- C-Alkylation of αβ-Acetylenic Esters using Electrochemically Generated Intermediates
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Electrolysis at a platinum cathode of ethyl alk-2-ynoates in the presence of an excess of alkyl iodide in hexamethylphosphoramide or dimethylformamide solution containing tetra-n-butylammonium iodide gave the corresponding non-conjugated dialkylation products, ethyl 2,2-dialkylalk-3-ynoates, in good yield.
- Tokuda, Masao,Nishio, Osamu
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Read Online
- One-pot mild and efficient synthesis of [1,3]thiazino[3,2-: A] indol-4-ones and their anti-proliferative activity
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A base mediated environmentally benign one-pot efficient methodology has been developed for the synthesis of [1,3]thiazino[3,2-a]indol-4-ones using indoline-2-thiones and propiolate esters in aqueous medium. The conjugate addition of thiones first results in ethyl (3-(indol-2-yl)thio)acrylates in situ, which subsequently undergoes intramolecular cyclization to produce indole-fused thiazin-4-ones in good to excellent yields. The cytotoxic screening of the synthesized compounds using MTT assay revealed the anti-proliferative nature of these frameworks against triple negative breast cancer cell lines with the highest activity emanating from 4H-[1,3]thiazino[3,2-a]indol-4-one and 8-methyl-2-propyl-4H-[1,3]thiazino[3,2-a]indol-4-one compounds.
- Rhodes, Steven,Short, Spencer,Sharma, Sidhika,Kaur, Ramneet,Jha, Mukund
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supporting information
p. 3914 - 3920
(2019/04/30)
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- Convergent One-Pot Oxidative [n + 1] Approaches to Spiroacetal Synthesis
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Two one-pot oxidative annulative approaches to spiroacetal synthesis are described. One approach uses a Lewis acid mediated Ferrier reaction in the fragment-coupling stage followed by DDQ-promoted oxidative carbon-hydrogen bond cleavage and cyclization. An alternative approach employs a Heck reaction for fragment coupling followed by DDQ-mediated enone formation and cyclization. These strategies provide convergent routes to common subunits in natural products, medicinal agents, and chemical libraries under mild reaction conditions.
- Peh, Guangrong,Floreancig, Paul E.
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supporting information
p. 3750 - 3753
(2015/08/18)
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- Copper(II)-catalyzed silylation of activated alkynes in water: Diastereodivergent access to E- or Z-β-silyl-α,β-unsaturated carbonyl and carboxyl compounds
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Copper(II)-catalyzed silylation of substituted alkynylcarbonyl compounds was investigated. Through the activation of Me2PhSiBpin in water at room temperature and open atmosphere, vinylsilanes conjugated to carbonyl groups are synthesized in high yield. A surprising diastereodivergent access to olefin geometry was discovered using a silyl conjugate addition strategy: aldehydes and ketones were Z selective while esters and amides were exclusively transformed into the E products. Dial a diastereomer: The title reaction proceeds through the activation of Me2PhSiBpin in water at room temperature and open atmosphere to produce high yields of vinylsilanes conjugated to carbonyl groups. A surprising diastereodivergent access to olefin geometry was discovered using this silyl conjugate addition strategy: aldehydes were Z selective while esters and amides exclusively delivered the E-configured products.
- Calderone, Joseph A.,Santos, Webster L.
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supporting information
p. 4154 - 4158
(2014/05/06)
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- SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
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Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of conditions such as depression and related disorders. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
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Paragraph 00303; page 125
(2014/08/19)
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- Selective one-pot synthesis of allenyl and alkynyl esters from β-ketoesters
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(Chemical Equation Presented) A convenient method is described for the dehydration of β-ketoesters to generate conjugated and deconjugated alkynyl esters and conjugated allenyl esters. This sequential one-pot method involves the formation of a vinyl trifl
- Maity, Pradip,Lepore, Salvatore D.
