New atropoisomeric alkenylphenylglycine derivatives: Synthesis of (5R*)- and (5S*)-isomers of (1R*,3aR*,4S*,11S*)-3a,5,9,11-tetramethyl-4,5-dihydro-3aH-1,4-methano[1,3]oxazolo[3,2-a]quinolin-2-one

We synthesized methyl ester of N-(1-methylbut-2-en-1-yl)-N-phenylglycine which underwent acid catalyzed aromatic amino Claisen rearrangement to provide methyl-N-[2-(1-methylbut-2-en-1-yl)phenyl]glycinate. A mixture of syn- and anti-atropisomeric methyl-N-acetyl-N-[4-methyl-2-(1-methylbut-2-en-1-yl)phenyl]glycinates was obtained either by the reaction of this ester with acetyl bromide or by the reaction of the sodium salt of N-acetyl-2-(1-methylbut-2-en-1-yl)-4-methylaniline with methyl bromoacetate. Upon saponification of the synthesized ester mixture the syn-atropisomer of N-acetyl-N-[4-methyl-2-(1-methylbut-2-en-1-yl)phenyl]glycine was isolated by fractional crystallization. Treatment of the obtained acids with acetic anhydride, ethyl chloroformate, dicyclohexylcarbodiimide or isopropenylacetate leads to compounds of 4,5-dihydro-3aH-methano[1,3]oxazolo[3,2-a]quinolin-2-one structure.     

Synthesis of N-acetyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]indoles from N- and 2-(cyclopent-2-en-1-yl)anilines

Reactions of 2-bromo-N-(cyclopent-2-en-1-yl)-4-methylaniline and N-(cyclopent-2-en-1-yl)-2-iodo-4,6-dimethylaniline with acetyl bromide in the presence of potassium carbonate gave mixtures of syn and anti atropisomers of the corresponding N-acetyl derivatives at ratios of 1: 1 and 3: 2 respectively. Heating of these mixtures in toluene in the presence of Pd(OAc)₂, PPh₃, Et₃N, and K₂CO₃ (KOAc) afforded mixtures of isomeric N-acetyl-7-methyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]indoles at a ratio of 3: 1 or N-acetyl-5,7-dimethyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]indoles at a ratio of 2: 3. N-Acetyl-3,3a,4,8b-tetrahydrocyclopenta[b]indole was found to undergo thermal isomerization into N-acetyl-1,3a,4,8btetrahydrocyclopenta[b]indole.     

Reaction of N-methylsulfonyl-and N-(p-tolylsulfonyl)-2-(cyclopent-1-en-1-yl)anilines with bromine in the presence of potassium thiocyanate and in methanol

The reactions of N-methylsulfonyl-and N-(p-tolylsulfonyl)-2-(cyclopent-1-en-1-yl)-6-methylaniline with molecular bromine in the presence of potassium thiocyanate gave N-methylsulfonyl-and N-(ptolylsulfonyl)-2-(5-isothiocyanatocyclopent-1-en-1-yl)-6-methylanilines. N-Methylsulfonyl-2-(cyclopent-1-en-1-yl)-6-methylaniline reacted with bromine in methanol in the presence of NaHCO₃ or with CuBr₂ in MeOH to afford N-methylsulfonyl-2-(5-methoxycyclopent-1-en-1-yl)-6-methylaniline. The reaction of N-methylsulfonyl-2-(5-isothiocyanatocyclopent-1-en-1-yl)-6-methylaniline with diethylamine led to the formation of N-methylsulfonyl-2-{5-[diethylamino(thioxo)methyl]aminocyclopent-1-en-1-yl}-6-methylaniline which was converted into 5-methyl-4-methylsulfonyl-2,3,3a,4-tetrahydrocyclopenta[b]indole by heating with potassium hydroxide.     

Self-cyclization of (E)-2-(trimethylsilylmethyl)pentadienol derivative. Synthesis of bicyclo[4.3.0]nonane ring systems

Utility and limitation of the title reaction was studied. When (E)-3-(4-t-butyl- and 4-phenylcyclohex-1-en-1-yl)-2-(trimethylsilylmethyl)prop-2-en-1-ols were treated with Ms₂O or MsCl, 3-t-butyl- and 3-phenyl-8-methylbicyclo[4.3.0]nona-1(6),7-dienes were obtained, respectively. The corresponding (Z)-isomer afforded a complex mixture, among which an elimination product was detected. (E)-4-(4-t-Butylcyclohexylidene)-2-(trimethylsilylmethyl)but-2-en-1-ol afforded only elimination product.     

