Acid-Base Catalysis Concept in Glycosidation

Abstract

Adduct formation between glycosyl acceptors (alcohols, thiols) and arylboron fluorides or arylsilicon fluorides, respectively, as catalyst permits acid-base-catalyzed glycoside bond formation with O-glycosyl trichloroacetimidates as glycosyl donors. Thus, from various glycosyl donors and acceptors, 1,2-trans glycosides could be obtained with very high yield and anomeric selectivity. This way, also 1,2-cis glycosides were accessible with reactive, sterically not-demanding glycosyl acceptors. By the results an intramolecular nucleophilic substitution (SN2-type) reaction course is supported that leads to concomitant donor and acceptor activation by the catalyst. Similarly, in the activation of O-glycosyl trichloroacetimidates by Bronsted acids as catalyst, the bis-N, N0-[3,5-bis-(trifluoromethyl)phenyl]-thiourea (8) as cocatalyst exhibits a cooperative behavior. This compound enables hydrogen-bond-mediated complex formation between the donor, the acceptor, and the acid catalyst. This way, an acid-base-catalyzed SN2-type glycoside bond formation is facilitated even at room temperature and in the absence of anchimeric assistance. Thus, a strong influence of 8 on reaction rate, yield, and anomeric selectivity is exerted.