Atom Transfer Radical Polymerization-Inspired Room Temperature (sp3)C-N Coupling

Alfred K. K. Fung, Li-Juan Yu, Michael S. Sherburn, Michelle L. Coote

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

A simple nonphotochemical procedure is reported for Cu(I)-catalyzed C-N coupling of aliphatic halides with amines and amides. The process is loosely based on the Goldberg reaction but takes place readily at room temperature. It uses Cu(I)Br, a commonly used and inexpensive atom transfer radical polymerization precatalyst, along with the cheap ligand N,N,N′,N″,N″-pentamethyldiethylenetriamine, to activate the R-X bond of the substrate via inner-sphere electron transfer. The procedure brings about productive C-N bond formation between a range of alkyl halide substrates with heterocyclic aromatic amines and amides. The mechanism of the coupling step, which was elucidated through application of computational methods, proceeds via a unique Cu(I) → Cu(II) → Cu(III) → Cu(I) catalytic cycle, involving (a) inner-sphere electron transfer from Cu(I) to the alkyl halide to generate the alkyl radical; (b) successive coordination of the N-nucleophile and the radical to Cu(II); and finally reductive elimination. In the absence of a nucleophile, debrominative homocoupling of the alkyl halide occurs. Control experiments rule out SN-type mechanisms for C-N bond formation.

Original languageEnglish
Pages (from-to)9723-9732
Number of pages10
JournalJournal of Organic Chemistry
Volume86
Issue number14
DOIs
Publication statusPublished - 16 Jul 2021
Externally publishedYes

Keywords

  • Atom
  • Polymerization
  • nonphotochemical
  • aliphatic
  • halides
  • amines
  • amides
  • inner-sphere electron transfer

Fingerprint

Dive into the research topics of 'Atom Transfer Radical Polymerization-Inspired Room Temperature (sp3)C-N Coupling'. Together they form a unique fingerprint.

Cite this