- Photoassisted Cross-Coupling Reaction of α-Chlorocarbonyl Compounds with Arylboronic Acids
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A Suzuki-Miyaura cross-coupling reaction of α-chloroacetates or α-chloroacetamides with arylboronic acids is made possible by visible-light irradiation. This reaction provides a useful method for the synthesis of α-arylacetates and α-arylacetamides from chlorides under mild reaction conditions. An indole-3-acetic acid derivative that is the key intermediate of the plant hormone auxin can be synthesized from 1-Boc-indole in two steps by combining an iridium-catalyzed C-H borylation and a palladium-catalyzed cross-coupling reaction.
- Miura, Tomoya,Murakami, Masahiro,Oku, Naoki
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supporting information
p. 1616 - 1619
(2022/03/14)
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- Enantioselective Desymmetrization of 2-Aryl-1,3-propanediols by Direct O-Alkylation with a Rationally Designed Chiral Hemiboronic Acid Catalyst That Mitigates Substrate Conformational Poisoning
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Enantioselective desymmetrization by direct monofunctionalization of prochiral diols is a powerful strategy to prepare valuable synthetic intermediates in high optical purity. Boron acids can activate diols toward nucleophilic additions; however, the design of stable chiral catalysts remains a challenge and highlights the need to identify new chemotypes for this purpose. Herein, the discovery and optimization of a bench-stable chiral 9-hydroxy-9,10-boroxarophenanthrene catalyst is described and applied in the highly enantioselective desymmetrization of 2-aryl-1,3-diols using benzylic electrophiles under operationally simple, ambient conditions. Nucleophilic activation and discrimination of the enantiotopic hydroxy groups on the diol substrate occurs via a defined chairlike six-membered anionic complex with the hemiboronic heterocycle. The optimal binaphthyl-based catalyst 1g features a large aryloxytrityl group to effectively shield one of the two prochiral hydroxy groups on the diol complex, whereas a strategically placed "methyl blocker"on the boroxarophenanthrene unit mitigates the deleterious effect of a competing conformation of the complexed diol that compromised the overall efficiency of the desymmetrization process. This methodology affords monoalkylated products in enantiomeric ratios equal or over 95:5 for a wide range of 1,3-propanediols with various 2-aryl/heteroaryl groups.
- Estrada, Carl D.,Ang, Hwee Ting,Vetter, Kim-Marie,Ponich, Ashley A.,Hall, Dennis G.
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supporting information
(2021/04/07)
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- INHIBITORS OF α-AMINO-β-CARBOXYMUCONIC ACID SEMIALDEHYDE DECARBOXYLASE
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The present disclosure discloses compounds capable of modulating the activity of α-amino-β-carboxymuconic acid semialdehyde decarboxylase (ACMSD), which are useful for the prevention and/or the treatment of diseases and disorders associated with defects in NAD+ biosynthesis, e.g., metabolic disorders, neurodegenerative diseases, chronic inflammatory diseases, kidney diseases, and diseases associated with ageing. The present application also discloses pharmaceutical compositions comprising said compounds and the use of such compounds as a medicament.
