Mechanistic studies on the Cu-catalyzed three-component reactions of sulfonyl azides, 1-alkynes and amines, alcohols, or water

Dichotomy via a common pathway

Jeong Yoo Eun, Mårten Ahlquist, Imhyuck Bae, K. Barry Sharpless, Valery V. Fokin, Sukbok Chang

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

(Chemical Equation Presented) Combined analyses of experimental and computational studies on the Cu-catalyzed three-component reactions of sulfonyl azides, terminal alkynes and amines, alcohols, or water are described. A range of experimental data including product distribution ratio and trapping of key intermediates support the validity of a common pathway in the reaction of 1-alkynes and two distinct types of azides substituted with sulfonyl and aryl(alkyl) groups. The proposal that bimolecular cycloaddition reactions take place initially between triple bonds and sulfonyl azides to give N-sulfonyl triazolyl copper intermediates was verified by a trapping experiment. The main reason for the different outcome from reactions between sulfonyl and aryl(alkyl) azides is attributed to the lability of the N-sulfonyl triazolyl copper intermediates. These species are readily rearranged to another key intermediate, ketenimine, into which various nucleophiles such as amines, alcohols, or water add to afford the three-component coupled products: amidines, imidates, or amides, respectively. In addition, the proposed mechanistic framework is in good agreement with the obtained kinetics and competition studies. A computational study (B3LYP/LACV3P*+) was also performed confirming the proposed mechanistic pathway that the triazolyl copper intermediate plays as a branching point to dictate the product distribution.

Original languageEnglish
Pages (from-to)5520-5528
Number of pages9
JournalJournal of Organic Chemistry
Volume73
Issue number14
DOIs
Publication statusPublished - 18 Jul 2008
Externally publishedYes

Fingerprint

Alkynes
Azides
Amines
Alcohols
Copper
Water
Imidoesters
Amidines
Nucleophiles
Cycloaddition
Amides
Kinetics
Experiments

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Mechanistic studies on the Cu-catalyzed three-component reactions of sulfonyl azides, 1-alkynes and amines, alcohols, or water : Dichotomy via a common pathway. / Eun, Jeong Yoo; Ahlquist, Mårten; Bae, Imhyuck; Sharpless, K. Barry; Fokin, Valery V.; Chang, Sukbok.

In: Journal of Organic Chemistry, Vol. 73, No. 14, 18.07.2008, p. 5520-5528.

Research output: Contribution to journalArticle

Eun, Jeong Yoo ; Ahlquist, Mårten ; Bae, Imhyuck ; Sharpless, K. Barry ; Fokin, Valery V. ; Chang, Sukbok. / Mechanistic studies on the Cu-catalyzed three-component reactions of sulfonyl azides, 1-alkynes and amines, alcohols, or water : Dichotomy via a common pathway. In: Journal of Organic Chemistry. 2008 ; Vol. 73, No. 14. pp. 5520-5528.
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