Three-Carbon Dowd−Beckwith Ring Expansion Reaction versus Intramolecular 1,5-Hydrogen Transfer Reaction:  A Theoretical Study

The evolution of the primary radicals formed by addition of AIBN/HSnBu3 to methyl 1-(3-iodopropyl)-5-oxocyclopentanecarboxylate, methyl (1R*,2R*)-1-(3-iodopropyl)-2-methyl-5-oxocyclopentanecarboxylate, and methyl (1R*,2S*)-1-(3-iodopropyl)-2-methyl-5-oxocyclopentanecarboxylate in benzene has been theoretically investigated by ROMP2/6-311++G(2d,2p)//UB3LYP/6-31G(d,p) calculations taking into account the effect of solvent through a PCM−UAHF model. According to the theoretical results, for methyl 1-(3-iodopropyl)-5-oxocyclopentanecarboxylate and methyl (1R*,2S*)-1-(3-iodopropyl)-2-methyl-5-oxocyclopentanecarboxylate the major product is the cyclooctane derivative from the three-carbon ring expansion, whereas for methyl (1R*,2R*)-1-(3-iodopropyl)-2-methyl-5-oxocyclopentanecarboxylate the major product is that corresponding to the 1,5-H transposition in agreement with the experimental findings. This different behavior is a consequence of several factors determining the relative energy barriers. The methyl substituent destabilizes the ring expansion process for methyl (1R*,2R*)-1-(3-iodopropyl)-2-methyl-5-oxocyclopentanecarboxylate because of steric repulsion but favors it in the case of the β-trans-substituted substrate because it makes possible the evolution of the system along more favorable conformations. The methyl group also favors the 1,5-H transposition rendering the transposed product a tertiary radical. The second stage of the ring expansion process is stabilized by resonance.