Pd-Catalyzed Enantioselective Synthesis of 2-Methyl Indolines

Significance

Reported is the enantioselective synthesis of indolines 2 via an intramolecular Pd-mediated C-H activation-cyclization of 2-halo­anilides 1. Reaction optimization details are reported demonstrating the importance of the palladium source and ligand selection. In addition, the use of cesium carbonate as base proved crucial to achieve high yields and enantioselectivity. The substrate scope of the process was briefly explored, which demonstrated the competency of both 2-bromo- and 2-iodoanilides in the transformation. In addition, the synthesis of fused indolines 4 resulting from the activation of N-cyclo­hexyl-derived substrates 3 is also reported.