CuAAC Click Reactions in the Gas Phase: Unveiling the Reactivity of Bis-Copper Intermediates

Claudio Iacobucci; Alexandre Lebon; Francesco De Angelis; Antony Memboeuf

doi:10.1002/chem.201603518

CuAAC Click Reactions in the Gas Phase: Unveiling the Reactivity of Bis-Copper Intermediates

Chemistry. 2016 Dec 23;22(52):18690-18694. doi: 10.1002/chem.201603518. Epub 2016 Nov 23.

Authors

Claudio Iacobucci¹, Alexandre Lebon¹, Francesco De Angelis², Antony Memboeuf¹

Affiliations

¹ UMR CNRS 6521, CEMCA, Université de Bretagne Occidentale, 6 Av. Le Gorgeu, CS 93837, 29238, Cedex 3, France.
² Department Physical and Chemical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy.

PMID: 27558289
DOI: 10.1002/chem.201603518

Abstract

Copper-catalysed azide alkyne cycloaddition (CuAAC) has been considered a breakthrough transformation over the last 15 years. Its debated mechanism arouses continuously growing interest. By means of a mass spectrometer modified ad hoc, the entire catalytic cycle of CuAAC reaction has been investigated in the gas phase. Ion-molecule reactions were performed inside the mass spectrometer to reproduce step-by-step, at a molecular level, the complete catalytic cycle of the click reaction. We successfully challenged the reactivity of elusive mono- and bis-copper intermediates by ion-molecule reactions leading to the production of mass-characterized triazole products, paving the way for detailed energetic studies to be performed in the gas phase. The structures of the relevant species, calculated at a DFT level, helped rationalise our experimental results.

Keywords: click chemistry; copper; cycloaddition; gas-phase reactions.