# Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

Loris Geminiani, Kathrin Junge, Matthias Beller, Jean-François Soulé

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Loris Geminiani, Kathrin Junge, Matthias Beller, Jean-François Soulé. Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives. Beilstein Journal of Organic Chemistry, 2025, 21, pp.2234-2242. 10.3762/bjoc.21.170. hal-05354014

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# Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

Loris Geminiani¹,², Kathrin Junge*², Matthias Beller*² and Jean-François Soulé*³

Full Research Paper

Open Access

Address:

¹Univ Rennes, CNRS, ISCR-UMR 6226, F-35000 Rennes, France,

²Leibniz Institut für Katalyse, Albert Einstein Straße 18059 Rostock,
Germany and ³Chimie ParisTech, PSL University, CNRS, Institute of
Chemistry for Life and Health Sciences, 75005 Paris, France

Email:

Kathrin Junge* - kathrin.junge@catalysis.de; Matthias Beller* -
matthias.beller@catalysis.de; Jean-François Soulé* -
jean-francois.soule@chimieparistech.psl.eu

Keywords:

azo compounds; cross-coupling; domino catalysis; palladium;
phosphine ligands

Beilstein J. Org. Chem. **2025**, *21*, 2234–2242.
https://doi.org/10.3762/bjoc.21.170

Received: 04 July 2025

Accepted: 30 September 2025

Published: 22 October 2025

Associate Editor: M. Desage-El Murr

<figure><img src="image_3.png" /></figure>

© 2025 Geminiani et al.; licensee Beilstein-Institut.
License and terms: see end of document.

## Abstract

Azobenzenes are photoresponsive compounds widely used in molecular switches, light-controlled materials, and sensors, but despite extensive studies on symmetric derivatives, efficient methods for synthesizing non-symmetric analogues remain scarce due to regioselectivity issues, multistep procedures, and limited applicability to tetra-*ortho*-substituted structures. Herein, we describe a direct, one-pot Pd-catalyzed dehydrogenative C–N coupling between aryl bromides and arylhydrazines to access non-symmetric azobenzenes. The use of bulky phosphine ligands and sterically tuned substrates promotes selective N-arylation at the terminal nitrogen. The protocol tolerates a wide range of functional groups and enables the synthesis of well-decorated azobenzenes, including tetra-*ortho*-substituted derivatives. Notably, the reaction proceeds under an O₂ atmosphere and in the presence of water, highlighting its robustness.

## Introduction

Azobenzenes are a widely studied class of compounds known for their distinctive photoresponsive properties, rendering them valuable in a variety of applications, including molecular switches, sensors, and light-controlled materials [1-8]. The photoswitching behavior arises from the reversible photoisomerization between the *E*- and *Z*-forms of the azobenzene

chromophore, driven by the isomerization of the N–N double bond. This photoswitching event involves a molecular size reduction between the *E*- and *Z* isomers, thereby driving structural changes that enable applications in molecular machines, biological allosteric modulators, and advanced functional materials (Figure 1a) [9-11]. Despite the widespread interest in

<footnote>* Corresponding author</footnote>
<figure><img src="image_4.png" /><figcaption>**Figure 1:** General overview of azobenzene chemistry. a) Selected examples and photoisomerization of azobenzenes; b) previous Pd-catalyzed methods for the synthesis of non-symmetric azobenzenes; c) this work: Pd-catalyzed dehydrogenative C–N coupling of arylhydrazine.</figcaption></figure>

azobenzenes, most synthetic methods have focused on the preparation of symmetric derivatives [12,13]. Traditional approaches, such as oxidative coupling of anilines [14-19], reducing coupling of nitroarenes [20-23], or cross-coupling between anilines and nitroarenes have proven efficacious but face significant challenges when applied to non-symmetric systems [24], particularly in achieving regioselectivity. These methods frequently require a particular reagent pair or an excess of one reactant, which limits their efficiency and versatility. In contrast, Baeyer–Mills reactions, which rely on nitroso-aniline couplings, provide a route for the synthesis of non-symmetric azobenzenes, but their substrate specificity and use of hazardous precursors limit their practical applicability [25-28]. An alternative approach involves the S<sub>E</sub>Ar reaction, which utilizes potentially hazardous diazonium salts and electron-rich arenes (mainly limited to phenols) [29-31], including metalated arenes [32,33].

