Ca2+-Mediated Regioselective Functionalization of Unprotected Mannopyranosides

Regioselective functionalization of unprotected monosaccharides is a long-standing challenge in synthetic organic chemistry. Recent methodological developments have established transient covalent adduction and organocatalytic approaches leveraging non-covalent interactions as potential solutions to this synthetic problem. In contrast, strategies employing biomimetic metal cation chelation as a mechanism for achieving substrate selectivity and regioselectivity have been comparatively underexplored. Herein, we report a Ca2+-mediated regioselective acylation reaction of unprotected mannopyranosides. By leveraging a CaCl2/collidine system, we were able to achieve the facile generation of C2 monofunctionalized mannopyranoside products in appreciable yields and high regioselectivity. A gram scale synthesis of C2-acetyled methyl α-D-mannopyranoside expedited access to key synthetic intermediates, thereby demonstrating the practical utility of this methodology.