Zwitterionic π-Allyl-Pd Species Enabled 2σ+2π Cycloaddition Reactions of Vinylbicyclo1.1.0butanes (VBCBs) with Alkenes, Carbonyls, and Imines

Transition-metal-catalyzed cycloaddition reactions of strained small-ring compounds are powerful methods for constructing carbo- and heterocyclic structures of medicinal interest. However, the application of this strategy to bicyclo1.1.0butanes (BCBs), which are among the most strained carbocycles known, remains underdeveloped. Herein, we report vinylbicyclo1.1.0butane (VBCB) as a platform synthon for palladium-catalyzed formal 2σ+2π cycloaddition reactions with various 2π-components, enabling the synthesis of BCHs, oxa-BCHs, and aza-BCHs under identical reaction conditions. The zwitterionic π-allyl-Pd species generated through the palladium-catalyzed activation of VBCBs is the key to circumventing potential carbene reactivity and serves as a common intermediate for cycloadditions with diverse 2π-systems, including alkenes, aldehydes, ketones, and imines. Notably, by utilizing Pd 2 (dba) 3 and an anthracene-derived Trost ligand, a wide array of BCHs bearing two vicinal chiral centers has been prepared in a highly diastereo-, and enantioselective manner. The generality and practicality of this method have been demonstrated by a broad substrate scope, scale-up reactions, and the versatile transformation of multiple functional groups into BCH scaffolds. Preliminary mechanistic studies support the formation of the π-allyl-Pd species.