Fluorination of 2-hydroxy-hexopyranosides by DAST: towards formyl C-glycofuranosides from equatorial-2-OH methyl hexopyranosides

Abstract

Reaction of diversely configured and substituted, unbranched methyl d-hexopyranosides with the DAST in dichloromethane or acetonitrile led to normal substitution products and/or rearranged fluoro compounds (ring-contracted 2,5-anhydro-1-fluoro-1- O-methylhexitol derivatives, 2-methoxy- d-hexopyranosyl fluorides, and, for some 3-azido substrates, rearranged 2-azido-3-fluoro- d-hexopyranosides). When the reaction was performed in acetonitrile, the solvent participation as a nucleophile (Ritter reaction) was observed in one case. For a 2,4-unprotected 3-azido substrate, 2,3-dehydration and fluorination at C(4), the latter with epimerization, took place. 19F/ 1H and 19F/ 13C coupling constant values were systematically applied to discriminate between isomeric structures for fluorinated products, and for some, previously described, coming from five 3-branched-chain d- or l-hexopyranosides, thus discarding the previously reported structural assignment. From the synthetic point of view, the most outstanding result was the preparation of 2,5-anhydro-1-fluoro-1- O-methylhexitols, showing a latent formyl group functionality, a transformation, which was achieved in one case. A rationalization for the formation of the different types of product is also proposed.