- Pd-Catalyzed Carbonylative Synthesis of 4H-Benzo[d][1,3]Oxazin-4-Ones Using Benzene-1,3,5-Triyl Triformate as the CO Source
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A facile synthesis of 4H-benzo[d][1,3]oxazin-4-one derivatives by Pd-catalyzed carbonylative cross-coupling between N-(ortho-bromoaryl)amides and benzene-1,3,5-triyl triformate (TFBen) was developed. This procedure does not require the toxic and flammable gas CO as the carbonyl source and tolerates a wide scope of functional groups. Remarkably, 4H-benzo[d][1,3]oxazin-4-ones incorporated to natural products and drugs can be constructed by this method.
- Zheng, Yan,Dong, Mengke,Qu, Erdong,Bai, Jin,Wu, Xiao-Feng,Li, Wanfang
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supporting information
p. 16219 - 16224
(2021/10/06)
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- Equivalent Loading of Directed Arenes in Pd(II)-Catalyzed Oxidative Cross-Coupling of Aryl C-H Bonds at Room Temperature
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The unsymmetrical biaryls (Ar1-Ar2) produced by the catalytic cross-couplings of aryl halides (Ar1-halo) with aryl metallics (Ar2-M) in the loading ratio of 1:1 are popular in chemical synthesis. In contrast, there has been less precedence on the same biaryls produced effectively from two normal aryl C-H bonds with equivalent loading. Here, we report that, in a palladium/oxidant/acid catalytic system at room temperature, one arene (Ar1-H, 1 equiv) can highly selectively couple with the other one (Ar2-H, 1 equiv) to afford the target Ar1-Ar2 just by controlling the directing groups and the substituted groups on their phenyl rings. The utility of this one-one cross-coupling is also demonstrated by synthesis of a few bioactive molecules.
- Mei, Chong,Zhao, Mengdi,Lu, Wenjun
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p. 2714 - 2733
(2021/02/01)
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- Novel and efficient heterogeneous polymer supported copper catalyst for synthesis of 2-substituted Benzoxazoles from 2-Haloanilides
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A novel polymer supported copper complex is prepared by the immobilization of copper iodide on chemically modified polyacrylonitrile and its application in heterogeneous catalysis is described. The catalyst was prepared by easy method via synthetic modification of Polyacrylonitrile (PAN) using ethylene diamine followed by the complexation with CuI. After characterization, this complex was explored as a green and efficient heterogeneous catalyst for the synthesis of 2-benzoxazoles from 2-haloanilides. The reaction was performed without adding additional ligand and the catalyst shows activity over a broad range of substrates with quantitative product yields. The catalyst was easily recovered by simple filtration and reused successfully for further cycle.
- Saranya, Thachora Venu,Sruthi, Pambingal Rajan,Raj, Veena,Anas, Saithalavi
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supporting information
(2021/02/27)
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- Photocatalyst- And Transition-Metal-Free Visible-Light-Promoted Intramolecular C(sp2)-S Formation
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A photocatalyst- and transition-metal-free visible-light-induced cyclization of ortho-halothiobenzanilides has been developed. Upon irradiation with visible light, substrates undergo dehalogenative cyclization to 2-aryl benzothiazoles with high efficiency and selectivity. This photocyclization exhibits a high tolerance to various functional groups, is applicable for the synthesis of 2-alkyl benzothiazoles, and is easy to set up for gram-scale reaction.
- Wang, Hao,Wu, Qi,Zhang, Jian-Dong,Li, Hai-Yan,Li, Hong-Xi
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supporting information
p. 2078 - 2083
(2021/04/05)
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- Nickel(II)- And Silver(I)-Catalyzed C-H Bond Halogenation of Anilides and Carbamates
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ortho -C-H bond halogenation of anilides and N -aryl carbamates using easily available N -halosuccinimides (NXS) as the active halogenation reagent in the presence of nickel or silver catalyst has been developed. This method provides a new approach to 2-haloanilides and carbamates, which may serve as starting materials for the synthesis of pharmaceutically and biologically active compounds.
