt to adsorb H₂. Indeed, the Pt activation of H₂ along with a higher pressure of H₂ was proposed to favour a higher concentration of H₂ in the proximity of the Cu centres, responsible for shifting the product formation from methanol to formaldehyde. These observations suggest that the formation of formaldehyde and methanol follows two distinct competitive pathways and that the accessibility of activated H₂ is part of the rate determining step for formaldehyde but not for methanol. In 2015, bimetallic Ni-Co nanoparticles (NPs) (C66) were produced in a bottom-up approach and their ability to catalyse CO₂ hydrogenation was studied.¹⁴⁴ Their catalytic activity was evaluated after deposition of the Ni-Co NPs on a mesoporous silica support and exposition to a CO₂:H₂:He (6.6:20.7:14.7) gas mixture at a total pressure of 6 atm. At 200 °C, a low conversion of CO₂ (0.24%) was observed by GC analysis with 30% selectivity for formaldehyde and 70% selectivity for CO generated as the major product. Only a trace amount of formaldehyde was detected upon increasing the temperature to 350 °C. Pt-Ni and Pt-Cu (C67) catalysts selectively afforded formaldehyde in methanol medium at 25 °C and a total gas pressure ($P_{CO₂} + P_{H₂}$) of 70 atm.¹⁴⁷ The catalysts were prepared by a wet impregnation method using γ-alumina as the support. The final Pt-Ni and Pt-Cu supported catalysts contained 10 wt% Ni or Cu content and 1 wt% Pt content. Once again, a high $P_{H₂}/P_{CO₂}$ ratio (16) led to the generation of formaldehyde with a molar yield of
0.9 × 10⁻⁴ M gcat⁻¹ in 22 h corresponding to 0.41 × 10⁻⁵ M gcat⁻¹ h⁻¹. This activity is still lower than the one reported with the C65 catalyst (5.22 × 10⁻³ M gcat⁻¹ h⁻¹).

Compound C68 is a heterogeneous catalyst consisting of highly dispersed Ru on layered double hydroxide (LDH). The use of 0.5 wt% Ru was recently shown to catalyse the hydrogenation of CO₂ (P<sub>CO₂</sub> = 10 atm, P<sub>H₂</sub> = 10 atm) into 0.446 M gcat⁻¹ of formaldehyde in water as the solvent in 12 h, corresponding to 0.037 M gcat⁻¹ h⁻¹.<sup>148</sup> The detection and quantification of formaldehyde was performed using the colorimetric method with 3-methyl-2-benzothiazolinone hydrazone (MBTH) and high-performance liquid chromatography (HPLC), respectively. In the same study, dihydrogen was replaced by glycerol as a transfer hydrogenation reagent. In a 0.2 M aqueous glycerol solution, catalytic transfer hydrogenation (CTH) of CO₂ afforded formaldehyde in a slightly better yield at 0.1 and 3 wt% Ru under otherwise the same conditions. It is worth mentioning that in the proposed mechanism, initiation of the reaction *via* the dehydrogenation of glycerol into the C₃ carbohydrate dihydroxyacetone (DHA) or glyceraldehyde is proposed. However, the possibility that glycerol – notably *via* the generation of these carbohydrates – could be a source of formaldehyde prior to the CTH of CO₂ was not investigated.<sup>150</sup>

## 5.2. Hydrogenation of CO₂ into acets

As presented above, the selective 4e⁻ hydrogenation of CO₂ into HCHO is still a widely open challenge. In contrast, the selective 4e⁻ hydrogenation of CO₂ into acetal was pioneered rather recently in 2016 and 2017 with homogeneous Ru- and Co-based catalytic systems.<sup>151</sup> The formation of an acetal from CO₂ hydrogenation consists in the addition of alcohol to stop at the 4e⁻ reduction stage with the formation of acetal species (Scheme 42b). Mechanistic investigations have shown that formaldehyde is never formed during the process which alternates between reduction (hydrogenation) and functionalization (with the alcohol) steps giving rise to the acetal. The interest in the formation of dialkoxymethane derivatives is dual. First, it provides a selective access to formaldehyde since some of them were found to release HCHO in strong acidic media,<sup>153</sup> although to our knowledge, the proof of concept from CO₂ has never been reported. Second, dialkoxymethane derivatives are compounds of interest as fuel additives to lower the formation of soot because of their high oxygen content and the absence of C–C bonds.<sup>151,153</sup> The catalytic performances of the reported systems, the in-depth optimization of the catalytic conditions, the proposed mechanism and the extent of the scope of alcohols employed are presented hereafter.

### 5.2.1. Catalytic systems for CO₂ hydrogenation into dimethoxymethane (DMM)
Currently, 10 catalytic systems (C69–C78) have been reported for the hydrogenation of CO₂ in the presence of methanol as the solvent and co-substrate affording dimethoxymethane (DMM). Their structures are depicted in Fig. 5 and the catalytic conditions and performances are reported in Table 6. It must be noted that in all reported studies, the reactions were monitored by ¹H and ¹³C NMR spectroscopy and the products characterized and quantified *in situ*.

<figure><img src="image_80.png" /><figcaption>Fig. 5 Catalytic systems C69–C78 leading to the hydrogenation of CO₂ into DMM.</figcaption></figure>

The characteristic methylene signal of DMM was observed at 4.39 ppm in the ¹H NMR analysis in CD₃OD. With the Ru-based precatalyst C69 featuring a triphosphine ligand (Scheme 44) and a Lewis acid co-catalyst (Al(OTf)₃), the hydrogenation of CO₂ in methanol was shown to afford the 2e⁻ reduction product methoxyformate (MF) and the 4e⁻ reduction product dimethoxymethane (DMM) (Scheme 5).<sup>151a</sup> Among the different conditions tested (variation of the Ru-based precatalyst, temperature, pressure, nature of the acid and time), the best TON of 214 was found with C69 under the following conditions: P<sub>CO₂</sub> = 20 atm, P<sub>H₂</sub> = 60 atm, 18 h, 80 °C, 2 mL of CH₃OH, 12.5 µmol of Ru-based precatalyst and 25 µmol of Al(OTf)₃ (Table 6, entry 1). The selectivity toward DMM *vs*. MF was 67%. Following this initial report, catalytic systems C70–C78 were investigated in the same reaction (Fig. 5).

Pre-catalysts C70–C72 are Co-based in contrast to all the other catalysts which are Ru-based.<sup>151b</sup> C70–C72 were found to generate DMM with slightly lower TON of 92 to 157 than C69 (Table 6, entries 2–4 *vs*. entry 1, resp.), with an interesting maximal selectivity of 81% for DMM. Better TONs were observed by replacing Al(OTf)₃ with HN(Tf)₂ as the acid, longer reaction time (22 h) and a higher temperature (100 °C). The impact of the triphosphine ligand was also probed. The use of triphosphine ligands featuring P(Xyl)₂ and P(Tol)₂ moieties increased the TON to 120 and 157 for C71 and C72, respectively. Optimization of the Ru-based system was further explored in detail by another group.<sup>154–156</sup> C73–C75 were tested in a first study.<sup>154</sup> While the phosphinite moieties in C73 gave lower TONs than the other reported catalytic systems (Table 6, entry 5), replacement of the

<figure><img src="image_81.png" /></figure>
<table><caption>Table 6 Catalytic conditions and performances of C69–78</caption><thead><tr><th>Entry</th><th>Cat, n (µmol)</th><th>Acid, n (µmol)</th><th>P<sub>H<sub>3</sub></sub> (atm)</th><th>P<sub>CO<sub>2</sub></sub> (atm)</th><th>V<sub>CH<sub>3</sub>OH</sub> (mL)</th><th>Time (h)</th><th>T (°C)</th><th>TON</th><th>TOF (h<sup>-1</sup>)</th><th>Sel<sup>a</sup> (%)</th><th>Ref.</th></tr></thead><tbody><tr><td>1</td><td>C69, 12.5</td><td>Al(OTf)<sub>3</sub>, 25</td><td>60</td><td>20</td><td>2</td><td>18</td><td>80</td><td>214</td><td>12</td><td>67</td><td>151</td></tr><tr><td>2</td><td>C70, 15</td><td>HN(Tf)<sub>2</sub>, 45</td><td>60</td><td>20</td><td>2</td><td>22</td><td>100</td><td>92</td><td>4</td><td>74</td><td>151b</td></tr><tr><td>3</td><td>C71, 15</td><td>HN(Tf)<sub>2</sub>, 45</td><td>60</td><td>20</td><td>2</td><td>22</td><td>100</td><td>120</td><td>5</td><td>79</td><td>151b</td></tr><tr><td>4</td><td>C72, 15</td><td>HN(Tf)<sub>2</sub>, 45</td><td>60</td><td>20</td><td>2</td><td>22</td><td>100</td><td>157</td><td>7</td><td>81</td><td>151b</td></tr><tr><td>5</td><td>C73, 1.5</td><td>Al(OTf)<sub>3</sub>, 6.25</td><td>60</td><td>20</td><td>0.5</td><td>18</td><td>80</td><td>32</td><td>2</td><td>28</td><td>154</td></tr><tr><td>6</td><td>C74, 1.5</td><td>Al(OTf)<sub>3</sub>, 6.25</td><td>60</td><td>20</td><td>0.5</td><td>18</td><td>80</td><td>221</td><td>12</td><td>71</td><td>154</td></tr><tr><td>7</td><td>C75, 1.5</td><td>Al(OTf)<sub>3</sub>, 6.25</td><td>60</td><td>20</td><td>0.5</td><td>18</td><td>80</td><td>292</td><td>16</td><td>72</td><td>154</td></tr><tr><td>8</td><td>C75, 1.5</td><td>Al(OTf)<sub>3</sub>, 6.25</td><td>90</td><td>5</td><td>0.5</td><td>18</td><td>90</td><td>97</td><td>5</td><td>92</td><td>154</td></tr><tr><td>9</td><td>C75, 0.38</td><td>Al(OTf)<sub>3</sub>, 1.56</td><td>90</td><td>20</td><td>0.5</td><td>18</td><td>90</td><td>786</td><td>44</td><td>60</td><td>154</td></tr><tr><td>10</td><td>C75, 0.075</td><td>Al(OTf)<sub>3</sub>, 3.576</td><td>105</td><td>12.5</td><td>0.55</td><td>21</td><td>105</td><td>2761</td><td>131</td><td>61</td><td>155</td></tr><tr><td>11</td><td>C75, 0.75</td><td>Al(OTf)<sub>3</sub>, 35.76</td><td>100</td><td>15</td><td>0.5</td><td>20</td><td>100</td><td>3874</td><td>194</td><td>73</td><td>155</td></tr><tr><td>12</td><td>C76, 0.38</td><td>Al(OTf)<sub>3</sub>, 3.13</td><td>90</td><td>20</td><td>0.5</td><td>18</td><td>90</td><td>685</td><td>38</td><td>60</td><td>156</td></tr><tr><td>13</td><td>C77, 0.38</td><td>Al(OTf)<sub>3</sub>, 3.13</td><td>90</td><td>20</td><td>0.5</td><td>18</td><td>90</td><td>439</td><td>24</td><td>46</td><td>156</td></tr><tr><td>14</td><td>C78, 3.1</td><td>Al(OTf)<sub>3</sub>, 25</td><td>20</td><td>100</td><td>5</td><td>20</td><td>100</td><td>1176</td><td>59</td><td>70</td><td>157</td></tr></tbody></table>

