B(C6F5)3-Catalyzed Formal (n+3) (n = 5,6) Cycloaddition of Bicyclo[1.1.0]butanes to Medium Bicyclo[n.1.1]alkanes

Herein, a B(C6F5)3-catalyzed formal (n+3) (n = 5,6) cycloaddition of bicyclo[1.1.0]butanes (BCBs) with imidazolidines/hexahydropyrimidines is described. The reaction provides a modular, atom-economical and efficient strategy to two libraries of synthetically challenging medium-bridged rings, 2,5-diazabicyclo[5.1.1]nonanes and 2,6-diazabicyclo[6.1.1]decanes, in moderate to excellent yields. This reaction also features simple operation, mild reaction conditions and broad substrate scope. A scale-up experiment and various synthetic transformations of products further highlight the synthetic utility. Control experiments support that the reaction mechanism involves a nucleophilic addition of imidazolidines/hexahydropyrimidines to B(C6F5)3-activated BCBs, succeeded by an intramolecular cyclization. As we know, this methodology represents the first high order (n+3) (n > 3) cycloaddition of BCBs to saturated bicyclo[n.1.1]alkanes. We anticipate that this report will promote the exploration of BCB-based high order cycloaddition chemistry to access diverse challenging medium-bridged rings.