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

An effective regiodivergent synthesis toward 1- and 3-thiosugars was achieved through palladium and cobalt catalysis, respectively. beta-1-Thiosugars were obtained from 3,4-O-carbonate-glycals and various thiols catalyzed by Pd-2(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.

Automated summary

An effective regiodivergent synthesis of 1- and 3-thiosugars was achieved using palladium and cobalt catalysis, respectively. The difference in the interaction of thiol moieties with Pd and Co catalysis conditions led to the selective formation of beta-1-thiosugars and (3S)-3-thiosugars. Experimental and theoretical calculations supported the proposed mechanism and provided insights into the regioselectivity based on the bond lengths of key intermediates.