Systematic Study of Regioselective Reductive Ring-Opening Reactions of 4,6-O-Halobenzylidene Acetals of Glucopyranosides

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 LiAlH4–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 Me3N·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 Et3SiH-BF3·Et2O combinations were highly effective in yielding the 6-halobenzyl ether/4-OH derivatives. Et3SiH, 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.

Synthesis of the Three Most Expensive l-Hexose Thioglycosides from d-Glucose

“…Under the conditions used, the sugar ring was opened and the open-chain sugar alcohol 66 was formed in the reaction in excellent yield (98%). Such endocyclic cleavage of the pyranoside ring is very rare, it was only observed earlier on α-alloside 67 and o -halobenzylidenated α-glucoside 68 derivatives, and conformationally restricted pyranosides. 69…”

“…Under the conditions used, the sugar ring was opened and the openchain sugar alcohol 66 was formed in the reaction in excellent yield (98%). Such endocyclic cleavage of the pyranoside ring is very rare, it was only observed earlier on -alloside 67 and o-halobenzylidenated -glucoside 68 derivatives, and conformationally restricted pyranosides. 69 Performing the ring-opening reaction with the milder LiAlH 4 /AlCl 3 reagent combination successfully resulted in the expected 6-OH derivative 67 in good yield (77%).…”