Stereoselective Synthesis of Polyfunctionalized Nitrones through Conjugate Addition of α-Halo Hydrazones to Nitroso Compounds

Abstract

In the presence of Na₂CO₃, conjugate addition of α-halo hydrazones to nitroso compounds proceeded readily to give polyfunctionalized nitrones in reasonable chemical yields and excellent stereoselectivities. The chemical structure and the stereochemical configuration of the products were unambiguously identified by an X-ray single-crystal structural analysis.

Key words

conjugate addition - halo hydrazones - nitroso compounds - nitrones - stereoselectivity

Publication History

Received: 26 April 2021

Accepted after revision: 14 May 2021

Accepted Manuscript online:
14 May 2021

Article published online:
14 June 2021

• References and Notes


For selected examples, see:
• 1a Rao PS, Kurumurthy C, Veeraswamy B, Kumar GS, Poornachandra Y, Kumar CG, Vasamsetti SB, Kotamraju S, Narsaiah B. Eur. J. Med. Chem. 2014; 80: 184
• 1b Buchlovič M, Kříž Z, Hofr C, Potáček M. Bioorg. Med. Chem. 2013; 21: 1078
• 1c Sklavounou E, Hay A, Ashraf N, Lamb K, Brown E, MacIntyre A, George WD, Hartley RC, Shiels PG. Biochem. Biophys. Res. Commun. 2006; 347: 420 ; corrigendum: Biochem. Biophys. Res. Commun. 2006, 347, 1206
• 1d Giner-Sorolla A. J. Med. Chem. 1969; 12: 717

For selected examples, see:
• 2a Li Z, Zhao J, Sun B, Zhou T, Liu M, Liu S, Zhang M, Zhang Q. J. Am. Chem. Soc. 2017; 139: 11702
• 2b Ferraz MC, Mano RA, Oliveira DH, Maia DS. V, Silva WP, Savegnago L, Lenardao EJ, Jacob RG. Medicines 2017; 4: 39
• 2c Nguyen D.-V, Prakash P, Gravel E, Doris E. RSC Adv. 2016; 6: 89238
• 2d Morales S, Guijarro FG, Alonso I, García Ruano JL, Cid MB. ACS Catal. 2015; 6: 84
• 2e Matassini C, Parmeggiani C, Cardona F, Goti A. Org. Lett. 2015; 17: 4082
• 2f Zeng Q, Zhang L, Yang J, Xu B, Xiao Y, Zhang J. Chem. Commun. 2014; 50: 4203
• 2g Nakamura I, Onuma T, Kanazawa R, Nishigai Y, Terada M. Org. Lett. 2014; 16: 4198
• 2h Medina SI, Wu J, Bode JW. Org. Biomol. Chem. 2010; 8: 3405
• 2i Racine E, Py S. Org. Biomol. Chem. 2009; 7: 3385
• 2j Moran J, Pfeiffer JY, Gorelsky SI, Beauchemin AM. Org. Lett. 2009; 11: 1895
• 2k Cheng HS, Seow A.-H, Loh T.-P. Org. Lett. 2008; 10: 2805

For selected examples, see:
• 3a Zonta C, Cazzola E, Mba M, Licini G. Adv. Synth. Catal. 2008; 350: 2503
• 3b Reidl TW, Son J, Wink DJ, Anderson LL. Angew. Chem. Int. Ed. 2017; 56: 11579
• 3c Katahara S, Kobayashi S, Fujita K, Matsumoto T, Sato T, Chida N. Bull. Chem. Soc. Jpn. 2017; 90: 893
• 3d Chavannavar AP, Oliver AG, Ashfeld BL. Chem. Commun. 2014; 50: 10853

For selected examples, see:
• 4a Volpe C, Meninno S, Roselli A, Mancinelli M, Mazzanti A, Lattanzi A. Adv. Synth. Catal. 2020; 362: 5457
• 4b Hiraoka S, Matsumoto T, Matsuzaka K, Sato T, Chida N. Angew. Chem. Int. Ed. 2019; 58: 4381
• 4c Moskal J, Milart P. Chem. Ber. 1985; 118: 4014

For examples, see:
• 5a Lopes SM. M, Cardoso AL, Lemos A, Pinho e Melo TM. V. D. Chem. Rev. 2018; 118: 11324
• 5b Li Z, Li S, Kan T, Wang X, Xin X, Hou Y, Gong P. Adv. Synth. Catal. 2020; 362: 2626
• 5c Yin W, Fang L, Wang Z, Gao F, Li Z, Wang Z. Org. Lett. 2019; 21: 7361
• 5d Wu Q, Shao P.-L, He Y. RSC Adv. 2019; 9: 21507
• 5e Zhang X, Pan Y, Wang H, Liang C, Ma X, Jiao W, Shao H. Adv. Synth. Catal. 2020; 363: 459
• 5f Shelke AM, Suryavanshi G. Org. Lett. 2016; 18: 3968
• 5g Deng Y, Pei C, Arman H, Dong K, Xu X, Doyle MP. Org. Lett. 2016; 18: 5884
• 5h Guo C, Sahoo B, Daniliuc CG, Glorius F. J. Am. Chem. Soc. 2014; 136: 17402
• 5i Chen J.-R, Dong W.-R, Candy M, Pan F.-F, Jörres M, Bolm C. J. Am. Chem. Soc. 2012; 134: 6924

