Highly Regio- and Enantioselective Cu/Pd Co-Catalyzed Allylic Alkylation of alpha-pyridyl-alpha-fluoroesters: Construction of Quaternary C-F Stereocenters

New methods for preparation of chiral alkyl fluorides have been studied intensively in recent years due to the favorable physicochemical and biological properties of those structures. Herein, we describe the regio- and enantio-selective allylic alkylation of alpha-pyridyl-alpha-fluoroesters with allyl acetates promoted by Cu/Pd synergistic catalysis, constructing the carbon- fluorine quaternary stereocenters. In this co-catalytic system, palladium catalyst mainly constructed the C-C bond, while chiral copper catalyst controlled the enantioselectivity. A series of aryl- and aliphatic-substituted allyl acetates are applied, giving the corresponding products in high yield, excellent enantioselectivity, and E/Z (up to 98% yield, 98: 2 er, E/Z> 20: 1).

Automated summary

In recent years, new methods for the preparation of chiral alkyl fluorides have been intensively studied due to their favorable physicochemical and biological properties. In this study, the regio- and enantio-selective allylic alkylation of alpha-pyridyl-alpha-fluoroesters with allyl acetates, promoted by Cu/Pd synergistic catalysis, was described, leading to the construction of carbon-fluorine quaternary stereocenters. The palladium catalyst primarily formed the C-C bond, while the chiral copper catalyst controlled the enantioselectivity. The reaction showed high yield, excellent enantioselectivity, and E/Z selectivity (up to 98% yield, 98:2 er, E/Z>20:1) with a series of aryl- and aliphatic-substituted allyl acetates.