Synthesis 2020; 52(08): 1215-1222
DOI: 10.1055/s-0039-1690241
special topic
© Georg Thieme Verlag Stuttgart · New York

A Base-Promoted One-Pot Asymmetric Friedel–Crafts Alkylation/Michael Addition of 4-Substituted Indoles

Robert Connon
a  Synthesis and Solid State Pharmaceutical Center (SSPC), School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland
b  Centre for Synthesis and Chemical Biology (CSCB), School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland   Email: p.guiry@ucd.ie
,
Laura Carroll
b  Centre for Synthesis and Chemical Biology (CSCB), School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland   Email: p.guiry@ucd.ie
,
Patrick J. Guiry
a  Synthesis and Solid State Pharmaceutical Center (SSPC), School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland
b  Centre for Synthesis and Chemical Biology (CSCB), School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland   Email: p.guiry@ucd.ie
› Author Affiliations
This publication has emanated from research conducted (RC) with the financial support of the Synthesis and Solid State Pharmaceutical Centre (SSPC), funded by Science Foundation Ireland (SFI) under Grant No. 12\RC\2275) and is co-funded under the European Regional Development Fund under Grant No. 14/SP/2750. We acknowledge facilities provided by the Centre for Synthesis and Chemical Biology (CSCB) funded by the Higher Education Authority’s PRTLI.
Further Information

Publication History

Received: 23 August 2019

Accepted after revision: 16 October 2019

Publication Date:
30 October 2019 (online)


Dedicated with respect and admiration to Professor Mark Lautens, a good friend and brilliant chemist, on the occasion of his 60th birthday.

Published as part of the Special Topic Domino C–H Functionalization/Cascade Catalysis

Abstract

Herein, we report a base-promoted Zn(II)–bis(oxazoline)-catalyzed one-pot Friedel–Crafts alkylation/Michael addition of 3-(indol-4-yl)acrylonitrile derivatives with trans-β-nitrostyrenes to yield the tricyclic core of the ergoline skeleton in up to 71% yield and 85% ee. During the purification of 3-(indol-4-yl)acrylonitrile, the key substrate for catalytic studies, a novel trans-cis-trans-cyclobutane derivative, thought to be formed via a [2+2] light-promoted cycloaddition, was identified by X-ray crystallographic analysis. Finally, a novel class of 4-substituted bis(indole)methane derivatives were serendipitously prepared in excellent yield by reacting 4-substituted indole derivatives with 4-nitrobenzaldehyde. One bis(indole)methane was characterized by X-ray crystallographic analysis.

Supporting Information

 
  • References

    • 1a Seigler DS. Plant Secondary Metabolism . Springer; Boston: 2001: 628
    • 1b Chadha N, Om S. Eur. J. Med. Chem. 2017; 134: 159
    • 1c Homer JA, Sperry J. J. Nat. Prod. 2017; 80: 2178
    • 2a Wang Y, Fukai X, Lin B, Cheng M, Liu Y. Chem. Eur. J. 2018; 24: 14302
    • 2b Rao RN, Maiti B, Chanda K. ACS Comb. Sci. 2017; 19: 199
    • 2c Liu X.-Y, Qin Y. Acc. Chem. Res. 2019; 52: 1877

      For examples of stereoselective domino reactions to synthesize 3,4-annulated indole scaffolds see:
    • 3a Caruana L, Fochi M, Franchini MC, Ranieri S, Mazzanti A, Bernardi L. Chem. Commun. 2014; 50: 445
    • 3b Romanini S, Galletti E, Caruana L, Mazzanti A, Himo F, Santoro S, Fochi M, Bernardi L. Chem. Eur. J. 2015; 21: 17578
    • 3c Caruana L, Fochi M, Bernardi L. Synlett 2017; 28: 1530
    • 3d Lu Y, Yuan H, Zhou S, Luo T. Org. Lett. 2017; 19: 620
  • 5 Antonaci F, Ghiotto N, Wu S, Pucci E, Costa A. SpringerPlus 2016; 5: 637
    • 6a Pezzoli G, Martignoni E, Pacchetti C, Angeleri V, Lamberti P, Muratorio A, Bonuccelli U, Mari MD, Foschi N, Cossutta E. Neurology 1995; 45 (03) S22
    • 6b Mantegani S, Brambilla E, Varasi M. Farmaco 1999; 54: 288

