- Tropylium-promoted Ritter reactions
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The Ritter reaction used to be one of the most powerful synthetic tools to functionalize alcohols and nitriles, providing valuableN-alkyl amide products. However, this reaction has not been frequently used in modern organic synthesis due to its employment of strongly acidic and harsh reaction conditions, which often lead to complicated side reactions. Herein, we report the development of a new method using salts of the tropylium ion to promote the Ritter reaction. This method works well on a range of alcohol and nitrile substrates, giving the corresponding products in good to excellent yields. This reaction protocol is amenable to microwave and continuous flow reactors, offering an attractive opportunity for further applications in organic synthesis.
- Doan, Son H.,Hussein, Mohanad A.,Nguyen, Thanh Vinh
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supporting information
p. 8901 - 8904
(2021/09/10)
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- Chiral-Directing-Group-Assisted Rhodium(III)-Catalyzed Asymmetric Addition of Inert Arene C?H Bond to Aldimines with Subsequent Intramolecular Cyclization
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By using a chiral directing group, an asymmetric rhodium(III)-catalyzed C?H bond addition to aldimines followed by intramolecular cyclization to form chiral isoindolinones has been achieved (up to 68 % yield, up to 93 % ee). A three-component variant that resembles Mannich reaction was also realized (41 % yield, 83 % ee). Product elaborations and preliminary mechanistic studies were described.
- Cai, Xuhong,Chen, Wenkun,Nie, Ruifang,Wang, Jun
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supporting information
p. 16611 - 16615
(2021/10/19)
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- Palladium-catalyzed dehydrogenative C-H cyclization for isoindolinone synthesis
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In this paper Pd-catalyzed intramolecular dehydrogenative C(sp3)-H amidation for the synthesis of isoindolinones is described. This method features the use of a Pd/C catalyst and the addition of a stoichiometric amount of oxidant is not necessary. A mechanistic study suggested the possible formation of H2gas during the reaction.
- Abe, Masahiro,Inamoto, Kiyofumi,Kimachi, Tetsutaro,Tanaka, Saki,Ueta, Kaho
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p. 26988 - 26991
(2021/08/17)
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- Highly Robust Iron Catalyst System for Intramolecular C(sp3)?H Amidation Leading to γ-Lactams
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Disclosed here is the use of an iron catalyst system for an intramolecular C?H amidation toward γ-lactam synthesis from dioxazolone precursors. (Phthalocyanine)FeIIICl was found to catalyze this cyclization with extremely high turnover numbers of up to 47 000 under mild and aerobic conditions. On the basis of experimental and computational mechanistic studies, the reaction is suggested to proceed by a stepwise radical pathway involving fast hydrogen atom abstraction followed by radical rebound. A plausible origin for the high turnover numbers along with air-compatibility is also rationalized.
- Kweon, Jeonguk,Chang, Sukbok
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supporting information
p. 2909 - 2914
(2020/12/11)
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- COMPOUND HAVING BET INHIBITORY ACTIVITY AND PREPARATION METHOD AND USE THEREFOR
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The invention relates to the field of pharmaceutical chemistry. Specifically, the present invention relates to a series of BET (bromodomain and extra-terminal domain) inhibitors having a novel structure, particularly inhibitors targeting BRD4 (Bromodomain-containing protein 4), and a preparation method and use therefor. The structure thereof is shown in the following general formula (I). Said compounds or a stereoisomer, racemate, geometric isomer, tautomer, prodrug, hydrate, solvate, or crystal form thereof, or a pharmaceutically acceptable salt thereof, and the pharmaceutical compsosition thereof can be used for the treatment and/or prevention of related diseases mediated by bromodomain proteins.
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Paragraph 0200-0201
(2020/12/22)
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- Tuning Triplet Energy Transfer of Hydroxamates as the Nitrene Precursor for Intramolecular C(sp3)-H Amidation
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Reported herein is the design of a photosensitization strategy to generate triplet nitrenes and its applicability for the intramolecular C-H amidation reactions. Substrate optimization by tuning physical organic parameters according to the proposed energy transfer pathway led us to identify hydroxamates as a convenient nitrene precursor. While more classical nitrene sources, representatively organic azides, were ineffective under the current photosensitization conditions, hydroxamates, which are readily available from alcohols or carboxylic acids, are highly efficient in accessing synthetically valuable 2-oxazolidinones and γ-lactams by visible light. Mechanism studies supported our working hypothesis that the energy transfer path is mainly operative.
