<figure><img src="image_171.png" /><figcaption>**Figure 5.** Synthesis of DTE-based photoswitchable phosphines.</figcaption></figure>

Upon light irradiation in cyclohexane solution, the obtained DTE-based ligands underwent successful reversible photoisomerization under UV (for ring-closing) and visible light irradiation (for ring-opening). In addition, TD-DFT calculations at the CAM-B3LYP-D3/6,31G(d,p) level were performed to further investigate the electronic excitations of these compounds, for which ground state geometries were first computed. For ligands, only their photocyclizable antiparallel conformation was considered in the calculations. All open state phosphine ligands were characterized by a strong absorption in the UV region with maxima around $\lambda_{abs} \approx 290$ nm (Figure 6), which was reproduced in computations and could be attributed to $\pi-\pi^*$ transitions (HOMO - LUMO+1 or HOMO - LUMO) of their core. In the case of DTE-COCF$_3$, a shallower absorption band ranging up to $\lambda_{abs} \approx 400$ nm was detected due to the lowering of the energy of the LUMO caused by the introduction of a strong EWG. For open state ligands, a broad, red-shifted absorption band emerged in the visible part of the spectrum upon UV illumination of their cyclohexane solutions, which changed from colorless to deep blue ($\lambda_{abs}$= 598 nm for DTE$^c$-COCF$_3$) or deep pink ($\lambda_{abs}$ $\approx$ 518 nm for DTE$^c$-C$_6$F$_5$ and DTE$^c$-Ph) (Figure 6).

<figure><img src="image_172.png" /><figcaption>**Figure 6.** Variation of the absorption spectrum of free ligands DTE$^o$-COCF$_3$ ($c$ = 3.0·10$^{-5}$ M), DTE$^o$-C$_6$F$_5$ ($c$ = 1.0·10$^{-5}$ M) and DTE-Ph ($c$ = 5.2·10$^{-5}$ M) in cyclohexane upon sequential irradiation with UV ($\lambda_{exc}$ = 355 or 312 nm) and green light ($\lambda_{exc}$ = 520 nm) until the corresponding ring-closing and ring-opening photostationary states (PSSs) are obtained, respectively.</figcaption></figure>

The equilibrium between the open (o) and closed (c) isomers achieved upon ring-closure was defined as a photostationary state (PSS), while the cycloreversion proceeds quantitatively. The best photoswitching performance was observed for the ligand containing a trifluoroacetyl group (DTE-COCF$_3$) (Table 1), exhibiting high ring-cyclization quantum yield and conversion (91% c at the PSS@365
nm) as well as good fatigue resistance. These favorable results were attributed to the effect of the strong EWG in its structure.

<table><caption>**Table 1.** Photochemical properties of DTE-based ligands and complexes.</caption><thead><tr><th></th><th>λ<sub>abs</sub><sup>o</sup> [nm]<br>(ε [M<sup>-1</sup> cm<sup>-1</sup>])<sup>a</sup></th><th>λ<sub>abs</sub><sup>c</sup> [nm]<br>(ε [M<sup>-1</sup> cm<sup>-1</sup>])<sup>b</sup></th><th>PSS<sub>o-c</sub><br>composition [%]<sup>c</sup></th><th>Φ<sub>o-c</sub><sup>d</sup></th><th>Φ<sub>c-o</sub><sup>e</sup></th></tr></thead><tbody><tr><td>DTE-COCF<sub>3</sub></td><td>268 (35 673),<br>339 (6 431)</td><td>598 (12 261)</td><td>9:91</td><td>0.480</td><td>0.012</td></tr><tr><td>[PdCl<sub>2</sub>(DTE-COCF<sub>3</sub>)<sub>2</sub>]</td><td>271 (34 149),<br>355 (19 065)</td><td>604 (18 870)</td><td>10:45:45</td><td>0.148/0.048</td><td>0.013/0.014</td></tr><tr><td>DTE-C<sub>6</sub>F<sub>5</sub></td><td>272 (28 303)</td><td>519 (11 379)</td><td>19:81</td><td>0.530</td><td>0.015</td></tr><tr><td>[PdCl<sub>2</sub>(DTE-C<sub>6</sub>F<sub>5</sub>)<sub>2</sub>]</td><td>268 (40 394),<br>357 (14 367)</td><td>532 (19 391)</td><td>30:45:25</td><td>0.047/0.019</td><td>0.015/0.018</td></tr><tr><td>DTE-Ph</td><td>273 (28 117)</td><td>518 (13 673)</td><td>61:39</td><td>0.485</td><td>0.011</td></tr><tr><td>[PdCl<sub>2</sub>(DTE-Ph)<sub>2</sub>]</td><td>270 (42 700),<br>359 (15 400)</td><td>538 (16 310)</td><td>29:44:27</td><td>0.060/0.023</td><td>0.015/0.014</td></tr></tbody></table>

<sup>a</sup> Wavelength and molar absorptivity coefficient of the absorption band maxima of the open isomer (for complexes, oo state) in cyclohexane. <sup>b</sup> Wavelength and molar absorptivity coefficient of the maximum of the visible absorption band of the closed isomer (for complexes, cc state) in cyclohexane. <sup>c</sup> Composition of the PSS reached for the photocyclization process in toluene-d<sub>8</sub> upon irradiation at λ<sub>exc</sub> = 365 nm (DTE-COCF<sub>3</sub> and all the complexes) or 312 nm (DTE-C<sub>6</sub>F<sub>5</sub> and DTE-Ph). DTE<sup>o</sup>:DTE<sup>c</sup> and DTE<sup>oo</sup>:DTE<sup>oc</sup>:DTE<sup>cc</sup> concentration ratios are given for free ligands and complexes, respectively. <sup>d</sup> Photocyclization quantum yields measured in cyclohexane at λ<sub>exc</sub> = 355 nm (DTE-COCF<sub>3</sub> and all the complexes) or 312 nm (DTE-C<sub>6</sub>F<sub>5</sub> and DTE-Ph). For the complexes, separate Φ<sub>o-c</sub> values are given for the oo → oc and oc → cc ring-closing processes. <sup>e</sup> Photocycloreversion quantum yields measured in cyclohexane at λ<sub>exc</sub> = 532 nm. For the complexes, separate Φ<sub>c-o</sub> values are given for the cc → oc and oc → oo ring-opening processes.

To estimate the change in electron density on the phosphorus atom of the ligands upon photoisomerization (Figure 7), phosphine selenides were prepared. The nature of the phosphine-selenium bond allowed the estimation of each ligand's σ-donating ability through NMR measurements. Experimental results demonstrated that electron density modulation depended on the introduced substituent, with DTE-COCF<sub>3</sub> showing the highest modulation.

To further investigate the photomodulation of the electronic features for the prepared DTE-based phosphines, a set of properties derived from the DFT calculations of their ground state structures was analyzed. As a first step, the variation of the Mulliken charges on the phosphorus atom (Δ<sup>c-o</sup>(q<sub>P</sub><sup>Mulliken</sup>)) and the percentage of s character of the lone pair of electrons at phosphorus (Δ<sup>c-o</sup>(%S<sub>P</sub>)) for open anti-parallel and closed conformations of DTE-COCF<sub>3</sub>, DTE-C<sub>6</sub>F<sub>5</sub> and DTE-Ph were considered (Table 2). According to the Mulliken charges, photocyclization decreases electron density on phosphorus, while through NBO analysis [32] an increase in s orbital participation in the phosphorus lone pair of electrons can be anticipated. More importantly, the variation of these parameters was found to increase with the electron-withdrawing power of the introduced electron-modulating group, thus again validating that DTE-COCF<sub>3</sub> and, to a lesser extent, DTE-C<sub>6</sub>F<sub>5</sub> suffer the largest change in the phosphine's electronic properties upon photoisomerization.
nm) as well as good fatigue resistance. These favorable results were attributed to the effect of the strong EWG in its structure.

<table><caption>**Table 1.** Photochemical properties of DTE-based ligands and complexes.</caption><thead><tr><th></th><th>λ<sub>abs</sub><sup>o</sup> [nm]<br>(ε [M<sup>-1</sup> cm<sup>-1</sup>])<sup>a</sup></th><th>λ<sub>abs</sub><sup>c</sup> [nm]<br>(ε [M<sup>-1</sup> cm<sup>-1</sup>])<sup>b</sup></th><th>PSS<sub>o-c</sub><br>composition [%]<sup>c</sup></th><th>Φ<sub>o-c</sub><sup>d</sup></th><th>Φ<sub>c-o</sub><sup>e</sup></th></tr></thead><tbody><tr><td>DTE-COCF<sub>3</sub></td><td>268 (35 673),<br>339 (6 431)</td><td>598 (12 261)</td><td>9:91</td><td>0.480</td><td>0.012</td></tr><tr><td>[PdCl<sub>2</sub>(DTE-COCF<sub>3</sub>)<sub>2</sub>]</td><td>271 (34 149),<br>355 (19 065)</td><td>604 (18 870)</td><td>10:45:45</td><td>0.148/ 0.048</td><td>0.013/ 0.014</td></tr><tr><td>DTE-C<sub>6</sub>F<sub>5</sub></td><td>272 (28 303)</td><td>519 (11 379)</td><td>19:81</td><td>0.530</td><td>0.015</td></tr><tr><td>[PdCl<sub>2</sub>(DTE-C<sub>6</sub>F<sub>5</sub>)<sub>2</sub>]</td><td>268 (40 394),<br>357 (14 367)</td><td>532 (19 391)</td><td>30:45:25</td><td>0.047/ 0.019</td><td>0.015/ 0.018</td></tr><tr><td>DTE-Ph</td><td>273 (28 117)</td><td>518 (13 673)</td><td>61:39</td><td>0.485</td><td>0.011</td></tr><tr><td>[PdCl<sub>2</sub>(DTE-Ph)<sub>2</sub>]</td><td>270 (42 700),<br>359 (15 400)</td><td>538 (16 310)</td><td>29:44:27</td><td>0.060/ 0.023</td><td>0.015/ 0.014</td></tr></tbody></table>

<sup>a</sup> Wavelength and molar absorptivity coefficient of the absorption band maxima of the open isomer (for complexes, oo state) in cyclohexane. <sup>b</sup> Wavelength and molar absorptivity coefficient of the maximum of the visible absorption band of the closed isomer (for complexes, cc state) in cyclohexane. <sup>c</sup> Composition of the PSS reached for the photocyclization process in toluene-d<sub>8</sub> upon irradiation at λ<sub>exc</sub> = 365 nm (DTE-COCF<sub>3</sub> and all the complexes) or 312 nm (DTE-C<sub>6</sub>F<sub>5</sub> and DTE-Ph). DTE<sup>o</sup>:DTE<sup>c</sup> and DTE<sup>oo</sup>:DTE<sup>oc</sup>:DTE<sup>cc</sup> concentration ratios are given for free ligands and complexes, respectively. <sup>d</sup> Photocyclization quantum yields measured in cyclohexane at λ<sub>exc</sub> = 355 nm (DTE-COCF<sub>3</sub> and all the complexes) or 312 nm (DTE-C<sub>6</sub>F<sub>5</sub> and DTE-Ph). For the complexes, separate Φ<sub>o-c</sub> values are given for the oo → oc and oc → cc ring-closing processes. <sup>e</sup> Photocycloreversion quantum yields measured in cyclohexane at λ<sub>exc</sub> = 532 nm. For the complexes, separate Φ<sub>c-o</sub> values are given for the cc → oc and oc → oo ring-opening processes.

To estimate the change in electron density on the phosphorus atom of the ligands upon photoisomerization (Figure 7), phosphine selenides were prepared. The nature of the phosphine-selenium bond allowed the estimation of each ligand's σ-donating ability through NMR measurements. Experimental results demonstrated that electron density modulation depended on the introduced substituent, with DTE-COCF<sub>3</sub> showing the highest modulation.

To further investigate the photomodulation of the electronic features for the prepared DTE-based phosphines, a set of properties derived from the DFT calculations of their ground state structures was analyzed. As a first step, the variation of the Mulliken charges on the phosphorus atom (Δ<sup>c-o</sup>(q<sub>P</sub><sup>Mulliken</sup>)) and the percentage of s character of the lone pair of electrons at phosphorus (Δ<sup>c-o</sup>(%S<sub>P</sub>)) for open anti-parallel and closed conformations of DTE-COCF<sub>3</sub>, DTE-C<sub>6</sub>F<sub>5</sub> and DTE-Ph were considered (Table 2). According to the Mulliken charges, photocyclization decreases electron density on phosphorus, while through NBO analysis [32] an increase in s orbital participation in the phosphorus lone pair of electrons can be anticipated. More importantly, the variation of these parameters was found to increase with the electron-withdrawing power of the introduced electron-modulating group, thus again validating that DTE-COCF<sub>3</sub> and, to a lesser extent, DTE-C<sub>6</sub>F<sub>5</sub> suffer the largest change in the phosphine's electronic properties upon photoisomerization.
<figure><img src="image_175.png" /><figcaption>**Figure 7.** Structure of the DTE-based phosphines prepared, where photoswitching of the dithienylethene backbone caused a change in phosphine electronic properties that was dependent on the introduced EWG substituent.</figcaption></figure>

As a second step, the effect of the light-induced modulation of the DTE-based phosphine ligands on the bond energy in their Pd¹¹ complexes was investigated. For this, the difference in phosphine-Pd¹¹ binding energy (Δc⁻o(BEₚ-Pd)) between the **oo** and **cc** isomers of their 2:1 trans phosphine palladium(II) complexes (Table 2) was calculated. As expected, due to the loss of the phosphine's σ-donating ability, a varying decrease in BEₚ-Pd for the complexes bearing ring-closed DTE ligands is observed, depending on the nature of the introduced electron-modulating group. Thus, weakening of the phosphine-palladium(II) binding upon photocyclization was observed for the ligands bearing the EWG pentafluorophenyl and, especially, trifluoroacetyl substituents.

<table><caption>**Table 2.** Experimental and computed parameters to estimate the photomodulation of the properties of the phosphine ligands **DTE-COCF₃**, **DTE-C₆F₅** and **DTE-Ph**.</caption><thead><tr><th rowspan="2"></th><th colspan="3">Free ligands</th><th>Pd¹¹ complexes<sup>a</sup></th></tr><tr><th>Δc⁻o(<sup>1</sup>J<sub>P,Se</sub>)<br>[Hz]<sup>b</sup></th><th>Δc⁻o(q<sup>Mulliken</sup><sub>P</sub>)<sup>c</sup></th><th>Δc⁻o(%s<sub>P</sub>)<sup>d</sup></th><th>Δc⁻o(BE<sub>P-Pd</sub>) [kcal·mol⁻¹]<sup>e</sup></th></tr></thead><tbody><tr><td>DTE-COCF<sub>3</sub></td><td>14</td><td>0.014</td><td>0.79</td><td>-1.98</td></tr><tr><td>DTE-C<sub>6</sub>F<sub>5</sub></td><td>7</td><td>0.004</td><td>0.42</td><td>-0.92</td></tr><tr><td>DTE-Ph</td><td>5</td><td>&lt;0.001</td><td>0.34</td><td>-0.64</td></tr></tbody></table>

<footnote><sup>a</sup> trans-[PdCl₂(DTE-COCF₃)₂], trans-[PdCl₂(DTE-C₆F₅)₂] and trans-[PdCl₂(DTE-Ph)₂]. <sup>b</sup> Difference in <sup>1</sup>J<sub>P,Se</sub> for the corresponding selenides measured in CDCl₃. <sup>c</sup> Difference in Mulliken charges in electronic units on the phosphorus atom. <sup>d</sup> Difference in percentage of s character of the phosphorus lone pair of electrons. <sup>e</sup> Difference in phosphine-Pd¹¹ bond energy (per one bond) between the **oo** and **cc** isomers.</footnote>
<figure><img src="image_173.png" /><figcaption>**Figure 7.** Structure of the DTE-based phosphines prepared, where photoswitching of the dithienylethene backbone caused a change in phosphine electronic properties that was dependent on the introduced EWG substituent.</figcaption></figure>

As a second step, the effect of the light-induced modulation of the DTE-based phosphine ligands on the bond energy in their Pd¹¹ complexes was investigated. For this, the difference in phosphine-Pd¹¹ binding energy (Δc⁻o(BEₚ-Pd)) between the **oo** and **cc** isomers of their 2:1 trans phosphine palladium(II) complexes (Table 2) was calculated. As expected, due to the loss of the phosphine's σ-donating ability, a varying decrease in BEₚ-Pd for the complexes bearing ring-closed DTE ligands is observed, depending on the nature of the introduced electron-modulating group. Thus, weakening of the phosphine-palladium(II) binding upon photocyclization was observed for the ligands bearing the EWG pentafluorophenyl and, especially, trifluoroacetyl substituents.

<table><caption>**Table 2.** Experimental and computed parameters to estimate the photomodulation of the properties of the phosphine ligands **DTE-COCF₃**, **DTE-C₆F₅** and **DTE-Ph**.</caption><thead><tr><th rowspan="2"></th><th colspan="3">Free ligands</th><th>Pd¹¹ complexes<sup>a</sup></th></tr><tr><th>Δc⁻o(<sup>1</sup>J<sub>P,Se</sub>)<br>[Hz]<sup>b</sup></th><th>Δc⁻o(q<sup>Mulliken</sup><sub>P</sub>)<sup>c</sup></th><th>Δc⁻o(%s<sub>P</sub>)<sup>d</sup></th><th>Δc⁻o(BE<sub>P-Pd</sub>) [kcal·mol⁻¹]<sup>e</sup></th></tr></thead><tbody><tr><td>DTE-COCF<sub>3</sub></td><td>14</td><td>0.014</td><td>0.79</td><td>-1.98</td></tr><tr><td>DTE-C<sub>6</sub>F<sub>5</sub></td><td>7</td><td>0.004</td><td>0.42</td><td>-0.92</td></tr><tr><td>DTE-Ph</td><td>5</td><td>&lt;0.001</td><td>0.34</td><td>-0.64</td></tr></tbody></table>

<footnote><sup>a</sup> trans-[PdCl₂(DTE-COCF₃)₂], trans-[PdCl₂(DTE-C₆F₅)₂] and trans-[PdCl₂(DTE-Ph)₂]. <sup>b</sup> Difference in <sup>1</sup>J<sub>P,Se</sub> for the corresponding selenides measured in CDCl₃. <sup>c</sup> Difference in Mulliken charges in electronic units on the phosphorus atom. <sup>d</sup> Difference in percentage of s character of the phosphorus lone pair of electrons. <sup>e</sup> Difference in phosphine-Pd¹¹ bond energy (per one bond) between the **oo** and **cc** isomers.</footnote>
When two equivalents of the phosphine ligands were used to react with trans-[PdCl₂(PhCN)₂], monometallic palladium(II) 1:2 type complexes were formed (Figure 8a). Single crystals suitable for X-ray structure determination were obtained for the three complexes, which revealed that formed Pd complexes have a square-planar geometry with trans orientation of the phosphine ligands (Figure 8b). The main difference observed between the crystal structures of these compounds was the conformation of their DTE ligands. In [PdCl₂(DTE°-Ph)₂] and [PdCl₂(DTE°-COCF₃)₂], the ligands are locked in a distorted parallel open state conformation with a distance of 4.31 Å and 5.19 Å, respectively, between the carbon atoms that should react upon ring-closing photoisomerization (C16 – C26). As previously described in the literature [26], this type of conformation cannot undergo the light-induced conrotatory electrocyclization reaction to produce the corresponding closed isomer and, consequently, no photochromism was observed in the solid state for [PdCl₂(DTE°-Ph)₂] and [PdCl₂(DTE°-COCF₃)₂]. Contrarily, in the case of [PdCl₂(DTE°-C₆F₅)₂], the DTE ligands are present in an antiparallel open state conformation with a shorter distance between the reactive carbons (C16 – C26, 3.69 Å), two structural features that are compatible with the photoinduced ring-closing reaction [33]. Indeed, irradiation at 312 nm yielded a color change from yellow to red and the process was reversed with irradiation at 520 nm, thus demonstrating solid state photoswitching for [PdCl₂(DTE°-C₆F₅)₂].

Irrespective of their behavior in the solid state, all DTE-based ligands and complexes prepared should photoisomerize in solution upon irradiation. However, while **DTE-COCF₃**, **DTE-C₆F₅** and **DTE Ph** should just photoconvert between their ring-open and ring-closed isomers, a more complex situation is expected for their complexes. Because of their 2:1 phosphine:metal stoichiometry, these compounds must toggle between three different states where DTE-based ligands are both ring-open (**oo**), one of them ring-open and the other ring-closed (**oc**), or both ring-closed (**cc**). Complexation detrimentally affected ring-closing quantum yields due to ligand-to-metal charge transfer, resulting in less efficient photochemical reactions (Table 1). Despite this, photoswitching was not fully hindered by metal complexation, prompting further catalytic studies for the ring-open and ring-closed states of the Pd(II) compounds.

Catalytic tests were conducted for a model Stille coupling reaction between iodobenzene and tributylvinyltin in THF-*d*₈, which revealed that higher conversions were achieved when using the ring-closed complexes bearing EWG substituents as pre-catalysts (Figure 3). Therefore, these results verified the initial hypothesis that the presence of these groups would selectively affect phosphine electron properties upon DTE photocyclization, thus ultimately modifying the catalytic performance of their metal complexes. In this case, reaction rate acceleration was expected to take place for the ring-closed state of the metal catalysts due to the lower binding strength of photocyclized DTE-based phosphines to palladium(0) species, a situation that was confirmed by DFT calculations of the catalytic cycle.
When two equivalents of the phosphine ligands were used to react with trans-[PdCl₂(PhCN)₂], monometallic palladium(II) 1:2 type complexes were formed (Figure 8a). Single crystals suitable for X-ray structure determination were obtained for the three complexes, which revealed that formed Pd complexes have a square-planar geometry with trans orientation of the phosphine ligands (Figure 8b). The main difference observed between the crystal structures of these compounds was the conformation of their DTE ligands. In [PdCl₂(DTE°-Ph)₂] and [PdCl₂(DTE°-COCF₃)₂], the ligands are locked in a distorted parallel open state conformation with a distance of 4.31 Å and 5.19 Å, respectively, between the carbon atoms that should react upon ring-closing photoisomerization (C16 – C26). As previously described in the literature [26], this type of conformation cannot undergo the light-induced conrotatory electrocyclization reaction to produce the corresponding closed isomer and, consequently, no photochromism was observed in the solid state for [PdCl₂(DTE°-Ph)₂] and [PdCl₂(DTE°-COCF₃)₂]. Contrarily, in the case of [PdCl₂(DTE°-C₆F₅)₂], the DTE ligands are present in an antiparallel open state conformation with a shorter distance between the reactive carbons (C16 – C26, 3.69 Å), two structural features that are compatible with the photoinduced ring-closing reaction [33]. Indeed, irradiation at 312 nm yielded a color change from yellow to red and the process was reversed with irradiation at 520 nm, thus demonstrating solid state photoswitching for [PdCl₂(DTE°-C₆F₅)₂].

Irrespective of their behavior in the solid state, all DTE-based ligands and complexes prepared should photoisomerize in solution upon irradiation. However, while **DTE-COCF₃**, **DTE-C₆F₅** and **DTE Ph** should just photoconvert between their ring-open and ring-closed isomers, a more complex situation is expected for their complexes. Because of their 2:1 phosphine:metal stoichiometry, these compounds must toggle between three different states where DTE-based ligands are both ring-open (**oo**), one of them ring-open and the other ring-closed (**oc**), or both ring-closed (**cc**). Complexation detrimentally affected ring-closing quantum yields due to ligand-to-metal charge transfer, resulting in less efficient photochemical reactions (Table 1). Despite this, photoswitching was not fully hindered by metal complexation, prompting further catalytic studies for the ring-open and ring-closed states of the Pd(II) compounds.

