Catalytic Asymmetric Chlorinative Dearomatization Reaction of Benzofurans

A catalytic asymmetric chlorinative dearomatization reaction of benzofuran derivatives was achieved by using hydroquinidine 1,4‐phthalazinediyl diether [(DHQD)₂PHAL] as the catalyst and N‐chlorophthalimide (NCP) as the chlorinating reagent. A series of chlorinated spiro[benzofuran‐2,5′‐oxazole]s bearing two contiguous stereogenic centers was obtained in high yields (up to 99%) with excellent enantioselectivity (up to 99% ee).

     

Ligand‐Free Nickel‐Catalysed 1,4‐Addition of Arylboronic Acids to α,β‐Unsaturated Carbonyl Compounds

A simple and efficient ligand‐free nickel‐based catalytic system has been developed for the 1,4‐addition of arylboronic acids to α,β‐unsaturated carbonyl compounds. With catalyst loadings of 1–2 mol%, a series of 1,4‐adducts from chalcones and cinnamates was obtained in moderate to excellent yields within 5–30 min under a nitrogen atmosphere and microwave irradiation. The 1,4‐addition of arylboronic acids to acrylates is less efficient.

     

Zinc‐Catalyzed Stereo‐ and Regioselective 1,4‐Hydrative Fluorination of 3‐En‐1‐ynamides with Selectfluor

Zinc‐catalyzed 1,4‐oxofluorinations of 3‐en‐1‐ynamides with Selectfluor in acetonitrile/water proceeded with high regio‐ and stereoselectivity, giving E‐configured γ‐fluoro‐α,β‐unsaturated amides efficiently. Our control experiments indicate that kinetically unstable C‐bound zinc dienolates are chemically reactive to undergo S_E2′‐electrophilic fluorinations whereas the detectable O‐bound dienolates preferably undergo protodemetalation reactions instead.

     

Diastereo‐ and Enantioselective Synthesis of Chiral Pyrrolidine‐Fused Spirooxindoles via Organocatalytic [3+2] 1,3‐Dipolar Cycloaddition of Azomethine Ylides with Maleimides

In the presence of a Cinchona alkaloid‐based squaramide organocatalyst, the [3+2] cycloaddition of isatin‐derived azomethine ylides with maleimides proceeded readily, thus delivering the desired pyrrolidine‐fused spirooxindoles in 61–89% yields with >20:1 dr and 12 to >99 % ee. The absolute configuration of 5‐chloro‐1,5′‐dimethyl‐3′‐phenyl‐3′,3a′‐dihydro‐2′H‐spiro[indoline‐3,1′‐pyrrolo[3,4‐c]pyrrole]‐2,4′,6′(5′H,6a′H)‐trione was unambiguously determined by means of X‐ray single crystal structure analysis. The reaction mechanism was hypothesized to account for the enantioselective formation of 5‐chloro‐1,5′‐dimethyl‐3′‐phenyl‐3′,3a′‐dihydro‐2′H‐spiro[indoline‐3,1′‐pyrrolo[3,4‐c]pyrrole]‐2,4′,6′(5′H,6a′H)‐trione.

     

Synthesis and characterization of new polyamides containing p‐phenylenediacryloyl moieties in the main chain

