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Synlett 2020; 31(09): 871-877
DOI: 10.1055/s-0040-1707997
letter
© Georg Thieme Verlag Stuttgart · New York

Ultrasound-Activated Atom-Economical Approach to the Synthesis of Highly Substituted Pyrrolidin-2-ones through a Four-Component Ugi/5-endo-trig Intramolecular Radical Cyclization Reaction

Atena Nashta Rahimi
a   Peptide Chemistry Research Center, K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran
,
Helya Janatian Ghazvini
a   Peptide Chemistry Research Center, K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran
,
Saeed Balalaie  ∗
a   Peptide Chemistry Research Center, K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran
b   Medical Biology Research Center, Kermanshah University of Medical Sciences, P. O. Box 6715847141, Kermanshah, Iran
,
Frank Rominger
c   Organisch-Chemisches Institut der Universität Heidelberg, Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany
,
Hossein Zahedian Tejeneki
a   Peptide Chemistry Research Center, K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran
,
Hamid R. Bijanzadeh
d   Department of Environmental Sciences, Faculty of Natural Resources and Marine Sciences, Tarbiat Modares University, Tehran, Iran   Email: balalaie@kntu.ac.ir
› Author AffiliationsWe thank the Iran National Science Foundation (INSF, Grant No 97020936) for financial support.
Further Information

Publication History

Received: 27 January 2020

Accepted after revision: 21 February 2020

Publication Date:
13 March 2020 (online)

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Abstract

An efficient and diversity-oriented access to functionalized pyrrolidin-2-ones through an Ugi reaction of readily available starting materials with a subsequent transformation is described. A two-step reaction sequence of a four-component Ugi reaction and an intramolecular radical-cyclization reaction leads to the chemo- and regioselective formation of a single product with high atom economy and good to high yields. The radicalization of the pseudopeptides generated from the first step by a cavitational mechanism produces the key intermediate for the ultrasound-activated formation of γ-lactams as the final products by β-Michael addition. Among the advantages of this approach are its use of cavitation bubble implosion as an exclusive path to radicalization of the polyfunctional Ugi adduct, its high selectivity, and its short reaction times.

Key words

Ugi reaction - multicomponent reaction - pyrrolidinones - ultrasound promotion - sonochemistry - lactams

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1707997.
  • Supporting Information
 