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body text
p. 158 - 162
(2009/04/07)
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- The asymmetric aza-claisen rearrangement: development of widely applicable pentaphenylferrocenyl palladacycle catalysts
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Systematic studies have been performed to develop highly efficient catalysts for the asymmetric aza-Claisen rearrangement of trihaloacetimidates. Herein, we describe the stepwise development of these catalyst systems involving four different catalyst generations finally resulting in the development of a planar chiral pentaphenylferrocenyl oxazoline palladacycle. This complex is more reactive and has a broader substrate tolerance than all previously known catalyst systems for asymmetric aza-Claisen rearrange-ments. Our investigations also reveal that subtle changes can have a big impact on the activity. With the enhanced catalyst activity, the asymmetric aza-Claisen rearrangement has a very broad scope: the methodology not only allows the formation of highly enantioenriched primary allylic amines, but also secondary and tertiary amines; al-lylic amines with N-substituted quaternary stereocenters are conveniently accessible as well. The reaction conditions tolerate many important functional groups, thus providing stereoselective access to valuable functionalized building blocks, for example, for the synthesis of unnatural amino acids. Our results suggest that face-selective olefin coordination is the enantioselectivitydetermining step, which is almost exclusively controlled by the element of planar chirality.
- Fischer, Daniel F.,Barakat, Assem,Xin, Zhuo-Qun,Weiss, Matthias E.,Peters, Rene
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supporting information; experimental part
p. 8722 - 8741
(2010/03/31)
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- Asymmetric formation of allylic amines with N-substituted quaternary stereocenters by PdII-catalyzed aza-Claisen rearrangements
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(Chemical Equation Presented) With the ferrocene imidazoline palladacycle FIP-Cl as precatalyst, quaternary N-substituted stereocenters can be generated in an asymmetric aza-Claisen rearrangement. Excellent enantioselectivities are obtained even if R and R′ have a similar or identical size (see scheme: e.g. 96% ee for CH3/CD3).
- Fischer, Daniel F.,Xin, Zhuo-Qun,Peters, Rene
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p. 7704 - 7707
(2008/09/18)
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- Palladium-catalyzed synthesis of N-vinyl pyrroles and indoles
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A stereospecific palladium-catalyzed N-vinylation of aza-heterocycles with vinyl inflates is described. Cyclic and acyclic vinyl triflates along with nonnucleophilic azaheterocycles were found to be substrates for this palladium-catalyzed synthesis of N-vinyl pyrrole and indole derivatives.
- Movassaghi, Mohammad,Ondrus, Alison E.
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p. 8638 - 8641
(2007/10/03)
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- Total synthesis of (+)-amphidinolide A. Assembly of the fragments
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The structure elucidation of (+)-amphidinolide A, a cytotoxic macrolide, has been accomplished by employing a combination of total synthesis and NMR spectroscopic analysis. Amphidinolide A possesses two skipped 1,4-diene subunits which are accessible by ruthenium-catalyzed alkene-alkyne couplings. Previous total syntheses had revealed that the reported structure was incorrect; therefore, to incorporate maximum flexibility into the synthesis, with the ultimate goal of determining the correct structure, a highly convergent approach was chosen. Furthermore, liberal use was made of catalytic asymmetric transformations to set individual stereocenters. Three different strategies were envisioned for the end game, and due to the highly convergent nature of the synthesis, all three routes disconnect to the same three key intermediates, 5, 6, and 7. Diastereomers of 6 and 7 were easily prepared by modification of the synthetic routes to allow access to multiple diastereomers of 1 for structural determination.
- Trost, Barry M.,Wrobleski, Stephen T.,Chisholm, John D.,Harrington, Paul E.,Jung, Michael
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p. 13589 - 13597
(2007/10/03)
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- Reaction of 1,2,3-selenadiazoles with phosphines
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Nucleophilic attack of tributyl- and triphenylphosphines on 4-phenyl- and 5-ethoxycarbonyl-4-methyl-1,2,3-selenadiazoles leads to the quantitative formation of selenophosphoranes and substituted acetylenes. The molecular structure of 4-phenyl-1,2,3-selenadiazole was confirmed by X-ray crystallography.