      For examples of syntheses of ergot derivatives see:
    • 7a Bennett JW, Klich M. Clin. Microbiol. Rev. 2003; 16: 497
    • 7b Kornfeld EC, Fornefeld EJ, Kline GB, Mann MJ, Jones RG, Woodward RB. J. Am. Chem. Soc. 1954; 76: 5256
    • 7c Kornfeld EC, Fornefeld EJ, Kline GB, Mann MJ, Morrison DE, Jones RG, Woodward RB. J. Am. Chem. Soc. 1956; 78: 3087
    • 7d Padwa A, Bur SK, Zhang H. J. Org. Chem. 2005; 70: 6833
    • 7e Julia M, Le Goffic F, Igolen J, Baillarge M. Tetrahedron Lett. 1969; 10: 1569
    • 7f Armstrong VW, Coulton S, Ramage R. Tetrahedron Lett. 1976; 17: 4313
    • 7g Oppolzer W, Francotte E, Battig K. Helv. Chim. Acta 1981; 64: 478
    • 7h Rebek J, Tai DF. Tetrahedron Lett. 1983; 24: 859
    • 7i Cacchi S, Ciattini PG, Morera E, Ortar G. Tetrahedron Lett. 1988; 29: 3137
    • 7j Moldvai I, Temesvari-Major E, Incze M, Szentirmay E, Gacs-Baitz E, Szantay C. J. Org. Chem. 2004; 69: 5993
    • 7k Kiguchi T, Hashimoto C, Ninomiya I. Heterocycles 1985; 23: 1377
    • 7l Kiguchi T, Hashimoto C, Ninomiya I, Barton DH. R, Lusinchi X, Milliet P. J. Chem. Soc., Perkin Trans. 1 1990; 707
    • 7m Somei M. Heterocycles 2008; 75: 1021
    • 7n Moldvai I, Temesvari-Major E, Incze M, Doernyei G, Szentirmay E, Szantay C. Helv. Chim. Acta 2005; 88: 1344
    • 7o Liu H, Jia Y. Nat. Prod. Rep. 2017; 34: 411
    • 7p Bhunia S, Chaudhuri S, Bisai A. Chem. Eur. J. 2017; 23: 11234
    • 7q Chaudhuri S, Bhunia S, Roy A, Das MK, Bisai A. Org. Lett. 2018; 20: 288
    • 8a Arcamone F, Chain EB, Ferretti A, Minghetti A, Pennella P, Tonolo A, Vero L. Proc. R. Soc. London, Ser. B 1961; 155: 26 LP-54
    • 8b Arcamone F, Bonino C, Chain EB, Ferretti A, Pennella P, Tonolo A, Vero L. Nature 1960; 187: 238
    • 8c Křen V, Mehta P, Rylko V, Flieger M, Kozová J, Sajdl P, Řeháček Z. Zentralbl. Mikrobiol. 1987; 142: 71
    • 8d Mapelli E, Alpegiani M, Paissoni P. Org. Process Res. Dev. 2006; 10: 198
    • 8e Misner JW, Kennedy JH, Biggs WS. Org. Process Res. Dev. 1997; 1: 77
  • 9 Despotopoulou C, McKeon SC, Connon R, Coeffard V, Muller-Bunz H, Guiry PJ. Eur. J. Org. Chem. 2017; 6734
  • 10 Connon R, Guiry PJ. Eur. J. Org. Chem. 2019; 5950
    • 11a Green BS, Heller L. J. Org. Chem. 1974; 39: 196
    • 11b D’Auria M, Racioppi R. Tetrahedron 1997; 53: 17307
    • 11c D’Auria M, Piancatelli G, Vantaggi A. J. Chem. Soc., Perkin Trans. 1 1990; 2999
    • 11d D’Auria M, Vantaggi A. Tetrahedron 1992; 48: 2523
    • 11e Chimichi S, Sarti-Fantoni P. J. Org. Chem. 1987; 52: 5124
    • 11f Curme HG, Natale CC, Kelley DJ. J. Phys. Chem. 1967; 71: 767

