Synthesis of 1,2,4-Oxadiazoles via DDQ-Mediated Oxidative Cyclization of Amidoximes

Abstract

An oxidative cyclization of amidoximes to form 1,2,4-oxadiazoles, mediated by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), is described. A range of alkyl, aryl, and heteroaryl substrates are tolerated under these conditions. This reaction serves as an alternate approach for the synthesis of functionally diverse oxadiazoles via a rapid and straightforward synthetic procedure.

Key words

oxidation - cyclization - heterocycles - radicals - medicinal chemistry

• References

• 1 Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257
• 2 For a review of the synthesis and applications of 1,2,4-oxadiazoles, see: Pace A, Pierro P. Org. Biomol. Chem. 2009; 7: 4337
• 3 Maftei CV, Fodor E, Jones PG, Franz MH, Kelter G, Fiebig H, Neda I. Beilstein J. Org. Chem. 2013; 9: 2202
• 4a Coupar IM, Hedges A, Metcalfe HL, Turner P. J. Pharm. Pharmacol. 1969; 21: 474
• 4b Tully WR, Gardner CR, Gillespie RJ, Westwood R. J. Med. Chem. 1991; 34: 2060
• 4c Rotbart HA. Antiviral Res. 2002; 53: 83
• 4d Ledford RM, Collett MS, Pevear DC. Antiviral Res. 2005; 68: 135
• 4e Wilschanski M, Miller LL, Shoseyov D, Blau H, Rivlin J, Aviram M, Cohen M, Armoni S, Yaakov Y, Pugatch T, Cohen-Cymberknoh M, Miller NL, Reha A, Northcutt VJ, Hirawat S, Donnelly K, Elfring GL, Ajayi T, Kerem E. Eur. Respir. J. 2011; 38: 59
• 4f Rele RV, Sawant SA. J. Chem. Pharm. Res. 2015; 7: 865
• 5 Terenzi A, Barone G, Piccionello AP, Giorgi G, Guarcello A, Pace A. Inorg. Chim. Acta 2011; 373: 62
• 6a Monchaud D, Teulade-Fichou M.-P. Org. Biomol. Chem. 2008; 6: 627
• 6b Petenzi M, Verga D, Largy E, Hamon F, Doria F, Teulade-Fichou M.-P, Guédin A, Mergny J.-L, Mella M, Freccero M. Chem. Eur. J. 2012; 18: 14487
• 7a Huisgen R, Mack W, Anneser E. Tetrahedron Lett. 1961; 2: 587
• 7b Huisgen R. Angew. Chem. 1963; 75: 604
• 7c Goldberg K, Clarke DS, Scott JS. Tetrahedron Lett. 2014; 55: 4433
• 8a Liang G.-B, Feng DD. Tetrahedron Lett. 1996; 37: 6627
• 8b Hébert N, Hannah AL, Sutton SC. Tetrahedron Lett. 1999; 40: 8547
• 8c Deegan TL, Nitz TJ, Cebzanov D, Pufko DE, Porco JA. Bioorg. Med. Chem. 1999; 9: 209
• 8d Braga VM. L, Melo SJ, Srivastava RM, Falcão EP. S. J. Braz. Chem. Soc. 2004; 15: 603
• 8e Augustine JK, Akabote V, Hegde SG, Alagarsamy P. J. Org. Chem. 2009; 74: 5640
• 9a Young JR, DeVita RJ. Tetrahedron Lett. 1998; 39: 3931
• 9b Zhou T, Chen Z.-C. Synth. Commun. 2006; 32: 887
• 10a Zhang F.-L, Wang Y.-F, Chiba S. Org. Biomol. Chem. 2013; 11: 6003

For selected reports of oxidative cyclizations to generate 1,2,4-oxadiazoles, see:
• 10b Guo W, Huang K, Ji F, Wu W, Jiang H. Chem. Commun. 2015; 51: 8857
• 10c Kuram MR, Kim WG, Myung K. Eur. J. Org. Chem. 2016; 438
• 11a Lemercier B, Pierce JG. Org. Lett. 2015; 17: 4542
• 11b Shymanska NV, An IH, Pierce JG. Angew. Chem. Int. Ed. 2014; 53: 5401
• 11c Lemercier B, Pierce JG. Synlett 2016; 27: 181
• 12 Liu K.-C, Shelton BR, Howe RK. J. Org. Chem. 1980; 45: 3916
• 13a Zhang Y, Li C.-J. J. Am. Chem. Soc. 2006; 128: 4242
• 13b Tu W, Liu L, Floreancig PE. Angew. Chem. Int. Ed. 2008; 47: 4184
• 13c Cui Y, Floreancig PE. Org. Lett. 2012; 14: 1720
• 13d Batista VS, Crabtree RH, Konezny SJ, Luca OR, Preatorius JM. New J. Chem. 2012; 36: 1141
• 13e Bhunia S, Ghosh S, Dey D, Bisai A. Org. Lett. 2013; 15: 2426
• 13f Sun S, Li C, Floreancig PE, Lou H, Liu L. Org. Lett. 2015; 17: 1684
• 13g Gillard RM, Sperry J. J. Org. Chem. 2015; 80: 2900
• 14a Zhu X, Wang Y.-F, Ren W, Zhang F.-L, Chiba S. Org. Lett. 2013; 15: 3214
• 14b Chen H, Chiba S. Org. Biomol. Chem. 2014; 12: 42
• 14c Chiba S, Chen H. Org. Biomol. Chem. 2014; 12: 4051
• 15 Zhu H, Chen Z. Org. Lett. 2016; 18: 488