Catalytic asymmetric hydrometallation of cyclobutenes with salicylaldehydes

Chiral, substituted cyclobutanes are common motifs in bioactive compounds and intermediates in organic synthesis but few asymmetric routes for their synthesis are known. Herein we report the Rh-catalyzed asymmetric hydrometallation of a range of meso-cyclobutenes with salicylaldehydes. The ortho-phenolic group promotes hydroacylation and can be used as a handle for subsequent transformations. The reaction proceeds via asymmetric hydrometallation of the weakly activated cyclobutene, followed by a C–C bond forming reductive elimination. A prochiral, spirocyclic cyclobutene undergoes a highly regioselective hydroacylation. This report will likely inspire the development of other asymmetric addition reactions to cyclobutenes via hydrometallation pathways.

Chiral, substituted cyclobutanes are common motifs in bioactive compounds and intermediates in organic synthesis but few asymmetric routes for their synthesis are known.