The growing demand for structurally complex compounds across diverse applications has rendered the synthesis of non-symmetrical azoarenes with differently substituted azo bonds intricate and inefficient using these standard synthetic protocols. The transition-metal-catalyzed C–N bond formation has

emerged as a viable route to access non-symmetric azobenzenes, owing to the broad functional group tolerance of Buchwald–Hartwig amination reactions [34-40]. Kong and co-workers developed a Chan–Evans–Lam-type oxidative cross-coupling reaction between N-arylphthalic hydrazides and arylboronic acids using copper catalysis [41]. Similarly, in 2003, Lee and co-workers introduced a desymmetrization approach employing simpler N=N precursors, specifically N-protected hydrazines. Their method involved a three-step process comprising Cu and Pd-catalyzed C–N bond formations followed by a dehydrogenative deprotection step (Figure 1b, top) [42]. This desymmetric approach was further employed by Oestreich and co-workers in 2022, who introduced silicon-masked diazenyl anions in a Pd-catalyzed three-step sequence to access a wide range of non-symmetric azobenzenes (Figure 1b, bottom) [43,44].

Inspired by these approaches and building on recent advances in the dehydrogenation of 1,2-diarylhydrazines to azobenzenes [45-50], we developed a one-pot strategy for synthesizing non-symmetric azobenzenes via a Pd-catalyzed cascade involving C–N coupling of arylhydrazines with aryl bromides, followed by oxidative dehydrogenation (Figure 1c). As our study was
nearing completion, Váňa and co-workers disclosed a related Buchwald–Hartwig approach employing the Pd(OAc)₂/BINAP catalytic system [51], which enabled selective C–N coupling at the terminal nitrogen and suppressed denitrogenative by-products [52–54]. Although the general strategy is similar, our method uses the [PdCl(C₃H₅)]₂/t-BuXPhos catalytic system, which provided higher yields and broader substrate scope (functional group tolerances), including challenging tetra-ortho-substituted azobenzenes.

## Results and Discussion

We started our investigation by using phenylhydrazine (1a) and 2-bromotoluene (2a) as model substrates. In the beginning,

standard Buchwald amination conditions were tested ([PdCl(allyl)]₂, XPhos, t-BuONa in 1,2-dimethoxyethane (DME)) [55]. The reaction outcomes were analyzed with both GC/MS and GC/FID analysis. Under these conditions, we were pleased to find that 1-phenyl-2-(o-tolyl)diazene (3a) was obtained with a GC yield of 50% (Table 1, entry 1). While all starting materials were consumed, various impurities, including biphenyls, diarylamines, aniline, and toluidine, were formed in varying amounts. Since a final dehydrogenation step is required to complete the reaction, the experiment was repeated with various oxidants tested as additives. The use of di-tert-butyl peroxide as an oxidant, combined with NaH as the base, increased the formation of 3a, achieving GC yields of up to 65%

<figure><img src="image_5.png" /><figcaption>**Table 1:** Selected optimization of conditions for the synthesis of azobenzene from phenylhydrazine and aryl bromides. The gray box provides a detailed list of all identified side-products.</figcaption></figure>

<figure><img src="image_6.png" /></figure>

<table><thead><tr><th>Entry</th><th>2a, 2b or 2c</th><th>Phosphine</th><th>Base</th><th>Additive</th><th>H<sub>2</sub>O (equiv)</th><th>Yield [%] in 3<sup>a</sup></th></tr></thead><tbody><tr><td>1<sup>b</sup></td><td>2a</td><td>XPhos</td><td>t-BuONa</td><td>no additive</td><td>0</td><td>50</td></tr><tr><td>2<sup>b</sup></td><td>2a</td><td>XPhos</td><td>NaH 60%</td><td>no additive</td><td>0</td><td>62</td></tr><tr><td>3<sup>b</sup></td><td>2a</td><td>XPhos</td><td>NaH 60%</td><td>t-Bu-O-O-t-Bu</td><td>0</td><td>65</td></tr><tr><td>4<sup>b</sup></td><td>2b</td><td>XPhos</td><td>NaH 60%</td><td>t-Bu-O-O-t-Bu</td><td>0</td><td>0</td></tr><tr><td>5<sup>b</sup></td><td>2a</td><td>P(t-Bu)<sub>3</sub></td><td>NaH 60%</td><td>t-Bu-O-O-t-Bu</td><td>0</td><td>51</td></tr><tr><td>6<sup>b</sup></td><td>2b</td><td>P(t-Bu)<sub>3</sub></td><td>NaH 60%</td><td>t-Bu-O-O-t-Bu</td><td>0</td><td>19</td></tr><tr><td>7<sup>b</sup></td><td>2a</td><td>t-BuXPhos</td><td>NaH 60%</td><td>t-Bu-O-O-t-Bu</td><td>0</td><td>27</td></tr><tr><td>8<sup>b</sup></td><td>2b</td><td>t-BuXPhos</td><td>NaH 60%</td><td>t-Bu-O-O-t-Bu</td><td>0</td><td>26</td></tr><tr><td>9<sup>b</sup></td><td>2a</td><td>t-BuXPhos</td><td>Cs<sub>2</sub>CO<sub>3</sub></td><td>t-Bu-O-O-t-Bu</td><td>0</td><td>62</td></tr><tr><td>10<sup>c,d</sup></td><td>2a</td><td>t-BuXPhos</td><td>Cs<sub>2</sub>CO<sub>3</sub></td><td>t-Bu-O-O-t-Bu</td><td>0</td><td>64</td></tr><tr><td>11<sup>c,d</sup></td><td>2a</td><td>t-BuXPhos</td><td>Cs<sub>2</sub>CO<sub>3</sub></td><td>t-Bu-O-O-t-Bu</td><td>2</td><td>71</td></tr><tr><td>12<sup>c,d</sup></td><td>2c</td><td>t-BuXPhos</td><td>Cs<sub>2</sub>CO<sub>3</sub></td><td>t-Bu-O-O-t-Bu</td><td>0</td><td>4</td></tr><tr><td>13<sup>c,d</sup></td><td>2c</td><td>t-BuXPhos</td><td>Cs<sub>2</sub>CO<sub>3</sub></td><td>t-Bu-O-O-t-Bu</td><td>2</td><td>69</td></tr><tr><td>14<sup>c,d,e,f</sup></td><td>2a</td><td>t-BuXPhos</td><td>Cs<sub>2</sub>CO<sub>3</sub></td><td>no additive</td><td>2</td><td>up to 77 (75%)</td></tr><tr><td>15<sup>c,d,e,f,g</sup></td><td>2a</td><td>t-BuXPhos</td><td>Cs<sub>2</sub>CO<sub>3</sub></td><td>no additive</td><td>2</td><td>71</td></tr><tr><td>16<sup>c,d,e,f,h</sup></td><td>2a</td><td>t-BuXPhos</td><td>Cs<sub>2</sub>CO<sub>3</sub></td><td>no additive</td><td>2</td><td>72</td></tr></tbody></table>

