Catalytic Regioselective Benzoylation of 1,2-trans-Diols in Carbohydrates with Benzoyl Cyanide: The Axial Oxy Group Effect and the Action of Achiral and Chiral Amine Catalysts

Regioselective protection of the polyfunctional carbohydrates with acyl groups under catalytic conditions is a prerequisite for efficient structural modification and chain extension via glycosidation. A general and also strong "axial oxy group effect" was now observed with benzoyl cyanide as the acylating agent and 4-dimethylaminopyridine as the catalyst, permitting the preferred O-acylation of equatorial hydroxy groups next to axial oxy groups. This effect is substantiated with 2,3-O-unprotected beta-D-galacto- and alpha-D-glucopyranosides and 3,4-O-unprotected mannopyranosides possessing vicinal trans-diol moieties. Moreover, vicinal trans-diols with axial oxy groups next to each hydroxy group, possessing expectedly comparable reactivity, could be differentiated with chiral tertiary amine catalysts. Particularly interesting in this regard is the action of bifunctional (S,S)-N-(N,N-dialkylaminocyclohexyl)-thioureas as catalysts; they favor 2-O-benzoylation of 2,3-O-unprotected alpha-galactopyranosides, as is also supported by density functional theory calculations. This directing effect can be reversed with quinidine as the catalyst or with bulky substituents at the anomeric position.