- Nickel-Catalyzed Reversible Functional Group Metathesis between Aryl Nitriles and Aryl Thioethers
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We describe a new functional group metathesis between aryl nitriles and aryl thioethers. The catalytic system nickel/dcype is essential to achieve this fully reversible transformation in good to excellent yields. Furthermore, the cyanide- and thiol-free reaction shows high functional group tolerance and great efficiency for the late-stage derivatization of commercial molecules. Finally, synthetic applications demonstrate its versatility and utility in multistep synthesis.
- Delcaillau, Tristan,Boehm, Philip,Morandi, Bill
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supporting information
p. 3723 - 3728
(2021/04/07)
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- Visible-Light-Driven Oxidative Cleavage of Alkenes Using Water-Soluble CdSe Quantum Dots
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The oxidative cleavage of C=C bonds is an important chemical reaction, which is a popular reaction in the photocatalytic field. However, high catalyst-loading and low turnover number (TON) are general shortcomings in reported visible-light-driven reactions. Herein, the direct oxidative cleavage of C=C bonds through water-soluble CdSe quantum dots (QDs) is described under visible-light irradiation at room temperature with high TON (up to 3.7×104). Under the same conditions, water-soluble CdSe QDs could also oxidize sulfides to sulfoxides with 51–84 % yields and TONs up to 3.4×104. The key features of this photocatalytic protocol include high TONs, wide substrates scope, low catalyst loadings, simple and mild reaction conditions, and molecular O2 as the oxidant.
- Li, Jianing,Zhao, Jingnan,Ma, Cunfei,Yu, Zongyi,Zhu, Hongfei,Yun, Lei,Meng, Qingwei
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p. 4985 - 4992
(2021/10/16)
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- Pd-Catalysed carbonylative Suzuki-Miyaura cross-couplings using Fe(CO)5under mild conditions: generation of a highly active, recyclable and scalable ‘Pd-Fe’ nanocatalyst
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The dual function and role of iron(0) pentacarbonyl [Fe(CO)5] has been identified in gaseous CO-free carbonylative Suzuki-Miyaura cross-couplings, in which Fe(CO)5supplied COin situ, leading to the propagation of catalytically active Pd-Fe nanoparticles. Compared with typical carbonylative reaction conditions, CO gas (at high pressures), specialised exogenous ligands and inert reaction conditions were avoided. Our developed reaction conditions are mild, do not require specialised CO high pressure equipment, and exhibit wide functional group tolerance, giving a library of biaryl ketones in good yields.
- Zhu, Zhuangli,Wang, Zhenhua,Jian, Yajun,Sun, Huaming,Zhang, Guofang,Lynam, Jason M.,McElroy, C. Robert,Burden, Thomas J.,Inight, Rebecca L.,Fairlamb, Ian J. S.,Zhang, Weiqiang,Gao, Ziwei
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supporting information
p. 920 - 926
(2021/02/09)
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- Kinetically Controlled, Highly Chemoselective Acylation of Functionalized Grignard Reagents with Amides by N?C Cleavage
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The direct transition-metal-free acylation of amides with functionalized Grignard reagents by highly chemoselective N?C cleavage under kinetic control has been accomplished. The method offers rapid and convergent access to functionalized biaryl ketones through transient tetrahedral intermediates. The direct access to functionalized Grignard reagents by in situ halogen–magnesium exchange promoted by the versatile turbo-Grignard reagent (iPrMgCl?LiCl) permits excellent substrate scope with respect to both the amide and Grignard coupling partners. These reactions enable facile, operationally simple and chemoselective access to tetrahedral intermediates from amides under significantly milder conditions than chelation-controlled intermediates. This novel direct two-component coupling sets the stage for using amides as acylating reagents in an alternative paradigm to the metal-chelated approach, acyl metals and Weinreb amides.