<footnote><sup>a</sup>Yields determined by GC/FID analysis using tetradecane as an internal standard, with isolated yields shown in parentheses. <sup>b</sup>Reactions performed on a 0.5 mmol scale in 1 mL of DME. <sup>c</sup>Reactions performed in 1 mL of DME (1 M). <sup>d</sup>New batch of Cs₂CO₃ dry. <sup>e</sup>Under O₂ atmosphere (100 mL, 0.84 mmol). <sup>f</sup>2 h. <sup>g</sup>Using 1.5 equiv of 1a. <sup>h</sup>Using 1.5 equiv of 2a.</footnote>
(Table 1, entry 3). Control experiments demonstrated that palladium, phosphine, and base were all essential for this reaction (Table S4 in Supporting Information File 1). However, under identical conditions with other aryl bromides like 4-bromotoluene, the reaction failed to form azobenzene **3b**, instead yielding 1-phenyl-1-(p-tolyl)hydrazine, resulting from arylation of the central nitrogen (Table 1, entry 4 and Supporting Information File 1). This unexpected result prompted us to further optimize the reaction conditions, with particular focus on the choice of ligand, especially for non-ortho-substituted aryl bromides as substrates. Notably, the use of bulkier phosphines, such as P(t-Bu)₃ and t-BuXPhos, was found to promote the reaction regardless of the substitution pattern of the bromotoluene (Table 1, entries 5–8). For subsequent optimizations, we selected t-BuXPhos for practical reasons, as it is less sensitive to oxidative conditions. Further optimization revealed that Cs₂CO₃ is more efficient than NaH for this reaction (Table 1, entry 9). However, reactions conducted with a new batch of Cs₂CO₃ showed a dramatic reduction in product yield (Table 1, entry 12). Control experiments with varying amounts of water (0–10 equiv) demonstrated that a small amount of water is crucial for the reaction (Supporting Information File 1, Table S7 and Table 1, entry 11). This effect, previously reported in Buchwald–Hartwig reactions, enhances yield by facilitating the reduction of Pd(II) to Pd(0) and improving the solubility of the base [56]. To ensure the generality of the conditions, 1-bromo-2-(trifluoromethoxy)benzene was also tested, yielding the desired azobenzene **3c** in 69% yield with the addition of 2 equivalents of water (Table 1, entries 12 and 13). Finally, the

oxidant t-Bu-OO-t-Bu could be replaced by O₂, yielding compound **3a** with GC yields of up to 79% (Table 1, entry 14, 75% isolated yield). In reactions giving <70% isolated yield, no single side-product dominates; the missing mass is apportioned among several minor by-products (and small handling losses), with no evidence for a favored competing pathway. Notably, this work led to the development of a reaction protocol that operates without the need for inert conditions and tolerates small amounts of water, simplifying practical implementation. We finally evaluated 1.5 equivalents of either aryl bromide or phenylhydrazine and observed no gain in yield (differences within experimental error) (Table 1, entries 15 and 16); accordingly, we retained a 1:1 stoichiometry, which maximizes atom economy, lowers PMI/E-factor by avoiding excess reagent, and simplifies purification and scale-up.

