Highly enantioselective hydrogenation of new 2-functionalized quinoline derivatives

The asymmetric hydrogenation of a new series of 2-functionalized quinolines has been developed in the presence of in situ generated catalysts obtained from [Ir(cod)Cl]₂/(R)-bisphosphine/I₂ combinations. The enantioselectivity levels were as high as 84-94% ee for the synthesis of 1,2,3,4-tetrahydroquinolines.     

Base-promoted regioselective synthesis of 1,2,3,4-terahydroquinolines and quinolines from N-boc-3-piperidone

An efficient synthesis of 1,2,3,4-tetrahydroquinolines with donor and acceptor group has been delineated by base mediated ring transformation of 6-aryl-4-substituted-2H-pyran-2-one-3-carbonitriles by N-boc-3-piperidone followed by consecutive deprotection of Boc group under acidic conditions. This reaction involves 2 new bond formations namely C4a-C5 and C8a-C8 in order to create the nucleus. Various donor and acceptor functional groups like aryl, heteroaryl, nitrile, methylsulfanyl and secondary amine were installed in 1,2,3,4-tetrahydroquinolines. We extended our approach to synthesize the fused 1,2,3,4-tetrahydroquinolines by using 2-oxobenzo[h]chromenes as precursor. Further, we synthesized fused and isolated quinolines through aromatization of 1,2,3,4-tetrahydroquinolines by DDQ in excellent yields. Single-crystal X-ray analysis of the Boc protected tetrahydroisoquinoline 6t showed the steric hindrance between N-Boc and aryl group.     

Synthesis of 7-(2-R-pyrimidin-4-yl)- and 7-(2-R-[1,2,4]triazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidin-7-yl)-2,2,4,6-tetramethyl-1,2,3,4-tetrahydroquinolines

Cyclization of 3-(dimethylamino)-1-(2,2,4,6-tetramethyl-1,2,3,4-tetrahydroquinolin-7-yl)prop-2-en-1-one with carboximidamides, guanidines, and 1,2,4-triazol-5-amines afforded a number of new 2,2,4,6-tetramethyl-7-(2-R-pyrimidin-4-yl)-1,2,3,4-tetrahydroquinolines and 2,2,4,6-tetramethyl-7-(2-R-[1,2,4]triazolo-[1,5-a]pyrimidin-7-yl)-1,2,3,4-tetrahydroquinolines.     

Synthesis of 1-iodo-1,2,3,4,4a,9a-hexahydrocarbazoles and their isomerization into 3-iodo-2,4-propano-1,2,3,4-tetrahydroquinolines

The reactions of 2-(cyclohex-2-enyl)-4,5-difluoroaniline or N-methyl-2-(cyclohex-2-enyl)aniline with I₂ in CCl₄ in the presence of NaHCO₃ give 1-iodo-1,2,3,4,4a,9a-hexahydrocarbazoles, which isomerize in MeCN into the corresponding 3-iodo-2,4-propano-1,2,3,4-tetrahydroquinolines in quantitative yields.     

An efficient synthesis of optically pure (S)-2-functionalized 1,2,3,4-tetrahydroquinoline

Using a copper-catalyzed coupling reaction of amino acid and aryl halide, followed by intramolecular cyclization of N-aryl-1-hydroxyl-3-propylamines under the Swern’s condition as the key steps, (S)-2-hydroxymethyl-1,2,3,4-tetrahydroquinoline was synthesized as an example of optically pure 2-functionalized 1,2,3,4-tetrahydroquinolines.     

Imino Diels-Alder Reactions: Efficient Synthesis of 2-Aryl-4-(2′-oxopyrrolidinyl-1′)-1,2,3,4-tetrahydroquinolines catalyzed by Antimony(III) Sulfate

Antimony(III) sulfate is found to catalyze the imino Diels-Alder reaction of Schiff’s bases with N-vinylpyrrolidin-2-one to afford 2-aryl-4-(2′-oxopyrrolidinyl-1′)-1,2,3,4-tetrahydroquinolines. One-pot synthesis of 1,2,3,4-tetrahydroquinolines from 3-nitro benzaldehyde and aromatic amines with N-vinylpyrrolidin-2-one catalyzed by antimony(III) sulfate is also reported. This catalyst is inexpensive, easily available, and it was also found that catalyst could be recovered quantitatively and reused without much loss of catalytic activity.     

CAN-catalyzed three-component reaction between anilines and alkyl vinyl ethers: stereoselective synthesis of 2-methyl-1,2,3,4-tetrahydroquinolines and studies on their aromatization

The CAN-catalyzed reaction between anilines and vinyl ethers at room temperature provides a convenient and efficient access to 4-alkoxy-2-methyl-1,2,3,4-tetrahydroquinolines. This reaction is stereoselective, favouring a cis arrangement for the alkoxy and methyl groups, and involves a three-component process that leaves a molecule of alcohol as the only side product. 2-Methylquinoline derivatives were efficiently prepared from 4-alkoxy-2-methyl-1,2,3,4-tetrahydroquinolines by Pd-C-promoted dehydrogenation.     

