- Iron-Catalyzed Asymmetric Decarboxylative Azidation
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The first iron-catalyzed asymmetric azidation of benzylic peresters has been reported with trimethylsilyl azide (TMSN3) as the azido source. Hydrocarbon radicals that lack of strong interactions were capable to be enantioselectively azidated. The reaction features good functional group tolerance, high yields, and mild conditions. The chiral benzylic azides can further be used in click reaction, phosphoramidation, and reductive amination, which demonstrate the synthetic values of this reaction.
- Wang, Kaikai,Li, Yajun,Li, Xiaoyan,Li, Daliang,Bao, Hongli
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supporting information
p. 8847 - 8851
(2021/11/24)
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- Electroreductive Carbofunctionalization of Alkenes with Alkyl Bromides via a Radical-Polar Crossover Mechanism
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Electrochemistry grants direct access to reactive intermediates (radicals and ions) in a controlled fashion toward selective organic transformations. This feature has been demonstrated in a variety of alkene functionalization reactions, most of which proceed via an anodic oxidation pathway. In this report, we further expand the scope of electrochemistry to the reductive functionalization of alkenes. In particular, the strategic choice of reagents and reaction conditions enabled a radical-polar crossover pathway wherein two distinct electrophiles can be added across an alkene in a highly chemo- and regioselective fashion. Specifically, we used this strategy in the intermolecular carboformylation, anti-Markovnikov hydroalkylation, and carbocarboxylation of alkenes - reactions with rare precedents in the literature - by means of the electroreductive generation of alkyl radical and carbanion intermediates. These reactions employ readily available starting materials (alkyl halides, alkenes, etc.) and simple, transition-metal-free conditions and display broad substrate scope and good tolerance of functional groups. A uniform protocol can be used to achieve all three transformations by simply altering the reaction medium. This development provides a new avenue for constructing Csp3-Csp3 bonds.
- Zhang, Wen,Lin, Song
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supporting information
p. 20661 - 20670
(2020/12/23)
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- Palladium-catalyzed α,β-dehydrogenation of acyclic ester equivalents promoted by a novel electron deficient phosphinooxazoline ligand
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A unique example of Pd-catalyzed decarboxylative dehydrogenation of fully substituted N-acyl allyl enol carbonates is enabled by a new electron deficient phosphinooxazoline (PHOX) ligand. The reaction proceeds from the Z-enol carbonate to provide dehydrogenation products exclusively in high E/Z selectivity, while the E-enol carbonate provides the α-allylation product with only minor dehydrogenation. The reaction proceeds with a broad scope of Z-enol carbonates derived from N-acyl indoles to furnish acyclic formal α,β-unsaturated ester equivalents.
- Fulton, Tyler J.,Wu, Brenda,Alexy, Eric J.,Zhang, Haiming,Stoltz, Brian M.
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supporting information
p. 4104 - 4109
(2019/06/20)
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- Photocarboxylation of Benzylic C-H Bonds
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The carboxylation of sp3-hybridized C-H bonds with CO2 is a challenging transformation. Herein, we report a visible-light-mediated carboxylation of benzylic C-H bonds with CO2 into 2-arylpropionic acids under metal-free conditions. Photo-oxidized triisopropylsilanethiol was used as the hydrogen atom transfer catalyst to afford a benzylic radical that accepts an electron from the reduced form of 2,3,4,6-tetra(9H-carbazol-9-yl)-5-(1-phenylethyl)benzonitrile generated in situ. The resulting benzylic carbanion reacts with CO2 to generate the corresponding carboxylic acid after protonation. The reaction proceeded without the addition of any sacrificial electron donor, electron acceptor or stoichiometric additives. Moderate to good yields of the desired products were obtained in a broad substrate scope. Several drugs were successfully synthesized using the novel strategy.
