Stereoselective construction of fused cyclopropane from ynamide and its application to synthesis of small drug candidate molecules

Abstract

Herein, we report the development of an asymmetric intramolecular cyclopropanation reaction under silver catalysis. The strategy is based on diazo-free silver–carbene generation, providing γ-lactam fused cyclopropane in an enantioenriched form. The ring system of the product is frequently encountered in bioactive molecules and pharmaceuticals. To highlight the utility of this method, the fused cyclopropane was converted into drug candidate molecules in short steps. In addition, computational investigations were performed to elucidate the reaction pathway. The computation based on density functional theory rationalized the experimentally observed chemoselectivity between the desired cyclopropanation and overoxidation process.