The Stereochemical Outcome of Galactosylations Is Influenced by Both the Position and Electron-Withdrawing Power of Distal Acyl Protecting Groups

The stereodirecting effect of various distal benzoyl esters on the anomeric selectivity in galactopyranosylations was investigated. It was found that esters on O-6 of galactosyl donors of the phenyl thioglycoside type had a negligible influence on the anomeric selectivity. Instead, α-selective galactosylations were observed with 4-<i>O</i>-benzoyl, 3,4-di-<i>O</i>-benzoyl, and 4,6-di-<i>O</i>-benzoyl protected galactosyl donors, with the highly electron-withdrawing <i>p</i>-nitrobenzoyl (<i>p</i>NO₂Bz) protecting group providing the most α-selective galactosylations. Furthermore, the α-selectivity was enhanced by replacing the thiophenyl aglycon functionality with the highly reactive cyclohexyl aglycon functionality. These findings enabled the successful synthesis of the biologically relevant α-d-Gal(1→4)Gal linkage. The obtained results do not suggest distal participation as a course for the observed anomeric selectivities.