Catalyst-Controlled Regiodivergent Synthesis of 1- and 3-Thiosugars with High Stereoselectivity and Chemoselectivity

Abstract

An effective regiodivergent synthesis toward 1- and 3-thiosugars was achieved through palladium and cobalt catalysis, respectively. β-1-Thiosugars were obtained from 3,4-O-carbonate-glycals and various thiols catalyzed by Pd2(dba)3 in good yields with exclusive stereoselectivity and chemoselectivity, while only (3S)-3-thiosugars were generated via Co(BF4)2. Experiments and DFT calculations supported the proposed mechanism that the thiol moiety preferred to form a hydrogen bond with C4-oxygen from top-face in Pd conditions but thiols would coordinate with cobalt from bottom-face in Co conditions. The difference between Pd/Co–C1 and Pd/Co–C3 bond lengths of key intermediates provided further insights into the 1,3-regioselectivity.