- Photoinduced Regioselective Olefination of Arenes at Proximal and Distal Sites
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The Fujiwara-Moritani reaction has had a profound contribution in the emergence of contemporary C-H activation protocols. Despite the applicability of the traditional approach in different fields, the associated reactivity and regioselectivity issues had
- Ali, Wajid,Anjana, S. S.,Bhattacharya, Trisha,Chandrashekar, Hediyala B.,Goswami, Nupur,Guin, Srimanta,Maiti, Debabrata,Panda, Sanjib,Prakash, Gaurav,Saha, Argha,Sasmal, Sheuli,Sinha, Soumya Kumar
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supporting information
p. 1929 - 1940
(2022/02/01)
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- Synthesis of oxadiazole-2-oxide derivatives as potential drug candidates for schistosomiasis targeting SjTGR
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Background: Schistosomiasis is a chronic parasitic disease that affects millions of people’s health worldwide. Because of the increasing drug resistance to praziquantel (PZQ), which is the primary drug for schistosomiasis, developing new drugs to treat schistosomiasis is crucial. Oxadiazole-2-oxides have been identified as potential anti-schistosomiasis reagents targeting thioredoxin glutathione reductase (TGR). Methods: In this work, one of the oxadiazole-2-oxides derivatives furoxan was used as the lead compound to exploit a series of novel furoxan derivatives for studying inhibitory activity against both recombinant Schistosoma japonicum TGR containing selenium (rSjTGR-Sec) and soluble worm antigen protein (SWAP) containing wild-type Schistosoma japonicum TGR (wtSjTGR), in order to develop a new leading compound for schistosomiasis. Thirty-nine novel derivatives were prepared to test their activity toward both enzymes. The docking method was used to detect the binding site between the active molecule and SjTGR. The structure–activity relationship (SAR) of these novel furoxan derivatives was preliminarily analyzed. Results: It was found that several new derivatives, including compounds 6a–6d, 9ab, 9bd and 9be, demonstrated greater activity toward rSjTGR-Sec or SWAP containing wtSjTGR than did furoxan. Interestingly, all intermediates bearing hydroxy (6a–6d) showed excellent inhibitory activity against both enzymes. In particular, compound 6d with trifluoromethyl on a pyridine ring was found to have much higher inhibition toward both rSjTGR-Sec (half-maximal inhibitory concentration, IC50,7.5nM) and SWAP containing wtSjTGR (IC50 55.8nM) than furoxan. Additionally, the docking method identified the possible matching sites between 6d and Schistosoma japonicum TGR (SjTGR), which theoretically lends support to the inhibitory activity of 6d. Conclusion: The data obtained herein showed that 6d with trifluoromethyl on a pyridine ring could be a valuable leading compound for further study.
- Li, Gongming,Guo, Qingqing,Feng, Chao,Chen, Huan,Zhao, Wenjiao,Li, Shu,Hong, Yang,Sun, Dequn
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- Structure?Activity Relationships of Cinnamate Ester Analogues as Potent Antiprotozoal Agents
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Protozoal infections are still a global health problem, threatening the lives of millions of people around the world, mainly in impoverished tropical and sub-tropical regions. Thus, in view of the lack of efficient therapies and increasing resistances against existing drugs, this study describes the antiprotozoal potential of synthetic cinnamate ester analogues and their structure-activity relationships. In general, Leishmania donovani and Trypanosoma brucei were quite susceptible to the compounds in a structure-dependent manner. Detailed analysis revealed a key role of the substitution pattern on the aromatic ring and a marked effect of the side chain on the activity against these two parasites. The high antileishmanial potency and remarkable selectivity of the nitro-aromatic derivatives suggested them as promising candidates for further studies. On the other hand, the high in vitro potency of catechol-type compounds against T. brucei could not be extrapolated to an in vivo mouse model.
- Bernal, Freddy A.,Kaiser, Marcel,Wünsch, Bernhard,Schmidt, Thomas J.
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- Electro-Olefination—A Catalyst Free Stereoconvergent Strategy for the Functionalization of Alkenes
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Conventional methods carrying out C(sp2)?C(sp2) bond formations are typically mediated by transition-metal-based catalysts. Herein, we conceptualize a complementary avenue to access such bonds by exploiting the potential of electrochemistry in combination with organoboron chemistry. We demonstrate a transition metal catalyst-free electrocoupling between (hetero)aryls and alkenes through readily available alkenyl-tri(hetero)aryl borate salts (ATBs) in a stereoconvergent fashion. This unprecedented transformation was investigated theoretically and experimentally and led to a library of functionalized alkenes. The concept was then carried further and applied to the synthesis of the natural product pinosylvin and the derivatization of the steroidal dehydroepiandrosterone (DHEA) scaffold.
- Baumann, Andreas N.,Dechent, Jonas,Didier, Dorian,Jagau, Thomas C.,Müller, Nicolas,Music, Arif
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supporting information
(2020/07/04)
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- Copper-catalyzed Mizoroki-Heck coupling reaction using an efficient and magnetically reusable Fe3O4@SiO2@PrNCu catalyst
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This study intends to design and prepare a new magnetic copper catalyst and its activity was assessed by carbon-carbon coupling reactions. For this purpose, 1-[3-(trimethoxysilyl) propyl] urea (TMSPU), hydrazine and CuI were used sequentially to modify Fe3O4@SiO2 core-shell magnetic nanoparticles to obtain an efficient magnetic transition metal catalyst. Various analytical techniques were used to characterize the catalyst to show that the achieved structure and its properties are well-suited for coupling reactions. Finally, Mizoroki-Heck and Ullmann coupling reactions were performed using Fe3O4@SiO2@PrNCu catalyst. The new catalyst offer simple synthetic procedure, convenient use for routine casework and low price. The Fe3O4@SiO2@PrNCu catalyst was easily separated by means of a permanent and ordinary magnet and the recovered catalyst was reused in six cycles without any significant loss of activity.
