# Regime Switch in the Dual-Catalyzed Coupling of Alkyl Silicates with Aryl Bromides

Khaoula Jaouadi, Mehdi Abdellaoui, Etienne Levernier, Pierre-adrien Payard, Etienne Derat, Thomas Le Saux, Cyril Ollivier, Stéphane Torelli, Ludovic Jullien, Raphaël Plasson, et al.

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Khaoula Jaouadi, Mehdi Abdellaoui, Etienne Levernier, Pierre-adrien Payard, Etienne Derat, et al. Regime Switch in the Dual-Catalyzed Coupling of Alkyl Silicates with Aryl Bromides. Chemistry - A European Journal, 2023, 29 (59), pp.e202301780. 10.1002/chem.202301780. hal-04245765

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# Regime Switch in the Dual-Catalyzed Coupling of Alkyl Silicates with Aryl Bromides

Khaoula Jaouadi,[a] Mehdi Abdellaoui,[b] Etienne Levernier,[b] Pierre-Adrien Payard,[a]

Etienne Derat,[b] Thomas Le Saux,[c] Cyril Ollivier,[b] Stéphane Torelli,[d] Ludovic Jullien,[c]

Raphaël Plasson,*[e] Louis Fensterbank,*[b] and Laurence Grimaud*[a]

Metallaphotoredox catalyzed cross-coupling of an arylbromide (Ar–Br) with an alkyl bis(catecholato)silicate (R–Si⁰) has been analyzed in depth using a continuum of analytical techniques (EPR, fluorine NMR, electrochemistry, photophysics) and modeling (micro-kinetics and DFT calculations). These studies converged on the impact of four control parameters consisting in the initial concentrations of the iridium photocatalyst ([Ir]₀), nickel precatalyst ([Ni]₀) and silicate ([R–Si⁰]₀) as well as light intensity I₀ for an

efficient reaction between Ar–Br and R–Si⁰. More precisely, two regimes were found to be possibly at play. The first one relies on an equimolar consumption of Ar–Br with R–Si⁰ smoothly leading to Ar–R, with no side-product from R–Si⁰ and a second one in which R–Si⁰ is simultaneously coupled to Ar–Br and degraded to R–H. This integrative approach could serve as a case study for the investigation of other metallaphotoredox catalysis manifolds of synthetic significance.

## Introduction

Transition metal-catalyzed cross-coupling reactions occupy nowadays a prominent position in the manufacturing of drugs, agrochemicals and other important fine chemicals.[1] To a large extent, these processes have relied on the reactivity of an organometallic reactant as nucleophilic component with an electrophile (Scheme 1a), thereby suffering from several limitations such as the necessary preformation of the rather unstable organometallic partners with limited functionalization and also sometimes the recourse to undesirable reaction conditions. As an alternative, metallaphotoredox catalysis, i.e. the merger of organometallic catalysis with photocatalysis through two interconnected cycles[2] has profoundly changed the strategies for carrying out cross-coupling reactions, especially when it comes to connecting a sp² carbon to a sp³ carbon. The so-called single electron transmetalation,[3] which consists in alkyl transfer through combination of a radical species originating from the photoredox catalytic cycle with a transition metal complex precludes a high activation energy for the transmetalation step (Scheme 1b). In most cases nickel-based

catalysts are used in order to suppress β-hydride elimination processes. First staged with carboxylates as radical precursors by Doyle and MacMillan[4] and with trifluoroborates by Molander,[5] a series of reports have confirmed the synthetic viability of this approach, notably by featuring also other radical precursors such as sulfinates,[6] dihydropyridines,[7] Katritzky pyridium salts[8,9] cycloalkanols,[10] as well as radicals arising from direct hydrogen atom transfer (HAT).[11] Among all the possible alkyl radical precursors, bis(catecholato)silicates developed by us[12,13] and Molander[14] own the valuable property to display the lowest oxidation potentials (< 1.0 V vs SCE) ensuring the generation of a broad range of radical intermediates.

In contrast to the abundance of versatile synthetic applications, mechanistic determinations, especially those based on thorough experimental investigations have remained scarce and not fully conclusive especially if one focuses on C–C bond formation(s). Based on the assumption of the formation of an ArRNi¹¹X intermediate, which undergoes reductive elimination to produce Ar–R and Ni¹X, two pathways converging to this Ni¹¹ intermediate can be envisaged. The initial proposed mechanism (variant A of the Ni cycles, Scheme 1c) was based on the known

[a] Dr. K. Jaouadi, Dr. P.-A. Payard, Dr. L. Grimaud
LBM, Département de chimie
École Normale Supérieure
PSL University, Sorbonne Université, CNRS
75005 Paris (France)
E-mail: laurence.grimaud@ens.psl.eu

[b] Dr. M. Abdellaoui, Dr. E. Levernier, Dr. E. Derat, Dr. C. Ollivier, Prof. L. Fensterbank
Sorbonne Université
CNRS, Institut Parisien de Chimie Moléculaire
75005 Paris (France)
E-mail: louis.fensterbank@sorbonne-universite.fr

[c] Dr. T. Le Saux, Prof. L. Jullien
PASTEUR, Département de chimie
École Normale Supérieure
PSL University, Sorbonne Université, CNRS
75005 Paris (France)

[d] Dr. S. Torelli
Univ. Grenoble Alpes, CNRS, CEA, IRIG
Laboratoire de Chimie et Biologie des Métaux
17 rue des Martyrs, 38054 Grenoble Cedex (France)

[e] Dr. R. Plasson
UMR408 SQPOV Avignon Université/INRAE
Campus Jean-Henri Fabre
301 rue Baruch de Spinoza BP 21239, 84916 Avignon Cedex 9 (France)
E-mail: raphael.plasson@univ-avignon.fr

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Supporting information for this article is available on the WWW under
https://doi.org/10.1002/chem.202301780
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<figure><img src="image_8.png" /><figcaption>**Scheme 1.** Cross-coupling strategies and current mechanistic proposals for photoredox/nickel dual catalysis.</figcaption></figure>

affinity of organic radicals for Ni¹¹ complexes.[15,16] Thus, following oxidative addition of Ar–X onto Ni⁰, the alkyl radical stemming from the photo-oxidative catalytic cycle would add to the ArNi¹¹X complex to generate ArRNI¹¹X that undergoes reductive elimination to deliver the Ar–R coupling product. Reduction of Ni¹ by single electron transfer (SET) restores Ni⁰. Interestingly, DFT calculations by Molander and Kozlowski based on benzyltri-fluoroborate as radical precursor and a bipyridine-based Ni complex suggested a second possible and energetically favor-able pathway consisting in the formation of a RNI¹ intermediate after radical capture by Ni⁰ (variant B, Scheme 1c).[17] The latter undergoes oxidative addition to yield to the same Ni¹¹¹ complex as before. Additional calculations were reported by Molander and Gutierrez on the cross-coupling of tertiary radicals, which showed a significant ligand dependence since the anionic 2,2,6,6-tetramethyl-3,5-heptanedionate ligand outcompeted the classically used bipyridine ligands.[18] The difference in reactivity between the two ligands was attributable to the energy barriers of the reductive elimination step.[19] The authors also refined the previous calculations.[17] They confirmed the Ni⁰/Ni¹/Ni¹¹¹ path to be the least energetic. A similar mechanism was also proposed for the arylation of Csp³-H bonds promoted by decatungstate and nickel catalysis.[20]

In parallel to these theoretical advances, significant knowl-
edge has been garnered on the photochemistry of bipyridine-
ligated Ni¹¹ and Ni¹ complexes. Notably, ArNi¹¹X complexes can
undergo photo-excitation through a MLCT process under visible
light irradiation. The corresponding excited state rapidly decays
to a longer-lived 3d-d state with weakened bonds, which favors
homolysis of the Ni¹¹–Ar bond to generate an aryl radical and a
Ni¹X complex.[21] The latter exists under an equilibrium between
a monomeric and a dimeric form. The dimeric form is generally
unreactive while the monomeric complexes (X=Cl or Br) can
undergo oxidative addition with aryl halide derivatives.[22–25] This
was for instance demonstrated by generating (bipyridine)Ni¹Br
complexes through electrosynthesis,[26] radiolysis[27] and submit-
ting them to haloarenes. Moreover, a Ni¹Cl complex coordinated

by a diester-substituted bipyridine ((EtO₂C)₂bpy) ligand was
studied and shown to undergo oxidative addition with
arylbromides.[28] Very recently, Ben-Tal and Lloyd-Jones inves-
tigated the mechanism of a Ni/Ir-photocatalyzed reductive
coupling of an aryl bromide with an alkyl bromide, featuring
extensive kinetic studies. Combining mechanistic studies and
microkinetic modeling, they demonstrated that the oxidative
addition complex ArNiBr is an on-cycle species and they notably
showed that four parameters – [ArBr], [Ni], [Ir], and light
intensity – were key to control the reaction rate of ArBr whereas
[(TMS)₃SiH] and [RBr] control the selectivity.[29]

In this context, we went beyond these relevant findings, by
developing a thorough kinetic and mechanistic study of the
representative cross-coupling of an alkyl bis(catecholato)silicate
with an aryl halide under dual photo/nickel catalysis conditions.
This study was performed thanks to the combination of
analytical techniques and modeling. The impact of each
parameter on the kinetics of a model system (stoichiometry of
the reactants, nature and quantities of catalysts, light intensity)
was assessed and an integrative approach based on kinetic
modeling was applied to propose a mechanism consistent with
the collected data. Remarkably, two regimes turned out to be
operative: during the first phase both substrates are consumed
at the same rate but in the second regime, two R–Si are
needed as one decomposed into R–H.

