A DFT Study on the General [3 + n] (n = 2–6) Cycloaddition Reaction Mechanism of Bicyclo[1.1.0]butanyl Ketones in Borane Catalysis

Abstract Bicyclo[1.1.0]butane (BCB) is a bridged-ring compound featuring the smallest ring yet the highest ring strain, which can promote cyclization reactions. However, why is “strain release” not sufficient to directly construct eight- or nine-membered bridged-ring products, whereas this can be achieved in organoborane catalysis? Herein, we suggest that the combination of strain release and participation of a Lewis acid organoborane catalyst would lead to the occurrence of cycloaddition reactions. Density functional theory (DFT) calculations have been performed to study the possible α,γ-[3 + n] and γ,α-[3 + n] cycloaddition pathways and the origin of chemoselectivity for achiral borane BR3 catalyzed [3 + n] (n = 5, 6) cycloaddition reactions of BCB ketones. The computational results unmasked that the γ,α-[3 + n] cycloaddition pathway is more energetically favorable, and the BCB-ring-opening process is the chemoselectivity-determining step. The frontier molecular orbital (FMO) and distortion/interaction analyses indicate that the participation of BR3 catalysts can indeed diminish the cycloaddition energy barrier by narrowing the energy gap to advance the reaction, and the distortion of the BCB-part moiety is one of the most important chemoselectivity-controlling factors. Moreover, electrophilic vector F+→analysis can be utilized to predict the origin of reaction chemoselectivity. Therefore, this work would be valuable not only for designing synthetic routes to multiple small-, medium-, or even large-bridged ring skeletons in organoborane catalysis but also for expanding the applications of a novel Projection of Orbital Coefficient Vector (POCV) analysis method in the organocatalytic field.