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Paragraph 00477
(2020/06/10)
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- Thermal Stability and Explosive Hazard Assessment of Diazo Compounds and Diazo Transfer Reagents
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Despite their wide use in academia as metal-carbene precursors, diazo compounds are often avoided in industry owing to concerns over their instability, exothermic decomposition, and potential explosive behavior. The stability of sulfonyl azides and other diazo transfer reagents is relatively well understood, but there is little reliable data available for diazo compounds. This work first collates available sensitivity and thermal analysis data for diazo transfer reagents and diazo compounds to act as an accessible reference resource. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and accelerating rate calorimetry (ARC) data for the model donor/acceptor diazo compound ethyl (phenyl)diazoacetate are presented. We also present a rigorous DSC dataset with 43 other diazo compounds, enabling direct comparison to other energetic materials to provide a clear reference work to the academic and industrial chemistry communities. Interestingly, there is a wide range of onset temperatures (Tonset) for this series of compounds, which varied between 75 and 160 °C. The thermal stability variation depends on the electronic effect of substituents and the amount of charge delocalization. A statistical model is demonstrated to predict the thermal stability of differently substituted phenyl diazoacetates. A maximum recommended process temperature (TD24) to avoid decomposition is estimated for selected diazo compounds. The average enthalpy of decomposition (?"HD) for diazo compounds without other energetic functional groups is-102 kJ mol-1. Several diazo transfer reagents are analyzed using the same DSC protocol and found to have higher thermal stability, which is in general agreement with the reported values. For sulfonyl azide reagents, an average ?"HD of-201 kJ mol-1 is observed. High-quality thermal data from ARC experiments shows the initiation of decomposition for ethyl (phenyl)diazoacetate to be 60 °C, compared to that of 100 °C for the common diazo transfer reagent p-acetamidobenzenesulfonyl azide (p-ABSA). The Yoshida correlation is applied to DSC data for each diazo compound to provide an indication of both their impact sensitivity (IS) and explosivity. As a neat substance, none of the diazo compounds tested are predicted to be explosive, but many (particularly donor/acceptor diazo compounds) are predicted to be impact-sensitive. It is therefore recommended that manipulation, agitation, and other processing of neat diazo compounds are conducted with due care to avoid impacts, particularly in large quantities. The full dataset is presented to inform chemists of the nature and magnitude of hazards when using diazo compounds and diazo transfer reagents. Given the demonstrated potential for rapid heat generation and gas evolution, adequate temperature control and cautious addition of reagents that begin a reaction are strongly recommended when conducting reactions with diazo compounds.
- Green, Sebastian P.,Wheelhouse, Katherine M.,Payne, Andrew D.,Hallett, Jason P.,Miller, Philip W.,Bull, James A.
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supporting information
p. 67 - 84
(2020/01/31)
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- N-Heterocyclic Carbenes as Key Intermediates in the Synthesis of Fused, Mesoionic, Tricyclic Heterocycles
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Coupling between 5-bromoimidazo[1,5-a]pyridinium salts and malonate or arylacetate esters leads to a facile and straightforward access to the new mesoionic, fused, tricyclic system of imidazo[2,1,5-cd]indolizinium-3-olate. Mechanistic studies show that the reaction pathway consists of nucleophilic aromatic substitution on the cationic, bicyclic heterocycle by an enolate-type moiety and in the nucleophilic attack of a transient free N-heterocyclic carbene (NHC) species on the ester group; the relative order of these two steps depends on the nature of the starting ester. This work highlights the valuable implementation of free NHC species as key intermediates in synthetic chemistry, beyond their classical use as stabilizing ligands or organocatalysts.
- Benaissa, Idir,Pallova, Lenka,Morantin, Marie-Emilie,Lafitte, Thomas,Huynh, Mathieu,Barthes, Cécile,Vendier, Laure,Lugan, No?l,Bastin, Stéphanie,César, Vincent
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supporting information
p. 13030 - 13036
(2019/11/05)
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- A novel serine racemase inhibitor suppresses neuronal over-activation in vivo
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Serine racemase (SRR) is an enzyme that produces D-serine from L-serine. D-Serine acts as an endogenous coagonist of NMDA-type glutamate receptors (NMDARs), which regulate many physiological functions. Over-activation of NMDARs induces excitotoxicity, which is observed in many neurodegenerative disorders and epilepsy states. In our previous works on the generation of SRR gene knockout (Srr-KO) mice and its protective effects against NMDA- and Aβ peptide-induced neurodegeneration, we hypothesized that the regulation of NMDARs’ over-activation by inhibition of SRR activity is one such therapeutic strategy to combat these disease states. In the previous study, we performed in silico screening to identify four compounds with inhibitory activities against recombinant SRR. Here, we synthesized 21 derivatives of candidate 1, one of four hit compounds, and performed screening by in vitro evaluations. The derivative 13J showed a significantly lower IC50 value in vitro, and suppressed neuronal over-activation in vivo.