- Meng, Qing-Yuan,Schirmer, Tobias E.,Berger, Anna Lucia,Donabauer, Karsten,K?nig, Burkhard
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supporting information
p. 11393 - 11397
(2019/08/20)
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- Preparation method of carboxylic acid compound
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The invention provides a preparation method of a carboxylic acid compound. The preparation method comprises the following step of taking a lactone component to react with hydrogen in the presence of a compound catalyst to obtain the carboxylic acid compound. The compound catalyst comprises a hydrogenation catalyst and Lewis acid. In the presence of the compound catalyst comprising the hydrogenation catalyst and the Lewis acid, the lactone component is subjected to hydrogenation ring-opening reaction to obtain the carboxylic acid compound. The preparation method has the advantages of moderate reaction conditions and high yield; compared with a traditional method, less byproducts are generated, green and chemical requirements are met and the industrial value is better.
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Paragraph 0113; 0196-0198
(2017/08/29)
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- A Comprehensive Study on Metal Triflate-Promoted Hydrogenolysis of Lactones to Carboxylic Acids: From Synthetic and Mechanistic Perspectives
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Direct hydrogenolysis of lactone to carboxylic acid (i.e., hydrogenolysis of the Calkoxy-O bond with the carbonyl group untouched) is generally difficult, as the current strategies employing Br?nsted acids as the catalyst usually require harsh conditions such as a high temperature and a high H2 pressure. Herein, we report a developed solvent-free catalytic transformation, in which W(OTf)6 is believed to promote the hydrogenolysis process. This strategy could efficiently hydrogenate lactones to carboxylic acids under extra mild conditions (e.g., a reaction temperature of 2) and showed a broad substrate scope. In addition, the catalytic protocol can be further applied to the hydrogenolysis of polyhydroxyalkanoate, as a renewable polymer, to the corresponding straight-chain carboxylic acids. An extensive mechanistic study was subsequently performed, and the density functional theory calculations revealed a reaction pattern, including the complete cleavage of the C=O bond with the assistance of the W(OTf)6 catalyst. Moreover, the key intermediate created in the mechanism, as an oxonium with an OTf moiety, was successfully detected by electrospray ionization mass spectra. Through a comparison with the Br?nsted acid-catalyzed system, the study confirmed that the existence of the OTf moiety can significantly lower the barriers associated with the rearrangement and elimination processes. Meanwhile, emphasis was placed on the critical role that the anion plays, as well as the fact that the anion effect is directly related to the chemoselectivity.
- Zhu, Rui,Jiang, Ju-Long,Li, Xing-Long,Deng, Jin,Fu, Yao
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p. 7520 - 7528
(2017/11/10)
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- PYRIMIDINE HYDROXY AMIDE COMPOUNDS AS HISTONE DEACETYLASE INHIBITORS
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Provided herein are compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with HDAC activity, particularly diseases or disorders that involve activity of HDAC1, HDAC2, and/or HDAC6. Also provided herein are methods for inhibiting migration of a neuroblastoma cell, inducing maturation of a neuroblastoma cell, and altering cell cycle progression of a neuroblastoma cell comprising administering to the cell a therapeutically effective amount of a HDAC1, HDAC2, and/or HDAC6 selective inhibitor or a pharmaceutically acceptable salt thereof.
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Paragraph 0349; 0350
(2015/04/21)
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- Oxidative rearrangement of malondialdehyde: Substrate scope and mechanistic insights
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A novel oxidative rearrangement of malondialdehyde was described. Under the effect of H2O2, malondialdehyde smoothly transferred to carboxylic acid with C-C bond cleavage in good to excellent yields. Mechanistic studies showed that this reaction proceeded via the formation of a 1,2-dioxolane intermediate, followed by concert C-C, O-O, C-H bond cleavage and a hydride shift.
