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Current Organic Chemistry


ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

Review Article

Trienamines for the Organocatalytic Synthesis of Nitrogen-Containing Heterocycles

Author(s): Jessica R. Gutiérrez Cano, Julio López, Miguel A. Vázquez, David Cruz Cruz* and Clarisa Villegas Gómez*

Volume 23 , Issue 10 , 2019

Page: [1078 - 1089] Pages: 12

DOI: 10.2174/1385272823666190617164651

Price: $65


Nitrogen-containing heterocycles (NCH), constitute an important group of molecules, which are widely extended in whole chemical space. These compounds are of great interest due to their diverse biological activities. Currently, many compounds derived from NCH are used as powerful drugs for the treatment of diseases ranging from bactericides to anticancer agents. During last decade, the enantioselective synthesis of numerous heterocyclic compounds has been achieved through the use of chiral organocatalysts. The present contribution explores the application of the aminocatalysis towards the synthesis of NCH, particularly through the trienamine catalysis.

Keywords: Nitrogen-containing heterocycles, organocatalysis, aminocatalysis, trienamine catalysis, activation mode, cycloaddition reactions.

Graphical Abstract
Cordell, G.A.; Quinn-Beattie, M.L.; Farnsworth, N.R. The potential of alkaloids in drug discovery. Phytother. Res., 2001, 15(3), 183-205. []. [PMID: 11351353].
For selected examples, see (a) Kishor, P.S.; Vasantrao, H.P.; Venkatrao, K.P.; Hanumantrao, K.V. Nitrogen containing secondary metabolites from endophytes of medicinalplants and their biological/pharmacological activities-A review. Syst. Rev. Pharm., 2018, 9, 22-30.
(b) Banwell, M.G. New process for the synthesis of biologically relevant heterocycles. Pure Appl. Chem., 2008, 80, 669-679. [].
(a) Hajos, Z.G.; Parrish, D.R. Asymmetric synthesis of bicyclic intermediates of natural product chemistry. J. Org. Chem., 1974, 39, 1615-1621.
(b) List, B.; Lerner, R.A.; Barbas, C.F., III Proline-catalyzed direct asymmetric aldol reactions. J. Am. Chem. Soc., 2000, 122, 2395-2396. [].
(a) Donslund, B.S.; Johansen, T.K.; Poulsen, P.H.; Halskov, K.S.; Jørgensen, K.A. The diarylprolinol silyl ethers: ten years after. Angew. Chem. Int. Ed. Engl., 2015, 54(47), 13860-13874. []. [PMID: 26423028]
(b) Klier, L.; Tur, F.; Poulsen, P.H.; Jørgensen, K.A. Asymmetric cycloaddition reactions catalysed by diarylprolinol silyl ethers. Chem. Soc. Rev., 2017, 46(4), 1080-1102. []. [PMID: 27883141].
(a) Jen, W.S.; Wiener, J.J.M.; MacMillan, D.W.C. New strategies for organic catalysis: The first enantioselective organocatalytic 1,3-dipolar cycloaddition. J. Am. Chem. Soc., 2000, 122, 9874-9875. [].
(b) Ahrendt, K.A.; Borths, C.J.; MacMillan, D.W.C. New strategies for organic catalysis: the first highly enantioselective organocatalytic Diels–Alder reaction. J. Am. Chem. Soc., 2000, 122, 4243-4244.
