title: Intermediates Stabilized by Tris(triazolylmethyl)amines in the CuAAC Reaction.
abstract: Tris(triazolylmethyl)amine ligands (TL) are widely used to accelerate the CuI-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, but its mechanistic role remains unclear. Using electrospray ionization mass spectrometry, we detected for the first time the trinuclear TL-CuI3-acetylide and the dinuclear TL-CuI2-acetylide complexes in aqueous solution. The apparent second-order rate constants of their reaction with an azide were 27 and 783 m-1⋅s-1when the alkyne was tethered to TL. In the catalytic system without the tether, the rate constant increased to >146 m-1⋅s-1for the TL-CuI3-acetylide, but dropped about 14-fold to approximately 55 m-1⋅s-1for the TL-CuI2-acetylide. The results indicated that TL accelerated the reaction by stabilizing the CuI2- and CuI3-acetylide and their azide-adduct intermediates, but this role is largely weakened by excess alkyne and other competing ligands under catalytic conditions.
authors.affiliation: Department of Chemistry, University of Houston, 3585 Cullen Blvd., Houston, Texas, 77204-5003, USA.
authors.forename: Haoqing
authors.identifier: http://orcid.org/0000-0002-4290-6092
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Chemistry, University of Houston, 3585 Cullen Blvd., Houston, Texas, 77204-5003, USA.
authors.forename: Chengzhi
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Chemistry, University of Houston, 3585 Cullen Blvd., Houston, Texas, 77204-5003, USA.
authors.forename: Siheng
authors.identifier: http://orcid.org/0000-0001-9582-3568
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, 1441 Moursund St., Houston, Texas, 77030, USA.
authors.forename: Yong
authors.identifier: http://orcid.org/0000-0001-5901-5440
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Chemical Engineering, Tsinghua University, Beijing, 100084, P. R. China.
authors.forename: Sijin
authors.initials: S
authors.lastname: Luozhong
authors.affiliation: Department of Chemistry, University of Houston, 3585 Cullen Blvd., Houston, Texas, 77204-5003, USA.
authors.forename: Zhiling
authors.identifier: http://orcid.org/0000-0003-3878-0391
authors.initials: Z
authors.lastname: Zhu
keywords: CuAAC; click chemistry; mass spectrometry; reactive intermediate; tri-copper acetylide