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
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
(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 17
(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 104
(a) Stompor M, Kału\(\dot{z}\)ny M and \(\dot{Z}\)arowska B 2016 Biotechnological methods for chalcone reduction using whole cells of Lactobacillus, Rhodococcus 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 3193
(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. 277
(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 2815
(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 2211
(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 11894
(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. 71 979
(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. 6 277
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 9721
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. 44 542
(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 8516
(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. 79 172
(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 1138
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
Special Section on Transition Metal Catalyzed Synthesis of Medicinally Relevant Molecules
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Patel, M., Sushmita & Verma, A.K. Copper-catalyzed stereo- and chemoselective synthesis of enaminones via Michael type addition. J Chem Sci 130, 70 (2018). https://doi.org/10.1007/s12039-018-1465-9
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12039-018-1465-9