- Kianmehr, Ebrahim,Afaridoun, Hadi
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p. 1513 - 1523
(2020/12/14)
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- Site-Selective C–H Functionalization of (Hetero)Arenes via Transient, Non-symmetric Iodanes
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Fosu, Hambira, and colleagues describe the direct C–H functionalization of medicinally relevant arenes or heteroarenes. This strategy is enabled by transient generation of reactive, non-symmetric iodanes from anions and PhI(OAc)2. The site-selective incorporation of Cl, Br, OMs, OTs, and OTf to complex molecules, including within medicines and natural products, can be conducted by the operationally simple procedure included herein. A computational model for predicting site selectivity is also included. The discovery of new medicines is a time- and labor-intensive process that frequently requires over a decade to complete. A major bottleneck is the synthesis of drug candidates, wherein each complex molecule must be prepared individually via a multi-step synthesis, frequently requiring a week of effort per molecule for thousands of candidates. As an alternate strategy, direct, post-synthetic functionalization of a lead candidate could enable this diversification in a single operation. In this article, we describe a new method for direct manipulation of drug-like molecules by incorporation of motifs with either known pharmaceutical value (halides) or that permit subsequent conversion (pseudo-halides) to medicinally relevant analogs. This user-friendly strategy is enabled by combining commercial iodine reagents with salts and acids. We expect this simple method for selective, post-synthetic incorporation of molecular diversity will streamline the discovery of new medicines. A strategy for C–H functionalization of arenes and heteroarenes has been developed to allow site-selective incorporation of various anions, including Cl, Br, OMs, OTs, and OTf. This approach is enabled by in situ generation of reactive, non-symmetric iodanes by combining anions and bench-stable PhI(OAc)2. The utility of this mechanism is demonstrated via para-selective chlorination of medicinally relevant arenes, as well as site-selective C–H chlorination of heteroarenes. Spectroscopic, computational, and competition experiments describe the unique nature, reactivity, and selectivity of these transient, unsymmetrical iodanes.
- Fosu, Stacy C.,Hambira, Chido M.,Chen, Andrew D.,Fuchs, James R.,Nagib, David A.
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supporting information
p. 417 - 428
(2019/02/14)
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- ERBB/BTK INHIBITORS
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Disclosed are compounds inhibiting ErbBs (e. g., EGFR or Her 2), especially mutant forms of ErbBs, and BTK, pharmaceutically acceptable salts, hydrates, solvates or stereoisomers thereof and pharmaceutical compositions comprising the compounds. The compou
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Page/Page column 198; 60
(2019/08/26)
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- Facile synthesis of 2-benzoxazoles via CuI/2,2'-bipyridine catalyzed intramolecular C–O coupling of 2-haloanilides
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Development of newer methods for the synthesis of Benzoxazoles has of greater interest due to their wide range of biological activities and pharmaceutical importance. We herein report a facile and general method for the synthesis of 2-substituted Benzoxazoles via copper catalyzed intramolecular C–O cross-coupling of 2-haloanilides. A combination of CuI (5 mol%), 2,2'-bipyridine (10 mol%), Cs2CO3 (2 equiv.) in DMF solvent with 4 ? molecular sieves at 140 °C, illustrated the scope for tuning the reactivity of 2-haloanilides toward the selective formation of a series of 2-alkyl benzoxazole derivatives in moderate to good yields. This is the first systematic study using CuI/2,2'-Bipyridine as the catalytic system for the synthesis of 2-substituted Benzoxazoles. The outcome of the reaction was found to be significantly influenced by the aromatic and amide substituents of 2-haloanilides.
- Venu Saranya, Thachora,Rajan Sruthi, Pambingal,Anas, Saithalavi
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supporting information
p. 297 - 307
(2019/01/18)
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- Domino Pd0-Catalyzed C(sp3)–H Arylation/Electrocyclic Reactions via Benzazetidine Intermediates
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The Pd0-catalyzed C(sp3)-H arylation of 2-bromo-N-methylanilides leads to unstable benzazetidine intermediates that rearrange to benzoxazines through 4π electrocyclic ring-opening and 6π electrocyclization. The introduction of a bulky, non-activatable amide group on the nitrogen atom was key to favor the challenging reductive elimination step and disfavor undesired reaction pathways.
