Photocatalyzed regioselective hydrosilylation for the divergent synthesis of geminal and vicinal borosilanes

Geminal and vicinal borosilanes are useful building blocks in synthetic chemistry and material science. Hydrosilylation/hydroborylation of unsaturated systems offer expedient access to these motifs. In contrast to the well-established transition-metal-catalyzed methods, radical approaches are rarely explored. Herein we report the synthesis of geminal borosilanes from α-selective hydrosilylation of alkenyl boronates via photoinduced hydrogen atom transfer (HAT) catalysis. Mechanistic studies implicate that the α-selectivity originates from a kinetically favored radical addition and an energetically favored HAT process. We further demonstrate selective synthesis of vicinal borosilanes through hydrosilylation of allyl boronates via 1,2-boron radical migration. These strategies exhibit broad scopes across primary, secondary, and tertiary silanes and various boron compounds. The synthetic utility is evidenced by access to multi-borosilanes in a diverse fashion and scaling up by continuous-flow synthesis.

In this work, geminal borosilanes are obtained from α-selective silylation of alkenyl boronic esters with photoinduced HAT catalysis 42,43 (Fig. 1C). The α-selectivity is general across a wide range of β-substituted alkenyl boronates (>11:1 selectivity in all cases). Furthermore, γ-selective silylation of allyl boronates is developed to provide access to vicinal borosilanes, relying on 1,2-boron radical migration (Fig. 1D). An extremely broad scope of borosilanes is effectively synthesized with these simple protocols, tolerating primary, secondary and tertiary silanes as well as different boryl alkenes. These metal-free transformations are operated under mild conditions and can be easily scaled-up in continuous flow reactors. Regiocontrollable stepwise hydrosilylation affords various types of multi-borosilanes which serve as attractive building blocks for material science.
The incorporation of different patterns of silanes such as primary, secondary and tertiary silanes in hydrosilylation could lead to silicon products with distinct reactivities 45 . However, transition-metal catalyzed methods for borosilane synthesis are generally limited to one type of silanes (e.g. secondary silanes) 7-14 . It was found that primary, secondary and tertiary silanes were all competent substrates in our transformation, delivering structurally diverse geminal borosilanes effectively (47)(48)(49)(50)(51)(52). A siloxane substrate was converted to 52 in 51% yield, indicating the potential utility of this method in silicone polymer chemistry 46 . Moreover, diverse boryl alkenes reacted smoothly under the optimal reaction conditions, embracing different boronates (53-56), a free boronic acid (57), and a boronic acid MIDA ester (58). The good efficiency, regioselectivity and functional-group tolerance prompted us to evaluate the potential of this method for derivatization of complex drug-like molecules, and the reactions proceeded well with carprofen, ibuprofen, gemfibrozil and indomethacin derivatives (59-62).

Further synthetic utilizations
The synthetic utility of the divergent photo-HAT hydrosilylation is further illustrated in Fig. 4. The selective synthesis of geminal borosilane 82 was achieved by two metal-free transformations from the herbicide clodinafop-propargyl in one pot (65% yield, Fig. 4a). The highly selective monofunctionalization of trihydrosilanes and dihydrosilanes through photo-HAT catalysis offers opportunities for stepwise decoration of silicon atoms to access structurally diverse multi- Article https://doi.org/10.1038/s41467-023-38224-y borosilanes. By selectively sequencing the α-selective silylation of alkenyl boronate or γ-selective silylation of allyl boronate processes, different types of multi-borosilanes (83-86) could be obtained (Fig. 4b). The boryl or silyl groups in the geminal and vicinal borosilanes are poised for conversion to a range of valuable products. For example, the silyl group in the products could be converted through Si-H bond functionalization to produce silicon-containing compounds such as silanols (87, 88), silylether (89), silylchloride (90), as shown in Fig. 4c. The boryl group represents an extremely versatile synthetic handle in organic synthesis, which are known to undergo amination, oxidation and arylation to assemble C-N, C-O and C-C bonds, respectively. To showcase this flexibility, the boryl group in the products was converted to amines, alcohols, and arenes with the silyl group intact (91-93) (Fig. 4c). By tuning the oxidative conditions, both the silyl and boryl group underwent oxidation, giving rise to 1,2-diol product 94. Furthermore, gram-scale reactions were demonstrated in a batch reactor (47, 78% yield, 1.19 g) as well as an operationally simple continuous-flow reactor (47, 85%, 7.44 g per day production) (Fig. 4d).