The preparation and some chemistry of 2,2-dimethyl-1,2-dihydroquinolines

The cyclisation of N-(1,1-dimethylpropargyl) anilines, using cuprous chloride in refluxing toluene, yields 6-substituted-2,2-dimethyl-1,2-dihydroquinolines. The reactivity of the double bond in the heterocyclic ring of these products is exemplified by chlorination, to yield 6-substituted-3,4-cis-dichloro-2,2-dimethyl-1,2,3,4-tetrahydroquinolines which can be selectively dechlorinated to provide 6-substituted-3-chloro-2,2-dimethyl-1,2,3,4-tetrahydroquinolines; epoxidation to yield an epoxide, which can be hydrogenolysed to the corresponding 3-hydroxy product and in turn oxidised to the 3-keto derivative; and oxymercuration to provide a 4-hydroxy product and hence a 4-keto derivative. Dehydrochlorination of a 3,4-dichloro product provides a 3-chloro-1,2-dihydroquinoline which can be hydrolysed to a 3-keto system. The formation of cis 3,4-dichloro products from the chlorination, as well as the formation of a cis chlorohydrin from the chlorination of N-acetyl-2,2,6-trimethyl-1,2-dihydroquinoline in partially aqueous solution, suggests that N-acetyl, or N-trifluoroacetyl groups, participate in the addition process.     

Substituent effects on the reductions of quinoline-N-boranes

Reductions of 2-substituted quinoline-$\text{N}$-boranes by sodium bis-(2-methoxyethoxy)aluminum dihydride lead to 1,2,3,4-tetrahydroquinolines by hydride attack at C-4 and subsequent reduction of the resulting enamine.     

Reaction of vinylidenecyclopropanes with aromatic imines in the presence of Lewis acids

1-Methyl-2-(2-methylpropenylidene)-1-phenylcyclopropane, 7-(2-methylpropenylidene)bicyclo[4.1.0]heptane, and (Z)-9-(2-methylpropenylidene)bicyclo[6.1.0]non-4-ene react with N-benzylideneanilines in the presence of boron trifluoride-ether complex to give pyrrolidine derivatives. Reactions of 1-methyl-1-phenyl-2-diphenylvinylidenecyclopropane with N-benzylideneanilines in the presence of BF₃·Et₂O, Yb(OTf)₃, or Sc(OTf)₃ lead to the formation of substituted 1,2,3,4-tetrahydroquinolines. 7-Diphenylvinylidenebicyclo[4.1.0]heptane in the presence of BF₃·Et₂O undergoes isomerization into 5-phenyl-8,9,10,11-tetrahydro-7H-cyclohepta[a]naphthalene.     

Imino <Emphasis Type="Italic">Diels-Alder</Emphasis> Reactions: Efficient Synthesis of 2-Aryl-4-(2′-oxopyrrolidinyl-1′)-1,2,3,4-tetrahydroquinolines catalyzed by Antimony(III) Sulfate

Summary. Antimony(III) sulfate is found to catalyze the imino Diels-Alder reaction of Schiff’s bases with N-vinylpyrrolidin-2-one to afford 2-aryl-4-(2′-oxopyrrolidinyl-1′)-1,2,3,4-tetrahydroquinolines. One-pot synthesis of 1,2,3,4-tetrahydroquinolines from 3-nitro benzaldehyde and aromatic amines with N-vinylpyrrolidin-2-one catalyzed by antimony(III) sulfate is also reported. This catalyst is inexpensive, easily available, and it was also found that catalyst could be recovered quantitatively and reused without much loss of catalytic activity.     

Synthesis of enantiopure 4-amino-3-hydroxymethyl-tetrahydroquinolines via an intramolecular nitrone cycloaddition

Enantiopure 4-amino-3-hydroxymethyl-1,2,3,4-tetrahydroquinolines are synthesized by using an intramolecular cycloaddition of chiral nitrones prepared from aldehydes 5 and (R)-α-(hydroxymethyl)benzylhydroxylamine. Reaction times of the nitrone cycloaddition were optimized by activation under MW-assisted conditions. The absolute configuration of the products was determined by X-ray analysis.     

Simple entry to new 2-alkyl-1,2,3,4-tetrahydroquinoline and 2,3-dialkylquinoline derivatives using BiCl3-catalyzed three component reactions of anilines and aliphatic aldehydes in the presence (or lack) of N-vinyl amides

A general protocol for the simple and efficient synthesis of 2-alkyl-1,2,3,4-tetrahydroquinolines and 2,3-dialkylquinolines was reported. Synthetic protocol describes the one-pot preparation of these tetrahydroquinoline and quinoline products using the same reagents (aliphatic aldehydes and anilines) in the BiCl₃-catalyzed multicomponent condensation process where the third component, N-vinyl amide is present.     