Six new polyamides 8a–f containing p‐phenylenediacryloyl moieties in the main chain were prepared by the direct polycondensation reaction of bis(p‐amidobenzoic acid)‐p‐phenylene diacrylic acid 6 with 1,4‐diphenylene diamine 7a , 1,3‐diamino toluene 7b , 1,5‐diamino naphthalene 7c , 4,4′‐diamino diphenyl ether 7d , 4,4′‐diamino diphenyl sulfone 7e , and 3,3′‐diamino diphenylsulfone 7f by using thionyl chloride, N‐methyl‐2‐pyrolidone, and pyridine as condensing agents. These new polymers 8a–f were obtained in high yield and inherent viscosity between 0.35–0.65 dL/g. The resulting polyamides were characterized by elemental analysis, viscosity measurements, thermal gravimetric analysis (TGA and DTG), solubility test, FTIR and UV–vis spectroscopy. Diacid acid 6 as a new monomer containing p‐phenylenediacryloyl moiety was synthesized by using a three‐step reaction. First, p‐phenylenediacrylic acid 3 was prepared by reaction of terephthal aldehyde 1 with malonic acid 2 in the presence of pyridine, then diacid 3 was converted to p‐phenylenediacryloyl chloride 4 by reaction with thionyl chloride. Finally, bis(p‐amidobenzoic acid)‐p‐phenylene diacrylic acid 6 was prepared by the condensation reaction of phenylenediacryloyl chloride 4 with p‐aminobenzoic acid 5 . © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Late Stage C?H Activation of a Privileged Scaffold; Synthesis of a Library of Benzodiazepines

A library of over twenty 5‐(2‐arylphenyl)‐1,3‐dihydro‐2H‐1,4‐benzodiazepin‐2‐ones has been formed by a microwave‐mediated late‐stage palladium‐catalysed arylation of 1,4‐benzodiazepines using diaryliodonium salts. This can also be applied to nordazepam (7‐chloro‐5‐phenyl‐1,3‐dihydro‐2H‐1,4‐benzodiazepin‐2‐one), the active metabolite of diazepam, and subsequent N‐alkylation and/or H/D exchange allows further diversification towards elaborated pharmaceuticals and their 3,3′‐deuterated analogues.

     

Synthese und Reaktionen von 2-Phenyl- und 2-Methyl-2.3-dihydro-1.4-dithiin-5.6-dicarbonsäureimiden

Synthesis and Reactions of 2-Phenyl- and 2-Methyl-2,3-dihydro-1,4-dithiin-5,6-dicarboxylic Acid Imide The hydrolysis of 2-phenyl- and 2-methyl-5,6-dicyano-2,3-dihydro-1,4-dithiine yields the corresponding dicarboxylic acids, diamides and the imides 1, 2 . Substitution reactions on the imido group of 1 and 2 give the N-potassium, N-bromo, N-hydroxymethyl, N-methoxymethyl and N-chloromethyl derivatives. The latter reacts with salts of P-esters forming compounds of the general formula: The reaction of primary or secondary amines with 1 and 2 in the presence of formaldehyde leads to as result of an α-aminomethylation. The structure of the prepared compounds is discussed on the basis of their ¹H-NMR-, mass- and IR-spectra.     

Planar‐Chiral Cyclopentadienyl‐Ruthenium‐Catalyzed Regio‐ and Enantioselective Asymmetric Allylic Alkylation of Silyl Enolates under Unusually Mild Conditions

We report the asymmetric allylic alkylation of allylic chlorides with silyl enolates as a carbon nucleophile using a planar‐chiral cyclopentadienyl‐ruthenium (Cp′Ru) catalyst. The reaction proceeds under unusually mild conditions to give the desired branched products with complete regioselectivity and high enantioselectivity, and reactive functional groups, such as aldehyde, can be tolerated. In this reaction system, Cp′Ru plays an important role in activating both silyl enolate and allylic chloride.

     

Untersuchungen zum anodischen Verhalten von Carbazolen und Indolo[3,2-b]carbazolen in Acetonitril

