1.2.3.4- Tetrahydroquinoline. reaction with

The relative ease of the reaction with the (l,l-dicyanopentynyl)pyrimi-dines induced studies of the reaction of 5-R-2-(l,l-dicyanohex-5-yn-1-yl)pyrimidine (R = H, NO2, Ar). They react with more difficulty, due to the longer tether between diene ad dienophile leading to a decreased entropic assistance. At a considerable higher temperature than observed for the (l,l-dicyanopentynyl)pyrimidines (210°C instead of 130°C and 8,8-dicyano-5,6,7,8-tetrahydroquinolines are formed (89T5151) (Scheme 33). 

Reaction of tetrahydroquinoline 257 with ethyl bromopyruvate afforded pyrroloquinoline 260 which upon transesterification by treatment with tropine in presence of sodium methoxide in toluene gave 261 which was found to be useful as 5-HT receptor antagonist (89EP322016). 

A synthesis for the enantiomerically pure 535 was developed starting with D-phenylalanine which upon reaction with methyl chloroformate gave 528 whose reaction with methoxylamine afforded 529. Cyclization with bis(trifluoroacetoxy)iodobenzene in presence of trifluoroacetic acid gave the tetrahydroquinoline derivative 530 which was demethoxylated to give 531. Treatment of 531 with either benzyl chloroformate or... 

Scheme 1.34 Test reaction with (+ )-pinocarvone-derived pyridine thioether ligands and 2-(2-phenylthiophenyl)-5,6,7,8-tetrahydroquinoline ligands.

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>. 

Consideration of the mechanism has to account for the fact, that hydrazoic acid and dinitrogen is liberated during the course of the reaction. The similarity to the Schmidt reaction is obvious, and it should be mentioned that quinisatine (2,3,4-trioxo-tetrahydroquinoline) reacts with sodium azide and sulfuric acid at 0 °C in moderate yield to give 14 [96TH000],... 

Sodium cyanide in DMF at 120 °C has been used for the decarboxylation of 1-substituted-4-oxoquinoline-3-carboxylic acids <94TL(35)8303>. Quinoline Reissert adducts have been epoxidized at the 3,4-bond. Its reaction with amine nucleophiles gave regiospecifically substituted 1,2,3,4-tetrahydroquinolines <95H(41)897>. Successive Claissen rearrangements of 2-(8-quinolinoxymethyl)-3-(8-quinolinoxy)-l-propene gave a product which shows excellent ability to extract heavy metal ions <95TL(36)5567>. An Eschenmoser approach has been used in a facile synthesis of monofunctional and difunctional A -substituted-4-alkylidenequinolines (54) (Scheme 39) <95S(St)56>. 

Dihydropyridines such as 56 have recently been reported to undergo Lewis acid-catalyzed multicomponent reactions with anilines and aldehydes to form pyrido-fused tetrahydroquinolines 58 (Equation 2) <2005JC033>. A wide variety of dihydropyridines, aldehydes, and anilines are tolerated, and the reaction proceeds well on numerous solid supports allowing the reaction to be performed combinatorially. 

Sequential Grubbs metathesis/Diels-Alder strategies can be used to produce tetrahydroquinolines. For example, intramolecular enyne metathesis followed by reaction with alkynes followed by oxidation serves as a useful route to multisubstituted systems (Scheme 78) <2000CC503>. 

Quinoline 82a could be prepared as a sole product by the following one-pot procedure after quenching the reaction with acetic acid, oxidation of the mixture with a 0.5 molar amount of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) gave quinoline 82a in 80% yield from 80a without forming tetrahydroquinoline 83a (Scheme 36). 

In the presence of 10 mol % Sc(OTf)3, A-benzylideneaniline reacts with 2-trans-l-methoxy-3-trimethylsiloxy-l, 3-butadiene (Danishefsky s diene) [23] to afford the corresponding aza Diels-Alder adduct, a tetrahydropyridine derivative, quantitatively (Eq. 7) [24]. In the reaction of A -benzylideneaniline with cyclopentadiene under the same conditions, on the other hand, the reaction course ehanged and a tetrahydroqui-noline derivative was obtained (Eq. 8). In this reaction, the imine aeted as an azadiene toward one of the double bonds of cyclopentadiene as a dienophile [25]. In the reaction with 2,3-dimethylbutadiene a mixture of tetrahydropyridine and tetrahydroqui-noline derivatives was obtained. A vinyl sulfide, a vinyl ether, and a silyl enol ether worked well as dienophiles to afford the tetrahydroquinoline derivatives in high yields [26,27]. 

Benzodithioles 197 (dienophiles) were employed in aza-Diels-Alder reactions with A -arylimines 198 as a versatile approach to tetrahydroquinolines 199. Subsequent transformations of the latter under reductive and oxidative conditions provided an access to 2,3-disubstituted tetrahydroquinolines 200, inaccessible through the conventional [4+2] cycloaddition strategy, and also to 2,3-dihydro-4-quinolones 201 and 4-quinolones 202 (Scheme 23) <20020L4411>. 

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