Synthesis 2016; 48(20): 3479-3503
DOI: 10.1055/s-0035-1561490
feature
© Georg Thieme Verlag Stuttgart · New York

Organocatalytic Multicomponent Reactions of 1,3-Dicarbonyls for the Synthesis of Enantioenriched Heterocycles

Haiying Du
,
Yohan Dudognon
,
Maria del Mar Sanchez Duque
,
Sébastien Goudedranche
,
Damien Bonne
,
Jean Rodriguez
,
Xavier Bugaut*
,
Thierry Constantieux*
Further Information

Publication History

Received: 13 May 2016

Accepted after revision: 01 June 2016

Publication Date:
16 August 2016 (online)


Both authors contributed equally to this study.

Abstract

In this feature article, a general perspective of the research program aimed towards the preparation of polycyclic heterocycles by the means of enantioselective organocatalytic multicomponent reactions is presented. Guidelines for reaction design, including the selection of substrates and organocatalysts are discussed. For all transformations, scope and limitations are presented, along with post-functionalization to afford diversified heterocyclic scaffolds.

1 Introduction

2 Type I Products: 1,4,5,6-Tetrahydropyridines

3 Type II Products: 1,2,3,4-Tetrahydropyridines

4 Type III Products: Bridged Perhydropyridines

5 Conclusion and Perspective

Supporting Information

 
  • References

  • 1 Present address: College of Materials, Chemistry & Chemical Engineering, Chengdu University of Technology, Dongsanlu, Erxianqiao, Chengdu 610059, Sichuan, P. R. of China.
  • 2 Present address: Département de Chimie Organique, Université de Genève, Quai Ernest Ansermet 30, 1211 Genève 4, Switzerland.
  • 3 Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257
    • 5a Yu J, Shi F, Gong L.-Z. Acc. Chem. Res. 2011; 44: 1156
    • 5b Thu Pham H, Chataigner I, Renaud J.-L. Curr. Org. Chem. 2012; 16: 1754
    • 5c Wan J.-P, Liu Y. RSC Adv. 2012; 2: 9763
    • 6a Moreau J, Duboc A, Hubert C, Hurvois J.-P, Renaud J.-L. Tetrahedron Lett. 2007; 48: 8647
    • 6b Jiang J, Yu J, Sun X.-X, Rao Q.-Q, Gong L.-Z. Angew. Chem. Int. Ed. 2008; 47: 2458
    • 7a Hayashi Y, Gotoh H, Hayashi T, Shoji M. Angew. Chem. Int. Ed. 2005; 44: 4212
    • 7b Franke PT, Johansen RL, Bertelsen S, Jørgensen KA. Chem. Asian J. 2008; 3: 216
    • 8a Jiang B, Rajale T, Wever W, Tu S.-J, Li G. Chem. Asian J. 2010; 5: 2318
    • 8b Touré BB, Hall DG. Chem. Rev. 2009; 109: 4439
    • 8c Ruijter E, Scheffelaar R, Orru RV. A. Angew. Chem. Int. Ed. 2011; 50: 6234
    • 8d Climent MJ, Corma A, Iborra S. RSC Adv. 2012; 2: 16
    • 8e Dömling A, Wang W, Wang K. Chem. Rev. 2012; 112: 3083
    • 8f Brauch S, van Berkel SS, Westermann B. Chem. Soc. Rev. 2013; 42: 4948
    • 8g Cioc RC, Ruijter E, Orru RV. A. Green Chem. 2014; 16: 2958
    • 8h Zhu J, Wang Q, Wang M.-X. Multicomponent Reactions in Organic Synthesis . Wiley-VCH; Weinheim: 2014
    • 9a Simon C, Constantieux T, Rodriguez J. Eur. J. Org. Chem. 2004; 4957
    • 9b Liéby-Muller F, Simon C, Constantieux T, Rodriguez J. QSAR Comb. Sci. 2006; 25: 432
    • 9c Sanchez Duque MM, Allais C, Isambert N, Constantieux T, Rodriguez J. Top. Heterocycl. Chem. 2010; 23: 227
    • 9d Coquerel Y, Boddaert T, Presset M, Mailhol D, Rodriguez J. Multiple Bond-Forming Transformations: The Key Concept toward Eco-Compatible Synthetic Organic Chemistry. In Ideas in Chemistry and Molecular Sciences. Pignataro B. Wiley-VCH; Weinheim: 2010: 187
    • 9e Green NJ, Sherburn MS. Aust. J. Chem. 2013; 66: 267
    • 9f Bonne D, Constantieux T, Coquerel Y, Rodriguez J. Chem. Eur. J. 2013; 19: 2218
    • 9g Bugaut X, Bonne D, Coquerel Y, Rodriguez J, Constantieux T. Curr. Org. Chem. 2013; 17: 1920
    • 9h Bugaut X, Constantieux T, Coquerel Y, Rodriguez J. 1,3-Dicarbonyls in Multicomponent Reactions . In Multicomponent Reactions in Organic Synthesis . Zhu J, Wang Q, Wang M.-X. Wiley-VCH; Weinheim: 2014: 109
    • 9i Stereoselective Multiple Bond-Forming Transformations in Organic Synthesis. Rodriguez J, Bonne D. Wiley; Hoboken: 2015
  • 10 For a review on organocatalytic enantioselective Michael additions, see: Zhang Y, Wang W. Catal. Sci. Tech. 2012; 2: 42
    • 11a Du H, Rodriguez J, Bugaut X, Constantieux T. Adv. Synth. Catal. 2014; 356: 851
    • 11b For the racemic version, see: Liéby-Muller F, Constantieux T, Rodriguez J. Synlett 2007; 1323
  • 12 Dudognon Y, Du H, Rodriguez J, Bugaut X, Constantieux T. Chem. Commun. 2015; 51: 1980
    • 13a Sanchez Duque MM, Baslé O, Génisson Y, Plaquevent J.-C, Bugaut X, Constantieux T, Rodriguez J. Angew. Chem. Int. Ed. 2013; 52: 14143