- Li, Guangchen,Szostak, Michal
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supporting information
p. 611 - 615
(2020/01/02)
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- Synthesis of biaryl ketones by arylation of Weinreb amides with functionalized Grignard reagents under thermodynamic controlvs.kinetic control ofN,N-Boc2-amides
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A highly efficient method for chemoselective synthesis of biaryl ketones by arylation of Weinreb amides (N-methoxy-N-methylamides) with functionalized Grignard reagents is reported. This protocol offers rapid entry to functionalized biaryl ketones after Mg/halide exchange with i-PrMgCl·LiCl under operationally-simple and practical reaction conditions. The scope of the method is highlighted in >40 examples, including bioactive compounds and pharmaceutical derivatives. Collectively, this transition-metal-free approach offers a major advantage over the recently established cross-coupling of amides by oxidative addition of N-C(O) bonds. Considering the utility of amide acylation reactions in modern synthesis, we expect that this method will be of broad interest.
- Li, Guangchen,Szostak, Michal
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supporting information
p. 3827 - 3831
(2020/06/03)
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- Transition-Metal-Free Aryl-Heteroatom Bond Formation via C-S Bond Cleavage
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Aryl-heteroatom bonds (C-Het) are almost ubiquitously present in chemical molecules. However, methods for diverse C-Het bond formations from a simple substrate are limited. Herein, we report a convenient and efficient C-S bond transformation of aryl sulfoniums to various C-Het bonds (C-O, C-S, C-Sn, C-Si, C-Se) in the absence of any transition-metal catalyst. These reactions proceeded in mild conditions with a wide substrate scope.
- Zhao, Jian-Nan,Kayumov, Muzaffar,Wang, Dong-Yu,Zhang, Ao
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supporting information
p. 7303 - 7306
(2019/10/02)
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- 4,5-Diaryl 3(2H)Furanones: Anti-inflammatory activity and influence on cancer growth
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Apart from their anti-inflammatory action, COX inhibitors have gathered the interest of many scientists due to their potential use for the treatment and prevention of cancer. It has been shown that cyclooxygenase inhibitors restrict cancer cell growth and are able to interact with known antitumor drugs, enhancing their in vitro and in vivo cytotoxicity. The permutation of hydrophilic and hydrophobic aryl groups in COX inhibitors leads to cardinal changes in the biological activity of the compounds. In the present study, thirteen heterocyclic coxib-like 4,5-diarylfuran-3(2H)-ones and their annelated derivatives-phenanthro[9,10-b]furan-3-ones-were synthesized and studied for anti-inflammatory and COX-1/2 inhibitory action and for their cytotoxic activity on the breast cancer (MCF-7) and squamous cell carcinoma (HSC-3) cell lines. The F-derivative of the -SOMe substituted furan-3(2H)-ones exhibited the best activity (COX-1 IC50 = 2.8 μM, anti-inflammatory activity (by carrageenan paw edema model) of 54% (dose 0.01 mmol/kg), and MCF-7 and HSC-3 cytotoxicity with IC50 values of 10 μM and 7.5 μM, respectively). A cytotoxic effect related to the COX-1 inhibitory action was observed and a synergistic effect with the anti-neoplastic drugs gefitinib and 5-fluorouracil was found. A phenanthrene derivative exhibited the best synergistic effect with gefitinib.
- Semenok, Dmitrii,Medvedev, Jury,Giassafaki, Lefki-P.,Lavdas, Iason,Vizirianakis, Ioannis S.,Eleftheriou, Phaedra,Gavalas, Antonis,Petrou, Anthi,Geronikaki, Athina
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- Decarboxylation with Carbon Monoxide: The Direct Conversion of Carboxylic Acids into Potent Acid Triflate Electrophiles
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We report a new strategy for the conversion of carboxylic acids into potent acid triflate electrophiles. The reaction involves oxidative carbonylation of carboxylic acids with I2 in the presence of AgOTf, and is postulated to proceed via acyl hypoiodites that react with CO to form acid triflates. Coupling this chemistry with subsequent trapping with arenes offers a mild, room temperature approach to generate ketones directly from broadly available carboxylic acids without the use of corrosive and reactive Lewis or Bronsted acid additives, and instead from compounds that are readily available, stable, and functional group compatible.
