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A short and efficient formal synthesis of (R)-pipecolic acid from the ring expansion of chiral aziridine

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Abstract

Ring expansion of 4-[(2R)-1-[(1R)-1-phenylethyl]aziridin-2-yl]butyl tosylate obtained from tosylation of 4-[(2R)-1-[(1R)-1-phenylethyl]aziridin-2-yl]butan-1-ol via formation of 1-azabicyclo[4.1.0]heptane tosylate gives substituted piperidine. The ring openings of azabicycloheptane tosylate with acetate nucleophiles proceeded in highly regio- and stereoselective manner with release of the ring-strain of the three-membered aziridine ring through the breakage of either C-N bond. This ring expansion streategy of aziridine provides a short route for asymmetric synthesis of biologically active natural alkaloid such as (R)-pipecolic acid.

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Data availability

1H NMR and 13C NMR of compounds are available as Supplementary Information.

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Acknowledgements

S.T.K. thanks the Ministry of Tribal Affairs (India) for the award of fellowships. For FT-NMR (both proton and carbon) as well as HRMS data, SAIF- CSIR-Central Drugs Research Institute (CDRI), Lucknow (India) was very helpful and provided all the necessary data.

Funding

Ministry of Tribal Affairs (MOTA),Govt. of India, 201819-NFST-ARU-01552, Sonam Tashi Khom

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Authors and Affiliations

  1. Department of Chemistry, North Eastern Regional Institute of Science and Technology (NERIST), Nirjuli, Arunachal Pradesh, 791109, India

    Archana Pareek, Sonam Tashi Khom, Pranjit Saikia & Nagendra Nath Yadav

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  1. Archana Pareek
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  2. Sonam Tashi Khom
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  3. Pranjit Saikia
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  4. Nagendra Nath Yadav
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Correspondence to Nagendra Nath Yadav.

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Pareek, A., Khom, S.T., Saikia, P. et al. A short and efficient formal synthesis of (R)-pipecolic acid from the ring expansion of chiral aziridine. Monatsh Chem 155, 525–529 (2024). https://doi.org/10.1007/s00706-024-03187-3

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  • DOI: https://doi.org/10.1007/s00706-024-03187-3

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