2.3.4- Trisubstituted tetrahydroquinolines

Another example of a MCR-based strategy for the synthesis of pyridines was reported by Kantevari et al. in 2007. Thus, the three-component condensation of enaminones, 1,3-dicarbonyls, and ammonium acetate in the presence of a catalytic amount of a tangstocobaltate salt as heterogeneous catalyst, either in refluxing solvent or under solvent-free conditions, allowed the regioselective formation of 2,3,6-trisubstituted pyridines and 2,7,7-trisubstituted tetrahydroquinolin-5-ones (Scheme 55) [155]. This methodology combines shorter reaction times and... 

Ori M, Toda N, Takami K, Tago K, Kogen H (2005) Stereospecific synthesis of 2,2,3-trisubstituted tetrahydroquinolines application to the total syntheses of henzastatin E and natural virantmycin. Tetrahedron 61 2075-2104... 

An InCl3-catalyzed domino reaction of aromatic amines and cyclic enol ethers has been reported and gives rise in good yields to a range of 2,3,4-trisubstituted 1,2,3,4-tetrahydroquinolines <2002JOC3969>. 

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>. 

A -Methyleneamine equivalents can be generated from 1,3,5-trisubstituted hexahydro-1,3,5-triazines in the presence of a Lewis acid (LA) and used for aminomethylation reactions with various nucleophiles at the -position of amines (Scheme 16). A -Methyleneaniline equivalents, as shown by 110 and 111, result from the breaking of all three carbon-nitrogen bonds of l,3,5-triphenylhexahydro-l,3,5-triazine 109. They have characteristics of imine and iminium ions similar to Mannich bases and can be used for various aminomethylation reactions. However, there have been no reports of using A -methyleneamine equivalents as azadienes, which may react with olefins via [47t-F2Jt] cycloaddition to afford 1,2,3,4-tetrahydroquinolines 112 <2000T5259>. 

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