    • For racemic versions, see:
    • 13b Liéby-Muller F, Constantieux T, Rodriguez J. J. Am. Chem. Soc. 2005; 127: 17176
    • 13c El Asri Z, Génisson Y, Guillen F, Baslé O, Isambert N, Sanchez Duque MM, Ladeira S, Rodriguez J, Constantieux T, Plaquevent J.-C. Green Chem. 2011; 13: 2549
    • 14a For a pseudo-three-component reaction, see: Bertelsen S, Johansen RL, Jørgensen KA. Chem. Commun. 2008; 3016
    • 14b For a trimolecular coupling involving the in situ generation of an α,β-unsaturated imine, see: Jiang J, Yu J, Sun X.-X, Rao Q.-Q, Gong L.-Z. Angew. Chem. Int. Ed. 2008; 47: 2458
    • 14c For a transformation with a nitroolefin as the Michael acceptor, see: Wang Y, Han R.-G, Zhao Y.-L, Yang S, Xu P.-F, Dixon DJ. Angew. Chem. Int. Ed. 2009; 48: 9834
    • 14d For the synthesis of seven-membered rings from β-diketones, phenylenediamines, and oxindoles, see: Wang Y, Shi F, Yao X.-X, Sun M, Dong L, Tu S.-J. Chem. Eur. J. 2014; 20: 15047
    • 14e For the synthesis of highly substituted spirooxindoles by a four-component coupling, see: Huang X, Pham K, Yi W, Zhang X, Clamens C, Hyatt JH, Jasinsk JP, Tayvah U, Zhang W. Adv. Synth. Catal. 2015; 357: 3820
    • 14f For a recent sequential one-pot coupling with benzylamine as ammonia surrogate, see: Rong C, Pan H, Liu M, Tian H, Shi Y. Chem. Eur. J. 2016; 22: 2887
  • 15 We have also recently described early results of organocatalytic multicomponent reactions with α-substituted enals, however, with low enantioselectivities: Du H, Rodriguez J, Bugaut X, Constantieux T. Synthesis 2015; 47: 2188 . These results will not be further discussed in this Feature Article
  • 16 There is also a possibility to prepare in a stepwise fashion suitably substituted 4-aryl-1,4-dihydropyridines with a free nitrogen atom and to oxidize them into axially chiral 4-arylpyridines with a central-to-axial conversion of chirality: Quinonero O, Jean M, Vanthuyne N, Roussel C, Bonne D, Constantieux T, Bressy C, Bugaut X, Rodriguez J. Angew. Chem. Int. Ed. 2016; 55: 1401
    • 17a For the original report, see: Franzén J, Fisher A. Angew. Chem. Int. Ed. 2009; 48: 787
    • 17b For a review, see ref. 9g.
    • 18a For the original report, see: Jin Z, Wang X, Huang H, Liang X, Ye J. Org. Lett. 2011; 13: 564
    • 18b For a review, see ref. 9g.
  • 19 Nigst TA, Westermaier M, Ofial AR, Mayr H. Eur. J. Org. Chem. 2008; 2369
    • 20a Zhang W, Franzén J. Adv. Synth. Catal. 2010; 352: 499
    • 20b Wu X, Dai X, Nie L, Fang H, Chen J, Ren Z, Cao W, Zhao G. Chem. Commun. 2010; 46: 2733
    • 20c Zhang W, Bah J, Wohlfarth A, Franzén J. Chem. Eur. J. 2011; 17: 13814
    • 21a Xu L.-W, Li L, Shi Z.-H. Adv. Synth. Catal. 2010; 352: 243
    • 21b Jensen KL, Dickmeiss G, Jiang H, Albrecht Ł, Jørgensen KA. Acc. Chem. Res. 2012; 45: 248
    • 21c Meninno S, Lattanzi A. Chem. Commun. 2013; 49: 3821
    • 22a Du H, Rodriguez J, Bugaut X, Constantieux T. Chem. Eur. J. 2014; 20: 8458

