- PdII-Catalyzed Site-selective β- and γ-C(sp3)-H Arylation of Primary Aldehydes Controlled by Transient Directing Groups
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Pd(II)-catalyzed site-selective β- and γ-C(sp3)-H arylation of primary aldehydes is developed by rational design of L,X-type transient directing groups (TDG). External 2-pyridone ligands are identified to be crucial for the observed reactivity. By minimizing the loading of acid additives, the ligand effect is enhanced to achieve high reactivities of the challenging primary aldehyde substrates. Site selectivity can be switched from the proximate to the relatively remote position by changing the bite angle of TDG to match the desired palladacycle size. Experimental and computational investigations support this rationale for designing TDG to potentially achieve remote site-selective C(sp3)-H functionalizations.
- Li, Yi-Hao,Ouyang, Yuxin,Chekshin, Nikita,Yu, Jin-Quan
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supporting information
p. 4727 - 4733
(2022/04/07)
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- Ligand-controlled divergent dehydrogenative reactions of carboxylic acids via C–H activation
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Dehydrogenative transformations of alkyl chains to alkenes through methylene carbon-hydrogen (C–H) activation remain a substantial challenge. We report two classes of pyridine-pyridone ligands that enable divergent dehydrogenation reactions through palladium-catalyzed b-methylene C–H activation of carboxylic acids, leading to the direct syntheses of a,b-unsaturated carboxylic acids or g-alkylidene butenolides. The directed nature of this pair of reactions allows chemoselective dehydrogenation of carboxylic acids in the presence of other enolizable functionalities such as ketones, providing chemoselectivity that is not possible by means of existing carbonyl desaturation protocols. Product inhibition is overcome through ligand-promoted preferential activation of C(sp3)–H bonds rather than C(sp2)–H bonds or a sequence of dehydrogenation and vinyl C–H alkynylation. The dehydrogenation reaction is compatible with molecular oxygen as the terminal oxidant.
- Wang, Zhen,Hu, Liang,Chekshin, Nikita,Zhuang, Zhe,Qian, Shaoqun,Qiao, Jennifer X.,Yu, Jin-Quan
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p. 1281 - 1285
(2021/12/10)
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- Enantioselective Synthesis of N?H-Free 1,5-Benzothiazepines
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An enantioselective sulfa-Michael-cyclization reaction was developed for the synthesis of 1,5-benzothiazepines with versatile pharmacological activities. The reaction between 2-aminothiophenol and α,β-unsaturated pyrazoleamides gave direct access to N?H-free 1,5-benzothiazepines in the presence of a chiral N,N′-dioxide/Yb(OTf)3complex. Excellent enantioselectivities (up to 96 % ee) and high yields (up to 99 %) were obtained for a broad range of substrates under mild reaction conditions. This method provided a facile approach to the antidepressant drug (R)-(?)-Thiazesim.
- Wang, Guojin,Tang, Yu,Zhang, Yu,Liu, Xiaohua,Lin, Lili,Feng, Xiaoming
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supporting information
p. 554 - 557
(2017/01/18)
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- Enantioselective Intermolecular Addition of Aliphatic Amines to Acyclic Dienes with a Pd-PHOX Catalyst
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We report a method for the catalytic, enantioselective intermolecular addition of aliphatic amines to acyclic 1,3-dienes. In most cases, reactions proceed efficiently at or below room temperature in the presence of 5 mol % of a Pd catalyst bearing a PHOX ligand, generating allylic amines in up to 97:3 er. The presence of an electron-deficient phosphine within the ligand not only leads to a more active catalyst but also is critical for achieving high site selectivity in the transformation.
- Adamson, Nathan J.,Hull, Ethan,Malcolmson, Steven J.
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supporting information
p. 7180 - 7183
(2017/06/05)
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- Method for synthesizing alpha, beta-unsaturated acid by using formic acid and alkine
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The invention relates to a method for synthesizing alpha, beta-unsaturated acid by using formic acid and alkine, in particular to a method for synthesizing alpha, beta-unsaturated acid by using formic acid and alkine under the effect of a nickel catalyst. The consumption of the catalyst is 0.01 to 2 mol percent of the quantity of a substrate substance; the consumption of estolide is 3 to 30 mol percent of the quantity of the substrate substance; the pressure of acetylene gas is 1 to 10 MPa; the reaction temperature is 25 to 100 DEG C; the reaction time is 5 to 12 hours. The method has the advantages that the existing alkine hydrocarboxylation defects are overcome; the use of toxic carbon monoxide gas does not needed; the reaction conditions of the whole process are mild; the efficiency is high; the selectivity is good; the method belongs to a method for preparing the alpha, beta-unsaturated acid with the advantages that the method conforms to green chemistry and has good application aspects; good industrial application prospects are realized.