Catalytic tests were conducted for a model Stille coupling reaction between iodobenzene and tributylvinyltin in THF-*d*₈, which revealed that higher conversions were achieved when using the ring-closed complexes bearing EWG substituents as pre-catalysts (Figure 3). Therefore, these results verified the initial hypothesis that the presence of these groups would selectively affect phosphine electron properties upon DTE photocyclization, thus ultimately modifying the catalytic performance of their metal complexes. In this case, reaction rate acceleration was expected to take place for the ring-closed state of the metal catalysts due to the lower binding strength of photocyclized DTE-based phosphines to palladium(0) species, a situation that was confirmed by DFT calculations of the catalytic cycle.
<figure><img src="image_176.png" /><figcaption>**Figure 8.** a) Synthesis of [PdCl₂(DTE°-COCF₃)₂], [PdCl₂(DTE°-C₆F₅)₂] and [PdCl₂(DTE°-Ph)₂]. b) Molecular structures of [PdCl₂(DTE°-Ph)₂], [PdCl₂(DTE°-COCF₃)₂] and [PdCl₂(DTE°-C₆F₅)₂]. Thermal ellipsoids set at 50% probability level. For clarity, P-bound phenyl rings are depicted in wireframe style, and co-crystallized solvent and hydrogen atoms are omitted. Distances between the reactive carbon atoms in DTE photoisomerization are marked with a dashed red line. c) Illustration of the solid-state photoisomerization of [PdCl₂(DTE°-C₆F₅)₂].</figcaption></figure>
<figure><img src="image_174.png" /><figcaption>**Figure 8.** a) Synthesis of [PdCl₂(DTE°-COCF₃)₂], [PdCl₂(DTE°-C₆F₅)₂] and [PdCl₂(DTE°-Ph)₂]. b) Molecular structures of [PdCl₂(DTE°-Ph)₂], [PdCl₂(DTE°-COCF₃)₂] and [PdCl₂(DTE°-C₆F₅)₂]. Thermal ellipsoids set at 50% probability level. For clarity, P-bound phenyl rings are depicted in wireframe style, and co-crystallized solvent and hydrogen atoms are omitted. Distances between the reactive carbon atoms in DTE photoisomerization are marked with a dashed red line. c) Illustration of the solid-state photoisomerization of [PdCl₂(DTE°-C₆F₅)₂].</figcaption></figure>
<figure><img src="image_177.png" /><figcaption>**Figure 8.** Comparison of the investigated complexes as pre-catalysts in the Stille coupling reaction between iodobenzene and tributylvinyltin (1.5 mol% [Pd], 0.30 mmol iodobenzene, 0.33 mmol tributylvinyltin, 1 mL THF). Data is shown for the open ([PdCl₂(DTE°-R)₂], light red, light pink and light blue) and closed state-enriched mixture ([PdCl₂(DTE°-R)₂], dark red, dark pink and dark blue) of the DTE-based complexes tested at rt (a) and 50 °C (b). The average yields of two repetitions were determined by ¹H NMR using 1,3,5,-trimethoxybenzene as a standard.</figcaption></figure>

As an extension of this strategy toward photoswitchable catalysis, a bisDTE ligand was designed that features two DTE moieties with trifluoroacetyl groups attached to phenylphosphine. To our knowledge, this would represent the first example reported of the introduction of more than one DTE unit to the phosphorus atom of phosphines. The synthesis of the bisDTE ligand **Bis(DTE-COCF₃)** was conducted similarly as for **DTE-COCF₃**, employing chlorine/lithium exchange reactions and quenching with an appropriate electrophile to install the desired phenylphosphine and trifluoromethyl ketone groups (Scheme 2). To study the complexation behavior of this ligand its gold(I) complex was also synthesized.

<figure><img src="image_178.png" /><figcaption>**Scheme 2.** Synthetic route to bisDTE-substituted phosphine Bis(DTE-COCF<sub>3</sub>) and its gold(I) complex.</figcaption></figure>

Photochemical studies in solution revealed that fully open ligand **Bis(DTE°-COCF₃)** can successfully undergo isomerization into ring-closed **Bis(DTE°-COCF₃)** and **Bis(DTE°°-COCF₃)** states, though with limited efficacy for the second photocyclization reaction (Table 3). To rationalize this behavior, the separate **oo→oc** and **oc→cc** photocyclization quantum yields were determined for **Bis(DTE-COCF₃)** ($Φ_{oo-oc}$ = 0.435 and $Φ_{oc-cc}$ = 0.020). On the one hand, $Φ_{oo-oc}$ closely resembles the photocyclization quantum yield of reference **DTE-COCF₃** ($Φ_{o-c}$ = 0.480), which indicates that the first ring-closing step in **Bis(DTE-COCF₃)** is not significantly affected by the presence of a nearby ring-open
<figure><img src="image_175.png" /><figcaption>**Figure 8.** Comparison of the investigated complexes as pre-catalysts in the Stille coupling reaction between iodobenzene and tributylvinyltin (1.5 mol% [Pd], 0.30 mmol iodobenzene, 0.33 mmol tributylvinyltin, 1 mL THF). Data is shown for the open ([PdCl₂(DTE°-R)₂], light red, light pink and light blue) and closed state-enriched mixture ([PdCl₂(DTE°-R)₂], dark red, dark pink and dark blue) of the DTE-based complexes tested at rt (a) and 50 °C (b). The average yields of two repetitions were determined by ¹H NMR using 1,3,5,-trimethoxybenzene as a standard.</figcaption></figure>

As an extension of this strategy toward photoswitchable catalysis, a bisDTE ligand was designed that features two DTE moieties with trifluoroacetyl groups attached to phenylphosphine. To our knowledge, this would represent the first example reported of the introduction of more than one DTE unit to the phosphorus atom of phosphines. The synthesis of the bisDTE ligand **Bis(DTE-COCF₃)** was conducted similarly as for **DTE-COCF₃**, employing chlorine/lithium exchange reactions and quenching with an appropriate electrophile to install the desired phenylphosphine and trifluoromethyl ketone groups (Scheme 2). To study the complexation behavior of this ligand its gold(I) complex was also synthesized.

<figure><img src="image_176.png" /><figcaption>**Scheme 2.** Synthetic route to bisDTE-substituted phosphine Bis(DTE-COCF<sub>3</sub>) and its gold(I) complex.</figcaption></figure>

Photochemical studies in solution revealed that fully open ligand **Bis(DTE°-COCF₃)** can successfully undergo isomerization into ring-closed **Bis(DTE°-COCF₃)** and **Bis(DTE°°-COCF₃)** states, though with limited efficacy for the second photocyclization reaction (Table 3). To rationalize this behavior, the separate **oo→oc** and **oc→cc** photocyclization quantum yields were determined for **Bis(DTE-COCF₃)** ($Φ_{oo-oc}$ = 0.435 and $Φ_{oc-cc}$ = 0.020). On the one hand, $Φ_{oo-oc}$ closely resembles the photocyclization quantum yield of reference **DTE-COCF₃** ($Φ_{o-c}$ = 0.480), which indicates that the first ring-closing step in **Bis(DTE-COCF₃)** is not significantly affected by the presence of a nearby ring-open
DTE unit. By contrast, a 20-fold reduction in Φ was measured for the second ring-closing reaction of **Bis(DTE-COCF<sub>3</sub>)**, which proceeds notably less effectively when a close-by DTE unit is already in the closed state. As reported for many other multiphotochromic systems [34–36], energy transfer from the photoexcited open DTE group to the closed DTE unit in **Bis(DTE<sup>oc</sup>-COCF<sub>3</sub>)** must account for this situation, which eventually leads to photoconversion back to **Bis(DTE<sup>oo</sup>-COCF<sub>3</sub>)** instead of full photocyclization in **Bis(DTE<sup>cc</sup>-COCF<sub>3</sub>)**. Complexation with the metal did not preclude the photoswitching ability of the ligand, although, further lowering the quantum yield of the second ring-closing.

<table><caption>**Table 3.** Photochemical properties of DTE-based ligands **Bis(DTE-COCF<sub>3</sub>)** and of gold(I) complex [AuCl(Bis(DTE-COCF<sub>3</sub>))].</caption><thead><tr><th></th><th>λ<sup>o</sup><sub>abs</sub> [nm]<br>(ε [M<sup>-1</sup> cm<sup>-1</sup>])<sup>a</sup></th><th>λ<sup>c</sup><sub>abs</sub> [nm]<br>(ε [M<sup>-1</sup> cm<sup>-1</sup>])<sup>b</sup></th><th>PSS<sub>o-c</sub><br>composition<br>[%]<sup>c</sup></th><th>Φ<sub>oo-oc</sub><sup>d</sup></th><th>Φ<sub>oc-cc</sub><sup>d</sup></th><th>Φ<sub>cc-oc</sub><sup>e</sup></th><th>Φ<sub>oc-oo</sub><sup>e</sup></th></tr></thead><tbody><tr><td><b>Bis(DTE-COCF<sub>3</sub>)</b></td><td>273 (32 423), 336<br>(5 820)</td><td>599 (22 000)</td><td>7:84:9</td><td>0.435</td><td>0.020</td><td>0.032</td><td>0.022</td></tr><tr><td>[AuCl(Bis(DTE-COCF<sub>3</sub>))]</td><td>262 (47 527), 336<br>(7 727)</td><td>589 (26 542)</td><td>10:77:13</td><td>0.246</td><td>0.007</td><td>0.026</td><td>0.023</td></tr></tbody></table>

<sup>a</sup> Wavelength and molar absorptivity coefficient of the absorption band maxima of the open isomer (the **oo** state) in cyclohexane. <sup>b</sup> Wavelength and molar absorptivity coefficient of the maximum of the visible absorption band of the closed isomer (the **cc** state) in cyclohexane. <sup>c</sup> Composition of the PSS reached for the photocyclization process in toluene-d<sub>8</sub> upon irradiation at λ<sub>exc</sub> = 365 nm. DTE<sup>oo</sup>:DTE<sup>oc</sup>:DTE<sup>cc</sup> concentration ratios are given. <sup>d</sup> Photocyclization quantum yields measured in cyclohexane at λ<sub>exc</sub> = 355 nm. <sup>e</sup> Photocycloreversion quantum yields measured in cyclohexane at λ<sub>exc</sub> = 532 nm.

Importantly, the preparation of the corresponding phosphine selenides and their analysis by NMR demonstrated that the fully closed form of the ligand **1cc** experienced the largest modulation of electron density reported to date for photoswitchable phosphines (Δ<sup>cc-oo</sup>(<sup>1</sup>J<sub>P,Se</sub>) = 19 Hz).

<figure><img src="image_179.png" /><figcaption>**Scheme 3.** Photoisomerization-induced variation of <sup>1</sup>J<sub>P,Se</sub> in the **oo**, **oc** and **cc** isomers of phosphine selenide.</figcaption></figure>

To corroborate this experimental result, several descriptors commonly used to assess the electronic properties of ground state phosphines were computed using DFT calculations at the B3LYP-D3/6,31G(d,p) level. On the one hand, clear decrements in the Mulliken charge on the phosphorus atom of **Bis(DTE-COCF<sub>3</sub>)** were predicted upon DTE ring-closing (Δ(q<sub>P</sub><sup>Mulliken</sup>), Table 4). While the first DTE photocyclization process in **Bis(DTE-COCF<sub>3</sub>)** should result in a similar Δ(q<sub>P</sub><sup>Mulliken</sup>), value as for monoDTE-
DTE unit. By contrast, a 20-fold reduction in Φ was measured for the second ring-closing reaction of **Bis(DTE-COCF<sub>3</sub>)**, which proceeds notably less effectively when a close-by DTE unit is already in the closed state. As reported for many other multiphotochromic systems [34–36], energy transfer from the photoexcited open DTE group to the closed DTE unit in **Bis(DTE<sup>oc</sup>-COCF<sub>3</sub>)** must account for this situation, which eventually leads to photoconversion back to **Bis(DTE<sup>oo</sup>-COCF<sub>3</sub>)** instead of full photocyclization in **Bis(DTE<sup>cc</sup>-COCF<sub>3</sub>)**. Complexation with the metal did not preclude the photoswitching ability of the ligand, although, further lowering the quantum yield of the second ring-closing.

<table><caption>**Table 3.** Photochemical properties of DTE-based ligands **Bis(DTE-COCF<sub>3</sub>)** and of gold(I) complex [AuCl(Bis(DTE-COCF<sub>3</sub>))].</caption><thead><tr><th></th><th>λ<sup>o</sup><sub>abs</sub> [nm]<br>(ε [M<sup>-1</sup> cm<sup>-1</sup>])<sup>a</sup></th><th>λ<sup>c</sup><sub>abs</sub> [nm]<br>(ε [M<sup>-1</sup> cm<sup>-1</sup>])<sup>b</sup></th><th>PSS<sub>o-c</sub><br>composition<br>[%]<sup>c</sup></th><th>Φ<sub>oo-oc</sub><sup>d</sup></th><th>Φ<sub>oc-cc</sub><sup>d</sup></th><th>Φ<sub>cc-oc</sub><sup>e</sup></th><th>Φ<sub>oc-oo</sub><sup>e</sup></th></tr></thead><tbody><tr><td><b>Bis(DTE-COCF<sub>3</sub>)</b></td><td>273 (32 423), 336<br>(5 820)</td><td>599 (22 000)</td><td>7:84:9</td><td>0.435</td><td>0.020</td><td>0.032</td><td>0.022</td></tr><tr><td>[AuCl(Bis(DTE-COCF<sub>3</sub>))]</td><td>262 (47 527), 336<br>(7 727)</td><td>589 (26 542)</td><td>10:77:13</td><td>0.246</td><td>0.007</td><td>0.026</td><td>0.023</td></tr></tbody></table>

<sup>a</sup> Wavelength and molar absorptivity coefficient of the absorption band maxima of the open isomer (the **oo** state) in cyclohexane. <sup>b</sup> Wavelength and molar absorptivity coefficient of the maximum of the visible absorption band of the closed isomer (the **cc** state) in cyclohexane. <sup>c</sup> Composition of the PSS reached for the photocyclization process in toluene-d<sub>8</sub> upon irradiation at λ<sub>exc</sub> = 365 nm. DTE<sup>oo</sup>:DTE<sup>oc</sup>:DTE<sup>cc</sup> concentration ratios are given. <sup>d</sup> Photocyclization quantum yields measured in cyclohexane at λ<sub>exc</sub> = 355 nm. <sup>e</sup> Photocycloreversion quantum yields measured in cyclohexane at λ<sub>exc</sub> = 532 nm.

Importantly, the preparation of the corresponding phosphine selenides and their analysis by NMR demonstrated that the fully closed form of the ligand **1cc** experienced the largest modulation of electron density reported to date for photoswitchable phosphines (Δ<sup>cc-oo</sup>(<sup>1</sup>J<sub>P,Se</sub>) = 19 Hz).

<figure><img src="image_177.png" /><figcaption>**Scheme 3.** Photoisomerization-induced variation of <sup>1</sup>J<sub>P,Se</sub> in the **oo**, **oc** and **cc** isomers of phosphine selenide.</figcaption></figure>

To corroborate this experimental result, several descriptors commonly used to assess the electronic properties of ground state phosphines were computed using DFT calculations at the B3LYP-D3/6,31G(d,p) level. On the one hand, clear decrements in the Mulliken charge on the phosphorus atom of **Bis(DTE-COCF<sub>3</sub>)** were predicted upon DTE ring-closing (Δ(q<sub>P</sub><sup>Mulliken</sup>), Table 4). While the first DTE photocyclization process in **Bis(DTE-COCF<sub>3</sub>)** should result in a similar Δ(q<sub>P</sub><sup>Mulliken</sup>), value as for monoDTE-
based phosphine **DTE-COCF<sub>3</sub>**, the second ring-closing reaction should lead to further lowering of the electron density on phosphorus. This effect is typically accompanied by changes in composition of the lone pair at the phosphorus atom with an increased participation of the s orbital. Indeed, according to NBO analysis, the photoconversion from the **Bis(DTE<sup>oo</sup>-COCF<sub>3</sub>)** to the **Bis(DTE<sup>cc</sup>-COCF<sub>3</sub>)** state must lead to a progressive increment of the contribution of the s orbital to the lone pair of electrons at phosphorus, eventually reaching twice the variation computed for phosphine **DTE-COCF<sub>3</sub>**.

Finally, the ligand-metal bond energies of the respective gold(I) complexes formed with **Bis(DTE-COCF<sub>3</sub>)** and **DTE-COCF<sub>3</sub>** were evaluated. As expected, weaker phosphorus-gold(I) bonds were predicted after DTE ring-closing in both ligands. More importantly, double DTE photocyclization in [AuCl(Bis(DTE-COCF<sub>3</sub>))] should result in almost a two-fold variation in ligand-metal binding energies compared to the complex with monoDTE-based phosphine **DTE-COCF<sub>3</sub>**. This result confirms the capacity to accomplish large photomodulation in the electronic properties of phosphines by tethering two photoswitchable DTE units to a central phosphorus atom.

<table><caption>**Table 4.** Experimental and computed parameters to estimate the photomodulation of properties for phosphines Bis(DTE-COCF<sub>3</sub>) and DTE-COCF<sub>3</sub>.</caption><thead><tr><th rowspan="2"></th><th colspan="2">Δ(<sup>1</sup>J<sub>P,Se</sub>) [Hz]<sup>a</sup></th><th colspan="2">Δ(q<sub>p</sub><sup>Mulliken</sup>)<sup>b</sup></th><th colspan="2">Δ(%S<sub>p</sub>)<sup>c</sup></th><th colspan="2">Δ(BE<sub>P-Au</sub>)<br/>[kcal·mol<sup>-1</sup>]<sup>d</sup></th></tr><tr><th>oo → oc</th><th>oo → cc</th><th>oo → oc</th><th>oo → cc</th><th>oo → oc</th><th>oo → cc</th><th>oo → oc</th><th>oo → cc</th></tr></thead><tbody><tr><td>Bis(DTE-COCF<sub>3</sub>)</td><td>11</td><td>19</td><td>0.011</td><td>0.036</td><td>0.52</td><td>1.58</td><td>1.52</td><td>2.13</td></tr><tr><td></td><td colspan="2">o → c</td><td colspan="2">o → c</td><td colspan="2">o → c</td><td colspan="2">o → c</td></tr><tr><td>DTE-COCF<sub>3</sub></td><td colspan="2">14<sup>26</sup></td><td colspan="2">0.014<sup>26</sup></td><td colspan="2">0.79<sup>26</sup></td><td colspan="2">1.23</td></tr></tbody></table>

## Diazocine-based photoswitchable phosphine

In an attempt to achieve metal catalyst photomodulation based on geometric effects, the use of diazocine photoswitches was explored. By introducing two phosphanyl groups to this type of photoswitchable scaffold, it was envisioned to modify their coordination mode to metals under irradiation. Through DFT calculations, the preferred substitution pattern of the diazocine core to accomplish this goal was identified: it involved installing the two phosphanyl substituents at positions 1,10 of the diazocine (Figure 5). For this particular type of ligand structures, variation of the coordination mode was computationally revealed, as their Z isomer could act as a bidentate ligand while their E isomer could only monocoordinate metal centers due to the increased separation distance between the phosphanyl groups.

Encouraged by these results, several synthetic routes were explored to prepare the desired 1,10-disubstituted diazocine-based bisphosphines. However, functionalization of these positions of the diazocine core with diphenylphosphine groups could not be accomplished, in contrast to what was observed for other positions of the photoswitch scaffold. This indicates that the derivatization of diazocines at the target positions 1,10 is severely hampered by steric hindrance effects.

<footnote><sup>a</sup> Difference in <sup>1</sup>J<sub>P,Se</sub> for the corresponding selenides measured in CDCl<sub>3</sub>. <sup>b</sup> Difference in Mulliken charges in electronic units on the phosphorus atom. <sup>c</sup> Difference in percentage of s character of the lone pair of electrons at phosphorus. <sup>d</sup> Difference in phosphine-Au bond energy.</footnote>
based phosphine **DTE-COCF<sub>3</sub>**, the second ring-closing reaction should lead to further lowering of the electron density on phosphorus. This effect is typically accompanied by changes in composition of the lone pair at the phosphorus atom with an increased participation of the s orbital. Indeed, according to NBO analysis, the photoconversion from the **Bis(DTE<sup>oo</sup>-COCF<sub>3</sub>)** to the **Bis(DTE<sup>cc</sup>-COCF<sub>3</sub>)** state must lead to a progressive increment of the contribution of the s orbital to the lone pair of electrons at phosphorus, eventually reaching twice the variation computed for phosphine **DTE-COCF<sub>3</sub>**.

Finally, the ligand-metal bond energies of the respective gold(I) complexes formed with **Bis(DTE-COCF<sub>3</sub>)** and **DTE-COCF<sub>3</sub>** were evaluated. As expected, weaker phosphorus-gold(I) bonds were predicted after DTE ring-closing in both ligands. More importantly, double DTE photocyclization in [AuCl(Bis(DTE-COCF<sub>3</sub>))] should result in almost a two-fold variation in ligand-metal binding energies compared to the complex with monoDTE-based phosphine **DTE-COCF<sub>3</sub>**. This result confirms the capacity to accomplish large photomodulation in the electronic properties of phosphines by tethering two photoswitchable DTE units to a central phosphorus atom.

<table><caption>**Table 4.** Experimental and computed parameters to estimate the photomodulation of properties for phosphines Bis(DTE-COCF<sub>3</sub>) and DTE-COCF<sub>3</sub>.</caption><thead><tr><th rowspan="2"></th><th colspan="2">Δ(<sup>1</sup>J<sub>P,Se</sub>) [Hz]<sup>a</sup></th><th colspan="2">Δ(q<sub>p</sub><sup>Mulliken</sup>)<sup>b</sup></th><th colspan="2">Δ(%S<sub>p</sub>)<sup>c</sup></th><th colspan="2">Δ(BE<sub>P-Au</sub>)<br/>[kcal·mol<sup>-1</sup>]<sup>d</sup></th></tr><tr><th>oo → oc</th><th>oo → cc</th><th>oo → oc</th><th>oo → cc</th><th>oo → oc</th><th>oo → cc</th><th>oo → oc</th><th>oo → cc</th></tr></thead><tbody><tr><td>Bis(DTE-COCF<sub>3</sub>)</td><td>11</td><td>19</td><td>0.011</td><td>0.036</td><td>0.52</td><td>1.58</td><td>1.52</td><td>2.13</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>DTE-COCF<sub>3</sub></td><td>14<sup>26</sup></td><td></td><td>0.014<sup>26</sup></td><td></td><td>0.79<sup>26</sup></td><td></td><td>1.23</td><td></td></tr></tbody></table>

## Diazocine-based photoswitchable phosphine

In an attempt to achieve metal catalyst photomodulation based on geometric effects, the use of diazocine photoswitches was explored. By introducing two phosphanyl groups to this type of photoswitchable scaffold, it was envisioned to modify their coordination mode to metals under irradiation. Through DFT calculations, the preferred substitution pattern of the diazocine core to accomplish this goal was identified: it involved installing the two phosphanyl substituents at positions 1,10 of the diazocine (Figure 5). For this particular type of ligand structures, variation of the coordination mode was computationally revealed, as their Z isomer could act as a bidentate ligand while their E isomer could only monocoordinate metal centers due to the increased separation distance between the phosphanyl groups.

Encouraged by these results, several synthetic routes were explored to prepare the desired 1,10-disubstituted diazocine-based bisphosphines. However, functionalization of these positions of the diazocine core with diphenylphosphine groups could not be accomplished, in contrast to what was observed for other positions of the photoswitch scaffold. This indicates that the derivatization of diazocines at the target positions 1,10 is severely hampered by steric hindrance effects.

<footnote><sup>a</sup> Difference in <sup>1</sup>J<sub>P,Se</sub> for the corresponding selenides measured in CDCl<sub>3</sub>. <sup>b</sup> Difference in Mulliken charges in electronic units on the phosphorus atom. <sup>c</sup> Difference in percentage of s character of the lone pair of electrons at phosphorus. <sup>d</sup> Difference in phosphine-Au bond energy.</footnote>
<figure><img src="image_180.png" /><figcaption>**Figure 5** – Computed structures of the Z and E states of the free ligands and palladium(II) complexes of a 1,10-disubstituted diazocine-based bisphosphine. A clear change in separation distance between the two phosphanyl groups occurs upon Z-E photoisomerization, which leads to a variation of the coordination mode to the metal center.</figcaption></figure>

Conclusions and outlook

A library of DTE-substituted ligands was developed in this thesis to validate two new concepts for the modulation of phosphine electron properties upon irradiation: (i) switching the communication between phosphanyl and electron-withdrawing groups installed at the 5 and 5' positions of the thiophene rings of the DTE core; and (ii) connecting two of these DTE photoswitches to the same phosphine. The resulting ligands showed ample variation of phosphine σ-donation ability upon DTE photoisomerization. Aiming to exploit this behavior in photoswitchable catalysis, they were complexed to metal centers and Pd" complexes were tested as pre-catalysts for a model Stille coupling reaction, where a change in catalytic activity was observed for the different isomerization states of the system. These results open new ways for the application of DTE-induced electronic changes on ligands in the field of photoswitchable catalysis.

As for the attempt to pioneer the use of diazocines to light-control metal-based catalysis, the synthesis of the target diazocine-based phosphines was not successful. Despite this, valuable knowledge was gained about how to use this type of scaffold for photoswitchable catalysis and what challenges must be faced during their derivatization. To ultimately bring this molecular design to life, further exploration of the synthetic approaches towards diazocine-based ligands is therefore required.