With the most suitable reaction conditions in hand, the substrate scope was examined. First, the reactivity of different aryl bromides with phenylhydrazine (**1a**) to form non-symmetric azobenzene was explored (Scheme 1). Most of the azobenzenes were obtained in purified yields between 70 and 85%. Various functional groups at the *ortho*- or *para*-position were well tolerated in this reaction, including electron-withdrawing groups such as trifluoromethoxy (**3c**, 69%), nitrile (**3e**, 81%), methyl ester (**3h**, 74%), N,N-dimethylamide (**3i**, 73%) and nitro (**3j**, 35%), as well as electron-donating groups such as methoxy (**3d**, 77%), dimethylamino (**3k** 55%), and thiomethoxy (**3l**, 71%). Moreover, the reaction tolerated C–F (**3f**, 86%) and C–Cl (**3g**, 66%) bonds, enabling orthogonal functionalization. It should be

<figure><img src="image_7.png" /><figcaption>**Scheme 1:** Scope of aryl bromides in palladium-catalyzed dehydrogenative C–N coupling with phenylhydrazine (**1a**). <sup>a</sup>Using 2 equiv of **1a**.</figcaption></figure>
noted that, as a general trend – and in contrast to classic Buchwald–Hartwig couplings – aryl bromides with substituents at the *ortho*-position (**3a** and **3c–g**) are more reactive than those with substituents at the *para*-position (**3b** and **3h–l**). This difference might be explained by steric repulsion, which may favor C–N-bond coupling with the terminal nitrogen over the internal nitrogen. From phenylhydrazine and phenyl bromide, azobenzene (**3m**) was isolated in 43% yield. Substituent placed at the *meta*-position did not affect the reaction yield, as azobenzenes **3n** and **3o** are isolated in 84% and 78% yield, respectively. Interestingly, 3-bromopyridine also proved to be a suitable coupling partner, enabling the preparation of azoarene **3p** in 70% yield. Moreover, starting from 1,4-dibromobenzene and 2 equivalents of **1a**, a double reaction occurred, enabling the one-step synthesis of 1,4-bis[(E)-2-phenyldiazenyl]benzene (**3q**) in high yield.

We next investigated the scope of arylhydrazines to assess their compatibility under the optimized reaction conditions (Scheme 2). While some arylhydrazines are commercially available, it was observed that their hydrochloride salts were ineffective, even with the addition of excess base. Examining the substituent effects, *para*-substituted hydrazines such as *p*-*(trifluoromethyl)phenylhydrazine (1b) and *p*-chlorophenylhydrazine (1c) reacted efficiently with 2-bromotoluene to deliver the corresponding azobenezenes **4a** and **4d** in 78% and 37% yield, respectively. Notably, 2-tolylhydrazine (1d) exhibited good reactivity, yielding **4c** in 63%. Additionally, 2-fluorophenylhydrazine provided the product in 55% yield, while 2-chloro-5-(trifluoromethyl)phenylhydrazine furnished the desired compound **4e** in a moderate yield of 32%. The lower yields ob-

served with substrates containing a C–Cl bond may be attributed to the competitive Pd-catalyzed side-reaction.

As shown above, the steric hindrance plays a significant role in driving the reaction. For this reason, we have applied our novel Pd methodology to synthesize a series of tetra-, tri-, and di-*ortho*-substituted azobenzenes (Scheme 3). Notably, this method demonstrates remarkable efficiency, as the reaction proceeds smoothly even when both coupling partners possess sterically hindered substituents at the 2,6-positions. For example, the coupling of 2,6-difluorophenylhydrazine with 1-bromo-2,6-dimethoxybenzene yielded tetra-*ortho*-substituted azobenzene **5a** in a notable yield of 63%, surpassing the performance of traditional approaches in similar contexts. Similarly, tri-*ortho*-substituted azobenzenes **5b** and **5c** were prepared in 42% and 47% yields, respectively. However, the isolation of these compounds in pure form remains challenging due to contamination with biphenyl side-products. Finally, di-*ortho*-substituted azobenzene **5d** was also successfully prepared using this approach, achieving an excellent yield of 80%.

