Synlett, Inhaltsverzeichnis Synlett 2020; 31(06): 553-558DOI: 10.1055/s-0039-1691533 cluster © Georg Thieme Verlag Stuttgart · New York Asymmetric Neber Reaction in the Synthesis of Chiral 2-(Tetrazol-5-yl)-2H-Azirines Cláudia Alves a CQC and Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal, eMail: tmelo@ci.uc.pt , Carla Grosso a CQC and Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal, eMail: tmelo@ci.uc.pt , Pedro Barrulas b Centro de Química de Évora and Department of Chemistry, University of Évora, 7000 Évora, Portugal c HERCULES Laboratory, Évora University, Largo Marquês de Marialva 8, 7000-809 Évora, Portugal , José A. Paixão d CFisUC and Department of Physics, University of Coimbra, Coimbra 3004-516, Portugal , Ana L. Cardoso a CQC and Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal, eMail: tmelo@ci.uc.pt , Anthony J. Burke b Centro de Química de Évora and Department of Chemistry, University of Évora, 7000 Évora, Portugal , Américo Lemos a CQC and Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal, eMail: tmelo@ci.uc.pt e FCT, University of Algarve, Campus Gambelas, 8005-139 Faro, Portugal , Teresa M. V. D. Pinho e Melo ∗ a CQC and Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal, eMail: tmelo@ci.uc.pt › Institutsangaben Artikel empfehlen Abstract Artikel einzeln kaufen Alle Artikel dieser Rubrik Published as part of the ISySyCat2019 Special Issue Abstract A successful one-pot methodology for the synthesis of chiral 2-tetrazolyl-2H-azirines has been established, resorting to organocatalysis. The protocol involves the in situ tosylation of β-ketoxime-1H-tetrazoles followed by the Neber reaction, in the presence of chiral organocatalysts. Among the organocatalysts studied a novel thiourea catalyst derived from 6β-aminopenicillanic acid afforded excellent enantioselectivities. Key words Key words2H-azirines - asymmetric Neber reaction - organocatalysis - tetrazoles - thiourea - 6β-aminopenicillanic acid Volltext Referenzen References and Notes 1 Khlebnikov AF, Norikov MS, Rostovskii NV. Tetrahedron 2019; 75: 2555 2 Khlebnikov AF, Novikov MS. Tetrahedron 2013; 69: 3363 3 Khlebnikov AF, Novikov MS. Ring Expansions of Azirines and Azetines . In Topics in Heterocylicic Chemistry . Maes BU. W, Cossy J, Slovenko P. Springer; Berlin: 2015: 1 4 Pinho e Melo TM. V. D, Rocha Gonsalves A. M. dA. Curr. Org. Synth. 2004; 1: 275 5 Palacios F, de Retana AM. O, de Marigorta EM, de los Santos JM. Eur. J. Org. Chem. 2001; 13: 2401 6 Padwa A. Cycloaddition and Cyclization Chemistry of 2H-Azirines. In Advances in Heterocyclic Chemistry, Vol. 99. Katritzky AR. Elsevier; Amsterdam: 2010: 31 7 Padwa A. Aziridines and Azirines: Monocyclic . In Comprehensive Heterocyclic Chemistry III, Vol. 1 . Katritzky AR. Elsevier; Amsterdam: 2008: 104 8 Miller TW, Tristram EW, Wolf FJ. J. Antibiot. 1971; 24: 48 9 Molinski TF, Ireland CM. J. Org. Chem. 1988; 53: 2103 10a Neber PW, Friedolsheim A. Justus Liebigs Ann. Chem. 1926; 449: 109 10b Neber PW, Burgard A, Their W. Justus Liebigs Ann. Chem. 1936; 526: 277 10c Verstappen MM. H, Ariaans GJ. A, Zwanenburg B. J. Am. Chem. Soc. 1996; 118: 8491 10d Skepper CK, Dalisay DS, Molinski TF. Org. Lett. 2008; 10: 5269 10e Skepper CK, Dalisay DS, Molinski TF. Bioorg. Med. Chem. Lett. 2010; 20: 2029 10f Kadam VD, Sudhakar G. Tetrahedron 2015; 71: 1058 11 Sakamoto S, Inokuma T, Takemoto Y. Org. Lett. 2011; 13: 6374 12a Zhao J.-Q, Yue D.-F, Zhang X.-M, Xu X.-Y, Yuan W.-C. Org. Biomol. Chem. 2016; 14: 10946 12b Deng-Feng YueD.-F, Zhao J.-Q, Wang Z.-H, Zhang X.-M, Xu X.-Y, Yuan W.