(c) Northrup, A.B.; MacMillan, D.W.C. The first general enantioselective catalytic Diels-Alder reaction with simple α,β-unsaturated ketones. J. Am. Chem. Soc., 2002, 124(11), 2458-2460. []. [PMID: 11890793]
(d) Brown, S.P.; Goodwin, N.C.; MacMillan, D.W.C. The first enantioselective organocatalytic Mukaiyama-Michael reaction: A direct method for the synthesis of enantioenriched γ-butenolide architecture. J. Am. Chem. Soc., 2003, 125(5), 1192-1194. []. [PMID: 12553821].
(a) Singh, R.P.; Bartelson, K.; Wang, Y.; Su, H.; Lu, X.; Deng, L. Enantioselective Diels-Alder reaction of simple α,β-unsaturated ketones with a cinchona alkaloid catalyst. J. Am. Chem. Soc., 2008, 130(8), 2422-2423. []. [PMID: 18251543]
(b) Liu, Y.; Kang, T-R.; Liu, Q-Z.; Chen, L-M.; Wang, Y-C.; Liu, J.; Xie, Y-M.; Yang, J-L.; He, L. Enantioselective [4 + 2] cycloaddition of cyclic N-sulfimines and acyclic enones or ynones: A concise route to sulfamidate-fused 2,6-disubstituted piperidin-4-ones. Org. Lett., 2013, 15(23), 6090-6093. []. [PMID: 24215326]
(c) Su, Z.; Lee, H.W.; Kim, C.K. Asymmetric 1,4-Michael addition reaction catalyzed by a cinchona alkaloid derived primary amine: a theoretical investigation of the reaction mechanism and enantioselectivity. Eur. J. Org. Chem., 2013, 2013, 1706-1715. [].
Ishikawa, H.; Shiomi, S. Alkaloid synthesis using chiral secondary amine organocatalysts. Org. Biomol. Chem., 2016, 14(2), 409-424. []. [PMID: 26625722].
(a) Lelais, G.; MacMillan, D.W.C. Modern strategies in organic catalysis: The advent and development of iminium activation. Aldrichim Acta, 2006, 39, 79-87.
(b) Erkkilä, A.; Majander, I.; Pihko, P.M. Iminium catalysis. Chem. Rev., 2007, 107(12), 5416-5470. []. [PMID: 18072802].
(a) List, B. Asymmetric aminocatalysis. Synlett, 2001, 11, 1675-1686. [].
(b) Notz, W.; Tanaka, F.; Barbas, C.F., III Enamine-based organocatalysis with proline and diamines: The development of direcatalytic asymmetric Aldol, Mannich, Michael, and Diels–Alder reactions. Acc. Chem. Res., 2004, 37(8), 580-591. []. [PMID: 15311957]
(c) List, B. Enamine catalysis is a powerful strategy for the catalytic generation and use of carbanion equivalents. Acc. Chem. Res., 2004, 37(8), 548-557. []. [PMID: 15311954]
(d) Mukherjee, S.; Yang, J.W.; Hoffmann, S.; List, B. Asymmetric enamine catalysis. Chem. Rev., 2007, 107(12), 5471-5569. []. [PMID: 18072803].
(a) Ramachary, D.B.; Reddy, Y.V. Dienamine catalysis: An emerging technology in organic synthesis. Eur. J. Org. Chem., 2012, 865-887.
(b) Marcos, V.; Alemán, J. Old tricks, new dogs: organocatalytic dienamine activation of α,β-unsaturated aldehydes. Chem. Soc. Rev., 2016, 45(24), 6812-6832. []. [PMID: 27805198].
(a) Kumar, I.; Ramaraju, P.; Mir, N.A. Asymmetric trienamine catalysis: New opportunities in amine catalysis. Org. Biomol. Chem., 2013, 11(5), 709-716. []. [PMID: 23247590]
(b) Reboredo, S.; Parra, A.; Alemán, J. Trienamines: their key role in extended organocatalysis for Diels-Alder reactions. Asymmetric Catal., 2013, 1, 24-31. [].