- Yavari, Issa,Mobaraki, Akbar,Hosseinzadeh, Zhila,Sakhaee, Nader
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supporting information
p. 236 - 246
(2019/07/19)
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- One-Pot Synthesis of α,β-Unsaturated Esters, Ketones, and Nitriles from Alcohols and Phosphonium Salts
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A general method for the synthesis of α,β-unsaturated esters, ketones, and nitriles is successfully achieved by a one-pot copper-catalyzed oxidation with O 2 in air as oxidant. The solvent mixture of acetonitrile and formamide (1:1) is optimized to ensure the oxidation of alcohols, deprotonation of phosphonium salt, and Wittig reaction occur efficiently in one pot. A broad range of substrates has been explored for this process, including three electron-withdrawing group (CO 2 Et, COPh, CN) functionalized phosphonium salts. They reacted not only with benzylic and heteroaromatic alcohols, but also with aliphatic alcohols, forming the corresponding α,β-unsaturated esters, ketones, and nitriles in moderate to excellent yields.
- Ding, Weijie,Hu, Juan,Jin, Huile,Yu, Xiaochun,Wang, Shun
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p. 107 - 118
(2017/09/28)
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- Facile synthesis of α, β-unsaturated esters through a one-pot copper-catalyzed aerobic oxidation-Wittig reaction
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An efficient one-pot synthesis of α, β-unsaturated esters through the aerobic oxidation – Wittig tandem reaction of alcohols and phosphorous ylide is developed. This new method operates under mild reaction conditions, and uses CuI/TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidine-N-oxyl) as co-catalyst and air (O2) as the oxidant. It tolerates a wide range of functionalized benzylic alcohol and aliphatic alcohols.
- Ren, Cheng,Shi, Zhenyu,Ding, Weijie,Liu, Zhiqing,Jin, Huile,Yu, Xiaochun,Wang, Shun
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supporting information
p. 14 - 17
(2017/12/06)
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- Bioactivity and structure–activity relationship of cinnamic acid derivatives and its heteroaromatic ring analogues as potential high-efficient acaricides against Psoroptes cuniculi
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A series of cinnamic acid derivatives and its heteroaromatic ring analogues were synthesized and evaluated for acaricidal activity in vitro against Psoroptes cuniculi, a mange mite. Among them, eight compounds showed the higher activity with median lethal concentrations (LC50) of 0.36–1.07 mM (60.4–192.1 μg/mL) and great potential for the development of novel acaricidal agent. Compound 40 showed both the lowest LC50 value of 0.36 mM (60.4 μg/mL) and the smallest median lethal time (LT50) of 2.6 h at 4.5 mM, comparable with ivermectin [LC50 = 0.28 mM (247.4 μg/mL), LT50 = 8.9 h], an acaricidal drug standard. SAR analysis showed that the carbonyl group is crucial for the activity. The type and chain length of the alkoxy in the ester moiety and the steric hindrance near the ester group significantly influence the activity. The esters were more active than the corresponding thiol esters, amides, ketones or acids. Replacement of the phenyl group of cinnamic esters with α-pyridyl or α-furanyl significantly increase the activity. Thus, a series of cinnamic esters and its heteroaromatic ring analogues with excellent acaricidal activity emerged.
- Chen, Dong-Dong,Zhang, Bing-Yu,Liu, Xiu-Xiu,Li, Xing-Qiang,Yang, Xin-Juan,Zhou, Le
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supporting information
p. 1149 - 1153
(2018/03/05)
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- Synthesis and evaluation of N-heteroaromatic ring-based analogs of piperlongumine as potent anticancer agents
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Piperlongumine (PL) selectively targets a wide spectrum of cancer cells and induces their death by triggering various pathways, including apoptosis, necrosis and autophagy. However, the poor solubility is a serious concern for intensive study and clinical application. We synthesized its analogs 1–9 by replacement of the trimethoxyphenyl of PL with an N-heteroaromatic ring and/or not introduction of 2-Cl. These compounds improved aqueous solubility and displayed potent anticancer activity. The most active compound 9 selectively enhanced ROS levels in colon cancer cells and inhibited the cell proliferation but sparing non-tumor colon cells. Importantly, 9 significantly repressed tumor growth in an HCT-116 xenograft mouse model, suggesting that these N-heteroaromatic ring-based analogs of PL warrant further investigation.
- Zou, Yu,Yan, Chang,Zhang, Huibin,Xu, Jinyi,Zhang, Dayong,Huang, Zhangjian,Zhang, Yihua
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p. 313 - 319
(2017/07/07)
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- Iridium-Catalyzed Enantioselective Allylic Substitution of Aliphatic Esters with Silyl Ketene Acetals as the Ester Enolates
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Enantioselective allylic substitution with enolates derived from aliphatic esters under mild conditions remains challenging. Herein we report iridium-catalyzed enantioselective allylation reactions of silyl ketene acetals, the silicon enolates of esters, to form products containing a quaternary carbon atom at the nucleophile moiety and a tertiary carbon atom at the electrophile moiety. Under relatively neutral conditions, the allylated aliphatic esters were obtained with excellent regioselectivity and enantioselectivity. These products were readily converted into primary alcohols, carboxylic acids, amides, isocyanates, and carbamates, as well as tetrahydrofuran and γ-butyrolactone derivatives, without erosion of enantiomeric purity.
