Copper-Catalyzed Asymmetric Radical 1,2-Alkylesterification of 1,3-Dienes with Cycloalkyl Hydroperoxides and Acids

Transition-metal-catalyzed radical relay cross-coupling reactions of 1,3-dienes have recently emerged as one of the most powerful methods for construction of structurally diverse allylic compound in a single chemical step. However, there still has been limited success in expanding substrate scope of radical precursors and coupling partners, as well as exploring catalytic asymmetric variants. Herein, we report a copper-catalyzed enantioselective three-component 1,2-alkylesterification of 1,3-dienes using cycloalkyl hydroperoxides as the carbonyl-containing alkyl radical sources and carboxylic acids as O-nucleophiles under mild and redox-neutral conditions. This protocol features broad substrate scope and good functional group tolerance with respect to each component, providing practical access to a variety of distally keto-functionalized allylic esters with high enantioselectivity. Mechanistic studies suggest the involvement of a sequential radical relay and C-O cross-coupling in this three-component radical reaction. Radical Cross-CouplingA copper-catalyzed enantioselective three-component radical relay 1,2-alkylesterification of 1,3-dienes using cycloalkyl hydroperoxides and carboxylic acids was reported. This protocol features broad substrate scope and good functional group tolerance with respect to each component, providing practical access to a variety of distally keto-functionalized chiral allylic esters with high enantioselectivity under mild and redox-neutral conditions.image

Automated summary

A copper-catalyzed enantioselective three-component radical relay 1,2-alkylesterification of 1,3-dienes using cycloalkyl hydroperoxides and carboxylic acids was reported. This protocol features broad substrate scope and good functional group tolerance with respect to each component, providing practical access to a variety of distally keto-functionalized allylic esters with high enantioselectivity under mild and redox-neutral conditions.