Ring Expansion toward Fused Diazabicyclo[3.1.1]heptanes through Lewis Acid Catalyzed Highly Selective C−C/C−N Bond Cross‐Exchange Reaction between Bicyclobutanes and Diaziridines
Heng-Xian He, Feng Wu, Xu Zhang, Jian‐Jun Feng
Abstract
Abstract The synthesis of bicyclic scaffolds has garnered considerable interest in drug discovery because of their ability to mimic benzene bioisosteres. Herein, we introduce a new approach that utilizes a Lewis acid (Sc(OTf) 3 )‐catalyzed σ‐bond cross‐exchange reaction between the C−C bond of bicyclobutanes and the C−N bond of diaziridines to produce multifunctionalized and medicinally interesting azabicyclo[3.1.1]heptane derivatives. The reaction proceeds well with different bicyclobutanes and a broad range of aryl‐ as well as alkenyl‐, but also alkyl‐substituted diaziridines (up to 98 % yield). Conducting a scale‐up experiment and exploring the synthetic transformations of the cycloadducts emphasized the practical application of the synthesis. Furthermore, a zinc‐based chiral Lewis acid catalytic system was developed for the enantioselective version of this reaction (up to 96 % ee ).