Asymmetric tandem conjugate addition-protonation to forge chiral secondary C-O bonds for quaternary carbon stereocenters at the nonadjacent β-position.

Abstract

A direct strategy to construct chiral secondary C-O bonds for quaternary carbon stereocenters at the nonadjacent β-position is described. Methylene 1,3-oxazolidine-2,4-diones were for the first time employed in an asymmetric reaction as viable electrophiles undergoing a tandem conjugate addition-protonation process. Using an l-amino acid-based urea-tertiary amine catalyst, the reaction with 3-substituted oxindoles gave valuable protonation adducts featuring 1,3-quaternary-tertiary (C-O) nonadjacent stereocenters in high yields and excellent stereoselectivities. The method was successfully extended to sulphur nucleophiles for synthesizing chiral 1,3-sulfur-tertiary alcohol derivatives with bioactive importance.