- Stereocontrolled Construction of Condensed γ-Lactam Ring Systems by Cationic Cyclizations. Rearrangement of a γ-Lactam to a δ-Lactam
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A new condensation of 3-alkenamides with benzaldehyde in acidic media, notably polyphosphoric acid, lead to γ-lactam rings with high regio- and stereocontrol.One such γ-lactam was shown to undergo a novel and stereocontrolled ring-expansion to a δ-lactam.
- Marson, Charles M.,Grabowska, Urszula,Walsgrove, Timothy,Eggleston, Drake S.,Baures, Paul W.
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Read Online
- Construction of N-Heterocyclic Systems Containing a Fully Substituted Allylic Carbon by Palladium/Phosphine Catalysis
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The unique cyclization of benzamide derivatives that contain an alkyne by a Pd(0)/dialkyl(biaryl)phosphine catalytic system is reported. The reaction efficiently provides a variety of six-membered N-heterocyclic compounds that contain a fully substituted carbon center without the need for a stoichiometric additive. Mechanistic studies suggest that this unprecedented cyclization starts with the cleavage of a propargylic C-O bond, and a 1,3-diene has been identified as a relevant intermediate.
- Ogiwara, Yohei,Suzuki, Yui,Sato, Kazuya,Sakai, Norio
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Read Online
- Synthesis of Spirobicyclic Pyrazoles by Intramolecular Dipolar Cycloadditions/[1s, 5s] Sigmatropic Rearrangements
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The formation of fused pyrazoles via intramolecular 1,3-dipolar cycloadditions of diazo intermediates with pendant alkynes is described. A subsequent thermal [1s, 5s] sigmatropic shift of these pyrazole systems resulted in a ring contraction, forming spirocyclic pyrazoles. The limitations of this rearrangement were explored by changing the substituents on the nonmigrating aromatic ring and by using substrates lacking an aromatic linkage to the propargyl group.
- Dimirjian, Christine A.,Casti?eira Reis, Marta,Balmond, Edward I.,Turman, Nolan C.,Rodriguez, Elys P.,Di Maso, Michael J.,Fettinger, James C.,Tantillo, Dean J.,Shaw, Jared T.
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supporting information
p. 7209 - 7212
(2019/10/02)
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- Cobalt-catalyzed versus uncatalyzed intramolecular Diels-Alder cycloadditions
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The intramolecular [4+2] cycloadditions of dienynes was investigated using cobalt-based catalysts. Substrates without substitution on alkyne moiety were found to react under thermal activation. The use of a cobalt salt as catalyst made reactions cleaner by limiting the formation of byproducts. Cycloadditions with dienynes possessing a substituent on the alkyne pattern occurred only in presence of a cobalt catalyst which displayed a moderate to good activity depending on the substrate patterns.
- Biletskyi, Bohdan,Tenaglia, Alphonse,Clavier, Hervé
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supporting information
p. 103 - 107
(2017/12/28)
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- Synthesis of Carbolines via Palladium/Carboxylic Acid Joint Catalysis
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The combination of a Pd(0) complex with benzoic acid converts propargylic tryptamines to the corresponding tetrahydro-β-carbolines. The method uses unprotected indoles and affords the desired products with ample functional group tolerance. Detailed modeling studies reveal a close synergy between the organic and metal catalysts, which enables sequential alkyne isomerization, indole C-H activation, and eventual C-C reductive elimination to afford the target heterocycles.
- Cera, Gianpiero,Lanzi, Matteo,Balestri, Davide,Della Ca, Nicola,Maggi, Raimondo,Bigi, Franca,Malacria, Max,Maestri, Giovanni
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supporting information
p. 3220 - 3224
(2018/06/11)
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- Gold-Catalyzed Regiodivergent [2 + 2 + 2]-Cycloadditions of Allenes with Triazines
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Gold-catalyzed regiodivergent cycloadditions of functionalized allenes with 1,3,5-triazines, providing diverse N-heterocycles in moderate to excellent yields under mild reaction conditions, are reported. Importantly, different types of allenes exhibit distinct selectivity and reactivity for the reactions. Mechanistic investigations reveal that all of the cycloadditions proceed through a stepwise [2 + 2 + 2]-cycloaddition process.