<figure><img src="image_82.png" /><figcaption>Scheme 44 DMM synthesis with C69.</figcaption></figure>

central C atom of the backbone of the ligand by a N atom in C74 and C75 enabled slight increase of the TON to 221 and 292, respectively (Table 6, entries 6 and 7). With C75, the optimization conditions led to a net increase of either the selectivity for DMM to 92% but with a TON of 97 (Table 6, entry 8) or of the TON to 786 but with a selectivity for DMM reduced to 60% (Table 6, entry 9). The quantities of the catalyst and co-catalyst were shown to be the main factor enabling this TON increase. In this optimization study for C75, all possible parameters were carefully optimized individually (univariate optimization) to improve the TON from 214 to 786 (Table 6, entries 1 and 9, resp.) which represents a 367% increase in TON. A subsequent study using a multivariate optimization led to a larger improvement of TON. The pre-catalyst C75 indeed provided TONs of 2761 and 3874 with a 10 fold increase of the scale of the reaction leading to the formation of 2.88 mmol of DMM (Table 6, entries 10 and 11, resp.).¹⁵⁵ This corresponds to a significant improvement of further 493% from the univariate optimization (Table 6, entry 9). These impressive results were made possible mainly by acting on the quantities of the catalyst and co-catalyst. In another report, the replacement of the heteroelement of the backbone by Si or P atoms (C76 and C77, respectively) did not enable any further increase of the catalytic performances or selectivity (Table 6, entries 12 and 13).¹⁵⁶ In order to have a closer look at the active catalyst, dihydride compound C78 was synthesized and tested (Table 6, entry 14).¹⁵⁷ Pre-catalysts C69–77 are indeed sought to generate M–H species which act as the active catalyst in the reaction. This study showed the beneficial aspect of adding tertiary phosphine or phosphite in order to prevent catalyst deactivation by the

formation of a carbonyl ligand from the $CO_2$ decarbonylation. Overall, optimization strategies presented with catalysts C69–C78 were dedicated to the improvement of TON as the most important parameter. Although interesting selectivities of DMM vs. MM were obtained, the lesser attention to this parameter can be explained by the possibility of hydrogenating MF into DMM in a second step.¹⁵⁴,¹⁵⁶ However, the TOF parameter was not optimized. As indicated in Table 6, it ranges between 2 and 194 $h^{-1}$, leaving room for improvement in these systems.

### 5.2.2. Extension to other dialkoxymethanes (DAMs).
Other alcohols beside methanol were tested to generate dialkoxy-methane (DAM) compounds. Using C69 ¹⁵¹a and C70 (Fig. 5),¹⁵¹b 11 examples were obtained and characterized with TON ranging from 16 to 118 (Scheme 45a). Aliphatic alcohols used included linear chain (containing 2 to 10 carbon atoms), branched (¹BuOH and ¹PrOH) and benzyl alcohol. In a subsequent study, the authors used bio-sourced diols to increase the sustainability of the process and the product scope.¹⁵⁸ These diols were shown to afford either a cyclic acetal (C-DAM) or a linear acetal (L-DAM) (Scheme 45b). In total, eight products were characterized and selectivity toward either C-DAM or L-DAM was reached depending on the nature of the diol substrate (n = 1–6). A selectivity of 92% was notably observed toward the formation of the C-DAM, 4-methyl-1,3-dioxane, while reversed selectivity of 99% to L-DAM was obtained with the diol featuring a 5-carbon linker.

### 5.2.3. Mechanism.
In the initial description of the formation of DMM from $CO_2$, the intermediary of methoxyformate (MF) and methoxymethanol (MM) was demonstrated

<figure><img src="image_83.png" /></figure>

<footnote>a Selectivity = $\frac{\text{TON(DMM)}}{\text{TON(MF)} + \text{TON(DMM)}}$.</footnote>
<figure><img src="image_84.png" /><figcaption>b) C/L-DAM synthesis</figcaption></figure>

Scheme 45 Synthesis of (a) linear DAM with C69 or C70 and (b) cyclic or linear C-DAM or L-DAM, respectively, with C69.

<figure><img src="image_85.png" /></figure>

Scheme 46 Proposed mechanism for the formation of DMM.

(Scheme 46).<sup>151a</sup> MF and MM were indeed observed during the reaction and the expected <sup>13</sup>C-labelled products and intermediates were characterized when starting from <sup>13</sup>CO<sub>2</sub> and <sup>12</sup>CH<sub>3</sub>OH reactants. In this reaction mechanism, formaldehyde was not an intermediate. One methanol molecule was indeed involved in the first reduction step leading to MF. Compared to formic acid, the methylated analogue MF was hypothesized to "activate" this reduction stage enabling further hydrogenation into MM under rather mild conditions compared to the CO<sub>2</sub> hydrogenation reaction to methanol in the absence of alcohol. It is reminiscent of pioneering strategies using alcohol<sup>159</sup> or amine<sup>20b,160</sup> to promote the hydrogenation of CO<sub>2</sub> into methanol under mild conditions in cascade reactions. One additional molecule of methanol is finally reacted with the MM intermediate affording DMM.

Two recent in-depth studies published concomitantly in 2021 proved to be particularly complementary since one is an experimental investigation of the most used C75/Al(OTf)<sub>3</sub> catalytic system,<sup>161</sup> while the other is a DFT investigation on the Co-based C70/HN(Tf)<sub>2</sub> system.<sup>153b</sup> It is noteworthy that these studies confirmed the elementary steps proposed initially in 2016. The C75/Al(OTf)<sub>3</sub> catalytic system was investigated by *in situ* infrared (IR) spectroscopy at three relevant temperatures: 333 K, 353 K and 373 K enabling the determination of rate constants and activation parameters for the three steps: CO<sub>2</sub> to MF, MF to MM and MM to DMM.<sup>161</sup> These key steps were included in a reaction network analysis. The rate determining step (rds) was shown to be the first CO<sub>2</sub> to MF step with an activation parameters ΔG<sup>h</sup> (333 K) of 119.0 kJ mol<sup>-1</sup> and the lowest rate constant of 1.41 × 10<sup>-6</sup> s<sup>-1</sup> M<sup>-2</sup> at the same temperature. In accord with the experiment, the competitive

formation of CH<sub>3</sub>OH from the hydrogenation of MM was shown to be accessible at higher temperature and the formation of DMM was favoured by the large excess of CH<sub>3</sub>OH used as the solvent. Furthermore, this reaction network analysis was also used as a predictive tool to propose new experimental conditions that would favour one product over the other. The positive effect of H<sub>2</sub>O removal on the formation of DMM was notably proposed.

The DFT study of the C70/HN(Tf)<sub>2</sub> system proposed a detailed kinetic and thermodynamic analysis of each elementary step accounting for the formation of DMM but also for the over-reduction to CH<sub>3</sub>OH.<sup>153b</sup> The thermodynamic values ΔG<sup>0</sup> for the subsequent formation of formic acid, MF, MM and DMM, indicated in Scheme 47, have been calculated to be 34, 19, 53 and 41 kJ mol<sup>-1</sup>, respectively. A major input of this study was to define the exact role of the TM-based catalyst and the acid co-catalyst. The active Co-based species were calculated to be the monohydride cationic Co complex ([P<sub>3</sub>Co-H]<sup>+</sup>) depicted in Scheme 47 (purple box) and was calculated to be the catalyst responsible for the hydrogenation of CO<sub>2</sub> into formic acid and of MF into MM. The two steps (i) and (iii) have been calculated with ΔG<sup>h</sup> of 79 and 98 kJ mol<sup>-1</sup>, respectively. On the other hand, the esterification of formic acid into MM (step ii) and the etherification of MM into DMM (step iv) are catalysed by the acid catalyst HN(Tf)<sub>2</sub>. It was found that the methylating agent responsible for the etherification of MM to DMM was not directly methanol, but CH<sub>3</sub>O-NTf<sub>2</sub> *in situ* generated from the reaction of CH<sub>3</sub>OH with HN(Tf)<sub>2</sub>. Nonetheless, the calculated Gibbs free energy barrier from the most stable Co-formate species is 179 kJ mol<sup>-1</sup> for the last step (iv), making it the rate determining step (rds) of the whole process. As in the previous study, the access to DMM *via* formaldehyde was calculated to be higher in energy and thus discarded. The formation of formaldehyde as an intermediate to DMM was proposed in a related Ru-based system using ethanol instead of methanol, but not with the same level of kinetic or thermodynamic investigations.<sup>162</sup>

### 5.3. Conclusion

In conclusion, the selective 4e<sup>-</sup> reduction of CO<sub>2</sub> by hydrogenation stands out for several reasons: (i) the development of highly active catalytic systems resulting in the reduction of CO<sub>2</sub> into acetals, achieving the highest reported turnover number (TON) of 3874 for this reduction stage, following extensive

<figure><img src="image_86.png" /></figure>
<figure><img src="image_87.png" /><figcaption>Scheme 47 Mechanism of formation of DMM based on calculations.</figcaption></figure>

optimization studies; (ii) the synthesis of acetals, which are of interest as fuel additives, in contrast to bis(silyl)acetal (BSA) and bis(boryl)acetal (BBA) compounds that lack known applications. Consequently, a variety of DAM derivatives have been synthesized, utilizing various alcohols, particularly those derived from biomass.