- Jiang, Xingyu,Hartwig, John F.
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supporting information
p. 8887 - 8891
(2017/07/17)
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- Flexible, dicationic imidazolium salts for in situ application in palladium-catalysed Mizoroki–Heck coupling of acrylates under aerobic conditions
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The synthesis, characterization and in situ catalytic performance of new unsymmetric N,N′-disubstituted imidazolium-based dicationic salts in Mizoroki–Heck coupling of acrylates with aryl bromides under aerobic conditions are described. A series of flexible dicationic salts with varying steric and electronic properties were synthesized in good to excellent yields. All the salts were well characterized using spectroscopic techniques. X-ray diffraction analysis of two salts with the same dicationic backbone and different counter anions shows that the ligand adopts two different conformations which are influenced by the nature of the anion. Thus, the ligand is capable of changing its conformation according to the change in environment due to its flexible nature. All the synthesized imidazolium salts were found to be active in in situ palladium-catalysed Mizoroki–Heck coupling under aerobic conditions. Amongst the salts, the hydroxyl-functionalized imidazolium salt, incorporating the features of both bidentate chelating O,O ligand and carbene, shows the maximum catalytic activity. A variety of aryl and heteroaryl methyl and ethyl cinnamates were synthesized using these imidazolium salts as preligands. In addition, NMR studies confirm in situ generation of normal N-heterocyclic carbenes from the C-2 position of imidazol-2-ylidene ring. The mercury poisoning test was also performed to ascertain the nature of catalytically active palladium species. Aerobic conditions, low catalytic loading (0.5?mol%), shorter reaction times, broad functional group tolerance and good to excellent isolated yields are some of the significant features of the novel catalytic systems described here. Copyright
- Milton, Marilyn Daisy,Garg, Parul
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p. 759 - 766
(2016/09/04)
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- Polyethyleneimine-Supported Triphenylphosphine and Its Use as a Highly Loaded Bifunctional Polymeric Reagent in Chromatography-Free One-Pot Wittig Reactions
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A polyethyleneimine-supported triphenylphosphine reagent has been synthesized and used as a highly loaded bifunctional homogeneous reagent in a range of one-pot Wittig reactions that afforded high yields of the desired products after simple purification procedures. The approach also served efficiently in tandem reaction sequences involving a one-pot Wittig reaction followed by conjugate reduction of the newly formed alkene product in situ. In these transformations, the phosphine oxide groups generated in the Wittig reaction served as the catalyst for activating trichlorosilane in the subsequent reduction reaction.
- Xia, Xuanshu,Toy, Patrick H.
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supporting information
p. 1737 - 1743
(2015/07/20)
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- Silylative cyclopropanation of allyl phosphates with silylboronates
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A potassium-bis(trimethylsilyl)amide-mediated cyclopropanation of allyl phosphates with silylboronates has been developed. Unlike the reported copper-catalyzed allylic substitution reactions, the nucleophile selectively attacks at the β-position of the allylic substrates under the present reaction conditions. The mechanism of this process has also been investigated, thus indicating the involvement of a silylpotassium species as the active nucleophilic component.
- Shintani, Ryo,Fujie, Ryuhei,Takeda, Momotaro,Nozaki, Kyoko
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supporting information
p. 6546 - 6549
(2014/06/24)
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- OMS-2 for aerobic, catalytic, one-pot alcohol oxidation-wittig reactions: Efficient access to α,β-unsaturated esters
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Manganese oxide octahedral molecular sieve (OMS) materials with well-defined pores have been extensively studied over two decades due to their intriguing chemical and physical properties. OMS-2, the synthetic cryptomelane form of manganese oxide, was synthesized by a modified reflux method and was found to be highly active for obtaining α,β-unsaturated esters (up to 95 % yield and with high diastereoselectivities) from a variety of benzyl, heteroaryl, allyl and alkyl alcohols via one-pot alcohol oxidation-Wittig reaction. The transformation utilizes air as the stoichiometric oxidant, and the inexpensive catalyst can be recovered and reused. Filter and use again! Porous manganese oxide molecular sieve based catalysts were found to efficiently promote the oxidation of a variety of alcohols to the aldehydes, which reacted insitu with stabilized Wittig reagent, providing almost exclusively E-α,β-unsaturated esters in good to excellent yields. The heterogeneous catalyst used was made from inexpensive starting materials, and the recovered catalyst was found to be reusable with a modest loss in activity.
- Kona, Jagadeswara R.,King'Ondu, Cecil K.,Howell, Amy R.,Suib, Steven L.
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p. 749 - 752
(2014/03/21)
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- (HETERO)ARYL CYCLOPROPYLAMINE COMPOUNDS AS LSD1 INHIBITORS
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The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula I as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection.
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Page/Page column 144
(2013/05/09)
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- (HETERO)ARYL CYCLOPROPYLAMINE COMPOUNDS AS LSD1 INHIBITORS
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The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula (I) as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection.