- Rocaboy, Ronan,Dailler, David,Zellweger, Florian,Neuburger, Markus,Salomé, Christophe,Clot, Eric,Baudoin, Olivier
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supporting information
p. 12131 - 12135
(2018/09/11)
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- Rhodium(III)-catalysed, redox-neutral C(sp2)-H alkenylation using pivalimide as a directing group with internal alkynes
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In the presence of [RhCp?Cl2]2, N-pivaloyl anilines react with internal alkynes to give the corresponding 2-alkenylpivalimides under redox neutral conditions through C-H activation. This redox neutral hydroarylation, which does not require an external organic acid, unlocks a regioselective synthetic route to 2-alkenyl anilines and is generally applicable to diversely substituted electron rich and electron poor pivalimides.
- Kathiravan, Subban,Nicholls, Ian A.
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supporting information
p. 1 - 4
(2016/12/23)
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- A unified strategy for silver-, base-, and oxidant-free direct arylation of C-H bonds
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Here, we report a dual catalytic approach for room temperature direct arylation of C-H bonds with aryldiazonium salts as a simple aryl group donor, also working as an internal oxidant via C-N2 bond cleavage. This unified strategy has been achieved by the synergistic combination of visible-light metal-free photoredox and palladium catalysis under silver-, base- and/or additive-free conditions. The broad substrate scope, functional group tolerance, excellent regioselectivity and redox-neutral conditions of this process make it attractive for the effective synthesis of a wide range of important N-heterocyclic commodities such as dibenzo[b,d]azepine, carbazole and phenanthridine.
- Sahoo, Manoj K.,Midya, Siba P.,Landge, Vinod G.,Balaraman, Ekambaram
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supporting information
p. 2111 - 2117
(2017/07/24)
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- Monoprotected l-Amino Acid (l-MPAA), Accelerated Bromination, Chlorination, and Iodination of C(sp2)?H Bonds by Iridium(III) Catalysis
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Halogenated arenes are important structural motifs commonly found in biologically active molecules and used for a variety of transformations in organic synthesis. Herein, we report the mono-protected l-amino acid (l-MPAA) accelerated iridium(III)-catalyzed halogenation of (hetero)anilides at room temperature. This reaction constitutes the first example of an iridium(III)/l-MPAA-catalyzed general halogenation of (hetero)arenes through C(sp2)?H activation. Furthermore, we demonstrate the potential utility of our method through its use in the synthesis of a quinolone derivative.
- Kathiravan, Subban,Nicholls, Ian A.
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supporting information
p. 7031 - 7036
(2017/05/29)
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- Enantiopure Sulfinyl Aniline as a Removable and Recyclable Chiral Auxiliary for Asymmetric C(sp3)?H Bond Activation
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An original and recyclable chiral bidentate aniline-sulfoxide-based directing group has been developed. This auxiliary allows challenging stereoselective Pd-catalyzed direct functionalization of small cycloalkanes through C–aryl and C–alkyl bond formation. Although moderate diastereoselectivities are observed, both optically pure enantiomers of the highly functionalized products can be obtained separately by simple silica gel chromatography and cleavage of the chiral auxiliary. This strategy was further applied to the preparation of enantiomerically pure 1,2,3-trisubstituted cyclopropane carboxylic acid derivatives, with three stereogenic centers and bearing both alkyl and aromatic substituents. These molecular scaffolds are not yet reported in the literature. The synthetic utility of this approach is validated by the chiral auxiliary being readily cleaved and recovered posteriori to the C?H activation step, without deterioration of its optical purity. Finally, an unprecedented palladacycle intermediate generated through C?H activation of the cyclopropane moiety has been isolated and fully characterized. Initial DFT calculations shed additional light on the reactivity of this original intermediate.
- Jerhaoui, Soufyan,Chahdoura, Faouzi,Rose, Clémence,Djukic, Jean-Pierre,Wencel-Delord, Joanna,Colobert, Fran?oise
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supporting information
p. 17397 - 17406
(2016/11/23)
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- Palladium-catalyzed C(sp3)-H activation: A facile method for the synthesis of 3,4-dihydroquinolinone derivatives
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3,4-Dihydroquinolinones were synthesized by the palladium-catalyzed, oxidative-addition-initiated activation and arylation of inert C(sp 3)-H bonds. Pd(OAc)2 and P(o-tol)3 were used as the catalyst and ligand, respectively, to improve the efficiency of the reaction. A further advantage of this reaction is that it could be performed in air. A relatively rare seven-membered palladacycle was proposed as a key intermediate of the catalytic cycle.
