Construction of Chiral Quaternary Carbon Centers via Asymmetric Metal Carbene gem‐Dialkylation

Abstract

AbstractThe catalytic asymmetric construction of all‐carbon quaternary stereocenters has received tremendous interest over the past decades, and numerous efficient protocols have been disclosed based on the formation of one C−C bond between two assembling reactants. However, the use of asymmetric multi‐component reactions that build two C−C bonds on the same carbonic center with concomitant assembly of quaternary stereocenters is rare and remains challenging. Herein, we disclose an enantioselective three‐component reaction of α‐diazo ketones with alkenes and 1,3,5‐triazines under dirhodium/chiral phosphoric acid cooperative catalysis, which leads to a practical and atom‐economic synthesis of poly‐functionalized chiral ketones that bear a α‐quaternary stereocenter in generally good to high yields with excellent enantioselectivities. In comparison to the previous method for the construction of tertiary and quaternary stereocenters via carbene gem‐difunctionalization reactions, this reaction features an unprecedented gem‐dialkylation process via sequential installation of two C−C bonds on the carbene center in one reaction, providing an essential complement to the asymmetric construction of all‐carbon quaternary stereocenters using common and readily available starting materials.