Stereoselective synthesis of iso-dolaproine via dynamic kinetic resolution

Abstract

(formula presented) An efficient multigram-scale synthesis of optically pure Boc-(2S,3R,4S)-iso-dolaproine is reported using dynamic kinetic resolution (DKR). The catalytic asymmetric hydrogenation of ethyl (4S)-3-(2́-pyrrolidinyl)-3-oxo-2-methyl propanoate hydrochloride using in situ generated Ru[(S)-MeO-BIPHEP]Br2 catalyst affords the anti β-hydroxy α-methyl ester quantitatively. The two new stereogenic centers are simultaneously controlled with high diastereoselectivity.