      For the initial synthesis of bis(oxazoline) ligands of type L1 see:
    • 12a McManus HA, Guiry PJ. J. Org. Chem. 2002; 67: 8566

    • For selected reports of their use in asymmetric catalysis see:
    • 12b McManus HA, Cozzi PG, Guiry PJ. Adv. Synth. Catal. 2006; 348: 551
    • 12c Hargaden GC, McManus HA, Cozzi PG, Guiry PJ. Org. Biomol. Chem. 2007; 5: 763
    • 12d O’Reilly S, Aylward M, Keogh-Hansen C, Fitzpatrick B, McManus HA, Müller-Bunz H, Guiry PJ. J. Org. Chem. 2015; 80: 10177
    • 12e Coeffard V, Aylward M, Guiry PJ. Angew. Chem. Int. Ed. 2009; 48: 9152
    • 12f Hargaden GC, O’Sullivan TP, Guiry PJ. Org. Biomol. Chem. 2008; 6: 562

      For reports of the use of ligands L1 in the asymmetric Friedel–Crafts alkylation see:
    • 13a Du D.-M, Liu H, Lu S.-F, Xu J. Chem. Asian J. 2008; 3: 1111
    • 13b Du D.-M, Liu H, Xu J. Org. Lett. 2007; 9: 4725
    • 13c Du D.-M, Lu S.-F, Xu J. Org. Lett. 2006; 8: 2135

    • For selected reviews on the use of oxazoline-containing ligands in asymmetric catalysis see:
    • 13d O’Reilly S, Guiry PJ. Synthesis 2014; 46: 722
    • 13e Desimoni G, Faita G, Jørgensen KA. Chem. Rev. 2011; 111: PR284
    • 13f Hargaden GC, Guiry PJ. Chem. Rev. 2009; 109: 2505
    • 13g McManus HA, Guiry PJ. Chem. Rev. 2004; 104: 4151

      For examples of domino reactions terminating in an aldol reaction:
    • 14a Tian J.-M, Yuan Y.-H, Xie Y.-Y, Zhang S.-Y, Ma W.-Q, Zhang F.-M, Wang S.-H, Zhang X.-M, Tu Y.-Q. Org. Lett. 2017; 19: 6618
    • 14b Guevara-Pulido JO, Andres JM, Pedrosa R. RSC Adv. 2015; 5: 65975

    • For selected reviews on domino reactions:
    • 14c Pellissier H. Adv. Synth. Catal. 2012; 354: 237
    • 14d Pellissier H. Adv. Synth. Catal. 2019; 361: 1733
  • 15 Ubukata S, Ito J.-I, Oguri R, Nishiyama H. J. Org. Chem. 2016; 81: 3347
  • 16 For an example of the metal-catalyzed synthesis of bis(indole)methane derivatives see: Beltra J, Gimeno MC, Herrera RP. Beilstein J. Org. Chem. 2014; 10: 2206
  • 17 For a short review on the isolation, biological activity and synthesis of bis(indole)methane derivatives see: Majik MS, Parameswaran PS, Praveen PJ. Synthesis 2015; 47: 1827
  • 18 Taylor RD, MacCoss M, Lawson AD. G. J. Med. Chem. 2014; 57: 5845