The mechanism of the reaction was further outlined to explain the formation of all identified main and side-products (Figure 2). A two-step cascade Pd-catalyzed reaction is proposed. In the first step a C–N-coupling reaction with phenylhydrazine occurs [57]. The catalytic cycle starts by the formation of Pd(0) in situ through reduction facilitated by phosphine and water [58]. This is followed by the oxidative addition of aryl bromides, leading to the formation of the Pd(II)–aryl intermediate (B). Subsequently, ligand exchange occurs, generating hydrazido complexes C and C'. When bulky substituents are

<figure><img src="image_8.png" /><figcaption>**Scheme 2:** Scope of arylhydrazines in palladium-catalyzed dehydrogenative C–N coupling with 2-bromotoluene (2a).</figcaption></figure>
$$ \chemfig{R^1-NH_2-[1]}
\quad
\chemfig{R^1-NH-[1]}
\quad
\chemfig{R^1-[1]} $$

1 (1 equiv)

+

$$ \chemfig{R^{(2)}-Br-[2]}
\quad
\chemfig{R^{(2)}} $$

2 (1 equiv)

$$ \begin{array}{c} \underset{\text{t-BuXPhos}}{[\text{PdCl(allyl)}]_2} \text{ (1 mol \%)} \\ \xrightarrow{\text{Cs}_2\text{CO}_3 \text{ (2 equiv)}} \\ \xrightarrow{\text{H}_2\text{O} \text{ (2 equiv)}} \\ \text{DME, 90 °C, 15 h} \\ \text{O}_2 \text{ (1 atm)} \end{array} $$

$$ \chemfig{R^{(2)}-N=N-[R^{(1)}]}
\quad
\chemfig{R^{(1)}} $$

5a-d

$$ \chemfig{F-[F]N=N-[O-CH_2CH_2CH_2CH_2O-[F]]}
\quad
\chemfig{F-[F]N=N-[O-CH_2CH_2CH_2CH_2O-[Me]]} $$

5a 63%

$$ \chemfig{F-[F]N=N-[O-CH_2CH_2CH_2CH_2O-[F]]}
\quad
\chemfig{F-[F]N=N-[O-CH_2CH_2CH_2CH_2O-[F]]} $$

5b 42%

$$ \chemfig{F-[F]N=N-[O-CH_2CH_2CH_2CH_2O-[Me]]}
\quad
\chemfig{F-[F]N=N-[O-CH_2CH_2CH_2CH_2O-[Me]]} $$

5c 47%

$$ \chemfig{F-[F]N=N-[O-CH_2CH_2CH_2CH_2O-[F]]}
\quad
\chemfig{F-[F]N=N-[O-CH_2CH_2CH_2CH_2O-[F]]} $$

5d 80%

**Scheme 3:** Application to the synthesis of tetra-, tri or di-**ortho**-substituted azobenzenes via palladium-catalyzed dehydrogenative C–N coupling.

<figure><img src="image_9.png" /><figcaption>**Figure 2:** a) Proposed catalytic cycle for the one-pot palladium-catalyzed dehydrogenative C–N coupling for the synthesis of azobenzene from aryl-hydrazine and aryl bromide. b) Proposed chemical pathway for azobenzene synthesis, including side-product formation as determined by GC/MS analysis.</figcaption></figure>

<footnote>ᵃIsolated with 85–95% purity.</footnote>
present on the phosphine ligand and/or (both) coupling partner(s) has *ortho*-substituent(s), the hydrazido complex C, chelating on the terminal nitrogen, is preferentially formed to minimize steric clashes. Finally, reductive elimination leads to the formation of *N*,*N*-diarylhydrazine (D), which has been identified and characterized during the optimization process (see Supporting Information File 1 for details). In a second catalytic cycle, the *N*,*N*-diarylhydrazine (D) undergoes dehydrogenation via a mechanism involving Pd and O₂, similar to the process reported by Huang and co-workers [59]. Initially, Pd(0) species E is oxidized to Pd(II) by O₂, forming a Pd-peroxo complex F [60]. Subsequently, ligand exchange occurs between the deprotonated *N*,*N*-diarylhydrazine and carbonate, yielding the Pd(II) intermediate G. This intermediate then undergoes β–H elimination to afford the desired azobenzene product, along with a Pd(II) species H. Finally, reductive elimination regenerates Pd(0), completing the catalytic cycle. Then, a general reaction pathway for the formation of product and side-products is presented in Figure 2B. The first reaction to be inhibited is the Pd-catalyzed denitrogenative cross-coupling, which leads to the formation of an array of biphenyl products [52–54]. This can be controlled by selecting appropriate catalysts and solvents. For instance, PdCl(allyl)₂ in DME with strong base (Cs₂CO₃) favors C–N-bond coupling, which may yield products resulting from arylation at either the terminal or internal nitrogen atoms. The selectivity can be influenced by the steric hindrance of the phosphine ligands and/or the substrates. Once *N*,*N*-diarylhydrazine is formed, minimizing the disproportionation side-reaction [61] becomes crucial, as this reaction produces the desired azobenzene along with equimolar amounts of aniline partners. These aniline derivatives can further participate in Pd-catalyzed cross-coupling, generating a range of diarylamines as side-products. The presence of oxidants such as O₂ mitigates this pathway by promoting oxidative dehydrogenation as the dominant pathway.