Synthesis and bromination/dehydrobromination of <Emphasis Type="Italic">N,N</Emphasis>-diallyltrifluoromethanesulfonamide

The reaction of triflluoromethanesulfonamide with allyl bromide in dimethyl sulfoxide gave N,N-diallyltrifluoromethanesulfonamide which was subjected to bromination with 1 and 2 equiv of bromine. The product of bromine addition to both allyl groups, CF₃SO₂N(CH₂CHBrCH₂Br)₂, was found to exist as a mixture of two diastereoisomers at a ratio of 9: 11. Its dehydrobromination by the action of sodium methoxide was chemoselective with successive elimination of one, two, and three hydrogen bromide molecules to afford N-(2-bromoprop-2-en-1-yl)-N-(2,3-dibromopropyl)trifluoromethanesulfonamide, N,N-bis(2-bromoprop-2-en-1-yl)trifluoromethanesulfonamide, and N-(2-bromoprop-2-en-1-yl)-N-(propadienyl)trifluoromethanesulfonamide, respectively.     

Approach to preparative synthesis of <Emphasis Type="Italic">ortho</Emphasis>-(1-methylbut-2-en-1-yl)anilines,precursors of new cytotoxic heterocycles

The reaction of aromatic Claisen rearrangement of N-(1-methylbut-2-en-1-yl)anilines in the presence of p-toluenesulfonic acid was investigated. N-Tosyl-2-(1-iodoethyl)-3-methylindoline derivatives were obtained; one of them exhibited a cytotoxic activity.     

Synthesis of (5R*)- and (5S*)-5,7,11-trimethyl-3a-phenyl-4,5-dihydro-3aH-1,4-methano[1,3]oxazolo[3,2-a]quinolin-2-ones

Heating of N-benzoyl-N-[2-(1-methylbut-2-en-1-yl)-4-methylphenyl]glycine with ethyl chloroformate or acetic anhydride gave (5R*) and (5S*) isomers of (1R*,3aS*,4S*,11S*)-5,7,11-trimethyl-3a-phenyl-4,5-dihydro-3aH-1,4-methano[1,3]oxazolo[3,2-a]quinolin-2-one.     

Preparation of methano[1,3]oxazolo[3,2-a]quinolin-2-ones from 2-(pent-3-en-2-yl)anilines

Acid-catalyzed Claisen aromatic rearrangement of ethyl N-(pent-3-en-2-yl)-N-phenylglycinate leads to the formation of ethyl N-[2-(pent-3-en-2-yl)phenyl]glycinate. The reaction of sodium salt of N-acetyl-2-(pent-3-en-2-yl)-4-methylaniline with methyl bromoacetate afforded ethyl N-acetyl-N-[4-methyl-2-(pent-3-en-2-yl)phenyl]glycinate. The hydrolysis of synthesized esters, the conversion of the obtained acids by treating with ethyl chloroformate into munchnones, and the subsequent [3+2]-cycloaddition provided methoxazoloquinoline structures.     

Stereoselective synthesis of cis and trans-fused 3a-aryloctahydroindoles using cyclization of N-vinylic α-(methylthio)acetamides: synthesis of (−)-mesembrane

Treatment of N-(2-arylcyclohex-1-en-1-yl)-α-(methylthio)acetamides with N-chlorosuccinimide (NCS) gave 3a-aryl-2,3,3a,4,5,6-hexahydro-3-(methylthio)indol-2-ones. Desulfurization of the cyclization products followed by a catalytic hydrogenation of the resulting hexahydroindol-2-ones gave predominantly or exclusively trans-fused octahydroindol-2-ones. On the other hand, reduction of the desulfurization products with Et₃SiH in CF₃CO₂H exclusively provided cis-fused octahydroindol-2-ones. A chiral induction of N-[2-(3,4-dimethoxy)phenylcyclohex-1-en-1-yl]-α-(methylthio)acetamide having an (R)-1-(1-naphthyl)ethyl group on the nitrogen atom led to the synthesis of (−)-mesembrane and (−)-trans-mesembrane.     