- Chang, Sukbok,Jung, Hoimin,Keum, Hyeyun,Kweon, Jeonguk
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supporting information
p. 5811 - 5818
(2020/04/10)
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- Synthesis of Lactams via Ir-Catalyzed C-H Amidation Involving Ir-Nitrene Intermediates
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x-membered lactams were synthesized via either an amidation of sp3 C-H bonds or an electrophilic substitution of arenes via Ir-nitrene intermediates. With the employment of a readily available iridium catalyst in dichloromethane or hexafluoro-2-propanol, a wide range of lactams were synthesized in good to excellent yields with high selectivity.
- Li, Xiaoxun,Liu, Jitian,Tang, Weiping,Wang, Shuojin,Ye, Wenjing,Zheng, Junrong
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- Strategic Approach to the Metamorphosis of γ-Lactones to NH γ-Lactams via Reductive Cleavage and C-H Amidation
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A new approach has elaborated on the conversion of γ-lactones to the corresponding NH γ-lactams that can serve as γ-lactone bioisosteres. This approach consists of reductive C-O cleavage and an Ir-catalyzed C-H amidation, offering a powerful synthetic tool for accessing a wide range of valuable NH γ-lactam building blocks starting from γ-lactones. The synthetic utility was further demonstrated by the late-stage transformation of complex bioactive molecules and the asymmetric transformation.
- Jung, Hoi-Yun,Chang, Sukbok,Hong, Sungwoo
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p. 7099 - 7103
(2019/09/07)
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- Harnessing Secondary Coordination Sphere Interactions That Enable the Selective Amidation of Benzylic C-H Bonds
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Engineering site-selectivity is highly desirable especially in C-H functionalization reactions. We report a new catalyst platform that is highly selective for the amidation of benzylic C-H bonds controlled by π-πinteractions in the secondary coordination sphere. Mechanistic understanding of the previously developed iridium catalysts that showed poor regioselectivity gave rise to the recognition that the π-cloud of an aromatic fragment on the substrate can act as a formal directing group through an attractive noncovalent interaction with the bidentate ligand of the catalyst. On the basis of this mechanism-driven strategy, we developed a cationic (ν5-C5H5)Ru(II) catalyst with a neutral polypyridyl ligand to obtain record-setting benzylic selectivity in an intramolecular C-H lactamization in the presence of tertiary C-H bonds at the same distance. Experimental and computational techniques were integrated to identify the origin of this unprecedented benzylic selectivity, and robust linear free energy relationship between solvent polarity index and the measured site-selectivity was found to clearly corroborate that the solvophobic effect drives the selectivity. Generality of the reaction scope and applicability toward versatile γ-lactam synthesis were demonstrated.
- Jung, Hoimin,Schrader, Malte,Kim, Dongwook,Baik, Mu-Hyun,Park, Yoonsu,Chang, Sukbok
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supporting information
p. 15356 - 15366
(2019/10/22)
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- Palladium-Catalyzed Direct C-H Carbonylation of Free Primary Benzylamines: A Synthesis of Benzolactams
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A protocol for palladium-catalyzed C-H carbonylation of readily available free primary benzylamines using NH2 as the chelating group under an atmospheric pressure of CO has been achieved, providing a general, atom- and step-economic approach to
- Zhang, Chunhui,Ding, Yongzheng,Gao, Yuzhen,Li, Shangda,Li, Gang
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supporting information
p. 2595 - 2598
(2018/05/22)
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- Selective formation of γ-lactams via C-H amidation enabled by tailored iridium catalysts
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Intramolecular insertion of met al nitrenes into carbon-hydrogen bonds to form γ-lactam rings has traditionally been hindered by competing isocyanate formation. We report the application of theory and mechanism studies to optimize a class of pentamethylcyclopentadienyl iridium(III) catalysts for suppression of this competing pathway. Modulation of the stereoelectronic properties of the auxiliary bidentate ligands to be more electron-donating was suggested by density functional theory calculations to lower the C-H insertion barrier favoring the desired reaction. These catalysts transform a wide range of 1,4,2-dioxazol-5-ones, carbonylnitrene precursors easily accessible from carboxylic acids, into the corresponding γ-lactams via sp3 and sp2 C-H amidation with exceptional selectivity. The power of this method was further demonstrated by the successful late-stage functionalization of amino acid derivatives and other bioactive molecules.