- Kinney, R. Garrison,Arndtsen, Bruce A.
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supporting information
p. 5085 - 5089
(2019/04/01)
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- Sequential Organozinc Formation and Negishi Cross-Coupling of Amides Catalysed by Cobalt Salt
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Herein, a cobalt-catalysed Negishi-type cross-coupling of amide derivatives is described. Apart from being the first example of cobalt-catalysed Negishi-type coupling of amides, the process described employs a unique, simple, and cheap catalytic system to perform both the organozinc formation and the Negishi-type coupling. Indeed, the same cobalt(II) bromide salt used to form the arylzinc species from aryl bromides is then re-used to perform the cross coupling of this resulting arylzinc with N-benzoyl glutarimides at room temperature. The main advantages of the reaction presented are its robustness and ease of use. Indeed, the reactions of organozinc formation and Negishi-type coupling are performed without precautions toward water or oxygen. (Figure presented.).
- Dorval, Céline,Dubois, Elodie,Bourne-Branchu, Yann,Gosmini, Corinne,Danoun, Grégory
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supporting information
p. 1777 - 1780
(2019/02/26)
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- Unusual Length Dependence of the Conductance in Cumulene Molecular Wires
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Cumulenes are sometimes described as “metallic” because an infinitely long cumulene would have the band structure of a metal. Herein, we report the single-molecule conductance of a series of cumulenes and cumulene analogues, where the number of consecutiv
- Xu, Wenjun,Leary, Edmund,Hou, Songjun,Sangtarash, Sara,González, M. Teresa,Rubio-Bollinger, Gabino,Wu, Qingqing,Sadeghi, Hatef,Tejerina, Lara,Christensen, Kirsten E.,Agra?t, Nicolás,Higgins, Simon J.,Lambert, Colin J.,Nichols, Richard J.,Anderson, Harry L.
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supporting information
p. 8378 - 8382
(2019/05/28)
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- Palladium-catalyzed synthesis of diaryl ketones from aldehydes and (hetero)aryl halides via C-H bond activation
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We developed a palladium-catalyzed C-H transformation that enabled the synthesis of ketones from aldehydes and (hetero)aryl halides. The use of picolinamide ligands was key to achieving the transformation. Heteroaryl ketones, as well as diaryl ketones, were synthesized in good to excellent yields, even in gram-scale, using this reaction. Results of density functional theory (DFT) calculations support the C-H bond activation pathway.
- Wakaki, Takayuki,Togo, Takaya,Yoshidome, Daisuke,Kuninobu, Yoichiro,Kanai, Motomu
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p. 3123 - 3128
(2018/04/14)
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- CO2-Catalyzed oxidation of benzylic and allylic alcohols with DMSO
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CO2-catalyzed transition-metal-free oxidation of alcohols has been achieved. Earlier, several methodologies have been explored for alcohol oxidations based on transition-metal catalysts. However, owing to the cheaper price, easy separation and nontoxicity, transition-metal-free systems are in high demand to the pharmaceutical industries. For this reason, various primary and secondary alcohols have been selectively oxidized to the corresponding carbonyl compounds using CO2 as a catalyst in the presence of different functional groups such as nitrile, nitro, aldehyde, ester, halogen, ether, and so on. At the end, transition-metal-free syntheses of pharmaceuticals have also been achieved. Finally, the role of CO2 has been investigated in detail, and the mechanism is proposed on the basis of experiments and DFT calculations.
- Riemer, Daniel,Mandaviya, Bhavdip,Schilling, Waldemar,G?tz, Anne Charlotte,Kühl, Torben,Finger, Markus,Das, Shoubhik
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p. 3030 - 3034
(2018/04/14)
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- N-Acylsuccinimides: Efficient acylative coupling reagents in palladium-catalyzed Suzuki coupling via C–N cleavage
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An acylative Suzuki coupling of activated amides with aryl boronic acids has been reported via palladium-catalyzed C–N bond cleavage. This protocol demonstrate amides can be activated by an atom-economic and cheap succinimide, which can be efficiently utilized to synthesize broad array of diaryl ketones in moderate to good yields.
