Tetrahydroquinoline from quinoline

Q Devise a synthesis of l-benzyl-l.2,3.4-tetrahydroquinoline from quinoline. 

Piperidines from pyridines s. 2, 71 1,2,3,4-tetrahydroquinolines from quinolines or 1,2-dihydroquinolines s. S.W. Goldstein, PJ. Dambek, Synthesis 1989, 221-2. 

Additions to quinoline derivatives also continued to be reported last year. Chiral dihydroquinoline-2-nitriles 55 were prepared in up to 91% ee via a catalytic, asymmetric Reissert-type reaction promoted by a Lewis acid-Lewis base bifunctional catalyst. The dihydroquinoline-2-nitrile derivatives can be converted to tetrahydroquinoline-2-carboxylates without any loss of enantiomeric purity <00JA6327>. In addition the cyanomethyl group was introduced selectively at the C2-position of quinoline derivatives by reaction of trimethylsilylacetonitrile with quinolinium methiodides in the presence of CsF <00JOC907>. The reaction of quinolylmethyl and l-(quinolyl)ethylacetates with dimethylmalonate anion in the presence of Pd(0) was reported. Products of nucleophilic substitution and elimination and reduction products were obtained . Pyridoquinolines were prepared in one step from quinolines and 6-substituted quinolines under Friedel-Crafts conditions <00JCS(P1)2898>. 

HDN of Quinoline. Satterfield et al.(8) proposed that there are two pathways for the HDN of the coal liquid model compound quinoline using a NiHMocatalyst. One pathway involves the successive formation from quinoline of 1,2,3,4-tetrahydroquino-line, o-propylaniline and then ammonia plus n-propylbenzene. A second pathway involves the successive formation of 5,6,7,8-tetrahydroquinoline, decahydroquinoline, propylcyclohexylamine... 

Dihydro- (93) and 1,2,3,4-tetrahydroquinoline Reissert compounds (94) can be the azomethine ylide precursors for the above purpose 93 is readily available from quinolines, acyl chlorides, trimethylsilyl cyanide, and aluminum chloride, and 94 by catalytic hydrogenation of 93. These Reissert compounds are first O-protonated with HBF in acetic acid or CF3SO3H in dichloromethane and the resulting salts, 95 and 95, are then heated... 

The reduction of quinolines was applied to the asymmetric preparation of the anti-bacterial agent (/ )-flumequine 18 [85, 86], starting from quinoline 12a and generating the key tetrahydroquinoline intermediate 14a for the total synthesis and using 17 as catalyst (Scheme 6) [87]. 

Taylor and coworkers report a copper(II) 2-ethylhexanoate catalyst for the synthesis of oxindoles, thio-oxindoles, 3,4-dihydro-l//-quinolin-2-ones, and 1,2,3,4-tetrahydroquinolines from linear precursors by direct C(sp )-H and Ar-H coupling using atmospheric oxygen as the oxidant (Scheme 8.91). The reaction procedure is open to the air and easy to handle [162]. 

Besides the domino Michael/SN processes, domino Michael/Knoevenagel reactions have also been used. Thus, Obrecht, Filippone and Santeusanio employed this type of process for the assembly of highly substituted thiophenes [102] and pyrroles [103]. Marinelli and colleagues have reported on the synthesis of various 2,4-disubstituted quinolines [104] and [l,8]naphthyridines [105] by means of a domino Michael addition/imine cyclization. Related di- and tetrahydroquinolines were prepared by a domino Michael addition/aldol condensation described by the Hamada group [106]. A recent example of a domino Michael/aldol condensation process has been reported by Brase and coworkers [107], by which substituted tetrahydroxan-thenes 2-186 were prepared from salicylic aldehydes 2-184 and cycloenones 2-185 (Scheme 2.43). 

The preparation of quinoline and tetrahydroquinoline derivatives from metal carbonyl-catalyzed reactions of Schiff bases with alkyl vinyl ethers in... 

HCA478). A similar route to quinolines via 1,2- dihydroquinolines starts fromN-propargyl-anilines and is copper catalyzed (62JOC4713). The allyl ether of cyclohexanone oxime (126) heated in benzene at 200 °C gives 5,6,7,8-tetrahydroquinoline (79S221) the proposed mechanism is reinforced by the isolation of a compound (128) formed from the ether (126) and a suggested intermediate (127). 