References

[1] T. Traut, *Enzyme Activity: Allosteric Regulation*, in *Encyclopedia of Life Sciences*, John Wiley & Sons, Ltd, **2014**. ISBN: 9780470015902. DOI: **10.1002/9780470015902.a0000865.pub3**.

[2] J. Choudhury, *Tetrahedron Lett.*, **2018**, *59*, 487-495. DOI: **10.1016/j.tetlet.2017.12.070**.

[3] V. Blanco, D. A. Leigh, V. Marcos, *Chem. Soc. Rev.*, **2015**, *44*, 5341-5370. DOI: **10.1039/C5CS00096C**.

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<figure><img src="image_178.png" /><figcaption>**Figure 5** – Computed structures of the Z and E states of the free ligands and palladium(II) complexes of a 1,10-disubstituted diazocine-based bisphosphine. A clear change in separation distance between the two phosphanyl groups occurs upon Z-E photoisomerization, which leads to a variation of the coordination mode to the metal center.</figcaption></figure>

Conclusions and outlook

A library of DTE-substituted ligands was developed in this thesis to validate two new concepts for the modulation of phosphine electron properties upon irradiation: (i) switching the communication between phosphanyl and electron-withdrawing groups installed at the 5 and 5' positions of the thiophene rings of the DTE core; and (ii) connecting two of these DTE photoswitches to the same phosphine. The resulting ligands showed ample variation of phosphine σ-donation ability upon DTE photoisomerization. Aiming to exploit this behavior in photoswitchable catalysis, they were complexed to metal centers and Pd" complexes were tested as pre-catalysts for a model Stille coupling reaction, where a change in catalytic activity was observed for the different isomerization states of the system. These results open new ways for the application of DTE-induced electronic changes on ligands in the field of photoswitchable catalysis.

As for the attempt to pioneer the use of diazocines to light-control metal-based catalysis, the synthesis of the target diazocine-based phosphines was not successful. Despite this, valuable knowledge was gained about how to use this type of scaffold for photoswitchable catalysis and what challenges must be faced during their derivatization. To ultimately bring this molecular design to life, further exploration of the synthetic approaches towards diazocine-based ligands is therefore required.

References

[1] T. Traut, *Enzyme Activity: Allosteric Regulation*, in *Encyclopedia of Life Sciences*, John Wiley & Sons, Ltd, **2014**. ISBN: 9780470015902. DOI: **10.1002/9780470015902.a0000865.pub3**.

[2] J. Choudhury, *Tetrahedron Lett.*, **2018**, *59*, 487-495. DOI: **10.1016/j.tetlet.2017.12.070**.

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[4] G. C. Thaggard, J. Haimerl, R. A. Fischer, K. C. Park, N. B. Shustova, *Angew. Chem. Int. Ed.*, **2023**, e202302859. DOI: **10.1002/anie.202302859**.

[5] D. Hugenbusch, M. Lehr, J.-S. von Glasenapp, A. J. McConnell, R. Herges, *Angew. Chem. Int. Ed.*, **2023**, *62*, e202212571. DOI: **10.1002/anie.202212571**.

[6] H. Lee, J. Tessarolo, D. Langbehn, A. Baksi, R. Herges, G. H. Clever, *J. Am. Chem. Soc.*, **2022**, *144*, 3099-3105. DOI: **10.1021/jacs.1c12011**.

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[9] H. Z. Wei, Y. Wei, M. Shi, *Chem. Asian J.*, **2023**, *18*, e202300633. DOI: **10.1002/asia.202300633**.
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[14] A. G. Orpen, N. G. Connelly, *Organometallics*, **1990**, *9*, 1206–1210. DOI: **10.1021/om00118a048**.

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[16] C. A. Tolman, *Chem. Rev.*, **1977**, *77*, 313–348. DOI: **10.1021/cr60307a002**.

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Paven KISTEN

ESR8

**Thesis co-directors**

Prof. Simon Duckett,
Prof. Jason Lynam,
Dr. John Slattery

University of York, York, United Kingdom

Prof. Rinaldo Poli

Laboratoire de Chimie de Coordination, Toulouse, France

**Thesis defense**

Department of Chemistry, University of York, 28 November 2023
Paven KISTEN

ESR8

**Thesis co-directors**

Prof. Simon Duckett,
Prof. Jason Lynam,
Dr. John Slattery

University of York, York, United Kingdom

Prof. Rinaldo Poli

Laboratoire de Chimie de Coordination, Toulouse, France

**Thesis defense**

Department of Chemistry, University of York, 28 November 2023
<figure><img src="image_181.png" /></figure>
<figure><img src="image_179.png" /></figure>
# Ir¹(η⁴-diene) Precatalyst Activation: Role of the Base

## Ir¹ (η⁴-diene) precatalyst activation by strong bases and formation of monohydrides

The reaction of 1<sup>dppe</sup> with NaOMe results in the formation of two iridium monohydride isomers, 2<sup>dppe</sup> and 3<sup>dppe</sup> (Scheme 1). These have been characterized by NMR spectroscopy and demonstrate the difference in the binding of the COD ligand. The hydride is proposed to form via beta hydrogen elimination from the alkoxide releasing acetone (formaldehyde in the case of methoxide).

<figure><img src="image_182.png" /><figcaption>**Scheme 1.** Reaction of 1<sup>dppe</sup> with a base containing a β-hydrogen to form 2<sup>dppe</sup> and 3<sup>dppe</sup>.</figcaption></figure>

Following the successful synthesis and characterisation of 2<sup>dppe</sup> and 3<sup>dppe</sup>, the isomerization process was tracked via <sup>31</sup>P NMR monitoring (Figure 1), which led to observable kinetic metrics. These values were used to obtain the Gibbs energy difference of 2.06 ± 0.16 kcal mol<sup>-1</sup>, and an energy barrier of 22.19 ± 0.04 kcal mol<sup>-1</sup> for the isomerization of 2<sup>dppe</sup> to 3<sup>dppe</sup>. These values rationalise the preference for 3<sup>dppe</sup> rather than 2<sup>dppe</sup>.

<figure><img src="image_183.png" /><figcaption>**Figure 1.** Time evolution of the <sup>31</sup>P({H}) data for the 1<sup>dppe</sup> decay and 2<sup>dppe</sup>-3<sup>dppe</sup> isomerization. The continuous lines are the result of the non-linear least-squares fit.</figcaption></figure>

While the kinetic study gives energy metrics, the exact nature of the isomerization process was unknown, as such a DFT study was performed to elucidate a potential isomerization mechanism. The results of this study indicate that the isomerization proceeds via a neutral intermediate
# Ir(I)(η^4^-diene) Precatalyst Activation: Role of the Base

## Ir(I)(η^4^-diene) precatalyst activation by strong bases and formation of monohydrides

The reaction of 1<sup>dppe</sup> with NaOMe results in the formation of two iridium monohydride isomers, 2<sup>dppe</sup> and 3<sup>dppe</sup> (Scheme 1). These have been characterized by NMR spectroscopy and demonstrate the difference in the binding of the COD ligand. The hydride is proposed to form via beta hydrogen elimination from the alkoxide releasing acetone (formaldehyde in the case of methoxide).

<figure><img src="image_180.png" /><figcaption>**Scheme 1.** Reaction of 1<sup>dppe</sup> with a base containing a β-hydrogen to form 2<sup>dppe</sup> and 3<sup>dppe</sup>.</figcaption></figure>

Following the successful synthesis and characterisation of 2<sup>dppe</sup> and 3<sup>dppe</sup>, the isomerization process was tracked via <sup>31</sup>P NMR monitoring (Figure 1), which led to observable kinetic metrics. These values were used to obtain the Gibbs energy difference of 2.06 ± 0.16 kcal mol<sup>-1</sup>, and an energy barrier of 22.19 ± 0.04 kcal mol<sup>-1</sup> for the isomerization of 2<sup>dppe</sup> to 3<sup>dppe</sup>. These values rationalise the preference for 3<sup>dppe</sup> rather than 2<sup>dppe</sup>.

<figure><img src="image_181.png" /><figcaption>**Figure 1.** Time evolution of the <sup>31</sup>P({H}) data for the 1<sup>dppe</sup> decay and 2<sup>dppe</sup>-3<sup>dppe</sup> isomerization. The continuous lines are the result of the non-linear least-squares fit.</figcaption></figure>

While the kinetic study gives energy metrics, the exact nature of the isomerization process was unknown, as such a DFT study was performed to elucidate a potential isomerization mechanism. The results of this study indicate that the isomerization proceeds via a neutral intermediate
[Ir(C<sub>8</sub>H<sub>13</sub>)(dppe)] (I<sup>dppe</sup>). Two transition states were proposed one that links 2<sup>dppe</sup> to I<sup>dppe</sup> (TS<sub>(2-1)</sub><sup>dppe</sup>) and the other linking I<sup>dppe</sup> to 3<sup>dppe</sup> (TS<sub>(3-1)</sub><sup>dppe</sup>) (Figure 2), the latter of which is observed experimentally.

To evaluate the effect of different bases, NaOMe was replaced by KO<sup>t</sup>Bu. Consequently, when KO<sup>t</sup>Bu was added to 1<sup>dppe</sup> in non-polar solvents such as benzene, toluene or THF two previously unreported complexes were seen (4<sup>dppe</sup> and 5<sup>dppe</sup>) (Scheme 2). These products correspond to structural isomers of an [IrH(C<sub>8</sub>H<sub>10</sub>)(dppe)] complex. Each product was extensively characterized using NMR spectroscopy, and the isomerization process between 4<sup>dppe</sup> and 5<sup>dppe</sup> was also studied using NMR spectroscopic methods (Figure 3).

<figure><img src="image_184.png" /><figcaption>**Scheme 2.** Reaction of 1<sup>dppe</sup> with KO<sup>t</sup>Bu in benzene to form 4<sup>dppe</sup> and 5<sup>dppe</sup>.</figcaption></figure>

<figure><img src="image_185.png" /><figcaption>**Figure 2.** Gibbs energy profile (in kcal mol<sup>-1</sup>) for the isomerization of 2<sup>dppe</sup> to 3<sup>dppe</sup>. Relative energies shown with 2<sup>dppe</sup> as the reference point.</figcaption></figure>

The immediate disappearance of 1<sup>dppe</sup> (within the time needed to record the first <sup>31</sup>P-{<sup>1</sup>H} NMR spectrum after the addition of KO<sup>t</sup>Bu to 1<sup>dppe</sup>) reflects a rapid first step, allowing clean timescale separation from the second step, such that analysis of the latter by standard reversible first-order reaction kinetics was possible. By using the experimentally determined rate constants – the energy barrier associated with the isomerization could then be calculated by applying the Eyring relationship 22.3 ± 0.1 kcal mol<sup>-1</sup>, and the energy difference between 4<sup>dppe</sup> and 5<sup>dppe</sup> of 0.51 ± 0.04 kcal mol<sup>-1</sup> (in benzene-d<sub>6</sub>).
[Ir(C<sub>8</sub>H<sub>13</sub>)(dppe)] (I<sup>dppe</sup>). Two transition states were proposed one that links 2<sup>dppe</sup> to I<sup>dppe</sup> (TS<sub>(2-1)</sub><sup>dppe</sup>) and the other linking I<sup>dppe</sup> to 3<sup>dppe</sup> (TS<sub>(3-1)</sub><sup>dppe</sup>) (Figure 2), the latter of which is observed experimentally.

To evaluate the effect of different bases, NaOMe was replaced by KO<sup>t</sup>Bu. Consequently, when KO<sup>t</sup>Bu was added to 1<sup>dppe</sup> in non-polar solvents such as benzene, toluene or THF two previously unreported complexes were seen (4<sup>dppe</sup> and 5<sup>dppe</sup>) (Scheme 2). These products correspond to structural isomers of an [IrH(C<sub>8</sub>H<sub>10</sub>)(dppe)] complex. Each product was extensively characterized using NMR spectroscopy, and the isomerization process between 4<sup>dppe</sup> and 5<sup>dppe</sup> was also studied using NMR spectroscopic methods (Figure 3).

<figure><img src="image_182.png" /><figcaption>**Scheme 2.** Reaction of 1<sup>dppe</sup> with KO<sup>t</sup>Bu in benzene to form 4<sup>dppe</sup> and 5<sup>dppe</sup>.</figcaption></figure>

<figure><img src="image_183.png" /><figcaption>**Figure 2.** Gibbs energy profile (in kcal mol<sup>-1</sup>) for the isomerization of 2<sup>dppe</sup> to 3<sup>dppe</sup>. Relative energies shown with 2<sup>dppe</sup> as the reference point.</figcaption></figure>

The immediate disappearance of 1<sup>dppe</sup> (within the time needed to record the first <sup>31</sup>P{<sup>1</sup>H} NMR spectrum after the addition of KO<sup>t</sup>Bu to 1<sup>dppe</sup>) reflects a rapid first step, allowing clean timescale separation from the second step, such that analysis of the latter by standard reversible first-order reaction kinetics was possible. By using the experimentally determined rate constants – the energy barrier associated with the isomerization could then be calculated by applying the Eyring relationship 22.3 ± 0.1 kcal mol<sup>-1</sup>, and the energy difference between 4<sup>dppe</sup> and 5<sup>dppe</sup> of 0.51 ± 0.04 kcal mol<sup>-1</sup> (in benzene-d<sub>6</sub>).
<figure><img src="image_186.png" /><figcaption>**Figure 3.** Time evolution of the <sup>31</sup>P({<sup>2</sup>H}) NMR data for the first order kinetics of the 4<sup>dppe</sup> to 5<sup>dppe</sup> isomerization in benzene-d<sub>6</sub> at 298 K.</figcaption></figure>

The exact nature of the formation of 4<sup>dppe</sup> from 1<sup>dppe</sup> without a β-hydrogen containing alkoxide initially caused much speculation about the exact nature of the reaction. Hence, a DFT study was conducted both on the formation of a monohydride from 1<sup>dppe</sup> and on the isomerization of 4<sup>dppe</sup> to 5<sup>dppe</sup>. It was proposed that the reaction proceeds first via deprotonation of the COD ligand leading to a neutral 16-electron [Ir(C<sub>8</sub>H<sub>11</sub>)(dppe)]

<figure><img src="image_187.png" /><figcaption>**Scheme 3.** Deprotonation of the COD ligand leading to two different [Ir(C<sub>8</sub>H<sub>11</sub>)(dppe)] (II<sup>dppe</sup> and II''<sup>dppe</sup>) isomers and their respective conformers with a flipped Ir(dppe) moiety (II''<sup>dppe</sup> and II'''<sup>dppe</sup>) (phenyl rings removed for clarity).</figcaption></figure>

The different pathways from [Ir(C<sub>8</sub>H<sub>11</sub>)(dppe)] to [IrH(C<sub>8</sub>H<sub>10</sub>)(dppe)] were all explored, however, the result that corresponded to the structural data for 4<sup>dppe</sup> and indeed the lowest energy isomer was
<figure><img src="image_184.png" /><figcaption>**Figure 3.** Time evolution of the $ ^{31}P\{^{1}H} $ NMR data for the first order kinetics of the $4^{dppe} $ to $5^{dppe} $ isomerization in benzene-d$_{6}$ at 298 K.</figcaption></figure>

The exact nature of the formation of 4<sup>dppe</sup> from 1<sup>dppe</sup> without a β-hydrogen containing alkoxide initially caused much speculation about the exact nature of the reaction. Hence, a DFT study was conducted both on the formation of a monohydride from 1<sup>dppe</sup> and on the isomerization of 4<sup>dppe</sup> to 5<sup>dppe</sup>. It was proposed that the reaction proceeds first via deprotonation of the COD ligand leading to a neutral 16-electron [Ir(C<sub>8</sub>H<sub>11</sub>)(dppe)]

<figure><img src="image_185.png" /><figcaption>**Scheme 3.** Deprotonation of the COD ligand leading to two different [Ir(C<sub>8</sub>H<sub>11</sub>)(dppe)] (II<sup>dppe</sup> and II''<sup>dppe</sup>) isomers and their respective conformers with a flipped Ir(dppe) moiety (II''<sup>dppe</sup> and II'''<sup>dppe</sup>) (phenyl rings removed for clarity).</figcaption></figure>

The different pathways from [Ir(C<sub>8</sub>H<sub>11</sub>)(dppe)] to [IrH(C<sub>8</sub>H<sub>10</sub>)(dppe)] were all explored, however, the result that corresponded to the structural data for 4<sup>dppe</sup> and indeed the lowest energy isomer was
when β-hydride elimination occurs at carbon C8 (Scheme 4, Figure 4).

<figure><img src="image_188.png" /><figcaption>**Scheme 4.** Generation of 4<sup>dppe</sup> from II<sup>dppe</sup>. The phenyl groups on the dppe are omitted for clarity. (Relative energy profiles in kcal mol<sup>-1</sup>).</figcaption></figure>

<figure><img src="image_189.png" /><figcaption>**Figure 4.** Gibbs-energy profile (in kcal mol<sup>-1</sup>) for all possible β-H elimination reactions from intermediate II<sup>dppe</sup>.</figcaption></figure>

It is notable that the lowest-energy product obtained from II<sup>dppe</sup> (4<sup>dppe</sup>) features the uncoordinated alkene moiety syn relative to the hydride ligand. No direct pathway is available to transform intermediate II<sup>dppe</sup> to isomer 5<sup>dppe</sup>, for which, on the other hand, the uncoordinated alkene moiety is located anti relative to the hydride ligand. Hence, the isomerization must occur through a different pathway. Exploration of the various possibilities to rotate the C<sub>8</sub>H<sub>10</sub> around the metal
when β-hydride elimination occurs at carbon C8 (Scheme 4, Figure 4).

<figure><img src="image_186.png" /><figcaption>**Scheme 4.** Generation of 4<sup>dppe</sup> from II<sup>dppe</sup>. The phenyl groups on the dppe are omitted for clarity. (Relative energy profiles in kcal mol<sup>-1</sup>).</figcaption></figure>

<figure><img src="image_187.png" /><figcaption>**Figure 4.** Gibbs-energy profile (in kcal mol<sup>-1</sup>) for all possible β-H elimination reactions from intermediate II<sup>dppe</sup>.</figcaption></figure>

It is notable that the lowest-energy product obtained from II<sup>dppe</sup> (4<sup>dppe</sup>) features the uncoordinated alkene moiety syn relative to the hydride ligand. No direct pathway is available to transform intermediate II<sup>dppe</sup> to isomer 5<sup>dppe</sup>, for which, on the other hand, the uncoordinated alkene moiety is located anti relative to the hydride ligand. Hence, the isomerization must occur through a different pathway. Exploration of the various possibilities to rotate the C<sub>8</sub>H<sub>10</sub> around the metal
coordination sphere revealed a low-energy pathway linking 4<sup>dppe</sup> to a different structural isomer of 5<sup>dppe</sup>, 5'<sup>dppe</sup>. 5'<sup>dppe</sup> has an ethylene bridge in the equatorial plane, essentially a diastereomer of 5<sup>dppe</sup>, 0.7 kcal mol<sup>-1</sup> higher than 5<sup>dppe</sup> and 0.2 kcal mol<sup>-1</sup> higher than 4<sup>dppe</sup>. The isomerization of 4<sup>dppe</sup> to 5<sup>dppe</sup> proceeds via the rearrangement schematically illustrated in Figure 5. This entails a rotation of the C<sub>8</sub>H<sub>10</sub> ligand relative to the Ir-H axis via TS<sub>(4-5)</sub><sup>dppe</sup> with simultaneous displacement toward the Ir atom of the two CH groups of the uncoordinated alkene, which become part of coordinated η<sup>3</sup> moiety, and the inverse displacement of the two CH groups of the coordinated η<sup>3</sup> moiety that end up forming the uncoordinated alkene moiety.

<figure><img src="image_190.png" /><figcaption>Figure 5. Gibbs energy profile (in kcal mol<sup>-1</sup>) for the isomerization of 4<sup>dppe</sup> to 5<sup>dppe</sup>.</figcaption></figure>

The solid-state structure indicates that the cyclooctadienyl ligand is disordered with respect to C2 and C8. The atomic displacement parameters of the disordered pairs of carbons were constrained to be equal (C2 & C2A, C8 & C8A). This disorder is due to the two possible positions of the uncoordinated double bond (C2=C3 or C7=C8A). Separation of the two superimposed structures, leads to two different structural isomers, that represent 4<sup>dppe</sup> (Figure 6) and 5<sup>dppe</sup> (Figure 7). Both of which correspond remarkably well to the respective optimized DFT structures.

<figure><img src="image_191.png" /></figure>
coordination sphere revealed a low-energy pathway linking 4<sup>dppe</sup> to a different structural isomer of 5<sup>dppe</sup>, 5'<sup>dppe</sup>. 5'<sup>dppe</sup> has an ethylene bridge in the equatorial plane, essentially a diastereomer of 5<sup>dppe</sup>, 0.7 kcal mol<sup>-1</sup> higher than 5<sup>dppe</sup> and 0.2 kcal mol<sup>-1</sup> higher than 4<sup>dppe</sup>. The isomerization of 4<sup>dppe</sup> to 5<sup>dppe</sup> proceeds via the rearrangement schematically illustrated in Figure 5. This entails a rotation of the C<sub>8</sub>H<sub>10</sub> ligand relative to the Ir-H axis via TS<sub>(4-5)</sub><sup>dppe</sup> with simultaneous displacement toward the Ir atom of the two CH groups of the uncoordinated alkene, which become part of coordinated η<sup>3</sup> moiety, and the inverse displacement of the two CH groups of the coordinated η<sup>3</sup> moiety that end up forming the uncoordinated alkene moiety.

<figure><img src="image_188.png" /><figcaption>**Figure 5.** Gibbs energy profile (in kcal mol<sup>-1</sup>) for the isomerization of 4<sup>dppe</sup> to 5<sup>dppe</sup>.</figcaption></figure>

The solid-state structure indicates that the cyclooctadienyl ligand is disordered with respect to C2 and C8. The atomic displacement parameters of the disordered pairs of carbons were constrained to be equal (C2 & C2A, C8 & C8A). This disorder is due to the two possible positions of the uncoordinated double bond (C2=C3 or C7=C8A). Separation of the two superimposed structures, leads to two different structural isomers, that represent 4<sup>dppe</sup> (Figure 6) and 5<sup>dppe</sup> (Figure 7). Both of which correspond remarkably well to the respective optimized DFT structures.

<figure><img src="image_189.png" /></figure>
**Figure 6.** DFT and solid-state structure of 4<sup>dppe</sup>. Anisotropic displacement ellipsoids are shown at 50% probability level. The hydrogen atoms on dppe are omitted for clarity.

<figure><img src="image_192.png" /></figure>

**Figure 7.** DFT and solid-state structure of 5<sup>dppe</sup>. Anisotropic displacement ellipsoids are shown at 50% probability level. The hydrogen atoms on dppe are omitted for clarity.

## Characterization of Anionic Ir<sup>III</sup> Tetrahydride Complexes and their role in Transfer Hydrogenation

A reproduceable route to form three different anionic Ir<sup>III</sup> tetrahydride complexes from the chloride containing precursors ([IrCl(COD)(L<sub>2</sub>)] (L<sub>2</sub> = dppe, dppf, S-BINAP) under hydrogenation and transfer hydrogenation conditions were demonstrated (Scheme 5).

<figure><img src="image_193.png" /></figure>

**Scheme 5.** Synthetic route towards forming an anionic tetrahydride 6<sup>L2</sup> from the corresponding chloride precursor 1<sup>L2</sup> under transfer hydrogenation conditions. L<sub>2</sub> = dppe, dppf, (S)-BINAP.

The clean formation of an anionic tetrahydrido product only occurred when a suitable counter cation is present in the solution (in this case from the base). In contrast, in the absence of a base, under hydrogenation conditions, a complicated mixture of iridium hydride derived products was observed. However, the subsequent addition of base to these mixtures results in a single tetrahydride product. In all cases the cyclooctadiene ligand was selectively removed as cyclooctene to yield what is deemed as the catalytically active species 6<sup>L2</sup> (Scheme 6).

In the absence of a substrate, and when H<sub>2</sub> pressure was released, 6<sup>dppe</sup> dimerizes to form a neutral trihydride dimer (Figure 8). The crystal structure obtained is sufficient to support the dimerization process, however, this structure does not pinpoint the exact positions of the hydride ligands. Based on other dimeric iridium hydride complexes with diphosphine ligands reported in the literature such as [Ir(H)<sub>2</sub>(dtbpe)]<sub>2</sub><sup>+</sup> (dtbpe = 1,2-bis(di-tert-butylphosphino)ethane) [1] and
**Figure 6.** DFT and solid-state structure of 4<sup>dppe</sup>. Anisotropic displacement ellipsoids are shown at 50% probability level. The hydrogen atoms on dppe are omitted for clarity.