As perspectives, future endeavours could focus on broadening the applicability of DAM, encouraging additional investigations into acetal syntheses via CO₂ hydrogenation, and exploring diverse catalytic processes beyond [P₃Ru] and [P₃Co] systems.¹⁶³ It would be intriguing to explore the potential use of the generated acetal as both C₁ and Cₙ sources, similar to what has been described with BSA and BBA. However, the hydrogenation of CO₂ into formaldehyde is still in its early stages, with only three selective systems described so far, operating in gas or liquid phases, involving catalysts C65, C67, and C68. Moreover, no isolation or utilization of the generated formaldehyde has been reported to date. Given its perfect atom efficiency and the reactive nature of formaldehyde, the primary challenge lies in developing an efficient system for hydrogenating CO₂ into formaldehyde, enabling its isolation and/or utilization.

Finally, although the processes of 4e⁻ reduction of CO₂ into formaldehyde and into acetal are at very different stages of maturity, it is noteworthy that the stabilization of the 4e⁻ reduction stage in the form of acetal parallels the stabilization of monomeric formaldehyde (HCHO) in the form of acetals of various lengths in formalin solution - the common commercial source of formaldehyde for chemical or biochemical transformations.²⁴⁻²⁶,¹²⁸α⁻¹³⁰,¹³²,¹⁶⁴ It is indeed noticeable that the two examples described in liquid medium for the

hydrogenation of CO₂ with C64 and C67 were conducted in H₂O, CH₃OH or glycerol. Presumably, these solvents stabilize the reactive *in situ* generated monomeric formaldehyde in the form of methanediol or acetal derivatives while avoiding its polymerization as paraformaldehyde.

## 6. Electroreduction

Electrochemical CO₂ reduction reaction (eCO₂RR) offers a green and sustainable approach for converting this gas into various products, under mild conditions (room temperature and pressure) and both in organic or aqueous media. Regarding C₁ products, while the formation of 2e⁻ reduction products has been performed with several catalysts with high selectivity and rate,¹⁰a the formation of 4, 6 and 8e⁻ reduction products has been much more rarely observed (Scheme 48).¹⁶⁵ If methanol and methane have been produced in a few cases, formaldehyde remains an elusive product to date.

### 6.1. Electrocatalytic systems

One of the early examples of CO₂ electrochemical reduction to formaldehyde concerned the use of a Ru based complex with a terpyridine-bipyridine ligand (Fig. 6) which was shown to produce a small amount of HCHO, through the formation of a formyl complex, in a mixture of water and ethanol, at low temperature (−20 °C) upon electrolysis at an Hg pool working electrode (E = −1.70 V vs. Ag/AgCl).¹⁶⁶ A faradaic efficiency (FE) of ca. 5% was obtained for HCHO, while methanol and remarkably C–C coupling products were also identified (H(O) CCOOH, HOCH₂COOH). Unexpectedly, a metal-free organic
<figure><img src="image_88.png" /></figure>

<figure><img src="image_89.png" /><figcaption>Scheme 48 Electrochemical reduction of CO₂ into C₁ products.</figcaption></figure>

<figure><img src="image_90.png" /><figcaption>Fig. 6 Examples of molecular catalysts capable of generating formaldehyde from CO₂ electroreduction.</figcaption></figure>

catalyst, 6,7-dimethyl-4-hydroxy-2-mercaptopteridine (a natural cofactor, Fig. 6) was reported to electrocatalyze CO₂ reduction to various products, including not only formate, but also methanol and formaldehyde (not quantified).¹⁶⁷ The reaction was conducted in a phosphate buffered solution at a reticulated vitreous carbon electrode (E = -0.65 V vs. Ag/AgCl), and it was suggested that CO₂ was first reduced to formate, which was subsequently reduced to formaldehyde and methanol (the latter product was obtained with FE 10-23%) via a carbamate compound. Recently, a transition metal based polyoxometalate (TOA)₆[a-SiW₁₁O₃₉-Co(_)] (TOA: tetraoctyl ammonium, _ = vacant position at the Co atom) was shown to electroreduce CO₂ under homogeneous

conditions in dichloromethane as the solvent, and a potential of -1.5 V vs. Hg₂Cl₂/Hg at a Hg electrode.¹⁶⁸ In the presence of an acid as a co-reactant (water and H₂SO₄), the products were identified as CO, with about 13% FE, and formaldehyde with a maximum efficiency (FE) of ca. 25%. The use of an organic and reducible solvent (which is shown to generate HCHO under an Ar atmosphere), limits the development of the process but this example is an interesting case of molecular electrochemical approach for CO₂-to-HCHO conversion. Another molecular cobalt complex, a Co corrole (triphenylphosphine 5,10,15-tris(2,3,5,6-tetrafluoro-4-(MeO-PEG(7)thiophenyl))), Fig. 6) modified at the para positions with thiol bound poly(ethylene
<figure><img src="image_91.png" /></figure>

glycol) chains terminated by methoxy groups was adsorbed at the carbon paper electrode and then investigated for the eCO₂RR into methanol and ethanol.¹⁶⁹ In 0.1 M phosphate buffer solutions with 0.1 M NaClO₄ at potentials ranging from -0.51 V to -0.8 V vs. NHE, low formaldehyde efficiencies from 10 to 1%, respectively, were obtained among other liquid phase products (formate, acetate, glyoxal), corresponding to low current densities (from 0.2 to 0.02 mA cm⁻² respectively).

Another strategy was developed upon polymerizing electrode films of metal complexes at the surface of conductive carbon. Cr, Co and Fe bis-terpyridine complexes bearing the vinyl group were used to grow electroactive films upon oxidation, which were further employed as catalysts in aqueous solutions with 0.1 M NaClO₄.¹⁷⁰ At potentials close to -1.1 V vs. Ag/AgCl, faradaic yields of 28% (Fe), 39% (Co) and 87% (Cr) were reported for formaldehyde, thus showing very high activity for first row transition metals while second and third row transition metals (Ru and Os respectively) gave barely any reactivity, which was assigned to the presence of metal-based redox processes in the former cases compared to ligand-based redox processes in the latter. The CO₂ to CO conversion being now a well-controlled reaction, and CO being a possible intermediate towards formaldehyde production, a parallel approach was developed using CO directly as the reactant and supramolecular catalysts: thin films of Co phthalocyanine and 4,4',4'',4'''-tetracarboxyphthalocyanine made at the carbon fibre were investigated and shown to produce mainly formaldehyde as the CO reduction product with very little methanol, at a potential of -0.7 V vs. SCE (Saturated Calomel Electrode) in sulfuric acid solutions.¹⁷¹ Recently, it was further shown that CO reduction with a phthalocyanine monomer complex also led to formaldehyde with unambiguous confirmation from labelled studies.¹⁷² These results opened the door to understanding the mechanism of formaldehyde pathway from both CO₂ and CO as reactants, with possibilities of tuning the quantity of formaldehyde being produced and the ratio between HCHO and methanol. It also opens the possibility of setting a cascade approach in which the CO produced from CO₂ reduction could further be used to generate HCHO. A very recent study explored such electro-reduction of CO to HCHO with Co phthalocyanine deposited at a carbon paper electrode. Upon optimization of the pH (12) and of the electrode potential, a partial current density of 0.64 mA cm⁻² (17.5% faradaic efficiency) was achieved for HCHO, with a maximum ratio between HCHO and CH₃OH of *ca.* 7.5. Mechanical insights illustrate that the binding of CO to the metal cobalt site is strong enough for further reducing it, while controlling the amount of protons and the electrode potential is key to favouring formaldehyde formation and release at the expense of methanol production.¹⁷³ A puzzling discovery was made upon direct electroreduction of CO₂ in various solutions (methanol, water and even sea water) at boron doped diamond (BDD) electrodes without any additional catalyst.¹⁷⁴ These materials have several advantages, including a large potential window, high stability and furthermore the presence of sp³-bonded carbon atoms on BDD which are believed to be active sites for triggering chemical transformations. Upon 1 h electrolysis at *E* = -1.7 V vs. Ag/AgCl, a maximum yield (FE) of 74%

was obtained for formaldehyde, along with formic acid and a very small amount of dihydrogen as a by-product. The formaldehyde was deemed to be formed from the 2e⁻ reduction of formic acid initially obtained from CO₂ conversion, while current densities were low, typically in the range of 0.1 to 0.2 mA cm⁻². Finally, an elegant indirect approach has been proposed with methanol as the solvent. While methanol itself was oxidized to formaldehyde in the anodic compartment, electroreduction of CO₂ at the Sn electrode led to formic acid, which reacted with the solvent to give methyl formate. Finally, the latter was reduced to formaldehyde, with faradaic efficiencies for HCHO from 10 to 50% depending on the electrolyte conditions.¹⁷⁵

## 6.2. Conclusion and perspectives

In conclusion, the electrochemical reduction of CO₂ to formaldehyde poses a formidable challenge, with only a limited number of examples identified thus far. These cases exhibit low yields, low current density, and, in many instances, uncertainties regarding the origin of the produced formaldehyde. The challenge of obtaining formaldehyde also arises from its susceptibility to further transformation at the electrode into more reduced products, such as methanol. Additionally, the precise catalytic mechanisms involved in these processes remain elusive with only very few mechanistic studies.¹⁷³

As perspectives, the prospect of *in situ* generating a substantial quantity of formaldehyde under mild conditions across a range of precisely controlled potentials is enticing. This potential development could pave the way for utilizing formaldehyde in subsequent chemical reactions, particularly in coupling reactions. As an early illustrative example, co-reduction scenarios involving CO₂ (or CO) with nitrogen-containing species like nitrite (NO₂⁻)¹⁷⁶ or nitrate (NO₃⁻)¹⁷⁶,¹⁷⁷ could facilitate C-N bond formation, yielding a diverse array of products, including amines and urea. The exploration of these processes, along with related ones, under the controlled conditions afforded by electrochemistry is poised to yield new and stimulating results.