- Mori, Hisashi,Wada, Ryogo,Takahara, Satoyuki,Horino, Yoshikazu,Izumi, Hironori,Ishimoto, Tetsuya,Yoshida, Tomoyuki,Mizuguchi, Mineyuki,Obita, Takayuki,Gouda, Hiroaki,Hirono, Shuichi,Toyooka, Naoki
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p. 3736 - 3745
(2017/06/13)
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- Mechanistic studies on gold-catalyzed direct arene c-h bond functionalization by carbene insertion: The coinage-metal effect
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The catalytic functionalization of the Csp2-H bond of benzene by means of the insertion of the CHCO2Et group from ethyl diazoacetate (N2= CHCO2Et) has been studied with the series of coinage-metal complexes IPrMCl (IPr = 1,3-bis- (diisopropylphenyl)imidazol-2-ylidene) and NaBArF 4 (BArF 4 = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate). For Cu and Ag, these examples constitute the first use of such metals toward this transformation, which also provides ethyl cyclohepta-2,4,6-trienecarboxylate as a byproduct from the so-called Buchner reaction. In the case of methyl-substituted benzenes, the reaction exclusively proceeds onto the aromatic ring, the Csp3-H bond remaining unreacted. A significant coinage-metal effect has been observed, since the gold catalyst favors the formation of the insertion product into the Csp2-H bond whereas copper and silver preferentially induce the formation of the cycloheptatriene derivative. Experimental studies and theoretical calculations have explained the observed selectivity in terms of the formation of a common Wheland intermediate, resembling an electrophilic aromatic substitution, from which the reaction pathway evolves into two separate routes to each product.
- Fructos, Manuel R.,Besora, Maria,Braga, Ataualpa A. C,Díaz-Requejo, M. Mar,Maseras, Feliu,Perez, Pedro J.
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p. 172 - 179
(2017/04/04)
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- Iron and manganese catalysts for the selective functionalization of arene C(sp2)-H bonds by carbene insertion
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The first examples of the direct functionalization of non-activated aryl sp2 C-H bonds with ethyl diazoacetate (N2CHCO2Et) catalyzed by Mn- or Fe-based complexes in a completely selective manner are reported, with no formation of the frequently observed cycloheptatriene derivatives through competing Buchner reaction. The best catalysts are FeII or MnII complexes bearing the tetradentate pytacn ligand (pytacn= 1-(2-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane). When using alkylbenzenes, the alkylic C(sp3)-H bonds of the substituents remained unmodified, thus the reaction being also selective toward functionalization of sp2 C-H bonds. Exclusive catalysis: Iron- and-manganese-based catalysts selectively functionalize the C(sp2)-H bonds of benzene or alkylbenzenes through the formal insertion of the CHCO2Et group from N2CHCO2Et (see scheme). When using alkylbenzenes, the alkylic C(sp3)-H bonds of the substituents remain unmodified.
- Conde, Ana,Sabenya, Gerard,Rodríguez, Mònica,Postils, Verònica,Luis, Josep M.,Díaz-Requejo, M. Mar,Costas, Miquel,Pérez, Pedro J.
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supporting information
p. 6530 - 6534
(2016/06/01)
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- Selective synthesis of arylacetic acid esters from ethyl acetoacetate and aryl halides in the presence of copper(II) on 4 ? molecular sieves
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A heterogeneous catalyst, copper(II) on 4 ? molecular sieves has successfully been used in the arylation of ethyl acetoacetate, selectively forming arylacetic esters in high yields. The air stable and easily handled catalyst can be simply filtered off during purification thus avoiding significant metal contamination of the product.
- Zsolczai, Dávid,Németh, János,Hell, Zoltán
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p. 6389 - 6392
(2015/11/16)
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- Alcohol assisted C-C bond breaking: Copper-catalyzed deacetylative α-arylation of β-keto esters and amides
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A method of alcohol-assisted copper-catalyzed highly selective deacetylative α-arylation of β-keto esters and amides has been demonstrated, which illustrated an efficient example of achieving α-aryl esters and amides. From the synthetic point of view, this arylation protocol is general and practical, representing a simple way to produce α-arylated carbonyl compounds from basic starting materials at low cost.
