Eco-friendly conjugate hydrocyanation of α-cyanoacrylates using potassium hexacyanoferrate(II) as cyanating reagent


The conjugate hydrocyanation of α-cyanoacrylates through chemoselective 1,4-addition to synthesise α,β-dicyanopropanoates by one-pot two-step procedure using potassium hexacyanoferrate(II) as an eco-friendly cyanide source, benzoyl chloride as a promoter and potassium carbonate as a catalyst is described. The advantages of this protocol are use of a non-toxic, non-volatile and inexpensive cyanating reagent, high product yields and simple working procedure

  • Aizencang, G., Frydman, R. B., Giorgieri, S., Sambrotta, L., Guerra, L., & Frydman, B. (1995). Synthesis of isoornithines and methylputrescines. An evaluation of their inhibitory effects on ornithine decarboxylase. Journal of Medicinal Chemistry, 38, 4337-4341. DOI: 10.1021/jm00021a024.

  • Das, S., Yasmin, H., Masud, M. M., Roy, S. C., Nahar, L., Rahman, M. M., Gibbons, S., Bachar, S. C., & Sarker, S. D. (2008). Total synthesis and analgesic activity of 6- fluoroindan-1-carboxylic acid. Tetrahedron, 64, 8642-8645. DOI: 10.1016/j.tet.2008.07.010.

  • Griffiths, G., Mettler, H., Mills, L. S., & Previdoli, F. (1991). Novel syntheses of gabapentin via addition of hydrocyanic acid to cyclohexylidenemalonate or cyano(cyclohexylidene) acetate. Helvetica Chimica Acta, 74, 309-314. DOI: 10.1002/ hlca.19910740208.

  • Li, Z., Shi, S. Y., & Yang, J. Y. (2006). AgI-PEG400-KI catalyzed environmentally benign synthesis of aroyl cyanides using potassium hexacyanoferrate(II) as the cyanating agent. Synlett, 2006, 2495-2497. DOI: 10.1055/s-2006-950407.

  • Li, Z., Tian, G. Q., & Ma, Y. H. (2010). One-pot threecomponent solvent-free cyanoaroylation of aldehydes using potassium hexacyanoferrate(II) as environmentally benign cyanide source. Synlett, 2010, 2164-2168. DOI: 10.1055/s-0030-1258495.

  • Li, Z., Liu, C. H., Zhang, Y. P., Li, R. Z.,Ma, B., & Yang, J. Y. (2012). Conjugate hydrocyanation of aromatic enones using potassium hexacyanoferrate(II) as an eco-friendly cyanide source. Synlett, 23, 2567-2571. DOI: 10.1055/s-0032-1317179.

  • Li, Z., Li, R. Z., Zheng, H. H.,Wen, F., Li, H. B., Yin, J. J., & Yang, J. Y. (2013). Hydrocyanation of sulfonylimines using potassium hexacyanoferrate(II) as an eco-friendly cyanide source. Journal of the Brazilian Chemical Society, 24, 1739-1743. DOI: 10.5935/0103-5053.20130218.

  • Li, Z., & Xu, J. (2014). Solvent-free synthesis of arylsulfonyl cyanides using potassium hexacyanoferrate(II) as an ecofriendly cyanide source. Phosphorus, Sulfur, and Silicon and the Related Elements, 189, 374-378. DOI: 10.1080/10426507.2013.819870.

  • Liu, Y., Shirakawa, S., & Maruoka, K. (2013). Phase-transfercatalyzed asymmetric conjugate cyanation of alkylidenemalonates with KCN in the presence of a Brønsted acid additive. Organic Letters, 15, 1230-1233. DOI: 10.1021/ol4001 43m.

  • Mazet, C., & Jacobsen, E. N. (2008). Dinuclear {(salen)Al} complexes display expanded scope in the conjugate cyanation of α,β-unsaturated imides. Angewandte Chemie International Edition, 47, 1762-1765. DOI: 10.1002/anie.200704461.