Investigations on the Anodic Behaviour of Carbazoles and Indolo[3,2-b]carbazoles The anodic oxidation of some substituted or condensed carbazole derivatives 1 – 6 has been investigated in acetonitrile using platinum electrodes. Substitution of the carbazoles in the 3-, 6-, and 9-positions prevents the anodic dimerization occurring otherwise in these positions. In these cases the electrochemical formation of stable cation radicals is possible. A stabilization of these anodie primary products and a decrease of the half-wave potentials is also effected by enlarging the π-electron system as in N-p-anisyl-dibenzo[e,g]carbazole 2 , in the indolo[3,2-b]-carbazoles 3 and in 9,9′-diphenyl-3,3′-dicarbazyl 4 . Due to the distortion of the C N-bonds neither a change of half-wave potentials nor a stabilization of the cation radicals by donor substitution or mesomeric effects has been observed in the case of N-p-anisylcarbazole 1 h , 1,4-bis-(9-carbazyl)-benzene 5 and 4,4′-bis-(9-carbazyl)-biphenyl 6 in comparison with N-phenyl-carbazole 1 e . The electrochemical preparation of 4 and the spectroscopical investigation of the cation radicals of some of the compounds are described.     

Die Nitril-Carboxamid-Umlagerung

The Nitrile Carboxamide Rearrangement By reaction of cyclohexanone-2-carboxamide ( 4 ) with cyan amide 1-cyano-cyclohex-1-en-2-yl-urea ( 6 ) is formed via nitrile carboxamide rearrangement. Whilst compound 6 with 1,2-diaminobenzene hydrochloride forms 11-amino-1 H-2,3,4,5-tetrahydrodibenzo[b,e][1,4]diazepin hydrochloride ( 8 and 8a ), compound 6 and 1,2-diaminobenzene form hexahydro-benzimidazo[1,2-c]-quinazolin-6-one ( 12 ). Compound 8 with sodium hydroxide yields 11-amino-1 H-2,3,4,11a-tetrahydrodibenzo[b,e]-[1,4]diazepin ( 9 ). Compound 6 reacts with cyclohexylamine to form N-(1-cyanocyclohex-1-en-2-yl)-N′-cyclohexyl urea ( 10 ). Compound 10 with 1,4- or 1,2-diaminobenzene hydrochloride yields compound 7 and 8 . In alkaline solution 10 cyclises to 4-amino-3-cyclohexyl-2,3,5,6,7,8-hexahydroquinazolin-2-one ( 11 ). Compound 4 and malonitrile form either 3-amino-4-cyano-1,2,5,6,7,8-hexahydro-isoquinol-1-one ( 13 ) or 1-amino-4-cyano-2,3,5,6,7,8-hexahydro-isoquinol-3-one ( 14 ). Compound 13 and alkaline formaldehyde react to cyanooctahydroisoquinoline-[2,3-c] [1,3,5]oxdiazin-6-one ( 17 ). 2-Cyanoethyl-cyclohexan-one-2-carboxamide ( 22 ), prepared by Michael-reaction from 4 and acrylonitrile, forms via nitrile carboxamide rearrangement 10-cyano-1,2,3,4,5,6,7,10-octahydroquinolin-2-one ( 24 ) and 2-(1′-cyano-cyclohexyl-2′-one)-propionic acid ( 25 ). Nucleophilic attack of the NH₂-group at the cyanogroup of compound 22 forms 5-(spirocyclohexan-2′-one)-hexahydropyridin-2,6-dione ( 27 ).     

New organic polymers,I. Synthesis and characterization of poly Schiff bases from benzidine-3,3′-dicarboxylic acid

Thermally stable and semiconducting polymers are synthesized by condensing benzidine-3,3′-dicarboxylic acid (BDC), with dicarbonyl compounds like glyoxal, cyclohexane-1,4-dione, 4,4′-diacetyl diphenyl ether and benzil under different experimental conditions. These poly Schiff bases are insoluble in common organic solvents. They are characterized by IR- and viscosity studies, thermal analysis, and the study of electrical properties at various temperatures. Variation of the electrical conductivity, σ, with temperature was found to confirm with the empirical relation:      

Umsetzung von (Z/E)-1-Aryl-4-arylmethylen-pyrrolidin-2,3,5-trionen mit Enaminocarbonylverbindungen

