- Iron-catalyzed domino decarboxylation-oxidation of α,β-unsaturated carboxylic acids enabled aldehyde C-H methylation
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A practical and general iron-catalyzed domino decarboxylation-oxidation of α,β-unsaturated carboxylic acids enabling aldehyde C-H methylation for the synthesis of methyl ketones has been developed. This mild, operationally simple method uses ambient air as the sole oxidant and tolerates sensitive functional groups for the late-stage functionalization of complex natural-product-derived and polyfunctionalized molecules.
- Gong, Pei-Xue,Xu, Fangning,Cheng, Lu,Gong, Xu,Zhang, Jie,Gu, Wei-Jin,Han, Wei
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supporting information
p. 5905 - 5908
(2021/06/18)
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- FGFR4 INHIBITOR AND PREPARATION METHOD AND USE THEREOF
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Provided are a class of compounds as shown in formula (I) as FGFR4 inhibitors, and pharmaceutically acceptable salts thereof, preparation methods therefor and the use thereof in the preparation of drugs for treating FGFR4-related diseases.
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Paragraph 0269-0272
(2019/10/10)
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- A simple synthesis of ketone from carboxylic acid using tosyl chloride as an activator
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An effective process for the conversion of carboxylic acid to ketone has been discovered. In this process, carboxylic acid has been activated using p-toluene sulphonyl group. Under the optimized condition, aromatic, aliphatic heteroaromatic carboxylic acids have been proved to be good substrates for this methodology. The byproduct of this reaction can be removed very easily during work up process. Also, one equivalent of organometallic reagent is sufficient to complete this transformation.
- Jana, Samaresh,Sahoo, Debasis,Sarkar, Sohini
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supporting information
(2019/09/06)
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- Iron(III)-Catalyzed Hydration of Unactivated Internal Alkynes in Weak Acidic Medium, under Lewis Acid-Assisted Br?nsted Acid Catalysis
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Alkylarylalkynes are converted with full regioselectivity into the corresponding arylketones by formal hydration of the triple bond under weak acidic conditions, at times and temperatures (≤95 °C) comparable to those used for terminal alkynes. The process catalyzed by Fe2(SO4)3nH2O in glacial acetic acid exhibits good functional group compatibility, including that with bulky triple bond substituents, and can be extended to the one-pot transformation of aryltrimethylsilylacetylenes into acetyl derivatives via a desilylation-hydration sequence. The overall reactivity pattern along with proton affinity data indicate that the triple bond is activated by proton transfer rather than by π-interaction with the metal ion. This mechanistic feature, at variance with that of noble metal catalysts, accounts for the total regioselectivity and the insensitivity to steric hindrance exhibited by the Fe2(SO4)3nH2O/AcOH catalytic system. (Figure presented.).
- Antenucci, Achille,Flamini, Piergiorgio,Fornaiolo, Marco Valerio,Di Silvio, Sergio,Mazzetti, Sara,Mencarelli, Paolo,Salvio, Riccardo,Bassetti, Mauro
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p. 4517 - 4526
(2019/08/26)
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- Generation of Aryl and Heteroaryl Magnesium Reagents in Toluene by Br/Mg or Cl/Mg Exchange
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The alkylmagnesium alkoxide sBuMgOR?LiOR (R=2-ethylhexyl), which was prepared as a 1.5 m solution in toluene, undergoes very fast Br/Mg exchange with aryl and heteroaryl bromides, producing aryl and heteroaryl magnesium alkoxides (ArMgOR?LiOR) in toluene. These Grignard reagents react with a broad range of electrophiles, including aldehydes, ketones, allyl bromides, acyl chlorides, epoxides, and aziridines, in good yields. Remarkably, the related reagent sBu2Mg?2 LiOR (R=2-ethylhexyl) undergoes Cl/Mg exchange with various electron-rich aryl chlorides in toluene, producing diorganomagnesium species of type Ar2Mg?2 LiOR, which react well with aldehydes and allyl bromides.
- Ziegler, Dorothée S.,Karaghiosoff, Konstantin,Knochel, Paul
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supporting information
p. 6701 - 6704
(2018/05/05)
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- HETEROCYCLIC INHIBITORS OF MCT4
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Disclosed herein are compounds and compositions useful in the treatment of MCT4 mediated diseases, such as proliferative and inflammatory diseases, having the structure of Formula I: Methods of inhibition MCT4 activity in a human or animal subject are also provided.
