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Alkyne synthesis through coupling of gem-diborylalkanes with carboxylic acid esters

Nature Synthesis volume 2, pages 413–422 (2023)Cite this article

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Abstract

Alkynes are fundamental molecular building blocks of great importance in synthetic chemistry and materials science. The efficient construction of alkynyl functionality from widely accessible functional groups is therefore highly valuable. Here we report the development of a modular synthesis of alkynes through reaction of carboxylic esters with lithiated gem-diborylalkanes and aryl triflimides. 1H, 13C and 11B NMR spectroscopic and X-ray crystallographic analyses identify and characterize an intermediate α-boryl lithium enolate, which upon triflation with an aryl triflimide followed by water quenching generates the alkyne product. The developed strategy allows a range of carboxylic acid esters to be converted into both internal and terminal alkynes, within a short reaction time, including the transformation of chiral α-substituted esters into chiral propargyl compounds without racemization. The method has been applied to the synthesis of 13C-labelled alkynes, using 13C-labelled gem-diborylmethane and 13C-labelled carboxylic esters, which enables access to 13C-labelled terminal alkyne fragments in drugs and natural products.

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Fig. 1: Modular synthesis of alkynes by coupling carboxylates with gem-diborylalkanes.
Fig. 2: 13C-labelling investigations and reaction mixture analysis.
Fig. 3: Chemoselectivity investigations for the alkynylation of multi-esters.
Fig. 4: Follow-up synthesis of the alkyne products.

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Data availability

All data are available in the main text or the Supplementary Information. Solid-state structure of I-B is freely available from the Cambridge Crystallographic Data Centre under the associated CCDC codes: 2183417.

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Acknowledgements

We thank the National Natural Science Foundation of China (number 22022113 to C.L.) and the Natural Science Foundation of Jiangsu Province (number BK20190002 to C.L.) for financial support. We also thank J. Song and K. Xiao (NJUPT) for assistance with the crystal structure analysis.

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  1. These authors contributed equally: Wei Sun, Liangxuan Xu.

Authors and Affiliations

  1. State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, China

    Wei Sun, Liangxuan Xu, Yucheng Qin & Chao Liu

  2. University of Chinese Academy of Sciences, Beijing, China

    Liangxuan Xu & Yucheng Qin

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Contributions

W.S. and L.X. conducted the experiments and collected data. Y.Q. helped to collect some data. C.L. directed the project and wrote the manuscript with input from all authors. All authors analysed the results and commented on the manuscript.

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Correspondence to Chao Liu.

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Nature Synthesis thanks Ahmad Masarwa and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Thomas West, in collaboration with the Nature Synthesis team.

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Supplementary Information

Supplementary sections 1–3, Figs. 1–5 and Tables 1 and 2.

Supplementary Data 1

Crystallographic data for compound I-B; CCDC 2183417.

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Sun, W., Xu, L., Qin, Y. et al. Alkyne synthesis through coupling of gem-diborylalkanes with carboxylic acid esters. Nat. Synth 2, 413–422 (2023). https://doi.org/10.1038/s44160-023-00243-4

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