- Copper-catalysed synthesis of 3-hydroxyisoindolin-1-ones from benzylcyanide 2-iodobenzamides
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An efficient one-pot two-step sequential reaction for the synthesis of biologically active 3-hydroxyisoindolin-1-one derivatives from 2-iodobenzamide derivatives and various substituted benzyl cyanides in the presence of CuCl and cesium carbonate in DMSO is reported. Furthermore, 3-hydroxyisoindolinone derivatives possessing bromo substituents were obtained from 2-iodobenzamide and 2-bromobenzyl cyanide substrates in two steps. Benzyl cyanide has been successfully used for the first time as a benzoyl synthon for the synthesis of 3-hydroxyisoindolin-1-ones. Interestingly, the mechanism of formation of 3-hydroxyisoindolin-1-ones is a novel pathway that involves carbon degradation followed by ring contraction.
- Kavala, Veerababurao,Wang, Chen-Yu,Wang, Cheng-Chuan,Patil, Prakash Bhimrao,Fang, ChiaChi,Kuo, Chun-Wei,Yao, Ching-Fa
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p. 988 - 998
(2020/02/15)
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- Eosin Y as a Redox Catalyst and Photosensitizer for Sequential Benzylic C?H Amination and Oxidation
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A new synergistic multicatalytic activation mode of eosin Y has been discovered by exploiting the redox potential of its ground state and excited state. This catalytic strategy proves to be an enabling tool for visible-light-driven sequential benzylic C?H amination and oxidation of o-benzyl-N-methoxyl-benzamides when using Selectfluor as a hydrogen atom transfer (HAT) reagent and O2 as oxidant. Efficient synthesis of a range of diversely functionalized 3-hydroxyisoindolinones can thus be achieved with good yields and selectivity at mild reaction conditions. Preliminary mechanistic studies and DFT calculations suggest that eosin Y works as a redox catalyst and photosensitizer.
- Yan, Dong-Mei,Zhao, Quan-Qing,Rao, Li,Chen, Jia-Rong,Xiao, Wen-Jing
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p. 16895 - 16901
(2018/10/26)
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- Base-promoted cascade C-C coupling/N-α-sp3C-H hydroxylation for the regiospecific synthesis of 3-hydroxyisoindolinones
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A base-promoted cascade reaction for the regiospecific synthesis of substituted 3-hydroxyisoindolinones under transition-metal-free conditions is developed. The base-mediated C-C bond coupling and N-α-sp3C-H bond hydroxylation are involved in t
- Shen, Jinhai,You, Qihua,Fu, Qi,Kuai, Changsheng,Huang, Huabin,Zhao, Li,Zhuang, Zhixia
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supporting information
p. 5170 - 5173
(2017/11/06)
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- 3-hydroxy isoindole-1-ketone derivative and preparation method thereof
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The invention discloses a preparation method of a 3-hydroxy isoindole-1-ketone derivative (formula 2). A compound as shown by formula (1) is used for carrying out substitution reaction in a solvent in the presence of alkali and air to obtain the 3-hydroxy
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Paragraph 0051; 0052; 0053; 0054
(2017/11/04)
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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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- Total spontaneous resolution by deracemization of isoindolinones
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Preferential crystallization is a powerful tool to obtain optically active materials from racemic mixtures without any chiral source, and has been utilized widely for optical resolution on large scales for example in industrial processes.[ 1] To resolve optically active materials by crystallization efficiently, dynamic preferential crystallization involving a racemization process, a so-called total spontaneous resolution, has been developed.[2] Many efforts have been invested in new variations of this method, and the racemization processes can be classified into three groups: 1) involving an intermediate enolate anion or enol at the a-position of a carbonyl group,[3] 2) involving atropisomerism of axially chiral materials,[4] and 3) involving an equilibrium reaction via an achiral intermediate.[5-7] We have now developed a new example of total spontaneous resolution of isoindolinones that involves a combination of an intramolecular equilibrium reaction via an achiral intermediate and preferential crystallization.