- Peng, Shiyong,Cao, Shengyu,Sun, Jiangtao
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supporting information
p. 524 - 527
(2017/02/10)
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- Kinetics of the reaction of N,N-dimethylaniline with 1-bromoalk-2-ynes
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Quaternization of N,N-dimethylaniline with propargyl bromide, 1-bromobut-2-yne, and 1-bromooct-2-yne were studied. It was shown that, with the lengthening chain of the substituent at the triple bond, the quaternization rate tends to increase.
- Andreev,Ryzhakov,Sobolev
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p. 1486 - 1489
(2017/09/01)
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- Palladium-catalyzed cyclization of alkynoic acids to form vinyl dioxanones bearing a quaternary allylic carbon
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A palladium-catalyzed intramolecular reaction of carboxylic acids and alkynes in a novel cyclization manner was developed. This unique cyclization efficiently provided a wide range of complex ring systems-vinyl dioxanones bearing a quaternary allylic carbon. Mechanistic studies suggest an allenyl carboxylate as an intermediate.
- Ogiwara, Yohei,Sato, Kazuya,Sakai, Norio
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supporting information
p. 5296 - 5299
(2017/11/06)
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- A 1 - bromo - 2 - ethyl-acetylene production method (by machine translation)
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The invention relates to a 1 - bromo - 2 - ethyl-acetylene production method, including in the THF bromoethane with magnesium metal in the reaction to prepare the Grignard reagent, then to the Grignard reagent in the form after adding poly-formaldehyde reaction, format after the reaction separation and recovery 2 - ethyl-acetylene - 1 - ol; and will 2 - ethyl-acetylene - 1 - ol with phosphorus tribromide bromination reaction, bromination reaction after the end of the separation and recovery of 1 - bromo - 2 - ethyl-acetylene. In this invention the format adopted for the more common reaction currently in use, and does not need special production equipment, the reaction condition is comparatively mild, in industrialized production process is more stable, with a low risk. The phosphorus tribromide to 2 - ethyl-acetylene - 1 - ol performing the bromination, the utilization rate of high, produce by-products phosphoric acid and in pyridine and easy processing. (by machine translation)
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Paragraph 0014
(2017/06/13)
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- Bioorthogonal Enzymatic Activation of Caged Compounds
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Engineered cytochrome P450 monooxygenase variants are reported as highly active and selective catalysts for the bioorthogonal uncaging of propargylic and benzylic ether protected substrates, including uncaging in living E. coli. observed selectivity is supported by induced-fit docking and molecular dynamics simulations. This proof-of-principle study points towards the utility of bioorthogonal enzyme/protecting group pairs for applications in the life sciences.
- Ritter, Cornelia,Nett, Nathalie,Acevedo-Rocha, Carlos G.,Lonsdale, Richard,Kr?ling, Katja,Dempwolff, Felix,Hoebenreich, Sabrina,Graumann, Peter L.,Reetz, Manfred T.,Meggers, Eric
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supporting information
p. 13440 - 13443
(2015/11/09)
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- Catalytic activation of diazo compounds using electron-rich, defined iron complexes for carbene-transfer reactions
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Carbene transfer: The electron-rich iron complex Bu4N[Fe(CO) 3(NO)] efficiently catalyzes different carbene-transfer reactions. Various diazo compounds can be used. The high stability of the employed iron complexes is demonstrated by the generation of the diazo reagent in situ and a sequential iron-catalyzed allylic sulfenylation/Doyle-Kirmse reaction. Copyright
- Holzwarth, Michael S.,Alt, Isabel,Plietker, Bernd
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supporting information; experimental part
p. 5351 - 5354
(2012/07/14)
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- Synthesis of carbazoles by gold(I)-catalyzed carbocyclization of 2-(enynyl)indoles
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A new synthetic protocol for carbazoles through gold(I)-catalyzed intramolecular hydroarylation of (Z)-2-(enynyl)indoles was achieved in good yields. The requisite (Z)-2-(enynyl)indoles were synthesized stereoselectively by trimethylgallium-promoted, Z-selective Wittig olefination of N-alkylindole-2-carboxaldehydes with propargyl ylides. Substrates possessing both alkyl as well as aromatic groups are well tolerated under these reaction conditions. Georg Thieme Verlag Stuttgart.