  • References and Notes

    • 1a Eicher T, Hauptmann S, Speicher A. The Chemistry of Heterocycles: Structures, Reactions, Synthesis, and Applications, 3rd ed. Wiley-VCH; Weinheim: 2013
      Search in Google Scholar
    • 1b Green Chemistry: Synthesis of Bioactive Heterocycles. Ameta KL, Dandia A. Springer; Berlin: 2011
      Search in Google Scholar
  • 2 Balalaie S, Shakeri P. Farmaco 2019; 22: 468
    Search in Google Scholar
  • 3 Sharma UK, Sharma N, Vachhani DD, Van der Eycken EV. Chem. Soc. Rev. 2015; 44: 1836
    CrossrefPubMedSearch in Google Scholar
  • 4 Mohammadkhani L, Heravi MM. ChemistrySelect 2019; 4: 10187
    CrossrefSearch in Google Scholar
  • 5 Chu S.-f, Zhang J.-t. Acta Pharm. Sin. B 2014; 4: 417
    CrossrefPubMedSearch in Google Scholar
  • 6 Winblad B. CNS Drug Rev. 2005; 11: 169
    PubMedSearch in Google Scholar
  • 7 Robson RH, Prescott LF. Br. J. Clin. Pharmacol. 1978; 7: 81
    Search in Google Scholar
  • 8 Ward JW, Gilbert DL, Franko BV, Woodard G, Mann GT. Toxicol. Appl. Pharmacol. 1968; 13: 242
    CrossrefSearch in Google Scholar
  • 9 de Waal CG, Hutten GJ, Kraaijenga JV, de Jongh FH, van Kaam AH. Neonatology 2019; 115: 85
    CrossrefPubMedSearch in Google Scholar
  • 10 Georgiou AD, Toutountzoglou V, Muir KW, Hadjipavlou-Litina D, Elemes Y. Bioorg. Med. Chem. 2012; 20: 5103
    CrossrefPubMedSearch in Google Scholar
  • 11 Caruano J, Muccioli GG, Robiette R. Org. Biomol. Chem. 2016; 14: 10134
    CrossrefPubMedSearch in Google Scholar
  • 12 Kammerer C, Prestat G, Madec D, Poli G. Acc. Chem. Res. 2014; 47: 3439
    CrossrefPubMedSearch in Google Scholar
  • 13 Hong SY, Park Y, Hwang Y, Kim YB, Baik M.-H, Chang S. Science 2018; 359: 1016
    CrossrefPubMedSearch in Google Scholar
  • 14 Donohoe TJ, Chiu JY. K, Thomas RE. Org. Lett. 2007; 9: 421
    CrossrefPubMedSearch in Google Scholar
  • 15 Dairo TO, Nelson NC, Slowing II, Angelici RJ, Woo LK. Catal. Lett. 2016; 146: 2278
    CrossrefSearch in Google Scholar
  • 16 Aoun R, Renaud J.-L, Dixneuf PH, Bruneau C. Angew. Chem. Int. Ed. 2005; 44: 2021
    CrossrefPubMedSearch in Google Scholar
  • 17 Qin B, Schneider U. J. Am. Chem. Soc. 2016; 138: 13119
    CrossrefPubMedSearch in Google Scholar
  • 18 Kuik D, McCubbin JA, Tranmer GK. Synthesis 2017; 49: 2555
    Thieme ConnectSearch in Google Scholar
  • 19 Pari S, Kaur B, Parmar A, Kumar H. Curr. Org. Chem. 2013; 17: 1790
    CrossrefSearch in Google Scholar
  • 20 Bryans JS, Chessum NE. A, Parsons AF, Ghelfi F. Tetrahedron Lett. 2001; 42: 2901
    CrossrefSearch in Google Scholar
  • 21 Fang G, Cong X, Zanoni G, Liu Q, Bi X. Adv. Synth. Catal. 2017; 359: 1422
    CrossrefSearch in Google Scholar
  • 22 Tucker JW, Stephenson CR. J. Org. Lett. 2011; 13: 5468
    CrossrefPubMedSearch in Google Scholar
  • 23 Schiesser CH, Wille U, Matsubara H, Ryu I. Acc. Chem. Res. 2007; 40: 303
    CrossrefPubMedSearch in Google Scholar
  • 24 Zhao Y, Li Z, Sharma UK, Sharma N, Song G, Van der Eycken EV. Chem. Commun. 2016; 52: 6395
    CrossrefPubMedSearch in Google Scholar
  • 25 Rentería-Gómez A, Islas-Jácome A, Jiménez-Halla JO. C, Gámez-Montaño R. Tetrahedron Lett. 2014; 55: 6567
    CrossrefSearch in Google Scholar
  • 26 Santra S, Andreana PR. Org. Lett. 2007; 9: 5035
    CrossrefPubMedSearch in Google Scholar
  • 27 Santra S, Andreana PR. Angew. Chem. Int. Ed. 2011; 50: 9418
    CrossrefPubMedSearch in Google Scholar
  • 28 Gao X, Shan C, Chen Z, Liu Y, Zhao X, Zhang A, Yu P, Galons H, Lan Y, Lu K. Org. Biomol. Chem. 2018; 16: 6096
    CrossrefPubMedSearch in Google Scholar