<figure><img src="image_190.png" /></figure>

**Figure 7.** DFT and solid-state structure of 5<sup>dppe</sup>. Anisotropic displacement ellipsoids are shown at 50% probability level. The hydrogen atoms on dppe are omitted for clarity.

## Characterization of Anionic Ir<sup>III</sup> Tetrahydride Complexes and their role in Transfer Hydrogenation

A reproduceable route to form three different anionic Ir<sup>III</sup> tetrahydride complexes from the chloride containing precursors ([IrCl(COD)(L<sub>2</sub>)] (L<sub>2</sub> = dppe, dppf, S-BINAP) under hydrogenation and transfer hydrogenation conditions were demonstrated (Scheme 5).

<figure><img src="image_191.png" /></figure>

**Scheme 5.** Synthetic route towards forming an anionic tetrahydride 6<sup>L2</sup> from the corresponding chloride precursor 1<sup>L2</sup> under transfer hydrogenation conditions. L<sub>2</sub> = dppe, dppf, (S)-BINAP.

The clean formation of an anionic tetrahydrido product only occurred when a suitable counter cation is present in the solution (in this case from the base). In contrast, in the absence of a base, under hydrogenation conditions, a complicated mixture of iridium hydride derived products was observed. However, the subsequent addition of base to these mixtures results in a single tetrahydride product. In all cases the cyclooctadiene ligand was selectively removed as cyclooctene to yield what is deemed as the catalytically active species 6<sup>L2</sup> (Scheme 6).

In the absence of a substrate, and when H<sub>2</sub> pressure was released, 6<sup>dppe</sup> dimerizes to form a neutral trihydride dimer (Figure 8). The crystal structure obtained is sufficient to support the dimerization process, however, this structure does not pinpoint the exact positions of the hydride ligands. Based on other dimeric iridium hydride complexes with diphosphine ligands reported in the literature such as [[Ir(H)<sub>2</sub>(dtbpe)]<sub>2</sub><sup>+</sup> (dtbpe = 1,2-bis(di-tert-butylphosphino)ethane) [1] and
[Ir(H)₃(dfepe)]₂ [2] (dfepe = (C₂F₅)₂-PCH₂CH₂P-(C₂F₅)₂) [3], a DFT investigation was conducted. Using the asymmetric unit cell structure of [Ir(dppe)]₂, six hydride ligands were added to create three different isomers, with bridging hydride ligands as shown in Scheme 7. Each of these systems were then computed to find a local minimum. The isomer with two bridging hydride ligands was found to be the most stable of the three computed, and the only structure that reached a local minimum. However, in the case of both dppf and dppe, the presence of coordinating DMSO suppressed the formation of the tetrahydrido species and a neutral trihydride resulted from the reaction (Scheme 8).

<figure><img src="image_194.png" /><figcaption>**Scheme 6.** Idealized stoichiometry for the generation of 6<sup>dppe</sup> from 1<sup>dppe</sup> under both hydrogenation and transfer hydrogenation conditions in isopropanol.</figcaption></figure>

<figure><img src="image_195.png" /><figcaption>**Figure 8.** X-Ray structure of [Ir(H)₃(dppe)]₂. Anisotropic displacement ellipsoids are drawn at the 50% probability level. Hydrogen atoms on dppe are omitted for clarity.</figcaption></figure>

<figure><img src="image_196.png" /></figure>
[Ir(H)₃(dfepe)]₂ [2] (dfepe = (C₂F₅)₂-PCH₂CH₂P-(C₂F₅)₂) [3], a DFT investigation was conducted. Using the asymmetric unit cell structure of [Ir(dppe)]₂, six hydride ligands were added to create three different isomers, with bridging hydride ligands as shown in Scheme 7. Each of these systems were then computed to find a local minimum. The isomer with two bridging hydride ligands was found to be the most stable of the three computed, and the only structure that reached a local minimum. However, in the case of both dppf and dppe, the presence of coordinating DMSO suppressed the formation of the tetrahydrido species and a neutral trihydride resulted from the reaction (Scheme 8).

<figure><img src="image_192.png" /><figcaption>**Scheme 6.** Idealized stoichiometry for the generation of 6<sup>dppe</sup> from 1<sup>dppe</sup> under both hydrogenation and transfer hydrogenation conditions in isopropanol.</figcaption></figure>

<figure><img src="image_193.png" /><figcaption>**Figure 8.** X-Ray structure of [Ir(H)₃(dppe)]₂. Anisotropic displacement ellipsoids are drawn at the 50% probability level. Hydrogen atoms on dppe are omitted for clarity.</figcaption></figure>

<figure><img src="image_194.png" /></figure>
**Scheme 7.** Geometries of the different isomers computed. The isomer on the left was found to be the lowest energy system.

<figure><img src="image_197.png" /></figure>

**Scheme 8.** Formation of a neutral trihydride from 1<sup>L2</sup> via the addition of DMSO. L<sub>2</sub> = dppe, dppf.

The three different [IrCl(COD)(L<sub>2</sub>)] complexes were then evaluated for the hydrogenation of acetophenone, all of which showed negligible ee. The activity for each system increased drastically in the presence of KO<sup>t</sup>Bu and was accredited to the formation of the anionic tetrahydrido complexes (Figure 9).

<figure><img src="image_198.png" /><figcaption>**Figure 9.** Results of the asymmetric hydrogenation of acetophenone with [IrCl(COD)(L<sub>2</sub>)] complexes.</figcaption></figure>

A DFT study was conducted to provide a plausible hydrogenation mechanism (Scheme 9), two key transition states were not found (Figure 10), but the study did give an insight into the importance of a proper solvation model for the cation.

The input of the correct starting geometry for the model is of the utmost importance. The lowest energy structure for 7<sup>dppe</sup>, is obtained when the cation is placed near the hydride side of the Ir anion rather than the ligand side, plus an acetone molecule infinitely far apart. When the acetone is closer to the catalyst, it can be observed that stabilization of the cation is provided by the MeOH molecules, and one of the hydrides (Figure 11). After the hydride transfer to the substrate, the K-H distance increases by 0.14 Å. At this point stabilization of the cation is provided by the substrate and is reflected in the close energy difference between 8<sup>dppe</sup> and 9<sup>dppe</sup>.
**Scheme 7.** Geometries of the different isomers computed. The isomer on the left was found to be the lowest energy system.

<figure><img src="image_195.png" /></figure>

**Scheme 8.** Formation of a neutral trihydride from 1<sup>L2</sup> via the addition of DMSO. L<sub>2</sub> = dppe, dppf.

The three different [IrCl(COD)(L<sub>2</sub>)] complexes were then evaluated for the hydrogenation of acetophenone, all of which showed negligible ee. The activity for each system increased drastically in the presence of KO<sup>t</sup>Bu and was accredited to the formation of the anionic tetrahydrido complexes (Figure 9).

<figure><img src="image_196.png" /><figcaption>**Figure 9.** Results of the asymmetric hydrogenation of acetophenone with [IrCl(COD)(L<sub>2</sub>)] complexes.</figcaption></figure>

A DFT study was conducted to provide a plausible hydrogenation mechanism (Scheme 9), two key transition states were not found (Figure 10), but the study did give an insight into the importance of a proper solvation model for the cation.

The input of the correct starting geometry for the model is of the utmost importance. The lowest energy structure for 7<sup>dppe</sup>, is obtained when the cation is placed near the hydride side of the Ir anion rather than the ligand side, plus an acetone molecule infinitely far apart. When the acetone is closer to the catalyst, it can be observed that stabilization of the cation is provided by the MeOH molecules, and one of the hydrides (Figure 11). After the hydride transfer to the substrate, the K-H distance increases by 0.14 Å. At this point stabilization of the cation is provided by the substrate and is reflected in the close energy difference between 8<sup>dppe</sup> and 9<sup>dppe</sup>.
<figure><img src="image_199.png" /><figcaption>**Scheme 9.** Proposed cycle for acetone hydrogenation catalysed by 7<sup>dppe</sup>.</figcaption></figure>

<figure><img src="image_200.png" /><figcaption>**Figure 10.** Computed Gibbs energy profiles for the hydrogenation of acetone with 7<sup>dppe</sup>. Energy profiles is in kcal mol<sup>-1</sup>. The labels shown reference the cycle in Scheme 9, TS<sub>(11-12)dppe</sub> and TS<sub>(12-13)dppe</sub> could not be located (shown in red).</figcaption></figure>
<figure><img src="image_197.png" /><figcaption>**Scheme 9.** Proposed cycle for acetone hydrogenation catalysed by 7<sup>dppe</sup>.</figcaption></figure>

<figure><img src="image_198.png" /><figcaption>**Figure 10.** Computed Gibbs energy profiles for the hydrogenation of acetone with 7<sup>dppe</sup>. Energy profiles is in kcal mol<sup>-1</sup>. The labels shown reference the cycle in Scheme 9, TS<sub>(11-12)dppe</sub> and TS<sub>(12-13)dppe</sub> could not be located (shown in red).</figcaption></figure>
<figure><img src="image_201.png" /><figcaption>**Figure 11.** Optimized structures for the hydride transfer step with 6<sup>dppe</sup>. Distances shown are in Å. C-H hydrogen (except on the alkoxide) atoms have been omitted for clarity.</figcaption></figure>

## Ketone Hydrogenation Catalysed by Anionic Tetrahydrido Ir<sup>III</sup> Complexes and the Cation Effect

The role of anionic hydride complexes as active catalysts in hydrogenation and hydrogen transfer reactions has now become well-established. The present chapter has illustrated one such case for the active catalyst produced *in situ* by activation of [IrCl(COD)(P,S<sup>R</sup>)] (P,S<sup>R</sup> = CpFe[1,2-C<sub>5</sub>H<sub>3</sub>(PPh<sub>2</sub>)(CH<sub>2</sub>S<sup>R</sup>)]; R = iPr, Ph, Bz, Cy) under H<sub>2</sub> in the presence of a strong base. The stark dependence of the catalytic activity on the nature of the base alkali cation (K<sup>+</sup> > Na<sup>+</sup> > Li<sup>+</sup>) and the severe activity dampening observed when 18-crown-6 is added to the K<sup>+</sup> system (Figure 12) confirm previous suggestions of an anionic active complex [4].

<figure><img src="image_202.png" /><figcaption>**Figure 12.** Results of the asymmetric hydrogenation of acetophenone with [IrCl(COD)(P,S<sup>R</sup>)] complexes. All catalysts show a preference for S-phenyl ethanol.</figcaption></figure>
<figure><img src="image_199.png" /><figcaption>**Figure 11.** Optimized structures for the hydride transfer step with 6<sup>dppe</sup>. Distances shown are in Å. C-H hydrogen (except on the alkoxide) atoms have been omitted for clarity.</figcaption></figure>

## Ketone Hydrogenation Catalysed by Anionic Tetrahydrido Ir<sup>III</sup> Complexes and the Cation Effect

The role of anionic hydride complexes as active catalysts in hydrogenation and hydrogen transfer reactions has now become well-established. The present chapter has illustrated one such case for the active catalyst produced *in situ* by activation of [IrCl(COD)(P,S<sup>R</sup>)] (P,S<sup>R</sup> = CpFe[1,2-C<sub>5</sub>H<sub>3</sub>(PPh<sub>2</sub>)(CH<sub>2</sub>S<sup>R</sup>)]; R = iPr, Ph, Bz, Cy) under H<sub>2</sub> in the presence of a strong base. The stark dependence of the catalytic activity on the nature of the base alkali cation (K<sup>+</sup> > Na<sup>+</sup> > Li<sup>+</sup>) and the severe activity dampening observed when 18-crown-6 is added to the K<sup>+</sup> system (Figure 12) confirm previous suggestions of an anionic active complex [4].

<figure><img src="image_200.png" /><figcaption>**Figure 12.** Results of the asymmetric hydrogenation of acetophenone with [IrCl(COD)(P,S<sup>R</sup>)] complexes. All catalysts show a preference for S-phenyl ethanol.</figcaption></figure>
The proposition, made solely on the basis of DFT calculations in the same contribution,[4] that such a species is the Ir<sup>III</sup> tetrahydrido complex M<sup>+</sup>[IrH<sub>4</sub>(P,S<sup>R</sup>)], has found strong support by the observed formation of the related (and more stable) K<sup>+</sup>[IrH<sub>4</sub>(dppe)]<sup>-</sup> from [IrCl(COD)(dppe)] in isopropanol and KO<sup>tBu</sup> under hydrogenation conditions (H<sub>2</sub> gas at 298 K) and even under transfer hydrogenation conditions (without H<sub>2</sub> at 353 K) [5]. This hypothesis is further supported by the DFT calculations carried out in this chapter, where the experimental trend of alkali metal cation-dependent activity has not only been reproduced but also rationalized, at the condition of using a fully explicit cation coordination sphere, M(MeOH)<sub>5</sub><sup>+</sup> (Scheme 10, Figure 13).

<figure><img src="image_203.png" /><figcaption>**Scheme 10.** Catalytic cycle of ketone hydrogenation catalysed by 7<sup>S,Ph</sup> proposed by DFT calculations (M = Li<sup>+</sup>, Na<sup>+</sup>, K<sup>+</sup>).</figcaption></figure>

Intriguingly, the activity does not appear to depend on any activating effect by the cation on either the ketone substrate or the iridium hydride species, but rather on the coordination sphere rearrangement at the alkali metal cation when, in the turnover-determining transition state, the incipient alkoxide establishes a bond with the alkali metal cation, replacing one or more alcohol molecules (Figure 13).
The proposition, made solely on the basis of DFT calculations in the same contribution,[4] that such a species is the Ir<sup>III</sup> tetrahydrido complex M<sup>+</sup>[IrH<sub>4</sub>(P,S<sup>R</sup>)], has found strong support by the observed formation of the related (and more stable) K<sup>+</sup>[IrH<sub>4</sub>(dppe)]<sup>-</sup> from [IrCl(COD)(dppe)] in isopropanol and KO<sup>tBu</sup> under hydrogenation conditions (H<sub>2</sub> gas at 298 K) and even under transfer hydrogenation conditions (without H<sub>2</sub> at 353 K) [5]. This hypothesis is further supported by the DFT calculations carried out in this chapter, where the experimental trend of alkali metal cation-dependent activity has not only been reproduced but also rationalized, at the condition of using a fully explicit cation coordination sphere, M(MeOH)<sub>5</sub><sup>+</sup> (Scheme 10, Figure 13).

<figure><img src="image_201.png" /><figcaption>**Scheme 10.** Catalytic cycle of ketone hydrogenation catalysed by 7<sup>S,Ph</sup> proposed by DFT calculations (M = Li<sup>+</sup>, Na<sup>+</sup>, K<sup>+</sup>).</figcaption></figure>

Intriguingly, the activity does not appear to depend on any activating effect by the cation on either the ketone substrate or the iridium hydride species, but rather on the coordination sphere rearrangement at the alkali metal cation when, in the turnover-determining transition state, the incipient alkoxide establishes a bond with the alkali metal cation, replacing one or more alcohol molecules (Figure 13).
<figure><img src="image_204.png" /><figcaption>**Figure 13.** Computed Gibbs energy profiles for the hydrogenation of acetone with 7<sup>P,SPh</sup>. All energy profiles in kcal mol<sup>-1</sup>. The labels shown reference the cycle in Scheme 10.</figcaption></figure>

These results indicate that the inclusion of explicit solvent molecules (and enough of them) in the DFT calculations is of paramount importance to allow the appropriate interpretation of certain effects that may be observed in catalytic cycles that involve anionic active species. Contrarily to the strong alkali cation effect on the catalytic activity, its influence on enantioselectivity is small. To understand the origin of this behaviour, DFT calculations have been performed on the enantio-determining hydride transfer step using the real prochiral acetophenone substrate while employing the (P,S<sup>Ph</sup>) ligand.
<figure><img src="image_202.png" /><figcaption>**Figure 13.** Computed Gibbs energy profiles for the hydrogenation of acetone with 7<sup>P,SPh</sup>. All energy profiles in kcal mol<sup>-1</sup>. The labels shown reference the cycle in Scheme 10.</figcaption></figure>

These results indicate that the inclusion of explicit solvent molecules (and enough of them) in the DFT calculations is of paramount importance to allow the appropriate interpretation of certain effects that may be observed in catalytic cycles that involve anionic active species. Contrarily to the strong alkali cation effect on the catalytic activity, its influence on enantioselectivity is small. To understand the origin of this behaviour, DFT calculations have been performed on the enantio-determining hydride transfer step using the real prochiral acetophenone substrate while employing the (P,S<sup>Ph</sup>) ligand.
<figure><img src="image_205.png" /><figcaption>**Figure 14.** Optimized structures for the hydride transfer step for each of the three cations. Li⁺ (top), Na⁺ (middle), K⁺ (bottom). Distances shown are in Å. C-H hydrogen atoms have been omitted for clarity.</figcaption></figure>

For this system, the *S* enantiomer of the ligand leads to a formation preference for the *S* enantiomer of the 1-phenylethanol product consistent with the experimental data, with all three alkali metal cations yielding essentially the same *ee*. The *pro-R* and *pro-S* transition states $TS_{(7-8)\text{dppe}}$ were computed for the three $[M(MeOH)_5]^+$ cations. Figure 15 shows the resulting transition state geometries, and important distances for each cation. The main interaction that discriminates between the two diastereomeric transition states involves a phenyl group of the phosphine ligand. This group interacts with the acetophenone methyl group (C-H-π) in the *pro-S* TS and with the acetophenone phenyl group (π-π) in the *pro-R* TS. The cation is in the less crowded space opposite to this key P-phenyl group. Consequently, the cation nature does not significantly alter the main interactions that govern
<figure><img src="image_203.png" /><figcaption>**Figure 14.** Optimized structures for the hydride transfer step for each of the three cations. Li⁺ (top), Na⁺ (middle), K⁺ (bottom). Distances shown are in Å. C-H hydrogen atoms have been omitted for clarity.</figcaption></figure>

For this system, the *S* enantiomer of the ligand leads to a formation preference for the *S* enantiomer of the 1-phenylethanol product consistent with the experimental data, with all three alkali metal cations yielding essentially the same *ee*. The *pro-R* and *pro-S* transition states TS(7-8)dppe were computed for the three [*M(MeOH)₅]*⁺ cations. Figure 15 shows the resulting transition state geometries, and important distances for each cation. The main interaction that discriminates between the two diastereomeric transition states involves a phenyl group of the phosphine ligand. This group interacts with the acetophenone methyl group (C-H-π) in the *pro-S* TS and with the acetophenone phenyl group (π-π) in the *pro-R* TS. The cation is in the less crowded space opposite to this key P-phenyl group. Consequently, the cation nature does not significantly alter the main interactions that govern
the ee. The calculated X<sub>Ph</sub>···HC<sub>Me</sub> and X<sub>Ph</sub>···X<sub>Ph</sub> distances for all computed systems, together with the Gibbs energy difference between both transition states (ΔΔG<sub>R-S</sub>) has been found. The geometrical parameters describing the substrate-ligand interaction are very similar in all cases, in agreement with the limited influence of the cation on enantioselectivity.

<figure><img src="image_206.png" /><figcaption>**Figure 15.** pro-S and pro-R transition states for hydride transfer to acetophenone, in presence of each cation. Distances in Å.</figcaption></figure>

Conclusion

Transfer hydrogenation catalysts are important in the synthesis of fine chemicals. Previous work has shown that a base is often necessary to achieve high activities for the asymmetric hydrogenation of polar substrates. New mechanistic views for such systems have emerged to account for the activity of such systems in which the ligand does not actively participate in proton donation which nevertheless need a strong base for activity. In this work, the role of the base in the associated chemistry of [IrCl(COD)(L<sub>2</sub>)] (L<sub>2</sub> = dppe, dppf, (S)-BINAP, P,S<sup>Pr</sup>, P,S<sup>Bz</sup>, P,S<sup>Ph</sup>, P,S<sup>Cy</sup>, (P,S<sup>R</sup> = CpFe[1,2-C<sub>5</sub>H<sub>3</sub>(PPh<sub>2</sub>)(CH<sub>2</sub>S<sup>R</sup>)]) systems was studied.

In the presence of an alkoxide with a β-hydrogen, two monohydride complexes of the form [IrH(C<sub>8</sub>H<sub>12</sub>)(dppe)] resulted from [IrCl(COD)(dppe)], which interconvert and this was supported by complementary DFT studies which gave a similar result. When no β-hydrogen was present on the base,
the ee. The calculated X<sub>Ph</sub>...HC<sub>Me</sub> and X<sub>Ph</sub>...X<sub>Ph</sub> distances for all computed systems, together with the Gibbs energy difference between both transition states (ΔΔG<sub>R-S</sub>) has been found. The geometrical parameters describing the substrate-ligand interaction are very similar in all cases, in agreement with the limited influence of the cation on enantioselectivity.

<figure><img src="image_204.png" /><figcaption>**Figure 15.** pro-S and pro-R transition states for hydride transfer to acetophenone, in presence of each cation. Distances in Å.</figcaption></figure>

Conclusion

Transfer hydrogenation catalysts are important in the synthesis of fine chemicals. Previous work has shown that a base is often necessary to achieve high activities for the asymmetric hydrogenation of polar substrates. New mechanistic views for such systems have emerged to account for the activity of such systems in which the ligand does not actively participate in proton donation which nevertheless need a strong base for activity. In this work, the role of the base in the associated chemistry of [IrCl(COD)(L<sub>2</sub>)] (L<sub>2</sub> = dppe, dppf, (S)-BINAP, P,S<sup>Pr</sup>, P,S<sup>Bz</sup>, P,S<sup>Ph</sup>, P,S<sup>Cy</sup>, (P,S<sup>R</sup> = CpFe[1,2-C<sub>5</sub>H<sub>3</sub>(PPh<sub>2</sub>)(CH<sub>2</sub>S<sup>R</sup>)]) systems was studied.

In the presence of an alkoxide with a β-hydrogen, two monohydride complexes of the form [IrH(C<sub>8</sub>H<sub>12</sub>)(dppe)] resulted from [IrCl(COD)(dppe)], which interconvert and this was supported by complementary DFT studies which gave a similar result. When no β-hydrogen was present on the base,
two isomeric monohydride complexes were formed through COD deprotonation, [IrH(1-κ-4,5,6-η³-C₈H₁₀)(dppe)]. DFT calculations were used to rationalize that the mechanism of interconversion proceeds *via* partial rotation of the cyclic C₈H₁₀ ligand. These model complexes were transformed by heating in the presence of KOtBu (or NaOMe) and isopropanol at 80 °C, to yield M[IrH₄(dppe)] (M = K, Na). Similar Irill products M[Ir(H)₄(L₂)] (L₂ = dppf, (S)-BINAP) were selectively generated from [IrCl(COD)(L₂)] and demonstrated that anionic tetrahydrido iridium complexes can be formed under catalytically relevant conditions.

Finally, the alkali metal-dependent hydrogenation activity of these complexes towards benzophenone was examined. The active catalyst, generated *in situ* from [IrCl(COD)]₂ and (P,SR) under H₂ in the presence of a strong base was the solvated M[Ir(H)₄(P,SR)] salt. Their activity increased, for all R derivatives, in the order Li < Na < K. On the other hand, the nature of the cation did not affect the ee. DFT calculations revealed that the rate-determining barrier corresponds to outer-sphere hydride transfer and that the enantio-discriminating interactions are largely unaffected by the cation but rather through π-π interactions. It was found that the model used to describe the alkali-metal cation coordination sphere in the DFT studies is critical for reproducing the experimental results.

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[4] J. M. Hayes, E. Deydier, G. Ujaque, A. Lledós, R. Malacea-Kabbara, E. Manoury, S. Vincendeau, R. Poli, *ACS Catal.* **2015**, *5*, 4368–4376. DOI: [10.1021/acscatal.5b00613](https://doi.org/10.1021/acscatal.5b00613).

[5] P. Kisten, E. Manoury, A. Lledós, A. C. Whitwood, J. M. Lynam, J. M. Slattery, S. B. Duckett, R. Poli, *Dalton Trans.* **2023**, *52*, 2495–2505. DOI: [10.1039/D2DT04036K](https://doi.org/10.1039/D2DT04036K).
two isomeric monohydride complexes were formed through COD deprotonation, [IrH(1-κ-4,5,6-η³-C₈H₁₀)(dppe)]. DFT calculations were used to rationalize that the mechanism of interconversion proceeds *via* partial rotation of the cyclic C₈H₁₀ ligand. These model complexes were transformed by heating in the presence of KOtBu (or NaOMe) and isopropanol at 80 °C, to yield M[IrH₄(dppe)] (M = K, Na). Similar Irill products M[Ir(H)₄(L₂)] (L₂ = dppf, (S)-BINAP) were selectively generated from [IrCl(COD)(L₂)] and demonstrated that anionic tetrahydrido iridium complexes can be formed under catalytically relevant conditions.