    • For related reports, see:
    • 22b Horitsugi N, Kojima K, Yasui K, Sohtome Y, Nagasawa K. Asian J. Org. Chem. 2014; 3: 445
    • 22c Goldys AM, Núñez MG, Dixon DJ. Org. Lett. 2014; 16: 6294
    • 23a Alemán J, Marcos V, Marzo L, García Ruano JL. Eur. J. Org. Chem. 2010; 4482
    • 23b Enders D, Grossmann A, Huang H, Raabe G. Eur. J. Org. Chem. 2011; 4298
  • 24 Liu Y.-Z, Zhang J, Xu P.-F, Luo Y.-C. J. Org. Chem. 2011; 76: 7551
  • 25 For seminal work in this direction in the racemic series, see: Simon C, Peyronel J.-F, Rodriguez J. Org. Lett. 2001; 3: 2145
  • 26 For a related sequential reaction, see: Rueping M, Volla CM. R, Bolte M, Raabe G. Adv. Synth. Catal. 2011; 353: 2853
  • 27 For a nonenantioselective related reaction, see: Wan J.-P, Zhong S, Liu Y. Synthesis 2015; 47: 3611
    • 28a For a key seminal study, see: Evans DA, Ennis MD, Le T, Mandel N, Mandel G. J. Am. Chem. Soc. 1984; 106: 1154

    • For applications in enantioselective catalysis, see:
    • 28b Liu Q, Rovis T. Org. Lett. 2009; 11: 2856
    • 28c Kim M.-h, Choi S.-h, Lee Y.-J, Lee J, Nahm K, Jeong B.-S, Park H.-g, Jew S.-s. Chem. Commun. 2009; 782
    • 28d Shin SH, Baek EH, Hwang G.-S, Ryu DH. Org. Lett. 2015; 17: 4746
  • 29 See experimental part for details.
  • 30 Elsner P, Jiang H, Nielsen JB, Pasi F, Jørgensen KA. Chem. Commun. 2008; 5827
    • 31a This reaction was already known with conventional heating: Sato M, Kanuma N, Kato T. Chem. Pharm. Bull. 1982; 30: 1315

