Studies of Catalyst-Controlled Regioselective Acetalization and Its Application to Single-Pot Synthesis of Differentially Protected Saccharides.

This article describes the studies of regioselective acetal protection of monosaccharide-based diols using chiral phosphoric acids (CPAs) as the catalysts. These catalyst-controlled regioselective acetalizations were found to proceed with high regioselectivities (up to >25:1 rr) on various D-glucose, D-galactose, D-mannose and L-fucose derived 1,2-diols and could be carried with immobilized and recyclable catalyst. The utility of CPA-catalyzed acetalizations was further demonstrated for the regioselective single-pot preparation of various differentially protected mono- and disaccharide building blocks. The computational and mechanistic studies indicate complex temperature-dependent interplay of two reaction mechanisms, one involving an anomeric phosphate intermediate and another via concerted asynchronous formation of acetal. The computational models explain the steric factors responsible for the observed C2-selectivities and are consistent with the experimentally observed selectivity trends.