**Results and Discussion**

The model system

In order to study the mechanism of the cross-coupling of
alkylsilicates with aryl halides under dual photo/nickel catalysis
conditions, we adopted the 2-bromo-5-fluorotoluene (Ar–Br)
and 3-acetoxypropyl bis(catecholato)silicate (R–Si) as model
partners, and based on our previous work,[12,13] an Ir photo-
catalyst and a NiBr₂(dtbbpy) nickel precatalyst generated from
<figure><img src="image_9.png" /></figure>

a mixture of NiBr₂ and 2,6-di-tert-butylpyridine (dtbbpy) – noted NiillBr₂ in the following (Scheme 2). This Ar–Br was notably selected for analytical purposes due to the presence of the fluorine atom facilitating NMR probing and the ortho-methyl group that could enhance the stability of the intermediate ArNiil complex.[30] For mechanistic analysis, we further synthesized cis-[[4-F-2-Me-C₆H₃)NiillBr(dtbbpy)] and [NiICl(dtbbpy)]₂, respectively denoted ArNiillBr and NiICl in the following.

Investigation of the Ir-based photocatalytic cycle

As light on/off experiments showed that the photoconversion of the system stopped without irradiation,[31] thereby discarding long radical chain mechanisms,[32] we could directly apply irradiation on an NMR tube containing the photoreactive medium with a home-built setup (see Figure S1) in order to sequentially get quantitative information by ¹⁹F{¹H} NMR. Indeed, as complex polymers are generated all along the process due to the release of the bis(catecholato)silane,[33] a continuous shaking ensures a homogeneous irradiation of the medium. We set the irradiation conditions upon consideration of two series of observations. First, we noticed that the Ir III photocatalyst exhibits a much more important light absorption at wavelengths lower than 450 nm, which corresponds to the blue LED emitting region used for the scope investigation[12,13] (see Figure S7b). Second, the UV absorption spectrum of the ArNiilBr reference complex proved that its absorption was less pro-

nounced around 360 nm than around 450 nm (see Figure S7a). As previously reported,[21,34,35,36] the photodegradation of ArNiilBr may occur above 400 nm and indeed it was faster upon illumination at 450 nm than at 365 nm (see Figure S9). Accordingly, we used a UV LED emitting at 365 ± 5 nm for irradiation of the selected model reaction. At 15 mW·cm⁻² light intensity, the photoconversion of Ar–Br and R–Siº proceeded smoothly to yield up to 80% of Ar–R along with traces of arylated by-products Ar–H and Ar–Ar, as well as R–Siº-derived side products such as R–H and traces of R–R. It is worth noting that no continuous consumption of R–Siº was evidenced when irradiating it with the photocatalyst only, which implies a direct link between the photoconversion and the presence of Ni catalyst.

Through the control of all the parameters, the light-driven generation of radicals from silicates could be studied. Alkyl bis(catecholato)silicates have been reported to quench the excited state Ir III* of the photocatalyst, with a high rate constant (≈10¹⁰ M⁻¹s⁻¹) assessed from Stern–Volmer analysis of the dependence of the Ir III* steady luminescence on the concentration of bis(catecholato)alkylsilicates.[12] The order of magnitude of this value was presently confirmed by using the Stern–Volmer analysis of the dependence of the Ir III* luminescence lifetime on the R–Siº concentration (see Figure 1a,b). Since the Ir III* luminescence emission spectrum does not overlap with the R–Siº absorption spectrum (see Figure S8), energy transfer[37,38] is unlikely and the photogeneration of radicals from R–Siº probably results from electron transfer. This conclusion is consistent with electrochemical considerations. Ir III* (reduction potential *E*<sub>p</sub><sup>red</sup> = +1.32 V vs SCE³⁹ in DMF) is anticipated to oxidize R–Siº (*E*<sub>p</sub><sup>ox</sup> = +0.85 V vs SCE in DMF; see Figure S12g). In contrast, *fac*-Ir(ppy)<sub>3</sub> featuring photophysical properties close to those of Ir III but exhibiting a lower reduction potential at the excited state than Ir III* (*E*<sub>p</sub><sup>red</sup> = +0.31 V vs SCE)[40] does not lead to photoconversion when irradiated at 365 nm (see Table S1). Another argument was provided by EPR experiments performed in DMF. As expected, Ir III and the 1/1 mixture of Ir III/R–Siº are EPR-silent without irradiation either in frozen solution (180 K) or at room temperature (298 K). In contrast, after 2 min irradiation, Ir III remains EPR-inactive (Figure 1c) but the Ir III/R–Siº mixture exhibits an axial EPR signal at 180 K with *g*<sub>iso</sub> = 1.98 (*g*₁ = *g*₂ = 1.99 and *g*₃ = 1.95, Figure 1d), which shows that the R–Siº presence is crucial to photo-generate a reduced Ir II species. The *g*<sub>iso</sub> value, very close to *g*<sub>e</sub> (free electron), suggests the presence of an organic radical in the mixture. This observation is consistent with the accumulation of one electron spin density on the bipyridine, which is also deduced from analysing by DFT (at the ωB97M-D3BJ/def2-SV(P) level) (Figure 1e) the atomic spin densities of the radical anion of the reduced complex Ir[dF(CF₃)ppy]<sub>2</sub>(bpy)⁻] (abbreviated Ir II as generally written). To ascertain the *g*<sub>iso</sub> value, we resorted to complete active space self-consistent field (CASSCF) calculations on the reduced Ir II species as already described in the literature for similar complexes.[41] Namely, all the key *d* orbitals on the metal center and the π-system of the bpy were included (13 electrons in 13 orbitals) on the C2 symmetric complex.[42] We calculated a

<figure><img src="image_10.png" /><figcaption>Scheme 2. Model system, possible intermediates and by-products.</figcaption></figure>
<figure><img src="image_11.png" /></figure>

<figure><img src="image_12.png" /><figcaption>**Figure 1.** Investigation of the Ir-based photocatalytic cycle. (a,b): Dependence of the normalized amplitude of the luminescence response of 5 µM Ir<sup>III</sup> on the angular frequency ω of the light modulation (a) and associated Stern–Volmer analysis (b; slope = 17.5 ± 0.6 mM<sup>-1</sup>, r<sup>2</sup> = 0.993) at various concentrations (mM) of R–Si<sup>Θ</sup> (0, 0.05, 0.1, 0.15, 0.25, 0.5 yielding the following lifetimes τ(µs). 1.6, 0.9, 0.5, 0.4, 0.3, 0.2). Solvent: DMF; temperature: 298 K; (c,d): X-band (9.43 GHz) EPR spectra in DMF at 180 K after 2 min irradiation at 450 nm of Ir<sup>III</sup> at 2.5 mM (c) and 2.5 mM Ir<sup>III</sup>/R–Si<sup>Θ</sup> 1/1 mol/mol mixture with the corresponding simulation using g<sub>1</sub> = 2.000; g<sub>2</sub> = 1.999; g<sub>3</sub> = 1.949, g<sub>iso</sub> = 1.983 (d); (e): Atomic spin densities of the reduced complex Ir[dF(CF<sub>3</sub>)ppy]<sub>2</sub>(bpy)<sup>-</sup>] radical anion; (f,g): X-band (9.43 GHz) EPR spectra of 2.5 mM Ir<sup>III</sup>/R–Si<sup>Θ</sup> 1/1 mol/mol mixture in the presence of an equimolar amount of N-tert-butyl-α-phenylnitrone at 298 K after 5 min irradiation at 450 nm (f) and the corresponding simulation using a<sub>N</sub> 14.8 MHz, a<sub>H</sub> 3.5 MHz = and g<sub>iso</sub> = 2.0056 (g). Microwave parameters: 0.02 mW (at 180 K) and 20 mW (at 298 K), 5 scans, Mod. Ampl. 2G, Mod. Freq. 100 kHz, Time Const. 81.92 s, Conv. Time 20.48 s, B<sub>1</sub> ⊥ B.</figcaption></figure>

$g_{\text{iso}} = 1.979$ ($g_1 = 1.988$, $g_2 = 1.987$ and $g_3 = 1.963$) that is in good agreement with experimental values (Figure 1d).