Finally, the alkali metal-dependent hydrogenation activity of these complexes towards benzophenone was examined. The active catalyst, generated *in situ* from [IrCl(COD)]₂ and (P,SR) under H₂ in the presence of a strong base was the solvated M[Ir(H)₄(P,SR)] salt. Their activity increased, for all R derivatives, in the order Li < Na < K. On the other hand, the nature of the cation did not affect the ee. DFT calculations revealed that the rate-determining barrier corresponds to outer-sphere hydride transfer and that the enantio-discriminating interactions are largely unaffected by the cation but rather through π-π interactions. It was found that the model used to describe the alkali-metal cation coordination sphere in the DFT studies is critical for reproducing the experimental results.

**References:**

[1] F. M. Chadwick, N. Olliff, A. S. Weller, *J. Organomet. Chem.* **2016**, *812*, 268–271. DOI: [10.1016/j.jorganchem.2015.12.001](https://doi.org/10.1016/j.jorganchem.2015.12.001).

[2] R. C. Schnabel, P. S. Carroll, D. M. Roddick, *Organometallics* **1996**, *15*, 655–662. DOI: [10.1021/om950722c](https://doi.org/10.1021/om950722c).

[3] R. C. Schnabel, D. M. Roddick, *Organometallics*, **1993**, *12*, 704–711. DOI: [10.1021/om00027a021](https://doi.org/10.1021/om00027a021).

[4] J. M. Hayes, E. Deydier, G. Ujaque, A. Lledós, R. Malacea-Kabbara, E. Manoury, S. Vincendeau, R. Poli, *ACS Catal.* **2015**, *5*, 4368–4376. DOI: [10.1021/acscatal.5b00613](https://doi.org/10.1021/acscatal.5b00613).

[5] P. Kisten, E. Manoury, A. Lledós, A. C. Whitwood, J. M. Lynam, J. M. Slattery, S. B. Duckett, R. Poli, *Dalton Trans.* **2023**, *52*, 2495–2505. DOI: [10.1039/D2DT04036K](https://doi.org/10.1039/D2DT04036K).
Chantal J. ABOU-FAYSSAL

ESR9

**Thesis co-directors**

Prof. Anders Riisager Danmarks Tekniske Universitet, Lyngby, Denmark

Dr. Eric Manoury, Laboratoire de Chimie de Coordination, Toulouse, France
Dr. Karine Philippot

**Thesis defense**

Department of Chemistry, Technical University of Denmark, 30 November 2023
Chantal J. ABOU-FAYSSAL

ESR9

**Thesis co-directors**

Prof. Anders Riisager Danmarks Tekniske Universitet, Lyngby, Denmark

Dr. Eric Manoury, Dr. Karine Philippot Laboratoire de Chimie de Coordination, Toulouse, France

**Thesis defense**

Department of Chemistry, Technical University of Denmark, 30 November 2023
<figure><img src="image_207.png" /></figure>
<figure><img src="image_205.png" /></figure>
# Metal Nanoparticles Embedded in Ligand-functionalized Water-soluble Core-shell Polymers for Application in Aqueous Biphasic Hydrogenation

## Introduction

The catalyzed transformation of organic compounds with metal nanoparticles (MNPs) [1] in micellar systems [2,3] combines the advantages of homogeneous and heterogeneous catalysis, including high activity, selectivity, and durability [4]. Nanocatalysis [5,6] with well-defined metal nanoparticle (MNPs) catalysts is a realm bridging homogeneous and heterogeneous catalysis. The nanoscale dimension of the catalysts provides distinctive properties not attainable with conventional, non-nanomaterials, thereby allowing for specific reactivity and advantageous properties, such as high efficiency, selectivity, stability, and ease of recovery/recycling [7–10]. In colloidal dispersions of ultrafine MNPs, surface energies and morphologies are influenced by the particle size leading to increased intrinsic surface reactivity [10]. For RhNPs multiple syntheses methods have been developed for size-control [11,12], including both methods based on the reduction of metal salts and the organometallic approach with the decomposition of Rh precursors. Typically, the size-control is achieved by employing various types of capping agents that prevent further growth of the RhNPs, whereas the following stabilization of the NPs in solution is ensured by the addition of stabilizing agents like e.g. surfactants (ammonium salts) [13–15], polymers [16–19], dendrimers [9] or ligands [12,20–26]. These stabilizers also facilitate good recyclability of the NPs when applied for catalysis. The MNPs provide a high surface-to-volume ratio resulting in a high number of potential catalytic sites [27], and the metal surface can be stabilized by appropriate ligands, similarly to molecular complexes. The confinement of MNPs inside a matrix (e.g. metal oxides, carbonaceous or polymeric materials) can further improve stability and catalytic performance. In particular, polymer-supported MNPs [26] have received significant attention in catalysis because of facile catalyst recovery and reuse. With such systems, using water as a solvent or dispersant phase yields aqueous biphasic systems [4,28,29] where simple phase separation facilitates catalyst recovery and recycling and allows reducing the use of volatile organic solvents and energy-intensive distillations, with a positive impact on the environment in the spirit of green chemistry. However, when the catalyst has low solubility in the organic reactant/product phase and the reactant has low solubility in water, the reaction may be limited to the organic/water interface and suffer from mass-transport restrictions. The use of surfactants or micellar systems can improve the mass-transport kinetics in biphasic aqueous/organic reactions by increasing the catalyst and substrate concentrations in the reaction zone [2,3,29,30]. Anchoring the catalyst in the hydrophobic cores of micelles permits to increase the local concentration of both catalyst and substrate and reduces the impact of mass transfer, provided the mass transport between the micellar cores and the bulk organic phase is facile. When the micelles are kinetically inert (slow exchange with the free surfactant in solution) or when they are rendered unimolecular by shell- or core-crosslinking, they operate as individual catalytic nanoreactors [31–33]. Some of us have developed synthetic protocols towards highly modular core-crosslinked micelles (CCMs) [34–41] as stable aqueous dispersions with a high polymer content (> 20 wt%), by reversible addition-fragmentation chain-transfer (RAFT) polymerization [42]. The first generation of CCMs displayed a neutral shell (CCM-N) made of random copolymer blocks of poly(ethylene oxide) (PEO) methacrylate and methacrylic acid [35]. Analogous CCMs with a polycationic shell (CCM-C) of homopolymer blocks
# Metal Nanoparticles Embedded in Ligand-functionalized Water-soluble Core-shell Polymers for Application in Aqueous Biphasic Hydrogenation

## Introduction

The catalyzed transformation of organic compounds with metal nanoparticles (MNPs) [1] in micellar systems [2,3] combines the advantages of homogeneous and heterogeneous catalysis, including high activity, selectivity, and durability [4]. Nanocatalysis [5,6] with well-defined metal nanoparticle (MNPs) catalysts is a realm bridging homogeneous and heterogeneous catalysis. The nanoscale dimension of the catalysts provides distinctive properties not attainable with conventional, non-nanomaterials, thereby allowing for specific reactivity and advantageous properties, such as high efficiency, selectivity, stability, and ease of recovery/recycling [7–10]. In colloidal dispersions of ultrafine MNPs, surface energies and morphologies are influenced by the particle size leading to increased intrinsic surface reactivity [10]. For RhNPs multiple syntheses methods have been developed for size-control [11,12], including both methods based on the reduction of metal salts and the organometallic approach with the decomposition of Rh precursors. Typically, the size-control is achieved by employing various types of capping agents that prevent further growth of the RhNPs, whereas the following stabilization of the NPs in solution is ensured by the addition of stabilizing agents like e.g. surfactants (ammonium salts) [13–15], polymers [16–19], dendrimers [9] or ligands [12,20–26]. These stabilizers also facilitate good recyclability of the NPs when applied for catalysis. The MNPs provide a high surface-to-volume ratio resulting in a high number of potential catalytic sites [27], and the metal surface can be stabilized by appropriate ligands, similarly to molecular complexes. The confinement of MNPs inside a matrix (e.g. metal oxides, carbonaceous or polymeric materials) can further improve stability and catalytic performance. In particular, polymer-supported MNPs [26] have received significant attention in catalysis because of facile catalyst recovery and reuse. With such systems, using water as a solvent or dispersant phase yields aqueous biphasic systems [4,28,29] where simple phase separation facilitates catalyst recovery and recycling and allows reducing the use of volatile organic solvents and energy-intensive distillations, with a positive impact on the environment in the spirit of green chemistry. However, when the catalyst has low solubility in the organic reactant/product phase and the reactant has low solubility in water, the reaction may be limited to the organic/water interface and suffer from mass-transport restrictions. The use of surfactants or micellar systems can improve the mass-transport kinetics in biphasic aqueous/organic reactions by increasing the catalyst and substrate concentrations in the reaction zone [2,3,29,30]. Anchoring the catalyst in the hydrophobic cores of micelles permits to increase the local concentration of both catalyst and substrate and reduces the impact of mass transfer, provided the mass transport between the micellar cores and the bulk organic phase is facile. When the micelles are kinetically inert (slow exchange with the free surfactant in solution) or when they are rendered unimolecular by shell- or core-crosslinking, they operate as individual catalytic nanoreactors [31–33]. Some of us have developed synthetic protocols towards highly modular core-crosslinked micelles (CCMs) [34–41] as stable aqueous dispersions with a high polymer content (> 20 wt%), by reversible addition-fragmentation chain-transfer (RAFT) polymerization [42]. The first generation of CCMs displayed a neutral shell (CCM-N) made of random copolymer blocks of poly(ethylene oxide) (PEO) methacrylate and methacrylic acid [35]. Analogous CCMs with a polycationic shell (CCM-C) of homopolymer blocks
of 4-vinyl-N-methylpyridinium iodide (4VPMe⁺I⁻) were also prepared [36] (Figure 1).

<figure><img src="image_208.png" /><figcaption>**Figure 1.** Cross-linked micelles functionalized with TPP (TPP@CCM) and various shells.</figcaption></figure>

All the developed so far have a polystyrene-based core with diethylene glycol dimethacrylate (DEGDMA) as crosslinker, but have been functionalized with different core-linked ligands, providing L@CCM nanoreactors with L = triphenylphosphine (TPP) [34,37,40,43], bis(4-methoxyphenyl)phenylphosphine [33], nixantphos [35], and N-heterocyclic carbene [39]. Molecular pre-catalysts (e.g. [Rh(acac)(CO)₂] or [Rh(COD)(µ-Cl)]₂; acac = acetylacetonate, COD = 1,5-cyclooctadiene) were successfully fixated in the CCM cores by ligand coordination, generating catalytic nanoreactors for aqueous biphasic olefin hydroformylation [35,41,44,45] and hydrogenation [37,39,40].

## MNPs confined in CCM-C for application in aqueous biphasic hydrogenation catalysis

During investigations into substrate scope, where catalytic hydrogenation of acetophenone was attempted, the latex [RhCl(COD)(TPP@CCM-C)] turned black [40], suggesting the reduction of the molecular Rh¹ complex to Rh⁰ metal. Retrospectively, this method proved highly effective in generating RhNPs within the cores of CCMs, prompting further investigations into biphasic hydrogenation involving RhNPs [35]. This objective was at the core of the current thesis project, specifically addressing significant challenges encountered in previous work. RhNP-TPP@CCM-C demonstrated excellent performance in the hydrogenation of 1-octene and styrene, with complete conversion and total selectivity towards the hydrogenation of the olefinic function. Notably, catalytic activity surpassed that of the Rh¹ molecular system. RhNP-TPP@CCM-C also proved recyclable for styrene hydrogenation over four cycles without loss of activity, with RhNPs remaining well dispersed when toluene was used for product recovery/catalyst recycling. However, when diethyl ether was used as the extraction solvent, a dramatic loss of activity was observed. This phenomenon was attributed to the extraction of RhNPs from the CCM-C core induced by diethyl ether, an oxygen-based solvent.
of 4-vinyl-N-methylpyridinium iodide (4VPMe⁺I⁻) were also prepared [36] (Figure 1).

<figure><img src="image_206.png" /><figcaption>**Figure 1.** Cross-linked micelles functionalized with TPP (TPP@CCM) and various shells.</figcaption></figure>

All the developed so far have a polystyrene-based core with diethylene glycol dimethacrylate (DEGDMA) as crosslinker, but have been functionalized with different core-linked ligands, providing L@CCM nanoreactors with L = triphenylphosphine (TPP) [34,37,40,43], bis(4-methoxyphenyl)phenylphosphine [33], nixantphos [35], and N-heterocyclic carbene [39]. Molecular pre-catalysts (e.g. [Rh(acac)(CO)₂] or [Rh(COD)(µ-Cl)]₂; acac = acetylacetonate, COD = 1,5-cyclooctadiene) were successfully fixated in the CCM cores by ligand coordination, generating catalytic nanoreactors for aqueous biphasic olefin hydroformylation [35,41,44,45] and hydrogenation [37,39,40].

## MNPs confined in CCM-C for application in aqueous biphasic hydrogenation catalysis

During investigations into substrate scope, where catalytic hydrogenation of acetophenone was attempted, the latex [RhCl(COD)(TPP@CCM-C)] turned black [40], suggesting the reduction of the molecular Rh¹ complex to Rh⁰ metal. Retrospectively, this method proved highly effective in generating RhNPs within the cores of CCMs, prompting further investigations into biphasic hydrogenation involving RhNPs [35]. This objective was at the core of the current thesis project, specifically addressing significant challenges encountered in previous work. RhNP-TPP@CCM-C demonstrated excellent performance in the hydrogenation of 1-octene and styrene, with complete conversion and total selectivity towards the hydrogenation of the olefinic function. Notably, catalytic activity surpassed that of the Rh¹ molecular system. RhNP-TPP@CCM-C also proved recyclable for styrene hydrogenation over four cycles without loss of activity, with RhNPs remaining well dispersed when toluene was used for product recovery/catalyst recycling. However, when diethyl ether was used as the extraction solvent, a dramatic loss of activity was observed. This phenomenon was attributed to the extraction of RhNPs from the CCM-C core induced by diethyl ether, an oxygen-based solvent.
## Scope of the thesis work

The discovery described above of the formation of catalytically active RhNPs in the TPP@CCM-C system forms the basis of the research conducted in the context of this doctoral thesis. The overall objective of the research was to develop innovative solutions to enhance the confinement of MNPs, primarily RhNPs, in CCM-C, in order to achieve efficient, stable, and recyclable catalytic systems for biphasic aqueous liquid-liquid hydrogenation catalysis as the application domain. To achieve this goal, synthesis tools from CCM polymer chemistry and organometallic nanochemistry were combined, and several approaches to achieve the sub-objectives described below were explored. The main results of the research are presented in the following paragraphs. New syntheses of polymers incorporating TPPO ligands and polycationic shells were developed to improve the confinement of RhNPs with the aim of refining their activity, selectivity, and scope.

## Confinement of Rh nanoparticles in cross-linked micelles with functionalized triphenylphosphine oxide cores for aqueous biphasic hydrogenation catalysis

Based on the hypothesis presented in the previous section, new nanoreactors L@CCM with triphenylphosphine oxide (TPPO) ligands as central oxygen-based anchoring functions for RhNPs were developed. The following describes the synthesis and characterization of the new polymer latex TPPO@CCM-C, its loading with preformed RhNPs, and the application of the resulting nanoreactors RhNP-TPPO@CCM-C in the catalytic hydrogenation of styrene under aqueous biphasic conditions.

## Synthesis and characterization of the polymer

The synthesis of the new TPPO@CCM-C polymer was carried out following the same strategy used for the preparation of the closely related TPP@CCM-C polymer (Scheme 1). The target degrees of polymerization of each block were kept identical to those of TPP@CCM-C, as they were already optimized to provide stable latexes with a narrow particle size distribution [37,38]. Thus, the first three steps leading to the synthesis of the amphiphilic diblock macroRAFT agent, $R_0-(\text{VPMe}^+\text{l})_{140-}b\text{-St}_{50}-\text{SC}(S)Sn\text{Pr}$, isolated as a stable solid and redispersed in water, were the same as in the TPP@CCM-C synthesis [38]. They involved the homogeneous RAFT polymerization of 4VP with CTPPA, $R_0\text{SC}(S)Sn\text{Pr}$ where $R_0 = \text{CMe}(\text{CN})\text{CH}_2\text{CH}_2\text{COOH}$, as transfer agent, forming $R_0-4\text{VP}_{140}-\text{SC}(S)Sn\text{Pr}$ (step 1), then chain extension with a short polystyrene block (average degree of polymerization of 50) forming an $R_0-\text{VP}_{140-}b\text{-St}_{50}-\text{SC}(S)Sn\text{Pr}$ diblock copolymer (step 2), and quaternization of the pyridine N-atoms with Mel (step 3).

The fourth step was a further chain extension of the $R_0-(\text{VPMe}^+\text{l})_{140-}b\text{-St}_{50}-\text{SC}(S)Sn\text{Pr}$ macroRAFT agent with a longer hydrophobic block (average degree of polymerization of 300) consisting of a statistical copolymer of styrene and a TPPO-functionalized styrene, namely SDPPO (4-styryldiphenylphosphine oxide) [33,46,47] (90/10 ratio), which was obtained by oxidation of SDPP with $\text{H}_2\text{O}_2$. This monomer has previously been homopolymerized [33,46,47] and copolymerized with styrene [48] and 9-(4-vinylphenyl)-9H-carbazole [49] by free radical polymerization, but not using the RAFT approach. All the polymerization steps were followed to completion (full consumption of monomers) by ¹H NMR and the generated $R_0-(\text{VPMe}^+\text{l})_{140-}b\text{-St}_{50-}b-(\text{St}_{0.9}\text{-co}-\text{SDPPO}_{0.1})_{300}-\text{SC}(S)Sn\text{Pr}$ amphiphilic macromolecules self-assembled in the form of micelles. The resulting latex remained well-dispersed over more than five months. The spherical micelles of the amphiphilic diblock copolymer
## Scope of the thesis work

The discovery described above of the formation of catalytically active RhNPs in the TPP@CCM-C system forms the basis of the research conducted in the context of this doctoral thesis. The overall objective of the research was to develop innovative solutions to enhance the confinement of MNPs, primarily RhNPs, in CCM-C, in order to achieve efficient, stable, and recyclable catalytic systems for biphasic aqueous liquid-liquid hydrogenation catalysis as the application domain. To achieve this goal, synthesis tools from CCM polymer chemistry and organometallic nanochemistry were combined, and several approaches to achieve the sub-objectives described below were explored. The main results of the research are presented in the following paragraphs. New syntheses of polymers incorporating TPPO ligands and polycationic shells were developed to improve the confinement of RhNPs with the aim of refining their activity, selectivity, and scope.

## Confinement of Rh nanoparticles in cross-linked micelles with functionalized triphenylphosphine oxide cores for aqueous biphasic hydrogenation catalysis

Based on the hypothesis presented in the previous section, new nanoreactors L@CCM with triphenylphosphine oxide (TPPO) ligands as central oxygen-based anchoring functions for RhNPs were developed. The following describes the synthesis and characterization of the new polymer latex TPPO@CCM-C, its loading with preformed RhNPs, and the application of the resulting nanoreactors RhNP-TPPO@CCM-C in the catalytic hydrogenation of styrene under aqueous biphasic conditions.

## Synthesis and characterization of the polymer

The synthesis of the new TPPO@CCM-C polymer was carried out following the same strategy used for the preparation of the closely related TPP@CCM-C polymer (Scheme 1). The target degrees of polymerization of each block were kept identical to those of TPP@CCM-C, as they were already optimized to provide stable latexes with a narrow particle size distribution [37,38]. Thus, the first three steps leading to the synthesis of the amphiphilic diblock macroRAFT agent, $R_0-(\text{VPMe}^+\text{I}')_{140-}b\text{-St}_{50}-\text{SC}(S)Sn\text{Pr}$, isolated as a stable solid and redispersed in water, were the same as in the TPP@CCM-C synthesis [38]. They involved the homogeneous RAFT polymerization of 4VP with CTPPA, $R_0\text{SC}(S)Sn\text{Pr}$ where $R_0 = \text{CMe}(\text{CN})\text{CH}_2\text{CH}_2\text{COOH}$, as transfer agent, forming $R_0-4\text{VP}_{140}-\text{SC}(S)Sn\text{Pr}$ (step 1), then chain extension with a short polystyrene block (average degree of polymerization of 50) forming an $R_0-\text{VP}_{140}-b\text{-St}_{50}-\text{SC}(S)Sn\text{Pr}$ diblock copolymer (step 2), and quaternization of the pyridine N-atoms with Mel (step 3).

The fourth step was a further chain extension of the $R_0-(\text{VPMe}^+\text{I}')_{140-}b\text{-St}_{50}-\text{SC}(S)Sn\text{Pr}$ macroRAFT agent with a longer hydrophobic block (average degree of polymerization of 300) consisting of a statistical copolymer of styrene and a TPPO-functionalized styrene, namely SDPPO (4-styryldiphenylphosphine oxide) [33,46,47] (90/10 ratio), which was obtained by oxidation of SDPP with $\text{H}_2\text{O}_2$. This monomer has previously been homopolymerized [33,46,47] and copolymerized with styrene [48] and 9-(4-vinylphenyl)-9H-carbazole [49] by free radical polymerization, but not using the RAFT approach. All the polymerization steps were followed to completion (full consumption of monomers) by ¹H NMR and the generated $R_0-(\text{VPMe}^+\text{I}')_{140-}b\text{-St}_{50}-b-(\text{St}_{0.9}\text{-co}-\text{SDPPO}_{0.1})_{300}-\text{SC}(S)Sn\text{Pr}$ amphiphilic macromolecules self-assembled in the form of micelles. The resulting latex remained well-dispersed over more than five months. The spherical micelles of the amphiphilic diblock copolymer
produced by step 4 had an average size of ca. 65 nm, as shown by DLS analysis (Figure 2a). These micelles were then crosslinked in a final step with DEGDMA (15 equiv. per chain), diluted with additional styrene (135 equiv. per chain), to yield the final product, R₀-(VPMe⁺I)₁₄₀-b-St₅₀-b-(St₀.₉-co-SDPPO₀.₁)₃₀₀-b-(St₀.₉-co-DEGDMA₀.₁)₁₅₀-SC(S)SnPr (TPPO@CCM-C), with a 10% crosslink density in the inner crosslinked core. The final TPPO@CCM-C polymer particles had spherical morphology and a slightly larger diameter (98.5 nm) than the intermediate micelles, as shown by DLS (Figure 2c) and TEM (Figure 2d) analyses. The size distribution became narrower and the D₂ of the distribution was slightly reduced after swelling with CHCl₃. This size reduction phenomenon upon swelling was also observed for related CCMs with an anionic shell (TPP@CCM-A) and was attributed to the dominant effect of micelles disaggregation rather than core swelling, which would cause an increase in average size [43]. Accordingly, the intensity profile in Figure 2b, which is more sensitive to the larger size micelles, became significantly narrower and shifted to lower values upon swelling.

<figure><img src="image_209.png" /><figcaption>**Scheme 1.** Synthesis route of the TPPO@CCM-C polymer.</figcaption></figure>

<figure><img src="image_210.png" /><figcaption>**Figure 2.** DLS size distributions of aqueous dispersions of (a) the diblock R₀-(VPMe⁺I)₁₄₀-b-St₅₀-b-(St₀.₉-co-SDPPO₀.₁)₃₀₀-b-SC(S)SnPr micelles and of TPPO@CCM-C (b) before and (c) after swelling with CHCl₃. Color coding: number (blue), volume (green) and intensity (red).</figcaption></figure>

## Synthesis of RhNP-TPPO@CCM-C

The first attempt to produce RhNP-TPPO@CCM-C consisted in loading the CCM-C with [Rh(COD)(μ-Cl)]₂, in order to generate a core-anchored [RhCl(COD)(TPPO@CCM-C)] complex that could
produced by step 4 had an average size of ca. 65 nm, as shown by DLS analysis (Figure 2a). These micelles were then crosslinked in a final step with DEGDMA (15 equiv. per chain), diluted with additional styrene (135 equiv. per chain), to yield the final product, R₀-(VPMe⁺I)₁₄₀-b-St₅₀-b-(St₀.₉-co-SDPPO₀.₁)₃₀₀-b-(St₀.₉-co-DEGDMA₀.₁)₁₅₀-SC(S)SnPr (TPPO@CCM-C), with a 10% crosslink density in the inner crosslinked core. The final TPPO@CCM-C polymer particles had spherical morphology and a slightly larger diameter (98.5 nm) than the intermediate micelles, as shown by DLS (Figure 2c) and TEM (Figure 2d) analyses. The size distribution became narrower and the D₂ of the distribution was slightly reduced after swelling with CHCl₃. This size reduction phenomenon upon swelling was also observed for related CCMs with an anionic shell (TPP@CCM-A) and was attributed to the dominant effect of micelles disaggregation rather than core swelling, which would cause an increase in average size [43]. Accordingly, the intensity profile in Figure 2b, which is more sensitive to the larger size micelles, became significantly narrower and shifted to lower values upon swelling.

