A regioselective etherification of pyridoxine via an ortho-pyridinone methide intermediate

The catalyst-free, regioselective synthesis of 4′-O-substituted pyridoxine derivatives under solventless conditions is described. The methodology relies on the highly regioselective formation of the ortho-pyridinone methide from pyridoxine and subsequent oxa-Michael addition of alcohol nucleophiles. This methodology provides good to excellent yields for primary and secondary alcohols and moderate yields for tertiary alcohols.