[5 + 1 + 2 + 1] vs [5 + 1 + 1 + 2] Rhodium-Catalyzed Cycloaddition Reactions of Vinylcyclopropanes with Terminal Alkynes and Carbon Monoxide: Density Functional Theory Investigations of Convergent Mechanistic Pathways and Reaction Regioselectivity

The mechanism of the Rh-catalyzed [5 + 1 + 2 + 1] cycloaddition of VCPs, terminal alkynes, and CO to yield hydroxydihydroindanones has been investigated by ωB97XD/SDD-6-31G* DFT calculations. The study has revealed the existence of two convergent cycloaddition pathways, [5 + 1 + 2 + 1] and [5 + 1 + 1 + 2], differing by only 2 kcal/mol. Both metal-catalyzed and off-metal electrocyclization/aromatization mechanisms for the final bicyclization reaction were investigated, with the traditional acid-catalyzed pathway dominating. The catalytic cycle is limited by the rate of alkyne insertion, which is consistent with mechanistic studies of the related [5 + 2] cycloaddition reaction. Monosubstituted alkyne insertion regioselectivity is kinetically controlled, with insertion via the unsubstituted alkyne terminus predominating. The alkyne insertion process does not appear to be sensitive to steric effects, with both the propyne and phenylacetylene model alkynes showing similar selectivities (TS energy differences of ca. 5 kcal/mol in both cases for the two regioisomeric transition states). C–C bond activation of disubstituted vinylcyclopropanes was investigated, suggesting that activation of the least substituted C–C bond is preferred unless an electron-withdrawing group is present on the VCP, in which case the most substituted bond will be cleaved