How Strain-Release Determines Chemoselectivity: A Mechanistic Study of Rhodium-Catalyzed Bicyclo[1.1.0]butane Activation

Bicyclo­[1.1.0]­butane (BCB) derivatives are versatile coupling partners, and various reaction modes for their activation and transformation have been proposed. In this work, three BCB-activation modes in Rh-catalyzed BCB transformations that construct diastereoselective α-quaternary β-lactones were investigated by density functional theory calculations. Our results show that, compared with C1–C3 insertion and C–C3 oxidative addition, C2–C3 oxidative addition is more favorable. The whole catalytic cycle involves five main steps: C–H activation, oxidative addition, β-C elimination/reductive elimination, Rh walking, and aldehyde insertion/protonation. Independent gradient model, intrinsic reaction coordinate, distortion–interaction energy, and Laplacian electron-density analyses were carried out to investigate the mode of BCB activation. Our calculation also showed that aldehyde-insertion is the diastereoselectivity determining step, which is controlled by the steric effect between the ligand, methyl group, and aldehyde.