- Praveen, Chandrasekaran,Perumal, Paramasivan Thirumalai
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scheme or table
p. 521 - 524
(2011/04/17)
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- Iron-catalyzed synthesis of functionalized 2H-chromenes via intramolecular alkyne-carbonyl metathesis
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An iron-catalyzed intramolecular alkyne-aldehyde metathesis strategy of the alkynyl ether of salicylaldehyde derivatives has been developed which works under mild reaction conditions to produce the functionalized 2H-chromene derivatives. This protocol is compatible toward a wide range of functional groups, such as methoxy, fluoro, chloro, bromo, and phenyl groups. This method provides an atom-economical and environmentally friendly approach for the synthesis of a series of substituted 2H-chromenes.
- Bera, Krishnendu,Sarkar, Soumen,Biswas, Srijit,Maiti, Sukhendu,Jana, Umasish
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experimental part
p. 3539 - 3544
(2011/06/23)
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- Iron-catalyzed, hydrogen-mediated reductive cyclization of 1,6-enynes and diynes: Evidence for bis(imino)pyridine ligand participation
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(Chemical Equation Presented) The bis(imino)pyridine iron dinitrogen complex (iPrPDI)Fe(N2)2 catalyzes the hydrogen-mediated reductive cyclization of enynes and diynes with turnover frequencies comparable to those of established precious metal catalysts. Amino, oxygenated, and carbon-based substrates are readily cyclized to the corresponding hetero- and carbocycles with 5 mol % iron and 4 atm H2 at 23°C. Stoichiometric reactions between selected substrates and the iron compound under a N2 atmosphere established transfer dehydrogenation from an isopropyl aryl substituent to either the enyne or diyne substrate. In situ monitoring of the catalytic reaction by 1H NMR spectroscopy coupled with deuterium labeling experiments established rapid cyclization followed by turnoverlimiting hydrogenation. Copyright
- Sylvester, Kevin T.,Chirik, Paul J.
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supporting information; experimental part
p. 8772 - 8774
(2009/12/04)
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- Palladium(II)-catalyzed enyne coupling reaction initiated by acetoxypalladation of alkynes and quenched by protonolysis of the carbon-palladium bond
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Divalent palladium-catalyzed inter- and intramolecular enyne coupling reactions initiated by acetoxypalladation of alkynes were developed. The reaction involves the acetoxypalladation of the alkyne, followed by the insertion of the alkene and the protonolysis of the carbon-palladium bond. The protonolysis of the carbon-palladium bond in the presence of bidentate nitrogen containing ligands is the key step in completing the Pd(II) catalytic cycle. The nitrogen-containing ligands, like halides, served to favor the protonolysis of the carbon-palladium bond over the β-H elimination in the Pd(II)-mediated reactions. The intermolecular coupling reactions provide an efficient method for synthesizing γ,δ-unsaturated carbonyls. The intramolecular coupling reactions offer a method to construct a variety of synthetically important carbo- and heterocycles. The asymmetric version of such a cyclization was developed with moderate enantioselectivity when employing pymox (pyridyl monooxazoline) as the ligand.
