5,6,7,8-Tetrahydroquinolines, synthesis Diels-Alder reactions

Catalytic asymmetric aza-Diels-Alder reactions using a chiral lanthanide Lewis acid. Enantioselective synthesis of tetrahydroquinoline derivatives using a catalytic amount of a chiral source [98]... 

Hetero-Diels-Alder reactions have been succesfully employed for the synthesis of arenoquinolizine systems. For example, as shown in Equation 10, treatment of tetrahydroquinoline 319 with Danishefsky s diene 320 in the presence of a Lewis acid gave the benzo[c]quinolizidine derivative 321 <2000JME3718>. 

Zhang W, Guo YP, Liu ZG, Jin XL, Yang L, Liu ZL (2005) Photochemically catalyzed Diels-Alder reaction of arylimines with N-vinylpyrrohdinone and N-vinylcarbazole by 2,4,6-triphenylpyrylium salt synthesis of 4-heterocycle-substituted tetrahydroquinoline derivatives. Tetrahedron 61 1325-1333... 

Savitha G, Perumal PT (2006) An efficient one-pot synthesis of tetrahydroquinoline derivatives via an aza Diels-Alder reaction mediated by CAN in an aqueous medium and oxidation to heteroaryl quinolines. Tetrahedron Lett 47 3589-3593... 

A three component coupling reaction of A-acetyl-2-azetine, aromatic imines and aromatic amines allows a rapid stereoselective entry to 2,3,4-trisubstituted tetrahydroquinolines, via fused tricyclic azetidines 1 <02CC444>. Fused heterocycles 1 were formed through an aza Diels-Alder reaction between aromatic imines and A-acetyl-2-azetine, which acts as an enamide substrate. This strategy has been used for the formal synthesis of luotonin A <02TL5469>. 

The synthesis of functionalized 8-hydroxy-l,2,3,4-tetrahydroquinolines 77 has been reported by Dai and co-workers [119] in moderate to good yields via an aza-Diels-Alder reaction of an 2-aminophenol, a substituted benzaldehyde and a cyclic alkene catalyzed by TFA under controlled microwave irradiation in acetonitrile. In general, when electron deficient aromatic aldehydes were used, the adducts could be isolated in 39-59% yields with a predominance of the trans isomer (Scheme 58). 

Xing X, Wua J, Dai W-M (2006) Acid-mediated three-component aza-Diels-Alder reactions of 2-aminophenols under controlled microwave heating for synthesis of highly functionalized tetrahydroquinolines. Part 9 Chemistry of aminophenols. Tetrahedron 62 11200-11206... 

Polymeric catalysts. A very useful modification of the catalyst is obtained by ligand exchange with a (polyallyl)triflamide, forming polymer-bound scandium triflamide bistriflate. The catalyst has been used in the combinatorial synthesis of a tetrahydroquinoline library from anilines, aldehydes, and alkenes. A related catalyst prepared from ScClj-bHjO and Nafion is effective in several useful synthetic reactions, including allylation, Diels-Alder reaction, and Friedel-Crafts acylation. ... 

The aza-Diels-Alder reaction can also be used as a convenient method for the synthesis of substituted tetrahydroquinolines by in situ generation of azadiene compounds, generated from the appropriate carbonates, and its reaction with dienophiles. ... 

Reproduced from Tan Y-J, Zhang Z, Wang F-J, Wu H-H, Li Q-H. Mechanochemical milling promoted solvent-free imho Diels-Alder reaction catalyzed by FeCIs diastereoselective synthesis of cis-2,4-diphenyl-1,2,3,4-tetrahydroquinolines. RSC Adv 2014 4 35635-35638, with permission from the Royal Society of Chemistry. 

M. Xie, X. Chen, Y. Zhu, B. Gao, L. Lin, X. Liu, X. Feng, Angew. Chem. Int Ed. 2010,49,3799-3802. Asymmetric three-component inverse electron-demand aza-Diels-Alder reaction efficient synthesis of ring-fused tetrahydroquinolines. 

The Povarov reaction is related to the previous examples in that it can be defined as the formal imino Diels-Alder reaction between aromatic imines and electron-rich olefins. It is one of the most popular methods for the synthesis of tetrahydro-quinolines [40], and two examples of Povarov reactions in water are summarized in Scheme 1.27. In an eaily example of the use of ceric ammonium nitrate as a catalyst in synthesis [41], Perumal reported a few examples of a CAN-catalyzed Povarov reaction of aldehydes, amines and N-viitylpyrroUdin-2-ones as the olefin component in water for the synthesis of heteroaiyl-substituted tetrahydroquinolines 54 [42]. Using a different approach, Vaultier later described an onium salt-supported Povarov three-component reaction in water at room temperature affording tricyclic compounds 55. In this study, either the aldehyde or the amine components were linked to a side chain containing an onium salt, which confers solubility to the reactant [43]. 

Zhang et al. [52] used iodine to catalyze the hetero-Diels-Alder reaction of pentafluorobenzylidineaniline (CgF5CH=NAr) with enol ethers to afford the corresponding tetrahydroquinoline derivatives 23 and 24 as a mixture of cis/trans stereoisomers. Mild and neutral reaction conditions, facile experimental procedure and the use of iodine made this method attractive for practical synthesis of many fluorinated tetrahydroquinoline derivatives (Scheme 10.18). 

Wang W Li YL, Wang XS (2012) Highly efficient synthesis of 7-aryl-pyrano[3,4-c] pyrazolo[4,3-f]quinoline derivatives catalyzed by iodine. ARKIVOC vi 214-221 Lin XF, Cui SL, Wang YG (2006) Molecular iodine catalyzed one-pot synthesis of substituted quinolines from imines and aldehydes. Tetrahedron Lett 47 3127-3130 Jin G, Zhao J, Han J, Zhu S, Zhang J (2010) Iodine-promoted imino-Diels-Alder reaction of fluorinated imine with enol ether synthesis of 2-perfluorophenyl tetrahydroquinoline derivatives. Tetrahedron 66 913-917... 

The reaction of l-vinylpyrrolidinone-2-one 124 or l-vinylazepan-2-one with aromatic amines 125 on refluxing in water leads to a diastereoselective synthesis of 2-methyl-4-amino-l,2,3,4-tetrahydroquinolines 126 in moderate to good yields (Scheme 42) [95]. No catalyst or any other additive is required for the reaction. The formation of products has been explained by an equilibrium between l-vinylpyrrolidinone-2-one 124 and its corresponding iminium ion 127 in water under reflux (Scheme 43). The active iminium ion could be easily attacked by anilines to form another intermediate 128, which subsequently be transformed into imine 129 with elimination of 2-pyrrolidinone. Finally, imine 129 xmdergoes an aza-Diels-Alder type cycloaddition with another molecule of l-vinylpyrrolidin-2-one forming the desired products. The reaction of a representative 128 with 1-vinylpyr-rolidin-2-one under similar conditions affords the 1,2,3,4-tetrahydroquinoline, which supports the proposed mechanism. 

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