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 SN2-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.