DFT Insight into a Strain-Release Mechanism in Bicyclo[1.1.0]butanes via Concerted Activation of Central and Lateral C–C Bonds with Rh(III) Catalysis

Transition-metal-catalyzed, strain-release-driven transformations of "spring-loaded" bicyclo[1.1.0]butanes (BCBs) are considered potent tools in synthetic organic chemistry. Previously proposed strain-release mechanisms involve either the insertion of the central C–C bond of BCBs into a metal–carbon bond, followed by β-C elimination, or the oxidative addition of the central or lateral C–C bond on the transition metal center, followed by reductive elimination. This study, employing DFT calculations on a Rh(III)-catalyzed model system in a three-component protocol involving oxime ether, BCB ester, and ethyl glyoxylate for constructing diastereoselective quaternary carbon centers, introduces an unusual strain-release mechanism for BCBs. In this mechanism, the catalytic reaction is initiated by the simultaneous cleavage of two C–C bonds (the central and lateral C–C bonds), resulting in the formation of a Rh-carbene intermediate. The new mechanism exhibits a barrier of 21.0 kcal/mol, making it energetically more favorable by 11.1 kcal/mol compared to the previously suggested most favorable pathway. This unusual reaction mode rationalizes experimental observation of the construction of quaternary carbon centers, including the excellent E-selectivity and diastereoselectivity. The newly proposed strain-release mechanism holds promise in advancing our understanding of transition-metal-catalyzed C–C bond activation mechanisms and facilitating the synthesis of transition metal carbene complexes.