Zwitterionic π‑Allyl-Pd\nSpecies Enabled\n[2σ+2π] Cycloaddition Reactions of Vinylbicyclo[1.1.0]butanes\n(VBCBs) with Alkenes, Carbonyls, and Imines

Transition-metal-catalyzed cycloaddition reactions of\nstrained\nsmall-ring compounds are powerful methods for constructing carbo-\nand heterocyclic structures of medicinal interest. However, the application\nof this strategy to bicyclo[1.1.0]butanes (BCBs), which are among\nthe most strained carbocycles known, remains underdeveloped. Herein,\nwe report vinylbicyclo[1.1.0]butane (VBCB) as a platform synthon for\npalladium-catalyzed formal [2σ+2π] cycloaddition reactions\nwith various 2π-components, enabling the synthesis of BCHs,\noxa-BCHs, and aza-BCHs under identical reaction conditions. The zwitterionic\nπ-allyl-Pd species generated through the palladium-catalyzed\nactivation of VBCBs is the key to circumventing potential carbene\nreactivity and serves as a common intermediate for cycloadditions\nwith diverse 2π-systems, including alkenes, aldehydes, ketones,\nand imines. Notably, by utilizing Pd<sub>2</sub>(dba)<sub>3</sub> and\nan anthracene-derived Trost ligand, a wide array of BCHs bearing two\nvicinal chiral centers has been prepared in a highly diastereo-, and\nenantioselective manner. The generality and practicality of this method\nhave been demonstrated by a broad substrate scope, scale-up reactions,\nand the versatile transformation of multiple functional groups into\nBCH scaffolds. Preliminary mechanistic studies support the formation\nof the π-allyl-Pd species.