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Page/Page column 139
(2013/05/09)
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- Preparations of 4-substituted 3-carboxypyrazoles
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The scopes of three synthetic methods reported for the preparation of an array of 3-pyrazolecarboxylates featuring substituents on position 4 were investigated. The first one is based on the potassium permanganate oxidation of methylpyrazoles. The second starts with the condensation between DMF dimethylacetal and ethyl pyruvate and is followed by the addition of hydrazine hydrochloride. The last one makes use of the cycloaddition of diazomethane on acrylate esters followed by a bromine-based oxidative rearrangement into 4-substituted 3-pyrazole esters.
- Janin, Yves L.
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p. 1410 - 1414
(2014/01/06)
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- Stereoselective olefination and regiospecific vicinal difunctionalization of imines with α-(benzothiazol-2-ylsulfonyl) carbonyl compounds
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Depending on their structures, imines are able to undergo either olefination or vicinal difunctionalization with various α-(benzothiazol-2- ylsulfonyl) carbonyl compounds in the absence of external bases. The olefination reaction of aromatic imines with α-(benzothiazol-2-ylsulfonyl) carbonyl compounds proceeds smoothly in tetrahydrofuran at 70 °C to give structurally diverse α,β-unsaturated esters, amides, and ketones in good to excellent yields and with extremely high (E) selectivity. In contrast, the carbon-nitrogen double bonds of cyclic imines and the carbon-carbon double bonds of α,β-unsaturated imines are subjected to regiospecific vicinal difunctionalization with α-(benzothiazol-2-ylsulfonyl) carbonyl compounds under the same reaction conditions to give a variety of benzothiazole derivatives in good to excellent yields. It is noteworthy that the benzothiazole moiety is present in a number of antitumor agents and bioluminescent molecules. In addition, plausible reaction pathways have been proposed to account for these transformations, and these are substantially supported by ESI-MS analysis of the reaction mixtures.
- Shao, You-Dong,Wu, Xue-Song,Tian, Shi-Kai
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supporting information; experimental part
p. 1590 - 1596
(2012/05/07)
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- Organocatalytic decarboxylative Doebner-Knoevenagel reactions between arylaldehydes and monoethyl malonate mediated by a bifunctional polymeric catalyst
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A bifunctional polystyrene bearing both DMAP and piperidine groups has been prepared and used as an organocatalyst for decarboxylative Doebner-Knoevenagel reactions of arylaldehydes and monoethyl malonate. Isolated yields of the resulting cinnamates were very high, and in all cases only the E-isomer was detected. When a polystyrene catalyst functionalized with only DMAP or piperidine groups was used in these reactions, catalysis was much less efficient. Furthermore, catalysis using a combination of the monofunctional polymers was also less efficient than with the bifunctional polystyrene. Thus, it appears that there is a synergistic effect obtained by co-locating the two different catalytic amine groups on the same polymer backbone. Georg Thieme Verlag Stuttgart · New York.
- Lu, Jinni,Toy, Patrick H.
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supporting information; experimental part
p. 1723 - 1726
(2011/09/12)
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- Ligand-promoted C-3 selective C-H olefination of pyridines with Pd catalysts
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Pd-catalyzed C-3 selective olefination of pyridines is developed for the first time using 1,10-phenanthroline as the ligand. This finding provides a novel disconnection for the synthesis of pyridine-containing alkaloids and drug molecules as well as a new approach for developing Pd-catalyzed C-H functionalizations of pyridines.
- Ye, Mengchun,Gao, Guo-Lin,Yu, Jin-Quan
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supporting information; experimental part
p. 6964 - 6967
(2011/06/19)
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- Study on the Heck reaction promoted by carbene adduct of cyclopalladated ferrocenylimine and the related reaction mechanism
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Carbene adduct of cyclopalladated ferrocenylimine has been successfully applied to Heck reaction of various aryl bromides with olefins. On the basis of kinetic studies, in situ 13C NMR spectra investigations and Hg poisoning experiments, it was proposed that the Heck reaction catalyzed by carbene adduct of cyclopalladated ferrocenylimine proceeded through a classical Pd(0)/Pd(II) cycle and such palladacycle was only a reservoir of the catalytically active Pd(0) species.
- Ren, Gerui,Cui, Xiuling,Yang, Erbing,Yang, Fan,Wu, Yangjie
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scheme or table
p. 4022 - 4028
(2010/07/05)
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- σ-alkylpalladium intermediates in intramolecular Heck reactions: Isolation and catalytic activity
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The isolation of σ-alkylpalladium Heck intermediates, possible when β-hydride elimination is inhibited, is a rather rare event. Performing intramolecular Heck reactions on Nallyl-2-halobenzylamines in the presence of [Pd(PPh3)4], we isolated and characterized a series of stable bridged palladacycles containing an iodine or bromine atom on the palladium atom. Indolyl substrates were also tested for isolation of the corresponding com- plexes. X-ray crystallographic analysis of one of the indolyl derivatives revealed the presence of a five-membered palladacycle with the metal center bearing a PPh3 ligand and an iodine atom in a cis position with respect to the nitrogen atom. The stability of the σ-alkylpalladium complexes is probably a consequence of the strong constraint resulting from the bridged junction that hampers the cisoid conformation essential for β-hydride elimination. Subsequently, the thus obtained bridged five-membered palladacycles were proven to be effective precatalysts in Heck reactions as well as in cross-coupling processes such as Suzuki and Stille reactions.