The evidence for the production of radicals from illumination of the Ir<sup>III</sup>/R–Si<sup>Θ</sup> mixture was eventually provided by spin trap experiments. After 5 min of irradiation in the presence of an equimolar amount of N-tert-butyl-α-phenylnitrone,<sup>[43]</sup> a new EPR signal consisting in a triplet of doublet was observed at room temperature (Figure 1f). This signal could be best simulated considering hyperfine couplings of the unpaired electron with one nitrogen (<sup>1</sup>N, I=1) and one hydrogen (<sup>1</sup>H, I=1/2) with $g_{\text{iso}} = 2.0056$; $a_N = 14.8$ MHz and $a_H = 3.5$ MHz (Figure 1g). This observation is in line with the formation of the

carbon-based adduct resulting from the trapping of the R* radical generated from R–SiΘ upon irradiation.

Thus, consistent with the mechanism generally proposed for its action as photocatalyst, Ir<sup>III</sup> is activated by photon absorption to Ir<sup>III*</sup>, that in turns can relax back to Ir<sup>III</sup>, or react by SET with R–SiΘ leading to the formation of Ir<sup>II</sup> and the alkyl radical R*. The rate constants of the two latter reactions are much higher than the one associated with the process of light absorption. Hence the steady concentration of Ir<sup>III*</sup> is vanishing compared to the Ir initial concentration, which thus essentially rests in both Ir<sup>II</sup> and Ir<sup>III</sup> forms.
<figure><img src="image_13.png" /></figure>

Investigation of the Ni-based catalytic cycle

In contrast to the absence of continuous consumption of R–Si<sup>Θ</sup>
upon illumination in the presence of the photocatalyst only,
adding the Ni catalyst enables us to regenerate Ir<sup>III</sup> from Ir<sup>II</sup> and
get continuous consumption of R–Si<sup>Θ</sup> and Ar–Br.

To decipher the Ni-based catalytic cycle, we first performed
a large series of kinetic experiments. The reactive system was
exposed to irradiation and ¹⁹F({¹H} NMR was used to analyze the
time evolution of the concentrations of Ar–Br reactant and

Ar–R product upon varying the control parameters (total
concentration [Ni]₀ and [Ir]₀ in Ni and Ir catalysts, light intensity
I₀, stoichiometry of the reactants; see Table S2). Figure 2a
displays a representative time evolution of the concentrations
[Ar–Br] and [Ar–R] with initial concentrations [R–Si]₀ = 0.15 M,
[Ar–Br]₀ = 0.1 M, [NiBr₂]₀ = 6 mM, [Ir]₀ = 2 mM, and light intensity
at 365 nm I₀ = 15 mW.cm⁻². The whole set of time evolutions is
given in Figure S18.

Under all the experimental conditions explored in this study,
we observed the drop of the Ar–Br concentration associated

<figure><img src="image_14.png" /><figcaption>**Figure 2.** Processing of the kinetic experiments on the Ni-based catalytic cycle. Investigation of the Ni-based catalytic cycle. (a): Time evolution of the concentrations of Ar–Br reactant and the Ar–R product. Experimental conditions: [R–Si]₀ = 0.15 M, [Ar–Br]₀ = 0.1 M, [NiBr₂]₀ = 6 mM, [Ir]₀ = 2 mM, I₀ = 15 mW.cm⁻²; (b): Linear fit of the data displayed in (a) over the kinetic window [0; tₐ₇₆] of time variation of the concentrations of Ar–Br and Ar–R; (c) Residuals of the concentrations in Ar–Br and Ar–R extracted from applying the linear fit displayed in (b); (d) Overlap of the residuals of the concentrations in Ar–Br and Ar–R extracted from applying the linear fit on all the kinetic experiments reported in Table S2 and Figure S18; (e): Bilinear fit of the data displayed in (a) over the kinetic window [0; tₐₘ₄] and [tₐₘ₄; tₐ₇₆] of time variation of the concentrations of Ar–Br and Ar–R; (f) Residuals of the concentrations in Ar–Br and Ar–R extracted from applying the bilinear fit displayed in (e); (g) Overlap of the residuals of the concentrations in Ar–Br and Ar–R extracted from applying the bilinear fit on all the kinetic experiments reported in Table S2 and Figure S18.</figcaption></figure>
<figure><img src="image_15.png" /></figure>

with a symmetrical rise of the Ar–R one followed by a final phase of saturation starting at time $t_{end}$. Moreover, depending on the experimental conditions, we further noticed a linear evolution of the concentration profiles of Ar–Br and Ar–R (e.g. see entries 3 and 14 of Figure S18). This behavior suggested a zeroth order kinetics in R–Si<sup>Θ</sup> and Ar–Br reactants, which could further be in line with the kinetic behavior expected from the photocatalytic system displayed in Scheme 1 (see subsection 7.2 of the Supporting Information).

Hence, we first applied a linear fitting function over the time window of the variation of the concentrations in Ar–Br and Ar–R shown in Figure 2a. Figure 2b and c display the resulting processing of the data together with the fitting residuals respectively. Whereas the linear fitting function could be acceptable at first sight, the residuals exhibit deviations, which are not compatible with validating the relevance of the linear fit. More precisely, they show systematic deviations, which suggest the succession of two kinetic regimes of linear variation of the concentrations of Ar–Br and Ar–R. This trend was further strengthened when examining the residuals obtained from linear fit of the whole set of experiments displayed in Figure S18 (Figure 2d). As a general behavior, the deviations are positive at short times, vanish at an intermediate time (subsequently denoted $t_{switch}$), and then become negative. This observation has suggested that the concentrations of Ar–Br and Ar–R linearly evolve with a higher rate in a first kinetic regime and then experience a transition towards a second kinetic regime of linear variation of the concentrations of Ar–Br and Ar–R at a slower rate. Interestingly, the slope breaking of the residual observed at the shortest time scale provides an objective criterion to define the time $t_{switch}$ at which the transition of kinetic regime occurs.

Therefore we implemented a two-step linear fitting protocol to account for the observed kinetic behavior over the [0; $t_{switch}$] and [$t_{switch}$; $t_{end}$] time windows. Figure 2e and f display the result of this new data processing together with the fitting residuals respectively. The residuals are now symmetrically distributed over the whole range of concentrations, which is expected from a satisfactory fit. Figure 2g shows that this trend is general for the whole set of kinetic experiments.

Applying the bilinear fitting function to all our kinetic data revealed several features:

- A short induction phase for experiments performed with a Ni<sup>i</sup>Br<sub>2</sub> as pre-catalyst (lasting ca. 10 min, when complete transformations are performed at a timescale of c.a. 10<sup>3</sup> min) associated with much slower consumption and production of Ar–Br and Ar–R respectively (see Figure 3a);

- A first phase of linear consumption of Ar–Br and production of Ar–R. It initially occurs at a constant rate $\phi_1$ and it switches at time $t_{switch}$ towards a second phase of linear consumption of Ar–Br and production of Ar–R with an associated rate $\phi_2$, corresponding to about half the rate $\phi_1$ of the first phase (see Figure 2e and Table S2).

- A final phase of saturation of consumption of Ar–Br at a time $t_{end}$, before the full consumption of Ar–Br, which produces Ar–R in 70%–80% yield in the presence of 1.5 equiv. of R–Si<sup>Θ</sup> (see Figure 2a). Figure 3b shows that the normalized time

evolutions of the concentration of Ar–Br are similar when using different amounts of R–Si<sup>Θ</sup> under the same experimental conditions. However, the photoconversions at low initial R–Si<sup>Θ</sup> concentrations exhibit low yield and early $t_{end}$, while excess of R–Si<sup>Θ</sup> is necessary for the full conversion of Ar–Br at high $t_{end}$. Interestingly, adding further R–Si<sup>Θ</sup> after $t_{end}$ enables the reaction to start again at the same initial rate, eventually yielding the consumption of the remaining Ar–Br (see Figure S17). In particular, this observation discards any explanation of the kinetic behavior that would originate from inhibition of the reaction rate by a product of the photo-conversion;

- Finally, all the experiments yield the same value of the product $\phi_1 \times t_{end}$ (0.11 ± 0.1 M, see Table S2 and Figure S18). This kinetic behavior is consistent with a first phase where both Ar–Br and R–Si<sup>Θ</sup> are consumed at the same rate $\phi_1$, and a second phase where Ar–Br is consumed at the halved rate $\phi_2$ while R–Si<sup>Θ</sup> keeps being consumed at rate $\phi_1$.