- Yan, Jia-Xuan,Li, Hu,Liu, Xiang-Wei,Shi, Jiang-Ling,Wang, Xin,Shi, Zhang-Jie
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supporting information
p. 4945 - 4949
(2014/05/20)
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- Palladium-catalyzed carbonylative synthesis of benzoxazinones from N -(o -bromoaryl)amides using paraformaldehyde as the carbonyl source
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Carbonylation reactions have been widely used in organic synthesis. However, the manipulation of toxic and pressurized carbon monoxide limited their applications in organic laboratories. The search for alternative carbonyl sources as an important method for carbonylative organic synthesis is spreading. Herein, a series of substituted benzoxazinones were synthesized from N-(o-bromoaryl)amides by palladium-catalyzed carbonylation with paraformaldehyde as the carbonyl source, which is inexpensive, stable, and easy to use. Notably, this is the first example of using paraformaldehyde as the CO source in palladium-catalyzed carbonylative synthesis of heterocycles.
- Li, Wanfang,Wu, Xiao-Feng
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p. 10410 - 10416
(2015/02/19)
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- Mild C - H halogenation of anilides and the isolation of an unusual palladium(I)-palladium(II) species
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Reducing the load: A facile palladium-catalyzed ortho-selective bromination and chlorination of anilides occurs under aerobic conditions at room temperature when N-halosuccinimides (NXS) are used in the presence of p-toluenesulfonic acid (PTSA). The orthopalladated PTSA complex is not only catalytically competent but also undergoes a reductive process to yield an unusual PdI-PdII tetramer (see structure; Pdgreen, Ored, Syellow, Cgray). Copyright
- Bedford, Robin B.,Haddow, Mairi F.,Mitchell, Charlotte J.,Webster, Ruth L.
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p. 5524 - 5527
(2011/07/31)
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- Umpolung direct arylation reactions: Facile process requiring only catalytic palladium and substoichiometric amount of silver salts
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An umpolung direct arylation process is described. The reaction requires only a catalytic amount of Pd(OAc)2 and a substoichiometric amount of silver salts, without any external base or ligand to proceed. The directed oxidative insertion of the transition metal followed by the coupling into the C-H bond of an unactivated arene has surprisingly not yet been reported, despite the clear advantages in the ease of starting material synthesis. The reaction is regioselective with regards to the arene partner, and the role of the acetate and carbonate groups has been elucidated. This methodology adds to the very few examples of benzene coupling without the inclusion of electron-withdrawing groups to increase acidity.
- Mousseau, James J.,Vallee, Frederic,Lorion, Melanie M.,Charette, Andre B.
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supporting information; experimental part
p. 14412 - 14414
(2010/12/24)
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- Solvent-free aromatic C-H functionalisation/halogenation reactions
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The solvent-free, palladium-catalysed reaction of anilides with CuCl 2 in the presence or absence of copper acetate yields ortho-chlorinated anilides in good to excellent yields, even on a large scale (100 mmol). By contrast, the equivalent reactions with copper bromide, either solvent free or in 1,2-dichloroethane, in the presence or absence of palladium, under air or inert conditions, gave the products of simple electrophilic bromination. Mechanistic studies highlighted the involvement of palladacyclic intermediates, one of which was characterised crystallographically, which undergo subsequent reaction with copper(ii) chloride to yield the chlorinated anilide products.
- Bedford, Robin B.,Engelhart, Jens U.,Haddow, Mairi F.,Mitchell, Charlotte J.,Webster, Ruth L.
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supporting information; experimental part
p. 10464 - 10472
(2011/01/05)
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- PROCESSES AND INTERMEDIATES FOR PRODUCING AMINOBENZIMIDAZOLE UREAS
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The present invention relates to processes and intermediates for the preparation of compounds useful as inhibitors of bacterial gyrase and Topoisomerase IV (Topo IV).
