1. Systematic Study of Regioselective Reductive Ring-Opening Reactions of 4,6- O -Halobenzylidene Acetals of Glucopyranosides.
- Author
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Mezö E, Herczeg M, Demeter F, Bereczki I, Csávás M, and Borbás A
- Subjects
- Indicators and Reagents, Lewis Acids, Monosaccharides, Acetals, Benzylidene Compounds
- Abstract
Reductive openings of cyclic acetals are widely used in modern synthetic organic chemistry for the regioselective introduction of protecting groups. A systematic study was performed on the applicability and efficacy of various hydride donor and protic or Lewis acid reagent combinations in the reductive ring opening of glucosidic 4,6-halobenzylidene acetals bearing an ortho -, meta -, and para -chloro- or -bromo substituent on the benzene ring. Most of the reagent combinations tested cleaved the 4,6- O -halobenzylidene acetal rings at O4 or O6 efficiently and with the expected regioselectivity. The LiAlH
4 -AlCl3 and the BH3 ·THF-TMSOTf combinations produced the 4- O -halobenzyl ether/6-OH products with complete regioselectivity and high yields. The use of Me3 N·BH3 -AlCl3 reagent system in toluene was also effective in cleaving the acetal ring at O6 but was accompanied by Al-chelation-assisted debenzylation side reactions. The NaCNBH3 -HCl and the Et3 SiH-BF3 ·Et2 O combinations were highly effective in yielding the 6-halobenzyl ether/4-OH derivatives. Et3 SiH, in combination with TfOH, produced the 6- O -ether/4-OH products in rapid reactions but also triggered silylation and reductive halobenzylation as secondary transformations. Reductive opening of the 1,3-dioxane ring of pyranosidic 4,6- O -halobenzylidene acetals by the proper reagent combination was found to be an efficient method for the regioselective introduction of versatile halobenzyl protecting groups onto the pyranose ring.- Published
- 2021
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