## Conclusion

In summary, we have developed robust and efficient conditions for the preparation of azobenzenes via C–N coupling and dehydrogenation, employing [PdCl(C₃H₅)]₂ with *t*-BuXPhos to promote selective C–N-bond formation. This approach makes use of commercially available starting materials and displays broad functional group tolerance. Notably, it enables access to sterically demanding tetra-*ortho*-substituted azobenzenes in moderate to good yields. The results demonstrate that arylhydrazines can serve as practical amine partners in Pd-catalyzed C–N coupling reactions, with regioselectivity toward arylation of the less nucleophilic terminal nitrogen governed by the steric profile of the substrates and the choice of phosphine ligand. These conditions represent a valuable addition to existing methodologies and open further opportunities for appli-

cations in molecular probe design, functional materials, and photoresponsive systems, where *ortho*-substitution is often critical.

## Supporting Information

### Supporting Information File 1

Details of optimization experiments, full characterization data, and NMR spectra (¹H, ¹³C, ¹⁹F) for all products. [https://www.beilstein-journals.org/bjoc/content/supplementary/1860-5397-21-170-S1.pdf]

## Funding

L.G. gratefully acknowledges Région Bretagne for the Ph.D. fellowship provided through the ARED program.

## Author Contributions

Loris Geminiani: conceptualization; data curation; investigation; methodology; writing – original draft. Kathrin Junge: supervision; writing – review & editing. Matthias Beller: funding acquisition; resources; supervision; writing – review & editing. Jean-François Soulé: conceptualization; data curation; funding acquisition; resources; supervision; writing – review & editing.

## ORCID® iDs

Jean-François Soulé - https://orcid.org/0000-0002-6593-1995

## Data Availability Statement

All data that supports the findings of this study is available in the published article and/or the supporting information of this article.

## Preprint

A non-peer-reviewed version of this article has been previously published as a preprint: https://doi.org/10.3762/bxiv.2025.45.v1

## References

1. Yesodha, S. K.; Sadashiva Pillai, C. K.; Tsutsumi, N. *Prog. Polym. Sci.* **2004**, *29*, 45–74. doi:10.1016/j.progpolymsci.2003.07.002

2. Bandara, H. M. D.; Burdette, S. C. *Chem. Soc. Rev.* **2012**, *41*, 1809–1825. doi:10.1039/c1cs15179g

3. Marturano, V.; Ambrogi, V.; Bandeira, N. A. G.; Tylkowski, B.; Giamberini, M.; Cerruti, P. *Phys. Sci. Rev.* **2017**, *20170138*. doi:10.1515/psr-2017-0138

4. Tylkowski, B.; Trojanowska, A.; Marturano, V.; Nowak, M.; Marciniak, L.; Giamberini, M.; Ambrogi, V.; Cerruti, P. *Coord. Chem. Rev.* **2017**, *351*, 205–217. doi:10.1016/j.ccr.2017.05.009

5. Crespi, S.; Simeth, N. A.; König, B. *Nat. Rev. Chem.* **2019**, *3*, 133–146. doi:10.1038/s41570-019-0074-6

6. Jerca, F. A.; Jerca, V. V.; Hoogenboom, R. *Nat. Rev. Chem.* **2022**, *6*, 51–69. doi:10.1038/s41570-021-00334-w
7. Dudek, M.; Kaczmarek-Kędziera, A.; Deska, R.; Trojnar, J.; Jasik, P.; Młynarz, P.; Samoć, M.; Matczyszyn, K. J. *Phys. Chem. B* **2022**, *126*, 6063–6073. doi:10.1021/acs.jpcb.2c03078

8. Xu, X.; Feng, J.; Li, W.-Y.; Wang, G.; Feng, W.; Yu, H. *Prog. Polym. Sci.* **2024**, *149*, 101782. doi:10.1016/j.progpolymsci.2023.101782

9. Beharry, A. A.; Woolley, G. A. *Chem. Soc. Rev.* **2011**, *40*, 4422–4437. doi:10.1039/c1cs15023e

10. Szymański, W.; Beierle, J. M.; Kistemaker, H. A. V.; Velema, W. A.; Feringa, B. L. *Chem. Rev.* **2013**, *113*, 6114–6178. doi:10.1021/cr300179f

11. Cheng, H.-B.; Zhang, S.; Qi, J.; Liang, X.-J.; Yoon, J. *Adv. Mater.* (Weinheim, Ger.) **2021**, *33*, 2007290. doi:10.1002/adma.202007290