- Beccalli, Egle M.,Borsini, Elena,Brenna, Stefano,Galli, Simona,Rigamonti, Micol,Broggini, Gianluigi
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supporting information; experimental part
p. 1670 - 1678
(2010/06/15)
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- New and facile approach for the synthesis of (E)-α,β-unsaturated esters and ketones
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A general and practical synthesis of (E)-α,β-unsaturated esters and ketones was achieved by the reaction of carbonyl compounds with ethyl-4,4,4-trifluoroacetoacetate and trifluoro-substituted 1,3-diketones in the presence of piperidine in dichloromethane at raoom temperature (≈40°C) with excellent stereoselectivity (see scheme).
- China Raju, Bhimapaka,Suman, Pathi
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supporting information; experimental part
p. 11840 - 11842
(2011/01/12)
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- 2,5-Disubstituted tetrahydrofurans as selective serotonin re-uptake inhibitors
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Enhancement of 5-hydroxytryptamine (5-HT, serotonin) neurotransmission is a viable means of treating depression. On the basis of this observation, agents that inhibit re-uptake of 5-HT were prepared based on (-)-cocaine and aryltropanes as lead compounds
- Voelker, Troy,Xia, Haiji,Fandrick, Keith,Johnson, Robert,Janowsky, Aaron,Cashman, John R.
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experimental part
p. 2047 - 2068
(2009/06/06)
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- Ruthenium-catalyzed, one-pot alcohol oxidation-wittig reaction producing αβ unsaturated esters
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By a one-pot process, αβ-unsaturated esters were synthesized in high yield through the Ru-catalyzed oxidation of primary alcohols and the coupling of the resulting aldehydes and stabilized Wittig reagents. The ruthenium catalyst is composed of ruthenium nanoparticles embedded in aluminum oxyhydroxide and can be recovered simply by filtration or decantation. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009.
- Lee, Eun Young,Kim, Youngkwon,Lee, Jae Sung,Park, Jaiwook
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experimental part
p. 2943 - 2946
(2009/10/11)
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- Task-specific ionic liquid as base, ligand and reaction medium for the palladium-catalyzed Heck reaction
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A novel ionic liquid, which was based on ethanolamine-functionalized quaternary ammonium salt was designed and synthesized. 4-Di(hydroxyethyl)aminobutyl tributylammonium bromide (DHEABTBAB) 1, a task-specific ionic liquid, which acts as a base, ligand and reaction medium, exhibits a very high activity and recyclability to palladium-catalyzed Heck reaction. The olefinations of iodoarenes, bromoarenes and chloroarenes with olefins generated the corresponding cross-coupling products in good to excellent yields only in the presence of DHEABTBAB and palladium acetate under phosphine-free reaction conditions. It is noteworthy that palladium and DHEABTBAB could be repeatedly recycled and reused for six consecutive trials without significant loss of their activities.
- Wang, Lei,Li, Hongji,Li, Pinhua
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experimental part
p. 364 - 368
(2009/04/06)
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- Preparation of Boc-protected cinnamyl-type alcohols: A comparison of the Suzuki-Miyaura coupling, cross-metathesis, and Horner-Wadsworth-Emmons approaches and their merit in parallel synthesis
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Three synthetic strategies for the construction of tert-butyl (E)-3-arylprop-2-en-1-ol carbonates are described. Complementary approaches employing Suzuki-Miyaura coupling and cross-metathesis reaction gave moderate yields of the title compounds in one-step, both methods are suitable for high-throughput and parallel chemistry. A detailed investigation into the Suzuki-Miyaura coupling reaction is provided along with the studies on the synthesis of pinacolyl 1-(tert-butyloxycarbonyl)propenol-3-ylboronate, the key building block. Conventional synthesis of the title compounds via the Horner-Wadsworth-Emmons reaction as a key step in a three-step-one-purification protocol was optimized and the results are compared with those of the latter reactions.
- Stambasky, Jan,Malkov, Andrei V.,Kocovsky, Pavel
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experimental part
p. 705 - 732
(2009/04/03)
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- A convenient method for the lewis base-catalyzed synthesis of α,β-unsaturated carboxylic esters using trimethylsilylketene ethyl trimethylsilyl acetal and carbonyl compounds
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A highly useful method for the synthesis of α,β-unsaturated carboxylic esters from various carbonyl compounds that uses trimethylsilylbetene ethyl trimethylsilyl acetal in the presence of a Lewis base catalyst such as acetate salts was established. This procedure gives the corresponding esters in high yields with excellent E stereoselectivity under mild conditions. Copyright
- Michida, Makoto,Mukaiyama, Teruaki
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p. 704 - 705
(2008/12/21)
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- Wittig reactions in water media employing stabilized ylides with aldehydes. Synthesis of α,β-unsaturated esters from mixing aldehydes, α-bromoesters, and Ph3P in aqueous NaHCO3
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(Chemical Equation Presented) Water is demonstrated to be an effective medium for the Wittig reaction over a wide range of stabilized ylides and aldehydes. Despite sometimes poor solubility of the reactants, good chemical yields normally ranging from 80 to 98% and high E-selectivities (up to 99%) are achieved, and the rate of the reactions in water is unexpectedly accelerated. The efficiency of water as a medium in the Wittig reaction is compared to conventional organic solvents ranging from carbon tetrachloride to methanol. The aqueous Wittig reaction works best when large hydrophobic entities are present, such as aromatic, heterocyclic aromatic carboxaldehydes, and long-chain aliphatic aldehydes with triphenylphosphoranes. The E/Z-isomeric ratio of the Wittig products appears dependent on the electron-accepting/donating capacity and the location of the substituents present in the aromatic ring. The effect of additives, such as benzoic acid, LiCl, and sodium dodecyl sulfate (SDS), on the Wittig reaction has been explored. The Wittig reaction can also be conducted in the presence of acidic entities, such as phenols and carboxylic acids. In addition, large α-substituents in the aliphatic aldehydes do not jeopardize the reaction. It is also demonstrated that hydrates of aldehydes can be used directly in the aqueous Wittig reaction as substrates. The scope of the aqueous Wittig reaction is extended to 24 examples of one-pot mixtures of Ph3P, α-bromoesters, and aldehydes in sodium bicarbonate solution (at 20°C for 40 min to 3 h) to provide Wittig products of up to 99% yield and up to 98% E-selectivity. Since water is inexpensive, extremely easy to handle, and represents no environmental concerns, it should be considered a possible medium for new organic reactions.
