Greatly Accelerated Condensation of d‑Mannose Diacetonide with Aqueous Formaldehyde (Formalin)

Condensation of d-mannose diacetate with aqueous formaldehyde, a long known quaternary center-generating transformation, was reinvestigated to solve the hidden problem of incomplete conversion, a lasting challenge since 1979 despite many previous efforts. The mysterious cause for the retarded transformation was found to be generation of formic acid by a Cannizzaro reaction. By using additional amounts of base, the reaction time was shortened from 48 h to 100 min and the product was readily isolated in 81% yield.