## 7. Photo(electro)reduction

The photochemical (PC) and photoelectrochemical (PEC) reduction of CO₂ (Scheme 49), mostly using semiconducting materials, have been extensively studied in the last four decades.¹⁷⁸ However, if compared to other reduction products such as CO or formate, only a limited number of studies so far reported the formation of formaldehyde as a major product and even less studies report a selective HCHO production, mainly because of its high reactivity.¹⁷⁹ Moreover, very few of these studies conducted proper isotope labelled measurements to confirm the origin of the carbon atom, which constitutes a severe drawback.¹⁸⁰

A very early report questioned the possible formation of formaldehyde from water and CO₂ as the first stage of the photosynthetic process forming carbohydrates.¹⁸¹ This study showed that an aqueous solution, free of catalyst, containing carbon dioxide gives formaldehyde when irradiated with
<figure><img src="image_92.png" /><figcaption>Scheme 49 Photochemical and photoelectrochemical reduction of CO₂.</figcaption></figure>

<figure><img src="image_93.png" /></figure>

UV-light (λ = 200 nm) in a first stage, and that subsequent irradiation with lower energy light (λ = 290 nm) induced the polymerization of HCHO to sugars. It also showed that the formation of HCHO can be photocatalyzed under visible light through the use of “coloured basic substances” such as malachite-green or methyl-orange. Remarkably, the role of HCHO in the course of the photochemically induced formation of highly reduced compounds from CO₂ was thus already questioned a century ago. Later, a pioneer work reported that using suspensions of various semiconductors (TiO₂, ZnO, CdS, GaP and SiC, Table 7, entries 1–5) in CO₂-saturated purified water, the generation of formic acid, formaldehyde and methanol was observed up to the millimolar concentration range after 7 h of visible light illumination (500 W Xe or Hg lamp).¹⁸² Trace of methane was also detected. The reduction products were quantified by gas chromatography although no labelled experiment was conducted to assert the origin of the products. The yield in methanol was observed to increase as the conduction band (CB) of the material was more negative compared to the reduction potential of the CO₂-to-CH₃OH reaction. A quantum yield of ca. 5 × 10⁻⁴ was reported for the formaldehyde production with both TiO₂ and SiC photo-catalysts. Using semiconductor electrodes polarized at -1.5 V vs. SCE, CO₂ reduction to formic acid, formaldehyde and methanol was also observed with non-illuminated TiO₂ and illuminated GaP. Since this seminal paper, the majority of studies published so far have explored various semiconductors,¹⁹⁸ based on metal and metal oxides, doped or not, eventually in combination with co-catalysts,³⁶,¹⁹⁹ in the form of suspensions, bulk materials or thin films. Some other examples, albeit quite rare, employed either a fully molecular, a heterogeneous material or even a photo-enzymatic approach.

## 7.1. Suspension of a semiconductor

Aqueous suspensions of semiconducting SiTiO₂, WO₃ and TiO₂ under both Hg lamp or natural sunlight were reported to generate a mixture of methanol (a few µmol per hour) and formaldehyde (a few tens of µmol per hour) from dissolved carbon dioxide, as quantified by gas chromatography (CH₃OH) and colorimetric (HCHO) measurements (Table 7, entries 6–8).¹⁸³ Traces of methane were also detected. In a follow-up study,¹⁸⁴ aqueous suspensions of strontium titanate (SrTiO₃)

treated with various transition metal–TiO₂ deposits, namely Rh, Pt, In and Au, and saturated with CO₂ were irradiated with a 75 W Hg-lamp or a solar concentrator. When using Ir oxide as an additive (4.55 mol%), formic acid was the main product with a rate of ca. 1 µmol h⁻¹. With Ru oxide (4.55 mol%) as the additive, methanol was the main product. The highest rate for formaldehyde formation was obtained with SrTiO₃ with 0.5 mole % of lanthanum chromite (LaCrO₃) as an additive (Table 7, entry 9). However, the change in selectivity with the nature of the additive was not discussed. Aqueous suspensions of n-type semiconductors such as bismuth (Bi₂S₃) and cadmium (CdS) sulphides were reported to generate formic acid and formaldehyde at ca. 10⁻⁵ M concentration after 1 h under wide spectrum irradiation (55 mW cm⁻²) when H₂S was present in the system (Table 7, entries 10 and 11).¹⁸⁵ This was explained by a sequential process producing first formic acid by 2e⁻/2H⁺ transfers then formaldehyde by additional electron transfers. The catalysis, which was shown to be proportional to the light intensity, stopped due to the poisoning deposition of elemental sulphur at the surface of the particles. The formation of HCHO as the only CO₂ reduction product was also observed at a rate up to 0.25 µmol h⁻¹ with a CO₂ saturated aqueous suspension of TiO₂ at 333 K under 500 W high pressure Xe lamp irradiation (Table 7, entry 12), but the origin of such selectivity is unknown.¹⁸⁶ TiO₂ doping with 0.1 mol% WO₃ further increased this rate up to 0.42 µmol h⁻¹ (Table 7, entries 13 and 14). The deposition of Rh on TiO₂ led to the formation of HCOOH (major), CH₃OH (secondary) and HCHO (minor) up to a total rate of 0.67 µmol h⁻¹ (Table 7, entry 15). The doping of TiO₂ with Au was more thoroughly studied. At 7 bars and 80 °C, a reactor containing 0.6 g of 0.1–0.5 wt% loading of Au/TiO₂ composites led to the highest yield of formaldehyde (270 mmol kgₐt⁻¹ h⁻¹, Table 7, entry 16).¹⁸⁷ Another study reported the use of a gold nanoparticle decorated TiO₂ photonic crystal as the photocatalyst (Au-PMTiNTs).¹⁸⁸ When irradiated with an AM1.5 G source, methane was the main reduction product (302 µmol gₐt⁻¹ h⁻¹, 89.3% selectivity), whereas, under the irradiation of a UV-poor white lamp, formaldehyde (420 µmol gₐt⁻¹ h⁻¹) and CO (323 µmol gₐt⁻¹ h⁻¹) were the major products (Table 7, entry 17). This so-called optical control of selectivity was explained by the plasmonic effects of the gold surface involving hot electrons but no discussion was made on the hydrogen atom source.
<figure><img src="image_94.png" /></figure>

<table><caption>**Table 7** Catalytic performance of photochemical and photoelectrochemical systems for CO₂ reduction to formaldehydeᵃ</caption><thead><tr><th colspan="7">Suspensions</th></tr><tr><th>Entry</th><th>Catalyst</th><th>Loading</th><th>Conditions</th><th>Light source</th><th>Products</th><th>Yield (µmol h<sup>-1</sup> g<sub>cat</sub><sup>-1</sup>)</th><th>Ref.</th></tr></thead><tbody><tr><td>1</td><td>TiO<sub>2</sub></td><td>1 g/100 mL</td><td>Water</td><td>500 W Xe or h-p. Hg arc lamp</td><td>HCOOH<br>CH<sub>3</sub>OH<br>HCHO</td><td>n.d<br>3.3<br>15.7</td><td>182</td></tr><tr><td>2</td><td>ZnO</td><td>1 g/100 mL</td><td>Water</td><td>500 W Xe or h-p. Hg arc lamp</td><td>HCOOH<br>CH<sub>3</sub>OH<br>HCHO</td><td>n.d<br>5</td><td>182</td></tr><tr><td>3</td><td>CdS</td><td>1 g/100 mL</td><td>Water</td><td>500 W Xe or h-p. Hg arc lamp</td><td>HCOOH<br>CH<sub>3</sub>OH<br>HCHO</td><td>n.d<br>17.1<br>16.7</td><td>182</td></tr><tr><td>4</td><td>GaP</td><td>1 g/100 mL</td><td>Water</td><td>500 W Xe or h-p. Hg arc lamp</td><td>HCOOH<br>CH<sub>3</sub>OH<br>HCHO</td><td>n.d<br>28.6<br>15.7</td><td>182</td></tr><tr><td>5</td><td>SiC</td><td>1 g/100 mL</td><td>Water</td><td>500 W Xe or h-p. Hg arc lamp</td><td>HCHO<br>CH<sub>3</sub>OH<br>HCHO</td><td>n.d<br>13.3<br>15.7</td><td>182</td></tr><tr><td>6</td><td>SrTiO<sub>3</sub></td><td>4–10 g L<sup>-1</sup></td><td>Water</td><td>70 W h-p. Hg lamp (&gt;300 nm)</td><td>CH<sub>3</sub>OH<br>HCHO</td><td>1.79<br>0.01</td><td>183</td></tr><tr><td>7</td><td>WO<sub>3</sub></td><td>4–10 g L<sup>-1</sup></td><td>Water</td><td>70 W h-p. Hg lamp (&gt;300 nm)</td><td>CH<sub>3</sub>OH<br>HCHO</td><td>1.26<br>0.05</td><td>183</td></tr><tr><td>8</td><td>TiO<sub>2</sub></td><td>4–10 g L<sup>-1</sup></td><td>Water</td><td>70 W h-p. Hg lamp (&gt;300 nm)</td><td>CH<sub>3</sub>OH<br>HCHO</td><td>0.51<br>0.08</td><td>183</td></tr><tr><td>9</td><td>SrTiO<sub>3</sub> + 0.5 mole %<br>LaCrO<sub>3</sub></td><td>1 g/160 mL</td><td>Water</td><td>70 W h-p. Hg lamp</td><td>HCOOH<br>CH<sub>3</sub>OH<br>HCHO</td><td>0.98<br>0.065</td><td>184</td></tr><tr><td>10</td><td>CdS</td><td>0.33 g L<sup>-1</sup></td><td>Water</td><td>100 W quartz-iodine lamp (&gt;350 nm)</td><td>HCOOH<br>HCHO</td><td>1.22<br>1.95</td><td>185</td></tr><tr><td>11</td><td>Bi<sub>2</sub>S<sub>3</sub></td><td>0.5 g L<sup>-1</sup></td><td>Water</td><td>100 W quartz-iodine lamp (&gt;350 nm)</td><td>HCOOH<br>HCHO</td><td>1.0<br>1.58</td><td>185</td></tr><tr><td>12</td><td>TiO<sub>2</sub> (MCB)</td><td>0.3 g</td><td>Water</td><td>500 W h-p. Xe lamp</td><td>HCOOH<br>HCHO</td><td>0.94<br>1.98</td><td>186</td></tr><tr><td>13</td><td>TiO<sub>2</sub> + 0.1 mole % WO<sub>3</sub></td><td>0.3 g</td><td>Water</td><td>500 W h-p. Xe lamp</td><td>HCHO<br>HCHO</td><td>1.18</td><td>186</td></tr><tr><td>14</td><td>TiO<sub>2</sub> + 2 mole % WO<sub>3</sub></td><td>0.3 g</td><td>Water</td><td>500 W h-p. Xe lamp</td><td>HCHO</td><td>1.4</td><td>186</td></tr><tr><td>15</td><td>1 mole % Rh/TiO<sub>2</sub></td><td>0.3 g</td><td>Water</td><td>500 W h-p. Xe lamp</td><td>HCHO</td><td>0.69<br>0.53<br>0.37</td><td>186</td></tr><tr><td>16</td><td>0.1 wt% Au/TiO<sub>2</sub></td><td>0.6 g/1.2 L</td><td>Water, Na<sub>2</sub>SO<sub>3</sub> 0.85 g L<sup>-1</sup><br>80 °C<br>7 bar CO<sub>2</sub></td><td>med-p. Hg lamp (254–364 nm)</td><td>HCOOH<br>CH<sub>3</sub>OH<br>HCHO</td><td>148<br>721<br>270</td><td>187</td></tr></tbody></table>
<figure><img src="image_95.png" /><figcaption>Table 7 (Contd.)</figcaption></figure>