Reaction of (Z/E)-1-Aryl-4-arylmethylene-pyrrolidine-2,3,5-triones with Enaminocarbonyl Compounds Treatment of the α, β-unsaturated ketones (Z/E)- 1a–e with alicyclic or aliphatic enamines afforded cyclic Michael adducts 2 and 3a–e , respectively. By dehydration of the N,O-hemiacetals 3b–d the corresponding 1,4-dihydropyridines 4a–c were obtained. The acid-catalyzed reaction of aminosubstituted maleimides with (Z/E)- 1e , aldehydes or indan-1,2,3-trione led to 5a–c , 6a–c , 7a–c and 8 . O-Methylation of the aryl-bis(maleinimidyl)methanes 5c , 6c by using diazomethane gave 5d , 6d , whereas 5a cyclized spontaneously to the 1,4-dihydropyridine 9a . Further 1,4-dihydropyridines were prepared by cyclocondensation of 6a , b in the presence of ammonium acetate and oxidized to the pyridine derivative 10 .     

Organocatalytic Reactions of Indoles with Quinone Imine Ketals: An Alternative Metal‐Free Approach to Bioactive meta‐Indolylanilines

An organocatalytic metal‐free strategy has been established for the synthesis of pharmaceutically relevant meta‐indolylanilines in generally excellent yields (up to 99 %). This strategy took advantage of the reaction of indoles and quinone imine ketals (QIKs) in the presence of racemic phosphoric acid, which proceeded via a 1,4‐addition/alcohol elimination reaction sequence. The control experiment demonstrated that the dual hydrogen‐bonding activation mode of the catalyst to the substrates played a crucial role in the reaction. This protocol provides a metal‐free and step‐economical approach to meta‐anilines bearing either 3‐indolyl or 2‐indolyl moiety, which is of high value for the synthesis of compounds with potential bioactivities.

     

Action of Grignard Reagents on 6-Arylpyridazin-3(2H)-thiones

6-Arylpyridazin-3(2H)-thiones ( 1a—c ) react with Grignard reagents by 1,4-addition to give either 4-substituted 6-aryl-4,5-dihydropyridazin-3(2H)-thiones ( 2a—c ) or their dehydrogenated products, namely 4-substituted 6-arylpyridazin-3(2H)-thiones ( 3d—k ). The reaction of Grignard reagents with 6-aryl-4-methylpyridazin-3(2H)-thiones ( 3d—f ) proceeds also by 1,4-addition yielding 4,4-disubstituted 6-aryl-4,5-dihydropyridazin-3(2H)-thiones ( 5 ). Structural assignments are based on analytical and spectral data and also on the synthesis of authentic samples in some cases.     

Regioselective Friedel–Crafts Reaction of Electron‐Rich Benzenoid Arenes and Spiroepoxyoxindole at the Spiro‐Centre: Efficient Synthesis of Benzofuroindolines and 2H‐ Spiro[benzofuran]‐3,3′‐oxindoles

Metal triflate‐catalysed intermolecular Friedel–Crafts reactions involving electron‐rich benzenoid arenes and spiroepoxyoxindoles at the spiro‐centre have been developed for the exclusive regioselective synthesis of 3‐aryl‐(3‐hydroxymethyl)oxindoles with an all‐carbon quaternary centre. Selective ring opening of spiroepoxyoxindoles with phenols provided a direct access to 3‐(hydroxymethyl)‐3‐(2‐hydroxyaryl)oxindoles. We have utilized this methodology successfully as the key step for the synthesis of benzofuroindolines and 2H‐spiro[benzofuran]‐3,3′‐oxindoles.

     

Control of Chain Orientation in Blends of Polypropylene and Polybutene‐1

An extruded sheet having unique molecular orientation is developed using a miscible blend of isotactic polypropylene (PP) and isotactic polybutene‐1 (PB). Blends containing a small amount of N ,N′‐dicyclohexyl‐2,6‐naphthalenedicarboxamide are extruded from a ribbon‐shaped die onto a chill roll at various temperatures. It is found that form‐I crystals of PB become oriented in the flow direction, whereas β‐form crystals of PP become oriented perpendicular to the flow direction. The molecular orientation is the most obvious for the blend containing 60 wt% of PB extruded at a chill roll temperature of 80 °C. The anisotropy in the tensile modulus of the obtained extruded sheet is reduced by its extraordinary molecular orientation.

