Copper-catalyzed regio- and stereo-selective hydrosilylation of terminal allenes to access (E)-allylsilanes

Regioselectivity and stereoselectivity control in hydrosilylation of terminal allenes is challeging. Although the selective synthesis of vinylsilanes, branched allylsilanes or linear (Z)-allylsilanes have been achieved, transition-metal catalyzed hydrosilylation of terminal allenes to access (E)-allylsilane is difficult. Herein, we report a copper-catalyzed selective hydrosilylation reaction of terminal allenes to access (E)-allylsilanes under mild reaction conditions. The reaction shows broad substrate scope, representing an efficient method to prepare trisubstituted (E)-allylsilanes through hydrosilylation reaction of allenes and can also be applied in the synthesis of disubstituted (E)-allylsilanes. The mechanism study reveals that the E-selectivity is kinetically controlled by the catalyst but not by the thermodynamically isomerization of the (Z)-isomer.

O rganosilicon compounds are widely used in synthetic chemistry and material science 1 . As a step-and atomeconomical approach to synthesize organosilicon compounds, transition-metal catalyzed hydrosilylation of unsaturated C-C bonds such as alkenes 2-10 , alkynes [11][12][13][14][15][16][17] and dienes [18][19][20][21][22][23][24] , has been extensively studied. However, the study of the selective hydrosilylation of allenes lags behind, probably because of the challenges associated with regioselectivity and stereoselectivity control 25 . As for terminal allenes, six possible isomers could be potentially generated in transition-metal catalyzed hydrosilylation reaction, due to the presence of two continuous orthogonal π bonds (Fig. 1a). Previous hydrosilylation of terminal allenes with Pd, Ni, Au, Ru or Al catalysis mainly occurred at the nonterminal C=C bonds, affording vinylsilanes as the major products [26][27][28][29][30][31][32] . The synthesis of branched allylsilanes with Pd or Ni catalysis have also been achieved, which also occurred at the non-terminal C=C bonds 27,28,31 . In 2016, Asako and Takai reported a molybdenum-catalyzed hydrosilylation at the terminal C=C bonds of allenes that yielded linear allylic silanes in moderate to good Z-selectivities 33 . Seminal work in the transitionmetal catalyzed synthesis of (Z)-allylsilanes were then reported by Ma and Huang groups and Ge group with cobalt catalysis 34,35 . However, there is still one challenge remained in transition-metal catalyzed hydrosilylation of terminal allenes, that is, the regioand stereoselective generation of (E)-allylsilanes. The only report to prepare (E)-allylsilanes via hydrosilylation of allenes was Yao's radical-based approach, but the reaction is limited to super reactive (TMS) 3 SiH and monoalkyl substituted allenes 36 . There are several other methods to access di-substituted (E)allylsilanes [37][38][39] , but no general catalytic hydrosilylation methods to prepare tri-substituted (E)-allylsilanes is availabe. To the best of our knowledge, transition metal catalyzed hydrosilylation of terminal allenes to obtain both trisubstituted and disubstituted (E)-allylsilanes has not been well studied.
It is worth to mention that copper is an earth abundant transition metal, which makes it an ideal candidate to develop transformations in sustainable chemistry. However, compared to relatively more extensively studied Ni, Co, Fe-catalyzed hydrosilylation reactions 2,40-42 , copper catalysis has been rarely used in hydrosilylation of unsaturated carbon carbon bonds 24,[43][44][45][46][47][48][49] . Herein, we report a copper-catalyzed hydrosilylation of allenes which affords linear (E)-allylsilanes with excellent regio-and stereoselectivity. The reaction shows broad substrate scope and is amenable to synthesize both di-substituted and tri-substituted (E)-allylsilanes. The mechanism study reveals that the E-selectivity is kinetically controlled by the catalyst but not by the thermodynamically isomerization of the (Z)-isomer.
Synthetic transformations of compound 3a. To test synthetic potential of this reaction, we scaled up the model reaction to 10 mmol scale, and allylsilane 3a was isolated in 83% yield (2.6 g) with 99:1 E:Z (Fig. 4a). Then we explored the conversion of Si-H bond of 3a with the retention of the carbon carbon double bond (Fig. 4b). Taking advantage of the E-configuration of compound 3a, we achieved the intramolecular dehydrogenative C-Si bond formation via Ir catalyzed C-H activation, affording the fivemembered silicon-containing compound 6 in 60% yield. The reaction of compound 3a with MeOH in the presence of a Nheterocyclic carbene catalyst afforded siloxane 7 in 85% yield. Treatment of 3a with MeLi at room temperature gave allylsilane 8 in 80% yield. Allylic alcohols are synthetically valuable intermediates in various organic transformations 50,51 . Oxidation of the (E)-allylsilanes with H 2 O 2 under basic conditions afford allylic alcohol 9 in 91% yield. In all of these reactions, the configurations of the double bond did not change. Moreover, Allyl silanol 10 could be obtained in 90% yield under the Pd-catalyzed conditions (Fig. 4c). Compound 11 was then synthesized in 77% yield through the Hiyama-Denmark cross-coupling reaction between silanol 10 and PhI (Fig. 4c).

