Cooperative Trifluoromethyl Group and Catalyst‐Enabled Regioselective 3,4‐Functionalization of Unsymmetric <i>β</i>‐<scp>CF₃</scp>‐1,3‐enynes via C–H Bond Activation

Comprehensive Summary 1‐Isoquinolin‐1(2 H )‐one skeleton exists widely in natural products, pharmaceuticals and materials. We disclose here a fluorine effect and catalyst cooperatively induced regioselective or regiospecific 3,4‐functionalization of unsymmetric 2‐CF 3 ‐1,3‐enynes. The presence of trifluoromethyl group is determinable for the regioselectivity. When the CF 3 group was replaced with the methyl or amide group, the regioselectivity decreased to a ratio of 1.3 : 1 or 1 : 1.7, respectively. For alkyl substituted β ‐CF 3 ‐1,3‐enynes, a regiospecificity was obtained. This strategy features excellent regioselectivity, broad substrate scope and high functional group tolerance. Mechanistic studies showed that C–H bond activation is the rate‐limiting step.