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This article describes studies on the regioselective acetal protection of monosaccharide-based diols using chiral phosphoric acids (CPAs) and their immobilized polymeric variants, ( R )-Ad-TRIP-PS and ( S )-SPINOL-PS, 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 out in a regiodivergent fashion depending on the choice of chiral catalyst. The polymeric catalysts were conveniently recycled and reused multiple times for gram-scale functionalizations with catalytic loadings as low as 0.1 mol %, and their performance was often found to be superior to the performance of their monomeric variants. These regioselective CPA-catalyzed acetalizations were successfully combined with common hydroxyl group functionalizations as single-pot telescoped procedures to produce 32 regioisomerically pure differentially protected mono- and disaccharide derivatives. To further demonstrate the utility of the polymeric catalysts, the same batch of ( R )-Ad-TRIP-PS catalyst was recycled and reused to accomplish single-pot gram-scale syntheses of 6 differentially protected d-glucose derivatives. The subsequent exploration of the reaction mechanism using NMR studies of deuterated and nondeuterated substrates revealed that low-temperature acetalizations happen via a syn -addition mechanism and that the reaction regioselectivity exhibits strong dependence on the temperature. The computational studies indicate a complex temperature-dependent interplay of two reaction mechanisms, one involving an anomeric phosphate intermediate and another via concerted asynchronous formation of an acetal, that results in syn -addition products. The computational models also explain the steric factors responsible for the observed C2 selectivities and are consistent with experimentally observed selectivity trends.

In control: A chiral phosphoric acid catalyst significantly enhances or completely overrides the inherent regioselective acetalization profiles exhibited by monosaccharide-derived 1,2-diol substrates. This study represents the first example of chiral-catalyst-directed regio- and enantioselective intermolecular acetalizations, which are complementary to existing methods for substrate-controlled functionalization of polyols., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In control: A chiral phosphoric acid catalyst (see scheme) significantly enhances or completely overrides the inherent regioselective acetalization profiles exhibited by monosaccharide‐derived 1,2‐diol substrates. This study represents the first example of chiral‐catalyst‐directed regio‐ and enantioselective intermolecular acetalizations, which are complementary to existing methods for substrate‐controlled functionalization of polyols. [ABSTRACT FROM AUTHOR]

The first example of a chiral-catalyst-controlled regioselective acetalization of C2/C3-OH carbohydrates such as (I) and (VIII) is described. [ABSTRACT FROM AUTHOR]