The Mechanism of the Rappe Rearrangement─A Stereochemical Investigation Using Density Functional Theory

Since it was first described in the 1950s, there has been no explanation of the extraordinarily high selectivity for the formation of the thermodynamically less stable cis-2-alkenoic acids from the treatment of α,α'-dibromoketones with aqueous base. Very early on, it was suggested that such specificity must arise via "concerted processes" but without elaboration. Provided here is a detailed mechanistic description of the reaction based on computational insight, identifying a stereospecific first step for the ring closure to a 3-ring cyclopropanone, which follows Woodward-Hoffmann rules for a two-electron allylic cation, accompanied by departure of a bromine atom in an S_N2-like process. The stereochemistry established in this step persists in the second step, which involves ring opening of the 3-ring to give a cis-2-alkenoic acid. Other mechanistic pathways have higher energies. With this new understanding, further synthetic applications of the Rappe Rearrangement are suggested.