Facile synthesis of 3-aryl benzofurans, 3-aryl benzothiophenes, 2-aryl indoles and their dimers

The preparation of 3-aryl benzofuran and benzothiophenes and their dimers at 2-position and, 2-aryl indoles and their 3-position dimers preparation is described.     

A novel synthesis of epoxides and allylic alcohols from carbonyl compounds through α, β-epoxy sulfoxides

Treatment of α,β-epoxy sulfoxides, easily prepared from carbonyl compounds with 1 equivalent of n-butyllithium at −100 °C gave the desulfinated epoxides in good yields. The similar α,β-epoxy sulfoxides having arylmethyl group at α-position, on treatment with excess n-butyllithium at −70 °C afforded 3-aryl allylic alcohols.     

Pyrimidones. 2. Synthesis and reactions of 2-chloropyrimidines

The treatment of 1-alkyl-5-aryl and 1-alkyl-4,5-diaryl-2-(1H)pyrimidones with phosphorus oxychloride and phosphorus pentachloride resulted in chlorination and dealkylation to furnish 2-chloro-5-aryl (or 4,5-diaryl)-pyrimidines. These chlorpyrimidines were reacted with a variety of nitrogen, oxygen, sulfur, and carbon nucleophiles to produce the corresponding 2-substituted pyrimidines. In the case of phenyllithium, attack occurred at the 4-position of the pyrimidine ring yielding 11 . Triazolopyrimidine 9 was synthesized via the treatment of 2d with hydrazine followed by reaction with triethyl orthoformate.     

Electrostatic medium effects and formal quantum structure–activity relationships in apomorphines interacting with D1 and D2 dopamine receptors

The binding of apomorphines (AM) to D₁ and D₂ dopamine receptors is analyzed through a formal quantum structure–activity relationship method. The calculations were carried out at the CNDO/2 level of the molecular orbital theory with a continuum representation of environmental effects. The results show that the D₁ receptor affinity variation is related to the variation of the electron-donating capacity of a C atom of the hydroxylic region of apomorphines in a low-polarity medium. The N-chain probably interacts with a hydrophobic region of the receptor. It is also concluded that the poor results for the D₂ binding affinity are explained by errors in the experimental measurements. Finally, it is proposed that future structure–activity relationship studies must be carried out for media of different polarities. © 1997 John Wiley & Sons, Inc.     

Experimental and computational study of the conrotatory ring opening of various 3-chloro-2-azetines

A combined experimental and theoretical study is presented on 2-azetines, a class of azaheterocyclic compounds, which are difficult to access but have shown a unique reactivity as strained cyclic enamines. New highly substituted 2-azetines bearing aryl substituents at the 2- and 4-position were synthesized from 3,3-dichloroazetidines. Whereas 2-aryl-3,3-dichloroazetidines gave stable 2-aryl-3-chloro-2-azetines upon treatment with sodium hydride in DMSO, 2,4-diaryl-3,3-dichloroazetidines showed a remarkably different reactivity in that they afforded benzimidoyl-substituted alkynes under similar mild treatment with base. The formation of the alkynes involves electrocyclic ring opening of intermediate 2,4-diaryl-3-chloro-2-azetines and elimination of hydrogen chloride. Ab initio theoretical calculations confirmed the experimental findings and demonstrated that the 4-aryl substituent is responsible for this remarkably enhanced reactivity of 2-azetines toward electrocyclic conrotatory ring opening by a significant decrease in reaction barrier of about 30 kJ/mol. This activation effect by an aryl group in the allylic position toward electrocyclic ring opening of unsaturated four-membered rings is of general importance since a similar increased reactivity of 4-aryloxetes, 4-arylthiete-1,1-dioxides, and 3-arylcyclobutenes has been reported in literature as well.     