- El-Batta, Amer,Jiang, Changchun,Zhao, Wen,Anness, Robert,Cooksy, Andrew L.,Bergdahl, Mikael
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p. 5244 - 5259
(2008/02/07)
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- Dimethyl sulfoxide mediated elimination reactions in 3-aryl 2,3-dihalopropanoates: Scope and mechanistic insights
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(Chemical Equation Presented) Dimethyl sulfoxide (DMSO) efficiently causes the reductive elimination of 3-aryl 2,3-dibromopropanoates to cinnamates with good yield. With 3-phenyl 2,3-dihalopropanoates, debromination is the major pathway providing 3-phenylacrylate derivatives in high yields, whereas dehydrobromination is a competing pathway with thiophene derivatives. 1H NMR, 81Br NMR, and MS techniques indicated the formation of brominated-DMSO, MeBr, and HBr as byproducts in this transformation with no evidence for the formation of Br2. The dual role of DMSO as a nucleophile and bromine scavenger accounts for the products formed in this reaction.
- Li, Wei,Li, Jianchang,Lin, Melissa,Wacharasindhu, Sumrit,Tabei, Keiko,Mansour, Tarek S.
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p. 6016 - 6021
(2008/02/10)
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- Synthesis, characterization, and applications in Heck and Suzuki coupling reactions of amphiphilic cyclopalladated ferrocenylimines
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A series of novel amphiphilic ferrocenylimines and their cyclopalladated complexes of general formula [Fe(η5-C5H5)(η5-C5H4CR1{double bond, long}NR2)] (R1=H, R2=C12H25-n 4a, R1=H, R2=C16H33-n 4b, R1=CH3, R2=C12H25-n 4c, R1=CH3, R2=C16H33-n 4d), [PdCl{[(η5-C5H5)]Fe[(η5-C5H3)CR1{double bond, long}NR2]}]2 (5a-d), [PdCl{[(η5-C5H5)]Fe[(η5-C5H3)-CR1{double bond, long}NR2]}(PPh3)] (6a-d), were prepared and characterized by 1H NMR, 13C NMR, 31P NMR, IR, HRMS, and elemental analysis. The crystal structures of 5c,d were determined by X-ray crystallography. These amphiphilic cyclopalladated complexes are thermally stable and insensitive to oxygen and moisture. The redox properties of 4a-d, 5a-d, 6a-d were also investigated using cyclic voltammetric technique. Compounds 5a-d, 6a-d displayed good activity in the Heck reaction of a variety of aryl halides with ethyl acrylate or styrene and the Suzuki-Miyaura cross-coupling reaction of aryl bromides with phenylboronic acid in bulk solution. They are also suitable for formation of Langmuir-Blodgett (LB) films.
- Mu, Bing,Li, Tiesheng,Xu, Wenjian,Zeng, Guoliang,Liu, Pingping,Wu, Yangjie
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p. 11475 - 11488
(2008/03/12)
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- MODULATORS OF CENTRAL NERVOUS SYSTEM NEUROTRANSMITTERS
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Disclosed are agents having pharmacological activity against cellular receptors and intracellular singaling, particularly receptors and sigaling pathways of central nervous system (CNS) neurotransmitters. Also disclosed are related methods and compositions for the treatment or prevention of diseases or disorders using the agents.
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Page/Page column 89
(2010/10/20)
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- Tricyclohexylphosphine-cyclopalladated ferrocenylimine complexes: Synthesis, crystal structures and application in Suzuki and Heck reactions
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A series of novel tricyclohexylphosphine (PCy3)-cyclopalladated ferrocenylimine complexes 2c-2g have been easily synthesized. These new palladacycles are thermally stable and are not sensitive to air and moisture. Their detailed structures have been determined by single-crystal X-ray analysis and six different types of intermolecular hydrogen bonds are found to be existed in the crystals of these complexes. The use of 2c-2g as catalysts for Suzuki and Heck reactions was examined. They were found to be very efficient for the Suzuki reaction of aryl chlorides with phenylboronic acid. Typically, using 0.1 mol% of catalyst in the presence of 1.5 equivalent of Cs2CO 3 as base in dioxane at 100 °C provided coupled products in excellent yields. These complexes also displayed good activity in the Heck reaction of a range of aryl bromides with acrylic acid ethyl ester although they were not particularly useful for the activation of aryl chlorides. The Royal Society of Chemistry 2006.