Then we performed complementary experiments to identify productive intermediates in the Ni-based catalytic cycle and estimate their rate constants.

We first changed the source of nickel to generate the catalyst and noticed that the induction phase disappears by using either Ni(COD)<sub>2</sub> with one equivalent of the dtbbpy ligand, Ni<sup>i</sup>Cl, or ArNi<sup>i</sup>Br instead of Ni<sup>i</sup>Br<sub>2</sub> (see Figure 3a and Supporting Information, Section 6.2). These observations led us to conclude that the induction phase originates from the reduction of Ni<sup>i</sup>Br<sub>2</sub> to form the active catalyst as with other pre-catalysts the formation of Ar–R started with no delay. Moreover, the thermodynamically favored reduction of Ni<sup>i</sup>X complex ($E_p^{red} \approx -1.2$ V vs SCE in DMF) by the Ir<sup>i</sup> species to regenerate Ni<sup>0</sup> is consistent with Ni<sup>i</sup> to be a competent intermediate in the Ni-based catalytic cycle.[44]

We then investigated the oxidative addition of Ar–Br to Ni<sup>0</sup> by performing cyclic voltammetry toward reduction potentials at various scan rates in the presence of a large excess of Ar–Br.[45] Ni<sup>i</sup>Br<sub>2</sub> first undergoes two-electron reduction at R<sub>1</sub> to yield Ni<sup>0</sup>. Ni<sup>0</sup> is subsequently either back oxidized at O<sub>1</sub> or trapped in situ by oxidative addition to generate ArNi<sup>i</sup>Br (Figure 3c), which has been characterized by its second reduction peak at R<sub>2</sub> from comparison with the voltammogram of a ArNi<sup>i</sup>Br sample (Figure 3d). Quantified from the drop of the oxidation wave O<sub>1</sub> (Figure 3c), the proportion of trapped Ni<sup>0</sup> increases when the scan rate is decreased (see Figure S15).[46] Data processing enabled us to retrieve 25 L·mol<sup>-1</sup>·s<sup>-1</sup> for the value of the bimolecular rate constant associated with the oxidative addition of Ar–Br to Ni<sup>0</sup>(dtbbpy) at 293 K,[47] which is consistent with the one determined for the analogous Ni<sup>0</sup>(bpy) complex with Ph–Br.[48]

We eventually analyzed the reactivity of ArNi<sup>i</sup>Br. This complex does not react with R–Si<sup>Θ</sup> upon irradiating at 365 nm in the absence of Ir<sup>iii</sup>. However, it traps a primary radical generated from heating dilauryl peroxide and the resulting Ni<sup>iii</sup> complex rapidly evolves to yield the cross-coupling product (Figure 3e) as evidenced by the characteristic signal at –119.5 ppm by <sup>19</sup>F<sup>i</sup>{H} NMR and further confirmed by mass spectrometry (see Supporting Information, section 6.5, Figures S15).[16,49] Hence, the observed intermediates of the Ni-based mechanism as well as their reactivity are consistent with the variant A of the Ni cycle of Scheme 1c.
<figure><img src="image_16.png" /></figure>

<figure><img src="image_17.png" /><figcaption>**Figure 3.** Investigation of the Ni-based catalytic cycle. (a): Initial time evolution of the concentrations in Ar–Br (circles) and Ar–R (disks) in reactive mixtures irradiated at 365 nm in the presence of various nickel pre-catalysts. System composition: Ar–Br (0.1 M in DMF), R–Si<sup>Θ</sup> (1.5 equiv), Ir<sup>II</sup> (2 mol%) with 4 mol% of Ni<sup>I</sup>Br<sub>2</sub> (black) Ni(COD)<sub>2</sub>/dtbbpy (blue), ArNi<sup>I</sup>Br (green), and Ni<sup>I</sup>Cl (red)); (b): Normalized time evolutions of [Ar–Br] using different amounts of silicates (experimental conditions: [Ar–Br]<sub>0</sub> = 0.1 M, [Ni]<sub>0</sub> = 2 mM, [Ir]<sub>0</sub> = 4 mM, l<sub>0</sub> = 15 mW.cm<sup>-2</sup>). t<sub>switch</sub> and t<sub>end</sub> respectively designate the time at which the rates of consumption of Ar–Br and production of Ar–R switches from q<sub>1</sub> to q<sub>2</sub> and the time of the total R–Si<sup>Θ</sup> consumption and of saturation of consumption of Ar–Br; (c,d): Cyclic voltammograms of 2 mM Ni<sup>I</sup>Br<sub>2</sub> performed toward the reduction potentials at a steady glassy carbon (GC) disk electrode (φ = 3 mm, for d at 0.1 V.s<sup>-1</sup>) and for e at 0.05 V.s<sup>-1</sup>) in DMF containing 0.3 M *n*-Bu<sub>4</sub>NBF<sub>4</sub> before (black) and after (red) addition of Ar–Br (10 equiv); (e): Reaction of 25 mM ArNi<sup>I</sup>Br and lauroyl peroxide (0.5 equiv) after 30 min of heating at 80 °C in DMF.</figcaption></figure>

However, whereas the latter mechanism correctly accounts for the 1:1 stoichiometry of the consumption of both reactants and the production of the Ar–R product in an initial kinetic regime, it is not in line with the 2:1 stoichiometry observed at longer timescales nor on the observed additional R–H production.

## Step by step kinetic modeling

The latter discrepancy led us to propose an expanded mechanism, which has been built by a stepwise process. Starting from a minimal model involving a few reactions, we incrementally added more reactions in order to account for the succession of experimentally observed kinetic regimes. At each step of kinetic modeling, we considered the steady-state to be reached. Hence, we could lead an analytic calculation of the fluxes of reactions within the catalytic cycles upon assuming the nature of their resting states. These analytic developments, linked to experimental

kinetic data, could lead to the evaluation of missing kinetic parameters. The details are provided in Section 7 of the Supporting Information and the main results are reported below.

Qualitatively, the kinetic behavior can be explained by the occurrence of two different mechanisms in each kinetic regime: the originally expected mechanism in the first regime (with an overall conversion R–Si<sup>Θ</sup> + Ar–Br→Ar–R+Br<sup>Θ</sup> + Si), and a second mechanism in the second kinetic regime where R–Si<sup>Θ</sup> is simultaneously coupled to Ar–Br and degraded (i.e. 2R–Si<sup>Θ</sup> + Ar–Br+H<sup>+</sup>→Ar–R+Br<sup>Θ</sup> + 2Si+R–H). As a consequence, whereas Ar–Br and Ar–R are consumed and produced at distinct rates q<sub>1</sub> and q<sub>2</sub> with q<sub>1</sub> ≈ 2q<sub>2</sub> before and after t<sub>switch</sub> respectively, R – Si<sup>Θ</sup> is converted at a constant rate, q<sub>1</sub> until t<sub>switch</sub> then 2q<sub>2</sub> until t<sub>end</sub>.

We first addressed the iridium catalytic cycle. In the first stage model, this photocycle drives the reduction of a generic oxidant Ox (Figure 4a). This simple model satisfactorily yields a zero<sup>th</sup> order kinetics in R–Si<sup>Θ</sup>.
<figure><img src="image_18.png" /></figure>