<table><thead><tr><th colspan="7">Suspensions</th></tr><tr><th>Entry</th><th>Catalyst</th><th>Loading</th><th>Conditions</th><th>Light source</th><th>Products</th><th>Yield (µmol h<sup>-1</sup> g<sub>cat</sub><sup>-1</sup>)</th><th>Ref.</th></tr></thead><tbody><tr><td>17</td><td>Au/TiO<sub>2</sub> NT photonic crystals</td><td>85 µg Au per TiO<sub>2</sub> wafer</td><td>Water vapor</td><td>50 W white-cold LED (&gt;400 nm)</td><td>CO</td><td>323</td><td>188</td></tr><tr><td>18</td><td>TiO<sub>2</sub></td><td>0.5 g L<sup>-1</sup></td><td>Water<br>80 °C<br>7 bar CO<sub>2</sub><br>"Wet" (70% humidity)</td><td>125 W med. p. Hg lamp (254–364 nm)</td><td>H<sub>2</sub><br>HCOOH</td><td>420<br>102<br>2954</td><td>189</td></tr><tr><td>19</td><td>TiO<sub>2</sub>/ZrO<sub>2</sub> (ZrO<sub>2</sub> 40 weight%)</td><td>0.2 g spread on a Cu plate</td><td>Water</td><td>Real sunlight</td><td>H<sub>2</sub>OH</td><td>732</td><td>190</td></tr><tr><td>20</td><td>NaTaO<sub>3</sub>–C (annealed at 650 °C)</td><td>100 mg/200 mL</td><td>Water</td><td>Pen ray lamp (254 nm)</td><td>HCHO</td><td>1392</td><td>191</td></tr><tr><td>21</td><td>Pd/TiO<sub>2</sub>–Fe<sub>2</sub>O<sub>3</sub></td><td>0.05 g/50 mL</td><td>Water pH 8.5<br>Na<sub>2</sub>CO<sub>3</sub></td><td>500 W Xe lamp</td><td>HCHO</td><td>19.5</td><td></td></tr><tr><td>22</td><td>CoPc/TiO<sub>2</sub> (1% mass ratio, calcined at 400 °C)</td><td>10 g/100 mL</td><td>0.1 N NaOH aq. sln</td><td>500 W tungsten-halogen lamp</td><td>HCHO</td><td>33.5</td><td>192</td></tr><tr><td>23</td><td>RuL1OH/TiO<sub>2</sub> (0.125 µM Ru complex per g<sub>cat</sub>)</td><td>10 mg/10 mL</td><td>0.8 mM TEOA aq. sln</td><td>250 W lamp (&gt;420 nm)</td><td>C<sub>2</sub>H<sub>5</sub>OH</td><td>101.7</td><td></td></tr><tr><td>24</td><td>Sn<sub>75</sub>–Cu<sub>25</sub>/C<sub>3</sub>N<sub>4</sub></td><td>1.5 mg/3.5 mL</td><td>0.1 M KHCO<sub>3</sub></td><td>300 W Xe lamp (&gt;420 nm)</td><td>CH<sub>3</sub>CO<sub>2</sub>H</td><td>51</td><td></td></tr><tr><td>25<sup>b</sup></td><td>K<sub>2</sub>Ti<sub>6</sub>O<sub>13</sub> + 0.3 wt% Pt</td><td>0.3 g/4 mL</td><td>Water<br>r.t</td><td>150 W Hg-lamp</td><td>HCOOH</td><td>15.7</td><td>193</td></tr><tr><td>26<sup>b</sup></td><td>Cu/ZnO/K<sub>2</sub>Ti<sub>6</sub>O<sub>13</sub> + 0.3 wt% Pt</td><td>0.3 g/4 mL</td><td>Water<br>r.t</td><td>150 W Hg-lamp</td><td>CO</td><td>1</td><td></td></tr><tr><td>27<sup>b</sup></td><td>K<sub>2</sub>Ti<sub>6</sub>O<sub>13</sub> + 0.3 wt% Pt</td><td>0.3 g/4 mL</td><td>Water<br>274 °C</td><td>Concentrated sunlight</td><td>CH<sub>4</sub><br>HCHO</td><td>0.5<br>0.8<br>2.5</td><td></td></tr><tr><td>28</td><td>TiO<sub>2</sub></td><td>30 mg/20 mL</td><td>Aq. sln pH 6.5, NADH 5 mM, [Cp*Rh(bpy)(H<sub>2</sub>O)]<sup>2+</sup> 0.25 mM</td><td>23 W UV lamps (max 365 nm)</td><td>CH<sub>4</sub><br>HCHO</td><td>1<br>11.3</td><td>194</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td>CH<sub>4</sub><br>HCHO</td><td>1<br>11.3</td><td>195</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td>HCHO</td><td>6.9</td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td>HCHO</td><td>10.8</td><td>196</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td>H<sub>2</sub></td><td>68</td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td>HCOOH</td><td>0.23</td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td>CH<sub>4</sub><br>HCHO</td><td>0.2<br>0.476</td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td>H<sub>2</sub></td><td>17</td><td>196</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td>HCOOH</td><td>3.04</td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td>CH<sub>4</sub><br>HCHO</td><td>0.27<br>0.57</td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td>H<sub>2</sub></td><td>32.8</td><td>196</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td>HCOOH</td><td>20.7</td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td>CH<sub>4</sub><br>HCHO</td><td>0.23<br>5.59</td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td>HCHO</td><td>27.6</td><td>197</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td>HCHO<br>(PB buff.)</td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td>HCHO<br>(NaOH-EDTA buff.)</td><td></td><td>548</td></tr></tbody></table>
<figure><img src="image_96.png" /></figure>

<table><caption>Table 7 (Contd.)</caption><thead><tr><th colspan="7">Suspensions</th></tr><tr><th>Entry</th><th>Catalyst</th><th>Loading</th><th>Conditions</th><th>Light source</th><th>Products</th><th>Yield (µmol h<sup>-1</sup> g<sub>cat</sub><sup>-1</sup>)</th><th>Ref.</th></tr></thead><tbody><tr><td>29</td><td>TiO<sub>2</sub> coupled to FDH: FADH (ratio 1 : 03) loaded membrane</td><td>30 mg/20 mL</td><td>Aq. sln pH 5.5, NADH 5 mM, [Cp*Rh(bpy)(H<sub>2</sub>O)]<sup>2+</sup> 0.25 mM</td><td>23 W UV lamps (max 365 nm)</td><td>HCHO (PB buff.)<br>HCHO (NaOH-EDTA buff.)</td><td>13.5<br>345</td><td>197</td></tr><tr><th colspan="8">Photoelectrodes</th></tr><tr><th>Entry</th><th>Catalyst</th><th>Bias (V)</th><th>Conditions</th><th>Light source</th><th>Products</th><th>Yield (µmol h<sup>-1</sup> cm<sup>-2</sup>)</th><th>Ref.</th></tr><tr><td>30</td><td>Polyaniline coated p-Si</td><td>-1.9 V vs. SCE</td><td>0.1 M LiClO<sub>4</sub> aq. sln</td><td>Xe lamp (150 mW cm<sup>-2</sup>)</td><td>HCOOH</td><td>60.5</td><td>200</td></tr><tr><td>31</td><td>p-GaAs</td><td>-0.5 V vs. SCE</td><td>4 M HCl aq. sln with 0.32 M V(II)/V(III) couple, 50 °C</td><td>150 W tungsten or Xe lamp</td><td>HCHO<br>CH<sub>3</sub>OH<br>HCHO</td><td>15<br>n.d</td><td>201</td></tr><tr><td>32</td><td>Bifunctional TiO<sub>2</sub> with Ru N719 dye</td><td>No bias</td><td>2 M NaOH aq. sln pH 10</td><td>300 W Xe lamp (cutoff > 420 nm)</td><td>HCOOH<br>CH<sub>3</sub>OH<br>HCHO</td><td>16.7<br>35.6<br>25.8</td><td>202</td></tr><tr><td>33<sup>b</sup></td><td>Cu<sub>2</sub>O film on Cu</td><td>No bias</td><td>0.1 M Na<sub>2</sub>CO<sub>3</sub>/NaHCO<sub>3</sub> aq. sln pH 9.0</td><td>125 W h.-p. Hg lamp</td><td>CH<sub>3</sub>OH<br>HCHO</td><td>9.5<br>125</td><td>203</td></tr><tr><td>34</td><td>040-BiVO<sub>4</sub>|Cu</td><td>+0.9 V vs. RHE</td><td>0.5 M NaCl aq. sln</td><td>300 W Xe lamp with an AM 1.5G filter</td><td>HCHO<br>CH<sub>3</sub>OH<br>C<sub>2</sub>H<sub>5</sub>OH<br>HCHO</td><td>108<sup>c</sup><br>n.d<br>n.d</td><td>204</td></tr><tr><td>35</td><td>Cu/rGO/PVP/Nafion</td><td>+0.68 V vs. RHE</td><td>0.1 M NaOH aq. sln</td><td>300 W Xe lamp with a KG3 filter</td><td>HCHO</td><td>1.18</td><td>205</td></tr></tbody></table>

