Herein, we present a relatively green method for constructing C8-chiral substituted 5,6,7,8-tetrahydroquinoline (THQs) derivatives via palladium-catalyzed enantioselective arylation of unactivated C(sp3)-H bonds, using (S)-2-((tert-butoxycarbonyl)amino)-3,3-diphenylpropanoic acid as the chiral ligand, ArBpin as a coupling reagent, O2 as the oxidant, and H2O/t-AmylOH as the solvent under mild conditions. The reaction exhibits broad functional group tolerance and affords the desired products with good to excellent enantioselectivities (up to 99:1 er) and yields (up to 76%), even on a gram scale. The H/D exchange experiments indicate that this reaction may operate as a dynamic kinetic resolution process. Furthermore, the derivatization of butyrylcholinesterase (BuChE) inhibitors and the application of the resulting compounds in asymmetric Michael addition demonstrate the synthetic utility of this reaction.
Guo et al. (Mon,) studied this question.