-C. Org. Biomol. Chem. 2016; 14: 1946 13a Rocha Gonsalves AM.dA, Cabral AM. T. D. P. V. Synthesis 1997; 673 13b Pinho e Melo TM. V. D, Rocha Gonsalves AM. dA, Lopes CS. J, Gilchrist TL. Tetrahedron Lett. 1999; 40: 789 13c Pinho e Melo TM. V. D, Lopes CS. J, Cardoso AL, Rocha Gonsalves AM. dA, Pinho e Melo TM. V. D, Gilchrist TL. Tetrahedron 2001; 57: 6203 14a Pinho e Melo TM. V. D, Lopes CS. J, Rocha Gonsalves AM. dA. Tetrahedron Lett. 2000; 41: 7217 14b Pinho e Melo TM. V. D, Lopes CS. J, Beja AM, Paixão JA, Silva MR, Veiga LA, Rocha Gonsalves AM. dA. J. Org. Chem. 2002; 67: 66 14c Fotsing JR, Banert K. Eur. J. Org. Chem. 2006; 3617 14d Lopes S, Nunes CM, Fausto R, Pinho e Melo TM. V. D. J. Mol. Struct. 2009; 919: 47 14e Shah SR, Navathe SS, Dikundwar AG, Row TN. G, Vasella AT. Eur. J. Org. Chem. 2013; 264 14f Novikov MS, Smetanin IA, Khlebnikov AF, Rostovskii NV, Yufit DS. Tetrahedron Lett. 2012; 53: 5777 14g Smetanin IA, Novikov MS, Rostovskii NV, Khlebnikov AF, Starova GL, Yufit DS. Tetrahedron 2015; 71: 4616 15 Cardoso AL, Henriques MS. C, Paixão JA, Pinho e Melo TM. V. D. J. Org. Chem. 2016; 81: 9028 16 Cardoso AL, Sousa C, Henriques MS. C, Paixão JA, Pinho e Melo TM. V. D. Molecules 2015; 20: 22351 17 Jorda R, Lopes SM. M, Řezníčková E, Kryštof V, Pinho e Melo TM. V. D. ChemMedChem 2017; 12: 701 18 Panice MR, Lopes SM. M, Figueiredo MC, Ruiz AL. T. G, Foglio M. -A, Sarragiotto MH, Pinho e Melo TM. V. D. Eur. J. Med. Chem. 2019; 179: 123 19 Cardoso AL, Gimeno L, Lemos A, Palacios F, Pinho e Melo TM. V. D. J. Org. Chem. 2013; 78: 6983 20 Cardoso AL, Lemos A, Pinho e Melo TM. V. D. Eur. J. Org. Chem. 2014; 5159 21 General Procedure for the Optimized Asymmetric Synthesis of 2H-azirines 7, 14a, and 14b To a solution of the appropriate β-ketoxime 5 or 13a,b (0.15 mmol), K2CO3 (1.50 mmol, 10 equiv), and tosyl chloride (0.17 mmol, 1.1 equiv) in toluene (4 mL) under a nitrogen atmosphere was added the organocatalyst (18 or 20 mol%) in toluene (1 mL). The mixture was stirred for 48 h at the appropriate temperature. The solvent was evaporated under reduced pressure, and the crude reaction was dissolved in ethyl acetate (20 mL) and washed with water (3 × 10 mL). The organic layer was dried over anhydrous Na2SO4 and filtered, and the solvent was evaporated under vacuum. The crude product was purified by flash chromatography (ethyl acetate/hexane, 1:1). The characterization data for 7, 14a, and 14b agreed with those previously reported.19 22a Barrulas PM. C. Dissertation. University of Évora; Portugal: 2014 22b Barrulas P, Benaglia M, Burke AJ. Tetrahedron: Asymmetry 2014; 25: 923 23 Rolinson GN, Geddes AM. Int. J. Antimicrob. Agents 2007; 29: 3 24 Emer E, Galleti P, Giacomini D. Eur. J. Org. Chem. 2009; 29: 3155 25 Sheehan JC, Commons TJ. J. Org. Chem. 1978; 11: 2203 26 Procedure for the Synthesis of (2S,6R)-Benzhydryl 6β-{3-[3,5-bis(trifluoromethyl)phenyl] thioureido}-aminopenicillanate (12) To a solution of benzhydryl 6β-aminopenicillanate 10b (1.94 mmol, 0.74 g) under inert atmosphere in dry THF (3.5 mL) was added dropwise 3,5-bis(trifluoromethyl)phenyl isothiocyanate (11, 1.94 mmol, 0.35 mL). After stirring for 3 h at room temperature, the solvent was evaporated, and the crude product was purified by flash chromatography (eluting with ethyl acetate/hexane, 1:2) and recrystallized with diethyl ether/hexane; yield 48%; white solid; mp 77.0–78.0 °C. IR (KBr): ν = 682, 697, 1128, 1251, 1175, 1276, 1491, 1735, 2968, 2933, 3032, 3066, 3271, 3291 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.93 (s, 1 H), 7.84 (s, 2 H), 7.50 (s, 1 H), 7.35–7.31 (m, 11 H), 6.96 (s, 1 H), 5.19 (d, J = 2 Hz, 1 H), 4.25 (dd, J = 3.2 Hz and J = 1.2 Hz, 1 H), 3.92 (s, 1 H), 1.64 (s, 3 H), 1.00 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 182.8, 170.6, 167.3, 139.1, 138.9, 133.9, 132.4 (q, J = 34.0 Hz, 2 C), 128.8, 128.9, 128.6, 128.5, 128.2, 127.9, 127.7, 126.9, 126.8, 126.6, 124.1, 122.9 (m, 1 C), 121.4, 78.7, 73.3, 66.5, 65.5, 65.1, 60.6, 26.3, 26.1 ppm. 19F NMR (376 MHz CDCl3): δ = 62.8 (s, 6 F). HRMS (ESI): m/z calcd for C30H26F6N3O3S2 [MH+]: 654.1314; found: 654.1301. Zusatzmaterial Zusatzmaterial Supporting Information
