Studies of Catalyst-Controlled Regioselective Acetalization and Its Application to Single-Pot Synthesis of Differentially Protected Saccharidesopen access
- Authors
- Wang, Sibin; Zhelavskyi, Oleksii; Lee, Jeonghyo; Arguelles, Alonso J.; Khomutnyk, Yaroslav Ya; Mensah, Enoch; Guo, Hao; Hourani, Rami; Zimmerman, Paul M; Nagorny, Pavel
- Issue Date
- Nov-2021
- Publisher
- AMER CHEMICAL SOC
- Citation
- JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v.143, no.44, pp.18592 - 18604
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
- Volume
- 143
- Number
- 44
- Start Page
- 18592
- End Page
- 18604
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/189282
- DOI
- 10.1021/jacs.1c08448
- ISSN
- 0002-7863
- Abstract
- 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.
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