- Xu, Chen,Gong, Jun-Fang,Yue, Su-Fang,Zhu, Yu,Wu, Yang-Jie
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p. 4730 - 4739
(2007/10/03)
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- Enantioselective synthesis of (+)(R)- And (-)(S)-nicotine based on Ir-catalysed allylic amination
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The synthesis of nicotine with enantiomeric excess of >99% ee was accomplished by asymmetric Ir-catalysed allylic amination followed by ring closing metathesis and racemisation-free double bond reduction. The Royal Society of Chemistry 2005.
- Welter, Carolin,Moreno, Rosa M.,Streiff, Stephane,Helmchen, Guenter
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p. 3266 - 3268
(2007/10/03)
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- Dialyzable carbosilane dendrimers as soluble supports for the functionalization of pyridine fragments via palladium-catalyzed coupling reactions
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(Chemical Equation Presented) The use of carbosilane (CS) dendrimers as soluble supports in liquid phase organic synthesis (LPOS) is described. Control of the three key steps is perfectly achieved by covalently binding a pyridine fragment to the soluble s
- Le Notre, Jerome,Firet, Judith J.,Sliedregt, Leo A. J. M.,Van Steen, Bart J.,Van Koten, Gerard,Gebbink, Robertus J. M. Klein
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p. 363 - 366
(2007/10/03)
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- Regioselectivity of Michael additions to 3-(pyridin-3-yl or pyrimidin-2-yl)-propenoates and their N-oxides - Experimental and theoretical studies
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We demonstrate that nucleophilic addition to α,β-unsaturated carbonyl compounds can be redirected from the usual β-carbon (Michael) to an α-carbon regioselectivity by attaching a π-deficient aromatic substituent to the β-carbon atom. In particular, propanethiol addition to 3-(pyridin-3-yl or pyrimidin-2-yl)propenoate gives a β-carbon adduct, while addition to the corresponding more π-deficient N-oxides gives the α-adduct or a mixture of α- and β-adducts. This adds to the number of carbon-carbon bond-forming reactions at the α-position of Michael receptors documented recently. Density functional calculations reveal that the regioselectivity is due to a combination of reduction of the barrier for α-addition and increase of the barriers for β-addition and carbonyl addition as the π-deficient character of the aromatic substituent is increased. The calculations predict a significant solvent effect on the regioselectivity in some cases. The regioselectivity is also consistent with Hammett constants σ-. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.
- Lewandowska, Elzbieta,Chatfield, David C.
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p. 3297 - 3303
(2007/10/03)
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- Nonpeptide αvβ3 Antagonists. 8. In Vitro and in Vivo Evaluation of a Potent αvβ3 Antagonist for the Prevention and Treatment of Osteoporosis
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3(S)-(6-Methoxypyridin-3-yl)-3-{2-oxo-3-[3-(5,6,7,8-tetrahydro-[1,8] -naphthyridin-2-yl)propyl]-imidazolidin-1-yl}propionic acid 6 was identified as a potent and selective antagonist of the αvβ3 receptor. This compound has an excellent in vitro profile (IC50 = 0.08 nM), a significant unbound fraction in human plasma (12%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in three in vivo models of bone turnover, the compound was selected for clinical development. To support the ongoing metabolism and safety studies, a novel strategy was employed in which a series of oxidized derivatives of 6 were prepared by exposure of 6 (or the methyl ester) to chemical oxidizing agents. These products proved useful in the identification of active metabolites generated by either in vitro or in vivo metabolism.
- Hutchinson, John H.,Halczenko, Wasyl,Brashear, Karen M.,Breslin, Michael J.,Coleman, Paul J.,Duong, Le T.,Fernandez-Metzler, Carmen,Gentile, Michael A.,Fisher, John E.,Hartman, George D.,Huff, Joel R.,Kimmel, Donald B.,Leu, Chih-Tai,Meissner, Robert S.,Merkle, Kara,Nagy, Rose,Pennypacker, Brenda,Perkins, James J.,Prueksaritanont, Thomayant,Rodan, Gideon A.,Varga, Sandor L.,Wesolowski, Greg A.,Zartman, Amy E.,Rodan, Sevgi B.,Duggan, Mark E.
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p. 4790 - 4798
(2007/10/03)
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- Kinetic study of microwave-assisted Wittig reaction of stabilised ylides with aromatic aldehydes
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The Wittig reaction of a pool of stabilised ylides and aromatic aldehydes was carried out in a microwave oven. Only a few minutes were needed for high conversion rates under microwave heating in comparison to hour time with traditional methods.
- Frattini, Sara,Quai, Monica,Cereda, Enzo
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p. 6827 - 6829
(2007/10/03)
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- Synthesis and antifungal activities of R-102557 and related dioxane- triazole derivatives
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Novel triazole compounds with a dioxane ring were synthesized. Condensation of the diol precursor 10 with various aromatic aldehydes 11 - 13 under acidic conditions afforded a series of dioxane-triazole compounds 14 - 16. The antifungal activities of the compounds 14 - 16 were evaluated in vivo in mice infection models against Candida and Aspergillus species. High activities were seen for the derivatives with one or two double bond(s) and an aromatic ring substituted with an electron-withdrawing group in the side chain. Among the derivatives, R-102557 (16R: Ar=4-(2,2,3,3- tetrafluoropropoxy)phenyl) showed excellent in vivo activities against Candida, Aspergillus and Cryptococcus species. It also showed high tolerance in a preliminary toxicity study in rats.