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Paragraph 0510; 0511
(2018/06/30)
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- Design, Synthesis and Anti-Proliferative Activities of 2,6-Substituted Thieno[3,2-d]pyrimidine Derivatives Containing ElectrophilicWarheads
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Thieno[3,2-d]pyrimidine as an effective pharmacophore has been extensively studied. However, its 2,6-substituted derivatives are rarely reported. In the present study, eighteen 2,6-substituted thieno[3,2-d]pyrimidine derivatives containing electrophilic warheads were designed based on the first known Fibroblast growth factor receptor-4 (FGFR4) inhibitor Blu9931. Unexpectedly, all of the derivatives exhibited negligible activity against FGFR4. However, most of the target compounds exhibited antiproliferative activities against four human cancer cell lines, including A431, NCI-H1975, Ramos and SNU-16. Compound 12 showed the most potent antiproliferative activities on the above four cell lines with IC50 values of 1.4 μM, 1.2 μM, 0.6 μM, and 2.6 μM, respectively. Additionally, the antiproliferative activity of 12 against MDA-MB-221 proved that 12 had the selectivity towards certain tumor cell lines. Furthermore, preliminary structure-Activity relationship analysis was discussed based on the experimental data.
- Zhang, Qiumeng,Hu, Zonglong,Shen, Qianqian,Chen, Yi,Lu, Wei
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- ISOQUINOLINE COMPOUNDS, A PROCESS FOR THEIR PREPARATION, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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A compound of formula (I): wherein the substituents are as defined in the description. Medicinal products containing the same which are useful in treating or preventing pathologies which are the result of activation of the RhoA/ROCK pathway and phosphorylation of the myosin light chain.
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Paragraph 0272; 0273; 0274; 0957; 0958; 0959
(2017/06/12)
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- A facile and practical total synthetic route for ampelopsin F and permethylated ?-viniferin
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Stilbene dimers (±)-ampelospin F and permethylated (±)-?-viniferin were synthesized by a practical synthetic route with overall yields of 10% and 27%. This route involves triethylsilane-mediated reduction of the 2,3-diarylbenzofuran, and BBr3-mediated one-pot demethylation and cascade intramolecular cyclization reaction.
- Zhang, Jifa,Zhang, Jianqiao,Kang, Yulong,Shi, Jiangong,Yao, Chunsuo
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supporting information
p. 1587 - 1591
(2016/06/14)
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- UREA COMPOUNDS AND THEIR USE AS FAAH ENZYME INHIBITORS
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There is provided a compound having Formula I:(I) wherein: R1 is aryl which is optionally substituted with one or more groups selected from hydroxyl, halogen and C1-4 alkoxy, or R1 is aryl which is substituted with a second aryl group or an aryloxy group, wherein the second aryl group or the aryloxy group is optionally substituted with one or more groups selected from hydroxyl, halogen and C1-4 alkoxy; R2 is C1-4 alkyl; R3 is selected from hydroxyl and OSO2CH3; R4 and R5 are independently selected from hydrogen, hydroxyl and halogen; and n is 0 or 1; or a pharmaceutically acceptable salt thereof; wherein when R3 is hydroxyl and R4 and R5 are not hydroxyl, the optionally substituted aryl group, second aryl group or aryloxy group of R1 is substituted with one or more hydroxyl groups or C1-4 alkoxy groups, or wherein when R3 is hydroxyl, one of R4 and R5 is hydroxyl, provided that the compound is not N-(1-benzylpiperidin-4-yl)-4-(3,4-dihydroxyphenyl)-N-methyl-1H-imidazole-1-carboxamide hydrobromide. The compound may be used as an inhibitor of fatty acid amide hydrolase.
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Page/Page column 28-29
(2015/02/25)
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- Metal-free trifluoromethylation of aromatic and heteroaromatic aldehydes and ketones
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The ability to convert simple and common substrates into fluoroalkyl derivatives under mild conditions remains an important goal for medicinal and agricultural chemists. One representative example of a desirable transformation involves the conversion of aromatic and heteroaromatic ketones and aldehydes into aryl and heteroaryl β,β,β-trifluoroethylarenes and -heteroarenes. The traditional approach for this net transformation involves stoichiometric metals and/or multistep reaction sequences that consume excessive time, material, and labor resources while providing low yields of products. To complement these traditional strategies, we report a one-pot metal-free decarboxylative procedure for accessing β,β,β- trifluoroethylarenes and -heteroarenes from readily available ketones and aldehydes. This method features several benefits, including ease of operation, readily available reagents, mild reaction conditions, high functional-group compatibility, and scalability.
- Qiao, Yupu,Si, Tuda,Yang, Ming-Hsiu,Altman, Ryan A.