Discussion
In order to understand the mechanism of the copper-catalyzed hydrosilylation of terminal allenes, we conducted a deuteriumlabeling reaction between 1a and Ph 2 SiD 2 . This reaction afforded the corresponding (E)-allylsilane with >99% D-incorporation, indicating that the hydrogen atom was from the silane, but not from the solvent (Fig. 5a). The KIE study indicated that Si-H bond might be involved in the rate-determining step (Fig. 5b).
(Z)-allylsilanes are thermodynamically less stable than (E)-allylsilanes. We wonder whether the high E-selectivity of our reaction was resulted from catalyst control or the thermodynamically isomerization of the less stable (Z)-isomer to the more stable (E)isomer? Firstly, we tested the reaction of (Z)-3a under the standard conditions in the presence of 1 equivalent of Ph 2 SiH 2 , and we found that there was no Z/E-isomerization (Fig. 5c). Moreover, compound 5h (91:9 E/Z) did not undergo Z/E-isomerization either (Fig. 5d). These experimental results strongly support that the E-stereoselectivity of our reaction is kinetically controlled. It is known that CuH intermediates could be generated from the reaction of copper salts and silanes and CuH could add to olefins to generate organocopper intermediates [43][44][45][46][47][48][49] . For the reaction of allenes with CuH, both terminal and internal double bonds of 1a could participate in the hydrocupration 47,48 .
In order to further understand the origin of the stereo-and regioselectivity of our reaction, density functional theory (DFT) calculations have been performed (Fig. 6  observed as the major products. According to DFT calculations, σ-bond metathesis step are the reaction rate-limiting step and the stereoselectivity determining step, which is consistent to result of the KIE study. Independent gradient model (IGM) analysis of the transition states 21-ts, 22-ts and 23-ts was also performed 54,55 . As shown in Fig. 6c, 21-ts is 1.3 and 1.7 kcal/mol more favorable than 22-ts and 23-ts, which is consistent with the stereo-and regioselectivity observed in the experiment. The leading factor that differentiates the three competing transition states is likely to be π-π interaction between the phenyl group of Xantphos and the phenyl group of the allene. This favorable π-π interaction stabilizes 21-ts (ΔE π−π = −2.1 kcal/mol) by 0.7 and 2.0 kcal/mol relative to 22-ts (ΔE π-π = −1.4 kcal/mol) and 23-ts (ΔE π−π = −0.1 kcal/mol) based on the calculations of interacting fragments. The green oval represents the presence of interactions between the highlighted fragments. Therefore, our calculations indicate noncovalent π-π interaction is the determinant of stereo-and regioselectivity.
In summary, we have developed a copper-catalyzed regio-and stereo-selective hydrosilylation of allenes to access (E)-allylsilanes.   Fig. 5 Mechanism study. a A deuterium-labeling reaction indicate that the hydrogen comes from the silane. b KIE study suggested that the ratedetermining step might involve in the reaction of Si-H bond. c No isomerization of Z-3a to E-3a suggest that the selectivity is kinetically controlled. d No change of the Z/E ratio of 5 h suggest that our Cu-catalyzed reaction is kinetically controlled.     A wide range of 1,1-disubstituted and monosubstituted terminal allenes reacted to afford the corresponding (E)-allylsilanes in good yields. The reaction conditions are simple and mild, and the product can be prepared in grams, which proves the practicability of this reaction. The mechanism study reveals that the E-selectivity is kinetically controlled by the catalyst but not by the thermodynamically isomerization of the (Z)-isomer.

Methods
General procedure for copper-catalyzed allene hydrosilylation. In a glovebox, to an oven-dried screw-capped 4 ml glass vial equipped with a magnetic stir bar was added Cu(OAc) 2 (0.01 mmol, 5 mol%), Xantphos (0.015 mmol, 7.5 mol%), THF (0.4 mL). The mixture was stirred for 15 min. Then terminal allene (0.2 mmol, 1.0 equiv.) and silane (0.24 mmol, 1.2 equiv. or 0.22 mmol, 1.1 equiv.) were added and the mixture was stirred at room temperature for 12 h (Figs. 2) or 6h (Fig. 3). The solvent was removed under vacuum and the residue was purified by column chromatography to afford the corresponding product. See section 1.3 and 1.4 in the Supplementary Information for more details.