12. Merino, E. *Chem. Soc. Rev.* **2011**, *40*, 3835–3853. doi:10.1039/c0cs00183j

13. Kurup, S. S.; Groysman, S. *Dalton Trans.* **2022**, *51*, 4577–4589. doi:10.1039/d2dt00228k

14. Zhang, C.; Jiao, N. *Angew. Chem., Int. Ed.* **2010**, *49*, 6174–6177. doi:10.1002/anie.201001651

15. Takeda, Y.; Okumura, S.; Minakata, S. *Angew. Chem., Int. Ed.* **2012**, *51*, 7804–7808. doi:10.1002/anie.201202786

16. Cai, S.; Rong, H.; Yu, X.; Liu, X.; Wang, D.; He, W.; Li, Y. *ACS Catal.* **2013**, *3*, 478–486. doi:10.1021/cs300707y

17. Singh, S.; Chauhan, P.; Ravi, M.; Taneja, I.; Wahajuddin, W.; Yadav, P. P. *RSC Adv.* **2015**, *5*, 61876–61880. doi:10.1039/c5ra12535a

18. Wang, M.; Ma, J.; Yu, M.; Zhang, Z.; Wang, F. *Catal. Sci. Technol.* **2016**, *6*, 1940–1945. doi:10.1039/c5cy01015b

19. Damiano, C.; Cavalleri, M.; Panza, N.; Gallo, E. *Eur. J. Org. Chem.* **2022**, e202200791. doi:10.1002/ejoc.202200791

20. Hu, L.; Cao, X.; Shi, L.; Qi, F.; Guo, Z.; Lu, J.; Gu, H. *Org. Lett.* **2011**, *13*, 5640–5643. doi:10.1021/ol202362f

21. Sakai, N.; Asama, S.; Anai, S.; Konakahara, T. *Tetrahedron* **2014**, *70*, 2027–2033. doi:10.1016/j.tet.2014.01.048

22. Zhang, Y.-F.; Mellah, M. *ACS Catal.* **2017**, *7*, 8480–8486. doi:10.1021/acscatal.7b02940

23. Ma, Y.; Wu, S.; Jiang, S.; Xiao, F.; Deng, G.-J. *Chin. J. Chem.* **2021**, *39*, 3334–3338. doi:10.1002/cjoc.202100470

24. Grirrane, A.; Corma, A.; Garcia, H. *Science* **2008**, *322*, 1661–1664. doi:10.1126/science.1166401

25. Mills, C. *J. Chem. Soc., Trans.* **1895**, *67*, 925–933. doi:10.1039/ct8956700925

26. Griwatz, J. H.; Kunz, A.; Wegner, H. A. *Beilstein J. Org. Chem.* **2022**, *18*, 781–787. doi:10.3762/bjoc.18.78

27. Griwatz, J. H.; Campi, C. E.; Kunz, A.; Wegner, H. A. *ChemSusChem* **2024**, *17*, e202301714. doi:10.1002/cssc.202301714

28. Kunz, A.; Oberhof, N.; Scherz, F.; Martins, L.; Dreuw, A.; Wegner, H. A. *Chem. – Eur. J.* **2022**, *28*, e202200972. doi:10.1002/chem.202200972

29. Haghbeen, K.; Tan, E. W. *J. Org. Chem.* **1998**, *63*, 4503–4505. doi:10.1021/j0972151z

30. Merrington, J.; James, M.; Bradley, M. *Chem. Commun.* **2002**, 140–141. doi:10.1039/b109799g

31. Esguerra, K. V. N.; Lumb, J.-P. *Chem. – Eur. J.* **2017**, *23*, 8596–8600. doi:10.1002/chem.201701226

32. Barbero, M.; Degani, I.; Dughera, S.; Fochi, R.; Perracino, P. *Synthesis* **1998**, 1235–1237. doi:10.1055/s-1998-6102

33. Hansen, M. J.; Lerch, M. M.; Szymanski, W.; Feringa, B. L. *Angew. Chem., Int. Ed.* **2016**, *55*, 13514–13518. doi:10.1002/anie.201607529

34. Kunz, K.; Scholz, U.; Ganzer, D. *Synlett* **2003**, 2428–2439. doi:10.1055/s-2003-42473

35. Schlummer, B.; Scholz, U. *Adv. Synth. Catal.* **2004**, *346*, 1599–1626. doi:10.1002/adsc.200404216

36. Beletskaya, I. P.; Cheprakov, A. V. *Organometallics* **2012**, *31*, 7753–7808. doi:10.1021/om300683c

37. Bariwal, J.; Van der Eycken, E. *Chem. Soc. Rev.* **2013**, *42*, 9283–9303. doi:10.1039/c3cs60228a

38. Ruiz-Castillo, P.; Buchwald, S. L. *Chem. Rev.* **2016**, *116*, 12564–12649. doi:10.1021/acs.chemrev.6b00512

39. Forero-Cortés, P. A.; Haydl, A. M. *Org. Process Res. Dev.* **2019**, *23*, 1478–1483. doi:10.1021/acs.oprd.9b00161

40. Emadi, R.; Bahrami Nekoo, A.; Molaverdi, F.; Khorsandi, Z.; Sheibani, R.; Sadeghi-Aliabadi, H. *RSC Adv.* **2023**, *13*, 18715–18733. doi:10.1039/d2ra07412e

