Palladium-catalyzed asymmetric dearomative [2π+2σ] cycloadditions of indoles with bicyclobutanes

Saturated bridged bicyclic frameworks, such as bicyclo[1.1.1]pentanes (BCPs), bicyclo[2.1.1]hexanes (BCHs), and bicyclo[3.1.1]heptanes (BCHeps) can replace planar benzene rings with the concept of "escape from flatland," which can enhance the pharmacokinetic and physicochemical properties of drug candidates and have attracted more and more research interest in recent years. Several outstanding studies have been reported on the diastereoselective dearomative [2π+2σ] cycloadditions of indoles with bicyclobutanes to form fused BCHs. Here, we report a unique approach for synthesizing chiral indoline-fused BCHs from 3-nitroindoles and bicyclo[1.1.0]butanes (BCBs) in the presence of a palladium catalyst. The palladium-catalyzed asymmetric [2π+2σ] cycloadditions were achieved through a key zwitterionic π-allyl-Pd intermediate under mild conditions, affording the products in good yields up to 99% with excellent enantiomeric ratio ( er ) values up to 99:1. The reaction mechanism and the origin of stereoselectivity were investigated by DFT calculations.