<figure><img src="image_207.png" /><figcaption>**Scheme 1.** Synthesis route of the TPPO@CCM-C polymer.</figcaption></figure>

<figure><img src="image_208.png" /><figcaption>**Figure 2.** DLS size distributions of aqueous dispersions of (a) the diblock R₀-(VPMe⁺I)₁₄₀-b-St₅₀-b-(St₀.₉-co-SDPPO₀.₁)₃₀₀-b-SC(S)SnPr micelles and of TPPO@CCM-C (b) before and (c) after swelling with CHCl₃. Color coding: number (blue), volume (green) and intensity (red).</figcaption></figure>

## Synthesis of RhNP-TPPO@CCM-C

The first attempt to produce RhNP-TPPO@CCM-C consisted in loading the CCM-C with [Rh(COD)(μ-Cl)]₂, in order to generate a core-anchored [RhCl(COD)(TPPO@CCM-C)] complex that could
be reduced to RhNPs by H₂, following the procedure previously developed to generate RhNPs embedded in TPP@CCM-C [40]. Mononuclear complexes with the [Rh(η²:η²-diene)Cl(L)] stoichiometry (e.g. diene = COD, norbornadiene) where L is an O-atom donor ligand are rare [50–53], but the [RhCl(COD)(Ph₃PO)] complex has been described [54–56]. Nevertheless, this method proved unsuccessful as the organic phase was observed to remain yellow-colored, even after heating the reaction mixture at 60°C for 1 h or after stirring at room temperature for 24 h. This indicates that the formation of a Rh¹-TPPO@CCM-C complex in the polymer core by cleavage of the di-μ-Cl-bridge moiety in [Rh(COD)(μ-Cl)]₂ is not favorable under the applied conditions.

Therefore, an alternative strategy involving *ex-situ* synthesis of RhNPs and their subsequent transfer to the TPPO@CCM-C nanoreactors was considered. For this purpose, the RhNPs were produced by reduction of [Rh(COD)(μ-Cl)]₂ with H₂ in the presence of pyridine and TPP as stabilizing ligands. This ligand combination was inspired by previous reports, which showed TPP to be an effective stabilizer to produce ultrasmall RhNPs [12, 20, 26, 57, 58], while pyridine was used for the formation of RhNPs in ionic liquids [57]. The RhNPs synthesis was conducted in toluene, which has a high swelling power for the polystyrene-based CCM-C core [59]. The optimized conditions (TPP/Pyridine/Rh = 1/1/1, 60°C, 20 bar H₂, 20 h) led to a stable, black colloidal suspension of RhNPs, which displayed a mean diameter of 1.2 ± 0.4 nm and a narrow size distribution (Figure 3).

<figure><img src="image_211.png" /><figcaption>**Figure 3.** TEM images of RhNPs stabilized by TPP and pyridine (left) and the corresponding size distribution histogram ($d_m = 1.2 \pm 0.4$ nm) (right).</figcaption></figure>

The addition of the RhNPs colloidal suspension to the TPPO@CCM-C latex (P/Rh = 4/1) led to a fast and complete discoloration of the toluene phase while the latex became grey. This indicated the successful transfer of the RhNPs across the P(4VPMe⁺I⁻) hydrophilic shell of the CCM-C and their anchoring to the TPPO functions in the polymer cores, which was corroborated by DLS and TEM characterization of the final RhNP-TPPO@CCM-C. The DLS analysis showed that the CCM-C polymer particles had very similar average size and size distribution before and after the loading with the RhNPs. The TEM analysis confirmed that the RhNPs were located inside the polymer particles and indicated an average size of ca. 1.5 ± 0.4 nm. Despite the presence of the polymer that renders the measurement more difficult, it can be concluded that the RhNPs had quite similar sizes to the as-synthesized RhNPs. This result indicates that the RhNPs are not significantly altered by the ligand exchange in the CCM-C core.

## Hydrogenation of Styrene with colloidal suspension of RhNPs in toluene

The catalytic activity of the toluene colloidal suspension of TPP/pyridine-stabilized RhNPs was evaluated for the hydrogenation of styrene under mild reaction conditions (20 bar H₂, 25°C, 0.25 h)
be reduced to RhNPs by H₂, following the procedure previously developed to generate RhNPs embedded in TPP@CCM-C [40]. Mononuclear complexes with the [Rh(η²:η²-diene)Cl(L)] stoichiometry (e.g. diene = COD, norbornadiene) where L is an O-atom donor ligand are rare [50–53], but the [RhCl(COD)(Ph₃PO)] complex has been described [54–56]. Nevertheless, this method proved unsuccessful as the organic phase was observed to remain yellow-colored, even after heating the reaction mixture at 60°C for 1 h or after stirring at room temperature for 24 h. This indicates that the formation of a Rh¹-TPPO@CCM-C complex in the polymer core by cleavage of the di-μ-Cl-bridge moiety in [Rh(COD)(μ-Cl)]₂ is not favorable under the applied conditions.

Therefore, an alternative strategy involving *ex-situ* synthesis of RhNPs and their subsequent transfer to the TPPO@CCM-C nanoreactors was considered. For this purpose, the RhNPs were produced by reduction of [Rh(COD)(μ-Cl)]₂ with H₂ in the presence of pyridine and TPP as stabilizing ligands. This ligand combination was inspired by previous reports, which showed TPP to be an effective stabilizer to produce ultrasmall RhNPs [12, 20, 26, 57, 58], while pyridine was used for the formation of RhNPs in ionic liquids [57]. The RhNPs synthesis was conducted in toluene, which has a high swelling power for the polystyrene-based CCM-C core [59]. The optimized conditions (TPP/Pyridine/Rh = 1/1/1, 60°C, 20 bar H₂, 20 h) led to a stable, black colloidal suspension of RhNPs, which displayed a mean diameter of 1.2 ± 0.4 nm and a narrow size distribution (Figure 3).

<figure><img src="image_209.png" /><figcaption>**Figure 3.** TEM images of RhNPs stabilized by TPP and pyridine (left) and the corresponding size distribution histogram ($d_m = 1.2 \pm 0.4$ nm) (right).</figcaption></figure>

The addition of the RhNPs colloidal suspension to the TPPO@CCM-C latex (P/Rh = 4/1) led to a fast and complete discoloration of the toluene phase while the latex became grey. This indicated the successful transfer of the RhNPs across the P(4VPMe⁺I⁻) hydrophilic shell of the CCM-C and their anchoring to the TPPO functions in the polymer cores, which was corroborated by DLS and TEM characterization of the final RhNP-TPPO@CCM-C. The DLS analysis showed that the CCM-C polymer particles had very similar average size and size distribution before and after the loading with the RhNPs. The TEM analysis confirmed that the RhNPs were located inside the polymer particles and indicated an average size of ca. 1.5 ± 0.4 nm. Despite the presence of the polymer that renders the measurement more difficult, it can be concluded that the RhNPs had quite similar sizes to the as-synthesized RhNPs. This result indicates that the RhNPs are not significantly altered by the ligand exchange in the CCM-C core.

## Hydrogenation of Styrene with colloidal suspension of RhNPs in toluene

The catalytic activity of the toluene colloidal suspension of TPP/pyridine-stabilized RhNPs was evaluated for the hydrogenation of styrene under mild reaction conditions (20 bar H₂, 25°C, 0.25 h)
with styrene/Rh = 10000/1. A styrene conversion of ~90% was observed, corresponding to a TOF of ~36900 h⁻¹ (cTOF of ~40700 h⁻¹), with complete selectivity towards ethylbenzene (EB). This catalytic performance is superior to those previously described with RhNPs stabilized by TPP (TOF of ~6000 h⁻¹) or diphosphate ligands (TOF of ~24000 h⁻¹) under 40 bar H₂ in heptane at room temperature and 0.25 h [20]. The selectivity in favor of EB is not surprising, because previous investigations have underlined the tuneable properties of RhNPs [11,12,20–22] and the role of their size in controlling the selectivity of styrene hydrogenation. For instance, RhNPs with size in the 2-10 nm range exhibited a propensity for ring hydrogenation [60]. Conversely, selective hydrogenation to EB occurred under mild conditions using RhNPs with an average diameter of 1.5 nm [61], though benzene ring hydrogenation was observed under more forcing conditions. The dependence of reaction selectivities on the metal NP size has also been highlighted in other contributions [17,62–64].

## Hydrogenation with RhNP-TPPO@CCM-C latex under biphasic conditions

Next, the RhNP-TPPO@CCM-C latex was applied to the aqueous biphasic hydrogenation of styrene under the same temperature and pressure conditions as with the colloidal RhNPs suspension (20 bar H₂, 25°C), with a styrene/Rh ratio of 2000/1, at different reaction times (Figure 4). Since styrene is a good solvent for polystyrene, no vectorizing solvent was needed and the hydrogenation was carried out with the neat substrate [37,40] using an agitation of 1200 rpm to ensure a good external mass transfer.

<figure><img src="image_212.png" /><figcaption>**Figure 4.** Time plot for the aqueous biphasic hydrogenation of styrene using RhNPs-TPPO@CCM-C. Reaction conditions: Styrene/Rh = 2000/1, 20 bar H₂, 25°C.</figcaption></figure>

A nearly complete styrene conversion (~94%) was obtained in only 0.25 h, corresponding to a TOF of 7733 h⁻¹ (cTOF of 9850 h⁻¹), with an excellent selectivity (>99%) towards EB (Table 1, entry 1). This catalytic performance is superior to that previously achieved with RhNPs embedded in the TPP@CCM-C [20,21,40]. This difference may be related to the smaller size of the *ex-situ* synthesized TPP/pyridine-stabilized RhNPs used to get RhNP-TPPO@CCM-C compared to the *in-situ* synthesized TPP@CCMC-stabilized RhNPs in RhNP-TPP@CCM-C (1.2 nm vs. < 5 nm). However, additional experiments indicated that the adsorbed TPP and pyridine stabilizers in the RhNP-TPPO@CCM-C catalyst also played a role (*vide infra*). An increase of the styrene/Rh ratio resulted in good and reproducible conversions within 0.25 h of 53% (styrene/Rh = 5000/1) and 24% (styrene/Rh = 10000/1), corresponding to TOFs of 10547 and 9062 h⁻¹ (cTOFs of 14300 and 12440 h⁻¹), respectively, again with full selectivity towards EB (Table 1, entries 2 and 3). Upon stopping the stirring, a rapid phase
with styrene/Rh = 10000/1. A styrene conversion of ~90% was observed, corresponding to a TOF of ~36900 h⁻¹ (cTOF of ~40700 h⁻¹), with complete selectivity towards ethylbenzene (EB). This catalytic performance is superior to those previously described with RhNPs stabilized by TPP (TOF of ~6000 h⁻¹) or diphosphate ligands (TOF of ~24000 h⁻¹) under 40 bar H₂ in heptane at room temperature and 0.25 h [20]. The selectivity in favor of EB is not surprising, because previous investigations have underlined the tuneable properties of RhNPs [11,12,20–22] and the role of their size in controlling the selectivity of styrene hydrogenation. For instance, RhNPs with size in the 2-10 nm range exhibited a propensity for ring hydrogenation [60]. Conversely, selective hydrogenation to EB occurred under mild conditions using RhNPs with an average diameter of 1.5 nm [61], though benzene ring hydrogenation was observed under more forcing conditions. The dependence of reaction selectivities on the metal NP size has also been highlighted in other contributions [17,62–64].

### Hydrogenation with RhNP-TPPO@CCM-C latex under biphasic conditions

Next, the RhNP-TPPO@CCM-C latex was applied to the aqueous biphasic hydrogenation of styrene under the same temperature and pressure conditions as with the colloidal RhNPs suspension (20 bar H₂, 25°C), with a styrene/Rh ratio of 2000/1, at different reaction times (Figure 4). Since styrene is a good solvent for polystyrene, no vectorizing solvent was needed and the hydrogenation was carried out with the neat substrate [37,40] using an agitation of 1200 rpm to ensure a good external mass transfer.

<figure><img src="image_210.png" /><figcaption>**Figure 4.** Time plot for the aqueous biphasic hydrogenation of styrene using RhNPs-TPPO@CCM-C. Reaction conditions: Styrene/Rh = 2000/1, 20 bar H₂, 25°C.</figcaption></figure>

A nearly complete styrene conversion (~94%) was obtained in only 0.25 h, corresponding to a TOF of 7733 h⁻¹ (cTOF of 9850 h⁻¹), with an excellent selectivity (>99%) towards EB (Table 1, entry 1). This catalytic performance is superior to that previously achieved with RhNPs embedded in the TPP@CCM-C [20,21,40]. This difference may be related to the smaller size of the *ex-situ* synthesized TPP/pyridine-stabilized RhNPs used to get RhNP-TPPO@CCM-C compared to the *in-situ* synthesized TPP@CCMC-stabilized RhNPs in RhNP-TPP@CCM-C (1.2 nm vs. < 5 nm). However, additional experiments indicated that the adsorbed TPP and pyridine stabilizers in the RhNP-TPPO@CCM-C catalyst also played a role (*vide infra*). An increase of the styrene/Rh ratio resulted in good and reproducible conversions within 0.25 h of 53% (styrene/Rh = 5000/1) and 24% (styrene/Rh = 10000/1), corresponding to TOFs of 10547 and 9062 h⁻¹ (cTOFs of 14300 and 12440 h⁻¹), respectively, again with full selectivity towards EB (Table 1, entries 2 and 3). Upon stopping the stirring, a rapid phase
separation (< 3 min) was observed in all reactions, thus facilitating the product separation and catalyst recovery, as already reported for the RhNP-TPP@CCM-C nanoreactors featuring the same outer shell [40].

<figure><img src="image_213.png" /><figcaption>**Table 1.** Hydrogenation of styrene using RhNP-TPPO@CCM-C.<sup>a</sup></figcaption></figure>

<table><thead><tr><th rowspan="2">Entry</th><th rowspan="2">Molar ratio of styrene/Rh</th><th rowspan="2">Conversion (%)</th><th colspan="2">Product Yield (%)</th><th rowspan="2">TOF (h<sup>-1</sup>)<sup>b</sup></th></tr><tr><th>Ethylbenzene</th><th>Ethylcyclohexane</th></tr></thead><tbody><tr><td>1</td><td>2000/1</td><td>94</td><td>94</td><td>&lt;0.1</td><td>7733 (9850)</td></tr><tr><td>2</td><td>5000/1</td><td>53</td><td>52</td><td>&lt;0.1</td><td>10547 (14300)</td></tr><tr><td>3</td><td>10000/1</td><td>24</td><td>23</td><td>&lt;0.1</td><td>9062 (12440)</td></tr></tbody></table>

The recycling of the catalytic RhNP-TPPO@CCM-C latex was evaluated in two series of experiments at a fixed styrene/Rh ratio of 5000/1, by extracting the reaction products with diethyl ether or toluene, respectively, prior to the addition of a new batch of substrate for the next catalytic run. The extraction protocol was identical to that used in the previously reported recycling studies with the RhNP-TPP@CCM-C [40] and with the molecular Rh<sup>l</sup>-TPP@CCM [37] catalytic systems. The first catalytic runs yielded styrene conversion of 53% in 0.25 h. However, a gradual decrease in conversion, from 53% to ca. 9-15%, was witnessed after the fifth run for both series of recycles, using either toluene or diethyl ether for product extraction (Figure 5a). The ICP-MS analyses showed only a cumulative loss of ~2% of the catalyst inventory after the five catalytic runs when using diethyl ether as extraction solvent, indicating that the activity decrease was not caused by metal leaching and mechanical loss of latex. Moreover, after catalyst separation, whether toluene or diethyl ether was used as the extraction solvent, the organic phase was completely transparent and colorless while the aqueous phase remained grey, thus indicating the retention of the RhNPs in the CCM-C latex. In both cases, the TEM images obtained for the RhNP-TPPO@CCM-C catalyst after the fifth run evidenced a preserved confinement of the RhNPs in the CCM-C cores with well dispersed RhNPs. These results indicate that the interaction of the RhNPs with the core-linked TPPO ligands is sufficiently strong to retain them within the hydrophobic CCM-C cores, validating the initial hypothesis of the superior efficiency of oxygen-coordinating ligands. Though an artifact cannot be ruled out due to the less defined polymer-embedded RhNPs, a notable change was an increase of the particle size (from 1.5 ± 0.4 nm to 2.2 ± 0.9 nm after the fifth catalytic run). This may indicate a slight growth or aggregation of the NPs. However, given that the standard deviation value is larger than the size change (0.9 nm vs. 0.7 nm), the NPs can also be considered as to be in a similar size range, thus the interpretation of the activity drop as a result of a size change does not appear satisfactory.

<footnote><sup>a</sup> Reaction conditions: 20 bar H<sub>2</sub>, 25 °C, 0.25 h. <sup>b</sup> Average values over the duration of the reaction, expressed as moles of substrate converted per moles of Rh in the catalyst per hour (TOF) or as moles of substrate converted per moles of surface Rh atoms per hour (cTOF, in parenthesis).</footnote>
separation (< 3 min) was observed in all reactions, thus facilitating the product separation and catalyst recovery, as already reported for the RhNP-TPP@CCM-C nanoreactors featuring the same outer shell [40].

<figure><img src="image_211.png" /><figcaption>**Table 1.** Hydrogenation of styrene using RhNP-TPPO@CCM-C.ª</figcaption></figure>

<table><thead><tr><th rowspan="2">Entry</th><th rowspan="2">Molar ratio of styrene/Rh</th><th rowspan="2">Conversion (%)</th><th colspan="2">Product Yield (%)</th><th rowspan="2">TOF (h<sup>-1</sup>)<sup>b</sup></th></tr><tr><th>Ethylbenzene</th><th>Ethylcyclohexane</th></tr></thead><tbody><tr><td>1</td><td>2000/1</td><td>94</td><td>94</td><td>&lt;0.1</td><td>7733 (9850)</td></tr><tr><td>2</td><td>5000/1</td><td>53</td><td>52</td><td>&lt;0.1</td><td>10547 (14300)</td></tr><tr><td>3</td><td>10000/1</td><td>24</td><td>23</td><td>&lt;0.1</td><td>9062 (12440)</td></tr></tbody></table>

The recycling of the catalytic RhNP-TPPO@CCM-C latex was evaluated in two series of experiments at a fixed styrene/Rh ratio of 5000/1, by extracting the reaction products with diethyl ether or toluene, respectively, prior to the addition of a new batch of substrate for the next catalytic run. The extraction protocol was identical to that used in the previously reported recycling studies with the RhNP-TPP@CCM-C [40] and with the molecular Rh¹-TPP@CCM [37] catalytic systems. The first catalytic runs yielded styrene conversion of 53% in 0.25 h. However, a gradual decrease in conversion, from 53% to ca. 9-15%, was witnessed after the fifth run for both series of recycles, using either toluene or diethyl ether for product extraction (Figure 5a). The ICP-MS analyses showed only a cumulative loss of ~2% of the catalyst inventory after the five catalytic runs when using diethyl ether as extraction solvent, indicating that the activity decrease was not caused by metal leaching and mechanical loss of latex. Moreover, after catalyst separation, whether toluene or diethyl ether was used as the extraction solvent, the organic phase was completely transparent and colorless while the aqueous phase remained grey, thus indicating the retention of the RhNPs in the CCM-C latex. In both cases, the TEM images obtained for the RhNP-TPPO@CCM-C catalyst after the fifth run evidenced a preserved confinement of the RhNPs in the CCM-C cores with well dispersed RhNPs. These results indicate that the interaction of the RhNPs with the core-linked TPPO ligands is sufficiently strong to retain them within the hydrophobic CCM-C cores, validating the initial hypothesis of the superior efficiency of oxygen-coordinating ligands. Though an artifact cannot be ruled out due to the less defined polymer-embedded RhNPs, a notable change was an increase of the particle size (from 1.5 ± 0.4 nm to 2.2 ± 0.9 nm after the fifth catalytic run). This may indicate a slight growth or aggregation of the NPs. However, given that the standard deviation value is larger than the size change (0.9 nm vs. 0.7 nm), the NPs can also be considered as to be in a similar size range, thus the interpretation of the activity drop as a result of a size change does not appear satisfactory.

<footnote>ª Reaction conditions: 20 bar H₂, 25 °C, 0.25 h. ᵇ Average values over the duration of the reaction, expressed as moles of substrate converted per moles of Rh in the catalyst per hour (TOF) or as moles of substrate converted per moles of surface Rh atoms per hour (cTOF, in parenthesis).</footnote>
<figure><img src="image_214.png" /><figcaption>**Figure 5.** Reuse of RhNP-TPPO@CCM-C in five catalytic reactions of styrene hydrogenation (a) with intermediate product extraction by diethyl ether (blue) and toluene (red), (b) with product extraction by diethyl ether under argon with and without intermediate treatment with H₂ (20 bar H₂, 25°C, 1 h). Reaction conditions: styrene/Rh = 5000/1, 20 bar H₂, 25°C, 0.25 h.</figcaption></figure>

Given that no significant metal leaching was detected and that no substantial NP agglomeration that may lead to loss of active surface was observed, progressive passivation of the RhNPs surface by rhodium oxide formation could be responsible for the decrease in catalytic performance over subsequent recycles. To verify this hypothesis, the catalyst recycling with product extraction by diethyl ether was completed under an inert argon atmosphere. In addition, the recovered RhNP-TPPO@CCM-C phase was treated with H₂ (20 bar H₂, 25°C, 1 h) prior to each catalytic run, to remove any rhodium oxide layer. Despite these precautions in the recycling experiments, the styrene conversion still decreased to 10% along the five runs (Figure 5b). The similarity of these results to those achieved without inert atmosphere and reductive treatment (Figure 5a), suggests that passivation of the RhNPs was not the unique reason behind the decrease in the activity. A reduction of the anchoring TPPO ligands to TPP by H₂, catalyzed by the RhNPs, is another possible hypothesis to explain the observed activity decrease, assuming a lower activity for RhNP-TPP relative to RhNP-TPPO. To assess this hypothesis, a toluene solution of TPPO- and TPP/pyridine-stabilized RhNPs (TPPO/Rh = 8/1) was exposed to H₂ (20 bar) at 60°C for 22 h. A ³¹P NMR monitoring of the solution revealed no detectable TPPO reduction. This result seems to indicate that the TPPO ligands in the CCM-C core most likely remained unchanged under the conditions of the aqueous biphasic styrene reduction catalysis. The absence of TPPO reduction to TPP is also indirectly indicated by the demonstrated ability of diethyl ether to extract the RhNPs from the RhNP-TPP@CCM-C [40] whereas the TEM analysis shows that the RhNPs are well-retained in the micellar core. A final working hypothesis is that the stabilizers used for the *ex-situ* synthesis of RhNPs (TPP/pyridine) partially remained in the TPPO@CCM-C core after loading and promoted the catalytic activity of the RhNPs, and that the activity gradually decreased as these stabilizers/promoters were continuously washed out during the work-up for catalyst recovering and recycling. This hypothesis was tested by washing the fresh RhNP-TPPO@CCM-C latex, after RhNPs loading, three times with diethyl ether prior to use in catalysis. A GC-MS analysis of the diethyl ether extracts showed two peaks with MS spectra yielding molecular ions at m/z 112 and 83, respectively. These peaks match cyclooctane and tetrahydropyridine, respectively, resulting from the hydrogenation of the COD ligand from [Rh(COD)(µ-Cl)]₂ and of pyridine during the *ex-situ* synthesis of the RhNPs [11,22,61]. Subsequently, five subsequent catalytic runs (all reproduced three times) were carried out (20 bar H₂, 25°C, 1 h) (Figure 6). The first catalytic run provided a low conversion of styrene
<figure><img src="image_212.png" /><figcaption>**Figure 5.** Reuse of RhNP-TPPO@CCM-C in five catalytic reactions of styrene hydrogenation (a) with intermediate product extraction by diethyl ether (blue) and toluene (red), (b) with product extraction by diethyl ether under argon with and without intermediate treatment with H₂ (20 bar H₂, 25°C, 1 h). Reaction conditions: styrene/Rh = 5000/1, 20 bar H₂, 25°C, 0.25 h.</figcaption></figure>