(a) Stiller, J.; Poulsen, P.H.; Cruz, D.C.; Dourado, J.; Davis, R.L.; Jørgensen, K.A. Organocatalytic [4+2] addition reactions via tetraenamina intermediate. Chem. Sci. (Camb.), 2014, 5, 2052-2056.
(b) Zhou, Q-Q.; Xiao, Y-C.; Yuan, X.; Chen, Y-C. Asymmetric Diels-Alder reactions of 2,4,6-trienals via tetraenamine catalysis. Asian J. Org. Chem., 2014, 3, 545-549. [].
(a) Jurberg, I.D.; Chatterjee, I.; Tannert, R.; Melchiorre, P. When asymmetric aminocatalysis meets the vinylogy principle. Chem. Commun. (Camb.), 2013, 49(43), 4869-4883. []. [PMID: 23598613]
(b) Hepburn, H.B.; Dell’Amico, L.; Melchiorre, P. Enantioselective vynylogous organocascade reactions. Chem. Rec., 2016, 16(4), 1787-1806. []. [PMID: 27256039].
Jia, Z-J.; Jiang, H.; Li, J-L.; Gschwend, B.; Li, Q-Z.; Yin, X.; Grouleff, J.; Chen, Y.C.; Jørgensen, K.A. Trienamines in asymmetric organocatalysis: Diels-Alder and tandem reactions. J. Am. Chem. Soc., 2011, 133(13), 5053-5061. []. [PMID: 21405125].
Cheng, R.P.; Gellman, S.H.; DeGrado, W.F. β-Peptides: From structure to function. Chem. Rev., 2001, 101(10), 3219-3232. []. [PMID: 11710070].
Jiang, H.; Gschwend, B.; Albrecht, Ł.; Hansen, S.G.; Jørgensen, K.A. Asymmetric trienamine catalysis for the construction of structurally rigid cyclic α,α-disubstituted amino acid derivatives. Chemistry, 2011, 17(33), 9032-9036. []. [PMID: 21744409].
Peifer, C.; Stoiber, T.; Unger, E.; Totzke, F.; Schächtele, C.; Marmé, D.; Brenk, R.; Klebe, G.; Schollmeyer, D.; Dannhardt, G. Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J. Med. Chem., 2006, 49(4), 1271-1281. []. [PMID: 16480264].
Rudi, A.; Evan, T.; Aknin, M.; Kashman, Y.; Polycitone, B.; Prepolycitrin, A. Polycitone B and prepolycitrin A: Two novel alkaloids from the marine ascidian Polycitor africanus. J. Nat. Prod., 2000, 63(6), 832-833. []. [PMID: 10869212].
Sellès, P. Synthesis and biological evaluation of himanimide C and unnatural analogues. Org. Lett., 2005, 7(4), 605-608. []. [PMID: 15704905].
Xiong, X-F.; Zhou, Q.; Gu, J.; Dong, L.; Liu, T-Y.; Chen, Y-C. Trienamine catalysis with 2,4-dienones: Development and application in asymmetric Diels-Alder reactions. Angew. Chem. Int. Ed. Engl., 2012, 51(18), 4401-4404. []. [PMID: 22344678].
Robertson, M.J.; Hadzic, G.; Ambrus, J.; Pomè, D.Y.; Hyde, E.; Whiting, A.; Mariana, A.; von Kleist, L.; Chau, N.; Haucke, V.; Robinson, P.J.; McCluskey, A. The Rhodadyns, a new class of small molecule inhibitors of dynamin GTPase activity. ACS Med. Chem. Lett., 2012, 3(5), 352-356. []. [PMID: 24900478].
Zhu, K.; Huang, H.; Wu, W.; Wei, Y.; Ye, J. Aminocatalyzed asymmetric Diels-Alder reaction of 2,4-dienals and rhodanine/hydantoin derivatives. Chem. Commun. (Camb.), 2013, 49(21), 2157-2159. []. [PMID: 23389754].
Zhou, Q-Q.; Yuan, X.; Xiao, Y-C.; Dong, L.; Chen, Y-C. Aminocatalytic asymmetric Diels-Alder reaction of phosphorus dienophiles and 2,4-dienals. Tetrahedron, 2013, 69, 10369-10374. [].