- Yu, Xin,Liu, Zheng,Xia, Zilei,Shen, Zhigao,Pan, Xixian,Zhang, Hui,Xie, Weiqing
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p. 53397 - 53401
(2015/01/16)
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- Highly enantioselective direct alkylation of arylacetic acids with chiral lithium amides as traceless auxiliaries
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A direct, highly enantioselective alkylation of arylacetic acids via enediolates using a readily available chiral lithium amide as a stereodirecting reagent has been developed. This approach circumvents the traditional attachment and removal of chiral auxiliaries used currently for this type of transformation. The protocol is operationally simple, and the chiral reagent is readily recoverable.
- Stivala, Craig E.,Zakarian, Armen
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supporting information; experimental part
p. 11936 - 11939
(2011/09/19)
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- N-heterocyclic carbene-mediated enantioselective addition of phenols to unsymmetrical alkylarylketenes
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Chiral N-heterocyclic carbenes (NHCs) mediate the enantioselective addition of 2-phenylphenol to unsymmetrical alkylarylketenes, delivering α-alkyl-α-arylacetic acid derivatives with good levels of enantiocontrol (up to 84% ee). Enantiodivergent stereochemical outcomes are observed using 2-phe-nylphenol and benzhydrol in the NHC-promoted esterification reaction using a triazolium precatalyst derived from pyroglutamic acid, consistent with distinct mechanistic pathways operating within these processes.
- Concellon, Carmen,Duguet, Nicolas,Smith, Andrew D.
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supporting information; experimental part
p. 3001 - 3009
(2010/03/26)
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- ARALKYL AMINES AS CANNABINOID RECEPTOR MODULATORS
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Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson’s disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, including alcohol and nicotine addiction, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, and cirrhosis of the liver.
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Page/Page column 55-56
(2010/02/11)
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- SUBSTITUTED SULFONAMIDES
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The substituted sulfonamides of the invention are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson's disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, and cirrhosis of the liver.
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Page/Page column 55
(2008/06/13)
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- SUBSTITUTED ARYL AMIDES
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Novel compounds of structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as psychotropic drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson s disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as, the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, and cirrhosis of the liver.
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Page/Page column 90
(2010/02/07)
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- Ligand effects on dirhodium(II) carbene reactivities. Highly effective switching between competitive carbenoid transformations
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Carboxylate and carboxamide ligands of dirhodium(II) catalysts control chemoselectivity in competitive metal carbene transformations of diazo compounds. For competitive intramolecular cyclopropanation versus intramolecular aromatic substitution with 1-diazo-3-aryl-5-hexen-2-ones, use of Rh2(OAc)4 results in the products from both transformations in nearly equal amounts, but dirhodium(II) perfluorobutyrate (Rh2(pfb)4) provides only the aromatic substitution product while dirhodium(II) caprolactamate (Rh2(cap)4) gives only the cyclopropanation product. Similar results are obtained from dirhodium(II) catalysts in competitive intramolecular cyclopropanation versus tertiary C-H insertion, aromatic cycloaddition versus C-H insertion, cyclopropanation versus aromatic cycloaddition, and C-H insertion versus aromatic substitution. The order of reactivity for metal carbenes generated from Rh2(pfb)4 is aromatic substitution > tertiary C-H insertion > cyclopropanation ~ aromatic cycloaddition > secondary C-H insertion, and the rate differences between them are as much as 100-fold. For Rh2(cap)4 the order of reactivity is cyclopropanation > tertiary C-H insertion > secondary C-H insertion > aromatic cycloaddition with aromatic substitution not observed as a competing process for the diazo compounds examined. Control of chemoselectivity through charge and/or frontier molecular orbital properties of the intermediate metal carbene has been evaluated. Competitive product formation from dirhodium(II) caprolactamate catalyzed reactions of N-tert-butyl-N-benzyldiazoacetoacetamide is temperature dependent over a narrow 15-deg range. The effect of carbene substituents other than the ligated dirhodium(II) on chemoselectivity is described and discussed.
- Padwa, Albert,Austin, David J.,Price, Alan T.,Semones, Mark A.,Doyle, Michael P.,Protopopova, Marina N.,Winchester, William R.,Tran, Andrea
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p. 8669 - 8680
(2007/10/02)
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