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On the regioselectivity of the mononuclear copper-catalyzed cycloaddition of azide and alkynes (CuAAC). A quantum chemical topological study

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Abstract

New density functional theory (DFT) calculations show that the nature of the mechanism for the classical copper-catalyzed cycloaddition of azide to terminal alkynes—widely known as the CuAAC reaction—also depends on the ligands attached to Cu(I). Further, the topological evolution of the charge density, ρ (r), the laplacian of ρ (r), ∇2ρ(r), and its gradient field along the reaction coordinate shed light on the regioselectivity of the process. The performance of most suitable functionals for DFT calculations in this kind of system was tested.

Contour map of ∇2ρ(r) for the TS1 point of the 1,4-CuAAC reaction path (green lines denoted regions of ∇2ρ(r) >0, and black, ∇2ρ(r) <0) computed at LC-wPBE(PCM)/6-311++G(2d,2p)/6-311++G(d,p). The chosen reference plane for the line plot was N6Cu1C2

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Authors and Affiliations

  1. Departamento de Química Física, Facultad de Ciencias, Universidad de Málaga, Campus de Teatinos, s/n., 29071, Málaga, Spain

    Saturnino Calvo-Losada & José Joaquín Quirante

  2. Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Málaga, Campus de Teatinos, s/n., 29071, Málaga, Spain

    María Soledad Pino

Authors
  1. Saturnino Calvo-Losada
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  2. María Soledad Pino
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  3. José Joaquín Quirante
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Correspondence to José Joaquín Quirante.

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This paper belongs to Topical Collection QUITEL 2013

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Calvo-Losada, S., Pino, M.S. & Quirante, J.J. On the regioselectivity of the mononuclear copper-catalyzed cycloaddition of azide and alkynes (CuAAC). A quantum chemical topological study. J Mol Model 20, 2187 (2014). https://doi.org/10.1007/s00894-014-2187-7

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