- Zhao, Ligang,Lu, Xiyan,Xu, Wei
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p. 4059 - 4063
(2007/10/03)
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- A new method for the synthesis of plurisubstituted pyrroles
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A versatile method for the synthesis of pyrroles is described using an intramolecular [3+2] cycloaddition reaction. This method allows the expedient preparation of 'plurisubstituted' compounds in which functionality is incorporated by choice, using appropriate readily available starting materials. Polycyclic pyrrole derivatives as well as 2-aryl monocyclic analogues are described. Several families of compounds are synthesized by sequential transformations. The method is designed to allow the creation of libraries with increased diversity of functionality by combinatorial or parallel synthesis.
- Bashiardes, George,Safir, Imad,Barbot, Francis,Laduranty, Joelle
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p. 8417 - 8420
(2007/10/03)
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- FUSED IMIDAZOLE COMPOUNDS AND REMEDIES FOR DIABETES MELLITUS
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The present invention provides a preventive or therapeutic agent for diabetes mellitus and diabetic complications, which is a new type based on an adenosine A2 receptor antagonist action. That is, it provides a novel condensed imidazole compound which has an adenosine A2 receptor antagonist action, is effective for preventing or treating diabetes mellitus and diabetic complications, and is represented by the formula (I): (wherein R1 represents e.g. an amino group which may be substituted with an alkyl group; R2 represents e.g. hydrogen atom, an alkyl group, a cycloalkyl group or an alkyl group, alkenyl group or alkynyl group which may be substituted with hydrox etc.; R3 represents e.g. an optionally substituted alkyl group, alkenyl group, alkynyl group, aryl group, heteroaryl group, pyridinone group, pyrimidinone group or piperadinone group; Ar represents e.g. an optionally substituted aryl or heteroaryl group; and Q and W are the same as or different from each other and each represents N or CH), a pharmacologically acceptable salt or hydrates thereof.
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- Subtype-selective NMDA receptor ligands and the use thereof
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The invention relates to subtype-selective NMDA receptor ligands and the use thereof for treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neuro-degenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the overstimulation of the excitatory amino acids, treating anxiety, psychosis, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headache, chronic pain, Parkinson's disease, glaucoma, CMV retinitis, urinary incontinence, opioid tolerance or withdrawal, and inducing anesthesia, as well as for enhancing cognition.
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- The aza-[2,3]-Wittig sigmatropic rearrangement of acyclic amines: Scope and limitations of silicon assistance
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The inclusion of a C-2 trialkylsilyl substituent into allylic amine precursors allows the base-induced aza-[2,3]-Wittig sigmatropic rearrangement to proceed in excellent yield and diastereoselectivity. The rearrangement precursors require a carbonyl-based nitrogen protecting group that must be stable to excess of strong base required for the reaction. The N-Boc and N-benzoyl group are very good at stabilizing the product anion and initiating deprotonation. The migrating groups (G) need to stabilize the intial anion by resonance and require G-CH3 pKa > 22 in order for the initial anion to be reactive enough for rearrangement. Products 7, 29b-d,f,g, and 23 are formed with high (10-20:1) anti diastereoselectivity. Product 23 containing the morpholine amide group is useful for preparing other carbonyl derivatives.
- Anderson,Flaherty,Swarbrick
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p. 9152 - 9156
(2007/10/03)
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- Synthesis of 5,6,7-trinor-4,8-inter-m-phenylene PGI2 and Beraprost
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We have disclosed a new class of stable PGI2 analogue, 5,6,7-trinor- 4,8-inter-m-phenylene PGI2 which has a phenyl ether moiety instead of enol- ether skeleton in PGI2. The m-phenylene PGI2 and its derivative (Betaprost) were synthesized via dihydrocyclopenta[b]benzofuran derivatives as key intermediates by ortho-selective metal-halogen exchange reaction with Grignard reagents and subsequent copper-catalyzed cyclization. The ω-side chains were introduced by stereoselective epoxide formation or Prins reaction.