  • Mita, T., Sasaki, K., Kanai, M., & Shibasaki, M. (2005). Catalytic enantioselective conjugate addition of cyanide to α,β- unsaturated N-acylpyrroles. Journal of the American Chemical Society, 127, 514-515. DOI: 10.1021/ja043424s.

  • Rajib, K. P., Hasina, Y., Lutfun, N., Bidyut, K. D., Abul, K. A. C., Joydeb, K. K., Siteh, C. B., & Satyajit, D. S. (2012). Synthesis of 5,6-dichloroindan-1-acids and their tetrazolyl derivatives as analgesic and anti-inflammatory agents. Medicinal Chemistry, 8, 874-882. DOI: 10.2174/157340612802084234.

  • Rappoport, Z. (1970). The chemistry of the cyano group. New York, NY, USA: Interscience Publishers. DOI: 10.1002/9780 470771242.

  • Ren, Y. L., Dong, C. H., Zhao, S., Sun, Y. P., Wang, J. J., Ma, J. Y., & Hou, C. D. (2012). Copper-catalyzed cyanation of benzyl chlorides with non-toxic K4[Fe(CN)6]. Tetrahedron Letters, 53, 2825-2827. DOI: 10.1016/j.tetlet.2012.03.109.

  • Saha, D., Adak, L., Mukherjee, M., & Ranu, B. C. (2012). Hydroxyapatite-supported Cu(I)-catalysed cyanation of styrenyl bromides with K4[Fe(CN)6]: an easy access to cinnamonitriles. Organic & Biomolecular Chemistry, 10, 952-957. DOI: 10.1039/c1ob06467c.

  • Sammelson, R. E., Caboni, P., Durkin, K. A., & Casida, J. E. (2004). GABA receptor antagonists and insecticides: common structural features of 4-alkyl-1-phenylpyrazoles and 4- alkyl-1-phenyltrioxabicyclooctanes. Bioorganic & Medicinal Chemistry, 12, 3345-3355. DOI: 10.1016/j.bmc.2004.03.069.

  • Sammis, G. M., Danjo, H., & Jacobsen, E. N. (2004). Cooperative dual catalysis: Application to the highly enantioselective conjugate cyanation of unsaturated imides. Journal of the American Chemical Society, 126, 9928-9929. DOI: 10.1021/ja046653n.

  • Schareina, T., Zapf, A., & Beller, M. (2004). Improving palladium-catalyzed cyanation of aryl halides: Development of a state-of-the-art methodology using potassium hexacyanoferrate( II) as cyanating agent. Journal of Organometallic Chemistry, 689, 4576-4583. DOI: 10.1016/j.jorganchem. 2004.08.020.

  • Wakita, Y., Kojima, M., Schwendner, S. W., McConnell, D., & Counsell, R. E. (1990). The synthesis and biodistribution of 3-(4_-[125I]-iodophenyl)-4-aminobutyric acid, a radioiodinated analogue of baclofen. Journal of Labelled Compounds and Radiopharmaceuticals, 28, 123-136. DOI: 10.1002/jlcr.2580280202.

  • Wang, J., Li, W., Liu, Y. L., Chu, Y. Y., Lin, L. L., Liu, X. H., & Feng, X. M. (2010). Asymmetric cyanation of activated olefins with ethyl cyanoformate catalyzed by a modular titanium catalyst. Organic Letters, 12, 1280-1283. DOI: 10.1021/ol100169r.

  • Yang, J. Y., Wang, Y. X., Wu, S. X., & Chen, F. X. (2009). The highly efficient 1,4-addition of TMSCN to aromatic enones catalyzed by CsF with water as the additive. Synlett, 2009, 3365-3367. DOI: 10.1055/s-0029-1218376.

  • Yang, J. Y., Wu, S. X., & Chen, F. X. (2010). Chiral sodium phosphate catalyzed enantioselective 1,4-addition of TMSCN to aromatic enones. Synlett, 2010, 2725-2728. DOI: 10.1055/s-0030-1258817.

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