Enantioselective Copper-Catalyzed Borylative Amidation of Allenes

An approach for the copper-catalyzed synthesis of enantioenriched amides bearing an alpha-stereogenic center is disclosed. This method involves the addition of an allyl copper species to an isocyanate and allows access to alpha-substituted chiral amides in high yields and high-to-excellent enantioselectivities. The utility of alpha-vinyl beta-boryl amides in synthesis is highlighted by the diversification of products to afford highly useful scaffolds. DFT calculations reveal that the catalyst preferentially coordinates to the oxygen of the isocyanate. Enantiocontrol arises from the steric repulsion between the boryl group and the stereodirecting phenyl of the chiral ligand.

Automated summary

This study reveals an approach for the copper-catalyzed synthesis of enantioenriched amides bearing an alpha-stereogenic center. The addition of an allyl copper species to an isocyanate allows access to alpha-substituted chiral amides in high yields and high-to-excellent enantioselectivities. The utility of alpha-vinyl beta-boryl amides in synthesis is highlighted by the diversification of products to afford highly useful scaffolds.