Copper-Catalyzed Highly Enantioselective Ring-Opening/Cyclopropanation of 1-Silylcyclopropenes

Abstract

The chiral cyclopropane framework is a crucial structural motif in bioactive molecules such as pharmaceuticals and natural products. Asymmetric cyclopropanation of alkenes via transition metal-catalyzed carbene transfer represents one of the most direct approaches for synthesizing chiral cyclopropanes. While significant progress has been made in the asymmetric cyclopropanation of α-C-substituted carbenes, the highly enantioselective cyclopropanation of α-silyl carbenes, which possess greater transformation potential, remains largely unexplored. In this study, we report a Cu(I)/chiral bisoxazoline catalytic system that enables highly enantioselective cyclopropanation and cyclopropanation/Cope rearrangement reactions between α-silyl-α-alkenyl carbenes (generated from ring opening of 1-silyl cyclopropene) and alkenes. This methodology provides access to a series of chiral cyclopropylsilanes containing stereogenic quaternary carbon centers as well as allylic silane moieties and chiral cycloheptadienylsilanes, thereby expanding the diversity of chiral organosilicon compounds. Theoretical calculations reveal that the rate-determining step involves the ring opening of cyclopropene, where the silyl group not only dictates the regioselectivity of the ring opening but also significantly influences the stereoselectivity of the reaction through its steric and rigid properties.

Keywords

Cyclopropanation / Chiral organosilicons / Cyclopropenes / Copper catalysis / Carbene / Asymmetric catalysis

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