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p. 7122 - 7131
(2014/08/18)
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- Copper acetoacetonate [Cu(acac)2]/BINAP-promoted Csp 3-N bond formation via reductive coupling of N-tosylhydrazones with anilines
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We report the the copper(II) acetoacetonate [Cu(acac)2]/BINAP- catalyzed synthesis of arylamines from N-tosylhydrazones and anilines. A fine tuning of the reaction conditions was required to accomplish the cross-coupling successfully, including the ligands effect and the addition of small amounts of water. The characteristic feature of this protocol is its functional group compatibility and its chemoselectivity when various aminophenol derivatives were used. Taking into consideration the interest for this copper-reductive coupling in which no stoichiometric metal hydride reagent is employed, this can be considered as an alternative to the conventional reductive amination.
- Aziz, Jessy,Brion, Jean-Daniel,Hamze, Abdallah,Alami, Mouad
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supporting information
p. 2417 - 2429
(2013/10/01)
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- Platinum(II) diphosphinamine complexes for the efficient hydration of alkynes in micellar media
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Highly active monomeric bis-cationic platinum(II) catalysts bearing small bite angle diphosphinamine [N,N-bis(diarylphosphino)amine] 'PNP' ligands efficiently catalyze Markovnikov hydration of terminal and internal alkynes to the corresponding ketones in water. Catalyst solubilization in water is achieved via ion pairing with anionic micelles formed by surfactant addition. The micelles ensure dissolution of apolar alkynes and promote the intimate contact between reagents and catalyst, while in organic-water media in the absence of surfactants the reaction is sluggish. Hydration products can be isolated by means of extraction with an apolar solvent and the catalyst, that remains confined in the aqueous phase, can be recycled up to four times without loss of catalytic activity. Copyright
- Trentin, Francesco,Chapman, Andrew M.,Scarso, Alessandro,Sgarbossa, Paolo,Michelin, Rino A.,Strukul, Giorgio,Wass, Duncan F.
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scheme or table
p. 1095 - 1104
(2012/05/20)
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- Development of a method for the preparation of ruthenium indenylidene-ether olefin metathesis catalysts
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The reactions between several derivatives of 1-(3,5-dimethoxyphenyl)-prop- 2- yn-1-ol and different ruthenium starting materials [i.e., RuCl 2(PPh3)3 and RuCl2(p-cymene)(L), where L is tricyclohexylphosphine di-t-butylmethylphosphine, dicyclohexylphenylphosphine, triisobutylphosphine, triisopropylphosphine, or tri-npropylphosphine] are described. Several of these reactions allow for the easy, in-situ and atom-economic preparation of olefin metathesis catalysts. Organic precursor 1-(3,5- dimethoxyphenyl)-1-phenyl-prop-2-yn-1-ol led to the formation of active ruthenium indenylidene-ether complexes, while 1-(3,5-dimethoxyphenyl)-prop-2-yn-1-ol and 1-(3,5- dimethoxyphenyl)-1-methyl- prop-2-yn-1-ol did not. It was also found that a bulky and strong α-donor phosphine ligand was required to impart good catalytic activity to the new ruthenium complexes.
- Jimenez, Leonel R.,Tolentino, Daniel R.,Gallon, Benjamin J.,Schrodi, Yann
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experimental part
p. 5675 - 5689
(2012/09/22)
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- Efficient synthesis of natural polyphenolic stilbenes: Resveratrol, piceatannol and oxyresveratrol
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The practical synthesis of important natural polyphenolic stilbenes, including resveratrol, piceatannol and oxyresveratrol, through Perkin methodology is described. Starting from 3,5-dihydoxyacetophenone (1), the common intermediate 3,5-dimethoxyphenylacetic acid (3) can be obtained via methylation and Willgerodt-Kindler reaction. Perkin condensations between (3) and substituted phenylaldehydes 4 furnished E-2,3-diarylacrylic acids 5, followed by decarboxylation in Cu/quinoline giving stilbene intermediates 6 which bear the Z-configuration. Finally, through a simultaneous demethylation/isomerization process in AlI3/CH3CN system, the target compounds 7a-c can be obtained respectively in good to high overall yields. The synthetic method proved to be more concise, trans-specific, mild, economical and commonly applicable.
