Asymmetric Synthesis of Indolines by Pd-Catalyzed C(sp³)–H Activation

Key words

palladium - C–H activation - cooperative catalysis - indolines - phosphine ligands

Significance

The development of a new class of phosphine ligands and their application to asymmetric C–H activation is described. The ligand design incorporates several features that distinguish it from other chiral phosphine ligands: the phosphine is electron-rich, monodentate, highly tunable (R³ and R⁴ groups) and bears a C ₂-symmetric phospholane rather than P-centered chirality. These ligands display excellent reactivity and selectivity in the synthesis of the important indoline motif.

Comment

Working under the hypothesis that the C–H activation step proceeds by a concerted ­deprotonation–metallation pathway, the authors screened various ligands and carboxylic acid co-catalysts. The bulky acid shown above was found to be optimal. The authors propose that the phosphine ligand induces a chiral environment through the spatial orientation of the carboxylate ligand. Indeed, chiral acids were also found to influence selectivity.