Mechanism of action of vitamin B12.: Ultrafast radical clocks provide no evidence for radical intermediates in cyclopropane models for the methylmalonyl-CoA to succinyl-CoA carbon skeleton rearrangement

To probe for free radical intermediates in the model studies for the coenzyme B-12-dependent, methylmalonyl-CoA to succinyl-CoA carbon-skeleton rearrangement, new models incorporating cyclopropane rings (unsubstituted 23 and 2-phenyl-substituted 28) at the 2-position were developed. The reaction of 23 or 28 with vitamin B-12s gives only rearranged succinate 24 or 29, respectively, with the cyclopropyl group intact. When this reaction was carried out in EtOD/D2O, a monodeuterided product, 24-d(1) or 29-d(1), was obtained and the deuterium was incorporated at the 2-position. Control reactions of the 2-phenylselenylsuccinate with tri-n-butyltin hydride yielded the ring-opened 2-propanylidenesuccinate via a free radical pathway. The results suggest that the skeletal rearrangement step in the B-12-catalyzed isomerization of methylmalonyl-CoA to succinyl-CoA occurs not by a radical pathway but by an anionic or organocobalt pathway.