Imines derived from aniline and glyoxylic acid esters can be regarded as electron-poor 2-azadienes, in which an aromatic carbon—carbon double bond takes part of the diene system. In this context, Prato and Scorrano et al. were able to achieve the [4 + 2] cycloaddition of ethyl N-phenyl glyoxylate imines with dihydrofuran and indene leading to hexahydrof-uro[3,2-c]- and tetrahydro-7//-indeno[2,l-c]quinolines, respectively, in moderate to good yields (88JHC1831). Similarly, tetrahydroquinoline derivatives were formed by [4 + 2] cycloaddition of 1,2-bis(trimethylsily-... 

Oximes are good precursors to reductive cyclization. A reductive base-induced cyclization of O-aryl oxime 4 will yield the tetrahydroquinoline <1998CL437>. The reduction prevented the normal dihydro-cyclization product from disproportionating to the quinoline and tetrahydroquinoline <1998BCJ2945>. By adding 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) after cyclization, the quinoline is the sole product (Scheme 9). 

Table I gives the results from the experiments with [M(PC)] supported on Si02 The conversion of quinoline is almost exclusively to 1,2,3,4-tetrahydroquinoline with only traces of other products (<1%). No propylaniline, propylbenzene, propyl-cyclohexane, 5,6,7,8-tetrahydroquinoline or decahydroquinoline were noted. No change is noted in the conversions when the SiC>2 is activated in vacuo at 400°C prior to supporting the complex. When the hydrogenations are run at 200°C only low conversions are...

Supported Cobalt Catalysts. Experiments were conducted with [Co(PC)]/Si02 at 340°C to determine the important variables for the catalysis of a typical [M(PC)]. Table IV gives the results for runs which were conducted for varying periods of time. It is seen that even at 100 hr. the conversion only reached 36%. The equilibrium conversion at 342°C can be estimated to be 97%. (9) Thus, the reaction is quite far from equilibrium even at long times. This may be taken as evidence for product inhibition of the catalysis. This might be expected since tetrahydroquinoline is a stronger Lewis base than quinoline. Thus, the product could bind to the metal center and prevent activation of the substrate and/or hydrogen. One important conclusion is that the reaction is not over in 24 hours and it can be assumed that the difference in conversions noted in Table I with different [M(PC)] are due to differences in inherent activity of the [M(PC)]. 

Carbon-sulfur bond formation by oxidative cyclization of a thiourea derivative using bromine will in the case of (521) furnish a thiazolo[/,/]quinoline (522 Z = NH). The same imine is obtained from 8-mercapto-l,2,3,4-tetrahydroquinoline on treatment with cyanogen bromide with phosgene the 2-oxo derivative (522 Z = 0) is formed (63JOC2581). 

Baylis-Hillman adducts such as 55 and 56 derived from 2-nitrobenzaldehydes were shown to function as useful precursors to functionalized (1H)-quinol-2-ones and quinolines. Treatment of 55 and 56 with iron and acetic acid at 110 °C afforded 57 and 58, respectively <02T3693>. A variety of other cyclization reactions utilized in the preparation of the quinoline scaffold were also reported. An iridium-catalyzed oxidative cyclization of 3-(2-aminophenyl)propanols afforded 1,2,3,4-tetrahydroquinolines <02OL2691>. The intramolecular cyclization of aryl radicals to prepare pyrrolo[3,2-c]quinolines was studied <02T1453>. Additionally, photocyclization reactions of /rans-o-aminocinnamoyl derivatives were reported to provide 2-quinolones and quinolines <02JHC61>. Enolizable quinone and mono- and diimide intermediates were shown to provide quinolines via a thermal 6jt-electrocyclization <02OL4265>. Quinoline derivatives were also prepared from nitrogen-tethered 2-methoxyphenols. The corresponding 2-methoxyphenols were subjected to a iodine(III)-mediated acetoxylation which was followed by an intramolecular Michael addition to afford the quinoline OAc O... 

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