Synthesis of methyl 3-amino-4-aryl(or methyl)sulfonyl-2-thiophenecarboxylates from 3-alkoxy-2-aryl(or methyl)-sulfonylacrylonitriles

The synthesis of a series of methyl 3-amino-4-aryl(or methyl)sulfonylthiophene-2-carboxylates by reaction of 3-alkoxy-2-aryI(or methyl)sulfonylacrylonitriles with methyl thioglycolate in the presence of triethylamine is described. Hydrolysis/decarboxylation of the ester at the 2-position and acylation of the resulting amine represents a convenient route to 4-arylsulfonyl-3-carboxamidothiophenes. Attempted acylation of a title aminothiophene under standard conditions was unsuccessful.     

Asymmetric baker’s yeast reductions of bridgehead-substituted bicyclo[2.2.2]octane-2,6-dione derivatives followed by conversion into catalytically active BODOLs for the diethylzinc addition to benzaldehyde

4-Substituted bicyclo[2.2.2]octane-2,6-diones have been synthesized and tested as substrates in the enantioselective reduction with baker’s yeast to give the corresponding hydroxy ketones. It was found that the derivative bearing a TIPSO group at the 4-position was not reduced at all while that with a TBDMSO group gave 87% yield and 46% ee. Other 4-oxy functionalized derivatives were reduced with varying yields (36–87%) and ees (10–82%). The best result was obtained for the 4-Oallyl derivative (80% yield, 82% ee). The hydroxy ketones carrying the benzyloxy and allyloxy groups at the 4-position were converted into the corresponding BODOLs, which were tested as catalysts in the diethylzinc addition to benzaldehyde. In this reaction the ees were 90% and 89%, respectively, which showed that BODOLs substituted at the 4-position are essentially as good catalysts in this reaction as those bearing a hydrogen.     

Remarkably efficient enantioselective titanium(IV)-(R)-H8-BINOLate catalyst for arylations to aldehydes by triaryl(tetrahydrofuran)aluminum reagents

Novel asymmetric triarylaluminum AlAr3(THF) additions to aldehydes catalyzed by 10 mol % of the titanium(IV) complex of (R)-H8-BINOL ligand are reported. The catalytic system is extremely efficient with reactions completing within 10 min. The system applies to the most diversified aldehydes to date, and more than 20 aldehydes were examined to afford diarylmethanols having an electron-donating or an electron-withdrawing group at the 2-, 3-, or 4-position on the aryl moiety, linear or branched 1-aryl aliphatic alcohols, aryl furyl methanols, 1-aryl allylic alcohols, and, especially, 1-aryl propargylic alcohols in excellent enantioselectivities of >/=90% ee, except for the case of 1-naphthyl addition to benzaldehyde. Noteworthily, diarylmethanols in both R- and S-configurations can be obtained.     

Atropisomers of meso Tetra(N-Mesyl Pyrrol-2-yl) Porphyrins: Synthesis,Isolation and Characterization of All-Pyrrolic Porphyrins

Atropisomerism has been observed in a variety of biaryl compounds and meso-aryl substituted porphyrins. However, in porphyrins, this phenomenon had been shown only with o-substituted 6-membered aromatic groups at the meso-position. We show herein that a 5-membered heteroaromatic (N-mesyl-pyrrol-2-yl) group at the meso-position leads to atropisomerism. In addition, we report a ‘one-pot’ synthetic route for the synthesis of ‘all-pyrrolic’ porphyrin (APP) with several N-protection groups (Boc, Cbz, Ms and Ts). Among these groups, we found that only the Ms group gave four individually separable atropisomers of meso-tetra(N-Ms-pyrrol-2-yl) porphyrin. Furthermore, the reductive removal of Cbz- was achieved to obtain meso-tetra(pyrrol-2-yl) porphyrin. Thus, our synthetic procedure provides an easy access to a group of APPs and stable atropisomers, which is expected to expand the application of novel APP-based materials.     

