Chiral Magnesium(II)-Catalyzed Asymmetric Hydroalkylation of Imine-Containing Vinylazaarenes through Conjugate Addition

Abstract

The synthesis of chiral azaarenes is of great importance for pharmaceutical development. A direct and versatile approach to obtaining such compounds is the functionalization of imine-containing 2-vinylazaarenes. We have developed a chiral N,N′-dioxide/Mg(II) Lewis acid catalytic system to control nucleophilic β-cyclic or acyclic ketone amides/esters and overcome strong background reaction, enabling highly efficient enantioselective hydroalkylation of imine-containing 2-vinylazaarenes via conjugate addition. As a result, a library of chiral azaarenes bearing an all-carbon quaternary stereocenter can be obtained in high yields with good to excellent ee values. DFT calculations indicate assistances of azaarenes in hydrogen transfer, and the CH−π interaction between the substrate and the ligand’s amide group in the enantioselective differentiation.