For selected examples, see:
• 6a Hu X.-Q, Chen J.-R, Gao S, Feng B, Lu LQ, Xiao W.-J. Chem. Commun. 2013; 49: 7905
• 6b Tong M.-C, Chen X, Li J, Huang R, Tao H, Wang C.-J. Angew. Chem. Int. Ed. 2014; 53: 4680
• 6c Zhao H.-W, Pang H.-L, Tian T, Li B, Chen X.-Q, Song X.-Q, Meng W, Yang Z, Liu Y.-Y, Zhao Y.-D. Adv. Synth. Catal. 2016; 358: 1826
• 6d Gao S, Chen J.-R, Hu X.-Q, Cheng H.-G, Lu L.-Q, Xiao W.-J. Adv. Synth. Catal. 2013; 355: 3539
• 6e Huang R, Tao H.-Y, Wang C.-J. Org. Lett. 2017; 19: 1176
• 6f Cheng B, Li Y, Wang T, Zhang X, Li H, Li Y, Zhai H. Chem. Commun. 2019; 55: 14606
• 6g Wang Z, Yang Y, Gao F, Wang Z, Luo Q, Fang L. Org. Lett. 2018; 20: 934

For selected examples, see:
• 7a Li J, Huang R, Xing Y.-K, Qiu G, Tao H.-Y, Wang C.-J. J. Am. Chem. Soc. 2015; 137: 10124
• 7b Semakin AN, Kokuev AO, Nelyubina YV, Sukhorukov AY, Zhmurov PA, Ioffe SL, Tartakovsky VA. Beilstein J. Org. Chem. 2016; 12: 2471
• 7c Hatcher JM, Coltart DM. J. Am. Chem. Soc. 2010; 132: 4546
• 7d Attanasi OA, Favi G, Filippone P, Mantellini F, Moscatelli G, Perrulli FR. Org. Lett. 2010; 12: 468
• 7e Chen Z, Yan Q, Liu Z, Xu Y, Zhang Y. Angew. Chem. Int. Ed. 2013; 52: 13324
• 7f Mantenuto S, Mantellini F, Favi G, Attanasi OA. Org. Lett. 2015; 17: 2014
• 7g Carbone A, Spanò V, Parrino B, Ciancimino C, Attanasi OA, Favi G. Molecules 2013; 18: 2518
• 7h Preti L, Attanasi OA, Caselli E, Favi G, Ori C, Davoli P, Felluga F, Prati F. Eur. J. Org. Chem. 2010; 2010: 4312
• 7i De Crescentini L, Perrulli FR, Favi G, Santeusanio S, Giorgi G, Attanasi OA, Mantellini F. Org. Biomol. Chem. 2016; 14: 8674
• 7j van Berkel SS, Brauch S, Gabriel L, Henze M, Stark S, Vasilev D, Wessjohann LA, Abbas M, Westermann B. Angew. Chem. Int. Ed. 2012; 51: 5343

For selected examples, see:
• 8a Roy SK, Purkait A, Aziz SM. T, Jana CK. Chem. Commun. 2020; 56: 3167
• 8b Purkait A, Saha S, Ghosh S, Jana CK. Chem. Commun. 2020; 56: 15032
• 8c González-Soria MJ, Alonso F. Adv. Synth. Catal. 2019; 361: 5005
• 8d Wang C.-C, Huang J, Li XH, Kramer S, Lin G.-Q, Sun X.-W. Org. Lett. 2018; 20: 2888
• 8e Mokar BD, Liu J, Liu R.-S. Org. Lett. 2018; 20: 1038
• 8f Vasilikogiannaki E, Gryparis C, Kotzabasaki V, Lykakis IN, Stratakis M. Adv. Synth. Catal. 2013; 355: 907
• 8g Bodnar BS, Miller MJ. Angew. Chem. Int. Ed. 2011; 50: 5630
• 8h Dochnahl M, Fu GC. Angew. Chem. Int. Ed. 2009; 48: 2391
• 8i Yamamoto H, Momiyama N. Chem. Commun. 2005; 3514

For selected examples, see:
• 9a Pilepić V, Uršić S. J. Mol. Struct.: THEOCHEM 2001; 538: 41
• 9b Uršić S, Lovrek M, VinkovićVrček I, Pilepić V. J. Chem. Soc., Perkin Trans. 2 1999; 1295
• 9c Uršić S, Pilepić V, Vrček V, Gabričević M, Zorc B. J. Chem. Soc., Perkin Trans. 2 1993; 509
• 9d Uršić S, Vrček V, Gabričević M, Zorc B. J. Chem. Soc., Chem. Commun. 1992; 296
• 10 N-(1Z,2Z)-2-[Oxido(phenyl)imino]-1-phenylethylidene}acetohydrazide (3aa); Typical ProcedureNa₂CO₃ (2.0 equiv, 0.40 mmol) was added to a solution of α-bromo hydrazone 1a (1.0 equiv, 0.20 mmol) and nitroso compound 2a (1.2 equiv, 0.24 mmol) in dry CH₂Cl₂ (1.0 mL) under air at rt, and the mixture was stirred for 20 h. When the reaction was complete (TLC), the mixture was concentrated under reduced pressure and the residue was purified by flash column chromatography [silica gel, PE–EtOAc (3:1)] to give a yellow solid; yield: 51.7 mg (92%); mp 133.3–133.8 °C. ¹H NMR (400 MHz, CDCl₃): δ = 11.05–10.42 (m, 1 H), 8.10 (s, 1 H), 7.83 (s, 2 H), 7.68 (s, 2 H), 7.54 (s, 3 H), 7.41 (s, 3 H), 2.41–2.10 (m, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 174.5, 146.8, 138.0, 135.8, 131.5, 131.0, 129.7, 129.5, 128.7, 127.2, 121.9, 20.4. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₁₆N₃O₂: 282.12370; found: 282.12405.
• 11 CCDC 2075055 contains the supplementary crystallographic data for compound 3aa. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.