Strain-Release-Driven [4 + 1] Annulation: Leveraging Bicyclo[1.1.0]butanes as C1 Synthons via Rh(III) Carbenoid

In this paper, we describe a Cp*Rh(III)-catalyzed C–H activation/[4 + 1] annulation of sulfoxonium ylides and N -carbamoylindoles utilizing BCBs as C1 synthons for ring construction via a strain-release protocol. Through Cp*Rh(III)-catalyzed C–H activation, an organometallic precursor is formed, which is readily tied with strained bicyclobutanes (BCBs) acting like carbene species to achieve 1,1-difunctionalization of BCBs. This protocol reveals a rare transformation pathway for BCBs in transition metal catalysis and shows the potential of BCBs as C1 synthons to facilitate an unconventional reaction process. This reaction is characterized by a broad substrate scope, ample functional group tolerance, scalability, and versatile synthetic transformations. Furthermore, DFT calculations indicate that the intermediates of rhodium carbenoid and metallocyclobutane species were involved in the reaction process. Notably, the heterocyclic compound 5q exhibits promising anticancer activity, highlighting the value of this methodology.