- Hong, Seung Youn,Park, Yoonsu,Hwang, Yeongyu,Kim, Yeong Bum,Baik, Mu-Hyun,Chang, Sukbok
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p. 1016 - 1021
(2018/03/09)
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- Traceless Directing Group Assisted Cobalt-Catalyzed C?H Carbonylation of Benzylamines
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The first example of cobalt-catalyzed C(sp2)?H carbonylation of benzylamines using a traceless directing group is reported, which was successfully applied to the synthesis of N?unprotected iso-indolinones through direct C?H/N?H bonds activation. This protocol tolerates a variety of functional groups and provides a facile and efficient method for the formal synthesis of (+)-garenoxacin. (Figure presented.).
- Ling, Fei,Ai, Chongren,Lv, Yaping,Zhong, Weihui
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supporting information
p. 3707 - 3712
(2017/10/07)
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- Exploiting the Bis-Nucleophilicity of α-Aminoboronates: Copper-Catalyzed, Intramolecular Aminoalkylations of Bromobenzoyl Chlorides
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α-Aminoboronate salts are interesting examples of heteroatomic species containing adjacent nucleophilic centers. We have developed an acylation/arylation reaction using 2-bromobenzoyl chlorides as bis-electrophiles that harnesses the nucleophilicity of both positions, leading to isoindolinones. The reactions proceed under mild conditions via an intramolecular, Cu-catalyzed sp3-sp2 coupling, giving products in up to 95% yield. These conditions enable arylation of α,α-disubstituted aminoboronates, which are difficult to accomplish using methods based on less abundant and more expensive transition metals.
- Dumas, Aaron M.,Sieradzki, Adrian J.,Donnelly, Liam J.
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supporting information
p. 1848 - 1851
(2016/05/19)
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- Copper-catalyzed C(sp3)-oh cleavage with concomitant c-c coupling: Synthesis of 3-substituted isoindolinones
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Copper(II) trifluoromethanesulfonate (Cu(OTf)2) efficiently catalyzes the C-C coupling of 3-hydoxyisoindolinones with a variety of aryl-, heteroaryl-, and alkenylboronic acids to furnish C(3) aryl-, heteroaryl-, and alkenyl-substituted isoindolinones. The coupling reactions work smoothly in 1,2-dicholoroethane (DCE) reflux, to effect both inter- and intramolecular versions. This is the first report on C(sp3)-OH cleavage with concomitant C-C coupling. The photolabile 2-nitrobenzyl protecting group is most appropriate for promotion of the coupling reaction and for deprotection. The tetracyclic ring motif of the alkaloid neuvamine was prepared by applying the newly developed copper-catalyzed C-C coupling.
- Rao, H. Surya Prakash,Rao, A. Veera Bhadra
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p. 1506 - 1516
(2015/02/19)
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- TfOH-catalyzed synthesis of 3-aryl isoindolinones via a tandem reaction
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A convenient metal-free method for the synthesis of 3-aryl isoindolinones via TfOH catalyzed aromatic C-H functionalization of electron-rich arenes with 2-formylbenzonitriles is developed. This process provided a new efficient strategy for the synthesis of isoindolinone derivatives in good to high yields and regioselectivities by forming two bonds.
- Hu, Jiaxing,Qin, Hua-Li,Xu, Wengang,Li, Junli,Zhang, Fanglin,Zheng, Hua
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supporting information
p. 15780 - 15783
(2015/01/08)
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- Hydrogenolysis of the C-O bond of hydroxylactams as a convenient method for the synthesis of substituted isoindolin-1-ones
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A simple and efficient method for the synthesis of isoindolin-1-ones containing alkyl or aryl substituents at positions 2 and (or) 3 was suggested. The method is based on the earlier unknown Pd0-catalyzed hydrogenolysis of hydroxylactams.