- Yagishita, Fumitoshi,Ishikawa, Hiroki,Onuki, Tatsuo,Hachiya, Shoko,Mino, Takashi,Sakamoto, Masami
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p. 13023 - 13025
(2013/03/13)
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- Small-molecule inhibitors of the MDM2-p53 protein-protein interaction based on an isoindolinone scaffold
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From a set of weakly potent lead compounds, using in silico screening and small library synthesis, a series of 2-alkyl-3-aryl-3-alkoxyisoindolinones has been identified as inhibitors of the MDM2-p53 interaction. Two of the most potent compounds, 2-benzyl-3-(4-chlorophenyl)-3-(3-hydroxypropoxy)-2,3- dihydroisoindol-1-one (76; IC50 = 15.9 ± 0.8 μM) and 3-(4-chlorophenyl)-3-(4-hydroxy-3,5-dimethoxybenzyloxy)-2-propyl-2, 3-dihydroisoindol-1-one (79; IC50 = 5.3 ± 0.9 μM), induced p53-dependent gene transcription, in a dose-dependent manner, in the MDM2 amplified, SJSA human sarcoma cell line.
- Hardcastle, Ian R.,Ahmed, Shafiq U.,Atkins, Helen,Farnie, Gillian,Golding, Bernard T.,Griffin, Roger J.,Guyenne, Sabrina,Hutton, Claire,K?llblad, Per,Kemp, Stuart J.,Kitching, Martin S.,Newell, David R.,Norbedo, Stefano,Northen, Julian S.,Reid, Rebecca J.,Saravanan,Willems, Henri?tte M. G.,Lunec, John
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p. 6209 - 6221
(2007/10/03)
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- Anionic ring-enlarging reaction of a hemiaminal system: Stereoselective approach to disubstituted tetrahydroisoquinolone
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Treatment of N-substituted phthalimide-derived hemiaminal with alkyllithium led to tetrahydroisoquinolones with high diastereoselectivity. Mechanistic studies furnish persuasive evidence that the present ring-enlarging reaction proceeds via tautomerizatio
- Tomooka, Katsuhiko,Tomoyasu, Takahiro,Hanji, Takayuki,Igawa, Kazunobu
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p. 2449 - 2453
(2008/02/10)
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- Isoindolinone-based inhibitors of the MDM2-p53 protein-protein interaction
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A series of 2-N-alkyl-3-aryl-3-alkoxyisoindolinones has been synthesised and evaluated as inhibitors of the MDM2-p53 interaction. The most potent compound, 3-(4-chlorophenyl)-3-(4-hydroxy-3,5-dimethoxybenzyloxy)-2-propyl-2,3- dihydroisoindol-1-one (NU8231), exhibited an IC50 of 5.3 ± 0.9 μM in an ELISA assay, and induced p53-dependent gene transcription in a dose-dependent manner, in the SJSA human sarcoma cell line.
- Hardcastle, Ian R.,Ahmed, Shafiq U.,Atkins, Helen,Calvert, A. Hilary,Curtin, Nicola J.,Farnie, Gillian,Golding, Bernard T.,Griffin, Roger J.,Guyenne, Sabrina,Hutton, Claire,Kaellblad, Per,Kemp, Stuart J.,Kitching, Martin S.,Newell, David R.,Norbedo, Stefano,Northen, Julian S.,Reid, Rebecca J.,Saravanan,Willems, Henriette M.G.,Lunec, John
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p. 1515 - 1520
(2007/10/03)
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- Lewis acid-promoted tandem desulfurization and hydroxylation of γ-phenylthio-substituted lactams: Novel synthetic strategy of isoindolobenzazepine alkaloid, chilenine
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Treatment of a variety of alicyclic and aromatic γ-phenylthio- substituted lactams with Lewis acids such as cuprous or cupric halides in aqueous solution at rt was found to undergo novel tandem desulfurization and hydroxylation reactions to generate γ-hydroxylated lactams without the ring-opened products in extremely high yields, respectively. This process was further applied to the total synthesis of an isoindolobenzazepine alkaloid, chilenine, by featuring the elaboration of the functionalized phthalimide derivative.