- Arsenyan,Oberte,Rubina,Belyakov,Lukevics
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p. 503 - 506
(2007/10/03)
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- A study on the scope of the photochemical ring contraction of substituted 2-amino-3-cyano-4H-pyrans to cyclobutenes: Crystal structure of 3-carbamoyl-3-cyano-1-ethoxycarbonyl-4-isopropyl-2-phenylcyclobutene
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A study on the influence of substitution on the photochemical reactivity of a series of differently substituted 2-amino-4H-pyrans 10a-h has been carried out. All of the compounds undergo ring contraction to the corresponding cyclobutenes 11a-h on direct irradiation. Variable amounts of the enamides 12 and the alkynes 13 were also obtained, as secondary photoproducts. The results obtained show that the cyclization takes place in reasonable yields with alkyl, phenyl and hydrogen substitution at C-4 and at C-6. Cyano, ethoxycarbonyl and benzoyl substitution at C-5 also promotes the reaction. A high degree of stereochemical control was observed in most cases. The molecular geometry of cyclobutene 11a1 has been established by X-ray diffraction analysis. This study also shows that the crystal packing is formed by a system of chains linked by strong hydrogen bonds.
- Armesto, Diego,Albert, Armando,Cano, Felix H.,Martin, Nazario,Ramos, Ana,Rodriguez, Miriam,Segura, Jose L.,Seoane, Carlos
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p. 3401 - 3405
(2007/10/03)
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- Palladium-mediated cross-coupling reactions involving 3-substituted alkyl (E)-2,3-dibromopropenoates and arylzinc or aryltin derivatives
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Stereodefined unsymmetrically 3,3-disubstituted alkyl 2-bromopropenoates, 5, were regioselectively prepared by Pd-mediated reactions between 3-alkyl, 3-aryl and 3-alkoxycarbonyl substituted (E)-2,3-dibromopropenoates, (E)-7, and aryl or 1-alkynylzinc chlorides. The stereospecificity of these reactions was found to be dependent on the type of substituent present in the 3-position of (E)-7. The (E)-stereochemistry of compounds 5b, 5d and 5i so prepared was confirmed by their conversion into the corresponding 4-substituted 3-bromocoumarins. Tetrasubstituted α,β-unsaturated esters 10 were then synthesized by Pd-mediated reactions either of (E)-7 with a molar excess of an arylzinc chloride or an aryltributylstannane, or of a compound of general formula 5 with an aryltributylstannane. An examination of the parameters which influence the stereochemistry and the yields of these arylations was made.
- Rossi, Renzo,Bellina, Fabio,Carpita, Adriano,Mazzarella, Felice
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p. 4095 - 4110
(2007/10/03)
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- Phosphonium Salts and Phosphoranes. Part 5. Thermal and Electron-Impact Induced Fragmentation of Heteroaroylmethylenetriphenylphosphoranes.
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A modification of Trippett's pyrolysis of aroylmethylenephosphoranes provides a general procedure for the synthesis of five-membered heteroarylethynes.The electron-impact induced fragmentation of the phosphoranes also produced ions corresponding in mass to the ethynes, but metastable ion data indicate that the extrusion of the ethyne follows the initial loss of H* from the molecular ion.
- Brittain, Judith M.,Jones, R. Alan,Taheri, Sayed Ali Naghi
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p. 7609 - 7618
(2007/10/02)
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- RAMFORD-STEVENS REACTION IN THE SERIES OF 1-ACYL-1-R-CYCLOPROPANES
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Investigation of the relationships governing the carbene decomposition of the monotosylhydrazones of 1-R-1-acylcyclopropanes showed that ?-accepting substituents at the gem position to the carbonyl group increase the stability of the three-membered ring under the conditions of the Bamford-Stevens reaction.This leads to partial suppression of the cyclopropylmethyl-cyclobutene isomerization process and, as a result, to the formation of 1,1-gem-alkenylcyclopropanes and bicyclobutanes.