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Paragraph 0024
(2016/10/27)
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- Nickel-catalyzed hydrocarboxylation of alkynes with formic acid
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A protocol for nickel-catalyzed hydrocarboxylation of alkynes with formic acid was developed. The protocol allowed for highly efficient synthesis of acrylic acid with a TON of up to 7700.
- Hou, Jing,Yuan, Ming-Lei,Xie, Jian-Hua,Zhou, Qi-Lin
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supporting information
p. 2981 - 2984
(2016/06/06)
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- Discovery of vinylcycloalkyl-substituted benzimidazole TRPM8 antagonists effective in the treatment of cold allodynia
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Thermosensitive transient receptor potential melastatin 8 (TRPM8) antagonists are considered to be potential therapeutic agents for the treatment of cold hypersensitivity. The discovery of a new class of TRPM8 antagonists that shows in vivo efficacy in the rat chronic constriction injury (CCI)-induced model of neuropathic pain is described.
- Calvo, Raul R.,Meegalla, Sanath K.,Parks, Daniel J.,Parsons, William H.,Ballentine, Shelley K.,Lubin, Mary Lou,Schneider, Craig,Colburn, Raymond W.,Flores, Christopher M.,Player, Mark R.
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scheme or table
p. 1903 - 1907
(2012/04/04)
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- Discovery of 4-[4-({(3R)-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-2,5- dioxo-1,4,9-triazaspiro[5.5]undec-9-yl}methyl)phenoxy]benzoic acid hydrochloride: A highly potent orally available CCR5 selective antagonist
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Based on the original spirodiketopiperazine design framework, further optimization of an orally available CCR5 antagonist was undertaken. Structural hybridization of the hydroxylated analog 4 derived from one of the oxidative metabolites and the new orally available non-hydroxylated benzoic acid analog 5 resulted in another potent orally available CCR5 antagonist 6a as a clinical candidate. Full details of a structure-activity relationship (SAR) study and ADME properties are presented.
- Nishizawa, Rena,Nishiyama, Toshihiko,Hisaichi, Katsuya,Minamoto, Chiaki,Murota, Masayuki,Takaoka, Yoshikazu,Nakai, Hisao,Tada, Hideaki,Sagawa, Kenji,Shibayama, Shiro,Fukushima, Daikichi,Maeda, Kenji,Mitsuya, Hiroaki
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experimental part
p. 4028 - 4042
(2011/08/21)
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- Spirodiketopiperazine-based CCR5 antagonist: Discovery of an antiretroviral drug candidate
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Following the discovery that hydroxylated derivative 3 (Fig. 1) was one of the oxidative metabolites of the original lead 1, it was found that hydroxylated compound 4 possesses higher in vitro anti-HIV potency than the corresponding non-hydroxylated compo
- Nishizawa, Rena,Nishiyama, Toshihiko,Hisaichi, Katsuya,Minamoto, Chiaki,Matsunaga, Naoki,Takaoka, Yoshikazu,Nakai, Hisao,Jenkinson, Stephen,Kazmierski, Wieslaw M.,Tada, Hideaki,Sagawa, Kenji,Shibayama, Shiro,Fukushima, Daikichi,Maeda, Kenji,Mitsuya, Hiroaki
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scheme or table
p. 1141 - 1145
(2011/04/16)
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- BENZIMIDAZOLE DERIVATIVES USEFUL AS TRP M8 RECEPTOR MODULATORS
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The present invention is directed to benzimidazole derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by TRP M8 (transient receptor potential M8 channel). More particularly, the compounds of the present invention are useful in the treatment of inflammatory pain, inflammatory hyperalgesia, inflammatory hypersensitivity condition, neuropathic pain, neuropathic cold allodynia, inflammatory somatic hyperalgesia, inflammatory visceral hyperalgesia, cardiovascular disease aggravated by cold, anxiety and depression.
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Page/Page column 46
(2010/12/17)
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- HETEROCYCLIC DERIVATIVE HAVING INHIBITORY ACTIVITY ON TYPE-I 11 -HYDROXYSTEROID DEHYDROGENASE
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Disclosed is a compound which is useful as an 11β-hydroxysteroid dehydrogenase type 1 inhibitor. A compound represented by the formula: its pharmaceutically acceptable salt, or a solvate thereof, wherein X is O or S, a broken line and a wavy line represent the presence or the absence of a bond, (i) when a broken line represents the presence of a bond, a wavy line represents the absence of a bond, R2 and R3 are each independently hydrogen, halogen, cyano, hydroxy, carboxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or the like, (ii) when a broken line represents the absence of a bond, a wavy line represents the presence of a bond, R1 and R4 are each independently hydrogen, halogen or the like, R2 and R3 are each independently hydrogen, halogen, cyano, hydroxy, carboxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or the like, and R5 and R6 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or the like.
