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A decarboxylative approach for regioselective hydroarylation of alkynes

Nature Chemistry volume 8, pages 1144–1151 (2016)Cite this article

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Abstract

Regioselective activation of aromatic C–H bonds is a long-standing challenge for arene functionalization reactions such as the hydroarylation of alkynes. One possible solution is to employ a removable directing group that activates one of several aromatic C–H bonds. Here we report a new catalytic method for regioselective alkyne hydroarylation with benzoic acid derivatives during which the carboxylate functionality directs the alkyne to the ortho-C–H bond with elimination in situ to form a vinylarene product. The decarboxylation stage of this tandem sequence is envisioned to proceed with the assistance of an ortho-alkenyl moiety, which is formed by the initial alkyne coupling. This ruthenium-catalysed decarboxylative alkyne hydroarylation eliminates the common need for pre-existing ortho-substitution on benzoic acids for substrate activation, proceeds under redox-neutral and relatively mild conditions, and tolerates a broad range of synthetically useful aromatic functionality. Thus, it significantly increases the synthetic utility of benzoic acids as easily accessible aromatic building blocks.

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Figure 1: Strategies for catalytic alkyne hydroarylation and the resulting regiochemistry.
Figure 2: Model reaction for the catalyst development of decarboxylative alkyne hydroarylation.
Figure 3: Proposed divergent reactivity of a cyclometallated alkenylruthenium(II) carboxylate intermediate.
Figure 4: Mechanism-guided efforts towards catalyst improvement.

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Acknowledgements

We thank the National Science Foundation (CHE-1301409 and RII-1330840 in association with the North Dakota Experimental Program to Stimulate Competitive Research (ND EPSCoR) to P.Z. and J.Z.) and ND EPSCoR (EPS-0447679, fellowship to J.Z.) for their financial support. The work of J.F.H. and R.S. was supported by the Director, Office of Science, US Department of Energy, under Contract no. DE-AC02-05CH11231. We also thank A. Ugrinov for assistance with the X-ray diffraction data collection and analysis.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, North Dakota State University, Fargo, 58102, North Dakota, USA

    Jing Zhang & Pinjing Zhao

  2. Department of Chemistry, University of California, Berkeley, 94720, California, USA

    Ruja Shrestha & John F. Hartwig

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  1. Jing Zhang
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Contributions

J.Z. performed the experiments and data analysis. R.S. participated in the high-throughput screening experiments for catalyst development. J.Z., J.F.H. and P.Z. designed the catalytic sequence and developed the reaction conditions. P.Z. and J.F.H. prepared this manuscript with feedback from J.Z. and R.S.

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Correspondence to Pinjing Zhao.

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The authors declare no competing financial interests.

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Crystallographic data for compound 9. (CIF 616 kb)

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Zhang, J., Shrestha, R., Hartwig, J. et al. A decarboxylative approach for regioselective hydroarylation of alkynes. Nature Chem 8, 1144–1151 (2016). https://doi.org/10.1038/nchem.2602

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