- Sun, Hong-Yi,Xiao, Chun-Fen,Cai, Yu-Chen,Chen, Yu,Wei, Wen,Liu, Xian-Ke,Lv, Ze-Liang,Zou, Yong
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experimental part
p. 1492 - 1496
(2010/12/25)
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- Hydrogen-bonding-promoted oxidative addition and regioselective arylation of olefins with aryl chlorides
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The first, general, and highly efficient catalytic system that allows a wide range of activated and unactivated aryl chlorides to couple regioselectively with olefins has been developed. The Heck arylation reaction is likely to be controlled by the oxidative addition of ArCl to Pd(0). Hence, an electron-rich diphosphine, 4-MeO-dppp, was introduced to facilitate the catalysis. Solvent choice is critical, however; only sluggish arylation is observed in DMF or DMSO, whereas the reaction proceeds well in ethylene glycol at 0.1-1 mol % catalyst loadings, displaying excellent regioselectivity. Mechanistic evidence supports that the arylation is turnover-limited by the oxidative addition step and, most importantly, that the oxidative addition is accelerated by ethylene glycol, most likely via hydrogen bonding to the chloride at the transition state as shown by DFT calculations. Ethylene glycol thus plays a double role in the arylation, facilitating oxidative addition and promoting the subsequent dissociation of chloride from Pd(II) to give a cationic Pd(II)-olefin species, which is key to the regioselectivity observed.
- Ruan, Jiwu,Iggo, Jonathan A.,Berry, Neil G.,Xiao, Jianliang
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supporting information; experimental part
p. 16689 - 16699
(2011/02/23)
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- Synthesis of functionalised acetophenone
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Nickel catalysed Heck arylation of the electron-rich olefin n-butyl vinyl ether with a wide variety of aryl bromides has been accomplished in the ionic liquid [bmim][BF4], affording an efficient green chemistry synthetic procedure for preparing functionalised acetophenone. The reaction gave a high regioselectivity and high yield without the need for the costely or toxic halide scavengers, leading predominantly to a branch-arylated α-product.
- Sun, Li,Pei, Wen,Shen, Chen
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p. 388 - 389
(2007/10/03)
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- Reaction of chalcones with basic hydrogen peroxide: A structure and reactivity study
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Chalcone epoxides are important intermediates for the synthesis of 3,5-diarylpyrazoles. Twenty different chalcones were oxidized with hydrogen peroxide and potassium carbonate in order to produce the corresponding epoxides. The electronic nature of the substituents on the A- and B-ring of the chalcones significantly affected the reaction outcome: (i) electron donating groups on the A-and B-ring aided the reversion of the chalcones to the corresponding benzaldehydes, (ii) electron withdrawing groups on the B-ring promoted formation of the desired chalcone-epoxides in high chemical yields, and (iii) the presence of electron withdrawing groups (A-ring of the chalcones), regardless of the substituents on the B-ring, produced a mixture of epoxide, unreacted chalcone, benzaldehyde and acetophenone.
- Holt Jr., Herman,LeBlanc, Regan,Dickson, John,Brown, Toni,Maddox, Jessica R.,Lee, Moses
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p. 465 - 470
(2007/10/03)
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- Antimony(V) chloride-benzyltriethylammonium chloride complex as an efficient catalyst for friedel-crafts acylation reactions
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A novel catalytic system, the complex of antimony(V) chloride (SbCl 5) and benzyltriethylammonium chloride (TEBA), C6H 5CH2NEt3(SbCl5)2Cl complex, is described for Friedel-Crafts acylation reactions of aromatics with acyl and sulfonyl chlorides. The catalyst has a number of useful characteristics, such as ready access, minimal toxicity, reusability, insensitivity to atmosphere and moisture, rapid acylation with high yield, and ease of operation.
- Huang, An-Ping,Liu, Xue-Yuan,Li, Lian-Hua,Wu, Xiao-Li,Liu, Wei-Min,Liang, Yong-Min
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p. 599 - 602
(2007/10/03)
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- Process for the preparation of imidazolyl macrolide immunosuppressants
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Imidazolmethyloxy-substituted tricyclo-macrolide immunosuppressants are prepared by reacting a tricyclo-macrolide with an imidazolmethyl trichloroacetimidate in the presence of an acid. The invention further provides a crystalline salt of imidazolmethyloxy-substituted tricyclo-macrolide, as well as novel compounds useful in the process of the present invention.
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- Wacker oxidation of alkenes using a fluorous biphasic system. A mild preparation of polyfunctional ketones
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Various alkenes are oxidized to the corresponding ketones using t-BuOOH in the presence of a palladium(II) catalyst bearing perfluorinated ligands using a biphasic solvent system of benzene and bromoperfluorooctane.
