Rapid Access to Chiral Spiro[2.3] Lactams: Stereoselective Hydroborylation and Hydrosilylation and Remote Control of Axial Chirality by Copper-Catalyzed Desymmetrization of Spirocyclopropenes

Abstract

Chiral spirocyclopropyl β-lactams are common motifs in bioactive compounds and pharmaceuticals. Here we disclose a diastereoselective and enantioselective hydroborylation and hydrosilylation of spirocyclopropenes, via a Cu-catalyzed desymmetrization strategy, for the rapid preparation of enantio-enriched spirocyclopropyl β-lactams. The efficient desymmetrization strategy allows the remote control of axial chirality, offering the borylated and silylated products bearing central, spiro, and axial chirality. The combination of multichiral elements would provide a novel motif for biological evaluation in potential drug discovery.

Enantioselective Synthesis of Axially and Centrally Chiral Styrenes via Nickel-Catalyzed Desymmetric Hydrocyanation of Biaryl Dienes

“…In 2022, Lin et al reported an atroposelective desymmetric cycloaddition of N -arylmaleimides using phosphine as the catalyst for the convenient construction of two central chiralites and a remote C Ar –N axial chirality . Very recently, Zhang et al presented a Cu-catalyzed desymmetrization of spirocyclopropenes for the access to central, spiro, and axial chiralities in one step . Despite this progress, the existing methods are limited to cyclic alkenes and the generation of C Ar –N axial chirality.…”