Haoxiang Wan, Yi Dai, Meng Sun, Pengyong Fang, Jinguo Long, Xianjie Fang
Chiral aza[3.1.0]bicyclic scaffolds and the acrylonitriles represent privileged structural motifs in numerous bioactive molecules and pharmaceuticals. Herein, we report a highly efficient palladium-catalyzed asymmetric bicyclization/cyanation reaction of propargylic ester-tethered 1,6-enynes, using Zn(CN)2 as the cyanide source. This transformation proceeds through a cascade sequence involving oxidative addition, isomerization, bicyclization, and cyanation, enabling the rapid construction of chiral aza[3.1.0]bicycles bearing an alkenyl nitrile moiety in good yields and with outstanding enantioselectivities.