    • For examples of the advantage of microwave irradiation for the synthesis of 1,3-dicarbonyl compounds through ketoketene intermediates, see:
    • 31b Presset M, Coquerel Y, Rodriguez J. J. Org. Chem. 2009; 74: 415
    • 31c Presset M, Mailhol D, Coquerel Y, Rodriguez J. Synthesis 2011; 2549
    • 31d Mohanan K, Presset M, Mailhol D, Coquerel Y, Rodriguez J. Chem. Eur. J. 2012; 18: 9217
    • 31e Dudognon Y, Presset M, Rodriguez J, Coquerel Y, Bugaut X, Constantieux T. Chem. Commun. 2016; 52: 3010
  • 32 Jurberg ID, Peng B, Wöstefeld E, Wasserloos M, Maulide N. Angew. Chem. Int. Ed. 2012; 51: 1950

    • For other examples of combination of multicomponent reactions, see:
    • 33a Paravidino M, Scheffelaar R, Schmitz RF, de Kanter FJ. J, Groen MB, Ruijter E, Orru RV. A. J. Org. Chem. 2007; 72: 10239
    • 33b Scheffelaar R, Nijenhuis RA. K, Paravidino M, Lutz M, Spek AL, Ehlers AW, de Kanter FJ. J, Groen MB, Orru RV. A, Ruijter E. J. Org. Chem. 2009; 74: 660
    • 33c Elders N, van der Born D, Hendrickx LJ. D, Timmer BJ. J, Krause A, Janssen E, de Kanter FJ. J, Ruijter E, Orru RV. A. Angew. Chem. Int. Ed. 2009; 48: 5856
    • 33d Znabet A, Polak MM, Janssen E, de Kanter FJ. J, Turner NJ, Orru RV. A, Ruijter E. Chem. Commun. 2010; 46: 7918
    • 33e Deng X.-X, Du F.-S, Li Z.-C. ACS Macro Lett. 2014; 3: 667
  • 34 For a review, see: Kouznetsov VV. Tetrahedron 2009; 65: 2721
  • 35 For means of comparison in 19F NMR, an authentic sample of product 30 was prepared by the treatment of 29 with potassium phenylethynyltrifluoroborate (24) in the presence of Sc(OTf)3. See experimental part for details.
  • 36 The known trapping of the activated iminium ion by the organotrifluoroborate salt was not observed, see: Lee S, MacMillan DW. C. J. Am. Chem. Soc. 2007; 129: 15438

    • For recent reviews on organo- and metal-dual catalysis, see:
    • 37a Du Z, Shao Z. Chem. Soc. Rev. 2013; 42: 1337
    • 37b Lohr TL, Marks TJ. Nat. Chem. 2015; 7: 477
    • 38a Sanchez Duque M.dM, Baslé O, Isambert N, Gaudel-Siri A, Génisson Y, Plaquevent J.-C, Rodriguez J, Constantieux T. Org. Lett. 2011; 13: 3296
    • 38b Mohanan K, Coquerel Y, Rodriguez J. Org. Lett. 2012; 14: 4686
    • 38c Mailhol D, Sanchez Duque MdM, Raimondi W, Bonne D, Constantieux T, Coquerel Y, Rodriguez J. Adv. Synth. Catal. 2012; 354: 3523
    • 38d Mailhol D, Castillo J.-C, Mohanan K, Abonia R, Coquerel Y, Rodriguez J. ChemCatChem 2013; 5: 1192
    • 38e Goudedranche S, Bugaut X, Constantieux T, Bonne D, Rodriguez J. Chem. Eur. J. 2014; 20: 410
    • 38f Quintard A, Cheshmedzhieva D, Sanchez Duque MdM, Gaudel-Siri A, Naubron J.-V, Génisson Y, Plaquevent J.-C, Bugaut X, Rodriguez J, Constantieux T. Chem. Eur. J. 2015; 21: 778