  • 29 Borja-Miranda A, Sánchez-Chávez AC, Polindara-García LA. Eur. J. Org. Chem. 2019; 2019: 2453
    CrossrefSearch in Google Scholar
  • 30 Ghabraie E, Balalaie S, Mehrparvar S, Rominger F. J. Org. Chem. 2014; 79: 7926
    CrossrefPubMedSearch in Google Scholar
  • 31 Amiri K, Balalaie S, Anwar MU, Al-Harrasi A. Synlett 2020;
    Thieme ConnectPubMed
  • 32 Balalaie S, Ghoroghaghaei HB, Alavijeh NS, Darvish F, Rominger F, Bijanzadeh HR. SynOpen 2018; 2: 222
    Thieme ConnectSearch in Google Scholar
  • 33 Balalaie S, Motaghedi H, Tahmassebi D, Bararjanian M, Bijanzadeh HR. Tetrahedron Lett. 2012; 53: 6177
    CrossrefSearch in Google Scholar
  • 34 Janatian Ghazvini H, Müller TJ. J, Rominger F, Balalaie S. J. Org. Chem. 2019; 84: 10740
    CrossrefPubMedSearch in Google Scholar
  • 35 Diphenylpyrrolidine-2-carboxamides 6a–k: General Procedure Aniline 2a–c (1 mmol) was added to a solution of benzaldehyde 1a–i (1 mmol) in MeOH (5 mL), and the mixture was stirred for 2 h at rt. Acid 3a–c (1 mmol) and isocyanide 4a or 4b (1 mmol) were added, and the mixture was stirred for 24 h at rt. When the reaction was complete (TLC; hexane–EtOAc, 3:1), the solvent was removed in vacuo. EtOAc (10 mL), Cu2O (30 mol%), and DCP (3 mmol) were added to the resulting precipitate, and the mixture was stirred with ultrasonic irradiation (400 W) for 45 min. When the reaction was complete (TLC; hexane–EtOAc, 7:1), the mixture was extracted with H2O (3 × 10 mL). The organic layer was dried (MgSO4), filtered, and concentrated in vacuo, and the residue was purified by flash column chromatography (silica gel, n-hexane:EtOAc 7:1). (2E)-N-[1-(4-Chlorophenyl)-2-(cyclohexylamino)-2-oxoethyl]-N,3-diphenylacrylamide (5a) Colorless powder; yield: 378 mg (80%); mp 187–190 °C (hexane–EtOAc, 5:1). IR (KBr): 1648 (C=O) cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.71 [d, J = 15.5 Hz, 1 H, C(sp2)–H], 7.29–7.24 (m, 8 H, H–Ar), 7.21–7.15 (m, 6 H, H–Ar), 6.21 [d, J = 15.5 Hz, 1 H, C(sp2)–H], 6.12 [s, 1 H, C(sp3)–H], 6.04 (d, J = 11.7 Hz, 1 H, N–H), 3.92–3.80 (m, 1 H, H–cyc-N), 2.01–1.86 (m, 2 H, H-cyc), 1.74–1.57 (m, 3 H, H-cyc), 1.45–1.29 (m, 2 H, H-cyc), 1.22–1.05 (m, 3 H, H-cyc). 13C NMR (75 MHz, CDCl3): δ = 168.3, 166.7, 142.8, 139.5, 134.9, 134.3, 133.3, 131.5, 130.4, 129.7, 129.0, 128.6, 128.4, 128.3, 127.9, 118.6, 118.5, 64.9, 48.7, 32.9, 32.8, 25.4, 24.8, 24.7. HRMS (ESI): m/z [M + H]+ Calcd for C29H30ClN2O2: 473.1990; found: 473.1989. [M + Na]+ Calcd for C29H29ClN2NaO2: 495.1810; found: 495.1810. 2-(4-Chlorophenyl)-N-cyclohexyl-5-oxo-1,3-diphenylpyrrolidine-2-carboxamide (6a) Colorless powder; yield: 378 mg (80%); mp 245–248 °C (hexane–EtOAc, 5:1). IR (KBr): 1711 (C=O), 1672 (C=O) cm–1.1H NMR (300 MHz, CDCl3): δ = 7.33–7.24 (m, 5 H, H-Ar), 7.19–7.13 (m, 5 H, H–Ar), 6.90 (d, J = 8.7 Hz, 2 H, H–Ar), 6.80 (d, J = 6.9 Hz, 2 H, H–Ar), 5.32 (d, J = 8.4 Hz, 1 H, N–H), 4.91 [dd, J = 12.4, 8.4 Hz, 1 H, C(sp3)–H], 3.65–3.54 (m, 1 H, H–cyc-N), 2.89–2.72 [m, 2 H, C(sp3)–H], 1.56–1.46 (m, 3 H, H-cyc), 1.33–1.12 (m, 4 H, H-cyc), 1.02–0.90 (m, 1 H, H-cyc), 0.79–0.69 (m, 1 H, H-cyc), 0.59–0.48 (m, 1 H, H-cyc).13C NMR (75 MHz, CDCl3): δ = 174.4, 166.8, 137.1, 135.5, 134.5, 133.1, 130.2, 129.1, 128.9, 128.2, 127.8, 127.7, 127.2, 125.9, 79.7, 48.9, 48.8, 33.9, 32.3, 31.8, 29.7, 25.2, 24.5. HRMS (ESI): m/z [M + Na]+ Calcd for C29H29ClN2NaO2: 495.1810; found: 495.1817.
  • 36 Gilmore K, Alabugin IV. Chem. Rev. 2011; 111: 6513
    CrossrefPubMedSearch in Google Scholar
  • 37 CCDC 1920023 contains the supplementary crystallographic data for compound 6a. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.