Copper-catalyzed stereo- and chemoselective synthesis of enaminones via Michael type addition

Regular Article

Abstract

An efficient strategy for the synthesis of \(\upalpha \),\(\upbeta \)-unsaturated enaminones by the nucleophilic addition of N-heterocycles such as indole and imidazoles onto electronically bias alkynones under mild reaction conditions is described. Key feature of this reaction is the chemoselective addition of N-heterocycles onto ynones without affecting the \(1^{\mathrm{o}}\) amino groups (aromatic and aliphatic) of 5-aminoindole and tryptamine. The stereochemistry of the products was controlled by the tuning of reaction time. The mechanism of the reaction involves the Michael type addition of N-heterocycles on ynones via allene formation.

Graphical Abstract

Keyword

Copper alkynones hydroamination Michael addition enaminones 

Notes

Acknowledgements

We gratefully acknowledge the Council of Scientific and Industrial Research, India [02(0264)/16/EMR-II] for financial support and USIC, University of Delhi for providing instrumentation facilities. M.P. and Sushmita are thankful to DST-SERB and UGC, New Delhi for fellowships.

Supplementary material

12039_2018_1465_MOESM1_ESM.pdf (3.5 mb)
Supplementary material 1 (pdf 3608 KB)

References

  1. 1.
    (a) Jioui I, Danoun K, Solhy A, Jouiad M, Zahouily M, Essaid B, Len C and Fihri A 2016 Modified fluorapatite as a highly efficient catalyst for the synthesis of chalcones via Claisen–Schmidt condensation reaction J. Indus. Eng. Chem. 39 218; (b) Li Z, Zhao H, Han H, Liu Y, Song J, Guo W, Chu W and Sun Z 2017 Graphene-supported ZnO nanoparticles: An efficient heterogeneous catalyst for the Claisen-Schmidt condensation reaction without additional base Tetrahedron Lett. 58 3984; (c) Sida A, Lamaraa K, Mokhtaria M, Ziania N and Mosset P 2011 Synthesis and characterization of 1-formyl-3-phenyl-5-aryl-2-pyrazolines Eur. J. Chem. 2 311; (d) Nasr-Esfahani M, Daghaghale M and Taei M 2017 Catalytic synthesis of chalcones and pyrazolines using nanorod vanadate sulfuric acid: An efficient and reusable catalyst J. Chin. Chem. Soc. 64 17Google Scholar
  2. 2.
    (a) Gayon E, Szymczyk M, Gerard H, Vrancken E and Campagne J M 2012 Stereoselective and catalytic access to \(\beta \)-enaminones: an entry to pyrimidines J. Org. Chem. 77 9205; (b) Palmieri G and Cimarelli C 2006 Chemo- and stereoselective reduction of enaminones for the preparation of biologically active compounds ARKIVOC vi 104Google Scholar
  3. 3.
    (a) Stompor M, Kału\(\dot{z}\)ny M and \(\dot{Z}\)arowska B 2016 Biotechnological methods for chalcone reduction using whole cells of LactobacillusRhodococcus and Rhodotorula strains as a way to produce new derivatives Appl. Microbiol. Biotechnol. 100 8371; (b) Ritter M, Martins R M, Rosa S A, Malavolta J L, Lund R G, Flores A F C and Pereira C M P 2015 Green synthesis of chalcones and microbiological evaluation J. Braz. Chem. Soc. 26 1201; (c) Valdameri G, Gauthier C, Terreux R, Kachadourian R, Day B J, Winnischofer S M B, Rocha M E M, Frachet V, Ronot X, Pietro A D and Boumendjel A 2012 Investigation of chalcones as selective inhibitors of the breast cancer resistance protein: critical role of methoxylation in both inhibition potency and cytotoxicity J. Med. Chem. 55 3193Google Scholar
  4. 4.
    (a) Lefemine D V, Damn M and Baratschi F 1962 Isolation and characterization mitiromycin and other antibiotics J. Am. Chem. Soc. 84 3184; (b) Collinus J F 1965 Application of chalcone in synthesis of 1-(1, 5-benzodiazepino) substituted analogues of indole Brit. Med. Bull. 21 223; (c) Schach V W M and Els H 1961 Intramolecular cyclization of unsaturated diazoketones J. Am. Chem. Soc. 83 4678; (d) Garattini S and Valzelli L 1965 Serotonin (Amsterdam: Elsevier) p. 277Google Scholar
  5. 5.
    (a) Karpov A S and Muller T J J 2003 New entry to a three-component pyrimidine synthesis by TMS-ynones via Sonogashira coupling Org. Lett. 5 3451; (b) Karpov A S and Muller T J J 2003 Straightforward novel one-pot enaminone and pyrimidine syntheses by coupling-addition-cyclocondensation sequences Synthesis 18 2815Google Scholar
  6. 6.
    (a) Dixon K and Greenhill J V 1974 A study of the rates of hydrolysis of certain enaminones J. Chem. Soc., Perkin Trans. 2 164; (b) Greenhill, J V 1976 Aromatic enaminones. Part 1. Ultraviolet absorption of \(N\)-aryl enaminones derived from dimedone J. Chem. Soc., Perkin I 2207; (c) Dixon K and Greenhill J V 1976 Use of cyclohexane-1,3-dione derivatives in the preparation of enaminones J. Chem. Soc., Perkin Trans. I 2211Google Scholar
