Cu-Catalyzed Three-Component Alkene Carboamination: Mechanistic Insights and Rational Design to Overcome Limitations

• DOI: 10.1021/jacs.4c08945
• Publication Date: 2024-08-28T15:01:15Z
• Authors: Tam D. Ho; Byung Joo Lee; Travis L. Buchanan; Micah E. Heikes; Ryan M. Steinert; E. Grace Milem; Sean T. Goralski; Ya-Nong Wang; SangHyun Lee; Vincent M. Lynch; Michael J. Rose; Katie R. Mitchell...; Kami L. Hull
• Keywords: Oxocarbenium; Alkene; SN2 reaction

Herein, we report mechanistic investigations into the Cu-catalyzed three-component carboamination of alkenes with α-halo carbonyls and aryl amines via an oxocarbenium intermediate. Monitoring reaction reveals formation transient atom transfer radical addition (ATRA) intermediates both electron-neutral deficient vinyl arenes as well unactivated alkenes. Based on our experimental studies density functional theory calculations, is generated through subsequent intramolecular substitution. Further, factors that dictate regioselectivity nucleophilic attack onto to afford γ-amino ester, γ-iminolactone, or γ-lactone are discussed. A strategy overcome scope limitation respect developed using insights gained herein. Finally, demonstrate under modified conditions, Cu catalyst enables ATRA between a variety alkyl halides arenes/α-olefins, present one-pot, two-step carbofunctionalization array nucleophiles ATRA/SN2.