Benzylidene acetal fragmentation route to 6-deoxy sugars: Direct reductive cleavage in the presence of ether protecting groups, permitting the efficient, highly stereocontrolled synthesis of β-D-rhamnosides from D-mannosyl glycosyl donors

An approach to the stereocontrolled synthesis of β-D-rhamnopyranosides is described in which 2,3-O-benzyl or related 4,6-O-[α-(2-(2-iodophenyl) ethylthiocarbonyl)benzylidene]-mannosyl thioglycosides are first used to introduce the β-D-mannopyranoside linkage in high yield and stereoselectivity. Following glycosylation, treatment with tributyltin hydride in toluene at reflux brings about reductive radical fragmentation directly to the 6-deoxy sugar in high yield. A variation of these donors bearing a carboxylated donor on O3 is a highly α-selective mannosyl and, after radical fragmentation, α-D-rhamnosyl donor. Using this stereoselective glycosylation/radical-fragmentation approach, a concise synthesis of the title tetrasaccharide is realized in which both the β-D- and α-D- rhamnopyranosyl units are obtained in a single step by a double radical fragmentation of the modified benzylidene acetals.