Cu-Catalyzed Three-Component Alkene Carboamination: Mechanistic insights and rational design to overcome limitations
Ho, Tam D. Lee, Byung Joo Buchanan, Travis L. Heikes, Micah E. Steinert, Ryan M. Milem, E. Grace Goralski, Sean T. Wang, Ya-Nong Lee, SangHyun Lynch, Vincent M.
Ho, Tam D.
Lee, Byung Joo
Buchanan, Travis L.
Heikes, Micah E.
Steinert, Ryan M.
Milem, E. Grace
Goralski, Sean T.
Wang, Ya-Nong
Lee, SangHyun
Lynch, Vincent M.
Citations
Altmetric:
Other Names
Location
Time Period
Advisors
Original Date
Digitization Date
Issue Date
2024-08-28
Type
Article
Genre
Keywords
Addition reactions,Catalysis,Free radical reactions,Atom transfer radical addition,Reaction intermediates
Subjects (LCSH)
Citation
J. Am. Chem. Soc. 2024, https://doi.org/10.1021/jacs.4c08945, Copyright © 2024 American Chemical Society
Abstract
Herein, we report mechanistic investigations into the Cu-catalyzed three-component carboamination of alkenes with ?-halo carbonyls and aryl amines via an oxocarbenium intermediate. Monitoring the reaction reveals the formation of transient atom transfer radical addition (ATRA) intermediates with both electron-neutral and deficient vinyl arenes as well as unactivated alkenes. Based on our experimental studies and density functional theory calculations, the oxocarbenium is generated through atom transfer and subsequent intramolecular substitution. Further, mechanistic factors that dictate the regioselectivity of the nucleophilic attack onto the oxocarbenium to afford the ?-amino ester, ?-iminolactone, or ?-lactone are discussed. A strategy to overcome scope limitation with respect to unactivated alkenes is developed using the mechanistic insights gained herein. Finally, we demonstrate that under modified conditions, our Cu catalyst enables the ATRA reaction between a variety of alkyl halides and vinyl arenes/?-olefins, and we present a one-pot, two-step carbofunctionalization with an array of nucleophiles through ATRA/SN2. © 2024 American Chemical Society
Table of Contents
Description
Click on the DOI link to access the article (may not be free).
Publisher
American Chemical Society
Journal
Journal of the American Chemical Society
Book Title
Series
Digital Collection
Finding Aid URL
Use and Reproduction
Archival Collection
PubMed ID
ISSN
0002-7863