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Exploring the regioselectivity in the cycloaddition of azides to alkynes catalyzed by dinuclear copper clusters (Cu2AAC reaction) using the topologies of ∇2 ρ (r) and ∇∇2 ρ (r)

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Abstract

The regioselectivity of the dinuclear-Cu(I)-catalyzed version of the Huisgen reaction, abbreviated in this paper to Cu2AAC, was analyzed using quantum topological methods in order to study how the electronic charge distribution evolved along different reaction paths. Electronic densities were computed at the LC-wPBE/6-311++G(2d,2p)//LC-wPBE/6-311++G(d,p) level. The presence of two copper ions in the catalyst was found to lead to an electrophilic site in the external alkyne carbon that, in a generalized Sharpless-type mechanism, undergoes an initial donor–acceptor interaction with the azide molecule, but with an inverted electrophile–nucleophile pattern when compared with the corresponding mononuclear process (CuAAC). Differences between the two competitive dinuclear-Cu(I)-catalyzed pathways, 1,4-Cu2AAC and 1,5-Cu2AAC, arise mainly from the presence of secondary interactions in the 1,5-Cu2AAC pathway and because different nitrogen atoms are involved in the formation of the second N···C bond. Overall descriptions of both processes are provided.

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Scheme 1
Fig. 1a–c
Fig. 2a–f
Fig. 3
Fig. 4a–d
Fig. 5a–b

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Notes

  1. Note that an atomic graph is not the same as a mathematical graph; see, e.g., [40].

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Acknowledgements

The authors express their gratitude for the generous allocation of time using the Picasso node of the Center of Supercomputation of the University of Málaga, and Rafael Larrosa for his assistance.

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

    S. Calvo-Losada & J. J. Quirante

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  1. S. Calvo-Losada
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  2. J. J. Quirante
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Correspondence to J. J. Quirante.

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Calvo-Losada, S., Quirante, J.J. Exploring the regioselectivity in the cycloaddition of azides to alkynes catalyzed by dinuclear copper clusters (Cu2AAC reaction) using the topologies of ∇2 ρ (r) and ∇∇2 ρ (r). J Mol Model 23, 337 (2017). https://doi.org/10.1007/s00894-017-3500-z

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