Tetrahydroquinoline derivative synthesis using

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]... 

As shown in Scheme 5.23, 1,2,3,4-tetrahydroquinoline derivatives were synthesized using 3-(2-aminophenyl)propanols as starhng materials and catalyzed by the I/K2CO3 system. This catalytic system was also applicable to the synthesis of 2,3,4,5-tetrahydro-l-benzazepine from 4-(2-aminophenyl)butanol. 

Rogers JL, Emat JJ, Yung H, Mohan RS (2009) Environmentally friendly organic synthesis using bismuth compounds Bismuth(III) bromide catalyzed synthesis of substituted tetrahydroquinoline derivatives. Catal Commun 10 625-626... 

The formation of a nitrene adjacent to a double bond can be used in the synthesis of novel heterocyclic systems. For example, the azide 721 converts smoothly into the tricyclic product 722 on irradiation and the same modus operandi is used for the synthesis of pyrrolo[2,3-J]pyrimidines from substituted 4-azidopyrimidines . Aziridine formation is also encountered in the cyclization of 723 to the tetrahydroquinoline derivatives 724 . Other cyclizations provide routes to imidazoindoles 725 " or thienopyrroles 726 . ... 

Togo, Yokoyama and coworkers have developed a useful synthetic procedure for the preparation of nitrogen heterocycles based on the N-radical cyclization onto an aromatic ring [247, 656-658], For example, various iV-alkylsaccharins 626 can be conveniently prepared in moderate to good yields by the reaction of arenesul-fonamides 625 with (diacetoxyiodo)benzene in the presence of iodine under irradiation with a tungsten lamp (Scheme 3.245) [656]. A similar procedure has been applied to the synthesis of 1,2,3,4-tetrahydroquinoline derivatives [247, 657] and 3,4-dihydro-2,l-benzothiazine 2,2-dioxides [658],... 

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). 

Hydrogenation with homogeneous catalysis has received increasing attention over the last few decades. Hexarhodium hexadecacarbonyl (181 Scheme 35) under water gas shift conditions forms 1,2,3,4-tetrahydroquinoline (128) or N-formyl-1,2,3,4-tetrahydroisoquinoline (182) with the parent hete-roaromatic. When hydrogen is substituted for carbon monoxide, 4-methylquinoline is reduced to 4-methyl-5,6,7,8-tetrahydroquinoline (183) exclusively.Isoquinoline behaves similarly generating A/-formyl-l,2,3,4-tetrahydroisoquinoline (184). Similar reductions under water gas shift or synthesis gas conditions using transition metal carbonyls derived from Mn, Co and Fe, have been recorded.Promotion by phase transfer agents is observed in some cases. 

Heterocyclic Synthesis. - The reactions of phosphorus ylides with phenan-threne-9,10-quinone (113) have been used to prepare phenanthrene [9,10-x]-fused compounds with four, five, and six membered heterocyclic rings. (E)-4-carbethoxymethylene-l,2,3,4-tetrahydro-2-quinolones 114 have been obtained from the stereoselective reaction of 3-hydroxy-1,2,3,4-tetrahydroquinoline-2,4-diones and ethyl(triphenylphosphoranylidene)acetate. A -trifluoroacetylanilines 115 react with Ph3P=C02Et producing enamine derivatives 116 as a mixture of (E)- and (Z)-isomers. Enamines 116 are useful precursors for the synthesis of indoles and quinolones. 

Chiral formamidines 1.115 have been developed by Meyers and cowoikers [388-392], These reagents are prepared from HC(NMe2XOMe)2 d a-aminoethers 1.60 (R = Me or ferf-Bu) [393], Once again, (5)-valinol and (S)-terf-leudnol derivatives 1.115 (R = /-Pr or tert-Bu) are the most effective chiral auxiliaries. The main applications of these reagents are enantioselective alkylations of tetrahydroquinolines, and the products of these alkylations are very useful in alkaloid synthesis [343, 391, 394], The chiral auxiliaiy is regenerated by treating the products with hydrazine. 

By combining regioselective Au(l)-catalyzed enamine synthesis with enantiose-lective transfer hydrogenation, the asymmetric synthesis of tetrahydroquinolines from simple 2-(2-propynyl)aniline derivatives has been achieved (Scheme 15.94). Here, a chiral Bronsted acid is used in combination with the Hantzsch ester to install the chiral center with up to 99% ee [316]. 

---