4,6‐ <i>O</i> ‐Phenylboronic Ester Protection for 1,2‐ <i>cis</i> ‐α‐Selective Glucosylation

Abstract 1,2‐ cis ‐α‐Selective glucosylation is highly desirable for synthesis of naturally occurring, biologically important α‐glucosides; however, its implementation remains challenging due to the absence of conventional neighboring group participation. In this study, we reinvestigated the α‐glucosylation using 4,6‐ O ‐phenylboronic ester‐protected thioglycoside donor, originally reported by Crich and coworkers in 2003. We report that methyl trifluoromethanesulfonate promoted glucosylation using glucosyl and 2‐azido‐2‐deoxyglucosyl donors in CH 2 Cl 2 under reflux conditions, achieving good to excellent α‐selectivity (up to α/β = &gt;20/1). Notably, the stereodirecting effect of 4,6‐ O ‐phenylboronic ester protection was greater than that of 4,6‐benzylidene protection. Mechanistic insight into the origin of the α‐selectivity in the glucosylation, obtained from substrate scope results and density function theory calculations, proposed an S N 1 pathway via the formation of an unprecedented borate‐type oxocarbenium intermediate favoring α‐selective nucleophilic attack. The phenyl boronic ester protecting group can be readily and quantitatively removed by phase‐switching aqueous workup using 1.0 m solution of d ‐sorbitol and Na 2 CO 3 after the glucosylation.