<footnote><sup>a</sup> n.d: not determined. <sup>b</sup> Catalyst deposited on a wet paper filter at the bottom of the reaction vessel. <sup>c</sup> In µmol L<sup>-1</sup> h<sup>-1</sup> cm<sup>-2</sup> (reactor volume not specified).</footnote>
<figure><img src="image_97.png" /></figure>

Another example of TiO₂ based photocatalysis was reported in which sodium sulfite was used as the reducing agent in order to fill in photogenerated holes. Under 7 bars of CO₂, at 80 °C and at a TiO₂ loading of 0.5 g⁻¹ in basic (pH 14) aqueous solutions, the formation of H₂ (102 µmol h⁻¹ gcat⁻¹), formaldehyde (16 537 µmol h⁻¹ gcat⁻¹) and formic acid (2954 µmol h⁻¹ gcat⁻¹) were measured depending on experimental conditions (time and pH) under UV irradiation from a medium pressure Hg vapor 125 W lamp introduced into the photoreactor (Table 7, entry 18).¹⁹⁰ The higher formation rate for formaldehyde was observed at the beginning of the reaction (few hours), which was explained by a branched mechanism, with on one hand a CO₂-to-formic acid reduction later generating gaseous products (only detected after several hours of irradiation once the hole scavenger is consumed), and on the other hand the direct reduction of carbonates into HCHO. Composites made of nanometre-sized TiO₂ particles and micrometre-sized zirconium oxide (ZrO₂) particles have been reported to generate high yields of formaldehyde and methanol (maximum 300 µmol gcat⁻¹ total after only 300 s) under real solar light illumination (Table 7, entry 19).¹⁹⁰ For that, the composite was scattered on a copper plate and allowed to humidify in a fridge to form a thin layer of water on the composite surface. The assembly was then placed in a gas-barrier plastic bag (allowing CO₂ diffusion only) containing ambient air and then was illuminated with solar light. It was proposed that reduction products originated from the reduction of bicarbonate ions resulting from the dissolution of CO₂ contained (from ambient air) in the thin layer of water. A highly crystalline carbon-doped NaTaO₃ perovskite was also reported to reduce CO₂ to formaldehyde in neutral aqueous solutions at room temperature and under 254 nm irradiation (4.4 mW cm⁻²), at the optimal rate of 39 µmol gcat⁻¹ after 2 h (Table 7, entry 20).¹⁹¹ This rate, determined through complexometric measurements, was shown to be dependent on the annealing temperature used to prepare the material as well as the carbon content since the undoped material showed very low formaldehyde yield. Three hematite-based materials, namely Fe₂O₃, TiO₂-Fe₂O₃ and Pd/TiO₂-Fe₂O₃ were suspended as nanoparticles in an aqueous sodium carbonate solution (pH 8.5) and illuminated with a 500 W xenon lamp. After 2 hours, the highest rate for formaldehyde was obtained with Pd/TiO₂-Fe₂O₃ (1338 µmol L⁻¹ gcat⁻¹, Table 7, entry 21), when compared with the simple Fe₂O₃ (878 µmol L⁻¹ gcat⁻¹) and TiO₂-Fe₂O₃ (399 µmol L⁻¹ gcat⁻¹) and was explained by the hydrogenation of formic acid with hydrogen atoms on the photocatalyst surface.¹⁹² An example of a system combining a semiconducting material and

a molecule consisted of cobalt phthalocyanine loaded TiO₂ nanoparticles (CoPc/TiO₂) of ca. 11 nm diameter prepared by a sol-gel method and dispersed in alkaline (NaOH) aqueous solutions under a CO₂ atmosphere.¹⁹³ When irradiated with a tungsten-halogen 500 W lamp, a mixture of products containing CO, HCOOH, CH₃OH, CH₄ and HCHO was produced at a maximum yield of 407 µmol gcat⁻¹ after 20 h under optimized conditions (CoPc/TiO₂ mass ratio, calcination temperature), the latter accounting for ca. 50 µmol gcat⁻¹ (Table 7, entry 22). The CO₂ reduction to formaldehyde utilizing a heteroleptic ruthenium metal complex covalently linked to TiO₂ nanoparticles was also reported to occur in aqueous medium at pH 7 under visible light (λ > 420 nm) illumination.¹⁹⁴ When the hybrid catalyst was dispersed in neutral water, in the presence of TEOA (triethanolamine) as a sacrificial donor agent, the formation of formaldehyde as the major product (maximum TON of 720 after 5 h, corresponding to a formation rate of 18 µmol h⁻¹ gcat⁻¹, Table 7, entry 23) was observed in the liquid phase as determined by HPLC, with CO and CH₄ as minor (TON 136 and 64, respectively), gaseous, products. Moreover, recyclability tests showed that the loss of activity was limited to 10–15% after the sixth cycle, due to some material loss during washing steps. In addition, this system used the *in situ* generated formaldehyde in a condensation reaction with amine, generating new H₂C-N bonds (Scheme 50). To the best of our knowledge, this represents the only example of reductive functionalization of CO₂ *via* formaldehyde in (photo)electroreduction systems.

Very recently,¹⁹⁵ a single-atom catalyst with dual-atom sites (DAS) composed of neighbouring Sn(II) and Cu(I) centres embedded in a C₃N₄ framework was reported to generate HCHO from CO₂ with a selectivity of 61% and a productivity of 259.1 µmol g⁻¹ (Table 7, entry 24) after 24 h irradiation. The catalyst was dispersed in a CO₂-saturated 0.1 M aqueous KHCO₃ containing 10 vol% triethylamine (TEA) as the sacrificial electron donor and was irradiated using a 300 W Xe lamp equipped with a 420 nm cut-off filter. The best productivity was obtained with the Sn₇₅-Cu₂₅/C₃N₄ composition, and the production of HCHO from CO₂, asserted by ¹³C labelled experiments and FTIR and NMR characterization, was attributed to the 2e⁻ reduction of HCHO through the synergetic action of the two metals.

An original strategy was also tested with a Pt-loaded potassium hexatitanate (Pt-K₂Ti₆O₁₃) photocatalyst (0.3 mg) deposited on a filter at the bottom of a flask containing 4 mL of water under a CO₂ atmosphere.¹⁹⁶ Upon illumination with a 150 W Hg-lamp, formaldehyde was detected as a secondary reduction product (H₂ as the main one) by GC at a rate of 0.48 µmol h⁻¹

<figure><img src="image_98.png" /><figcaption>**Scheme 50** Visible light reduction of CO₂ into formaldehyde followed by *in situ* condensation with an amine.¹⁹⁴</figcaption></figure>
$g_{\text{cat}}^{-1}$, together with CH$_4$ and HCOOH (Table 7, entry 25). When combined with a Cu/ZnO catalyst, the resulting composite produced HCHO as the secondary product (H$_2$ – major) at a rate of 0.57 µmol h$^{-1}$ $g_{\text{cat}}^{-1}$ along with CH$_4$ and HCOOH (Table 7, entries 26 and 27).

Finally, semiconductors can also be associated with an enzymatic process. For example, a very recent study reported the immobilization of two kinds of dehydrogenases, namely formate dehydrogenase (FDH) and formaldehyde dehydrogenase (FADH) (see Section 8 for more details on these enzymes), on the surface of polyethylene hollow fibre membranes, coupled with UV induced, TiO$_2$-based photocatalytic coenzyme regeneration.¹⁹⁷ In this system, the excitation of TiO$_2$ causes charge separation and electrons are transferred to the NAD$^+$ formed during the enzymatic cascade CO$_2$ reduction, for coenzyme NADH regeneration, using EDTA as the electron donor and pentamethylcyclopentadienyl rhodium bipyridine $([\text{Cp}^*\text{Rh(bpy)}(\text{H}_2\text{O})]^{2+})$ as the redox mediator. In the absence of an enzyme, HCHO was formed at a maximum rate of 0.207 mM (with H$_2$O as the electron donor) and 4.11 mM (with EDTA as the electron donor), at pH 6.5 and after 5 h UV irradiation (365 nm max). With the photo-enzyme assembly, the best results were obtained at pH 5.5 with EDTA as the electron donor, reaching 2.59 mM of formaldehyde after 5 h of reaction (Table 7, entries 28 and 29). The production of HCHO proceeded for 48 h with limited loss of activity.