     

Microwave‐assisted polycondensation of 4,4′‐(hexafluoroisopropylidene)‐N,N′‐bis(phthaloyl‐L‐leucine) diacid chloride with aromatic diols

A new facile and rapid polycondensation reaction of 4,4′‐(hexafluoroisopropylidene)‐N,N′‐bis(phthaloyl‐L ‐leucine) diacid chloride (1) with several aromatic diols such as phenol phthalein (2a), bis phenol‐A (2b), 4,4′‐hydroquinone (2c), 1,4‐dihydroxyanthraquinone (2d), 1,8‐dihydroxyanthraquinone (2e), 1,5‐dihydroxy naphthalene (2f), dihydroxy biphenyl (2g), and 2,4‐dihydroxyacetophenone (2h) was performed by using a domestic microwave oven in the presence of a small amount of a polar organic medium such as o‐cresol. The polymerization reactions proceeded rapidly, compared with the conventional solution polycondensation, and was completed within 10 min, producing a series of optically active poly(ester‐imide)s with quantitative yield and high inherent viscosity of 0.50–1.12 dL/g. All of the above polymers were fully characterized by IR, elemental analyses, and specific rotation. Some structural characterization and physical properties of this optically active poly(ester‐imide)s are reported. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 3003–3009, 2000     

Synthesis of novel poly(amide‐imide)s containing trimellitylimido‐DL/L‐alanine moieties via direct polycondensation

N‐Trimellitylimido‐DL and L ‐alanine ( 3 ) were prepared from the reaction of trimellitic anhydride ( 1 ) with DL and L ‐alanine ( 2 ) in N,N‐dimethyl formamide (DMF) solution at refluxing temperature. The direct polycondensation reaction of the monomers imide‐diacid ( 3 ) with 4,4′‐diaminodiphenylsulfone ( 4a ), 4,4′‐diaminodiphenylmethane ( 4b ), 1,4‐phenylenediamine ( 4c ), 1,3‐phenylenediamine ( 4d ), 2,4‐diaminotoluene ( 4e ), and 4,4′‐diaminodiphenylether ( 4f ) was carried out in a medium consisting of triphenyl phosphite, N‐methyl‐2‐pyrolidone (NMP), pyridine, and calcium chloride. The resulting poly(amide‐imide)s PAIs, with inherent viscosities 0.32–0.66 dL/g, were obtained in high yield. All of the above‐mentioned compounds were fully characterized by IR, elemental analyses, and specific rotation. Some structural characterization and physical properties of these new optically active PAI s are reported. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 1312–1318, 2001     

The Synthesis and in vivo Evaluation of 2′,2′‐Difluoro KRN7000

The synthesis of 2′,2′‐difluoro KRN7000 is described. In vivo evaluation demonstrates that this fluorinated glycolipid induces CD1d‐dependent TCR activation of NKT cells, with a bias towards Th2 cytokine production.

     

Asymmetric α‐Hydroxylation of β‐Indanone Esters and β‐Indanone Amides Catalyzed by C‐2′ Substituted Cinchona Alkaloid Derivatives

The highly catalytic asymmetric α‐hydroxylation of β‐indanone esters and β‐indanone amides using peroxide as the oxidant was realized with a new C‐2′ substituted Cinchona alkaloid derivatives. The two enantiomers of α‐hydroxy‐β‐indanone esters could be obtained by simply changing the oxidant. This protocol allows a convenient access to the corresponding α‐hydroxy‐β‐indanone esters and α‐hydroxy‐β‐indanone amides with up to 99% yield and 98% ee.