Radical cation salts induced domino reaction of anilines with enol ethers:Synthesis of 1,2,3,4-tetrahydroquinoline derivatives

A domino reaction of anilines with cyclic and acyclic enol ethers induced by catalytic amounts of TBPA^·+（5 mol%） was investigated and a series of 2,4-disubstituted-1,2,3,4-tetrahydroquinolines were synthesized.Different from cyclic enol ethers, when acyclic enol ethers were used in the reaction,they serve as surrogates of acetaldehyde,producing a series of 2-methyl-4- anilino-1,2,3,4-tetrahydroquinolines.A single electron transfer mechanism was proposed to rationalize the products formation.     

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 new hydroquinolinecarbaldehydes

A number of new N-alkyl-6(8)-formylhydroquinolines have been synthesized. The Vilsmeier—Haack reaction of 7(8)-substituted N-alkyl-1,2-dihydroand N-alkyl-1,2,3,4-tetrahydroquinolines led to 6-formylhydroquinolines, whereas N-methyl-8-formylhydroquinolines were formed in the case of 6-substituted N-methyl-1,2-dihydroand N-methyl-1,2,3,4-tetrahydroquinolines.

     

Highly diastereoselective synthesis of new heterolignan-like 6,7-methylendioxy-tetrahydroquinolines using the clove bud essential oil as raw material

The diastereoselective synthesis toward novel heterolignan-like 2-aryl-4-(4-hydroxy-3-methoxyphenyl)-6,7-methylendioxy-1,2,3,4-tetrahydroquinolines using for the first time clove bud essential oil as a renewable material was carried out. The synthetic protocol consisted of the hydrodistillation of dried flower buds, the solid base-catalyzed isomerization of the obtained essential oil enriched with eugenol in order to give isoeugenol and its participation, as a chemical reagent (dienophile) in the BF₃·OEt₂-catalyzed three component Povarov reaction, without previous purification. Final products were obtained as racemic mixtures of new trans-2,4-diaryl-r-3-Me-1,2,3,4-tetrahydroquinolines in moderate to good yields.     

Reactions of N- and C-Alkenylanilines: III. Synthesis and Cyclization of Substituted 2-(1-Methyl-2-butenyl)anilines

Reactions of substituted 2-(1-methyl-2-butenyl)anilines with iodine result in cyclization and formation of 3-iodo-1,2,3,4-tetrahydroquinolines; N-methylsulfonyl-2-(1-methyl-2-butenyl)anilines give rise exclusively to the corresponding 2-(1-iodoethyl)-3-methyl-2,3-dihydroindoles.     

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.     

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.     

Synthesis of 2-alkyl(aryl,hetaryl)-4-methyl-1,2,3,4-tetrahydroquinolines

We have developed a preparative, three stage of synthesis of substituted 1,2,3,4-tetrahydroquinolines. Treatment of N-aryl-imines with allylmagnesium bormide gave N-aryl-N-alkenylamines which were cyclized to the tetrahydroquinolines. The configurations and conformations of the 4-methyl-1,2,3,4-tetra-hydroquinolines containing different 2- substituents have been determined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 73–78, January, 1994.     

Reactions of cyclammonium cations

The action of acylating agents on 2-methylquinoline gives extremely unstable N-acyl salts, which, as a result of hydride-ion capture, are converted to 1-acyl-2-methyl-1,2,3,4-tetrahydroquinolines. Under similar conditions, 1-acyllepidinium salts form 1-acyl-4-methyl-1,2-dihydroquinolines or dimerize.See [1] for communication XIXTranslated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1105–1110, August, 1972.     

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.     

Ionic diamine rhodium complex catalyzed hydroaminomethylation of 2-allylanilines

Ionic diamine rhodium complexes catalyze the hydroaminomethylation of 2-allylanilines. The reaction involves initial hydroformylation followed by reductive amination, which provides direct access to 1,2,3,4-tetrahydroquinolines and 2,3,4,5-1H-1-benzazepines.     