- Sagirova,Starodubtseva,Turova,Vinogradov
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p. 1032 - 1037
(2014/03/21)
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- Asymmetric hydrogenolysis of racemic tertiary alcohols, 3-substituted 3-hydroxyisoindolin-1-ones
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Asymmetric hydrogenolysis of racemic tertiary alcohols, 3-substituted 3-hydroxyisoindolin-1-ones, was developed using chiral phosphoric acid as catalyst and a Hantzsch ester as the hydrogen source with up to 95% ee. The reaction process of this asymmetric
- Chen, Mu-Wang,Chen, Qing-An,Duan, Ying,Ye, Zhi-Shi,Zhou, Yong-Gui
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supporting information; experimental part
p. 1698 - 1700
(2012/03/11)
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- Rhodium-catalyzed synthesis of branched amines by direct addition of benzamides to imines
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Rhodium-catalyzed addition of benzamide C-H bonds to a range of aromatic N-sulfonyl aldimines has been developed and proceeds with high functional group compatibility. The synthetic utility of the resulting branched amine products has also been demonstrated by the preparation of isoindoline and isoindolinone frameworks.
- Hesp, Kevin D.,Bergman, Robert G.,Ellman, Jonathan A.
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p. 2304 - 2307
(2012/06/30)
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- Rhodium(iii)-catalyzed oxidative carbonylation of benzamides with carbon monoxide
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An efficient strategy for the oxidative carbonylation of aromatic amides via C-H/N-H activation to form phthalimides using an Rh(iii) catalyst has been developed. The reaction shows a preference for C-H bonds of electron-rich aromatic amides and tolerates a variety of functional groups. The Royal Society of Chemistry 2011.
- Du, Ya,Hyster, Todd K.,Rovis, Tomislav
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p. 12074 - 12076
(2011/12/14)
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- N-Capping of primary amines with 2-Acylbenzaldehydes to give isoindolinones
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A unique reactivity pattern, first observed in the conversion of the marine natural product pestalone into pestalachloride A, was investigated. It was shown that 2-formyl-arylketones smoothly react with ammonia and primary amines, respectively, under mild
- Augner, Daniel,Gerbino, Dario C.,Slavov, Nikolay,Neudoerfl, Joerg-Martin,Schmalz, Hans-Guenther
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supporting information; experimental part
p. 5374 - 5377
(2011/12/03)
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- Preparation and use of compounds as protease inhibitors
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Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein Q is a bond or —N(R5)—;T is a bond, —O—, —C(O)—; S, —N(R5)—, or —C(R6′R7′);U
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Page/Page column 25
(2008/12/07)
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- A Practical Two-Step Synthesis of 3-Alkyl-2,3-dihydro-1H-isoindolin-1-ones
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A flexible approach to 3-alkyl-2,3-dihydro-1H-isoindolin-1-ones via the reductive-alkylation procedure is described. Present method is versatile in scope, allowing the easy introduction of various C-3 carbon-substituents by Grignard addition to phthalimid
- Ruan, Yuan-Ping,Chen, Ming-De,He, Ming-Zhu,Zhou, Xiang,Huang, Pei-Qiang
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p. 853 - 861
(2007/10/03)
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- A new synthesis of 3-alkyl-1-isoindolinones
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A new, concise, and efficient method for the synthesis of 3-alkyl-1-isoindolinones was described. 3-Alkyl-3-hydroxy-2,3-dihydro-1-isoindolinones, prepared from the reaction of phthalimide and alkyl lithium, were treated with sodium cyanoborohydride in aci
- Wang, Eng-Chi,Chen, Hsien-Fan,Feng, Pei-Kuan,Lin, Yu-Li,Hsu, Ming-Kuan
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p. 9163 - 9165
(2007/10/03)
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- A new simple and convenient synthesis of 3-substituted phthalimidines
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An efficient and versatile synthesis of 3-substituted phthalimidines based upon an organometallic reagent addition reduction sequence performed on an appropriate N-protected phthalimide is described. (C) 2000 Elsevier Science Ltd.
- Deniau, Eric,Enders, Dieter
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p. 2347 - 2350
(2007/10/03)
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- Structure-activity relationships in a series of bisquaternary bisphthalimidine derivatives modulating the muscarinic M2-receptor allosterically
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Hexane-bisammonium-type compounds containing lateral phthalimide moieties are well-established ligands of the common allosteric binding site of muscarinic M2 receptors. Previous structure-activity relationships (SAR) revealed two positively charged centers and two lateral phthalimide moieties in a defined arrangement to be essential of a high allosteric potency. The purpose of this study was to replace one carbonyl group of the phthalimides with hydrogens, hydroxy, alkoxy, phenyl, benzyl, and benzylidene groups in order to check the influence of these substituents on the allosteric activity in antagonist-linked receptors. The analysis of the quantitative SAR indicated that a high allosteric potency is related to a certain amount of rigidity as well as polarizibility and the ability to form hydrophobic interactions.