- Ke, Jie,He, Chuan,Liu, Huiying,Xu, Huan,Lei, Aiwen
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supporting information
p. 6767 - 6769
(2013/07/26)
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- PROCESS FOR SYNTHESIZING PHENYLACETIC ACID BY CARBONYLATION OF TOLUENE
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A production process for substituted phenylacetic acids or ester analogues thereof is disclosed. In this process toluene or toluene substituted with various substituents, an alcohol, an oxidant and carbon monoxide are used as raw materials to obtain compounds comprising structure of phenylacetic acid ester or analogues thereof by catalysis of the complex catalyst formed from transition metal and ligand, and such compounds are hydrolyzed to obtain various substituted phenylacetic acid based compounds. This type of compounds and their derivatives serve as important fine chemicals used widely in the industries of pharmaceuticals, pesticides, perfume and the like.
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Paragraph 0044; 0045
(2013/11/19)
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- Palladium-catalyzed oxidative carbonylation of benzylic C-H bonds via nondirected C(sp3)-H activation
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A new strategy for generating benzylpalladium reactive species from toluenes via nondirected C(sp3)-H activation has been developed. This led to construction of an efficient Pd-catalyzed reaction protocol for the oxidative carboxylation of benzylic C-H bonds to form substituted 2-phenylacetic acid esters and derivatives from inexpensive, commercially available starting materials.
- Xie, Pan,Xie, Yinjun,Qian, Bo,Zhou, Han,Xia, Chungu,Huang, Hanmin
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supporting information; experimental part
p. 9902 - 9905
(2012/08/08)
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- Pd-catalyzed decarboxylative cross-couplings of potassium malonate monoesters with aryl halides
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An efficient catalytic protocol for Pd-catalyzed decarboxylative cross-coupling of potassium malonate monoesters and derivatives with aryl bromides and chlorides are described. Because of its broad applicability, this new catalytic system provides an alternative method for the preparation of diverse aryl acetic acids and derivatives.
- Feng, Yi-Si,Wu, Wei,Xu, Zhong-Qiu,Li, Yan,Li, Ming,Xu, Hua-Jian
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experimental part
p. 2113 - 2120
(2012/03/26)
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- NOVEL COMPOUNDS
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The present invention relates to new CGRP-antagonists of general formula I wherein U, V, X, Y, R1, R2, R3 and R4 are defined as mentioned in the description, the tautomers thereof, the isomers thereof, the diastereomers thereof, the enantiomers thereof, the hydrates thereof, the mixtures thereof and the salts thereof as well as the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, medicaments containing these compounds, the use thereof and processes for the preparation thereof.
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Page/Page column 88
(2011/08/22)
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- Exclusive aromatic vs aliphatic C-H bond functionalization by carbene insertion with gold-based catalysts
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The direct functionalization of aromatic C-H bonds by carbene insertion from diazo compounds catalyzed by gold complexes with N-heterocyclic ligands is described. The reaction is completely selective toward the C sp2-H bonds, other C sp3-H bonds remaining unreacted. A study with several NHC ligands in Au(I) and Au(III) complexes has been performed. The potential application of this strategy to give profen derivatives has also been explored.
- Rivilla, Ivan,Gomez-Emeterio, B. Pilar,Fructos, Manuel R.,Diaz-Requejo, M. Mar,Perez, Pedro J.
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experimental part
p. 2855 - 2860
(2011/07/08)
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- Water works: An efficient palladium-catalyzed cross-coupling reaction between boronic acids and bromoacetate with aminophosphine ligand
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Water greatly restrained the formation of self-coupling of boronic acids in a palladium-catalyzed cross-coupling reaction between boronic acids and ethyl bromoacetate with an aminophosphine ligand; good to excellent yields of cross-coupling product were obtained.
- Peng, Zhi-Yong,Wang, Jian-Ping,Cheng, Jiang,Xie, Xiao-Min,Zhang, Zhaoguo
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experimental part
p. 8238 - 8241
(2010/10/21)
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- A gold catalyst for carbene-transfer reactions from ethyl diazoacetate
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(Chemical Equation Presented) Approaching El Dorado: A gold catalyst has been discovered that transfers a carbene unit from ethyl diazoacetate to aromatic substrates (see scheme) as well as olefins, amines, and alcohols. The insertion of carbene units into the C-H bonds of the aromatic ring of benzene, toluene, and styrene is a novel reaction. R = H, CH3, CH=CH 2; IPr = 1,3-bis(diisopropylphenyl)imidazol-2-ylidene.
- Fructos, Manuel R.,Belderrain, Tomas R.,De Fremont, Pierre,Scott, Natalie M.,Nolan, Steven P.,Diaz-Requejo, M Mar,Perez, Pedro J.
