Enantioselective Palladium-Catalyzed α-Arylation of Acyclic Esters

Abstract

A Pd-catalyzed enantioselective α-arylation of α,α-disubstituted esters with aryl bromides is established for the first time by employing P-chiral monophosphorus ligand 3-Pent-BIDIME as chiral ligand, leading to a series of enantioenriched α,α-diaryl esters possessing quaternary carbon stereocenters in moderate to good yields and high enantioselectivities. The method features a broad substrate scope, mild conditions, excellent functional group compatibility, and low Pd loadings (as low as 1 mol %). The synthetic power of this protocol is exemplified by efficient preparation of a chiral α,α-diaryl substituted γ-lactone and asymmetric synthesis of (R)-amolanone. DFT calculation revealed a NaBr-bridged downstream transmetalation and the importance of noncovalent interaction in controlling the enantioselectivity.