Given that no significant metal leaching was detected and that no substantial NP agglomeration that may lead to loss of active surface was observed, progressive passivation of the RhNPs surface by rhodium oxide formation could be responsible for the decrease in catalytic performance over subsequent recycles. To verify this hypothesis, the catalyst recycling with product extraction by diethyl ether was completed under an inert argon atmosphere. In addition, the recovered RhNP-TPPO@CCM-C phase was treated with H₂ (20 bar H₂, 25°C, 1 h) prior to each catalytic run, to remove any rhodium oxide layer. Despite these precautions in the recycling experiments, the styrene conversion still decreased to 10% along the five runs (Figure 5b). The similarity of these results to those achieved without inert atmosphere and reductive treatment (Figure 5a), suggests that passivation of the RhNPs was not the unique reason behind the decrease in the activity. A reduction of the anchoring TPPO ligands to TPP by H₂, catalyzed by the RhNPs, is another possible hypothesis to explain the observed activity decrease, assuming a lower activity for RhNP-TPP relative to RhNP-TPPO. To assess this hypothesis, a toluene solution of TPPO- and TPP/pyridine-stabilized RhNPs (TPPO/Rh = 8/1) was exposed to H₂ (20 bar) at 60°C for 22 h. A ³¹P NMR monitoring of the solution revealed no detectable TPPO reduction. This result seems to indicate that the TPPO ligands in the CCM-C core most likely remained unchanged under the conditions of the aqueous biphasic styrene reduction catalysis. The absence of TPPO reduction to TPP is also indirectly indicated by the demonstrated ability of diethyl ether to extract the RhNPs from the RhNP-TPP@CCM-C [40] whereas the TEM analysis shows that the RhNPs are well-retained in the micellar core. A final working hypothesis is that the stabilizers used for the *ex-situ* synthesis of RhNPs (TPP/pyridine) partially remained in the TPPO@CCM-C core after loading and promoted the catalytic activity of the RhNPs, and that the activity gradually decreased as these stabilizers/promoters were continuously washed out during the work-up for catalyst recovering and recycling. This hypothesis was tested by washing the fresh RhNP-TPPO@CCM-C latex, after RhNPs loading, three times with diethyl ether prior to use in catalysis. A GC-MS analysis of the diethyl ether extracts showed two peaks with MS spectra yielding molecular ions at m/z 112 and 83, respectively. These peaks match cyclooctane and tetrahydropyridine, respectively, resulting from the hydrogenation of the COD ligand from [Rh(COD)(µ-Cl)]₂ and of pyridine during the *ex-situ* synthesis of the RhNPs [11,22,61]. Subsequently, five subsequent catalytic runs (all reproduced three times) were carried out (20 bar H₂, 25°C, 1 h) (Figure 6). The first catalytic run provided a low conversion of styrene
~6%), whereas a constant styrene conversion of ca. 25% was achieved in the following four runs, corresponding to an average TOF of ~1025 h⁻¹ (cTOF ~1440 h⁻¹). The low conversion in the first run might indicate that an induction time would be necessary to deblock the active sites and/or the RhNPs experienced significant changes under catalytic conditions. Comparison of a series of TEM measurements performed with the diethyl ether-washed catalyst (prior to catalysis) before/after H₂ treatment and after the first and fifth catalytic runs (Fig. S10), confirmed that the RhNPs mean size indeed changed from 4.2 ± 0.2 nm to 2.2 ± 0.2 nm before and after H₂ treatment, respectively, and was further reduced to a static size of 1.8 ± 0.1-0.3 nm after the first catalytic run. Thus, the removal of the stabilizers likely induced a slight size increase or agglomeration of the RhNPs, resulting in lower catalytic activity, as also previously reported for RhNPs in styrene hydrogenation [38,47], while the successive H₂ treatment prompted reconstruction of the NPs possibly aided by the presence of TPPO@CCM-C. Notably, although a different reaction time was applied (1 h vs. 0.25 h), the styrene conversion value of ca. 25% obtained after the initial run is comparable to that obtained in the fourth and fifth recycles performed with intermediate product extraction by diethyl ether (Figure 6). This suggests that the diethyl ether washings performed between the consecutive catalytic runs (Figure 5) have a similar effect to those carried out on the fresh RhNP-TPPO@CCM-C prior to its implementation in catalysis. This indicates a possible role of the RhNP stabilizers (TPP, pyridine and tetrahydropyridine, see GC-MS results above) on the hydrogenation of styrene when they are not eliminated by solvent washings [66–69]. It is also to be noted that, as shown above, the RhNP-catalyzed styrene hydrogenation in toluene yields a much higher TOF for the RhNPs stabilized by TPP and pyridine (~36000 h⁻¹) with respect to other RhNPs synthesized using other stabilizers, under similar experimental conditions [58]. This highlights that a careful choice of stabilizers to pre-synthesized RhNPs for their transfer in the CCM-C, or the integration of co-ligands in the cores of CCM-C could be a way to boost the catalytic performance, but this is out of the scope of the present work.

<figure><img src="image_215.png" /><figcaption>**Figure 6.** Hydrogenation of styrene with RhNP-TPPO@CCM-C after three washings with diethyl ether (run 1) and recycling of the catalyst in four additional reaction runs with product extraction by diethyl ether and intermediate H₂ treatment (20 bar H₂, 25°C, 1 h). Reaction conditions: Styrene/Rh = 5000/1, 20 bar H₂, 25°C, 1 h.</figcaption></figure>
~6%), whereas a constant styrene conversion of ca. 25% was achieved in the following four runs, corresponding to an average TOF of ~1025 h⁻¹ (cTOF ~1440 h⁻¹). The low conversion in the first run might indicate that an induction time would be necessary to deblock the active sites and/or the RhNPs experienced significant changes under catalytic conditions. Comparison of a series of TEM measurements performed with the diethyl ether-washed catalyst (prior to catalysis) before/after H₂ treatment and after the first and fifth catalytic runs (Fig. S10), confirmed that the RhNPs mean size indeed changed from 4.2 ± 0.2 nm to 2.2 ± 0.2 nm before and after H₂ treatment, respectively, and was further reduced to a static size of 1.8 ± 0.1-0.3 nm after the first catalytic run. Thus, the removal of the stabilizers likely induced a slight size increase or agglomeration of the RhNPs, resulting in lower catalytic activity, as also previously reported for RhNPs in styrene hydrogenation [38,47], while the successive H₂ treatment prompted reconstruction of the NPs possibly aided by the presence of TPPO@CCM-C. Notably, although a different reaction time was applied (1 h vs. 0.25 h), the styrene conversion value of ca. 25% obtained after the initial run is comparable to that obtained in the fourth and fifth recycles performed with intermediate product extraction by diethyl ether (Figure 6). This suggests that the diethyl ether washings performed between the consecutive catalytic runs (Figure 5) have a similar effect to those carried out on the fresh RhNP-TPPO@CCM-C prior to its implementation in catalysis. This indicates a possible role of the RhNP stabilizers (TPP, pyridine and tetrahydropyridine, see GC-MS results above) on the hydrogenation of styrene when they are not eliminated by solvent washings [66–69]. It is also to be noted that, as shown above, the RhNP-catalyzed styrene hydrogenation in toluene yields a much higher TOF for the RhNPs stabilized by TPP and pyridine (~36000 h⁻¹) with respect to other RhNPs synthesized using other stabilizers, under similar experimental conditions [58]. This highlights that a careful choice of stabilizers to pre-synthesized RhNPs for their transfer in the CCM-C, or the integration of co-ligands in the cores of CCM-C could be a way to boost the catalytic performance, but this is out of the scope of the present work.

<figure><img src="image_213.png" /><figcaption>**Figure 6.** Hydrogenation of styrene with RhNP-TPPO@CCM-C after three washings with diethyl ether (run 1) and recycling of the catalyst in four additional reaction runs with product extraction by diethyl ether and intermediate H₂ treatment (20 bar H₂, 25°C, 1 h). Reaction conditions: Styrene/Rh = 5000/1, 20 bar H₂, 25°C, 1 h.</figcaption></figure>
## Aqueous biphasic hydrogenation with Rh nanoparticles synthesized in a single step within micelles with a polycationic shell and a cross-linked core functionalized with triphenylphosphine oxide

Given the previous results, a new one-step synthesis approach is described for the RhNP-TPPO@CCM-C catalyst, which does not require the use of additional stabilizers. The resulting catalyst has been carefully characterized and applied in the aqueous biphasic hydrogenation of styrene, as well as other selected substrates such as alkenes, alkynes, and carbonyl compounds.

## One-pot synthesis and characterization of RhNP-TPPO@CCM-C

RhNPs embedded in the hydrophobic cores of a stable latex of TPPO@CCM-C were synthesized in a single step by heating a biphasic mixture containing the aqueous TPPO@CCM-C latex and a toluene solution of [Rh(COD)(μ-Cl)]₂ under H₂ pressure. This could be performed without any additional stabilizer or base additive (Table 2, Entry 1) and without the need for a preliminary ex-situ synthesis of the RhNPs (as previously reported [70]). Comparative syntheses were also carried out in the presence of a base such as pyridine or NEt₃ (Table 2, Entries 2 and 3, respectively), which can assist the reaction by trapping the HCl produced during the reduction of Rh¹ to Rh⁰, in addition to potentially contribute to the RhNP stabilization [40,70]. After the synthesis and phase separation, all three produced RhNP-TPPO@CCM-C latexes were black, signaling the successful formation and confinement of RhNPs in the core of the CCMs.

<table><caption>**Table 2.** Synthesis of RhNP-TPPO@CCM-C.ª</caption><thead><tr><th rowspan="2">Entry</th><th rowspan="2">Base</th><th rowspan="2">Molar TPPO/Rh/Base ratio</th><th colspan="2">RhNPs average size (nm)</th></tr><tr><th>Before catalysis</th><th>After catalysis</th></tr></thead><tbody><tr><td>1</td><td>-</td><td>4/1/0</td><td>1.7 ± 0.2</td><td>1.9 ± 0.6</td></tr><tr><td>2</td><td>Pyridine</td><td>4/1/4</td><td>2.9 ± 0.6</td><td>3.1 ± 0.1</td></tr><tr><td>3</td><td>NEt<sub>3</sub></td><td>4/1/4</td><td>2.1 ± 0.1</td><td>1.8 ± 0.2</td></tr></tbody></table>

TEM analyses confirmed the successful incorporation of the RhNPs in the TPPO@CCM-C in all cases (Figure 7). The RhNPs synthesized without base (Entry 1) showed a particularly narrow size distribution with a mean diameter (d<sub>m</sub>) of 1.7 ± 0.2 nm. On the other hand, the RhNPs produced in the presence of pyridine or NEt₃ (Table 2 Entries 2 and 3, respectively), were found agglomerated and with slightly larger average diameters (d<sub>m</sub> = 2.9 ± 0.6 nm and d<sub>m</sub> = 2.1 ± 0.1 nm, respectively, Figure 7).

When using only molecular TPPO (i.e. not linked to the CCM support) as a stabilizer under the same reaction conditions (toluene, TPPO/Rh = 4/1, 20 bar of H₂, 60 °C, 1200 rpm, for 20 h) and no base additive, a black colloidal suspension of RhNPs was also obtained. These RhNPs were also found to have a slightly larger average diameter (d<sub>m</sub> = 2.4 ± 0.2 nm) than those embedded in the TPPO@CCM-C latex obtained without a base and were relatively well dispersed (Figure 8).

<footnote>ªReaction conditions: 20 bar H₂, 20 h, 60 °C, toluene, 1200 rpm.</footnote>
## Aqueous biphasic hydrogenation with Rh nanoparticles synthesized in a single step within micelles with a polycationic shell and a cross-linked core functionalized with triphenylphosphine oxide

Given the previous results, a new one-step synthesis approach is described for the RhNP-TPPO@CCM-C catalyst, which does not require the use of additional stabilizers. The resulting catalyst has been carefully characterized and applied in the aqueous biphasic hydrogenation of styrene, as well as other selected substrates such as alkenes, alkynes, and carbonyl compounds.

## One-pot synthesis and characterization of RhNP-TPPO@CCM-C

RhNPs embedded in the hydrophobic cores of a stable latex of TPPO@CCM-C were synthesized in a single step by heating a biphasic mixture containing the aqueous TPPO@CCM-C latex and a toluene solution of [Rh(COD)(μ-Cl)]₂ under H₂ pressure. This could be performed without any additional stabilizer or base additive (Table 2, Entry 1) and without the need for a preliminary *ex-situ* synthesis of the RhNPs (as previously reported [70]). Comparative syntheses were also carried out in the presence of a base such as pyridine or NEt₃ (Table 2, Entries 2 and 3, respectively), which can assist the reaction by trapping the HCl produced during the reduction of Rh¹ to Rh⁰, in addition to potentially contribute to the RhNP stabilization [40,70]. After the synthesis and phase separation, all three produced RhNP-TPPO@CCM-C latexes were black, signaling the successful formation and confinement of RhNPs in the core of the CCMs.

<table><caption>**Table 2.** Synthesis of RhNP-TPPO@CCM-C.ª</caption><thead><tr><th rowspan="2">Entry</th><th rowspan="2">Base</th><th rowspan="2">Molar TPPO/Rh/Base ratio</th><th colspan="2">RhNPs average size (nm)</th></tr><tr><th>Before catalysis</th><th>After catalysis</th></tr></thead><tbody><tr><td>1</td><td>-</td><td>4/1/0</td><td>1.7 ± 0.2</td><td>1.9 ± 0.6</td></tr><tr><td>2</td><td>Pyridine</td><td>4/1/4</td><td>2.9 ± 0.6</td><td>3.1 ± 0.1</td></tr><tr><td>3</td><td>NEt<sub>3</sub></td><td>4/1/4</td><td>2.1 ± 0.1</td><td>1.8 ± 0.2</td></tr></tbody></table>

TEM analyses confirmed the successful incorporation of the RhNPs in the TPPO@CCM-C in all cases (Figure 7). The RhNPs synthesized without base (Entry 1) showed a particularly narrow size distribution with a mean diameter (d_m) of 1.7 ± 0.2 nm. On the other hand, the RhNPs produced in the presence of pyridine or NEt₃ (Table 2 Entries 2 and 3, respectively), were found agglomerated and with slightly larger average diameters (d_m = 2.9 ± 0.6 nm and d_m = 2.1 ± 0.1 nm, respectively, Figure 7).

When using only molecular TPPO (i.e. not linked to the CCM support) as a stabilizer under the same reaction conditions (toluene, TPPO/Rh = 4/1, 20 bar of H₂, 60 °C, 1200 rpm, for 20 h) and no base additive, a black colloidal suspension of RhNPs was also obtained. These RhNPs were also found to have a slightly larger average diameter (d_m = 2.4 ± 0.2 nm) than those embedded in the TPPO@CCM-C latex obtained without a base and were relatively well dispersed (Figure 8).

<footnote>ªReaction conditions: 20 bar H₂, 20 h, 60 °C, toluene, 1200 rpm.</footnote>
<figure><img src="image_216.png" /><figcaption>**Figure 7.** TEM images of the three one-pot-synthesized RhNP-TPPO@CCM-C latexes (left), and corresponding RhNP size distribution (right), obtained (a) without base, (b) with pyridine and (c) with NEt₃.</figcaption></figure>

<figure><img src="image_217.png" /><figcaption>**Figure 8.** TEM image of RhNPs obtained using only molecular TPPO as a stabilizer (TPPO/Rh = 4/1) with the corresponding size distribution ($d_m = 2.4 \pm 0.2$ nm). Reaction conditions: toluene solution, 20 bar H₂, 60 °C, 20 h.</figcaption></figure>

Furthermore, when treating a [Rh(COD)(μ-Cl)]₂ solution in toluene under an H₂ pressure in the absence of any polymer, stabilizer, and base, only large agglomerates were produced under the same reaction conditions (Figure 9).
<figure><img src="image_214.png" /><figcaption>**Figure 7.** TEM images of the three one-pot-synthesized RhNP-TPPO@CCM-C latexes (left), and corresponding RhNP size distribution (right), obtained (a) without base, (b) with pyridine and (c) with NEt₃.</figcaption></figure>

<figure><img src="image_215.png" /><figcaption>**Figure 8.** TEM image of RhNPs obtained using only molecular TPPO as a stabilizer (TPPO/Rh = 4/1) with the corresponding size distribution ($d_m = 2.4 \pm 0.2$ nm). Reaction conditions: toluene solution, 20 bar H₂, 60 °C, 20 h.</figcaption></figure>

Furthermore, when treating a [Rh(COD)(μ-Cl)]₂ solution in toluene under an H₂ pressure in the absence of any polymer, stabilizer, and base, only large agglomerates were produced under the same reaction conditions (Figure 9).
<figure><img src="image_218.png" /><figcaption>**Figure 9.** TEM image of Rh agglomerates generated in the absence of stabilizers. Reaction conditions: toluene solution, 20 bar H₂, 60 °C, 20 h.</figcaption></figure>

The smaller size of the RhNPs in the TPPO@CCM-C obtained from the base-free one-pot procedure may result from a more efficient stabilization in the polymer, due to the combined interaction with the oxygen lone pairs of TPPO ligands in the CCM-C core and π-electrons of the phenyl groups in the styrene monomers. The confinement effect may also provide an improved rate of nucleation, resulting in a greater number of NPs and a consequent decrease in their average size [18,58,71–77]. In principle, the nucleation may predominantly occur either within the CCM cores or in the bulk toluene phase, followed by migration and anchoring within the CCM cores. Since small-sized NPs ($d_m$ = 2.4 ± 0.2 nm) were generated in the presence of molecular TPPO in the toluene phase, even without base, whereas large agglomerates were generated in toluene without stabilizer, it seems likely that faster nucleation occurred within the CCM-C cores that contain TPPO ligands.

TG/DSC analyses of the TPPO@CCM-C and RhNP-TPPO@CCM-C polymers were further performed under N₂ to examine their relative thermal stability (Figure 10). The TPPO@CCM-C sample showed an initial decomposition phase at 239 °C (ca. 20 wt.% loss), followed by a gradual weight loss at higher temperatures with a peak at 413 °C (total weight loss ca. 88 wt.%). The RhNP-TPPO@CCM-C sample, on the other hand, exhibited an initial degradation phase at a higher temperature (264 °C, ca. 50 wt.% loss) and a lower total weight loss (77 wt.%) with a second peak at 403 °C, suggesting an effect of the RhNPs on the decomposition of the Rh loaded polymer. The thermal stability of the RhNP-TPPO@CCM-C latex was insufficient to perform further investigations of the RhNPs active sites by conventional techniques such as carbon monoxide temperature-programmed desorption (CO-TPD), which requires high temperatures for the CO desorption [78,79] and may be affected by the polymer degradation.

To further corroborate the interaction between the polymer and the RhNPs, ATR-FTIR spectra of TPPO@CCM-C and RhNP-TPPO@CCM-C were compared to that of molecular TPPO (Figure 11). The strong P=O stretching band of TPPO (1182 cm⁻¹) [80] was quite evident in TPPO@CCM-C, and a P=O signal was also visible in RhNP-TPPO@CCM-C, but this band was broad and redshifted (~1180-1140 cm⁻¹). This likely indicates that the P=O group is bound to the RhNP surface, as also previously observed for other metal-coordinated TPPO ligands [81,82].
<figure><img src="image_216.png" /><figcaption>**Figure 9.** TEM image of Rh agglomerates generated in the absence of stabilizers. Reaction conditions: toluene solution, 20 bar H₂, 60 °C, 20 h.</figcaption></figure>

The smaller size of the RhNPs in the TPPO@CCM-C obtained from the base-free one-pot procedure may result from a more efficient stabilization in the polymer, due to the combined interaction with the oxygen lone pairs of TPPO ligands in the CCM-C core and π-electrons of the phenyl groups in the styrene monomers. The confinement effect may also provide an improved rate of nucleation, resulting in a greater number of NPs and a consequent decrease in their average size [18,58,71–77]. In principle, the nucleation may predominantly occur either within the CCM cores or in the bulk toluene phase, followed by migration and anchoring within the CCM cores. Since small-sized NPs ($d_m$ = 2.4 ± 0.2 nm) were generated in the presence of molecular TPPO in the toluene phase, even without base, whereas large agglomerates were generated in toluene without stabilizer, it seems likely that faster nucleation occurred within the CCM-C cores that contain TPPO ligands.

TG/DSC analyses of the TPPO@CCM-C and RhNP-TPPO@CCM-C polymers were further performed under N₂ to examine their relative thermal stability (Figure 10). The TPPO@CCM-C sample showed an initial decomposition phase at 239 °C (ca. 20 wt.% loss), followed by a gradual weight loss at higher temperatures with a peak at 413 °C (total weight loss ca. 88 wt.%). The RhNP-TPPO@CCM-C sample, on the other hand, exhibited an initial degradation phase at a higher temperature (264 °C, ca. 50 wt.% loss) and a lower total weight loss (77 wt.%) with a second peak at 403 °C, suggesting an effect of the RhNPs on the decomposition of the Rh loaded polymer. The thermal stability of the RhNP-TPPO@CCM-C latex was insufficient to perform further investigations of the RhNPs active sites by conventional techniques such as carbon monoxide temperature-programmed desorption (CO-TPD), which requires high temperatures for the CO desorption [78,79] and may be affected by the polymer degradation.

To further corroborate the interaction between the polymer and the RhNPs, ATR-FTIR spectra of TPPO@CCM-C and RhNP-TPPO@CCM-C were compared to that of molecular TPPO (Figure 11). The strong P=O stretching band of TPPO (1182 cm⁻¹) [80] was quite evident in TPPO@CCM-C, and a P=O signal was also visible in RhNP-TPPO@CCM-C, but this band was broad and redshifted (~1180-1140 cm⁻¹). This likely indicates that the P=O group is bound to the RhNP surface, as also previously observed for other metal-coordinated TPPO ligands [81,82].
<figure><img src="image_219.png" /><figcaption>**Figure 10.** TGA (a,c) and DSC (b,d) profiles of TPPO@CCM-C (red, top) and RhNP-TPPO@CCM-C (blue, bottom).</figcaption></figure>

<figure><img src="image_220.png" /><figcaption>**Figure 11.** ATR-FTIR spectra of TPPO@CCM-C (red), RhNP-TPPO@CCM-C (blue), solid residue after TGA (black), and molecular TPPO (green), in the range of 700-2000 cm⁻¹.</figcaption></figure>

In line with this, XPS analyses performed on the TPPO@CCM-C and RhNP-TPPO@CCM-C systems indicated also a shift in binding energy in the presence of RhNPs in the core of the TPPO@CCM-C polymer, which is particularly notable for the O1s excitation (ΔE = 0.58 eV), further supporting the existence of RhNPs-polymer interactions in RhNP-TPPO@CCM-C.
<figure><img src="image_217.png" /><figcaption>**Figure 10.** TGA (a,c) and DSC (b,d) profiles of TPPO@CCM-C (red, top) and RhNP-TPPO@CCM-C (blue, bottom).</figcaption></figure>

<figure><img src="image_218.png" /><figcaption>**Figure 11.** ATR-FTIR spectra of TPPO@CCM-C (red), RhNP-TPPO@CCM-C (blue), solid residue after TGA (black), and molecular TPPO (green), in the range of 700-2000 cm⁻¹.</figcaption></figure>

In line with this, XPS analyses performed on the TPPO@CCM-C and RhNP-TPPO@CCM-C systems indicated also a shift in binding energy in the presence of RhNPs in the core of the TPPO@CCM-C polymer, which is particularly notable for the O1s excitation (ΔE = 0.58 eV), further supporting the existence of RhNPs-polymer interactions in RhNP-TPPO@CCM-C.
## Aqueous biphasic hydrogenation with RhNP-TPPO@CCM-C

### Hydrogenation of styrene without base additive

Using the RhNP-TPPO@CCM-C latex produced in the absence of base, an initial series of catalytic runs with different reaction times were carried out at 25 °C, 20 bar of H₂ pressure and stirring of 1200 rpm to limit external mass transfer, with a styrene/Rh ratio of 5000/1 (Figure 12). A complete conversion of styrene was reached after 2 h corresponding to an average TOF of 3000 h⁻¹ (cTOF 4300 h⁻¹).

<figure><img src="image_221.png" /><figcaption>**Figure 12.** Time plot for the aqueous biphasic hydrogenation of styrene using RhNP-TPPO@CCM-C prepared without base. Reaction conditions: styrene/Rh = 5000/1, 20 bar H₂, 25 °C, 1200 rpm.</figcaption></figure>

Additional catalytic runs with a fixed reaction time of 0.25 h and different styrene/Rh ratios yielded the results reported in Table 3, Entries 1-3. The system showed excellent selectivity (>99%) towards the formation of ethylbenzene (EB) with formation of only trace amounts of the fully saturated product ethylcyclohexane (ECH), as also previously described for styrene hydrogenation using other RhNP-CCM catalysts [40,70]. Moreover, phase separation was fast in all reactions (< 3 min), facilitating product separation and catalyst recovery, as already observed for other aqueous biphasic applications of nanoreactors featuring the same outer shell (CCM-C) [37,40,70].

