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Communication Dans Un Congrès Année : 2018

Bicyclic halogenated aminocyclopropanes as versatile precursors for the synthesis of functionalized azepanes and piperidines

Yvan Six

Résumé

A series of N-Boc protected bicyclic aminocyclopropanes substituted with two halogen atoms at the cyclopropane ring were prepared. The synthesis of a range of secondary or tertiary amines from these compounds was investigated, showing that the amine products undergo cyclopropane-ring cleavage to typically afford ring-expanded products.[1] A minor competitive pathway was identified, which can become predominant with some substrates. It involves the cleavage of the other cyclopropane bond adjacent to the nitrogen atom. Monochloro substrates can also participate in the ring expansion process, provided that relative configuration of the chlorine substituent is endo. All these transformations readily take place at room temperature, after the amine function is created, which can be done either by a reductive amination reaction or by simple deprotonation of the corresponding hydrochloride salt. In contrast, amides or N-Boc carbamate substrates require activation (e.g. heating) for the ring-expansion to proceed,[2] still on the condition that a halogen substituent is present with the endo relative configuration. 1. Chen, C.; Kattanguru, P.; Tomashenko, O. A.; Karpowicz, R.; Siemiaszko, G.; Bhattacharya, A.; Calasans, V.; Six, Y. Org. Biomol. Chem. 2017, 15, 5364. 2. This is in agreement with previous literature results; see for instance: a) Perchonock, C. D.; Lantos, I.; Finkelstein, J. A.; Holden, K. G. J. Org. Chem. 1980, 45, 1950; b) Xu, J.; Ahmed, E.-A.; Xiao, B.; Lu, Q.-Q.; Wang, Y.-L.; Yu, C.-G.; Fu, Y. Angew. Chem. Int. Ed. 2015, 54, 8231.
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hal-04370587 , version 1 (03-01-2024)

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  • HAL Id : hal-04370587 , version 1

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Yvan Six. Bicyclic halogenated aminocyclopropanes as versatile precursors for the synthesis of functionalized azepanes and piperidines. PERCH-CIC Congress X - 2018 International Congress for Innovation in Chemistry, Center of Excellence for Innovation in Chemistry - Office of the Higher Education Commission, Ministry of Education (Implementation Unit – IU, Mahidol University), Thailand, Jul 2018, Pattaya, Thailand. ⟨hal-04370587⟩
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