- Cui, Ming,Chen, Zeyu,Liu, Tingting,Wang, Hui,Zeng, Zhuo
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p. 3819 - 3822
(2017/09/15)
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- Base free Suzuki acylation reactions of sodium (aryl trihydroxyborate) salts: A novel synthesis of substituted aryl ketones
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The first simple and efficient base free Pd(PPh3)4 catalysed synthesis of substituted aryl ketones from acyl chlorides and easily accessible sodium aryl trihydroxyborate salts in aqueous toluene is reported. The reaction conditions appeared versatile and tolerable to a variety of functional groups including, CF3, OMe, SMe, Br, NO2, F, OH and NH2 furnishing 25 examples of substituted aryl ketones in isolated yields of up to 96% in 24 h. Beside the high purity, the ease and convenience of the isolation compared to boronic acids, sodium aryl trihydroxyborate salts could be used subsequently without the addition of excess amount of an activator and are more user-friendly in terms of the use of accurate reaction stoichiometry.
- Sithebe, Siphamandla,Molefe, Patience
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p. 305 - 311
(2017/07/13)
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- Coupling of aromatic aldehydes with aryl halides in the presence of nickel catalysts with diazabutadiene ligands
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Nickel catalysts with diazabutadiene ligands promote cross-coupling of benzaldehydes with aryl halides in the presence of zinc as reducing agent, which leads to the corresponding benzhydrols and benzophenones. The benzophenone percentage considerably increases when lithium chloride additive is used.
- Asachenko,Valaeva,Kudakina,Uborsky,Izmer,Kononovich,Voskoboynikov
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p. 456 - 463
(2017/03/08)
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- An efficient combination of Zr-MOF and microwave irradiation in catalytic Lewis acid Friedel-Crafts benzoylation
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A zirconium-based metal-organic framework, an effective heterogeneous catalyst, has been developed for the Friedel-Crafts benzoylation of aromatic compounds under microwave irradiation. Constructed by a Zr(iv) cluster and a linker 1,4-bis(2-[4-carboxyphenyl]ethynyl)benzene (H2CPEB), the MOF, possessing large pores and high chemical stability, was appropriate for the enhancement of Lewis acid activity under microwave irradiation. The reaction studies demonstrated that the material could give high yields for a few minutes and maintain its reactivity and structure over several cycles.
- Doan, Tan L. H.,Dao, Thong Q.,Tran, Hai N.,Tran, Phuong H.,Le, Thach N.
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supporting information
p. 7875 - 7880
(2016/05/24)
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- Erbium trifluoromethanesulfonate catalyzed Friedel-Crafts acylation using aromatic carboxylic acids as acylating agents under monomode-microwave irradiation
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Erbium trifluoromethanesulfonate is found to be a good catalyst for the Friedel-Crafts acylation of arenes containing electron-donating substituents using aromatic carboxylic acids as the acylating agents under microwave irradiation. An effective, rapid and waste-free method allows the preparation of a wide range of aryl ketones in good yields and in short reaction times with minimum amounts of waste.
- Tran, Phuong Hoang,Hansen, Poul Erik,Nguyen, Hai Truong,Le, Thach Ngoc
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p. 612 - 618
(2015/02/19)
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- Improvement of the Friedel-Crafts benzoylation by using bismuth trifluoromethanesulfonate in 1-butyl-3-methylimidazolium trifluoromethanesulfonate ionic liquid under microwave irradiation
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Bismuth trifluoromethanesulfonate (bismuth triflate) catalyzed the Friedel-Crafts benzoylation of activated aromatic compounds when dissolved in 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([BMIM]OTf) ionic liquid. Immobilization of bismuth triflate (5 mol %) in [BMIM]OTf allowed the synthesis of aryl ketones in good to excellent yields with short reaction times under microwave irradiation. This catalytic system was easily recovered and reused several times without any significant loss of the activity.
