Palladium-Catalyzed Highly Enantioselective Arylation of Cyclic N-Sulfonyl α-Ketimino Esters towards the Synthesis of α-Quaternary Chiral Amino Acid Derivatives

We have developed a highly effective palladium/PHOX catalyst system for efficient asymmetric 1,2-addition of arylboronic acids to six-membered 1,2,6-thiadiazine-1,1-dioxide type cyclic N-sulfonyl α-iminoesters. The protocol allows convenient synthesis of a variety of nearly optically pure α-quaternary amino acid derivatives under mild reaction conditions. The synthetic utility of the reaction is demonstrated by simple product transformations. It allows the convenient construction of α,γ-substituted chiral γ-lactams having two carbon stereogenic centres, including one quaternary centre, in a highly enantiomerically pure form. This chemistry may be used to generate analogous molecules of BMS-561392 for bioactivity screening and drug discovery.