      For related studies by other research groups, see:
    • 39a Jakubec P, Helliwell M, Dixon DJ. Org. Lett. 2008; 10: 4267
    • 39b Paixão MW, Nielsen M, Jacobsen CB, Jørgensen KA. Org. Biomol. Chem. 2008; 6: 3467
    • 39c Yang T, Ferrali A, Sladojevich F, Campbell L, Dixon DJ. J. Am. Chem. Soc. 2009; 131: 9140
    • 39d Jakubec P, Cockfield DM, Dixon DJ. J. Am. Chem. Soc. 2009; 131: 16632
    • 39e Jakubec P, Cockfield DM, Hynes PS, Cleator E, Dixon DJ. Tetrahedron: Asymmetry 2011; 22: 1147
    • 39f Dai X, Wu X, Fang H, Nie L, Chen J, Deng H, Cao W, Zhao G. Tetrahedron 2011; 67: 3034
    • 39g Kyle AF, Jakubec P, Cockfield DM, Cleator E, Skidmore J, Dixon DJ. Chem. Commun. 2011; 47: 10037
    • 39h Chen X, Zhu W, Qian W, Feng E, Zhou Y, Wang J, Jiang H, Yao Z.-J, Liu H. Adv. Synth. Catal. 2012; 354: 2151
    • 39i Wu X, Liu Q, Fang H, Chen J, Cao W, Zhao G. Chem. Eur. J. 2012; 18: 12196
    • 39j De Fusco C, Meninno S, Tedesco C, Lattanzi A. Org. Biomol. Chem. 2013; 11: 896
    • 39k Huang Y.-m, Zheng C.-w, Zhao G. J. Org. Chem. 2015; 80: 3798
    • 39l Zeng X.-M, Meng C.-Y, Bao J.-X, Xu D.-C, Xie J.-W, Zhu W.-D. J. Org. Chem. 2015; 80: 11521
    • 39m Goodman CG, Johnson JS. J. Am. Chem. Soc. 2015; 137: 14574
    • 40a Okino T, Hoashi Y, Takemoto Y. J. Am. Chem. Soc. 2003; 125: 12672
    • 40b Okino T, Hoashi Y, Furukawa T, Xu X, Takemoto Y. J. Am. Chem. Soc. 2005; 127: 119
  • 41 Relative configuration of the additional stereogenic center was attributed by NOESY analysis. See Supporting Information for details.
  • 42 Charonnet E, Filippini M.-H, Rodriguez J. Synthesis 2001; 788
  • 43 NOESY analysis shows correlations for the hydrogen atom linked on the carbon atom bearing the bromine atom only with its direct neighbors. The absence of longer distance correlations is, however, not conclusive for the relative configuration of the additional stereocenter.

    • For reviews on multicomponent reactions with isonitriles, see:
    • 44a Ugi I, Werner B, Dömling A. Molecules 2003; 8: 53
    • 44b Dömling A. Chem. Rev. 2006; 106: 17
    • 44c El Kaïm L, Grimaud L. Ugi–Smiles and Passerini–Smiles Couplings . In Multicomponent Reactions in Organic Synthesis . Zhu J, Wang Q, Wang M.-X. Wiley-VCH; Weinheim: 2014: 73-108
    • 44d Váradi A, Palmer T, Notis Dardashti R, Majumdar S. Molecules 2016; 21: 19
  • 45 Molander GA, Katona BW, Machrouhi F. J. Org. Chem. 2002; 67: 8416
  • 46 Ley SV, Smith SC, Woodward PR. Tetrahedron 1992; 48: 1145