Enantioselective Copper-Catalyzed Synthesis of Hydroxylamines via Hydrofunctionalization of Alkenes using Nitroalkanes
Name
enantioselective-copper-catalyzed-synthesis-of-hydroxylamines-via-hydrofunctionalization-of-alkenes-using-nitroalkanes.pdf
Description
Published version
Size
3.37 MB
Format
Adobe PDF
Checksum (MD5)
217bbcd87af9dca24fe6d0587cec5873
Author(s)
Law, James A
Mai, Binh Khanh
Hung, Hsuan-Min
Hendon, Tobianna
Dong, Yuyang
Zhang, Yu
Liu, Peng
Buchwald, Stephen L
Date Issued
March 10, 2026
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society
Citation
James A. Law, Binh Khanh Mai, Hsuan-Min Hung, Tobianna Hendon, Yuyang Dong, Yu Zhang, Peng Liu, and Stephen L. Buchwald. Journal of the American Chemical Society 2026 148 (11), 11431-11437.
Version
Final published version
Abstract
Herein, we report that nitroalkanes are competent electrophiles for the enantioselective copper hydride (CuH)-catalyzed alkene hydrofunctionalization of vinyl(hetero)arenes to generate hydroxylamines in good yields and with high levels of enantioselectivity. Control experiments and density functional theory (DFT) calculations suggest that the nitro group constitutes the active electrophile. The direct addition of the enantioenriched alkyl copper intermediate to the nitro group outcompetes competitive reduction or deprotonation of the nitroalkane. DFT calculations indicate that the addition of the stereoenriched alkyl copper intermediate to nitroalkane electrophiles occurs through a six-membered cyclic transition state featuring dearomatization of the vinyl arene. Overall, this process constitutes a one-step route to access enantioenriched N-alkylhydroxylamine from vinylarenes and nitroalkanes.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivatives
Persistent DSpace Link
DOI of Published Version
10.1021/jacs.5c20561
