Enantioselective Nickel-Catalyzed Si–C(sp2) Bond Activation and Migratory Insertion to Aldehydes: Reaction Scope and Mechanism

Abstract

Transition-metal-catalyzed silicon–carbon bond activation is one of the most important processes in both organosilicon chemistry and homogeneous catalysis that is still rarely reported in the past decades, and the enantioselective versions based on transition-metal-catalyzed Si–C bond activation remain an ongoing challenge in asymmetric catalysis. Herein, we report a convenient and enantioselective Si–C bond cleavage-initiated [4 + 2] annulation of benzosilacyclobutenes with aldehydes, which provides an access to the direct synthesis of chiral six-membered oxasilacycles and their derivatives with high yields and enantioselectivities (up to 97% ee). The catalytic asymmetric reaction proceeds smoothly with the aid of a chiral TADDOL-derived phosphoramidite ligand and its chiral Ni complex with a suitable cavity. By switching the work-up of the reaction involved, the present strategy may be extended to subsequent downstream transformations of silyl ether-containing oxasilacycles to give chiral o-tolyl arylmethanols with high ees and quantitative conversions. A series of experimental results support that the strategy of silicon-mediated organic synthesis controlled by nickel catalysis demonstrates a powerful potential for the facile synthesis of chiral alcohols and its drug-like derivatives. Finally, mechanistic and computational investigations of the nickel-catalyzed Si–C bond activation offer insights into the origin of the observed stereoselective outcome, and the density functional theory calculation shows that the nickel-controlled Si–C(sp2) bond activation enables the controllable migratory insertion of benzaldehyde into the Ni–Si bond, which is recognized as the enantioselectivity-determining step.