  7. 7.
    (a) Yang Y, Shen Y, Wang X, Zhang Y, Wang D and Shi X 2016 Triazole acetyl gold (III) catalyzed Meyer–Schuster rearrangement of propargyl alcohols Tetrahedron Lett. 57 2280; (b) Gandeepan P, Rajamalli P and Cheng C H 2014 palladium-catalyzed dehydrogenative \(\beta \)-arylation of simple saturated carbonyls by aryl halides ACS Catal. 4 4485; (c) García-Álvarez J, Díez J, Vidal C and Vicent C 2013 New Ag (I)–Iminophosphorane coordination polymers as efficient catalysts precursors for the mw-assisted meyer–schuster rearrangement of propargylic alcohols Inorg. Chem. 52 6533; (d) Mattia E, Porta A, Merlini V, Zanoni G and Vidari G 2012 One-pot consecutive reactions based on the synthesis of conjugated enones by the re-catalysed meyer–schuster rearrangement Chem. Eur. J. 18 11894Google Scholar
  8. 8.
    (a) Smirnova Y V and Krasnaya Z A 2000 Methods of synthesis of conjugated \(\omega \)-amino ketones Russ. Chem. Rev. 69 1021; (b) Michael J P, De Koning C B, Gravestock D, Hosken G D, Howard A S, Jungmann C M, Krause R W M, Parsons A S, Pelly S C and Stanbury T V 1999 Enaminones: versatile intermediates for natural product synthesis Pure Appl. Chem. 71 979Google Scholar
  9. 9.
    (a) Lue P and Greenhill J V 1997 Enaminones in heterocyclic synthesis Adv. Heterocycl. Chem. 67 207; (b) Zhang T, Jia Y M, Yan S J, Yu C and Huang Z T 2009 Synthesis of BF\(_{2 }\)complex of 3-methylthio enaminones 2009 156; (c) Michael J P and Gravestock D 1997 Enaminones as a intermediate in the synthesis of indolizidines alkaloids Pure Appl. Chem. 69 583; (d) Greenhill J V 1977 Enaminones Chem. Soc. Rev. 6 277Google Scholar
  10. 10.
    Jiang H F, Li J H and Chen Z W 2010 One-pot domino reactions for synthesis of heterocyclic[3.3.3]propellanes and spiro[cyclopenta[\(b\)]pyridine-4,2\(^{\prime }\)-indenes] Tetrahedron 66 9721CrossRefGoogle Scholar
  11. 11.
    Chauhan R, Dwivedi J, Anees A A S and Kishore D 2011 Synthesis and antimicrobial activity of chalcone derivatives of indole nucleus Pharma Chem. J. 44 542Google Scholar
  12. 12.
    (a) Trofimov B A, Schmidt E Y, Zorina N V, Ivanova E V and Ushakov I A 2012 Transition-metal-free superbase-promoted stereoselective \(\alpha \)-vinylation of ketones with arylacetylenes: a general strategy for synthesis of \(\beta \),\(\gamma \)-unsaturated ketones J. Org. Chem. 77 6880; (b) Trofimov B A, Schmidt E Y, Ushakov I A, Zorina N V, Skitaltseva E V, Protsuk N I and Mikhaleva A I 2010 Base-catalyzed stereoselective vinylation of ketones with arylacetylenes: a new c(sp\(^{3})\)- c(sp\(^{2})\) bond-forming reaction Chem. Eur. J. 16 8516Google Scholar
  13. 13.
    (a) Patel M, Saunthwal R K and Verma A K 2017 Base-mediated hydroamination of alkynes Acc. Chem. Res. 50 240; (b) Verma A K, Joshi M and Singh V P 2011 base-mediated regio- and stereoselective intermolecular addition of alkynes to \(N\)-heterocycles Org. Lett. 13 1630; (c) Patel M, Saunthwal R K, Dhaked D K, Bharatam P V and Verma A K 2016 Metal-free intermolecular hydrophenoxylation of aryl alkynes Asian J. Org. Chem. 5 213; (d) Joshi M, Patel M, Tiwari R and Verma A K 2012 Base-mediated selective synthesis of diversely substituted \(N\)-heterocyclic enamines and enaminones by the hydroamination of alkynes J. Org. Chem. 77 5633; (e) Patel M, Saunthawal R K and Verma A K 2014 Base-catalyzed stereoselective intermolecular addition of imidazoles onto alkynes: an easy access to imidazolyl enamines Tetrahedron Lett. 55 1310; (f) Verma A K, Patel M, Joshi M, Likhar P R, Tiwari R K and Parang K 2014 Base-mediated chemo and stereoselective addition of 5-aminoindole/tryptamine and histamines onto alkynes J. Org. Chem. 79 172Google Scholar
  14. 14.
    (a) Joshi M, Tiwari R and Verma A K 2012 regioselective preferential nucleophilic addition of \(n\)-heterocycles onto haloarylalkynes over \(N\)-arylation of aryl halides Org. Lett. 14 1106; (b) Verma A K, Kesharwani T, Singh J, Tandon V and Larock R C 2009 Regioselective preferential nucleophilic addition of \(N\)-heterocycles onto haloarylalkynes over \(N\)-arylation of aryl halides Angew. Chem. Int. Edit. 48 1138Google Scholar

Copyright information

© Indian Academy of Sciences 2018

Authors and Affiliations

  1. 1.Synthetic Organic Chemistry Research Laboratory, Department of ChemistryUniversity of DelhiDelhiIndia

Personalised recommendations