Mechanistic considerations
To shed some light on the reaction mechanism and the origin of regioselectivity, a series of control experiments as well as computational studies were conducted. The radical nature of these transformations was confirmed by radical scavenger and radical clock experiments (see Supplementary Discussion). Stern-Volmer fluorescence quenching studies indicated that the excited photocatalyst can   . At this stage, the thiyl radical I could oxidize the reduced photocatalyst 4CzIPN •to close the photocatalytic cycle. Alternatively, thiyl radical I could react further with silane via radical chain pathways. However, the light on/off experiments and the calculated quantum yields (Ф = 0.109) did not support an efficient radical chain process ( Supplementary Figs. 15-17). Computational analysis was then conducted. It was found that the back electron transfer from the reduced photocatalyst 4CzIPN•to thiyl radical I has an energy barrier of only 1.02 kcal/mol, while HAT from silane to thiyl radical I has a much higher energy barrier of 7.63 kcal/ mol ( Supplementary Figs. 20 and 21). We attribute the ineffective chain propagation and low quantum yield to the unproductive back electron transfer. We next sought to elucidate the origin of α-selectivity in the hydrosilylation of alkenyl boronates. It is noted that α-selectivity was also observed in the hydrosilylation of alkenyl boronates using engineered carbon nitrides as heterogeneous photocatalysts 20 . However, the reaction scope is very limited and the reason for αselectivity in this heterogeneous process remains unknown. Here, the silyl radical addition and subsequent hydrogen atom transfer with thiols were analyzed by calculations using (E)−1-pentenylboronic acid pinacol ester (R 1 ) and phenylsilane as the model substates ( Fig. 6 and Supplementary Fig. 23). The calculated energy diagram illustrates that the addition of silyl radical to alkenyl boronic esters determines the regioselectivity because the transition states (S 1 or S 2 ) have the highest energy in the reaction pathways 52,53 . This also explains why similar regioselectivity was observed with different thiols (Supplementary Table 1). The energy barrier of silyl radical adding to α-position of R 1 is 1.64 kcal·mol −1 lower than that to β-position (S 1 vs S 2 ), which means the α-addition rate is approximately 16 times faster than β-addition. This is very close to the observed selectivity in the crude reaction mixture (α/ β = 14:1). Despite higher stability of the generated intermediate T 2 after β-addition [33][34][35][36][37][38][39] , there are two reasons for the kinetic-controlled α-selectivity. The radical addition processes are nearly irreversible at room temperature, thus the equilibrium between αand βaddition products cannot be reached. Moreover, HAT from thiol N to the radical intermediate T 1 is both kinetically and thermodymically favored (ΔG ≠ = 11.71 kcal·mol -1 , ΔG = −7.89 kcal·mol −1 ) due to polarity-match 29,54 . The higher HAT rate of T 1 compared to T 2 further reduces the concentration of the radical T 1 . Overall, the kinetically favored radical addition and energetically favored back HAT process contribute to the α-selective silylation of alkenyl boronates. Similar elucidation is also found for cis-alkenyl boronates ( Supplementary Fig. 23).
A plausible mechanism for the hydrosilylation of allyl boronates was also proposed ( Supplementary Fig. 19), and the γ-selectivity was analyzed by calculations (Fig. 7). The silyl radical M generated from HAT selectively adds to the sterically more accessible γ-position of the allyl boronic ester to give a β-boryl carbon-centered radical intermediate T 5 . The α-addition is not favored (Supplementary Fig. 24). At this stage, a 1,2-boron migration process influenced by the αsubstituents on the allyl boronates took place [47][48][49][50] . The migration was steered by thermodynamic effects to generate a more stable carbon radical T 7 which undergoes polarity-matched HAT process with thiol N to give vicinal borosilanes. DFT calculations indicate the migration energy barrier for α,α-dimethyl allyl boronate is low (ΔG ≠ = 9.23 kcal·mol −1 ) and the rearranged radical intermediate T 7 is more stable than the non-migrated radical T 5 (ΔG = −1.69 kcal·mol −1 ) (Supplementary Fig. 24). Moreover, the HAT reaction rate of rearranged radical T 7 with thiol is much faster compared to T 5 , thereby allowing selective synthesis of vicinal borosilanes. Finally, the generated thiyl radical I could accept an electron from 4CzIPN •to close both catalytic cycles or engage in chain propagations. Article https://doi.org/10.1038/s41467-023-38224-y In summary, we have developed efficient photo-HAT catalyzed α-selective silylation of alkenyl boronates and γ-selective silylation of allyl boronates, providing a broad range of structurally diverse geminal and vicinal borosilanes. Unlike transition-metal catalysis, the regioselectivity is determined by kinetic and thermodynamic effects in radical addition and HAT processes. These protocols featured merits such as metal-free, atom-economy, extremely broad substrate scopes and good functional group tolerance. The silyl or boryl groups in the products demonstrated versatile synthetic utility for subsequent diversification. Gram-scale reactions were smoothly achieved in a batch reactor and an operationally simple continuousflow reactor.
General procedure of α-selective silylation of alkenyl boronates to synthesized β-aryl geminal borosilanes A 10 mL microwave tube equipped with a magnetic stir bar was charged with 4CzIPN (1.6 mg, 0.002 mmol, 1 mol%), alkenyl boronate (0.2 mmol), silane (0.24 mmol, 1.2 equiv.) and anhydrous MTBE (2 mL). The tube was capped with a Supelco aluminum crimp seal with septum (PTFE/butyl). The resulting mixture was cooled to 0°C using an icewater bath and bubbled with an argon balloon for 10 min. DIPEA (7.2 μL, 0.04 mmol, 20 mol%), and EtO 2 CCH 2 SH (4.4 μL, 0.04 mmol, 20 mol%) were then added. After that, the reactor was placed under blue LED (Kessil light, 80 W, 456 nm) and irradiated for 24 h at room temperature. And then, add 4CzIPN (1.6 mg, 0.002 mmol) into the microwave tube in the glovebox, and removed it from the dry box. The reaction was irradiated for additional 24 h under the same conditions. The solvent was removed under vacuum. Purification by flash column chromatography over silica gel (eluent: n-hexane/EtOAc mixtures) gave the desired product.

Data availability
The authors declare that all other data supporting the findings of this study are available within the article and Supplementary Information files, and also are available from the corresponding author upon request. Source data are provided with the publication. Source data are provided with this paper.