Stereoselective access to 2-deoxy-2-trifluoromethyl sugar mimetics by trifluoromethyl-directed 1,2-trans glycosylation

Abstract

Fluorinated carbohydrate mimetics are valuable molecular fragments in contemporary Glycoscience. Available synthetic protocols are mainly restricted to the preparation of ‘standard’ monofluorinated derivatives, whereas their more complex C(sp³)–CF₃ congeners remain virtually underdeveloped. A protocol for accessing a series of previously uncharted 2-deoxy-2-trifluoromethyl-D-hexopyranosides from D-glycals is disclosed. The stereoselectivity of the glycosylation step, which is mainly governed by a combination of electronic and more dominant steric factors, revealed a pronounced substrate control rendering 1,2-trans glycosides as a result of the configuration of the CF₃ moiety at C-2. The synthetic utility of this approach was demonstrated in the preparation of 2-CF₃-glycoconjugates of natural origin, including disaccharides, cholesterol analogs, amino acids, and sphingosine/phytosphingosine derivatives.