- Hoangtran, Phuong,Bichle Do, Ngoc,Ngocle, Thach
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p. 205 - 208
(2014/01/06)
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- Microwave-assisted facile and rapid friedel-crafts benzoylation of arenes catalyzed by bismuth trifluoromethanesulfonate
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The catalytic activity of metal triflates was investigated in Friedel-Crafts benzoylation under microwave irradiation. Friedel-Crafts benzoylation with benzoyl chloride of a variety of arenes containing electron-rich and electron-poor rings using bismuth triflate under microwave irradiation is described. This method allows the preparation of aryl ketones under solventless conditions in good to excellent yields and short reaction time. Bismuth triflate was easily recovered and reused five times without significant loss of the catalytic activity.
- Tran, Phuong Hoang,Hansen, Poul Erik,Pham, Thuy Thanh,Huynh, Vy Thanh,Huynh, Vy Hieu,Thi Tran, Thao Du,Huynh, Thanh Van,Le, Thach Ngoc
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p. 2921 - 2929
(2014/10/15)
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- Investigation of the scope and mechanism of copper catalyzed regioselective methylthiolation of aryl halides Dedicated to Professor Dr. Irina Beletskaya
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Methylthiolation of structurally diverse aryl halides was accomplished under fluoride free conditions using catalytic amounts of CuI, and DMSO as the methylthiolation source. Optimization studies unveiled several varieties of promoters among which Zn(OAc)2 was found ideal. The analogous reaction with DMSO-d6 afforded corresponding deuterated aryl methyl thioether with 99% purity. Mechanistic studies revealed CuSMe as the active methylthiolation agent.
- Joseph, P.J. Amal,Priyadarshini,Kantam, M. Lakshmi,Sreedhar
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supporting information
p. 8276 - 8283
(2013/09/02)
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- Catalytic Friedel-Crafts acylation: Magnetic nanopowder CuFe 2O4 as an efficient and magnetically separable catalyst
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Catalytic regioselective Friedel-Crafts acylation of an array of anisoles/arenes with various acid chlorides using 5-20 mol % of magnetic nanopowder CuFe2O4 is reported. Unlike the conventional Friedel-Crafts reactions, which are catalyzed by moisture sensitive homogeneous catalysts/promoters, the nanopowder CuFe2O4 catalyst is moisture insensitive and the product/ketone-catalyst isolation is easily achieved using the magnetic properties of CuFe2O4.
- Parella, Ramarao,Naveen,Kumar, Amit,Babu, Srinivasarao Arulananda
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p. 1738 - 1742
(2013/03/28)
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- Friedel-Crafts acylation using bismuth triflate in [BMI][PF6]
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Bismuth trifluoromethanesulfonate was found to be a good catalyst for the Friedel-Crafts acylation. Bismuth triflate immobilized in an ionic liquid was the most efficient catalytic system. Bismuth triflate in [BMI][PF6] catalyzes this reaction under microwave irradiation allowing the rapid synthesis of aryl ketones in excellent yields. The catalyst system was easily recovered and reused several times.
- Tran, Phuong Hoang,Duus, Fritz,Le, Thach Ngoc
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experimental part
p. 222 - 224
(2012/01/30)
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- Highly atom-economic, catalyst- and solvent-free oxidation of sulfides into sulfones using 30% aqueous H2O2
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Highly atom-efficient oxidation of sulfides into sulfones under solvent- and catalyst-free reaction conditions using a 30% aqueous solution of H 2O2 at 75 °C is reported. A structurally diverse set of phenyl alkyl-, phenyl benzyl-, benzyl alkyl-, dialkyl-, heteroaryl alkyl- and cyclic sulfides were transformed into sulfones regardless of the aggregate state and electronic nature of the substituents. In spite of the heterogeneous reaction mixtures throughout the work, no difficulties with stirring and reaction progress were noted. In numerous cases, only 10 mol% excess of H 2O2 was used, thus contributing considerably to the high atom economy of the process. Some solid substrates required a variable excess of hydrogen peroxide; however, the reactions were performed strictly without organic solvents. The transformation was demonstrated to be amenable for scale-up with both liquid and solid sulfides. In addition, isolation and purification of the crude products can be simply done with only filtration and crystallization.
