An Azirine Strategy for the Synthesis of Alkyl 4-Amino-5-(trifluoromethyl)-1H-pyrrole-2-carboxylates

Abstract

1-(3,3,3-Trifluoro-2,2-dihydroxypropyl)pyridin-1-ium bromide serves as a trifluoromethyl-containing building block for the preparation of trifluoromethyl-substituted aminopyrroles based on the 2H-azirine ring expansion strategy. The primary products, 3-aryl-2-(methoxycarbonyl)-4-(pyridin-1-ium-1-yl)-5-(trifluoromethyl)pyrrol-1-ides, can be hydrogenated by H₂/PtO₂ to form alkyl 3-aryl-4-(piperidin-1-yl)-5-(trifluoromethyl)-1H-pyrrole-2-carboxylates and transformed into alkyl 4-amino-3-aryl-1-methyl-5-(trifluoromethyl)-1H-pyrrole-2-carboxylates via methylation/hydrazinolysis.

Key words

trifluoromethylpyrrole - aminopyrrole - trifluoromethylated pyridinium ylide - pyridine - piperidine

• References


For a recent review, see:
• 1a Bhardwaj V, Gumber D, Abbot V, Dhiman S, Sharma P. RSC Adv. 2015; 5: 15233
• 1b Clive DL. J, Cheng P. Tetrahedron 2013; 69: 5067
• 1c Wu Y.-J. Heterocycles and Medicine: A Survey of Heterocyclic Drugs Approved by U.S. FDA from 2000 to Present. In Progress in Heterocyclic Chemistry. Vol. 24. Gribble GW, Joule JA. Elsevier; Oxford: 2012: 1-54
• 1d Shinohara K.-I, Bando T, Sugiyama H. Anti-Cancer Drugs 2010; 21: 228
• 1e Hagfeldt A, Boschloo G, Sun L, Kloo L, Pettersson H. Chem. Rev. 2010; 110: 6595
• 1f Young IS, Thornton PD, Thompson A. Nat. Prod. Rep. 2010; 27: 1801

For a recent review, see:
• 2a Olivier WJ, Smith JA, Bissember AC. Org. Biomol. Chem. 2018; 16: 1216
• 2b Trofimov BA, Mikhaleva AI, Schmidt EYu, Sobenina LN. Chemistry of Pyrroles 2014; 398
• 2c Estévez V, Villacampa M, Menéndez JC. Chem. Soc. Rev. 2014; 43: 4633
• 2d Yurovskaya MA, Alekseyev RS. Chem. Heterocycl. Compd. 2014; 49: 1400
• 2e Sobenina LN, Tomilin DN, Trofimov BA. Russ. Chem. Rev. 2014; 83: 475
• 3 Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
• 4 Kirsch P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications. Wiley-VCH; Weinheim: 2013: 379
• 5 Nenajdenko V, Muzalevskiy VM, Serdyuk OV. Chemistry of Fluorinated Pyrroles . In Fluorine in Heterocyclic Chemistry . Vol. 1. Nenajdenko V. Springer; Switzerland: 2014: 55-116

For recent examples, see:
• 6a Sommer H, Braun M, Schröder B, Kirschning A. Synlett 2018; 29: 121
• 6b Rahmani F, Darehkordi A. Synlett 2017; 28: 1224
• 6c Huang C, Zeng Y, Cheng H, Hu A, Liu L, Xiao Y, Zhang J. Org. Lett. 2017; 19: 4968
• 7 Cirrincione G, Almerico AM, Aiello E, Dattolo G. Aminopyrroles . In Chemistry of Heterocyclic Compounds, Pyrroles, Pt. 2 . Vol. 48. Jones RA. John Wiley & Sons, Inc; Chichester: 1992: 299-523
• 8 Jacobs J, Van Hende E, Claessens S, De Kimpe N. Curr. Org. Chem. 2011; 15: 1340
• 9 Khlebnikov AF, Golovkina MV, Novikov MS, Yufit DS. Org. Lett. 2012; 14: 3768
• 10a Khlebnikov AF, Tomashenko OA, Funt LD, Novikov MS. Org. Biomol. Chem. 2014; 12: 6598
• 10b Galenko EE, Tomashenko OA, Khlebnikov AF, Novikov MS. Beilstein J. Org. Chem. 2015; 11: 1732
• 10c Tomashenko OA, Novikov MS, Khlebnikov AF. J. Org. Chem. 2017; 82: 616
• 11a Funt LD, Tomashenko OA, Khlebnikov AF, Novikov MS, Ivanov YuA. J. Org. Chem. 2016; 81: 11210
• 11b Funt LD, Tomashenko OA, Mosiagin IP, Novikov MS, Khlebnikov AF. J. Org. Chem. 2017; 82: 7583
• 12 Funt LD, Novikov MS, Starova GL, Khlebnikov AF. Tetrahedron 2018; 74: 2466
• 13a Zincke T, Heuser G, Möller W. Justus Liebigs Ann. Chem. 1904; 333: 296
• 13b Zincke T. Justus Liebigs Ann. Chem. 1904; 330: 361
• 13c Zincke T, Wurker W. Justus Liebigs Ann. Chem. 1905; 338: 107
• 14a Galenko EE, Tomashenko OA, Khlebnikov AF, Novikov MS. Org. Biomol. Chem. 2015; 13: 9825
• 14b Galenko EE, Galenko AV, Khlebnikov AF, Novikov MS, Shakirova JR. J. Org. Chem. 2016; 81: 8495
• 14c Galenko EE, Galenko AV, Novikov MS, Khlebnikov AF, Kudryavtsev IV, Terpilowski MA, Serebriakova MK, Trulioff AS, Goncharov NV. ChemistrySelect 2017; 2: 7508
• 15 Galenko AV, Khlebnikov AF, Novikov MS, Avdontseva MS. Tetrahedron 2015; 71: 1940
• 16 Wittmann H, Ziegler E, Peters K, Peters EM, von Schnering HG. Monatsh. Chem. 1983; 114: 1097
• 17 CCDC 1826517 (3a) contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
• 18 Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257
• 19 Smetanin IA, Novikov MS, Agafonova AV, Rostovskii NV, Khlebnikov AF, Kudryavtsev IV, Terpilowski MA, Serebriakova MK, Trulioff AS, Goncharov NV. Org. Biomol. Chem. 2016; 14: 4479
• 20 Rostovskii NV, Agafonova AV, Smetanin IA, Novikov MS, Khlebnikov AF, Ruvinskaya JO, Starova GL. Synthesis 2017; 49: 4478
• 21 An D, Guan X, Guan R, Jin L, Zhang G, Zhang S. Chem. Commun. 2016; 11211
• 22 Loy NS. I, Singh A, Xu X, Park C.-M. Angew. Chem. Int. Ed. 2013; 52: 2212
• 23 Rostovskii NV, Ruvinskaya JO, Novikov MS, Khlebnikov AF, Smetanin IA, Agafonova AV. J. Org. Chem. 2017; 82: 256
• 24 Ruvinskaya JO, Rostovskii NV, Filippov IP, Khlebnikov AF, Novikov MS. Org. Biomol. Chem. 2018; 16: 38
• 25 Dubrovskiy AV, Larock RC. Org. Lett. 2010; 12: 1180
• 26 Zhao Y.-Z, Yang H.-B, Tang X.-Y, Shi M. Chem. Eur. J. 2015; 21: 3562
• 27 Sakai T, Liu Y, Ohta H, Korenaga T, Ema T. J. Org. Chem. 2005; 70: 1369