- Betzemeier, Bodo,Lhermitte, Frederic,Knochel, Paul
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p. 6667 - 6670
(2007/10/03)
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- Unsaturated side chain β-11-hydroxyhexahydrocannabinol analogs
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The cannabinoid side chain is a key pharmacophore in the interaction of cannabinoids with their receptors (CB1 and CB2). To study the stereochemical requirements of the side chain, we synthesized a series of cannabinoids in which rotation around the C1'-C2' bond is blocked. The key steps in the synthesis were the cuprate addition of a substituted resorcinol to (+)- apoverbenone, the TMSOTf-mediated formation of the dihydropyran ring, and the stereospecific introduction of the β-11-hydroxymethyl group. All the analogs tested showed nanomolar affinity for the receptors, the cis-hept-1-ene side chain having the highest affinity for CB1 (K(i) = 0.89 nM) and showing the widest separation between CB1 and CB2 affinities. The parent n-heptyl-β-11- hydroxyhexahydrocannabinol was the least potent binding to CB1 (K(i) = 8.9 nM) and had the lowest selectivity between CB1 and CB2.
- Busch-Petersen, Jakob,Hill, W. Adam,Fan, Pusheng,Khanolkar, Atmaram,Xie, Xuang-Qun,Tius, Marcus A.,Makriyannis, Alexandros
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p. 3790 - 3796
(2007/10/03)
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- Chiral Building Blocks for the Synthesis of Nitrogen-Containing Natural Products, 5. The Enantioselective Synthesis of Optically Active, Benzene Nucleus-Substituted 1-Phenylethylamines from the Corresponding Acetophenones
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An efficient two-step procedure for the synthesis of enantiomerically pure, benzene nucleus-substituted 1-phenylethylamines 1 is described, with predictable absolute configuration at the stereogenic center: Imine formation from the substituted acetophenones 6 with (S)- or (R)-1-phenylethylamine and subsequent hydrogenation of the resulting Schiff bases 8 over Raney nickel leads to the secondary amines 9 and 10 in high diastereoselectivities.These dibenzylamines are cleaved regioselectively, usually next to the less substituted aromatic ring, giving the desired chiral 1-phenylethylamines 1 in high yields and enantiomeric purities.Scope and limitations of this new and facile approach to the versatile building blocks 1 are reported.
- Bringmann, Gerhard,Geisler, Joerg-Peter,Geuder, Torsten,Kuenkel, Georg,Kinzinger Lioba
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p. 795 - 805
(2007/10/02)
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- Photochemical Transformation. 48. The Nonconcertedness of Nucleofuge Loss and anti-Aryl Migration in Photochemical Wagner-Meerwein Rearrangements
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Preparation of the two diastereomeres of 3-(3,5-dimethoxyphenyl)-2-butanol and of their 2-deuterio analogues has been carried out.When the methanesulfonate esters of the diastereomers were solvolyzed by heating at reflux in 50percent aqueous methanol, the resulting alcohols and methyl ethers were formed with complete retention of diastereomeric identity and without measurable hydride migration to give the 2-aryl-2-butyl isomer.Similar treatment of the methanesulfonates of the deuterio analogues gave complete deuterium scrambling, that is, gave equal mixtures of 3-aryl-2-deuterio -2-butyl and 3-aryl-3-deuterio-2-butyl derivatives.These results of ground-state solvolyses are consistent with aryl participation coincident with nucleofuge loss, with bridged phenonium ions as sole intermediates.On the other hand, irradiations of the methanesulfonates with 300-nm light in the same solvent gave photosolvolysis with considerable diastereomeric mixing, although again complete deuterium scrambling was observed here as well.In addition, significant amounts of 2-aryl-2-butanol were formed.The excited-state results require a much more complicated reaction course than the ground-state results, probably involving syn-hydrogen migration to give the tertiary alcohol, along one path, and requiring that the observed aryl migrations, along another path, occur later than, rather than concerted with, nucleofuge loss.
- Cristol, Stanley J.,Ali, Mahfuza B.,Sankar, Iyer V.
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p. 8207 - 8211
(2007/10/02)
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- Halogenation of Phenols and Phenyl Ethers with Potassium Halides in the Presence of 18-Crown-6 on Oxidation with m-Chloroperbenzoic Acid
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Several types of phenyl ethers have been monobrominated in the ring in good yields with potassium bromide in the presence of 18-crown-6 on oxidation with m-chloroperbenzoic acid.Monoiodination takes place with both phenyl ethers and free phenols when potassium iodide is employed.
- Srebnik, Morris,Mechoulam, Raphael,Yona, Irene
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p. 1423 - 1428
(2007/10/02)
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