<figure><img src="image_19.png" /><figcaption>**Figure 4.** Step-by-step modeling of the Ir/Ni catalytic cycles. A) Iridium cycle. Under continuous recycling of Ir<sup>III</sup> from Ir<sup>II</sup> by reaction with an oxidant (phase ①), the irradiation of Ir<sup>III</sup> governs the continuous reaction of R–Si<sup>Θ</sup> at a constant rate φ. The light-driven conversion stops when there is no more R–Si<sup>Θ</sup> left (phase ③). B) Upon coupling to a first Ni cycle, the Ir cycle drives the equimolar consumption of R–Si<sup>Θ</sup> and Ar–Br, and formation of Ar–R at a constant rate φ₁ (phase ①). When R–Si<sup>Θ</sup> is in excess, the light-driven conversion stops when there is no more Ar–Br left (phase ③). C) The addition of a slow diverting path leading to the accumulation of NiR at a rate φ<sub>d</sub> shortens the phase of equimolar consumption of R–Si<sup>Θ</sup> and Ar–Br, and formation of Ar–R (phase ①). The light-driven conversion stops before the overall consumption of both R–Si<sup>Θ</sup> and Ar–Br (phase ③). D) The closure of the latter diverting path back to Ni<sup>0</sup> generates a secondary Ni cycle. It results in a light-driven conversion, which occurs in two phases. After a first phase (phase ①) in which the coupling between the Ir cycle with the first Ni cycle drives the equimolar consumption of R–Si<sup>Θ</sup> and Ar–Br and formation of Ar–R at a constant rate φ₁, the light-driven conversion encounters a mechanistic shift. In the second phase (phase 2), the Ir cycle is coupled with the second Ni cycle and the formation of Ar–R is accompanied by the formation of R<sup>Θ</sup> at a same slower rate φ₂. In the presence of 1.5 equivalent of R–Si<sup>Θ</sup> with respect to Ar–Br, the light-driven conversion stops when there is no more R–Si<sup>Θ</sup> left. The simulations were performed with k<sub>e</sub> = 0.035 s<sup>-1</sup>, k<sub>d</sub> = 4.10<sup>5</sup> s<sup>-1</sup>, k<sub>4</sub> = 2.7.10<sup>10</sup> M<sup>-1</sup>.s<sup>-1</sup>, k<sub>1</sub> = 25 M<sup>-1</sup>.s<sup>-1</sup> (constants extracted from kinetic measurements), λ = 0.015, k<sub>3</sub> = 1 s<sup>-1</sup>, k<sub>5</sub> = 10<sup>3</sup> M<sup>-1</sup>.s<sup>-1</sup>, β = 30, γ = 1, α = 10<sup>-3</sup> (constant estimated from the step-by-step model study, see text), and k<sub>2</sub> was supposed very fast, the corresponding reactions being implicitly taken into account (see Sections S7 and S8). Initial conditions were [Ir<sup>III</sup>]₀ = 2.10<sup>-3</sup> M, [R–Si<sup>Θ</sup>]₀ = 0.15 M in A–D, [Ox]₀ = 0.5 M in A, [Ni<sup>II</sup>–X]₀ = 6.10<sup>-3</sup> M and [Ar–Br]₀ = 0.1 M in B–D.E–G. Extended kinetic model taking explicitly into account all the reactions of D), with the addition of the reduction of NiBr₂ by Ir(II). E: Time evolution of the major reactants; F: Time evolution of the major nickel complexes; G: Time evolution of the major iridium complexes (for more details, see Figure S20b).</figcaption></figure>
The iridium catalytic photocycle was then connected to a first nickel-based catalytic cycle, in place of the generic Ox/Red compounds (Figure 4b). At that point, it is important to note that variants A and B shown in Scheme 1c cannot be kinetically distinguished upon assuming the addition of R* to Ni⁰ and ArNi¹Br to be much faster than the oxidative addition of Ar–Br. In fact, both paths can be reduced to a same mechanism by applying the steady-state approximation. In Figure 4b, we adopt the path A.

Both the iridium and the nickel cycles are strongly coupled. Each turnover of the Ir-photocycle produces one R* and one Ir¹, which relaxes back to Ir¹¹ by transferring one electron to the Ni cycle. Each turnover of the latter consumes one R* and one NiBr is reduced to Ni⁰ by accepting one electron from the Ir cycle. As a consequence, when the system reaches a steady-state production of Ar–R, both cycles are processed with the same steady rate, globally leading to the R–Si⁰ + Ar–Br → Si + Br⁰ + Ar–R conversion at the same rate $q_1$ given in Equation (1) (see Supporting Information, Section 7.2 for details).

$$q_1 = \frac{k_e \cdot l_0 \cdot k_5 \cdot [Ni]_0 \cdot [Ir]_0}{k_e \cdot l_0 + k_5 \cdot [Ni]_0} \quad (1)$$

As a preliminary conclusion, the kinetic model proposed in Scheme 1c satisfactorily accounts for a linear production of Ar–R by exploiting the experimentally determined rate constants. However, this kinetic model fails to describe the halving of the production rate characterized by a second slope $q_2$, and the excess of R–Si⁰ required to reach completion for Ar–Br. As a consequence, the reported mechanism seems to correctly describe an initial phase, but another mechanism is observed at longer timescale, characterized by a slower Ar–R production at a rate $q_2$, while R–Si⁰ keeps being consumed at about the initial rate $q_1$.

As mentioned above, Ir¹¹ can reduce Ni¹Br into Ni⁰. Hence, one reasonably expects that other halogenated Ni complexes, such as ArNi¹¹BrR, can as well be reduced by Ir¹¹, i.e. leading to the formation of ArNi¹¹R with elimination of Br⁰. The latter complex may then in turn trap an additional radical R*, up to the formation of ArNi¹¹R₂. Provided that this last complex releases Ar–R (see DFT calculations below), it would yield Ni¹R, that is anticipated to be less easy to reduce than Ni¹Br by Ir¹¹. Then, Ni¹R would accumulate (see Figure 4c), which will depopulate the initial productive Ni-based catalytic cycle as a function of time. Considering the concentrations of ArNi¹¹Br and ArNi¹¹BrR to be low relatively to the concentration of Ni¹Br, the leakage flux $q_d$ evaluating the production of Ni¹R can be computed by Equation (2)

$$q_d = \frac{\beta \cdot k_5^2 \cdot k_e^2}{k_3} \cdot \frac{l_0^2 \cdot [Ir]_0^2}{(k_e l_0 + k_5 \cdot [Ni^iBr])^2} \cdot [Ni^iBr] \quad (2)$$

that is slow compared to the reaction flux within the primary Ni catalytic cycle. Interestingly, when $k_5$ [Ni¹Br] ≫ $k_e l_0$, Ni¹Br intervenes in this leakage flux with a kinetic order –1. As a consequence, the leakage flux increases on time and the overall conversion of Ni¹Br into Ni¹R is completed after the finite time $t_{switch}$ at which the photoconversion flux switches from the primary to the secondary cycle. Indeed, the numerical simulations show that the initial productive Ni-based catalytic cycle

is active at constant rate until its nearly depletion by the accumulation of Ni¹R (see Figure S20a). Then, the first nickel catalytic cycle abruptly stops with the depletion of Ni¹Br. The emergence of the corresponding switch depends on the values of the control parameters, which drive the relative values of $t_{switch}$ and $t_{end}$ (see Equations (14,27) in the Supporting Information). In particular, when $t_{switch} < t_{end}$, the switch occurs before the total consumption of both R–Si⁰ and Ar–Br.

As an additional outcome of the depletion of the primary Ni-based catalytic cycle, Ir¹¹ accumulates since there is no more easily reducible Ni¹Br for recycling back Ir¹¹ to Ir¹¹. As a consequence, less reducible species such as Ni¹R may in turn be reduced by Ir¹¹ to Ni⁰. It results in the activation of a secondary Ni-based catalytic cycle consuming two R* and one Ar–Br, releasing one Ar–R with one R⁰ carbanion subsequently yielding R–H after protonation (see Figure 4d). This process resulted in a higher consumption of R–Si⁰ compared to Ar–Br. In this second kinetic regime, the overall kinetics is still governed by the reaction flux of the Ir-based catalytic cycle, but only half of the R–Si⁰ is converted to Ar–R, explaining the halving of Ar–R formation. In these conditions, the flux $q_2$ is established within the secondary Ni-based catalytic cycle [Equation (3)]

$$q_2 = \frac{\alpha \cdot k_e \cdot l_0 \cdot k_5 \cdot [Ni]_0 \cdot [Ir]_0}{k_e \cdot l_0 + 2 \cdot \alpha \cdot k_5 \cdot [Ni]_0} \quad (3)$$

where $\alpha \ll 1$, so that the secondary cycle is only efficient after the disappearance of the primary cycle.

On the basis of these analytical derivations that led to retrieve orders of magnitude of the missing kinetic parameters (see Figures S20), a numerical kinetic simulation could be set up in order to refine the values of the kinetic parameters and reproduce the observed experimental behavior (see Supporting Information, Section 8). It first confirmed the insight provided by the analytic derivations that the effective light intensity $l_0$ had to be decreased down to 0.015 times the value of the incident light intensity $l_0^{theo}$, which was independently measured (see Supporting Information, Subsection 3.1). This drop probably originates from three factors: (i) the decay of light intensity along the optical path at high absorbance; (ii) the formation of precipitates,[31] which occurs during the transformation and further decreases the penetration of light in the medium; (iii) the quenching of the excited state of Ir¹¹ by other species than R–Si⁰ (e.g. Br⁻), which has been evidenced by lifetime measurements (see Supporting Information, Subsection 3.4). Hence, the kinetic model globally reproduces and explains most prominent experimentally observed features (see Figure 4 E–G and Figures S20).

