Highly Regioselective Monoacylation of Unprotected Glucopyranoside Using Transient Directing‐Protecting Groups

The regioselective functionalization of monosaccharides is notoriously achieved using metal catalysis, lengthy synthetic strategies requiring protection/deprotection, various enzymes, or other methods that target cis ‐diols (and thus cannot be used with glucopyranose derivatives), In this paper, we report a new method using selected boronic acids as temporary protecting groups, and describe its application to the regioselective functionalization of methyl α‐ d ‐glucopyranoside, the most difficult monosaccharide to functionalize regioselectively. Generally, reactions of glucopyranosides may lead to a plethora of mono‐ and polyfunctionalized derivatives, yet our method gave the 3‐ O ‐acetylated, 2‐ O ‐benzoylated, and 2‐ O ‐pivaloylated derivatives of methyl α‐ d ‐glucopyranoside as major products. We focused on the use of recyclable and green temporary protecting groups (in a one‐pot reaction) and on the modulation of the intramolecular hydrogen‐bonding network using selected arylboronic acids. A complete scalable procedure leading to a single regioisomer from unprotected methyl α‐ d ‐glucopyranoside is presented.