- Botero Cid, Hector M.,Tr?nkle, Christian,Baumann, Knut,Pick, Rainer,Mies-Klomfass, Elisabeth,Kostenis, Evi,Mohr, Klaus,Holzgrabe, Ulrike
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p. 2155 - 2164
(2007/10/03)
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- Ligands for the common allosteric site of acetylcholine M2-receptors: Development and application
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Ligands for the allosteric site of acetylcholine M2 receptors are able to retard the dissociation of simultaneously bound ligands for the orthosteric site. This effect promotes receptor occupation by the orthosteric ligand. The allosteric effec
- Holzgrabe,Bender,Botero Cid,Staudt,Pick,Pfletschinger,Balatkova,Traenkle,Mohr
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p. 149 - 155
(2007/10/03)
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- Study of the photochemical and in vitro phototoxicity of chlortalidone [2-chloro-5-(1-hydroxy-3-oxo-1-isoindolinyl)benzene sulfonamide]
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The photodegradation process of the phototoxic diuretic drag chlorthalidone was studied. The products of its photolysis under UV-B were isolated and identified. Chlorthalidone was found to be active when examined by photohemolysis on human erythrocytes, but not in the presence of the isolated photoproducts. Inhibition of the photohemolysis process induced by chlorthalidone on addition of reduced glutathione (GSH) or ascorbic acid suggests the involvement of radicals species. The inhibition with 1,4- diazabycyclo [2.2.2] octane (DABCO), sodium azide (NAN3) sowie 2,5- dimethylfuran proof the participation of singlet oxygen (1O2) in this process.
- Vargas, Franklin,Mendez
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p. 920 - 922
(2007/10/03)
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- Formation of Isoindoline Derivatives from o-Bromoacetylbenzophenones
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o-Dibromoacetylbenzophenone, 2 or o-bromoacetylbenzophenone 3 reacted with aqueous ammonia to produce 3-phenylisoindolin-1-one 5.The reaction of 3 with methylamine afforded 3-hydroxy-2-methyl-3-phenyl-isoindolin-1-one 4 and 2-methyl-3-phenylisoindolin-1-o
- Nan'ya, Seiko,Ishida, Hirofumi,Butsugan, Yasuo
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p. 1725 - 1726
(2007/10/02)
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- Untersuchungen zur Chemie von Isoindolen und Isoindoleninen, XXXVIII. 3-Alkoxy-1H-isoindole mit Substituenten am 5-Ring - Heterocycliche Imidsaeureester mit fixierter benzoider Struktur.
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3-Alkoxy-1H-isoindoles bearing substituents at the five-membered ring have been synthesized starting with substituted isoindoline-1-ones via regiospecific O-alkylation with trialkyl oxonium tetrafluoroborates or alkyl trifluoromethanesulfonates and subsequent NH-deprotonation.The dependence of spectroscopic properties on the substituents has been investigated.The heterocyclic imidates exist exclusively in the benzenoid 1H-structure; the tautomeric o-quinonoid 2H-form cannot be detected by spectroscopic means.
- Kreher, Richard P.,Hennige, Hans,Konrad, Michael,Uhrig, Juergen,Clemens, Andrea
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p. 809 - 828
(2007/10/02)
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- HYDROXYIMINOISOQUINOLIN-3(2H)-ONES, VIII. ACID-CATALIZED RING CONTRACTION AND SEMMLER-WOLFF TYPE REARRANGEMENT
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The refluxing of 4-hydroxyimino-1,4-dihydroisoquinolin-3(2H)-ones (1a-e) with formic acid resulted in a hitherto unknown rearrangement to give 4-formamidoisoquinolin-3(2H)-ones (2a-e).Acetylation of the deformylated compound (3) with acetic anhydride in a
- Tikk, Istvan,Deak, Gyula,Tamas, Jozsef
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p. 289 - 294
(2007/10/02)
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