Pd(II)-catalyzed oxidative cyclization reaction for the preparation of 2-substituted 1,2,3,4-tetrahydroquinolines with halide functionality

The first Pd(II)-catalyzed oxidative cyclization reaction was developed for preparation of 2-substituted 1,2,3,4-tetrahydroquinolines from olefinic tosylamides. Under the optimized conditions, up to 86% yield was obtained. This reaction provides direct and easy access to 2-substituted 1,2,3,4-tetrahydroquinolines with halide functionality.     

Visible-Light-Induced Synthesis of 1,2,3,4-Tetrahydroquinolines through Formal [4+2] Cycloaddition of Acyclic α,β-Unsaturated Amides and Imides with N,N-Dialkylanilines

1,2,3,4-Tetrahydroquinolines should be applicable to the development of new pharmaceutical agents. A facile synthesis of 1,2,3,4-tetrahydroquinolines that is achieved by a photoinduced formal [4+2] cycloaddition reaction of acyclic α,β-unsaturated amides and imides with N,N-dialkylanilines under visible-light irradiation, in which a new Ir^III complex photosensitizer, a thiourea, and an oxidant act cooperatively in promoting the reaction, is reported. The photoreaction enables the synthesis of a wide variety of 1,2,3,4-tetrahydroquinolines, while controlling the trans/cis diastereoselectivity (>99:1) and constructing contiguous stereogenic centers. A chemoselective cleavage of an acyclic imide auxiliary is demonstrated.     

Radical cation salt induced tandem cyclization between anilines and N-vinyl amides: synthesis of 2-methyl-4-anilino-1,2,3,4-tetrahydroquinoline derivatives

A tandem cyclization of imines with N-vinyllactams induced by TBPA⁺ was investigated, and a series of 2-methyl-4-anilino-1,2,3,4-tetrahydroquinolines were synthesized based on a domino process in which N-vinyllactams serve as an acetaldehyde surrogate. A single electron transfer mechanism was proposed and radical cation salt acts as both a Lewis acid and one electron oxidant to induce such transformation.     

The dramatic effect of thiophenol on the reaction pathway of ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with thiophenolates: ring expansion versus nucleophilic substitution

Ethyl 4-methyl-2-oxo-7-phenylthio-2,3,6,7-tetrahydro-1H-1,3-diazepine-5-carboxylate and/or ethyl 6-methyl-2-oxo-4-(phenylthiomethyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate were obtained in the reaction of ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with PhSNa or PhSK with or without PhSH, depending on the reagent ratio, reaction time, or temperature, as a result of ring expansion and/or nucleophilic substitution. The reaction pathway was affected strongly by the basicity-nucleophilicity of the reaction media. The results obtained were confirmed by reactions of 4-mesyloxymethyl-6-methyl-5-tosyltetrahydropyrimidin-2-one with PhSNa/PhSH and ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with NaCN/HCN or NaCH(COOEt)₂/CH₂(COOEt)₂.     

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 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.     

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.     

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.     

Intramolecular iminium ene reaction with Cu(I) catalysts: facile formation of 4-amino-3-methylenechromans from O-propargyl salicylaldehydes and dialkylamines

Reaction of O-propargyl salicylaldehyde and related compounds with dialkylamines in the presence of copper(I) iodide gave 4-(alkylamino)-3-methylenechroman derivatives in good yields through the loss of one alkyl group of the dialkylamine. The reaction also worked well by employing 2-amino benzaldehyde derivatives to afford 4-(alkylamino)-3-methylene-1,2,3,4-tetrahydroquinolines. A deuterium-labeling experiment suggested that the α-hydrogen of the dialkylamine was transferred intramolecularly into the terminal methylene. This result indicated the reaction mechanism, which involved the formation of iminium ion between the aldehyde and the dialkylamine followed by ene-type C-C bond formation with inverse electron demand and hydrolysis.