One-Pot Synthesis of Enantioenriched β-Amino Secondary Amides via an Enantioselective [4+2] Cycloaddition Reaction of Vinyl Azides with N-Acyl Imines Catalyzed by a Chiral Brønsted Acid

A catalytic enantioselective synthesis of β-amino secondary amides was achieved using vinyl azides as the enamine-type nucleophile and chiral N-Tf phosphoramide as the chiral Brønsted acid catalyst through a five-step sequential transformation in one pot. The established sequential transformation involves an enantioselective [4+2] cycloaddition reaction of vinyl azides with N-acyl imines as the key stereo-determining step that is efficiently accelerated by a chiral N-Tf phosphoramide catalyst in a highly enantioselective manner in most cases. Further generation of the iminodiazonium ion intermediate through ring opening of the cycloaddition product and subsequent skeletal rearrangement involving Schmidt-type 1,2-aryl group migration followed by recyclization of the resulting nitrilium ion were also initiated by the same acid catalyst. Final acid hydrolysis of the recyclized products in the same pot gave rise to enantioenriched β-amino amides through C−C bond formation at the α-position of the secondary amides.     

Porphyrin-Stabilized Nitrenium Dication

An azepine-fused Ni^II-porphyrin dimer was synthesized by oxidative amination of β–β linked Ni^II-porphyrin dimer, and its N-aryl congener was synthesized by twofold Buchwald–Hartwig amination of β-to-β linked and dichlorinated Ni^II-porphyrin dimer. Oxidation of the NH congener gave neutral aminyl radical and nitrenium ion successively in a similar manner to the previously reported NH-bridged Ni^II-porphyrin dimer. Oxidation of the N-aryl congener afforded formal nitrenium dication in a single-step two-electron oxidation. Stable nitrenium dications that are isoelectronic to neutral trivalent boron compounds and tertiary carbocations are rare. The chemical stability of the nitrenium dication was improved by chlorine substitution at the most reactive β-position. The structural, optical, magnetic, electrochemical properties of these compounds were fully characterized.     

Preparation of 2-aryl and 2-aryloxymethyl imidazo[1,2-a]pyridines and related compounds

A series of substituted 2-aryl imidazo[1,2-a]pyridines has been prepared in which a variety of substituents are introduced on the 4′-position of the phenyl ring and on the 3, 5 , 6 or 7 position of the heterocyclic ring. Most examples have acetamido, bromo, cyano, or formyl substituents at the 4′-position. Analogous imidazo-[2,1-b]fhiazoles and imidazo[1,2-a]pyrimidines have also been prepared. Another series of compounds consisting of 4′-formylphenoxymethyl derivatives of imidazole, the three positional isomers of pyridine, thiazole, benzimidazole and ring-substituted imidazo[1,2-a]pyridines has been prepared. 2-(4′-Formylphenylethenyl) derivatives of imidazole and imidazo[1,2-a]pyridine were also prepared.     

Remarkable wavelength-dependent photoreactions of the bis(diazo) ketone having inequivalent diazo groups: studies in fluid solutions and in low-temperature matrixes

The photoreactions of the bis(diazo) ketone 11, which has two inequivalent diazo groups, have been investigated in solutions at room temperature and in matrixes at 12 K. Irradiation of 11 in benzene containing methanol gave a mixture of the spironorcaradiene 13 and the diazo ketone 17 as primary isolable photoproducts. The former 13 originated from the diazo ketene 20, which was formed from the initial extrusion of N(2) from the 2-position of 11, while the latter product 17 was derived from the diazo ketene 24 which was generated by the initial decomposition of the diazo group at the 4-position of 11. The product distribution was remarkably dependent upon the excitation wavelength: 13 was predominantly obtained in the photolysis with light of >350 nm, while the irradiation with long-wavelength light (>420 nm) exclusively gave 17. The consistent wavelength effects were observed in photoreactions in an Ar matrix at 12 K. The irradiation of 11 matrix-isolated in Ar with light of >350 nm afforded 20 in preference to the isomer 24 as the first-formed intermediates, while 24 was mainly obtained in the long-wavelength irradiation (>420 nm). On the basis of these experimental data, we conclude that the short-wavelength irradiation of 11 causes a preferential cleavage of the diazo group at the 2-position and that the selective extrusion of N(2) from the 4-position is practically achieved by the irradiation with long-wavelength light. The reason for the selective cleavage of the two inequivalent diazo groups of 11 is discussed on the basis of theoretical calculations with the PM3 CI method.     

