Abstract
Typical methods for the synthesis of P-stereogenic allenylphosphine derivatives depend on chirality transfer from P-stereogenic substrates and require multiple synthetic steps. Now we report a Ni-catalysed enantioselective propargylic substitution reaction for the synthesis of P-stereogenic allenylphosphine derivatives from propargylic carbonates and secondary phosphines. Using in situ generated secondary phosphines, after a reduction of the corresponding phosphine oxides, a wide range of allenylphosphine derivatives with a P-stereogenic centre were synthesized with a high enantiocontrol (up to 97% e.e.). The method was also applied to the enantioconvergent synthesis of the P,axial-stereogenic 1,3-disubstituted allenylphosphines, using secondary propargylic carbonates as substrates with excellent enantio- and diastereocontrol (up to 97% e.e. and 14:1 d.r.) without the need for racemization or symmetrization of the secondary propargylic carbonates. The chiral phosphine products were readily incorporated into transition metal complexes with retention of stereopurity. Experimental and computational mechanistic studies suggest that the process proceeds through an enantioconvergent reaction mechanism, which gives enantioenriched phosphine products from a racemic mixture of secondary propargylic carbonates.
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Data availability
All data are available in the manuscript or the Supplementary materials. Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2079669 (3av), 2079668 (3a-Ir) and 2071745 (Ni-PH). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.
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Acknowledgements
We are grateful for financial support from the National Key R&D Program of China (2018YFA0702001), NSFC (22071224, 21901235), USTC (KY2060000143) and USTC Research Funds of the Double First-Class Initiative (YD2060002010). The numerical calculations in this paper weere done on the supercomputing system in the Supercomputing Center of University of Science and Technology of China. Y. Shao of Lanzhou University is acknowledged for refinement of the XRD data of compounds 3a-Ir and Ni-PH.
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W.-H.W. carried out the experimental and data-analysis work. Y.W. carried out the computational studies. H.-T.W., P.-J.Q. and W.-N.L. performed the synthesis of the substrates. Q.-W.Z. designed the reaction, directed the project and wrote the paper with feedback from all the authors.
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Supplementary Information
Supplementary Table 1, Figs, 1–8, detailed experimental data and copies of NMR spectrum and HPLC chromatography.
Supplementary Data 1
X-ray crystallographic data for compound 3a-Ir. CCDC 2079668.
Supplementary Data 2
X-ray crystallographic data for compound 3av. CCDC 2079669.
Supplementary Data 3
X-ray crystallographic data for compound Ni-PH. CCDC 2071745.
Supplementary Data 4
.xyz file of computed structures.
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Wang, WH., Wu, Y., Wang, HT. et al. Enantioselective synthesis of P-stereogenic allenylphosphines through Ni-catalysed propargylic substitution. Nat. Synth 1, 738–747 (2022). https://doi.org/10.1038/s44160-022-00123-3
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DOI: https://doi.org/10.1038/s44160-022-00123-3