New captodative polyheterofunctionalized cyclopentenones from 2,3,5-Trichloro-4,4-dimethoxy-5-(2-methylfuran-3-yl)cyclopent-2-en-1-one and secondary amines

2,3,5-Trichloro-4,4-dimethoxy-5-(2-methylfuran-3-yl)cyclopent-2-en-1-one reacted with secondary amines to give unusual Ad_NE-substitution-fragmentation products, 5-[(1Z,2E)-1-acetyl-3-dialkylaminoprop-2-en-1-ylidene]-3-dialkylamino-2-chloro-4,4-dimethoxycyclopent-2-en-1-ones.     

Synthesis,Characterization, and Antioxidant Properties of Novel 1-(4-Aryl-1,3-thiazol-2-yl)-2-{[1-(3-methylbut-2-en-1-yl)-1H-indol-3-yl]methylidene}hydrazines

Russian Journal of Organic Chemistry - A series of novel 1-(4-aryl-1,3-thiazol-2-yl)-2-{[1-(3-methylbut-2-en-1-yl)-1H-indol-3-yl]methyli­dene}hydrazines were synthesized and properly...     

Synthesis and structure of 5,5′-[(E,E)-2,5-diiodohexa-1,5-diene-1,6-diyl]bis(2,3-dichloro-4,4-dimethoxycyclopent-2-en-1-one)

Treatment of 2,3,5-trichloro-5-[(E)-2,3-diiodoprop-1-en-1-yl]-4,4-dimethoxycyclopent-2-en-1-one with SmI₂ in THF gives 5,5′-[(1E,5E)-2,5-diiodohexa-1,5-diene-1,6-diyl]bis(2,3-dichloro-4,4-dimethoxycyclopent-2-en-1-one) and its meso form at a ratio of 3:1.     

Synthesis of (1′S*,2R*,3R*)- and (1′S*,2R*,3S*)-N-arylsulfonyl-2-(1′-halogenethyl)-3-methylindolines and their selective toxicity against SH-SY5Y cell line

N-tosyl-2- and N-tosyl-4-halogen-substituted derivatives of 2-(1-methylbut-2-en-1-yl)aniline were synthesized and their molecular iodine-mediated cyclization was investigated. The cyclization upon interaction of N-tosyl-6-methyl-2-(1-methylbut-2-en-1-yl)aniline with molecular iodine in methyl tert-butyl ether or acetonitrile was studied, as well as the interaction of this sulfonamide with N-bromosucinimide in dichloromethane. Synthesized (2R*,3R*)- and (2R*,3S*)-N-arylsulfonyl-2-(1-halogenoethyl)-3-methylindoline derivatives showed cytotoxic activity against HEK293 cells, SH-SY5Y, Jurkat, and HepG2 cell lines. The compounds (2R*,3S*)-N-arylsulfonyl-7-bromo-2-(1-halogenoethyl)-3-methylindoline cis- 4a , stereoisomeric (2R*,3R*)-trans- 4h and (2R*,3S*)-N-tosyl-7-chloro-2-(1-halogenoethyl)-3-methylindoline cis- 4h demonstrated selective toxicity against SH-SY5Y cell line (IC₅₀ ≈ 3 ÷ 5 μM), and did not affect HEK293, Jurkat, and HepG2 cells.     

Stereocontrolled synthesis of (+)-α-skytanthine by means of an intramolecular Pauson-Khand reaction

Diastereoselective synthesis of (+)-α-skytanthine was established by means of an intramolecular Pauson-Khand reaction of N-but-2-yn-1-yl-N-[(2R)-2-methylbut-3-en-1-yl]-1-(2-nitrobenzene)sulfonamide, in which the newly generated stereogenic center was stereoselectively constructed to be R by reflection of the stereochemistry of the methyl group in the starting material.     

