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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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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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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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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DOI: https://doi.org/10.1038/s44160-023-00243-4
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