DFT Study on Rhodium-Catalyzed Intermolecular [2+2] Cycloaddition of Terminal Alkynes with Electron-Deficient Alkenes

Density functional theory (DFT) calculations with the B3LYP functionals elucidated the reactivity, selectivity, and mechanisms of a rhodium-catalyzed intermolecular [2 + 2] cycloaddition of terminal alkynes with electron-deficient alkenes. The most plausible reaction pathway was discussed as three distinct processes in full catalytic cycles, including (1) substrate exchange, (2) nucleophilic addition and cyclization, and (3) separation of product and recycling of catalyst; the formal [2 + 2] cycloaddition indeed proceeded through a rate-determining and stepwise addition cyclization process. We then compared the outer-sphere and inner sphere mechanisms for the formation of cyclobutene intermediates and reported that the former pathway is more accessible kinetically and thus more competitive, being contrary to the proposed mechanism for some nickel-catalyzed cycloaddition reactions in the literature. Furthermore, the substituent effect has been investigated using various alkenes CH2=CHR (R = COOMe, CN, H, CH3) as reaction partners, which disclosed that the reaction pathway for electron-deficient alkenes was mediated by a zwitterion intermediate, whereas that for electron-neutral alkenes was characterized as a diradical-like mechanism with an inaccessible free energy barrier of more than 46 kcal mol(-1). In addition, the effects of ligand and base have been discussed in detail from the perspective of Houk's distortion/interaction model, providing a valuable case study for understanding the roles played by different phosphine ligands and additives.