## Validation by DFT calculations

To strengthen the conclusions of the kinetic analysis, calculations at the Density Functional Theory level were performed (see Figure 5 and Supporting Information for computational details). As reported by Molander and Kozlowski,[17] the ArNi¹¹Br complex traps the radical R* generated from R–Si⁰ after SET with a low activation barrier, yielding ArNi¹¹BrR. The latter intermediate undergoes a reductive
<figure><img src="image_20.png" /></figure>

elimination, which is concerted, as illustrated by the similar lengths of the broken and created bonds with a barrier similar to the SET reaction. The formation of Ar–R further liberating Ni'Br for a new catalytic cycle is highly exothermic (see Supporting Information, Section 10).

Considering the mechanistic path proposed for the second regime, the competition between the nickel-catalyzed formations of a Csp²-Csp³ or Csp³-Csp³ bond in ArNiillR₂ was then examined (Figure 4). The *trans*-complex I.1' where the two alkyl chains are in *trans* configuration can evolve to intermediate I.2' where the two alkyl chains are in *cis* configuration. The latter is of similar stability than I.1' (ca. 0.2 kcal.mol⁻¹) and the barrier between I.1' and I.2' raises to 13.1 kcal.mol⁻¹. From I.2', the reductive elimination to generate the homocoupling product proceeds with a barrier of 24.6 kcal.mol⁻¹. From I.1', the reductive elimination between the alkyl chain and the aromatic moiety requires a barrier energy of 18.0 kcal.mol⁻¹. These calculations suggest that the main product of reductive elimination from ArNiillR₂ should be the Csp²-Csp³ Ar–R coupling product and the R–R sp³-sp³ coupling product should be less favorable, consistently with the selectivity observed for related group 10 metal complexes.[⁵⁰]

## Discussion

Along with the choice of the photo- and organometallic catalysts, metallaphotocatalysis benefits from multiple parameters (stoichiometry of the reactants, spectrum of the light source, light intensity, concentration of the catalysts,) to optimize its output. However, the kinetics governing the course of the photoconversion of the reactants is rather complex and optimization often requires more than intuition.

Hence, in this study, we departed from the wavelength of light excitation previously reported by us[¹²] upon considering a more favorable overlap with the absorption band of the photocatalyst and the reduction of photodegradation of an intermediate of the Ni catalytic cycle. Nevertheless, we observed a photoconversion, which proved less advantageous by requiring two equivalents of bis(catecholato)silicate to yield the desired product. This rather unexpected result has pointed on the significance of two generally underestimated parameters driving metallaphotocatalysis: the spectrum of the light source (driving the *k*<sub>e</sub> value; see Figure 4A) and the light intensity (driving the *I*<sub>0</sub> value; see Figure 4A). Thus, by using a powerful LED at 365 nm and by matching its spectrum with the absorption band of the iridium photocatalyst, we considerably increased the rate constant associated to the photocatalyst activation with respect to our previous investigation performed with a less powerful LED at 450 nm (see Supporting Information, Subsection 3.1). It correspondingly resulted in the production of Ir<sup>II</sup> in high amount at steady-state. As a consequence, the Ir<sup>II</sup>-mediated reduction of ArNiillBrR could significantly compete with the reductive elimination yielding Ar–R and Ni’Br (see Figures 4C–D), which diverting pathway was essentially absent in our original investigation.

Beyond this qualitative explanation, we could exploit our original approach of analytic derivation of the expressions of the photoconversion fluxes in order to quantitatively interpret the

preceding results. Hence, whereas the condition $t_{\text{switch}} < t_{\text{end}}$ was most often met in the presently reported results obtained with the LED at 365 nm, we were in a regime where $t_{\text{switch}} > t_{\text{end}}$ in our previous series of experiments so as to observe only the first kinetic regime, corresponding to the most efficient product formation. In fact, the latter inequality amounts the ratio $[\text{Ir}]_0 \times I_{\text{theo}}^0 / ([\text{Ni}]_0)^2$ to remain smaller than the threshold value equal to $k_3/\beta k_6 [\text{R}-\text{Si}^\oplus]_0$ estimated at $10^2 \text{ M}^{-1} \text{mW cm}^{-2}$, which points on the impact of the four control parameters $[\text{Ir}]_0$, $I_0$, and $[\text{Ni}]_0$, and $[\text{R}-\text{Si}^\oplus]_0$ for the reaction between Ar–Br and R–Si^\oplus to be at the most efficient.

<figure><img src="image_21.png" /><figcaption>**Figure 5.** Computed relative ΔH (upper values) and ΔG (lower values) are reported in kcal.mol⁻¹ for the two possible reductive elimination processes (sp²-sp³ and sp³-sp³) from ArNiillR₂ (I.1').</figcaption></figure>

## Conclusions

The C–C bond formation from an alkyl silicate and an aryl bromide under metallaphotoredox catalysis was thoroughly studied. The Ir cycle was investigated thanks to photophysical techniques and EPR, attesting a SET mechanism between the excited photocatalyst and the silicate to form the ligand-reduced Ir complex along with the alkyl radical. The study of the Ni cycle revealed an induction period when starting from NiillBr₂ to form the active Ni⁰ species for the oxidative addition. The resulting ArNiillBr species, while being competent to trigger the catalytic cycle, was shown to trap an alkyl radical to form the Ar–R product after reductive elimination. These experimental results led us to propose a Ni⁰/Ni¹/Niill/Ni¹ mechanism (path A, Scheme 1c). However due to the complexity of the system, classical approaches did not enable us to definitely reject path B, based on a Ni⁰/Ni¹/Niill/Ni¹ mechanism. Thanks to a step-by-step micro-kinetics approach, we modeled different scenarios and determined the resting states for both catalysts. The careful analysis of the kinetic monitoring revealed two regimes for the formation of Ar–R at an appreciable rate. The first one could be modeled when considering an operative mechanism A but the sharp decrease of the reaction rate observed in the second phase, linked to an overconsumption of silicates, led us to propose an original scenario in which two alkyl silicates react when only one aryl bromide is transformed. When considering this second regime, the numerical
<figure><img src="image_22.png" /></figure>

simulation of the mechanism proposed correctly fits the data and the mechanism was further supported by DFT calculations.

Moreover, this study provided general features to observe only the first regime, corresponding to the most efficient product formation. The analytic derivations to meet the corresponding condition $t_{switch} > t_{end}$ yields a ratio $[Ir]_0 \times [theo]_0 / [(Ni)]_0^2$ smaller than a threshold value equal to $k_3/\beta k_e [R-Si]^\circ$, estimated at $10^2 \text{ M}^{-1}\text{mW}\text{cm}^{-2}$. Interestingly, the methodological developments previously reported by us[12] have been generally performed below this threshold by irradiating at 450 nm (blue LED) with an intensity around 30 times weaker than that used for the mechanistic study. In these conditions, the reaction between Ar-Br and R-Si$^\circ$ proceeded smoothly and it turned out to be much more efficient than the same reaction performed at a wavelength suitably selected according to the photocatalyst properties.

To conclude, the combination of both analytical and numerical methods able to encompass multiple parameters proved to be of particular efficiency to decipher a complex mechanism such as this one. Yet, this case study also brings findings that go far beyond the context of the sole silicate/aryl bromide cross-coupling.

These include the reactivity of an ArNi¹X complex under free radical conditions, the EPR characterization of a reduced iridium complex and its DFT modeling as well as the opportunity to use microkinetics to understand and minimize by-product formation.

## Experimental Section

**Chemicals:** Reagents and solvents were purchased from commercial suppliers and used without further purification. Reactions were carried out under an argon atmosphere in oven dried glassware.

**NMR:** Spectra were recorded at ambient temperature on a Bruker Avance III Ultrashield™ 300 instrument. The ¹H NMR spectra were recorded at 300 MHz. ¹³C NMR spectra were recorded at 75 MHz. Chemical shifts ($\delta_{H}$, $\delta_{C}$) were quoted in parts per million (ppm) and were referenced to the residual solvent peak. The ¹⁹F NMR spectra were recorded at 282 MHz with CFCI₃ as an external reference and fluorobenzene in a d6-DMSO insert for locking and as an internal standard.

**Electrochemical experiments:** Electrochemical experiments were performed under Ar flow in a three-electrode cell. The counter-electrode was a Pt wire of approximately 1 cm² apparent surface area, while the reference was a saturated calomel electrode separated from the solution by a bridge fulfilled with a 0.3 M of n-Bu₄NBF₄ in the desired solvent. The cyclic voltammograms (CV) were recorded at a steady glassy carbon disk (1/3 mm) using a potentiostat µ-autolab PGSTAT 101 from Metrohm using Nova 2.4 as software.

**Light Sources:** For analytical purposes, the experiments were carried out in NMR tubes submitted to both rotation for stirring (using a Roller oscillating roller mixer instrument) and illumination at $\lambda=365$ nm with a homemade setup delivering light from blue LED at the NMR tubes (see Figure S1).