- Yoda, Hidemi,Inoue, Kei-Ichi,Ujihara, Yasuaki,Mase, Nobuyuki,Takabe, Kunihiko
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p. 9057 - 9060
(2007/10/03)
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- Synthesis of 3-alkoxy- and 3-alkylamino-2-alkyl-3-arylisoindolinones
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Solvent-controlled regioselectivity in the reactions of 3- chloroisoindolinones with primary amines allows the rational synthesis of isoindolinones by a route suitable for parallel combinatorial chemistry.
- Kitching, Martin S.,Clegg, William,Elsegood, Mark R. J.,Griffin, Roger J.,Golding, Bernard T.
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p. 997 - 999
(2007/10/03)
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- SYNTHESIS OF 1-SUBSTITUTED 3,4-DIARYLISOQUINOLINE DERIVATIVES
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3,4-Diaryl-2H-isoquinolin-2-ones and corresponding 1-chloro derivatives were easily prepared in a way involving i) condensation of 2-aroylbenzyl chlorides with arylmethylamines; ii) treatment of the resulting 1-aryl-N-1-hydroxyarylmethylisoindol-3-ones wi
- Delcey, Martine Croisy,Huel, Christiane,Bisagni, Emile
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p. 1721 - 1730
(2007/10/03)
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- Photochimie organique: photolyse de O-benzoylbenzamides secondaires et tertiaires
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Intramolecular photoreduction of ketones leads to a diradical likely to undergo cleavage or cyclization to yield cyclobutanols (Norrish type II reaction).Examples of intramolecular δ- or ε-H-abstraction are known to lead to 1,5- or 1,6-diradicals, the cyclization of which gives rise to five or six-membered rings.We have prepared a series of O-benzoyl-benzamides and studied their photolysis in order to establish a pathway to phenyltetrahydroisoqoinolines.We have thus prepared N-ethyl, N-isopropyl and N-benzyl-O-benzoylbenzamides and shown that in solution these compounds have a cyclic structure (3-hydroxy-3-phenylphtalimidine) in which the ketone carbonyl is hidden.These compounds are photochemically inert.Four tertiary O-benzoylbenzamides have been prepared (N,N-diethyl, N,N-di-n-butyl, N-butyl-N-methyl, and N-benzyl-N-methyl).These compounds exhibit an n?* absorption above 300 nm.Their photolysis (λ > 300 nm) gives rise in all four cases to the 3-phenylphtalide 9 and to their dimer 10 of the 3-phenylphtalid-3-yl radical (meso and d,l) mixture.Upon irradiation below 300 nm (253.7 nm in quartz), formation of the diphtalide (dimer 10), not of the phenylphtalide 9, is observed.Finally no cyclic photoproducts derived from a 1,6-diradical are observed.In thus appears that deactivation of the excited state of tertiary O-benzolylbenzamides does not occur by intramolecular abstraction of the hydrogen α to the amide nitrogen atom, but rather by homolytic cleavage of the amide C-N bond.The radical thus formed cyclizes, giving a 3-phenylphtalid-3-yl radical which further yields, either the 3-phenylphtalide 9 by hydrogen capture, or the dimer 10 by coupling.During irradiation at 253.7 nm the optical density of the solution is very high (of the order of 1000) because of the high ε values of the starting compounds.The local concentration of 3-phenylphtalid-3-yl radicals is thus high, promoting their coupling to dimer at the expense of hydrogen capture, which would lead to the 3-phenylphtalide 9.
- Gramain, Jean-Claude,Lhomme, Marie-France
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p. 141 - 146
(2007/10/02)
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