Evidence for Efficient Unpromoted Regioselective Reactions of Vicinal and Non-Vicinal Diols

Abstract

A 1965 publication from Angyal's laboratory reported that the cis-vicinal diol group of tetra-O-benzyl myo-inositol reacted regioselectively, sometimes exclusively, with acylating agents at the equatorial OH, but with alkylating agents at the axial OH. Recent reports by Fraser-Reid and coworkers showed that such selectivities were also found for the trans-1,3-diol of tetra-O-benzyl myo-inositol, as well as the C2-C4 hydroxyls of a di-O-allyl mannopyranoside. In addition, the latter workers reported that regioselectivities could be extended to glycosidation reactions. Thus, n-pentenyl ortho ester (NPOE) and 2-O-acyl n-pentenyl glycoside (NPG_AC) donors reacted preferentially, if not exclusively, at the equatorial OH, whereas 2-O-alkyl counterparts (NPG_ALK) gave mixtures, usually with major glycosidation occuring at the axial OH. The present manuscript examines several vicinal diols, and reports that the NPOE and (NPG_AC) donors frequently react at only one of the two hydroxy groups in good yield, whereas the corresponding benzylated donor (NPG_ALK) is less discriminating, and frequently gives lower yields. In a key experiment to examine the basis of the selectivity, it was found that the highly hindered C3 OH of 4,6-O-benzylidene methyl a-D-altropyranoside was selectively glycosylated with NPOE in 92% yield, thereby establishing that the glycosidation preference is not due to steric hindrance.