Convenient synthesis of 1,2,3,4-tetrahydroquinolines via direct intramolecular reductive ring closure

A simple and convenient procedure for the synthesis of 3-aryl-1,2,3,4-tetrahydroquinolines is reported. 3-Aryl-1,2,3,4-tetrahydroquinolines are directly obtained by reductive ring closure of 2-phenyl-3-(2-nitrophenyl)-propionitrile derivatives in moderate to high yields.     

An efficient synthesis of enantiomerically pure aromatic-fused N-containing heterocycles from common chiral aziridines

An efficient synthesis of enantiomerically pure aromatic-fused N-containing heterocycles was successfully achieved via Pd-catalyzed intramolecular C-N bond formation between the nitrogen originated from the aziridine and the halogen containing aromatic carbon. This reaction has a broad substrate scope to provide various enantiomerically pure (3,4-dihydro-2H-benzo[b][1,4]oxazin-3-yl)methanols, 2-hydroxymethyl-1,2,3,4-tetrahydroquinolines and (1,2,3,4-tetrahydroquinoxalin-2-yl)methanols from common chiral aziridines in good yields.     

New stable nitroxyl radicals from hydrogenated quinolines

Conclusions Syntheses were reported for 6-triphenylmethyl derivatives of 2,2,4-trimethyl-1,2-dihydroquinolines and 2,2,4-trimethyl-1,2,3,4-tetrahydroquinolines as well as 4-phenpl-1,2,3,4-tetrahydroquinoline. The oxidation of these compounds by H₂O₂ in the presence of Na₂WO₄ and also by m-chloroperbenzoic acid gave nitroxyl radicals, whose structures were supported by EPR spectroscopy.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimichesksya, No. 12, pp. 2870–2873, December, 1988.     

C-N bond forming reaction under copper catalysis: a new synthesis of 2-substituted 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolines

We report copper-catalyzed intramolecular cyclization of 8-alkynyl-1,2,3,4-tetrahydroquinolines, obtained via a Pd/C-mediated Sonogashira coupling in water, to afford 2-substituted 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolines. Further functionalization of the compounds synthesized was carried out under Heck, Sonogashira, and Suzuki reaction conditions.     

Synthesis and structures of 3-hydroxy-6-(R-phenylazo)-7,8-benzo-1,2,3,4-tetrahydroquinolines as products of analytical test reactions for nitrite and nitrate anions

An improved procedure was proposed for the synthesis of 3-hydroxy-7,8-benzo-1,2,3,4-tetrahydroquinoline, which is used as a reagent for the analytical test reaction for nitrate and nitrite anions based on azo coupling with diazo compounds. 3-Hydroxy-6-(R-phenylazo)-7,8-benzo-1,2,3,4-tetrahydroquinolines (R = 2-COOH, 4-COOH, or 4-SO₃H) were synthesized by azo coupling reactions in 65–70% yields. The structures of these compounds were confirmed by elemental analysis, ¹H NMR and IR spectroscopy, and X-ray diffraction. Based on the X-ray data, the bathochromic shift in the UV spectrum of the o-carboxy isomer compared to the p-carboxy isomer (Δλ_max = 50 nm) is attributed to a strong intramolecular hydrogen bond. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1027–1031, June, 2006     

Addition reactions to chiral aziridine-2-carboxaldimine toward various enantiopure nitrogen-containing heterocycles

Chiral (2R,1′R)-(1′-phenylethyl)aziridine-2-carboxaldimine was utilized as a nitrogen-containing starting substrate for the preparation of various enantiopure nitrogen-containing heterocycles. The additions of nucleophiles including organomagnesium reagents, cyanotrimethylsilane and ketene acetal to the chiral (2R,1′R)-(1′-phenylethyl)aziridine-2-carboxaldimine proceeded in highly stereoselective manner via chelation controlled transition states. Subsequent treatment of adducts with triphosgene and NaH yielded 5-substituted-4-chloromethylimidazolidin-2-ones. This imine was also served as either aza-diene or aza-dienophile with olefin or diene to provide hetero-Diels-Alder adducts 2-aziridinylpiperidines or 1,2,3,4-tetrahydroquinolines.     

Synthesis of 1,2,3,4-tetrahydroquinolines and 1,2,3,4-tetrahydro- 1,6-naphthyridines by a directed lithiation reaction

N-(tert-butoxycarbonyl)anilines (7), are easily converted in a one pot reaction sequence into the N- (tert-butoxycarbonyl)-1,2,3,4-tetrahydroquinolines (8), by directed ortho lithiation followed by reaction with 1- chloro-3-iodopropane, hence providing a new versatile quinoline ring nucleus synthesis. In an analogous reaction 2-N-(tert-butoxycarbonyl)- and an 2-N-(pivaloylamino) pyridine are converted to 1,2,3,4-tetrahydro-1,6- naphthyridines.