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Page/Page column 173-174
(2010/08/07)
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- Copper(I)-catalyzed carboxylation of aryl- and alkenylboronic esters
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(Chemical Equation Presented) The copper(I)-catalyzed carboxylation reaction of aryl- and alkenylboronic esters proceeded smoothly under CO 2 to give the corresponding carboxylic acid in good yield. This reaction showed wide generality with higher functional group tolerance compared to the corresponding Rh(I)-catalyzed reaction.
- Takaya, Jun,Tadami, Satoshi,Ukai, Kazutoshi,Iwasawa, Nobuharu
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supporting information; experimental part
p. 2697 - 2700
(2009/05/26)
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- Methods for producing D-beta-hydroxyamino acids
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An objective of the present invention is to provide efficient methods for producing D-β-hydroxyamino acids (formula 2 or 4), such as D-erythro-2-amino-3-cyclohexyl-3-hydroxypropionic acid, which are useful as intermediates in the synthesis of pharmaceutical products and others. The present invention makes it possible to efficiently produce D-erythro-2-amino-3-cyclohexyl-3-hydroxypropionic acid by cleaving unnecessary L-erythro-2-amino-3-cyclohexyl-3-hydroxypropionic acid in industrially feasible concentrations of DL-erythro-2-amino-3-cyclohexyl-3-hydroxypropionic acid used as starting material by using Pseudomonas putida-derived L-phenylserine aldolase.
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Page/Page column 12
(2008/06/13)
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- Stereospecific electrochemical carboxylation of β-bromostyrene by use of nickel(II) catalyst
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Electrochemical carboxylation of (E)- and (Z)-β-bromostyrenes (1) under an atmospheric pressure of carbon dioxide with a platinum cathode and a magnesium anode in the presence of 20 mol % of NiBr2·bpy proceeded with retention of stereochemistry to give the corresponding (E)- or (Z)-cinnamic acids (2). The stereochemical outcome of nickel(II)-catalyzed electrochemical carboxylations was discussed by comparison with predominant formation of a (Z)-isomer from either (E)- or (Z)-β-bromostyrenes. Copyright
- Kuang, Chunxiang,Yang, Qing,Senboku, Hisanori,Tokuda, Masao
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p. 528 - 529
(2007/10/03)
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- Novel compounds as histone deacetylase inhibitors
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The present invention is directed to compounds of the general formula (I) or pharmaceutical acceptable salts or physiologically functional derivatives thereof wherein: n is a non-aromatic ring system containing two to seven carbon atoms, wherein the ring
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Page/Page column 6
(2008/06/13)
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- NOVEL COMPOUNDS AS HISTONE DEACETYLASE INHIBITORS
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The present invention is directed to compounds of the general formula (I) or pharmaceutical acceptable salts or physiologically functional derivatives thereof wherein: n is a non-aromatic ring system containing two to seven carbon atoms, wherein the ring
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- Base-Catalyzed Reactions of α,β-Unsaturated Esters and Nitriles. 4. Dimerization of β-Alkyl-Substituted Acrylates
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2-Butenoates 1-C4 alkyl, cyclohexyl, or 1-bornyl> and higher β-alkyl-substituted acrylates 2-C9 n-alkyl> undergo highly selective (>95percent) dimerization in the presence of promoted potassium or sodium catalysts to yield corresponding 2-alkylidene-3-alkylglutarates (3).The reaction involves metalation of the β-alkylacrylate at the C-2 position, followed by addition at C-3 of a second monomeric molecule.Changes in the relative extent of dimerization (Kr) as a function of structural and experimentalvariables were determined.Kr is strongly dependent upon the inductive and steric characteristics of the alcoholic (R) group and of the β-alkyl substituent (R').For an n-alkyl group as R' the Kr value increases with increase in chain length from C1 to C4 but then decreases for longer substituents (C5-C9).Among the two geometric isomers in the dimeric product 3, the isomer with an α-vinylic hydrogen cis to the carboalkoxy group is predominant in all cases, but its relative concetration decreases with an increase in the size of R'.Branched or cyclic β-substituents in 2 prevent dimerization due to steric hindrance in the rate-determining addition step.Promoted potassium or sodium catalysts show much higher dimerization activity compared to supported alkali metals or to alkoxides.For conversions of up to 60percent, Kr values in proton-exchanging alkylbenzene solvents and in nonexchanging alkylcyclohexanes are closely similar, indicating faster abstraction of an α-vinylic hydrogen from the monomer, rather than a benzylic hydrogen from the solvent, in the chain regeneration step of the reaction.
- Shabtai, Joseph,Ney-Igner, Eva
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p. 3795 - 3802
(2007/10/02)
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