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Page/Page column 37-38
(2009/06/27)
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- SOLID FORMS OF 1-ETHYL-3-(5-(5-FLUOROPYRIDIN-3-YL)-7-(PYRIMIDIN-2-YL)-1H-BENZO[D]IMIDAZOL-2-YL)UREA
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Solid forms of crystalline1-ethyl-3-(5-(5-fluoropyridin-3-yl)-7-(pyrimidin-2-yl)- 1H-benzo[d]imidazol-2-yl)urea, compositions containing solid forms of crystalline 1- ethyl-3-(5-(5-fluoropyridin-3-yl)-7-(pyrimidin-2-yl)-1H-benzo[d]imidazol-2-yl)urea and m
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Page/Page column 57-58
(2009/07/17)
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- Manipulation of an intramolecular NH ... O hydrogen bond by photoswitching between stable E/Z isomers of the cinnamate framework
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Novel carboxylic acid derivatives were synthesized, which allowed switching of the intramolecular distance between amide group and carboxylic oxygen atoms using E to Z photoisomerization of the cinnamate framework. An intramolecular NH ... O hydrogen bond was formed in the Z carboxylate compound not only in solution but also in the solid state. The pKa value of the carboxylic acid was lowered as a consequence of the E/Z photoisomerization. The Royal Society of Chemistry.
- Matsuhira, Takashi,Yamamoto, Hitoshi,Okamura, Taka-Aki,Ueyama, Norikazu
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experimental part
p. 1926 - 1933
(2009/01/31)
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- A palladium-catalyzed regiospecific synthesis of N-aryl benzimidazoles
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(Chemical Equation Presented) Highly tolerated: A catalytic method employing [Pd2(dba)3] and XPhos or RuPhos permits the efficient synthesis of N-aryl benzimidazoles in regioisomerically pure form starting from ortho-halo-anilides (see scheme), and tolerates a wide range of functional groups, dba = trans,trans-dibenzylideneacetone.
- Zheng, Nan,Anderson, Kevin W.,Huang, Xiaohua,Nguyen, Hanh Nho,Buchwald, Stephen L.
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p. 7509 - 7512
(2008/09/17)
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- Ruthenium-catalyzed carbon-carbon bond formation via the cleavage of an unreactive aryl carbon-nitrogen bond in aniline derivatives with organoboronates
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The RuH2(CO)(PPh3)3-catalyzed reaction of 2-amino-6-methylacetophenone with phenylboronic acid 2,2-dimethyl-1,3-propanediol ester in refluxing toluene gave the corresponding phenylation product in 83% yield via aryl carbon
- Ueno, Satoshi,Chatani, Naoto,Kakiuchi, Fumitoshi
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p. 6098 - 6099
(2008/02/08)
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- INTERMEDIATE IN PRODUCTION OF [2-(3,3,5,5-TETRAMETHYLCYCLOHEXYL)PHENYL]PIPERAZINE COMPOUND
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A compound represented by the general formula below or a salt thereof is a useful intermediate in the production of a [2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazine compound that has excellent cell adhesion inhibitory effect and cell invasion inhibitory effect and therefore is useful as a therapeutic or prophylactic agent for various inflammatory diseases and autoimmune diseases induced by the adhesion and invasion of leukocytes, such as inflammatory bowel diseases (particularly ulcerative colitis or Crohn's disease), irritable bowel syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, asthma and atopic dermatitis. [Chemical formulae] wherein R1 and R2 independently represent a hydrogen atom or an amino-protecting group for an amino group, or R1 and R2 may together form a pyrrole ring which may have a substituent.
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Page/Page column 33
(2008/06/13)
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- Synthesis of 2-substituted-benzothiazoles by palladium-catalyzed intramolecular cyclization of o-bromophenylthioureas and o-bromophenylthioamides
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2-Amino-, and 2-alkyl-benzothiazoles have been efficiently prepared by palladium catalyzed cyclization of o-bromophenylthioureas and o-bromophenylthiamides. Results were best with the Pd2(dba)3/monophosphine catalytic system.