(a) Shie, J-J.; Fang, J-M.; Lai, P-T.; Wen, W-H.; Wang, S-Y.; Cheng, Y-S.E.; Tsai, K-C.; Yang, A-S.; Wong, C-H. A practical synthesis of zanamivir phosphonate congeners with potent anti-influenza activity. J. Am. Chem. Soc., 2011, 133(44), 17959-17965. []. [PMID: 21942552]
(b) Mucha, A.; Kafarski, P.; Berlicki, Ł. Remarkable potential of the α-aminophosphonate/phosphinate structural motif in medicinal chemistry. J. Med. Chem., 2011, 54(17), 5955-5980. []. [PMID: 21780776].
Liu, J-X.; Zhou, Q-Q.; Deng, J-G.; Chen, Y.C. An asymmetric normal-electron-demand aza-Diels-Alder reaction via trienamine catalysis. Org. Biomol. Chem., 2013, 11(47), 8175-8178. []. [PMID: 24193264].
Xiao, Y-C.; Yue, C-Z.; Chen, P-Q.; Chen, Y-C. Asymmetric dearomatic Diels-Alder reactions of diverse heteroarenes via π-system activation. Org. Lett., 2014, 16(12), 3208-3211. []. [PMID: 24892780].
Chen, P-Q.; Xiao, Y-C.; Yue, C-Z.; Chen, Y-C. Trienamine catalysis with linear deconjugated 3,5-dienones. Org. Chem. Front., 2014, 1, 490-493. [].
Chintalapudi, V.; Galvin, E.A.; Greenaway, R.L.; Anderson, E.A. Combining cycloisomerization with trienamine catalysis: a regiochemically flexible enantio- and diastereoselective synthesis of hexahydroindoles. Chem. Commun. (Camb.), 2016, 52(4), 693-696. []. [PMID: 26558507].
Hirose, T.; Izawa, Y.; Koyama, K.; Natori, S.; Iida, K.; Yahara, I.; Shimaoka, S.; Maruyama, K. The effects of new cytochalasins from Phomopsis sp. and the derivatives on cellular structure and actin polymerization. Chem. Pharm. Bull. (Tokyo), 1990, 38(4), 971-974. []. [PMID: 2199089].
Sellstedt, M.; Schwalfenberg, M.; Ziegler, S.; Antonchick, A.P.; Waldmann, H. Trienamine catalyzed asymmetric synthesis and biological investigation of a cytochalasin B-inspired compound collection. Org. Biomol. Chem., 2016, 14(1), 50-54. []. [PMID: 26606903].
Halskov, K.S.; Johansen, T.K.; Davis, R.L.; Steurer, M.; Jensen, F.; Jørgensen, K.A. Cross-trienamines in asymmetric organocatalysis. J. Am. Chem. Soc., 2012, 134(31), 12943-12946. []. [PMID: 22835208].
(a) Galliford, C.V.; Scheidt, K.A. Pyrrolidinyl-spirooxindole natural products as inspirations for the development of potential therapeutic agents. Angew. Chem. Int. Ed. Engl., 2007, 46(46), 8748-8758. []. [PMID: 17943924]
(b) El-Sharief, A.M.S.; Ammar, Y.A.; Belal, A.; El-Sharief, M.A.M.S.; Mohamed, Y.A.; Mehany, A.B.M.; Elhag Ali, G.A.M.; Ragab, A. Design, synthesis, molecular docking and biological activity evaluation of some novel indole derivatives as potent anticancer active agents and apoptosis inducers. Bioorg. Chem., 2019, 85, 399-412. []. [PMID: 30665034]
(c) Saraswat, P.; Jeyabalan, G.; Hassan, M.Z.; Rahman, M.; Nyola, N. Review of synthesis and various biological activities of spiro heterocyclic compounds comprising oxindole and pyrrolidine moities. Synth. Commun., 2016, 46, 1643-1664.
(d) Yin, L.; Hu, Q.; Emmerich, J.; Lo, M.M.; Metzger, E.; Ali, A.; Hartmann, R.W. Novel pyridyl- or isoquinolinyl-substituted indolines and indoles as potent and selective aldosterone synthase inhibitors. J. Med. Chem., 2014, 57(12), 5179-5189. []. [PMID: 24899257]