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p. 5284 - 5288
(2007/10/03)
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- 1,2-disubstituted-6-oxo-3-phenyl-piperidine-3-carboxamides and combinatorial libraries thereof
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The invention relates to combinatorial libraries containing two or more novel piperidine-3-carboxamide derivative compounds, methods of preparing the piperidine-3-carboxamide derivative compounds and piperidine-3-carboxamide derivative compounds bound to a resin
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- Remarkable co-catalysis by copper(I) oxide in the palladium catalyzed cross-coupling of arylboronic acids with ethyl bromoacetate
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Copper(I) oxide can effectively co-catalyze the Suzuki type cross-coupling reactions of arylboronic acids with ethyl bromoacetate. As an alternative protocol for introducing the methylenecarboxy group into functionalized molecules, this reaction occurs in
- Liu, Xing-Xin,Deng, Min-Zhi
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p. 622 - 623
(2007/10/03)
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- One-carbon homologation of carboxylic acids via BtCH2TMS: A safe alternative to the Arndt-Eistert reaction
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Carboxylic acids are converted into the corresponding homologated acids or esters, using easily available 1-(trimethylsilylmethyl)benzotriazole (1) as a one-carbon synthon. The effectiveness of the reaction has been investigated on six aryl and seven alkyl carboxylic acids.
- Katritzky,Zhang,Haleem,Hussein,Fang,Steel
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p. 5606 - 5612
(2007/10/03)
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- Synthesis of substituted chrysenes and phenanthrenes
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3-Methylchrysene (9a), 2, 3, 9-trimethylchrysene (9b), 2, 6-dimethylphenanthrene (16a) and 1-isopropyl-4,6-dimethylphenanthrene (16b) have been synthesised in the following steps. β-(1-Naphthyl)ethyl bromide (6a), β-(6,7-dimethyl-1-naphthyl)ethyl bromide (6b), β-(3-methylphenyl)ethyl bromide (13a) and β-(2-isopropyl-5-methylphenyl)ethyl bromide (13b) are separately condensed with potassium salt of 1-carbethoxy-4-methylcyclohexane-2-one (1) to give respectively 7a, 7b, 14a and 14b. PPA cyclisation of 7a and 7b affords 8a and 8b while 14a affords 15a and 14b gives a mixture of 15b and 15c. Aromatisation of 8a and 8b leads to 9a and 9b and that of 15a gives 16a while 15b and 15c both produce 16b. The structures assigned are consistent with their spectral data.
- Mitra, Ashutosh,Ghoshe, Swati
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p. 785 - 789
(2007/10/03)
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- IODIDE ION PROMOTION BENZYL CHLORIDE-BORATE ESTER CARBONYLANION REACTIONS
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Esters are isolated in fine yields from the rhodium(I) catalyzed reaction of benzyl chlorides with borate esters and carbon monoxide, in the presence of potassium iodide.
- Alper, Howard,Hamel, Nathalie,Smith, David J. H.,Woell, James B.
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p. 2273 - 2274
(2007/10/02)
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- Palladium-catalyzed Displacement of Aryl Halide by Tin Analogue of Reformatsky Reagent
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Reaction of ethyl α-(tributylstannyl)acetate with aryl bromides in the presence of zinc bromide or chloride and a catalytic amount of dichlorobis(tri-o-tolylphosphine)palladium was found to give ethyl arylacetates in good yields except with the aryl bromide having p-acetyl or p-nitro group.
- Kosugi, Masanori,Negishi, Yoshikazu,Kameyama, Masayuki,Migita, Toshihiko
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p. 3383 - 3384
(2007/10/02)
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- SYNTHESIS OF ESTERS BY RHODIUM(I) CATALYZED BORATE ESTER-BENZYLIC BROMIDE CARBONYLATION REACTIONS
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Benzylic halides react with trialkylborates and carbon monoxide, in the presence of 1,5-hexadienerhodium chloride dimer, to give esters in excellent yields.The reaction is applicable to the synthesis of primary, secondary and even tertiary esters.
- Woell, James B.,Alper, Howard
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p. 3791 - 3794
(2007/10/02)
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