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Metal-free carbon–carbon bond-forming reductive coupling between boronic acids and tosylhydrazones

Nature Chemistry volume 1, pages 494–499 (2009)Cite this article

Abstract

The formation of carbon–carbon bonds is a fundamental transformation in organic synthesis. In spite of the myriad methods available, advantageous methodologies in terms of selectivity, availability of starting materials, operational simplicity, functional-group tolerance, environmental sustainability and economy are in constant demand. In this context, the development of new cross-coupling reactions that use catalysts based on inexpensive and non-toxic metals is attracting increasing attention. Similarly, efficient processes that do not require a metal catalyst are of extraordinary interest. Here, we report a new and efficient metal-free carbon–carbon bond-forming coupling between tosylhydrazones and boronic acids. This reaction is very general and functional-group tolerant. As the required tosylhydrazones are easily generated from carbonyl compounds, it can be seen as a reductive coupling of carbonyls, a process of high synthetic relevance that requires several steps using other methodologies.

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Figure 1: Possible mechanistic pathways for the reductive arylation of tosylhydrazones with aryl boronic acids.
Figure 2: Metal-free arylations of diazo compounds 5a and 5b with aryl boronic acid 2a.
Figure 3: Evidence for the formation of an alkyl boronic acid intermediate.

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Acknowledgements

This work was funded by Ministerio de Ciencia of Spain (CTQ2007-61048/BQU) and Consejería de Educación y Ciencia of Principado de Asturias (IB08-088). A FPU from predoctoral fellowship Ministerio Ciencia e Innovación of Spain to M.T.-G. is gratefully acknowledged.

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Authors and Affiliations

  1. Instituto Universitario de Química Organometálica “Enrique Moles”, Unidad Asociada al C.S.I.C. Universidad de Oviedo, Julián Clavería, 8, Oviedo, E-33006, Spain

    José Barluenga, María Tomás-Gamasa, Fernando Aznar & Carlos Valdés

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  1. José Barluenga
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  2. María Tomás-Gamasa
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  3. Fernando Aznar
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  4. Carlos Valdés
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Contributions

M.T.-G. carried out the experimental work. All authors analysed the data, discussed the results and commented on the manuscript.

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Correspondence to José Barluenga or Carlos Valdés.

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Barluenga, J., Tomás-Gamasa, M., Aznar, F. et al. Metal-free carbon–carbon bond-forming reductive coupling between boronic acids and tosylhydrazones. Nature Chem 1, 494–499 (2009). https://doi.org/10.1038/nchem.328

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