- Jereb, Marjan
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supporting information
p. 3047 - 3052,6
(2020/09/16)
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- New preparation and reactions of arylaluminum reagents using Barbier conditions
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The reaction of various aryl bromides with magnesium turnings, LiCl and R2AlCl (R = Et, i-Bu) provides at room temperature arylaluminum reagents in high yields. These organometallic species undergo readily 1,4-additions, acylations, allylations, and Pd-catalyzed cross-couplings with various aryl iodides and bromides. Georg Thieme Verlag Stuttgart.
- Gao, Hongjun,Knochel, Paul
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experimental part
p. 1321 - 1325
(2009/12/01)
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- PROCESS FOR PREPARING KETONES FROM ALPHA-OXO CARBOXYLATES AND ARYL BROMIDES
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A process for preparing ketones of the general formula (III) where R is an optionally substituted carbocyclic aromatic radical having 6 to 24 carbon atoms or an optionally substituted alkyl radical or an optionally substituted heteroaromatic radical having 5 to 24 carbon atoms, andR1 is an optionally substituted carbocyclic aromatic radical having 6 to 24 carbon atoms or an optionally substituted heteroaromatic radical having 5 to 24 carbon atoms, by reacting alpha-oxo carboxylates of the general formula (I) wherein n and m is a number in the range from 1 to 6, M(m+) is a cation, and R has the meaning indicated for formula (III), with aryl bromides of the general formula (II) [in-line-formulae]R1—Br ??(II)[/in-line-formulae] where R1 has the meaning indicated for formula (III), in the presence of two transition metals or compounds thereof as catalyst, is described.
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Page/Page column 3-4
(2009/09/08)
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- Synthesis of ketones from α-oxocarboxylates and aryl bromides by Cu/Pd-catalyzed decarboxylative cross-coupling
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(Chemical Equation Presented) The power of two metals: A Pd/Cu catalyst system mediates the in situ formation of acyl nucleophiles by decarboxylation of readily accessible and stable salts of α-oxocarboxylic acids and their cross-coupling with aryl or heteroaryl bromides to give ketones. The reaction may be usedin the presence of many functional groups and provides good yields.
- Goossen, Lukas J.,Rudolphi, Felix,Oppel, Christoph,Rodriguez, Nuria
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p. 3043 - 3045
(2008/12/23)
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- Ring contraction during the 6π-electrocyclisation of naphthopyran valence tautomers
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The thermal and photochemical ring-opening of spiro(3H-naphtho[2,1-b]pyran- 3,9′-thioxanthene-10,10-dioxide) 3 results in the facile ring-contraction to 9-(naphtho[2,1-b]furan-2-yl)-9H-thioxanthene-10,10-dioxide 6. Similar behaviour is displayed by the is
- Gabbutt, Christopher D.,Heron, B. Mark,Kolla, Suresh B.,Kilner, Colin,Coles, Simon J.,Horton, Peter N.,Hursthouse, Michael B.
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scheme or table
p. 3096 - 3104
(2009/02/03)
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- An efficient method for aromatic Friedel-Crafts acylation reactions
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Friedel-Crafts acylation of aromatic compounds was carried out using FeCl3-based ionic liquid. This liquid serves as an efficient media as well as a Lewis acid catalyst. The significant advantages of this methodology are excellent yields, short reaction times, mild reaction conditions, environmentally friendly method, simple work-up procedure, low cost, and easy preparation and handling of the catalyst. Copyright
- Khodaei, Mohammad Mehdi,Bahrami, Kiumars,Shahbazi, Fomeida
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p. 844 - 845
(2008/12/22)
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- Photoinduced nucleophilic substitution of aryl halides with potassium thioacetate - A one-pot approach to aryl methyl and diaryl sulfides
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Aryl methyl sulfides and diaryl sulfides were prepared by photoinduced reactions of potassium thioacetate with aryl halides under entrainment conditions. Without isolation, the arene thiolates obtained by the aromatic substitution were quenched with methyl iodide to afford the aryl methyl sulfides in 26-59% yields in a "one-pot" procedure together with the diaryl sulfides in variable yields (3-31 %). By optimization of the reaction conditions it was possible to improve the formation of the Ar2S, going from moderate to good yields (64-83%). Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Schmidt, Luciana C.,Rey, Valentina,Penenory, Alicia B.