- Wakita, Hisanori,Matsumoto, Kazuhisa,Yoshiwara, Hideo,Hosono, Yutaka,Hayashi, Ryoji,Nishiyama, Hisao,Nagase, Hiroshi
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p. 2449 - 2474
(2007/10/03)
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- Pharmaceutical compounds
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Pharmaceutical compounds of the formula STR1 in which n is 0, 1 or 2 and m is 1 or 2, R1 is hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, phenyl, naphthyl, C1-10 alkyl-phenyl, C2-10 alkenyl-phenyl or C2-10 alkynyl-phenyl, said phenyl and naphthyl groups being optionally substituted, R2 is hydrogen or a protecting group, and Q is an acidic group; or a salt or ester thereof.
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- Asymmetric hydrolysis of pro-chiral 3,3-disubstituted 2,4-diacetoxy-cyclohexa-1,4-dienes
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Asymmetric enzymatic hydrolysis of pro-chiral 3,3-disubstituted 2,4-diacetoxycyclohexa-1,4-dienes 2 affords in high yields optically pure 2,2-disubstituted 3-acetoxycyclohex-3-enones 1 (>98% ee). Under mild conditions Candida cylindracea lipase (enzyme/substrate ratio = 2%) hydrolyses specifically the pro-S enol ester function of the pro-chiral starting material 2.
- Renouf, Philippe,Poirier, Jean-Marie,Duhamel, Pierre
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p. 1739 - 1745
(2007/10/03)
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- Dihydropyridazinones, pyridazinones and related compounds as fungicides
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This invention relates to substituted dihydropyridazinones, pyridazinones and related compounds, of the formula STR1 wherein A, Q, D and R1 are as defined within, compositions containing these compounds and methods of controlling agricultural and mammalian fungal diseases.
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- The synthesis of substituted pyrrolidines by a samarium (II) iodide mediated ring closure. Part 2
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Samarium (II) iodide-mediated ring closures, of substituted N-propargyl substrates derived from L-serine, have been used to generate a series of 2,3,4-trisubstituted pyrrolidine derivatives.
- Baldwin, Jack E.,MacKenzie Turner, Sean C.,Moloney, Mark G.
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p. 9425 - 9438
(2007/10/02)
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- Anticonvulsant and neurotoxic activities of twelve analogues of valproic acid.
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Twelve racemic analogues of the antiepileptic drug valproic acid (VPA) were tested and compared with VPA for anticonvulsant activity by the subcutaneous pentylenetetrazol (PTZ) seizure threshold test and for neurotoxicity by the rotorod test. Four compounds produced maximal anticonvulsant activity (100% protection) in equimolar doses (1.5 mmol/kg) to VPA and two compounds showed a similar effect with lower doses (1.0 mmol/kg). Four compounds produced lower activity (38-80% protection), and two compounds showed no anticonvulsant activity at the dose used (1.5 mmol/kg). Two of the 12 compounds, (+/-)-2-n-propyl-4-hexynoic acid (11) and (+/-)-4-methyl-2-n-propyl-4-pentenoic acid (12), showed no sedation at doses that produced the maximum anticonvulsant effect. For the first time we succeeded to develop two compounds with higher protective index and safety ratios than VPA. Compound 11 had a longer duration of action and higher protective index but a lower safety ratio than 12. Comparisons of the anticonvulsant and minimal neurotoxic effects of these compounds with their calculated lipophilicity (C log P) revealed that compounds with the desired high anticonvulsant activity and minimal neurotoxicity showed C log P values between 1.84 and 2.64 and had nine carbon atoms (in contrast to eight carbon atoms for VPA).
- Elmazar,Hauck,Nau
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p. 1255 - 1258
(2007/10/02)
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- CONVERSION OF ALCOHOLS INTO ALKYL BROMIDES AND IODINES VIA O-ALKYLISOUREAS
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Treatment of O-alkylisoureas with trifluoromethanesulphonic acid and a tetrabutylammonium salt (bromide or iodide) affords alkyl halides in high yields.