- Kuznetsova, T. S.,Kozhushkov, S. I.,Gromov, A. V.,Vatlina, L. P.,Kozlovskii, V. I.,Zefirov, N. S.
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p. 256 - 262
(2007/10/02)
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- Deconjugative Alkylation of α,β-Acetylenic Esters by Electrogenerated Base
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Electrolysis of ethyl propiolate (1) and an excess of methyl iodide at a platinum cathode in hexamethylphosphoric triamide (HMPA) or N,N-dimethylformamide (DMF) solution containing tetra-n-butylammonium salt gave the acetylenic esters 2, 3, and 4.Similar electrochemical reactions of α,β-acetylenic esters 2, 5, and 9 with methyl iodide took place in good yields to give the corresponding α,α-dimethyl-β,γ-acetylenic esters 3 and 4, 4, and 10, respectively.Electrochemical reactions of 5 with ethyl, butyl, and allyl iodides also gave α,α-dialkyl β,γ-acetylenic esters 6, 7, and 8, respectively.These facile deconjugative alkylations appeared to take place by the action of the electrogenerated base (EGB) which was formed by the electrochemical reduction of alkyl iodides.Alkyl iodides worked as both a probasic compound of the EGB and as an electrophile.Reaction pathways of the present deconjugative alkylations are also discussed.
- Tokuda, Masao,Nishio, Osamu
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p. 1592 - 1596
(2007/10/02)
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- Synthetic and Biological Studies of Compactin and Related Compounds. 3. Synthesis of the Hexalin Portion of Compactin
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Several synthons for the hexalin moiety of compactin (1) have been prepared, and a procedure for production of the key alcohol 5 in enantiomerically homogeneous form is presented.Diels-Alder reaction of ethyl (Z)-crotonate and Danishefsky's diene affords cycloadduct 6 (78percent).Hydride reduction followed by silylation of the resulting primary alcohol gives enone 8 (72percent).Two-step cyclohexene annelation furnishes enone 11 (42-55percent), which is elaborated to diene 21 by using a modification of the Shapiro olefin synthesis (three steps, 60percent).Dithiane hydrolysis followed by L-Selectride (Aldrich) reduction of the resulting ketone affords axial alcohol 28.Compound 28 possesses the correct relative stereochemistry at the four contiguous asymmetric carbon atoms in the hexalin portion of 1, and the synthesis is suitable for large-scale preparation (ten steps, 10-14 percent, no isomer separations).Functional group manipulations give synthons 36-39.Acid-catalyzed dehydration of allylic alcohol 19 affords diene isomer 20 (11:1).A simple procedure for the preparation of large quantities of ethyl (Z)-crotonate is also presented.
- Rosen, Terry,Taschner, Michael J.,Thomas, James A.,Heathcock, Clayton H.
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p. 1190 - 1201
(2007/10/02)
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- SYNTHESIS AND BIOLOGICAL ACTIVITY OF THE HEXALIN MOIETY OF COMPACTIN (ML-236B)
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Alcohols 14 and 21 and the derived half-glutarate esters 15 and 22 have been prepared and evaluated as inhibitors of HMG CoA reductase.Compound 14, the hexalin moiety of the natural fungal metabolite compactin (ML-236B) and compound 21, its isomeric diene, have essentially no inhibitory properties.Compound 15 and 22 show definite activity, although several orders of magnitude lower than that shown by compactin.
- Heathcock, Clayton H.,Taschner, Michael J.,Rosen, Terry,Thomas, James A.,Hadley, Cheri R.,Popjak, George
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p. 4747 - 4750
(2007/10/02)
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