## 7.2. Photoelectrodes

A p-type Si photoelectrode was coated with a polyaniline film of *ca.* 50 nm thickness upon electro polymerization. Under illumination with a Xe lamp (150 mW cm$^{-2}$) at a bias potential of -1.9 V vs. SCE, the photocathode immersed in a CO$_2$-saturated 0.1 M LiClO$_4$ aqueous solution generated several micromoles of formic acid and formaldehyde as determined by a colorimetric method (Table 7, entry 30).²⁰⁰ The bare photoelectrode did not show any activity towards CO$_2$ reduction. The total faradaic yield reached 20 to 28% even though no methane or methanol could be detected by gas chromatography. In the presence of the V(II)–V(III) chloride redox couple presumably acting as an electron relay, a p-type GaAs photoelectrode was reported to generate formic acid, formaldehyde and methanol in low yields (from 1 to 3% faradaic yields) in an acidic (4 M HCl) aqueous solution under visible light illumination (tungsten–halogen lamp, 980 mW cm$^{-2}$) at a bias potential of -0.5 V vs. SCE and at 50 °C (Table 7, entry 31).²⁰¹

The sequential formation of formic acid (detected by HPLC), formaldehyde (UV-Vis) and methanol (GC) was reported with a bifunctionalized TiO$_2$ film under visible-light irradiation (300 W Xe lamp with a cut-off filter) in acetonitrile solution containing DMPImI electrolyte and the iodide/triiodide couple as a redox mediator.²⁰² The film was separated into two zones, a sensitized area containing a ruthenium complex (N719) as the dye and a catalytic area composed of a pure TiO$_2$ zone. Under illumination, electrons generated in the sensitized zone migrate to the catalytic one through TiO$_2$ particles. This film was used as the reduction half-cell in a H-type reactor with Pt as the anode

material, in order to prevent re-oxidation of CO$_2$ reduction products. Formic acid was generated first, then formaldehyde and methanol, with a respective yield of *ca.* 0.05 mmol cm$^{-2}$ after 5 h (Table 7, entry 32). This yield was enhanced when an external voltage was applied between the reference electrode and the anode thus enabling the regeneration of the redox mediator and consequently of the dye. The effect of the bias potential and the pH on the product distribution was studied with a PEC assembly composed of the Cu/Cu$_2$O electrode irradiated with a 125 W high pressure mercury lamp.²⁰³ In 0.1 M Na$_2$CO$_3$/NaHCO$_3$ electrolyte (pH 9.0) saturated with CO$_2$, a high rate for HCHO was observed at 0 V bias (Table 7, entry 33), whereas methanol was the main product at +0.2 V bias. At the positive potential bias, some HCHO was also observed at pH 8 to 11 as a minor product.

A PEC assembly consisting of a (040)-facet engineered BiVO$_4$ plate as the photoanode (040-BVO) and a Cu plate immersed in NaCl electrolyte as the cathode has been reported to generate various C$_1$ products from CO$_2$ when illuminated with solar light under an external bias potential.²⁰⁴ Depending on the applied potential, the selectivity could be tuned towards a specific product, with a general trend showing that at low potentials, kinetically favourable products are dominant, whereas at high potentials, thermodynamically stable products are dominant. Formaldehyde is produced with 85% faradaic efficiency at an applied potential of 0.90 V vs. RHE, corresponding to a yield of 143 µM h$^{-1}$ (Table 7, entry 34). Very recently, it has been shown that a system combining calcium and iron co-doped TiO$_2$ films as the photoanode and multilayered Cu based dark electrode as the cathode was able to selectively generate formaldehyde and/or acetaldehyde at the cathode surface by tuning the anode bias potential.²⁰⁵ Both electrodes were immersed in a 0.1 NaOH aqueous electrolyte saturated with CO$_2$, and formaldehyde was detected as the only product with a reduced graphene oxide (rGO) coated copper electrode (Table 7, entry 35). The highest yield was 470 µM cm$^{-2}$ after 8 h (25% faradaic efficiency) under solar simulated irradiation with an applied bias of 0.68 V vs. RHE. It is important to note that in the last example $^{13}$C labelled experiments were conducted to confirm the origin of the products.

## 7.3. Solid material approaches

Some studies were also conducted with catalytic solid materials. Two Mo-based heterogeneous catalysts, namely a mixed-valence polyoxomolybdate cluster and composite consisting of a molybdenum keplerate cluster embedded in reduced graphene oxide (RGO), were shown to reduce CO$_2$ and oxidize water at the same time, generating sub-mmol amounts of formic acid as the main product and formaldehyde as the secondary product, as quantified by HPLC.²⁰⁶ Experiments were conducted in pure water with no sensitizer and light irradiation was set at 373 nm (19 mW cm$^{-2}$). The turnover number and frequency for formic acid (not calculated for formaldehyde) were claimed to reach *ca.* 10⁶ and *ca.* 6 × 10² s$^{-1}$, respectively. This study shows the possibility of using cheap metal oxides such as oxometalates as catalytic materials for both CO$_2$ reduction and water oxidation.
## 7.4. Molecular approaches

To the best of our knowledge, only two studies employing a fully molecular approach have been reported. A homogeneous system employing pyridine as a catalyst in aqueous solution in the presence of Ru(phen)₃ photosensitizer, ascorbic acid as an electron donor and KCl as an electrostatic stabilizing agent reported the formation, under 470 nm monochromatic illumination, of formate (NMR quantified) as the main product with methanol (GC-MS) as the minor product and traces of formaldehyde detected by NMR.²⁰⁷ Two ruthenium(II) polypyridyl complexes covalently modified with a pendant pyridyl function have also been shown to be active towards CO₂ reduction under both electrochemical and photochemical conditions in a DMF: water mixture. In the presence of TEA (triethylamine) as a sacrificial donor agent and under 470 nm irradiation, the formation of formate (main product), formaldehyde and methanol (minor) was observed after 1 h irradiation albeit with a very low TON of 16, 7 and 1, respectively.²⁰⁸ The rapid loss of activity was attributed to ligand photolabilization leading to complex degradation. In neither of these examples has the mechanism been elucidated.

## 7.5. Conclusion and perspectives

In conclusion, achieving the selective conversion of CO₂ into formaldehyde (HCHO) using light as the primary, if not the sole, energy source is far from realized, as outlined in Table 7 with key examples. The predominant outcome in the majority of studies involves a product mixture, lacking control over selectivity, with low yields and demonstrating limited mechanistic understanding. The inherent high reactivity of HCHO poses a clear challenge to its detection. Therefore, improvements in analytical detection methodologies are imperative. The use of

visible (solar) light still remains scarce, with most systems requiring UV light.

As perspectives, functionalized materials, in particular associating a photoactive material and molecular tuneable unit, open new possibilities to finely control the local environment of the catalytic site and thus to favour the formaldehyde pathway.

# 8. Enzyme-catalysed CO₂ reduction into formaldehyde

Biological fixation of CO₂ occurs through six major pathways including the Calvin-Benson-Bassham (CBB) cycle which represents the most common pathway.²⁰⁹ Interestingly, the transformation of CO₂ into carbohydrates in the CBB cycle was initially hypothesized to occur *via* a formaldehyde pathway.¹⁸¹,²¹⁰ However, it was later demonstrated that the CBB cycle does not involve the intermediate formation of formaldehyde, but the CO₂ fixation to form a carboxylate which is then further reduced in subsequent steps.²¹¹ It is only with isolated enzymes that HCHO and CH₃OH were obtained from CO₂. The dehydrogenases, formate dehydrogenases (FDHs, EC 1.2.1.2),²¹² formaldehyde dehydrogenase (FaldDH, EC 1.2.1.46)²¹¹ and alcohol dehydrogenase (ADH, EC 1.1.1.1)²¹³ are able to catalyse the reduction of CO₂, HCOOH and HCHO into HCOOH, HCHO and CH₃OH, respectively.¹¹⁶,²¹⁴ Although most of the reports focused on the selective generation of formate, notably because of its implication as an intermediate in the Wood-Ljungdah pathway in acetogens²¹⁵ or methanol,²¹⁶ only a handful of studies focused on the selective generation of formaldehyde. The two-step enzyme cascade combining formate dehydrogenase (FDH) and formaldehyde dehydrogenase (FaldDH) is currently the only reported process (Scheme 51) for the enzymatic conversion of CO₂ into HCHO. Both enzymes are commercially available and

<figure><img src="image_99.png" /><figcaption>Scheme 51 Enzymatic sequential generation of formate and formaldehyde with FDH (formate dehydrogenase) and FaldDH (formaldehyde dehydrogenase).</figcaption></figure>
<table><caption>**Table 8** Conditions and performances of bio-cascade systems for CO₂ reduction into formaldehydeᵃ</caption><thead><tr><th>Entry</th><th>Immobilization</th><th>Substrate</th><th>P or [C]</th><th>NADH regeneration</th><th>Time (h)</th><th>HCHO generation (mmol L<sup>-1</sup>)</th><th>Ref.</th></tr></thead><tbody><tr><td>1</td><td>Free enzymes</td><td>KHCO<sub>3</sub></td><td>100 mM</td><td>No</td><td>72</td><td>0.060</td><td>217</td></tr><tr><td>2</td><td>Free enzymes</td><td>CO<sub>2(g)</sub></td><td>0.5 MPa</td><td>No</td><td>12</td><td>0.901</td><td>218</td></tr><tr><td>3</td><td>HDMMC-based system</td><td>CO<sub>2(g)</sub></td><td>0.3 MPa</td><td>No</td><td>8</td><td>0.022</td><td>219</td></tr><tr><td>4</td><td>TiO<sub>2</sub>-NPs</td><td>CO<sub>2(g)</sub></td><td>0.3 MPa</td><td>No</td><td>4</td><td>—</td><td>220</td></tr><tr><td>5</td><td>NPSCs</td><td>CO<sub>2(g)</sub></td><td>0.3 MPa</td><td>No</td><td>4</td><td>0.125</td><td>221</td></tr><tr><td>6</td><td>MCF-MP</td><td>KHCO<sub>3</sub></td><td>200 mM</td><td>No</td><td>—</td><td>0.037</td><td>222</td></tr><tr><td>7</td><td>3% TCPP@ZIF-8</td><td>NaHCO<sub>3</sub></td><td>10 μM</td><td>Yes</td><td>8</td><td>0.008</td><td>223</td></tr><tr><td>8</td><td>PE-HFMs</td><td>CO<sub>2(g)</sub></td><td>3 mL min<sup>-1</sup></td><td>Yes</td><td>4</td><td>0.034</td><td>197</td></tr></tbody></table>

ᵃ HMDCs = hybrid double membrane microcapsules, NPs = nanoparticles, NPSCs = nanoparticle-stabilized capsules, MCF-MP = siliceous mesostructured cellular foams functionalized with mercaptopropyl groups, TCPP = 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin, ZIF = zeolite-like imidazole framework material, PE-HFMs = polyethylene hollow fibre membranes.

have similar pH and temperature optima. Each step of the cascade is endowed with a 2e⁻ reduction of CO₂ and requires one equivalent of NADH (nicotinamide adenine dinucleotide hydride) as a co-factor, serving as the reductant. Two molecules of NADH are thus oxidized into the corresponding NAD⁺ during the biocatalyzed reduction of CO₂ to formaldehyde.