Hydrogenation of styrene was also performed with the same RhNP-TPPO@CCM-C latex at higher temperatures (30 °C-55 °C) with a styrene/Rh ratio of 5000/1 (Table 3, Entries 4-7). At 55°C, a conversion of 83% could be obtained after 0.25 h, yielding a very high average TOF of 16100 h⁻¹ (cTOF 23600 h⁻¹).

The more moderate conversions obtained in the 25-35 °C range allowed to estimate an apparent reaction activation energy (Ea) of 69 ± 6 kJ/mol from an Arrhenius plot (Figure 13) which is comparable to the Ea obtained for the gas-phase hydrogenation of styrene [83]. However, at higher reaction temperatures the apparent Ea decreased to 4 ± 1 kJ/mol, indicating diffusion limitations (internal mass transfer).
## Aqueous biphasic hydrogenation with RhNP-TPPO@CCM-C

### Hydrogenation of styrene without base additive

Using the RhNP-TPPO@CCM-C latex produced in the absence of base, an initial series of catalytic runs with different reaction times were carried out at 25 °C, 20 bar of H₂ pressure and stirring of 1200 rpm to limit external mass transfer, with a styrene/Rh ratio of 5000/1 (Figure 12). A complete conversion of styrene was reached after 2 h corresponding to an average TOF of 3000 h⁻¹ (cTOF 4300 h⁻¹).

<figure><img src="image_219.png" /><figcaption>**Figure 12.** Time plot for the aqueous biphasic hydrogenation of styrene using RhNP-TPPO@CCM-C prepared without base. Reaction conditions: styrene/Rh = 5000/1, 20 bar H₂, 25 °C, 1200 rpm.</figcaption></figure>

Additional catalytic runs with a fixed reaction time of 0.25 h and different styrene/Rh ratios yielded the results reported in Table 3, Entries 1-3. The system showed excellent selectivity (>99%) towards the formation of ethylbenzene (EB) with formation of only trace amounts of the fully saturated product ethylcyclohexane (ECH), as also previously described for styrene hydrogenation using other RhNP-CCM catalysts [40,70]. Moreover, phase separation was fast in all reactions (< 3 min), facilitating product separation and catalyst recovery, as already observed for other aqueous biphasic applications of nanoreactors featuring the same outer shell (CCM-C) [37,40,70].

Hydrogenation of styrene was also performed with the same RhNP-TPPO@CCM-C latex at higher temperatures (30 °C-55 °C) with a styrene/Rh ratio of 5000/1 (Table 3, Entries 4-7). At 55°C, a conversion of 83% could be obtained after 0.25 h, yielding a very high average TOF of 16100 h⁻¹ (cTOF 23600 h⁻¹).

The more moderate conversions obtained in the 25-35 °C range allowed to estimate an apparent reaction activation energy (Ea) of 69 ± 6 kJ/mol from an Arrhenius plot (Figure 13) which is comparable to the Ea obtained for the gas-phase hydrogenation of styrene [83]. However, at higher reaction temperatures the apparent Ea decreased to 4 ± 1 kJ/mol, indicating diffusion limitations (internal mass transfer).
<figure><img src="image_222.png" /><figcaption>**Table 3.** Hydrogenation of styrene using RhNP-TPPO@CCM-C prepared without base.ª</figcaption></figure>

<table><thead><tr><th rowspan="2">Entry</th><th rowspan="2">Molar<br>styrene/Rh<br>ratio</th><th rowspan="2">T (°C)</th><th rowspan="2">Conversion<br>(%)</th><th colspan="2">Selectivity (%)</th><th rowspan="2">TOF (cTOF)<sup>b</sup><br>(h<sup>-1</sup>)</th></tr><tr><th>EB</th><th>ECH</th></tr></thead><tbody><tr><td>1</td><td>2000/1</td><td>25</td><td>82</td><td>&gt;99</td><td>&lt;0.1</td><td>7800 (11500)</td></tr><tr><td>2</td><td>5000/1</td><td>25</td><td>21</td><td>&gt;99</td><td>&lt;0.1</td><td>4500 (6500)</td></tr><tr><td>3</td><td>10000/1</td><td>25</td><td>8</td><td>&gt;99</td><td>&lt;0.1</td><td>3000 (4450)</td></tr><tr><td>4</td><td>5000/1</td><td>30</td><td>35</td><td>&gt;99</td><td>&gt;0.1</td><td>8000 (11600)</td></tr><tr><td>5</td><td>5000/1</td><td>35</td><td>58</td><td>&gt;99</td><td>&lt;0.1</td><td>11200 (16400)</td></tr><tr><td>6</td><td>5000/1</td><td>45</td><td>65</td><td>&gt;99</td><td>&lt;0.1</td><td>12900 (19000)</td></tr><tr><td>7</td><td>5000/1</td><td>55</td><td>83</td><td>&gt;99</td><td>&lt;0.1</td><td>16100 (23600)</td></tr></tbody></table>

<figure><img src="image_223.png" /><figcaption>**Figure 13.** Arrhenius plot of the hydrogenation of styrene using RhNP-TPPO@CCM-C prepared without base. Reaction conditions: styrene/Rh = 5000/1, 20 bar H₂, 0.25 h, 1200 rpm, accuracy of temperature measured with ± 0.5-1 °C.</figcaption></figure>

The RhNP-TPPO@CCM-C latex recycling was further evaluated for a series of runs with a styrene/Rh ratio of 5000/1 and 0.25 h of reaction time with intermediate product extraction by diethyl ether (Figure 14). The extraction procedure was similar to that previously applied to recycle the RhNP-TPP@CCM-C and RhNP-TPPO@CCM-C latexes [37,40,70], as well as the latex of the molecular Rh¹-TPP@CCM [37,40]. A rather constant styrene conversion of ca. 21%, corresponding to an average TOF

<footnote>ª Reaction conditions: 20 bar H₂, 25 °C, 0.25 h, 1200 rpm. ᵇ Corrected TOF (cTOF) calculated by considering only the surface Rh atoms (see Experimental Part). EB: ethylbenzene, ECH: ethylcyclohexane.</footnote>
<figure><img src="image_220.png" /><figcaption>**Table 3.** Hydrogenation of styrene using RhNP-TPPO@CCM-C prepared without base.ª</figcaption></figure>

<table><thead><tr><th rowspan="2">Entry</th><th rowspan="2">Molar<br>styrene/Rh<br>ratio</th><th rowspan="2">T (°C)</th><th rowspan="2">Conversion<br>(%)</th><th colspan="2">Selectivity (%)</th><th rowspan="2">TOF (cTOF)<sup>b</sup><br>(h<sup>-1</sup>)</th></tr><tr><th>EB</th><th>ECH</th></tr></thead><tbody><tr><td>1</td><td>2000/1</td><td>25</td><td>82</td><td>&gt;99</td><td>&lt;0.1</td><td>7800 (11500)</td></tr><tr><td>2</td><td>5000/1</td><td>25</td><td>21</td><td>&gt;99</td><td>&lt;0.1</td><td>4500 (6500)</td></tr><tr><td>3</td><td>10000/1</td><td>25</td><td>8</td><td>&gt;99</td><td>&lt;0.1</td><td>3000 (4450)</td></tr><tr><td>4</td><td>5000/1</td><td>30</td><td>35</td><td>&gt;99</td><td>&gt;0.1</td><td>8000 (11600)</td></tr><tr><td>5</td><td>5000/1</td><td>35</td><td>58</td><td>&gt;99</td><td>&lt;0.1</td><td>11200 (16400)</td></tr><tr><td>6</td><td>5000/1</td><td>45</td><td>65</td><td>&gt;99</td><td>&lt;0.1</td><td>12900 (19000)</td></tr><tr><td>7</td><td>5000/1</td><td>55</td><td>83</td><td>&gt;99</td><td>&lt;0.1</td><td>16100 (23600)</td></tr></tbody></table>

<figure><img src="image_221.png" /><figcaption>**Figure 13.** Arrhenius plot of the hydrogenation of styrene using RhNP-TPPO@CCM-C prepared without base. Reaction conditions: styrene/Rh = 5000/1, 20 bar H₂, 0.25 h, 1200 rpm, accuracy of temperature measured with ± 0.5-1 °C.</figcaption></figure>

The RhNP-TPPO@CCM-C latex recycling was further evaluated for a series of runs with a styrene/Rh ratio of 5000/1 and 0.25 h of reaction time with intermediate product extraction by diethyl ether (Figure 14). The extraction procedure was similar to that previously applied to recycle the RhNP-TPP@CCM-C and RhNP-TPPO@CCM-C latexes [37,40,70], as well as the latex of the molecular Rh¹-TPP@CCM [37,40]. A rather constant styrene conversion of ca. 21%, corresponding to an average TOF

<footnote>ª Reaction conditions: 20 bar H₂, 25 °C, 0.25 h, 1200 rpm. ᵇ Corrected TOF (cTOF) calculated by considering only the surface Rh atoms (see Experimental Part). EB: ethylbenzene, ECH: ethylcyclohexane.</footnote>
of ~4500 h⁻¹ (cTOF of 6500 h⁻¹), was obtained over the six consecutive reaction runs, but only when the recovered catalyst system was reactivated with H₂ (20 bar, 1 h, 25 °C) prior to addition of new batch of substrate. A recycling experiment without this reactivation treatment gave erratic results, possibly because of passivation of the RhNPs by surface oxide layer formation during the work-up recycling procedures [58,65,70]. A TEM analysis (Figure 15) on the recovered latex after run six showed that the RhNPs remained well-dispersed, with a similar size distribution (1.9 ± 0.6 nm) as prior to catalysis (see Table 2).

<figure><img src="image_224.png" /><figcaption>**Figure 14.** Reuse of RhNP-TPPO@CCM-C catalyst in six catalytic runs of styrene hydrogenation with product extraction by diethyl ether and intermediate H₂ treatment (20 bar H₂, 25 °C, 1 h, 1200 rpm) and product extraction by diethyl ether. Reaction conditions: Styrene/Rh = 5000/1, 20 bar H₂, 25 °C, 0.25 h, 1200 rpm.</figcaption></figure>

<figure><img src="image_225.png" /><figcaption>**Figure 15.** TEM image of RhNP-TPPO@CCM-C recording from an aliquot during recycling after run six (left) and corresponding size distribution ($d_m$ = 1.9 ± 0.6 nm) (right).</figcaption></figure>

A reference hydrogenation experiment was carried out under the same conditions using a toluene phase of the TPPO-stabilized RhNPs as catalyst (20 bar of H₂, 25 °C, styrene/Rh = 10000/1, 0.25 h). This resulted in a styrene conversion of 53% (average TOF ~20000 h⁻¹, cTOF 21500 h⁻¹) with >99% of EB selectivity. Using EB as substrate under the same reaction conditions yielded only 0.6% of ECH, confirming the high selectivity of the TPPO-stabilized RhNPs under these mild reaction conditions. The cTOF decreased from ~21500 h⁻¹ for the reaction carried out with the RhNP-TPPO/toluene catalytic system to ~6500 h⁻¹ for that conducted with the RhNP-TPPO@CCM-C/biphasic system, which indicate that the latter was influenced by internal mass transport restrictions of the styrene substrate and/or the EB product.
of ~4500 h⁻¹ (cTOF of 6500 h⁻¹), was obtained over the six consecutive reaction runs, but only when the recovered catalyst system was reactivated with H₂ (20 bar, 1 h, 25 °C) prior to addition of new batch of substrate. A recycling experiment without this reactivation treatment gave erratic results, possibly because of passivation of the RhNPs by surface oxide layer formation during the work-up recycling procedures [58,65,70]. A TEM analysis (Figure 15) on the recovered latex after run six showed that the RhNPs remained well-dispersed, with a similar size distribution (1.9 ± 0.6 nm) as prior to catalysis (see Table 2).

<figure><img src="image_222.png" /><figcaption>**Figure 14.** Reuse of RhNP-TPPO@CCM-C catalyst in six catalytic runs of styrene hydrogenation with product extraction by diethyl ether and intermediate H₂ treatment (20 bar H₂, 25 °C, 1 h, 1200 rpm) and product extraction by diethyl ether. Reaction conditions: Styrene/Rh = 5000/1, 20 bar H₂, 25 °C, 0.25 h, 1200 rpm.</figcaption></figure>

<figure><img src="image_223.png" /><figcaption>**Figure 15.** TEM image of RhNP-TPPO@CCM-C recording from an aliquot during recycling after run six (left) and corresponding size distribution ($d_m$ = 1.9 ± 0.6 nm) (right).</figcaption></figure>

A reference hydrogenation experiment was carried out under the same conditions using a toluene phase of the TPPO-stabilized RhNPs as catalyst (20 bar of H₂, 25 °C, styrene/Rh = 10000/1, 0.25 h). This resulted in a styrene conversion of 53% (average TOF ~20000 h⁻¹, cTOF 21500 h⁻¹) with >99% of EB selectivity. Using EB as substrate under the same reaction conditions yielded only 0.6% of ECH, confirming the high selectivity of the TPPO-stabilized RhNPs under these mild reaction conditions. The cTOF decreased from ~21500 h⁻¹ for the reaction carried out with the RhNP-TPPO/toluene catalytic system to ~6500 h⁻¹ for that conducted with the RhNP-TPPO@CCM-C/biphasic system, which indicate that the latter was influenced by internal mass transport restrictions of the styrene substrate and/or the EB product.
## Hydrogenation of styrene with base additive

The RhNP-TPPO@CCM-C latexes obtained in the presence of pyridine (Table 2, Entry 2) or $NEt_3$ (Table 2, Entry 3) were also evaluated for styrene hydrogenation, after extensive prewashing with diethylether prior to the first catalytic run (Figure 16).

<figure><img src="image_226.png" /><figcaption>**Figure 16.** Reuse of the RhNP-TPPO@CCM-C latexes prepared with base additives in styrene hydrogenation with intermediate $H_2$ treatment (20 bar $H_2$, 25 °C, 0.25 h, 1200 rpm) as well as product extraction by diethyl ether. Reaction conditions: Styrene/Rh = 5000/1 (*6500/1), 20 bar $H_2$, 25 °C, 0.25 h, 1200 rpm.</figcaption></figure>

When using the RhNP-TPPO@CCM-C latex prepared with $NEt_3$, the first catalytic run yielded a styrene conversion of ~10%, but the subsequent runs converged to a stable conversion of ca. 25-30%. Similar difference between the first and consecutive reaction runs were reported for the RhNP-TPPO@CCM-C latex obtained by transfer of *ex-situ* synthesized RhNPs [70] as well as other studies using $NEt_3$ [58]. This can be explained by an induction time, possibly resulting from restructuring of the RhNPs surface under catalytic conditions which produced more catalytically active sites and consecutive higher conversion. On the other hand, the RhNP-TPPO@CCM-C latex prepared with pyridine showed much higher activity (conversion of ca. 97%), with an average TOF of ~18200 $h^{-1}$ (cTOF 40000 $h^{-1}$) in the first run. However, the activity steadily decreased over the subsequent runs, most likely as a consequence of the continuous removal of adsorbed pyridine from the RhNPs surface during the successive recycling treatments that involve diethyl ether extractions. This result is analogous to that shown by the RhNP-TPPO@CCM-C latex obtained by incorporating the *ex-situ* synthesized RhNPs with stabilization by TPP and pyridine as stabilizers [70], and confirms that the presence of pyridine has a beneficial effect on the RhNPs catalytic activity, that might be due to a cleaner Rh surface as the result of less chlorides, present in the organometallic dimer, that may be better eliminated. The intimate reason for this promotion effect is currently unknown. Interestingly, when the catalyst recyclability was performed with a higher styrene/Rh ratio of 6500/1, the activity dropped in the first run (as expected) to an average TOF of ~10000 $h^{-1}$ (cTOF 23000 $h^{-1}$), and the system proved less stable compared to the RhNP-TPPO@CCM-C synthesized in one-pot without base (Figure 17). A potential factor that influences the results may be alterations in internal mass transfer limitations, which are
## Hydrogenation of styrene with base additive

The RhNP-TPPO@CCM-C latexes obtained in the presence of pyridine (Table 2, Entry 2) or $NEt_3$ (Table 2, Entry 3) were also evaluated for styrene hydrogenation, after extensive prewashing with diethylether prior to the first catalytic run (Figure 16).

<figure><img src="image_224.png" /><figcaption>**Figure 16.** Reuse of the RhNP-TPPO@CCM-C latexes prepared with base additives in styrene hydrogenation with intermediate $H_2$ treatment (20 bar $H_2$, 25 °C, 0.25 h, 1200 rpm) as well as product extraction by diethyl ether. Reaction conditions: Styrene/Rh = 5000/1 (*6500/1), 20 bar $H_2$, 25 °C, 0.25 h, 1200 rpm.</figcaption></figure>

When using the RhNP-TPPO@CCM-C latex prepared with $NEt_3$, the first catalytic run yielded a styrene conversion of ~10%, but the subsequent runs converged to a stable conversion of ca. 25-30%. Similar difference between the first and consecutive reaction runs were reported for the RhNP-TPPO@CCM-C latex obtained by transfer of *ex-situ* synthesized RhNPs [70] as well as other studies using $NEt_3$ [58]. This can be explained by an induction time, possibly resulting from restructuring of the RhNPs surface under catalytic conditions which produced more catalytically active sites and consecutive higher conversion. On the other hand, the RhNP-TPPO@CCM-C latex prepared with pyridine showed much higher activity (conversion of ca. 97%), with an average TOF of ~18200 $h^{-1}$ (cTOF 40000 $h^{-1}$) in the first run. However, the activity steadily decreased over the subsequent runs, most likely as a consequence of the continuous removal of adsorbed pyridine from the RhNPs surface during the successive recycling treatments that involve diethyl ether extractions. This result is analogous to that shown by the RhNP-TPPO@CCM-C latex obtained by incorporating the *ex-situ* synthesized RhNPs with stabilization by TPP and pyridine as stabilizers [70], and confirms that the presence of pyridine has a beneficial effect on the RhNPs catalytic activity, that might be due to a cleaner Rh surface as the result of less chlorides, present in the organometallic dimer, that may be better eliminated. The intimate reason for this promotion effect is currently unknown. Interestingly, when the catalyst recyclability was performed with a higher styrene/Rh ratio of 6500/1, the activity dropped in the first run (as expected) to an average TOF of ~10000 $h^{-1}$ (cTOF 23000 $h^{-1}$), and the system proved less stable compared to the RhNP-TPPO@CCM-C synthesized in one-pot without base (Figure 17). A potential factor that influences the results may be alterations in internal mass transfer limitations, which are
likely to be more significant when the St/Rh ratio is higher (St/Rh = 5000/1 vs 6500/1). Additionally, TEM analyses of the recovered latexes synthesized in the presence of pyridine or NEt₃ showed similar dispersion and RhNPs size distributions after the fifth catalytic runs (3.1 ± 0.1 nm and 1.8 ± 0.2 nm, for pyridine and NEt₃ respectively, Figure 17) as prior to the first catalytic runs (2.9 ± 0.6 nm and 2.1 ± 0.1 nm for pyridine and NEt₃ respectively) (see Figure 7).

<figure><img src="image_227.png" /><figcaption>**Figure 17.** TEM images and ( overlayed ) the corresponding size distributions of spent RhNP-TPPO@CCM-C prepared with ( a ) pyridine ( Table 2, Entry 2 ) and with ( b ) NEt$_{3}$ ( Table 2, Entry 3 ).</figcaption></figure>

Hydrogenation of styrene in the presence of Hg

To examine whether the RhNP-TPPO@CCM-C latex (synthesized without base) also contained catalytically active Rh¹ species in addition to RhNPs, a styrene hydrogenation experiment (styrene/Rh = 5000/1) was also carried out in the presence of a large excess of Hg (Hg/Rh = 500/1), which is known to poison and deactivate the RhNPs[84]. No significant styrene conversion was observed (<0.1%) after 0.25 h of reaction, suggesting that no Rh¹ is present in the TPPO@CCM-C core. A control TEM analysis of the recovered latex after the catalytic run with Hg (Figure 18) still showed the presence of small RhNPs in the polymer, but with a larger average diameter (ca. 2.7 ± 0.1 nm vs. 1.7 ± 0.2 nm) than prior to catalysis, along with much larger particles (average size 16 ± 5 nm) that can be attributed to nanoscopic Hg droplets. The increase in the apparent size of the RhNPs could result from the formation of a Hg-Rh amalgam at the surface of the RhNPs [84,85]. This result indicates that Hg is able to cross the CCM hydrophilic shell.
likely to be more significant when the St/Rh ratio is higher (St/Rh = 5000/1 vs 6500/1). Additionally, TEM analyses of the recovered latexes synthesized in the presence of pyridine or NEt₃ showed similar dispersion and RhNPs size distributions after the fifth catalytic runs (3.1 ± 0.1 nm and 1.8 ± 0.2 nm, for pyridine and NEt₃ respectively, Figure 17) as prior to the first catalytic runs (2.9 ± 0.6 nm and 2.1 ± 0.1 nm for pyridine and NEt₃ respectively) (see Figure 7).

<figure><img src="image_225.png" /><figcaption>**Figure 17.** TEM images and (overlayed) the corresponding size distributions of spent RhNP-TPPO@CCM-C prepared with (a) pyridine (Table 2, Entry 2) and with (b) NEt₃ (Table 2, Entry 3).</figcaption></figure>

## Hydrogenation of styrene in the presence of Hg

To examine whether the RhNP-TPPO@CCM-C latex (synthesized without base) also contained catalytically active Rh¹ species in addition to RhNPs, a styrene hydrogenation experiment (styrene/Rh = 5000/1) was also carried out in the presence of a large excess of Hg (Hg/Rh = 500/1), which is known to poison and deactivate the RhNPs[84]. No significant styrene conversion was observed (<0.1%) after 0.25 h of reaction, suggesting that no Rh¹ is present in the TPPO@CCM-C core. A control TEM analysis of the recovered latex after the catalytic run with Hg (Figure 18) still showed the presence of small RhNPs in the polymer, but with a larger average diameter (ca. 2.7 ± 0.1 nm vs. 1.7 ± 0.2 nm) than prior to catalysis, along with much larger particles (average size 16 ± 5 nm) that can be attributed to nanoscopic Hg droplets. The increase in the apparent size of the RhNPs could result from the formation of a Hg-Rh amalgam at the surface of the RhNPs [84,85]. This result indicates that Hg is able to cross the CCM hydrophilic shell.
<figure><img src="image_228.png" /><figcaption>**Figure 18.** TEM images (left) of a) RhNPs and b) Hg particles and the corresponding size distributions (right) RhNPs ($d_m$ = 2.7 ± 0.1 nm; left) and Hg particles ($d_m$ = 16 ± 5 nm; right) in RhNP-TPPO@CCM-C.</figcaption></figure>

## Hydrogenation of other substrates

Lastly, the applicability of the RhNP-TPPO@CCM-C latex synthesized without base was screened for the aqueous biphasic hydrogenation of other substrates, including selected aromatics, alkenes, alkynes and carbonyl compounds (substrate/Rh = 5000/1; performed with neat substrate and not optimized) (Table 4). The results confirmed a rather high hydrogenation activity (average TOFs of 1000-1100 h⁻¹) and high selectivity towards the reduction of both double and triple carbon-carbon bonds in phenylacetylene (Entry 1) and 4-vinylpyridine (Entry 3). The catalytic activity was, however, significantly lower than for styrene under similar reaction conditions (cTOF 4500 h⁻¹; see Table 4). Highly sterically hindered Z-stilbene (Entry 2) and the aliphatic α,β-unsaturated substrate (E)-hex-2-enal (Entry 5) were only hydrogenated to a low extent under the applied conditions. Also, the carbonyl group of the aliphatic compound 5-nonanone (Entry 4) was hardly hydrogenated, whereas the cyclic (and activated) α,β-unsaturated substrate 2-cyclohexen-1-one (Entry 6) yielded a good conversion (cTOF of 1000 h⁻¹) with high selectivity (63.7%) to cyclohexanol, and acetophenone (Entry 7) showed an even higher conversion (cTOF of 3000 h⁻¹), with a nearly quantitative selectivity toward phenylethanol (>99%). Notably, no significant hydrogenation of the aromatic ring was observed in any of the reactions. Overall, the non-optimized results obtained during the screening clearly indicate the potential of the RhNP-TPPO@CCM-C catalyst synthesized without base for the hydrogenation of other types of unsaturated substrates than styrene.