biostudies-literatureChang YBoston CollegeAlfred P. Sloan FoundationNational Institute of General Medical SciencesNIGMS NIH HHS2441-2455https://www.ebi.ac.uk/biostudies/studies/S-EPMC8058014biostudies-literatureUnknown143(5)We disclose a catalytic method for β-C(sp³)-H functionalization of <i>N</i>-alkylamines for the synthesis of enantiomerically enriched β-substituted amines, entities prevalent in pharmaceutical compounds and used to generate different families of chiral catalysts. We demonstrate that a catalyst system comprising of seemingly competitive Lewis acids, B(C₆F₅)₃, and a chiral Mg- or Sc-based complex, promotes the highly enantioselective union of <i>N</i>-alkylamines and α,β-unsaturated compounds. An array of δ-amino carbonyl compounds was synthesized under redox-neutral conditions by enantioselective reaction of a <i>N</i>-alkylamine-derived enamine and an electrophile activated by the chiral Lewis acid co-catalyst. The utility of the approach is higJournal of the American Chemical SocietyEnantioselective Synthesis of <i>N</i>-Alkylamines through β-Amino C-H Functionalization Promoted by Cooperative Actions of B(C₆F₅)₃ and a Chiral Lewis Acid Co-Catalyst.PMC8058014GM-128695R35 GM128695Cao MZhao CWasa MYang RChan JZWang YChang YfalseEnantioselective Synthesis of <i>N</i>-Alkylamines through β-Amino C-H Functionalization Promoted by Cooperative Actions of B(C₆F₅)₃ and a Chiral Lewis Acid Co-Catalyst.We disclose a catalytic method for β-C(sp³)-H functionalization of <i>N</i>-alkylamines for the synthesis of enantiomerically enriched β-substituted amines, entities prevalent in pharmaceutical compounds and used to generate different families of chiral catalysts. We demonstrate that a catalyst system comprising of seemingly competitive Lewis acids, B(C₆F₅)₃, and a chiral Mg- or Sc-based complex, promotes the highly enantioselective union of <i>N</i>-alkylamines and α,β-unsaturated compounds. An array of δ-amino carbonyl compounds was synthesized under redox-neutral conditions by enantioselective reaction of a <i>N</i>-alkylamine-derived enamine and an electrophile activated by the chiral Lewis acid co-catalyst. The utility of the approach is hig2021-01-01T00:00:00Z2021 Feb2025-04-18T21:40:51.454Z2022-02-09T15:50:35.609ZS-EPMC80580143351299810.1021/jacs.0c13200