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p. 2210 - 2214
(2007/10/03)
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- Highly selective catalytic Friedel-Crafts acylation and sulfonylation of activated aromatic compounds using indium metal
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The Friedel-Crafts acylation of activated benzenes with various aromatic and aliphatic acid chlorides was studied in the presence of indium metal. The reaction was accomplished in high isolated yields under solvent or solvent-less conditions. The method is also applicable for preparing diaryl sulfones from aromatic compounds and aryl sulfonyl chlorides.
- Jang, Doo Ok,Moon, Kyung Soo,Cho, Dae Hyan,Kim, Joong-Gon
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p. 6063 - 6066
(2007/10/03)
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- Synthesis and biological evaluation of acyclic triaryl (Z)-olefins possessing a 3,5-di-tert-butyl-4-hydroxyphenyl pharmacophore: Dual inhibitors of cyclooxygenases and lipoxygenases
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A new class of regioisomeric acyclic triaryl (Z)-olefins possessing a 3,5-di-tert-butyl-4-hydroxyphenyl (DTBHP) 5-lipoxygenase (5-LOX) pharmacophore that is vicinal to a para-methanesulfonylphenyl cyclooxygenase-2 (COX-2) pharmacophore were designed for evaluation as selective COX-2 and/or 5-LOX inhibitors. The target compounds were synthesized via a highly stereoselective McMurry olefination cross-coupling reaction. This key synthetic step afforded a (Z):(E) olefinic mixture with a predominance for the (Z)-olefin stereoisomer. Structure-activity studies for the (Z)-1-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-(4-methanesulfonylphenyl)-1-phenylalk-1-ene regioisomers showed that COX-1 inhibition decreased, COX-2 inhibition increased, and the COX-2 selectivity index (SI) increased as the chain length of the alkyl substituent attached to the olefinic double bond was increased (Et → n-butyl → n-heptyl). In this group of compounds, inhibition of both 5-LOX and 15-LOX was dependent upon the length of the alkyl substituent with the hex-1-ene compound 9c having a n-butyl substituent exhibiting potent inhibition of both 5-LOX (IC50 = 0.3 μM) and 15-LOX (IC50 = 0.8 μM) relative to the inactive (IC50 > 10 μM) Et and n-heptyl analogs. Compound 9c is of particular interest since it also exhibits a dual inhibitory activity against the COX (COX-1 IC50 = 3.0 μM, and COX-2 IC50 = 0.36 μM, COX-2 SI = 8.3) isozymes. A comparison of the relative inhibitory activities of the two groups of regioisomers investigated shows that the regioisomers in which the alkyl substituent is attached to the same olefinic carbon atom (C-2) as the para-methanesulfonylphenyl moiety generally exhibit a greater potency with respect to COX-2 inhibition. The 4-hydroxy substituent in the 3,5-di-tert-butyl-4-hydroxyphenyl moiety is essential for COX and LOX inhibition since 3,5-di-tert-butyl-4-acetoxyphenyl derivatives were inactive inhibitors. These structure-activity data indicate acyclic triaryl (Z)-olefins constitute a suitable template for the design of dual COX-2/LOX inhibitors.
- Moreau, Anne,Praveen Rao,Knaus, Edward E.