Fusion of 2-(furan-2-yl)thiazole to 1-methyl-1<Emphasis Type="Italic">H</Emphasis>-benzimidazole

Methylation of 5(6)-nitro-1H-benzimidazole with methyl iodide in the presence of potassium hydroxide and N-methylpyrrolidin-2-one gave a mixture of isomeric 1-methyl-5-nitro- and 1-methyl-6-nitro-1H-benzimidazoles which were reduced with tin in concentrated aqueous HCl on heating. The resulting amines reacted with furan-2-carbonyl chloride in N-methylpyrrolidin-2-one to give furan-2-carboxamides which were treated with excess P₂S₅ in pyridine. Oxidation of isomeric furan-2-carbothioamides with K₃[Fe(CN)₆] in alkaline medium afforded a mixture of intramolecular cyclization products, 2-(furan-2-yl)-6-methyl-6H-imidazo[4,5-g][1,3]benzothiazole and 2-(furan-2-yl)-8-methyl-8H-imidazo[4,5-g][1,3]benzothiazole which were separated by column chromatography and identified.     

BF3·OEt2-catalyzed synthesis of 1-(tetrahydropyran-3-yl)-1,3-dihydroisobenzofuran and trans-fused hexahydropyrano[3,2-c]chromene derivatives

A novel intramolecular Prins cyclization of (E)-5-(2-(hydroxymethyl)phenyl)pent-4-en-1-ol with aldehydes has been achieved using 10 mol % BF₃·Et₂O to produce 1-(tetrahydropyran-3-yl)-1,3-dihydroisobenzofuran derivatives in good to excellent yields with high selectivity. Similar type of coupling with salicylaldehydes provides the trans-fused hexahydropyrano[3,2-c]chromene derivatives in excellent yields.     

Reactions of allenylphosphonates with 1,2-diaminoethane

The reactions of dialkyl 3-methylbuta-1,2-dien-1-ylphosphonates with 1,2-diaminoethane lead to the formation of symmetrical N,N′-bis(1-dialkoxyphosphoryl-3-methylbut-1-en-2-yl)-1,2-diaminoethanes.     

DFT theoretical studies of anions of aniline and its several derivatives

Detailed studies of the molecular and electronic structures, vibrational frequencies, and infrared intensities of [M ⁻] and [M-H ⁻] anions of aniline and its derivatives (2-, 3-, 4-fluoroanilines, N-[(2E)-1-methylbut-2-en-1-yl]aniline, (2-cyclopent-2-en-1-ylphenyl)amine, N-[(2E)-1-methylbut-2-en-1-yl]aniline, and N-cyclopent-2-en-1-ylaniline) have been carried out using the density functional method with UB3LYP functional and 6-31G** basis set augmented with sp diffuse functions on nitrogen, fluorine, and three carbon atoms of benzene ring (in 2, 4, and 6 positions). For comparison, similar calculations were carried out for the closed-shell neutral molecules ([M]). The studies have provided detailed insight into the structure changes that take place in negative ions of aniline and its derivatives.     

Palladium(II)-catalyzed Amination of Isoprene with Aniline

The reaction of isoprene with aniline, catalyzed by the Pd(acac)₂-(RO)₃P-CF₃CO₂H system, 1 : 4 : 4 [R = Me, Et; acac = (CH₃CO)₂CH], in MeCN provides N-(3-methylbut-2-en-1-yl)aniline with a high selectivity (up to 84%) and a nearly quantitative yield (75%). At 1 : 4 : 20 and 1 : 4 : 40 molar component ratios in the catalytic system, up to 28–31% of N,N-(2,3-dimethylprop-2-en-1-yl)aniline is formed. Telomeric reaction products appear at 1 : 2 : 4 and 1 : 1 : 10 ratios.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 6, 2005, pp. 963–968.Original Russian Text Copyright © 2005 by Petrushkina, Mysova, Orlinkov.     

Synthesis of 4,6-dimethyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile by condensation of cyanothioacetamide with acetaldehyde and 1-(prop-1-en-2-yl)piperidine

Three-component condensation of cyanothioacetamide with acetaldehyde and 1-(prop-1-en-2-yl)-piperidine afforded 4,6-dimethyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile which was alkylated with alkyl halides to obtain substituted 2-alkylsulfanyl-4,6-dimethylpyridine-3-carbonitriles, (3-amino-4,6-dimethylthieno-[2,3-b]pyridin-2-yl)(4-cyclohexylphenyl)methanone, and 2,2′-[ethane-1,2-diylbis(sulfanediyl)]bis(4,6-dimethylpyridine-3-carbonitrile).