(e) Peddibhotla, S. 3-Substituted-3-hydroxy-2-oxindole, an emerging new scaffold for drug discovery with potential anti-cancer and other biological activities. Curr. Bioact. Compd., 2009, 5, 20-38.
(f) Eleftheriadis, N.; Neochoritis, C.G.; Leus, N.G. van der, Wouden P.E.; Domling, A.; Dekker, F.J. Rational development of a potent 15-lipoxygenase-1 inhibitor with in vitro and ex vivo anti-inflammatory properties. J. Med. Chem., 2015, 58(19), 7850-7862. []. [PMID: 26331552].
Zhou, Z.; Wang, Z.X.; Ouyang, Q.; Xiao, W.; Du, W.; Chen, Y.C. Cross-conjugated trienamine catalysis with a´-alkylidene 2-cyclohexenones: application in β, γ-regioselective aza-Diels-Alder reaction. Chemistry, 2017, 23(12), 2945-2949. []. [PMID: 28019058].
(a) Magdziak, D.; Meek, S.J.; Pettus, T.R.R. Cyclohexadienone ketals and quinols: four building blocks potentially useful for enantioselective synthesis. Chem. Rev., 2004, 104(3), 1383-1430. []. [PMID: 15008626]
(b) Albrecht, Ł.; Gómez, C.V.; Jacobsen, C.B.; Jørgensen, K.A. 1,4-Naphthoquinones in H-bond-directed trienamine-mediated strategies. Org. Lett., 2013, 15(12), 3010-3013. []. [PMID: 23730740]
(c) Johansen, T.K.; Gómez, C.V.; Bak, J.R.; Davis, R.L.; Jørgensen, K.A. Organocatalytic enantioselective cycloaddition reactions of dienamines with quinones. Chemistry, 2013, 19(49), 16518-16522. []. [PMID: 24281799].
Gu, J.; Xiao, B.X.; Chen, Y.R.; Du, W.; Chen, Y.C. Asymmetric diels-alder and cascade reaction of quinone imine ketals and 2,4-dienals: construction of chiral benzo [de] quinolone derivatives. Adv. Synth. Catal., 2016, 358, 296-302. [].
Li, Y.; Barløse, C.; Jørgensen, J.; Carlsen, B.D.; Jørgensen, K.A. Asymmetric catalytic aza-Diels-Alder/ring-closing cascade reaction forming bicyclic azaheterocycles by trienamine catalysis. Chemistry, 2017, 23(1), 38-41. []. [PMID: 27779801].
(a) Chen, F-E.; Huang, J. Reserpine: A challenge for total synthesis of natural products. Chem. Rev., 2005, 105(12), 4671-4706. []. [PMID: 16351058]
(b) Varchi, G.; Battaglia, A.; Samorì, C.; Baldelli, E.; Danieli, B.; Fontana, G.; Guerrini, A.; Bombardelli, E. Synthesis of deserpidine from reserpine. J. Nat. Prod., 2005, 68(11), 1629-1631. []. [PMID: 16309312]
(c) Herlé, B.; Wanner, M.J.; van Maarseveen, J.H.; Hiemstra, H. Total synthesis of (+)-yohimbine via an enantioselective organocatalytic Pictet-Spengler reaction. J. Org. Chem., 2011, 76(21), 8907-8912. []. [PMID: 21950549].
Gómez, C.V.; Cruz, D.C.; Mose, R.; Jørgensen, K.A. Organocatalytic cascade reactions: diversity-oriented synthesis for the construction of hydroisoquinoline scaffolds. Chem. Commun. (Camb.), 2014, 50(45), 6035-6038. []. [PMID: 24769648].
Li, Y.; Tur, F.; Nielsen, R.P.; Jiang, H.; Jensen, F.; Jørgensen, K.A. Enantioselective formal [4+2] cycloadditions to 3-nitroindoles by trienamine catalysis: Synthesis of chiral dihydrocarbazoles. Angew. Chem. Int. Ed. Engl., 2016, 55(3), 1020-1024. []. [PMID: 26636665].

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