1,2-Migrations in Free Radicals Related to Coenzyme B12 Dependent Rearrangements

Article abstract of DOI:10.1021/ja00218a020

The free radicals XC(CH3)(COOR)CH2., where X=C(=O)Me (1), C(=O)SEt (2), C(=O)OEt (3), C(=CH2)Me (4), and C6H5 (5), were generated by reaction of the corresponding bromides with (n-Bu)3SnH.The rates of rearrangement involving 1,2-migration of X (to form .C(CH3)(COOR)(CH2X)) were measured in competition with trapping by (n-Bu)3SnH.The measurements yielded the following rearrangement rate constants, k_r, and activation parameters, ΔH⁺ and ΔS⁺: (1) 1.2E4 s^-1 at 45 deg C, 11.0 kcal/mol, -4 cal/mol.K; (2) 23.5 s^-1 at 60.5 deg C, 13.8 kcal/mol, -11 cal/mol.K; (3) <10 s^-1 at 113 deg C; (4) 3.0E5 s^-1 at 45 deg C, 10.0 kcal/mol, -2 cal/mol.K; (5) 5.0E3 s^-1 at 61 deg C.From the results of crossover experiments it is concluded that the rearrangements of 1 and 2 are intramolecular processes, probably proceeding through cyclopropyloxy radical intermediates or transition states.The carbanions corresponding to 1-5 (i.e., XC(CH3)(COOR)CH2^-, generated by reduction of the corresponding bromides with sodium naphthalene) also rearrange rapidly but, in each case, with some contribution from migration of the ester group.This represents the first demonstration of spontaneous 1,2-migration of a thioester group in a free radical and models the coenzyme B12 dependent methylmalonyl-CoA mutase rearrangement.The results support a free-radical rearrangement mechanism for the latter reaction.