Triethylamin-mediated addition of 2-aminoethanethiol hydrochloride to chalcones: Synthesis of 3-(2-aminoethylthio)-1-(aryl)-3-(thiophen-2-yl) propan-1-ones and 5,7-diaryl-2,3,6, 7-tetrahydro-1,4-thiazepines

The triethylamin-mediated addition of 2-aminoethanethiol hydrochloride to chalcone analogs was investigated. This addition, bearing a 2-thienyl group at the 3-position, gave the only addition adduct at room temperature in 3 h, whereas the chalcones bearing the 2-furyl group at the 1-position gave an addition-cyclization product (1, 4-thiazepine) in the same conditions. The effect of the groups to the reaction was investigated by changing the 1- and 3-position groups. The chalcones bearing the 2-thienyl group at the 1-position and the others afforded the mixture of products in different ratio at rt for 0.5–24 h. Moreover, the addition–cyclization products (1,4-thiazepine) were obtained under reflux conditions in 36 h. The structures of the synthesized compounds were elucidated by ¹H NMR, ¹³C NMR, infrared, and elemental analysis.     

一些含氮杂环的脱氢松香酸甲酯衍生物的合成

以歧化松香为原料,将其纯化得到脱氢松香酸,用硫酸二甲酯酯化后,通过12位溴代、7位氧化、脱异丙基硝化等步骤,得到了3个重要的中间体.该3个中间体分别经过亲核取代、还原关环反应后,得到了一些脱氢松香酸甲酯含氮杂环衍生物;产物结构经红外光谱、核磁共振谱、质谱和元素分析进行了表征.     

Direct arylation of oxazoles at C2. A concise approach to consecutively linked oxazoles

The synthesis of bis- and trisoxazoles via direct arylation is discussed. A variety of aryl groups can be installed at the 2-position of 5-aryl and 5-carboxy-substituted oxazoles under mild conditions using palladium catalysis on water. The direct arylation method can be extended to the synthesis of bis- and trisoxazoles if 2-triisopropylsilyl-4-iodooxazole is used as the electrophile in the arylation.     

Regioselective ortho lithiation of 3-aryl and 3-styryl furans

[structure: see text]. An unusual regioselectivity pattern for the ortho lithiation of 3-aryl and 3-styryl furans has been uncovered wherein lithiation occurs preferentially at the sterically encumbered 2-position. The results are attributed, at least in part, to stabilization of the intermediate furyl anion by through-space donation of pi-electron density from the substituent appended at the 3-position to the lithium cation. This ortho lithiation reaction may be applied as a useful synthetic tool for accessing 2,3-disubstituted furans.     

Intramolecular photocycloadditions of 6,6′-dimethyl-4,4′-polymethylenedioxy-di-2-pyrones

Photosensitized reactions of 4,4′-polymethylene-di-2-pyrones 2b-e afforded [2+2]-cycloadducts 3-5 , site-selectively. The selectivity depended upon the methylene chain length. Namely, the three carbon chain gave a syn head-to-head adduct 3b at the 3,4-position of the 2-pyrone ring, the four to six carbon chains gave syn head-to-head adducts 4c-e at the 5,6-position and/or anti head-to-head adducts 5d,e at the 5,6-position, respectively. The intramolecular cycloaddition mechanism was also explained from results calculated by means of PM3-CI method.     

Synthesis of 3-amino-6-methyl-5-ethoxycarbonyl-4,7-dihydrothieno[2,3-b]pyridine derivatives

The alkylation of piperidinium salts of substituted 1,4-dihydropyridine-2-thiols with chloroacetonitrile or iodoacetamide gave 2-cyanomethylthio- and 2-carbamoylmethylthio-substituted 6-methyl-4-aryl(pyridyl)-5-ethoxycarbonyl-3-cyano-1,4-dihydropyridines, which undergo intramolecular cyclization in basic media to give 3-amino-6-methyl-4-aryl(pyridyl)-5-ethoxycarbonyl-2-cyano(carbamoyl)-4,7-dihydrothieno[2,3-b]pyridines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 124–128, January, 1987.