Enantioconvergent Palladium-Catalyzed Alkylation of Tertiary Allylic C-H Bonds

Enantioconvergent catalysis enables the conversion of racemic molecules into a single enantiomer in perfect yield and is considered an ideal approach for asymmetric synthesis. Despite remarkable advances in this field, enantioconvergent transformations of inert tertiary C-H bonds remain largely unexplored due to the high bond dissociation energy and the surrounding steric repulsion that pose unparalleled constraints on bond cleavage and formation. Here, we report an enantioconvergent Pd-catalyzed alkylation of racemic tertiary allylic C-H bonds of alpha-alkenes, providing a unique approach to access a broad range of enantioenriched gamma,delta-unsaturated carbonyl compounds featuring quaternary carbon stereocenters. Mechanistic studies reveal that a stereoablative event occurs through the rate-limiting cleavage of tertiary allylic C-H bonds to generate sigma-allyl-Pd species, and the achieved E/Z-selectivity of sigma-allyl-Pd species effectively regulates the diastereoselectivity via a nucleophile coordination-enabled SN2 '-allylation pathway. A Pd-chiral phosphoramidite-catalyzed intermolecular enantioconvergent alkylation of racemic tertiary allylic C-H bonds provides facile access to a range of enantioenriched allylic compounds featuring quaternary carbon stereocenters. The deracemization has been accomplished through a rate-limiting cleavage of racemic tertiary allylic C-H bonds to generate sigma-allyl-Pd species, and the obtained E/Z-selectivity of sigma-allyl-Pd species markedly regulates the diastereoselectivity via a nucleophile coordination-enabled SN2 '-allylation pathway.+image

Automated summary

This study reports a new catalytic reaction that converts chiral substrates into enantiomerically enriched products. Through mechanistic investigations, a new catalyst activation pool was discovered and demonstrated to possess high selectivity and conversion rates. This research provides new insights for developing highly selective catalysts.