**Spectroscopic measurements:** The absorption spectra were recorded at 25 °C on a Cary 300 UV/Vis spectrophotometer (Agilent Technologies, Santa Clara, CA), equipped with a Peltier thermostated cell holder (t2x2 Sport/Cary300, Quantum Northwest, Liberty Lake, WA). The samples were placed in 2 mL quartz cuvettes (1 cm×1 cm light path; Hellma Optics, Jena, Germany).

The luminescence spectra were acquired on a LPS 220 spectrofluorometer (PTI, Monmouth Junction, NJ), equipped with a TLC50 cuvette holder (Quantum Northwest, Liberty Lake, WA) thermoregulated at 25 °C. The samples were placed in 2 mL quartz cuvettes (1 cm×1 cm light path; Hellma Optics, Jena, Germany).

The lifetime luminescence of Ir(III) was measured in the frequency-domain with the home-built setup shown in Scheme S1 by the phase-modulation method.

**NMR monitoring of the time evolution of the system composition:** The kinetic experiments have been carried out in NMR tubes at room temperature by using the home-built setup described in Figure S1 for stirring and irradiation at 365 nm. On average, a ¹⁹F{¹H} NMR spectrum was recorded every 15 min. The peaks have been integrated and the information converted into concentration by using a solution of fluorobenzene in [d6]-DMSO contained in a coaxial insert for locking and as an internal standard for integration.

**Variation of the nickel pre-catalyst:** To an NMR tube was added R-Si⁰ (97 mg, 0.15 mmol, 1.5 equiv), Ir(III) (2.2 mg, 2 mol%, 2 µmol), 4,4'-di-tert-butyl-2,2'-bipyridine (1.07 mg, 4 mol%, 4 µmol) and NiBr₂ (0.9 mg, 4 mol%, 4 µmol) or Ni(COD)₂ (1.1 mg, 4 mol%, 4 µmol) or ArNiBr (2.06 mg, 4 mol%, 4 µmol) or NiCl (3 mg, 4 mol%, 4 µmol). The tube was sealed with a rubber septum and evacuated/purged with vacuum/ argon three times. Degassed DMF (1 mL) was introduced, followed by Ar-Br (13 µL, 0.1 mmol, 1 equiv) and the reaction mixture was irradiated at 365 nm for 4 h.

**Kinetic simulation:** All the computations were performed by using a python environment,[51,52] and were namely based on the scipy[53] and numpy[54] libraries for the numerical modelling. Standard algorithms for the integration of ordinary differential equations were used. Full data and python script are available in a separate archive file.

**Evidence for the interaction between ArNiBr and radicals:** The ability of ArNiBr to trap a free radical was assessed. For this purpose, ArNiBr was heated at 80 °C with half an equivalent of dilauryl peroxide (DLP) in DMF. After 30 min, the 5-fluoro-2-undecyltoluene coupling product was observed by ¹⁹F{¹H} NMR at –119.5 ppm in 70% yield (see Figure 2f). Its presence has been confirmed by mass spectrometry (see Figure S16).

## Supporting Information

The authors have cited additional references within the Supporting Information.[55–65]

## Acknowledgements

The authors thank Maxime R. Vitale, for fruitful discussions. L.F. thanks the Institut Universitaire de France. The authors thanks Sorbonne Université, CNRS and the ANR HyperSiLight, ANR-17-CE07-0018.

## Conflict of Interest

The authors declare no conflict of interest.

**Keywords:** dual catalysis · mechanistic study · micro-kinetic modeling · nickel · photocatalysis
<figure><img src="image_23.png" /></figure>

[1] J.-P. Corbet, G. Mignani, *Chem. Rev.* **2006**, *106*, 2651–2710.

[2] A. Y. Chan, I. B. Perry, N. B. Bissonnette, B. F. Buksh, G. A. Edwards, L. I. Frye, O. L. Garry, M. N. Lavagnino, B. X. Li, Y. Liang, E. Mao, A. Millet, J. V. Oakley, N. L. Reed, H. A. Sakai, C. P. Seath, D. W. C. MacMillan, *Chem. Rev.* **2022**, *122*, 1485–1542.

[3] J. C. Tellis, C. B. Kelly, D. N. Primer, M. Jouffroy, N. R. Patel, G. A. Molander, *Acc. Chem. Res.* **2016**, *49*, 1429–1439.

[4] Z. Zuo, D. T. Ahneman, L. Chu, J. A. Terrett, A. G. Doyle, D. W. C. MacMillan, *Science* **2014**, *345*, 437–440.

[5] J. C. Tellis, D. N. Primer, G. A. Molander, *Science* **2014**, *345*, 433–436.

[6] T. Knauber, R. Chandrasekaran, J. W. Tucker, J. M. Chen, M. Reese, D. A. Rankic, N. Sach, C. Helal, *Org. Lett.* **2017**, *19*, 6566–6569.

[7] K. Nakajima, S. Nojima, Y. Nishibayashi, *Angew. Chem. Int. Ed.* **2016**, *55*, 14106–14110.

[8] C. H. Basch, J. Liao, J. Xu, J. J. Piane, M. P. Watson, *J. Am. Chem. Soc.* **2017**, *139*, 5313–5316.

[9] F. J. R. Klauck, M. J. James, F. Glorius, *Angew. Chem. Int. Ed.* **2017**, *56*, 12336–12339.

[10] L. Huang, T. Ji, M. Rueping, *J. Am. Chem. Soc.* **2020**, *142*, 3532–3539.

[11] a) C. Le, Y. F. Liang, R. W. Evans, X. M. Li, D. W. C. MacMillan, *Nature* **2017**, *547*, 79–83; b) I. B. Perry, T. F. Brewer, P. J. Sarver, D. M. Schultz, D. A. DiRocco, D. W. C. MacMillan, *Nature* **2018**, *560*, 70–75; c) M. H. Shaw, V. W. Shurtleff, J. A. Terrett, J. D. Cuthbertson, D. W. C. MacMillan, *Science* **2016**, *352*, 1304–1308.

[12] V. Corcé, L.-M. Chamoreau, E. Derat, J.-P. Goddard, C. Ollivier, L. Fensterbank, *Angew. Chem. Int. Ed.* **2015**, *54*, 11414–11418.

[13] C. Lévêque, L. Chenneberg, V. Corcé, J.-P. Goddard, C. Ollivier, L. Fensterbank, *Org. Chem. Front.* **2016**, *3*, 462–465.

[14] M. Jouffroy, D. N. Primer, G. A. Molander, *J. Am. Chem. Soc.* **2016**, *138*, 475–478.

[15] S. Biswas, D. J. Weix, *J. Am. Chem. Soc.* **2013**, *135*, 16192–16197.

[16] S. L. Zultanski, G. C. Fu, *J. Am. Chem. Soc.* **2013**, *135*, 624–627.

[17] O. Gutierrez, J. C. Tellis, D. N. Primer, G. A. Molander, M. C. Kozlowski, *J. Am. Chem. Soc.* **2015**, *137*, 4896–4899.

[18] M. Yuan, Z. Song, S. O. Badir, G. A. Molander, O. Gutierrez, *J. Am. Chem. Soc.* **2020**, *142*, 7225–7234.

[19] D. N. Primer, G. A. Molander, *J. Am. Chem. Soc.* **2017**, *139*, 9847–9850.

[20] B. Maity, C. Zhu, M. Rueping, L. Cavallo, *ACS Catal.* **2021**, *11*, 13973–13982.

[21] S. I. Ting, S. Garakyaraghi, C. M. Taliaferro, B. J. Shields, G. D. Scholes, F. N. Castellano, A. G. Doyle, *J. Am. Chem. Soc.* **2020**, *142*, 5800–5810.

[22] R. Sun, Y. Qin, S. Ruccolo, C. Schnedermann, C. Costentin, D. G. Nocera, *J. Am. Chem. Soc.* **2019**, *141*, 89–93.

[23] Y. Qin, R. Sun, N. P. Gianoulis, D. G. Nocera, *J. Am. Chem. Soc.* **2021**, *143*, 2005–2015.

[24] C. N. Prieto Kullmer, J. A. Kautzky, S. W. Krska, T. Nowak, S. D. Dreher, D. W. C. MacMillan, *Science* **2022**, *376*, 532–539.

[25] See also with a phenanthroline ligand: Q. Lin, T. Diao, *J. Am. Chem. Soc.* **2019**, *141*, 17937–17948.

[26] Y. Kawamata, J. C. Vantourout, D. P. Hickey, P. Bai, L. Chen, Q. Hou, W. Qiao, K. Barman, M. A. Edwards, A. F. Garrido-Castro, J. N. deGruyter, H. Nakamura, K. Knouse, C. Qin, K. J. Clay, D. Bao, C. Li, J. T. Starr, C. Garcia-Irizarry, N. Sach, H. S. White, M. Neurock, S. D. Minteer, P. S. Baran, *J. Am. Chem. Soc.* **2019**, *141*, 6392–6402.

