Telescoped Synthesis of [gamma]-Bromo-[beta]-Lactones from Allylic Bromides Employing Carbon Dioxide

A direct synthesis of the title compounds involving a stepwise Zn-mediated carboxylation of allylic bromides with CO2 delivering [beta], [gamma]-unsaturated carboxylic acids and a subsequent bromolactonization is reported. The described method demonstrates the use of readily prepared allylzinc bromides by the method of Knochel for fixation of CO2 employing commodity chemicals and zinc dust. This process was then optimized into a two-stage, telescoped process for the direct synthesis of [gamma]-bromo-[beta]-lactones from allyl bromides. The described strategy delivers functionalized [beta]-lactones with dual reactivity as acylating and alkylating agents, which have utility as synthetic intermediates and are attracting growing interest as proteomic tools for activity-based protein profiling.