The main parameters and performances of these selective catalytic systems are summarized in Table 8. The results are described in three sections: (i) optimized reaction conditions with free enzyme systems, (ii) immobilized and compartmentalized enzymes and, finally, (iii) systems coupled to the NADH regeneration process.

## 8.1. Optimization of the reaction conditions with free enzyme systems

Studies have shown that FDH/FaldDH ratio lower than 1 is beneficial for the production of formaldehyde over formate since the formate is a good substrate for the FDH (Table 8, entry 1).²¹⁷ In the same vein, an excess of NADH (NADH/NAD⁺ molar ratio > 2000) was also found necessary to drive the reaction. Under optimized conditions, 60 µM of formaldehyde was produced from KHCO₃ instead of CO₂ in 72 h with 15 g L⁻¹ of FaldDH and 1 g L⁻¹ of FDH. The formaldehyde concentration was quantified using a colorimetric test (Nash reagent)¹⁴⁹ as it was found that indirect detection through UV quantification of NADH disappearance could be erroneous due to interaction with CO₂. Following this study, the same cascade was explored with gaseous CO₂ (Table 8, entry 2).²¹⁸ Higher amount of FaldDH as compared to FDH was again necessary and the study disclosed the positive impact of a high CO₂ pressure (from 0.2 to 0.5 MPa) to generate a high amount of formaldehyde. Under optimized conditions, 901 µM of formaldehyde was produced (0.5 MPa of CO₂) after 12 h. A plateau was found at 10–12 h before a net decrease of formaldehyde, tentatively explained by the consumption of formaldehyde *via* the reverse reaction (*i.e.*, oxidation of HCHO into CO₂) and/or the instability of formaldehyde in the reaction medium.

## 8.2. Enzyme immobilization and compartmentalization

Immobilized systems were explored to improve the performances of the FDH/FaldDH cascade with the aim to increase

enzyme stability, activity²²⁴ and reusability compared to the enzymes freely diffusing systems. FDH and FaldDH were immobilized and spatially separated at organic–inorganic hybrid double membrane microcapsules (HDMMCs) (Table 8, entry 3).²¹⁹ FDH was encapsulated in the lumen of the HDMMCs while FaldDH was encapsulated in the intermembrane space. The study showed an improved activity with formaldehyde production of 22 µmol compared to the control experiment with free enzymes (9 µmol). The same group encapsulated FDH in Ti nanoparticles (NPs) while FaldDH was immobilized at the surface of the particles (Table 8, entry 4).²²⁰ The size of the NPs (from 75 to 375 nm) was shown to have a significant impact on the reaction. The best performances were obtained with NP size of 75 nm. The recycling stability of the enzyme-containing NPs was evaluated and displayed a loss of half of the initial performance after 10 cycles. It was improved in a following report describing the preparation of nanoparticle-stabilized capsules (NPSCs) containing FDH entrapped in the capsule and FaldDH conjugated on the capsule surface (Table 8, entry 5).²²¹ Furthermore, the distance between both enzymes was evaluated using Förster resonance energy transfer (FRET) analysis on the enzyme labelled with carbocyanine dyes (Table 8, entry 6).²²² While no detectable FRET was observed free in the enzyme system with an estimated distance of 40 nm between the two enzymes, co-immobilization of the enzymes in the silica materials displayed an increased transfer efficiency >50% with an estimated distance of less than 10 nm. This feature was proposed to be responsible for the enhanced activity in the particles compared to the enzyme free system, due to probability increase of direct substrate transfer between the two enzymes.

## 8.3. NADH regeneration

NADH is a co-factor that is regenerated in biological systems. When implemented *in vitro*, its stoichiometric use negatively impacts the atom-efficiency of any given transformation. The regeneration of NADH from NAD⁺ has thus been the subject of intense investigation with the development of bio-, electro- and photo-regeneration systems.²²⁵ In the case of the FDH/FaldDH cascade reaction transforming CO₂ into formaldehyde, only two reports described the combination of the cascade with a regeneration process. FDH and FaldDH were co-immobilized in the cavities of the zeolitic imidazolate framework-8 (ZIF-8)

<figure><img src="image_100.png" /></figure>
combined with 5,10,15,20-tetrakis(4-carboxyphenyl) porphyrin (TCPP) as a photosensitizer fixed to the surface of the zeolite (Table 8, entry 7).<sup>223</sup> Triethanolamine (TEOA) was used as an electron donor, Cp*Rh(bpy)Cl (M, Cp* = pentamethylcyclopentadienyl, bpy = bipyridine) as an electron mediator and water as a proton donor. Under optimum conditions (1 mg mL<sup>-1</sup> 3% TCPP@ZIF-8, pH = 8.0) the NADH regeneration reached 75% yield after 3 h under visible-light exposure. Combining this regeneration system with FDH/FaldDH (2:1 ratio) afforded the conversion of 10 µM of NaHCO<sub>3</sub> into 7.74 µM of formaldehyde (conversion rate 77%) after 8 h under visible-light exposure. The use of titanium dioxide (TiO<sub>2</sub>) in a photocatalytic system<sup>182</sup> was also probed with immobilized FDH/FaldDH on the surface of polyethylene (PE) hollow fibre membranes (HFMs) (Table 8, entry 8).<sup>197</sup> Despite side reactions due to the known ability of the UV/TiO<sub>2</sub> system to photoreduce CO<sub>2</sub> into various products (e.g., CO, HCOOH, HCHO, CH<sub>3</sub>OH, CH<sub>4</sub>),<sup>182</sup> NADH regeneration was observed and 34 µM of formaldehyde was generated under the best conditions (ratio FDH: FaldDH = 1:0.3, CO<sub>2</sub> 3 mL min<sup>-1</sup>, H<sub>2</sub>O as the electron donor, PB buffer, pH 7.0, [NADH] = 1 mmol L<sup>-1</sup>, exposure to two 23 W UV lamps at λ = 365 nm).

## 8.4. Conclusion and perspectives

In conclusion, the enzymatic conversion of CO<sub>2</sub> into formaldehyde is still at an early stage of development. Only a few reports have highlighted the selective formation of formaldehyde in cascade reactions involving FDH and FaldDH. Strategies for enzyme immobilization were identified to enhance both the reusability and activities of FDH and FaldDH when compared to free enzyme systems.

As perspectives, discovering more active and/or robust enzymes from diverse organisms or engineering existing enzymes for improved stability and activity is crucial for advancing current strategies. Additionally, the development of

efficient co-factor regeneration systems is essential to establish an energetically sustainable and cost-effective process. The design of an effective co-immobilized system for enzymes coupled with a co-factor regeneration process remains undisclosed. An attractive approach involves substituting the natural co-factor NADH with a more sustainable electron and proton supplier system, as previously demonstrated in the biocatalyzed generation of formate or methanol from CO<sub>2</sub>.<sup>11b,213</sup> Similarly, electrochemically driven enzymatic systems represent a promising avenue. Finally, the biocatalyzed four-electron reduction of CO<sub>2</sub> to formaldehyde has yet to be explored in subsequent transformations. While such processes are enticing, the undefined form taken by the generated formaldehyde and its instability in the enzymatic reaction medium have so far hindered its isolation or utilization in subsequent transformations for the synthesis of more complex products.

# 9. General conclusions

In this comprehensive review, we have examined the reduction of CO<sub>2</sub> with four electrons, leading to the production of formaldehyde and acetal derivatives through thermal (hydrogenation or hydroelementation reactions), electrochemical, photoelectrochemical, and bio-driven processes. Formaldehyde holds considerable appeal for both energy carrier applications and use as a chemical feedstock. Particularly noteworthy is its versatility for the latter application compared to formic acid, methanol, or methane obtained from the CO<sub>2</sub> reduction reaction (CO<sub>2</sub>RR). Despite its promising attributes, synthesizing and isolating formaldehyde from the CO<sub>2</sub>RR remains significantly more challenging than the aforementioned C<sub>1</sub> compounds. To date, only a limited number of systems have been reported to generate formaldehyde from CO<sub>2</sub> as the major product, and in many cases, conclusive evidence regarding the origin of formaldehyde is lacking. The most notable performances of these systems are summarized in Table 9.

<table><caption>**Table 9** Best catalytic performances of the different reduction systems reported for the generation of formaldehyde from electro-, photo-electrochemical, enzymatic and hydrogenation processes and further use as a C<sub>1</sub> source in subsequent transformations</caption><thead><tr><th>Reduction system</th><th>Hydrogenation</th><th>Electroreduction</th><th>Photoelectroreduction</th></tr></thead><tbody><tr><td>Yield</td><td>0.037 M g<sub>cat</sub><sup>-1</sup> h<sup>-1</sup></td><td></td><td>400–500 µmol h<sup>-1</sup> g<sub>cat</sub><sup>-1</sup> (1 bar CO<sub>2</sub>)<br>16 500 µmol h<sup>-1</sup> g<sub>cat</sub><sup>-1</sup> (7 bars CO<sub>2</sub>)</td></tr><tr><td>TON</td><td>—</td><td>10<sup>4</sup></td><td></td></tr><tr><td>Selectivity (%)</td><td>—</td><td>90</td><td>60–70</td></tr><tr><td>Faradaic efficiency (%)</td><td>n.a</td><td>85–90</td><td>NA</td></tr><tr><td>Current density (mA cm<sup>-2</sup>)</td><td>n.a</td><td>0.1–0.2</td><td>NA</td></tr><tr><td>C<sub>1</sub> source</td><td>X</td><td>X</td><td>CH<sub>2</sub>-N</td></tr><tr><td>C<sub>n</sub> source</td><td>X</td><td>X</td><td>X</td></tr><tr><td>Asymmetric C center</td><td>X</td><td>X</td><td>X</td></tr></tbody></table>

<figure><img src="image_101.png" /></figure>