- Collingwood, Stephen P,Davies, Alan P,Golding, Bernard T
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p. 4445 - 4448
(2007/10/02)
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- YNENOLACTONE PROTEASE INHIBITORS
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Compounds of the formula STR1 wherein n is 1-3; R 1, R. sup.2 and R 3 are the same or different and are hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl or aryl lower alkyl wherein when aryl is phenyl it is unsubstituted or independently substituted with one or more halo, lower alkyl or lower alkoxy groups; and R 4 is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, trialkylsilyl, aryl or aryl lower alkyl wherein when aryl is phenyl it is unsubstituted or independently substituted by one or more halo, lower alkyl or lower alkoxy groups; excluding those compounds wherein R. sup.1 and R 2 are hydrogen and R 4 is ethyl, propyl or butyl. These compounds are useful as protease inhibitors.
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- Novel 9-substituted carbacyclin analogs
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Novel compounds of the following general formula: STR1
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- 9-Substituted carbacyclin analogs
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Novel compounds of the following general formula: STR1
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- 5,6,7-Trinor-4,8-inter-m-phenylene prostaglandin I2 derivatives useful in anti-ulcer, hypotensive and platelet aggregation inhibiting compositions
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A compound of the formula STR1 wherein R1 is a pharmaceutically acceptable cation, hydrogen or n-alkyl of 1 to 12 carbon atoms; R2 is hydrogen, acyl of 2 to 10 carbon atoms or aroyl of 7 to 13 carbon atoms; R3 is hydrogen, acyl of 2 to 10 carbon atoms or aroyl of 7 to 13 carbon atoms; R4 is hydrogen, methyl or ethyl; R5 is n-alkyl of 1 to 5 carbon atoms; n is an integer of 0 to 4; A is --CH2 --CH2 -- or trans --CH=CH--; and X is --CH2 --CH2 -- or trans --CH=CH--. The compounds are useful in anti-ulcer, hypotensive and platelet aggregation inhibiting compositions.
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- Carbacyclin analogs
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Novel compounds of the following general formula: STR1
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- 9-Substituted carbacyclin analogs
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Novel compounds of the following formula: STR1
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- Alteration of relative affinities toward myocardial and vascular β adrenoceptors induced by side-chain substitution of aryloxypropanolamines1
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Several conformationally defined aryloxypropanolamines of the type ArOCH2CH(OH)CH(R)NHR1 have been synthesized and tested in vivo for β-adrenoceptor blockade. Key intermediates in the syntheses were the appropriate cis- and trans-disubstituted olefins. Epoxidation of the olefins, followed by amination of the resulting cis- and trans-epoxides, yielded the desired diastereomeric model compounds with a defined threo and erythro stereochemistry, respectively. All active compounds in this series exhibit a simple, bimolecular, competitive antagonism at β adrenoceptors. Proper substitutions of the alkanolamine side chain result in vascular selective or cardioselective β-adrenoceptor antagonists, probably as a consequence of the sterically altered ability to interact with β1 and β2 adrenoceptors. dl-erythro-1-Phenoxy-3-[3,4-dimethoxyphenethyl)amino] butan-2-ol is a cardioselective β-adrenoceptor antagonist with a selectivity ratio significantly higher than that of practolol (β1/β2>40 vs. β1/β2=22) but of equal potency (pA2 values = 6.66 and 6.64, respectively). Phenyl substitution at C-3 of the alkanolamine side chain drastically reduces affinity to both types of β adrenoceptors (pA25.0), thus representing a cutoff point. It is concluded that steric factors, as manifested by bulk tolerance at various parts of the aryloxypropanolamine side chain, are major determinants of affinity toward β-adrenoceptor subtypes. β-Adrenoceptor blockade is unrelated to the lipophilic character of the test compounds.
- Shtacher,Rubinstein,Somani
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p. 678 - 683
(2007/10/04)
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