title: Direct evidence of a dinuclear copper intermediate in Cu(I)-catalyzed azide-alkyne cycloadditions.
abstract: Copper(I)-catalyzed azide-alkyne cycloaddition has become a commonly employed method for the synthesis of complex molecular architectures under challenging conditions. Despite the widespread use of copper-catalyzed cycloaddition reactions, the mechanism of these processes has remained difficult to establish due to the involvement of multiple equilibria between several reactive intermediates. Real-time monitoring of a representative cycloaddition process via heat-flow reaction calorimetry revealed that monomeric copper acetylide complexes are not reactive toward organic azides unless an exogenous copper catalyst is added. Furthermore, crossover experiments with an isotopically enriched exogenous copper source illustrated the stepwise nature of the carbon-nitrogen bond-forming events and the equivalence of the two copper atoms within the cycloaddition steps.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: B T
authors.initials: BT
authors.lastname: Worrell
authors.forename: J A
authors.initials: JA
authors.lastname: Malik
authors.forename: V V
authors.initials: VV
authors.lastname: Fokin
references.citation: J Org Chem. 2002 May 3;67(9):3057-64
references.pmid: 11975567
references.citation: Chem Rev. 2008 Aug;108(8):2952-3015
references.pmid: 18698735
references.citation: Angew Chem Int Ed Engl. 2009;48(43):8018-21
references.pmid: 19774581
references.citation: Angew Chem Int Ed Engl. 2005 Jul 11;44(28):4302-20
references.pmid: 15997457
references.citation: Eur J Med Chem. 2010 Oct;45(10):4631-9
references.pmid: 20708826
references.citation: Angew Chem Int Ed Engl. 2002 Jul 15;41(14):2596-9
references.pmid: 12203546
references.citation: J Am Chem Soc. 2007 Oct 24;129(42):12705-12
references.pmid: 17914817
references.citation: Org Lett. 2002 Dec 26;4(26):4727-9
references.pmid: 12489972
references.citation: J Am Chem Soc. 2006 Dec 27;128(51):16514-5
references.pmid: 17177396
references.citation: Angew Chem Int Ed Engl. 2007;46(12):2101-3
references.pmid: 17300119
references.citation: J Am Chem Soc. 2005 Jan 12;127(1):210-6
references.pmid: 15631470
references.citation: J Org Chem. 2010 Oct 1;75(19):6540-8
references.pmid: 20806948
references.citation: Chem Commun (Camb). 2007 Oct 7;(37):3868-70
references.pmid: 18219789
references.citation: Angew Chem Int Ed Engl. 2005 Apr 8;44(15):2210-5
references.pmid: 15693051
references.citation: Angew Chem Int Ed Engl. 2010 Mar 29;49(14):2607-10
references.pmid: 20198674
references.citation: Chem Soc Rev. 2010 Apr;39(4):1302-15
references.pmid: 20309487
references.citation: J Am Chem Soc. 2011 Sep 7;133(35):13984-4001
references.pmid: 21809811
references.citation: Angew Chem Int Ed Engl. 2009;48(38):6954-71
references.pmid: 19681081
references.citation: J Am Chem Soc. 2009 Aug 12;131(31):11249-55
references.pmid: 19610646
references.citation: Angew Chem Int Ed Engl. 2003 Nov 17;42(44):5400-49
references.pmid: 14618572