Unusual Outcome of Glycosylation: Hydrogen‐Bond Mediated Control of Stereoselectivity by N‐Trifluoroacetyl Group?

Abstract

During the synthesis of protected tetrasaccharide fragment of the repeating unit of polysaccharide of Azospirillum brasilense sp7 we found that glycosylation with a mixture of protected N‐trifluoroacetyl (TFA)‐protected glucosamine N‐phenyltrifluoroacetimidate and the corresponding 2‐trifluoromethyl‐oxazoline led to 1,2‐cis‐linked glycoside along with the expected 1,2‐trans‐linked isomer. This fact looks quite unusual bearing in mind that both N‐TFA‐containing glycosyl donor and 2‐trifluoromethyl‐oxazoline are usually expected to favor the formation of 1,2‐trans‐glycosides. Formation of 1,2‐cis‐glycoside was explained by hydrogen‐bond mediated complexation of hydrogen atom of NHTFA at C‐2 of oxacarbenium ion derived from glycosyl donor and oxygen atom of hydroxy group of the incoming nucleophile. Conversely, glycosylations with N‐phthaloyl protected glycosyl donors resulted in exclusive formation of 1,2‐trans‐isomer presumably due to a significant steric effect and the absence of additional hydrogen‐bonding sites of N‐phthaloyl group.