Remote Stereocenter through Amide-Directed, Rhodium-Catalyzed Enantioselective Hydroboration of Unactivated Internal Alkenes

Despite the frequent occurrence of gamma-branched amines in bioactive molecules, the direct catalytic asymmetric synthesis of this structural motif containing a remote stereocenter remains an important synthetic challenge. Here, we report an amide-directed, rhodium-catalyzed highly diastereo-and enantioselective hydroboration of unactivated internal alkenes. This method provided facile access to enantioenriched amines containing beta,gamma-vicinal stereocenters. The application of this strategy to the synthesis of bioactive molecules was demonstrated. Computational studies indicated that migratory insertion of the alkene into rhodium hydride controls the enantioselectivity.

Automated summary

This study presents an amide-directed, rhodium-catalyzed highly diastereo- and enantioselective hydroboration reaction which provides a facile access to enantioenriched amines containing beta,gamma-vicinal stereocenters. Computational studies indicate that migratory insertion of the alkene into rhodium hydride controls the enantioselectivity.