- Oida, Sadao,Tajima, Yawara,Konosu, Toshiyuki,Nakamura, Yoshie,Somada, Atsushi,Tanaka, Teruo,Habuki, Shinobu,Harasaki, Tamako,Kamai, Yasuki,Fukuoka, Takashi,Ohya, Satoshi,Yasuda, Hiroshi
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p. 694 - 707
(2007/10/03)
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- Synthesis and evaluation of a series of novel 2-[(4- chlorophenoxy)methyl]benzimidazoles as selective neuropeptide Y Y1 receptor antagonists
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A series of novel benzimidazoles (BI) derived from the indole 2 was synthesized and evaluated as selective neuropeptide Y (NPY) Y1 receptor antagonists with the aim of developing antiobesity drugs. In our SAR approach, the (4-chlorophenoxy)methyl group at
- Zarrinmayeh, Hamideh,Nunes, Anne M.,Ornstein, Paul L.,Zimmerman, Dennis M.,Arnold, M. Brian,Schober, Douglas A.,Gackenheimer, Susan L.,Bruns, Robert F.,Hipskind, Philip A.,Britton, Thomas C.,Cantrell, Buddy E.,Gehlert, Donald R.
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p. 2709 - 2719
(2007/10/03)
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- Activated Alumina Promoted Stereoselective Wittig Reaction
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Aldehydes undergo efficient E-stereoselective Wittig olefination with alkylidenetriphenylphosphoranes in the presence of activated alumina under mild conditions with high yields.
- Dhavale, Dilip D.,Sindkhedkar, Milind D.,Mali, Raghao S.
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p. 414 - 415
(2007/10/03)
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- (3-pyridyl)tetrafuran-2-yl substituted carboxylic acids
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Disclosed are compounds of formula STR1 wherein R is OR'' and R'' is aryl-lower alkyl, biaryl-lower alkyl, lower alkyl or cycloalkyl-lower alkyl; or R is arylsulfonylamido;n is 1, 2 or 3;m is 1, 2 or 3;Y is vinylene, ethylene or methyleneoxy; a stereoisomer or optical isomer thereof; and their pharmaceutically acceptable esters or salts; which are useful as thromboxane synthetase inhibitors and thromboxane receptor antagonists.
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- Symmetry-Based Inhibitors of HIV Protease. Structure-Activity Studies of Acylated 2,4-Diamino-1,5-diphenyl-3-hydroxypentane and 2,5-Diamino-1,6-diphenylhexane-3,4-diol
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The structure-activity relationships in two series of novel, symmetry-based inhibitors of HIV protease, the enzyme responsible for maturation of the human immunodeficiency virus, are described.Beginning with lead compounds 3-6, the effect of adding polar, heterocyclic end groups to one or both ends of the symmetric or pseudosymmetric inhibitors was probed.Aqueous solubility was enhanced >1000-fold while maintaining potent inhibition of purified HIV-1 protease and anti-HIV activity in vitro.Pharmacokinetic studies in rats indicated a substantial difference in the absorption properties of mono-ol-based and diol-based inhibitors.The oral bioavailability of inhibitor 19 in rats was 19percent; however, the Cmax obtained failed to exceed the anti-HIV EC50 in vitro.Substantial plasma levels of potent inhibitors of the diol class were not obtained after oral administration in rats; however, the optimal combination of aqueous solubility and in vitro antiviral activity of several inhibitors support their potential use in intravenous therapy.
- Kempf, Dale J.,Codacovi, Lynnmarie,Wang, Xiu Chun,Kohlbrenner, William E.,Wideburg, Norman E.,et al.
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p. 320 - 330
(2007/10/02)
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- Substituted heterocyclic derivatives useful as platelet aggregation inhibitors
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Novel substituted heterocyclic derivatives are provided which inhibit platelet aggregation. This invention also pertains to pharmaceutical compositions and methods of using such derivatives.
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- HMPT/zinc mediated one-pot convenient synthesis of β-substituted acrylates
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A new one pot convenient synthesis of β-substituted acrylates involving the reaction of aldehydes with ethyl bromoacetate via concomitant Reformatsky and dehydration reactions prompted by HMPT and zinc has been described.
- Khan, R H,Rastogi, R C
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- Palladium-catalyzed conversion of aldehydes to alkenes in the presence of tri-n-butylphosphine
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Palladium-catalyzed conversion of aldehydes to alkenes in the presence of tri-n-butylphosphine is described.
- Shen, Yanchang,Zhou, Yuefen
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p. 513 - 514
(2007/10/02)
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- Palladium-Catalyzed Cyclocarbonylation of 3-(Heteroaryl)allyl Acetates1
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Acetoxybenzofurans, acetoxybenzothiophenes, acetoxyindoles, and acetoxycarbazoles were obtained in high yields by cyclocarbonylation of 3-furyl-, 3-thienyl-, 3-pyrrolyl-, and 3-indolylallyl acetates, respectively, in the presence of Ac2O, NEt3, and a catalytic amount of PdCl2(PPh3)2 at 130 - 170 deg C under 50 - 70 atm of CO. 3-(3-Furyl)allyl and 3-(3-thienyl)allyl acetates cyclized selectively at the 2-position of the heterocyclic nucleus to give 7-acetoxybenzofuran and 7-acetoxybenzothiophene, respectively.The synthetic utility of the reaction was demonstrated by the synthesis of canabifuran from isothymol.
- Iwasaki, Masakazu,Kobayashi, Yoshihiro,Li, Ji-Ping,Matsuzaka, Hiroyuki,Ishii, Youichi,Hidai, Masanobu
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p. 1922 - 1927
(2007/10/02)
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