Hydrogen‐Bond‐Mediated Aglycone Delivery (HAD): A Highly Stereoselective Synthesis of 1,2‐<i>cis</i> α‐<scp>D</scp>‐Glucosides from Common Glycosyl Donors in the Presence of Bromine

Abstract

Described herein is the expansion of the picoloyl protecting-group assisted H-bond mediated aglycone delivery (HAD) method recently introduced by our laboratory. At first it was noticed that high α-stereoselectivity is only obtained with S-ethyl glycosyl donors and only in the presence of dimethyl(methylthio)sulfonium trifluoromethanesulfonate (DMTST), in high dilution, and low temperature. Combining the mechanistic studies of the HAD reaction and bromine-promoted glycosylations allowed a very effective method to be devised that allows for highly stereoselective α-glycosidation of practically all common leaving groups (S-phenyl, S-tolyl, S/O-imidates) at regular concentrations and ambient temperature.