- Benedí, Carolina,Bravo, Fernando,Uriz, Pedro,Fernández, Elena,Claver, Carmen,Castillón, Sergio
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p. 6073 - 6077
(2007/10/03)
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- 1H-1,3-benzazaphospholes: The organometallic route and a new three-step synthesis with reductive ring closure
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Primary and N-secondary 2-phosphanylanilines were synthesized via metallation of 2-bromoanilines, coupling with CIP(NMe2)2, alcoholysis and reduction with LiAlH4, and subsequently reacted with formimidoester hydrochloride to give 1,3-benzazaphospholes. For 1H-1,3-benzazaphospholes, a shorter alternative three-step synthesis was developed, based on N-acylation of 2-bromoaniline, NiCl2-catalyzed arylation of triethyl phosphite and a new reductive cyclization of amidophosphonic acid ester with excess LiAlH4.
- Bansal, Raj K.,Gupta, Neelima,Heinicke, Joachim,Nikonov, George N.,Saguitova, Farida,Sharma, Dinesh C.
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p. 264 - 269
(2007/10/03)
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- Electroreduction of Organic Compounds, 19. Formation of Benzoanellated Sulfur Heterocycles by Intramolecular Cathodic Cyclization of Dithiocarboxylic Esters
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Cathodic reduction of aryl (3) and benzyl (5) dithiopivaloates and related dithioesters with leaving groups at the benzene ring or a side chain yield the sulfur heterocycles 23, 30 - 32, and 34 depending on the nature of the starting material and the reaction conditions.In the case of the α-oxo-dithioester 22, thioindigo (44) is formed. - The corresponding thioamides 14, 16, and 18 show a strong tendency to reductive dehalogenation but the S,N-heterocycles 38 and 39 are also formed in minor amounts. - The formation of the rearranged products 29 - 32, and 34 isdiscussed in terms of C,S-splitting in the primarily formed radical anion and subsequent C,C-coupling of the fragments and follow-up reactions.Key Words: Dithiopivaloates, S-aryl, S-benzyl / Electroreduction
- Gade, Thomas,Streek, Michael,Voss, Juergen
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p. 127 - 142
(2007/10/02)
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- Uses of aza-cope rearrangement-mannich cyclization reactions to achieve a general entry to melodinus and aspidosperma alkaloids. stereocontrolled total syntheses of (±)-deoxoapodine, (±)-meloscine, and (±)-epimeloscine and a formal synthesis of (±)-1-acetylaspidoalbidine
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The first total syntheses of the structurally unusual pentacyclic Melodinus alkaloids (±)-meloscine (1) and (±)-epimeloscine (2) and the hexacyclic Aspidosperma alkaloids (±)-deoxoapodine (4) are reported. The syntheses proceed via a highly functionalized common tetracyclic intermediate 7, which is accessed (with complete stereocontrol) by the title rearrangement of pyrindinol 10. These syntheses provide excellent examples of the power of tandem of aza-Cope rearrangement-Mannich cyclization reactions as the key element of stereocontrolled alkaloid synthesis design.
- Overmann, Larry E.,Robertson, Graeme M.,Robichaud, Albert J.
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p. 2598 - 2610
(2007/10/02)
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- Synthesis Applications of Cationic Aza-Cope Rearrangements. Stereocontrolled Synthesis of Hexahydro-1H-pyrrolocarbazoles
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The synthesis of a series of 5-substituted octahydro-1H-pyrrolocarbazoles 4, potential intermediates for the synthesis of the Strychnos alkaloid akuammicine 2, is described.The known β-keto ester 9 was converted to the (E)-epoxy alcohol 7 in 39perc
- Overman, Larry E.,Angle, Steven R.
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p. 4021 - 4028
(2007/10/02)
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- METHODOLOGY FOR THE FACILE AND REGIO-CONTROLLED SYNTHESIS OF INDOLES
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A method based on organodimetallic reagents is described for the regiocontrolled synthesis of indoles which proceeds, generally, in one to two operations from commercially or readily available reactants.The method is applied to the synthesis of indole itself, 2-substituted, 3-substituted, 2,3-disubstituted and 6-substituatd indoles.
- Wender, Paul A.,White, Alan W.
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p. 3767 - 3776
(2007/10/02)
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