A Stoichiometric Haloform Coupling for Ester Synthesis with Secondary Alcohols

Abstract The haloform reaction from methyl ketones to carboxylic acids is one of the oldest known synthetic organic reactions, which has been used in myriad applications over the decades. The corresponding reaction to produce esters is, however, less developed, as the reaction is generally limited to simple, primary alcohols that are used in solvent‐level quantities, thereby restricting the complexity of esters that can be directly formed. Herein, we detail the development of a general ester‐forming haloform coupling reaction using one equivalent of alcohol. Mechanistic and kinetic modelling studies demonstrated that the key intermediates are formed under equilibrium, which facilitated the development of conditions that are amenable to secondary alcohols.