41. Wang, Y.; Xie, R.; Huang, L.; Tian, Y.-N.; Lv, S.; Kong, X.; Li, S. *Org. Chem. Front.* **2021**, *8*, 5962–5967. doi:10.1039/d1q000945a

42. Lim, Y.-K.; Lee, K.-S.; Cho, C.-G. *Org. Lett.* **2003**, *5*, 979–982. doi:10.1021/ol027311u

43. Finck, L.; Oestreich, M. *Angew. Chem., Int. Ed.* **2022**, *61*, e202210907. doi:10.1002/anie.202210907

44. Chauvier, C.; Finck, L.; Hecht, S.; Oestreich, M. *Organometallics* **2019**, *38*, 4679–4686. doi:10.1021/acs.organomet.9b00654

45. Xu, Y.; Gao, C.; Andréasson, J.; Grøtli, M. *Org. Lett.* **2018**, *20*, 4875–4879. doi:10.1021/acs.orglett.8b02014

46. Lv, H.; Laishram, R. D.; Yang, Y.; Li, J.; Xu, D.; Zhan, Y.; Luo, Y.; Su, Z.; More, S.; Fan, B. *Org. Biomol. Chem.* **2020**, *18*, 3471–3474. doi:10.1039/d0ob00103a

47. Tuck, J. R.; Tombari, R. J.; Yardeny, N.; Olson, D. E. *Org. Lett.* **2021**, *23*, 4305–4310. doi:10.1021/acs.orglett.1c01230

48. Lin, Y.; Wu, H.; Liu, Z.; Li, J.; Cai, R.; Hashimoto, M.; Wang, L. *Tetrahedron Lett.* **2022**, *108*, 154132. doi:10.1016/j.tetlet.2022.154132

49. Orvoš, J.; Pančík, F.; Fischer, R. *Eur. J. Org. Chem.* **2023**, *26*, e202300049. doi:10.1002/ejoc.202300049

50. Phadnis, N.; Molen, J. A.; Stephens, S. M.; Weierbach, S. M.; Lambert, K. M.; Milligan, J. A. *J. Org. Chem.* **2024**, *89*, 5841–5845. doi:10.1021/acs.joc.3c02752

51. Kocúrik, M.; Konopáčová, P.; Kolman, L.; Kryl, P.; Růžička, A.; Bartáček, J.; Hanusek, J.; Váňa, J. *ACS Omega* **2024**, *9*, 47105–47113. doi:10.1021/acsomega.4c07485

52. Rao, H.; Jin, Y.; Fu, H.; Jiang, Y.; Zhao, Y. *Chem. – Eur. J.* **2006**, *12*, 3636–3646. doi:10.1002/chem.200501473

53. Huang, Y.; Choy, P. Y.; Wang, J.; Tse, M.-K.; Sun, R. W.-Y.; Chan, A. S.-C.; Kwong, F. Y. *J. Org. Chem.* **2020**, *85*, 14664–14673. doi:10.1021/acs.joc.0c01599

54. Sudharsan, M.; Thirumoorthy, K.; Nethaji, M.; Suresh, D. *ChemistrySelect* **2019**, *4*, 9253–9261. doi:10.1002/slect.201902137

55. Ikawa, T.; Barder, T. E.; Biscoe, M. R.; Buchwald, S. L. *J. Am. Chem. Soc.* **2007**, *129*, 13001–13007. doi:10.1021/ja0717414

56. Fors, B. P.; Krattiger, P.; Strieter, E.; Buchwald, S. L. *Org. Lett.* **2008**, *10*, 3505–3508. doi:10.1021/ol801285g

57. Wang, J. Y.; Choi, K.; Zuend, S. J.; Borate, K.; Shinde, H.; Goetz, R.; Hartwig, J. F. *Angew. Chem., Int. Ed.* **2021**, *60*, 399–408. doi:10.1002/anie.202011161

58. DeAngelis, A. J.; Gildner, P. G.; Chow, R.; Colacot, T. J. *J. Org. Chem.* **2015**, *80*, 6794–6813. doi:10.1021/acs.joc.5b01005

59. Gao, W.; He, Z.; Qian, Y.; Zhao, J.; Huang, Y. *Chem. Sci.* **2012**, *3*, 883–886. doi:10.1039/c1sc00661d

60. Steinhoff, B. A.; Fix, S. R.; Stahl, S. S. *J. Am. Chem. Soc.* **2002**, *124*, 766–767. doi:10.1021/ja016806w
61. Karnbrock, S. B. H.; Golz, C.; Mata, R. A.; Alcarazo, M.

*Angew. Chem., Int. Ed.* **2022**, *61*, e202207450.

doi:10.1002/anie.202207450

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