Mechanistic study of cobalt(I)-catalyzed asymmetric coupling of ethylene and enynes to functionalized cyclobutanes

Density functional theory (DFT) calculations have been performed to gain insight into the reaction mechanism of the Co(I)-catalyzed asymmetric [2 + 2] cycloaddition reaction of enyne 1a with ethylene 2 to give the functionalized cyclobutene E-4a possessing a chiral, all-carbon quaternary center in the ring framework (Science, 361, 68–72). This study reveals that the whole catalysis can be characterized via three stages: (i) oxidative dimerization followed by reductive elimination gives the intermediate IM3, (ii) the alkenyl-Co(III) metallacycloheptene IM6 formation with the addition of another equivalent ethylene via an oxidative dimerization process, (iii) β-Hydrogen elimination and reductive elimination from IM6 to result in the final product E-4a and regenerate the active speices IM1 for the next catalytic cycle. Each stage is kinetically and thermodynamically feasible for experimental realization under mild conditions, and the formation of the alkenyl-Co(III) metallacycloheptene IM6, with a barrier of 27.2 kcal mol⁻¹ (i.e., IM2 → TS4), should be the rate-determining step (RDS) during the whole catalysis. In addition, the origins of enantioselectivity and regioselectivity of the product are discussed.