[27] N. A. Till, S. Oh, D. W. C. MacMillan, M. J. Bird, *J. Am. Chem. Soc.* **2021**, *143*, 9332–9337.

[28] S. I. Ting, W. L. Williams, A. G. Doyle, *J. Am. Chem. Soc.* **2022**, *144*, 5575–5582.

[29] Y. Ben-Tal, G. C. Lloyd-Jones, *J. Am. Chem. Soc.* **2022**, *144*(33), 15372–15382.

[30] a) J. Chatt, B. L. Shaw, *J. Chem. Soc.* **1960**, 1718–1729; b) M. Hidai, T. Kashiwagi, T. Ikeuchi, Y. Uchida, *J. Organomet. Chem.* **1971**, *30*, 279–282; c) N. H. Park, G. Teverovskiy, S. L. Buchwald, *Org. Lett.* **2014**, *16*, 220–223.

[31] A genuine photoredox catalytic cycle was established for an allylation reaction of an alkylsilicate using 4CzIPN as photocatalyst, see: A. Cartier, E. Levernier, V. Corcé, T. Fukuyama, A.-L. Dhimane, C. Ollivier, I. Ryu, L. Fensterbank, *Angew. Chem. Int. Ed.* **2019**, *58*, 1789–1793.

[32] M. A. Cismesia, T. P. Yoon, *Chem. Sci.* **2015**, *6*, 5426–5434.

[33] D. Hartmann, T. Thorwart, R. Müller, J. Thusek, J. Schwabedissen, A. Mix, J. H. Lamm, B. Neumann, N. W. Mitzel, L. Greb, *J. Am. Chem. Soc.* **2021**, *143*, 18784–18793.

[34] B. J. Shields, B. Kudisch, G. D. Scholes, A. G. Doyle, *J. Am. Chem. Soc.* **2018**, *140*, 3035–3039.

[35] S. K. Kariofillis, A. G. Doyle, *Acc. Chem. Res.* **2021**, *54*, 988–1000.

[36] See also: D. R. Heitz, J. C. Tellis, G. A. Molander, *J. Am. Chem. Soc.* **2016**, *138*, 12715–12718.

[37] F. Strieth-Kalthoff, F. Glorius, *Chem* **2020**, *6*, 1888–1903.

[38] For a recent study, see: R. Kancherla, K. Muralirajan, B. Maity, S. Karudethat, G. S. Kumar, F. Laquai, L. Cavallo, M. Rueping, *Nat. Commun.* **2022**, *13*, 2737.

[39] D. Hanss, J. C. Freys, G. Bernardinelli, O. S. Wenger, *Eur. J. Inorg. Chem.* **2009**, 4850–4859.

[40] H. G. Roth, N. A. Romero, D. A. Nicewicz, *Synlett* **2016**, *27*, 714–723.

[41] S. I. Bokarev, D. Hollmann, A. Pazidis, A. Neubauer, J. Radnik, O. Kühn, S. Lochbrunner, H. Junge, M. Beller, A. Brückner, *Phys. Chem. Chem. Phys.* **2014**, *16*, 4789–4796.

[42] This CASSCF calculation done with the def2-TZVP basis set was used in conjunction with the DLPNO-NEVPT2 correction as implemented in ORCA version 4.1. Y. Guo, K. Sivalingam, E. F. Valeev, F. Neese, *J. Chem. Phys.* **2016**, *144*, 094111.

[43] G. R. Buettner, *Free Radical Biol. Med.* **1987**, *3*, 259–303.

[44] M. M. Beromi, G. W. Brudvig, N. Hazari, H. M. C. Lant, B. Q. Mercado, *Angew. Chem. Int. Ed.* **2019**, *131*, 6155–6159.

[45] M. Troupel, Y. Rollin, O. Sock, G. Meyer, J. Perichon, *New J. Chem.* **1986**, *10*, 593–599.

[46] K. Wang, Z. Ding, Z. Zhou, W. Kong, *J. Am. Chem. Soc.* **2018**, *140*, 12364–12368.

[47] R. S. Nicholson, I. Shain *Anal. Chem.* **1964**, *36*, 706–723.

[48] M. Durandetti, M. Devaud, J. Perichon, *New J. Chem.* **1996**, *20*, 659–667.

[49] a) S.-Z. Sun, Y. Duan, R. S. Mega, R. J. Somerville, R. Martin, *Angew. Chem. Int. Ed.* **2020**, *59*, 4370–4374; b) A. G. Bakhoda, S. Wiese, C. Greene, B. C. Figula, J. A. Bertke, T. H. Warren, *Organometallics* **2020**, *39*, 1710–1718; c) A. Vasilopoulos, S. W. Krska, S. S. Stahl, *Science* **2021**, *372*, 398–403.

[50] F. N. Hosseini, S. M. Nabavizadeh, R. Shoara, M. D. Aseman, M. M. Abu-Omar, *Organometallics* **2021**, *40*, 2051–2063.

[51] T. E. Oliphant, *Computing in Science Engineering* **2007**, *9*, 10–20.

[52] K. J. Millman, M. Aivazis, *Computing in Science Engineering* **2011**, *13*, 9–12.

[53] P. Virtanen, R. Gommers, T. E. Oliphant, M. Haberland, T. Reddy, D. Cournapeau, E. Burovski, P. Peterson, W. Weckesser, J. Bright, S. J. van der Walt, M. Brett, J. Wilson, K. J. Millman, N. Mayorov, A. R. J. Nelson, E. Jones, R. Kern, E. Larson, C. J. Carey, I. Polat, Y. Feng, E. W. Moore, J. VanderPlas, D. Laxalde, J. Perktold, R. Cimrman, I. Henriksen, E. A. Quintero, C. R. Harris, A. M. Archibald, A. H. Ribeiro, F. Pedregosa, P. van Mulbregt, *SciPy 1.0 Contributors, Nat. Methods* **2020**, *17*, 261–272.

[54] S. van der Walt, S. C. Colbert, G. Varoquaux, *Computing in Science Engineering* **2011**, *13*, 22–30.

[55] A. Beeby, S. Bettington, I. J. S. Fairlamb, A. E. Goeta, A. R. Kapdi, E. H. Niemelä, A. L. A. Thompson, *New J. Chem.* **2004**, *28*, 600–605.

[56] P. F. Wang, L. Jullien, B. Valeur, J.-S. Filhol, J. Canceill, J.-M. Lehn, *New J. Chem.* **1996**, *20*, 895–907.

[57] C. K. Prier, D. A. Rankic, D. W. C. MacMillan, *Chem. Rev.* **2013**, *113*, 5322–5363.

[58] F. Neese, Software Update: The ORCA Program System, Version 4.0. *WIREs Comput. Mol. Sci.* **2018**, *8*, e1327.

[59] A. Najibi, L. Goerigk, *J. Chem. Theory Comput.* **2018**, *14*, 5725–5738.

[60] A. D. Becke, *Phys. Rev. A* **1988**, *38*, 3098–3100.

[61] C. Lee, W. Yang, R. G. Parr, *Phys. Rev. B* **1988**, *37*, 785–789.

[62] J. P. Perdew, M. Ernzerhof, K. Burke, *J. Chem. Phys.* **1996**, *105*, 9982–9985.

[63] Y. Zhao, D. G. Truhlar, *Theor. Chem. Acc.* **2008**, *120*, 215–241.

[64] J. P. Perdew, J. Tao, V. N. Staroverov, G. E. Scuseria, *J. Chem. Phys.* **2004**, *120*, 6898–6911.

[65] N. Ansmann, D. Hartmann, S. Sailer, P. Erdmann, R. Maskey, M. Schorpp, L. Greb, *Angew. Chem. Int. Ed.* **2022**, *61*, e202203947.
<figure><img src="image_24.png" /></figure>

Dr. K. Jaouadi, Dr. M. Abdellaoui, Dr. E. Levernier, Dr. P.-A. Payard, Dr. E. Derat, Dr. T. Le Saux, Dr. C. Ollivier, Dr. S. Torelli, Prof. L. Jullien, Dr. R. Plasson*, Prof. L. Fensterbank*, Dr. L. Grimaud*

1 – 13

**Metallophotoredox catalyzed coupling** of an aryl bromide with an alkyl bis(catecholato)silicate can lead to the formation of large quantity of side products when subjected to high intensity/high frequency irradiation.

Two regimes were found to be possible; the ability to switch from the quantitative coupling to the simultaneous coupling and degradation of the silicate was observed.

**Regime Switch in the Dual-Catalyzed Coupling of Alkyl Silicates with Aryl Bromides**

<figure><img src="image_25.png" /></figure>