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p. 5340 - 5350
(2008/02/07)
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- One-Pot Two-Step Synthesis of Aryl Sulfur Compounds by Photoinduced Reactions of Thiourea Anion with Aryl Halides
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(Equation presented) The photoinduced reactions of aryl halides with the thiourea anion afford arene thiolate ions in DMSO. These species without isolation, and by a subsequent aliphatic nucleophilic substitution, S RN1 reaction, oxidation, or protonation, yield aryl methyl sulfides, diaryl sulfides, diaryl disulfides, and aryl thiols with good yields (50-80%). This is a simple and convenient approach which involves the use of the commercially available and inexpensive thiourea in a one-pot two-step process for the synthesis of aromatic sulfur compounds.
- Argueello, Juan E.,Schmidt, Luciana C.,Penenory, Alicia B.
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p. 4133 - 4136
(2007/10/03)
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- A highly active ytterbium(III) methide complex for truly catalytic Friedel-Crafts acylation reactions
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The Friedel-Crafts acylation of anisole with acetic anhydride using ytterbium(III) tri[tris(nonafluorobutanesulfonyl)methide] was studied with respect to catalyst loading. A strong inhibitory effect due to the product became apparent from doping experiments and from examination of the kinetic data. This understanding allowed catalyst loadings to be reduced to as little as 0.1 mol% for effective acylation under a suitable temperature and pressure regime.
- Barrett, Anthony G. M.,Bouloc, Nathalie,Braddock, D. Christopher,Chadwick, David,Henderson, David A.
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p. 1653 - 1656
(2007/10/03)
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- An efficient method for aromatic Friedel-Crafts alkylation, acylation, benzoylation, and sulfonylation reactions
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Aromatic electrophilic substitution reactions such as alkylation, acylation, benzoylation, and sulfonylation were studied in the presence of a catalytic amount of Cu(OTf)2 and Sn(OTf)2. Cu(OTf)2 was very efficient for alkylation, acylation, and benzoylation reactions. However, in case of sulfonylation reactions, Sn(OTf)2 gave better results.
- Singh, Ravi P,Kamble, Rajesh M,Chandra, Kusum L,Saravanan,Singh, Vinod K
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p. 241 - 247
(2007/10/03)
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- Diarylmethylidenefuran derivatives and their uses in therapeutics
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The present invention relates to the derivatives of the formula STR1 and to their use in therapeutics, especially as drugs with anti-inflammatory and analgesic properties.
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- "SAFETY-CATCH" PROTECTING GROUPS IN PEPTIDE SYNTHESIS
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A new benzhydryl-type protective groups for amides based on the concept of converting a stable protecting group into a labile one (safety-catch principle) are described.The p-substituted benzhydrylamine derivatives III(a, b), IV(a, b) are shown to be labi
- Patek, Marcel,Lebl, Michal
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p. 508 - 524
(2007/10/02)
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- ELECTRON TRANSFER INDUCED REACTIONS. ELECTROCHEMICALLY STIMULATED AROMATIC NUCLEOPHILIC SUBSTITUTION IN ORGANIC SOLVENTS.
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The main difference between organic solvents and solvents such as liquid ammonia as far as electrochemically induced aromatic nucleophilic substitution is concerned regards the role of H-atom abstraction from the solvent. This reaction and electron transfer at the electrode and in the solution are major side reactions competing with nucleophilic attack on the aryl radical. The resulting four-cornered competition is analyzed in the context of cyclic voltammetry and preparative scale electrolysis. In most cases, the experimental conditions can be adjusted so that the competition only involves nucleophilic attack, heterogeneous electron transfer, and H-atom abstraction. This allows a quantitative evaluation of the role of the latter reaction. Experimentally, a detailed investigation of the substitution of 9-haloanthracenes by cyanide and thiophenoxide ions has been made. Other systems for which preparative scale results were previously gathered are analyzed in the same context. A general mechanistic picture of the S//R//N1 reaction can be drawn which is applicable to the case of electrochemical inducement but also to the other modes of stimulation.
- Amatore,Pinson,Saveant,Thiebault
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p. 817 - 826
(2007/10/02)
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