One‐pot Multistep Regioselective Protection of Carbohydrates Catalyzed by Acids

Beau, Jean‐Marie; Bourdreux, Yann; Despras, Guillaume; Gouasmat, Alexandra; Jose, Géraldine San; Urban, Dominique; Vauzeilles, Boris

doi:10.1002/9783527697014.ch7

Cited by 3 publications

(3 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is also noteworthy that the single-pot procedures leading to 6a , 6b , 6f , 6k , 6p , and 8e were readily scalable and proceeded with improved overall yields. Altogether, these studies suggest that immobilized CPA catalysts 2 and 3 hold great potential for the regioselective preparation of differentially protected monosaccharide derivatives and that the use of the regioselective CPA-catalyzed acetalization allows the expansion of the single-pot methods previously developed by Hung and others. , …”

Section: Resultsmentioning

confidence: 99%

“…Synthesis of such differentially protected monosaccharides often requires multiple-step sequences to differentiate numerous hydroxyl groups and may suffer from low yields and tedious purification due to the formation of undesirable regioisomers throughout these sequences . To address the challenges associated with the selective functionalization of monosaccharides, numerous methods, including a single-pot functionalization approach by the Hung group, have been previously developed. , However, the majority of such methods rely on the reagents and catalysts that discriminate between the axial and the equatorial hydroxyl groups, while only a few methods exist for the selective differentiation of equatorial hydroxyl groups that are in a similar steric and electronic environment (cf. Scheme A). , While possible with achiral reagents or catalysts, such transformations often exhibit strong electrophile and substrate structure dependence and lack generality (cf.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Despite a significant progress in this area, and the availability of streamlining one-pot processes, 7–12 in a majority of the applications a large number of protecting group manipulation steps are required to obtain the desired regioselectively substituted product. While orthogonal, semi-orthogonal, or selectively removable protecting groups represent a very important direction of carbohydrate synthesis, discussed herein in the synthesis of partially protected carbohydrates by manipulating only one type of a protecting group for a given derivative.…”

Section: Introduction and Basic Considerationsmentioning

confidence: 99%