New photocyclization of 2-(tert-butoxycarbonyl) amino-3,3-dichloroacrylonitrile

Authors

DOI:

https://doi.org/10.15407/dopovidi2022.05.079

Keywords:

intramolecular [2 2] cycloaddition, 2-amino-3,3-dichloroacrylonitrile, 2,4-methanoproline nitrile

Abstract

For the first time, a 2-(allylamino)-3, 3-dichloroacrylonitrile derivative was used in a photoinitiated intramolecular [2+2] cycloaddition, which led to the formation of N-Boc-protected 5, 5-dichloro-2-azabicyclo[2. 1. 1]- hexane-1-carbonitrile — a unique 2-azabicyclo[2. 1. 1]hexane derivative with nitrile group and dichloromethylene moiety. Intramolecular [2+2] photocyclization of 2-(allylamino)acrylates is the foremost way to build 2, 4-methanoprolines, that are still a small group conformationally rigid analogue of Proline derivatives. But this reaction has not been studied for the corresponding acrylonitriles. The capable substrate for [2+2] photocyclization — tert-butyl allyl(2, 2-dichloro-1-cyanovinyl)carbamate — was synthesized by us in high yield from available reagents. Simple synthetic techniques was using: one pot conversion tert-butyl (2, 2, 2-trichloro-1-hydroxyethyl) carbamate to tert-butyl (2, 2-dichloro-1-cyanovinyl)carbamate with subsequent N-allylation. Intramolecular [2+2] cycloaddition was carried out in acetonitrile solution by irradiation with the light of 368 nm wavelength; the use of xanthone instead of the standard photosensitizer acetophenone can reduce the time of target product formation from 12 to 6 hours. The successful using of substituted 2-amino-3, 3-dichloroacrylonitrile in photochemical isomerization make it possible to consider these compounds as promising substrates for the synthesis of bridged bicyclic amines.

Downloads

Download data is not yet available.

References

Trabocchi, A., Scarpi, D. & Guarna, A. (2007). Structural diversity of bicyclic amino acids. Amino Acids, 34, Iss. 1, pp. 1-24. https://doi.org/10.1007/s00726-007-0588-y

Wu, G., Kou, B., Tang, G., Zhu, W., Shen, H. C., Liu, H. & Hu, T. (2016). Synthesis of novel and conformationally constrained bridged amino acids as compact modules for drug discovery. Tetrahedron Lett., 57, Iss. 5, pp. 599-602. https://doi.org/10.1016/j.tetlet.2015.12.097

Mikhailiuk, P. K., Afonin, S., Chernega, A. N., Rusanov, E. B., Platonov, M. O., Dubinina, G. G., Berditsch, M., Ulrich, A. S. & Komarov, I. V. (2006). Conformationally rigid trifluoromethyl-substituted α-amino acid designed for peptide structure analysis by solid-state 19F NMR spectroscopy. Angew. Chem., 118, Iss. 34, pp. 5787-5789. https://doi.org/10.1002/ange.200600346

Hughes, P., Martin, M. & Clardy, J. (1980). Synthesis of 2, 4-methanoproline. Tetrahedron Lett., 21, Iss. 48, pp. 4579-4580. https://doi.org/10.1016/0040-4039(80)80078-5

Elliott, L. D., Kayal, S., George, M. W. & Booker-Milburn, K. (2020). Rational design of triplet sensitizers for the transfer of excited state photochemistry from UV to visible. J. Am. Chem. Soc., 142, Iss. 35, pp. 14947-14956. https://doi.org/10.1021/jacs.0c05069

Mykhailiuk, P., Kubyshkin, V., Bach, T. & Budisa, N. (2017). A peptidyl-prolyl model study: how does the electronic effect influence the amide bond conformation? J. Org. Chem., 82, Iss. 17, pp. 8831-8841. https://doi.org/10.1021/acs.joc.7b00803

Esslinger, C. S., Koch, H. P., Kavanaugh, M. P., Philips, D. P., Chamberlin, A. R., Thompson, C. M. & Bridges, R. J. (1998). Structural determinants of substrates and inhibitors: probing glutamate transporters with 2, 4-methanopyrroldidine-2, 4-dicarboxylate. Bioorg. Med. Chem. Lett., 8, Iss. 21, pp. 3101-3106. https://doi.org/10.1016/S0960-894X(98)00560-5

Kurasawa, O., Miyazaki, T., Homma, M., Oguro, Y., Imada, T., Uchiyama, N., Iwai, K., Yamamoto, Y., Ohori, M., Hara, H., Sugimoto, H., Iwata, K., Skene, R., Hoffman, I., Ohashi, A., Nomura, T. & Cho, N. (2020). Discovery of a novel, highly potent, and selective thieno[3, 2-d]pyrimidinone-based Cdc7 inhibitor with a quinuclidine moiety (TAK-931) as an orally active investigational anti-tumor agent. J. Med. Chem., 63, Iss. 3, pp. 1084-1104. https://doi.org/10.1021/acs.jmedchem.9b01427

Juvvadi, P., Dooley, D. J., Humblet, C. C., Lu, G. H., Lunney, E. A., Panek, R. L., Skeean, R. & Marshall, G. R. (1992). Bradykinin and angiotensin II analogs containing a conformationally constrained proline analog. Int. J. Pept. Protein Res., 40, Iss. 3-4, pp. 163-170. https://doi.org/10.1111/j.1399-3011.1992.tb00289.x

Henness, S. & Keam, S. J. (2006). Vildagliptin. Drugs, 66, Iss. 15, pp. 1989-2001. https://doi.org/10.2165/00003495-200666150-00007

Pat. WO2006040625A1, Novel dipeptidyl peptidase IV inhibitors, pharmaceutical compositions containing them, and process for their preparation, Thomas, A., Gopalan, B., Lingam, P. R. V. S. & Shah, D. M. (Glenmark Pharmaceuticals SA), Publ. ·20. 04. 2006.

Drach, B. S., Brovaret, V. S., & Smolii, B. S. (1992). Syntheses of nitrogen-containing heterocyclic compounds based on amidoalkylation agents. Kyiv: Naukova Dumka (in Russian).

Vidal J., Hannachi J. -C., Hourdin G., Mulatier J. -C. & Collet A. (1998). N-Boc-3-trichloromethyloxazi ridine: a new, powerful reagent for electrophilic amination. Tetrahedron Lett., 39, Iss. 48, pp. 8845-884. https://doi.org/10.1016/S0040-4039(98)01983-2

Published

28.10.2022

How to Cite

Melnychuk П. ., Shablykin О. ., & Shablykina О. . (2022). New photocyclization of 2-(tert-butoxycarbonyl) amino-3,3-dichloroacrylonitrile. Reports of the National Academy of Sciences of Ukraine, (5), 79–86. https://doi.org/10.15407/dopovidi2022.05.079