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Electrophilic functionalization of N-substituted vicinal alkynyl(amino)cyclopropanes via selective lithiation

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Abstract

N-Alkyl-N-Boc-substituted 1-amino-2-alkynylcyclopropanes undergo selective lithiation at the carbon atom in α-position relative to the triple bond under the action of BunLi in THF at −65 °C. Lithiation of the starting compounds representing mixtures of cis- and trans-isomers affords the trans-isomers of organolithium derivatives which react with electrophiles (acetaldehyde, acetone, dimethyl disulfide, CO2, methyl chloroformate, and iodomethane) to give the corresponding 2-substituted 1-amino-2-alkynylcyclopropanes in up to 93% yields exclusively as isomers with the cis-arrangement of the amino group and the incoming substituent. When DMF is used as the electrophilic reagent, the initially formed cyclopropane carbaldehyde is selectively isomerized to the corresponding dihydrofuran derivative. Reactions of 1-(N-benzyl-N-Boc-amino)-2-alkynylcyclopropanes with BunLi occur mainly at the PhCH2N group without affecting the cyclopropane ring.

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Authors and Affiliations

  1. N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991, Moscow, Russian Federation

    V. D. Gvozdev, K. N. Shavrin & M. P. Egorov

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  1. V. D. Gvozdev
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  2. K. N. Shavrin
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  3. M. P. Egorov
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Correspondence to V. D. Gvozdev.

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No human or animal subjects were used in this research.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, Vol. 72, No. 8, pp. 1781–1790, August, 2023.

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Gvozdev, V.D., Shavrin, K.N. & Egorov, M.P. Electrophilic functionalization of N-substituted vicinal alkynyl(amino)cyclopropanes via selective lithiation. Russ Chem Bull 72, 1781–1790 (2023). https://doi.org/10.1007/s11172-023-3960-5

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  • DOI: https://doi.org/10.1007/s11172-023-3960-5

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