A high-yielding synthesis of allyl glycosides from peracetylated glycosyl donors

Abstract

β-Configured peracetylated sugars are often used as easily accessible glycosyl donors that are typically activated with common Lewis acids such as boron trifluoride or trimethylsilyltrifluoromethane sulfonate. Often these glycosylations occur with unsatisfactory yields due to incomplete reactions or extensive byproduct formation, primarily as a result of loss of an additional acetyl group generating partially unprotected glycosides. Here we report a simple glycosylation-reacetylation protocol for the generation of predominantly β-configured peracetylated allyl glucoside, -galactoside, -lactoside, and -maltoside with substantially improved reaction yields.

Scheme 1

Lewis acid (LA) promoted glycosylation with peracetylated glycosyl donors (1): Allyl alcohol may attack the cationic species 2 at two different positions leading to the allylglycoside 3 or to the ortho-ester 4, which can rearrange to produce allylglycoside 3, or react with allyl alcohol to the partially deprotected allylglycosides 5 and possibly 6, which may be reacetylated to 3.

Scheme 2

Conversion of peracetyl- -glycosyl donors into their predominantly -configured allylglycosides: a) AllOH, CH₂Cl₂, BF₃·Et₂O or TMSOTf, rt; b) aqueous workup with refrigerated solvents (~ 5 C); c) AcsO, pyr, rt.