A new synthesis of 3-alkyl-1-isoindolinones

Wang, Eng-Chi; Chen, Hsien-Fan; Feng, Pei-Kuan; Lin, Yu‐Li; Hsu, Ming-Kuan

doi:10.1016/s0040-4039(02)02273-6

Cited by 40 publications

(12 citation statements)

References 16 publications

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“…As outlined in Scheme 4, the product 3-hydroxyisoindolin-1-ones can be further diversified through a variety of reactions. Treatment with sodium cyanoborohydride leads to 3-alkyl-1-isoindolinones 25, 3 whereas treatment of the same species with sodium borohydride in alcoholic solvents generates 3-alkoxy esters 26. 3,15 Treatment of the 3-hydroxyisoindolin-1-ones with acid results in the dehydration product, generating a cis/trans mixture of the corresponding alkenes 27.…”

Section: Methodsmentioning

confidence: 99%

“…1 In addition to the development of previously unknown transformations and couplings, transition-metal catalysis can provide greater control over known reactions through the use of less forceful reaction conditions, ultimately allowing the use of a broader range of substrates. For example, the reaction of strongly nucleophilic organometallic reagents, such as Grignards 2 and organolithiums, 3 with imides is well precedented. These reactions, however, are often plagued by uncontrolled multiple nucleophile additions to generate complex mixtures of products.…”

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confidence: 99%

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Nickel-Catalyzed Direct Addition of Diorganozinc Reagents to Phthalimides: Selective Formation of Gamma-Hydroxylactams

Dennis

Calyore

Sjoholm

et al. 2013

Synlett

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Index General Information S2 General Method for Direct Addition of Et 2 Zn to Phthalimides S2 Method for Direct Addition with in situ Diorganozinc Reagents S3 Characterization of New Compounds S4 Method for the formation and characterization of compounds 25-28 S11 1 H and 13 C NMR Spectra of New Compounds S15 S2 General Methods. All reactions were carried out under an atmosphere of nitrogen or argon in oven-dried glassware with magnetic stirring. Solvents, including toluene, tetrahydrofuran, and diethyl ether were purged with argon and passed through two columns of neutral alumina or molecular sieves. All starting materials are commercially available and used without purification or prepared according to procedures provided. All phthalimides were obtained commercially or prepared via the condensation of phthalic acid with the appropriate amine in either refluxing toluene (Dean-Stark conditions) or in refluxing acetic acid. 1 Compounds 2, 2 4, 3 12, 4 13, 4 15, 4 16, 4 21, 5 and 24 4 have been previously described in varying levels of detail-full data are included herein. Full characterization data is provided for all new compounds. 1 H and 13 C NMR spectra were obtained using standard acquisition parameters and are referenced to TMS. All HRMS measurements were made using ESI with TOF detection. General Method for Direct Addition of Et 2 Zn to Phthalimides will be illustrated with a specific example. PPh 3 (13.1 mg, 0.055 mmol) and N-phenylphthalimide (111.6 mg, 0.50 mmol) were combined with a stirbar in an oven dried 25 mL round-bottomed flask. The flask was transferred into an inert atmosphere glove box, where Ni(COD) 2 (140 mg, 0.051 mmol) was added. The flask was sealed with a septum and removed from the glove box, whereupon THF (2 mL) was added, followed by Et 2 Zn (56.5 μL, 0.055 mmol, 1.1 equiv). The solution was then brought up to temperature in a 55 °C oil bath and allowed to stir for 16 h. Following reaction, the reaction was cooled to room temperature, the septum was removed and the reaction mixture was diluted with Et 2 O (15 mL). The addition of 2 M aq HCl (15 mL) quenched the reaction, which was then S3 extracted with Et 2 O (3× 15 mL). The combined organic layers were washed with brine (15 mL), dried over MgSO 4 and concentrated under reduced pressure. The resulting yellow oil was purified by column chromatography (4:1 hexane:ethyl acetate) to provide 1 in 81% yield. General Method for Direct Addition with in situ Generated Diorganozinc Reagents will be illustrated with a specific example. 1-bromo-4-tert-1.33 mmol) was added to an oven-dried 10-mL round-bottomed flask, sealed with a septum, evacuated and refilled with Ar (3×) and dissolved in THF (2 mL). The reaction mixture was cooled to-78 °C and n stirred at-78 °C for 1 h. In a separate flask, ZnCl 2 (92.1 mg, 0.68 mmol) was dried by heating under vacuum and then dissolved in THF (1 mL). This solution was then added to the solution of ArLi, still at-78 °C. The reaction was removed from the cold bath and allowed to warm to room temperature while s...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Nickel-Catalyzed Direct Addition of Diorganozinc Reagents to Phthalimides: Selective Formation of Gamma-Hydroxylactams

Dennis

Calyore

Sjoholm

et al. 2013

Synlett

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“…A typical protocol involves sodium mediated anionic heterocyclization of 2‐alkynylbenzonitriles followed by methanolysis reaction . Wang et al described an improved synthesis of 3‐alkylisoindolin‐1‐ones from phthalimide and organometallic reagents, through alkylation, dehydration, and with concomitant reduction by sodium cyanoborohydrate in an acidic medium . In addition, a Horner reaction between phosphorylated isoindolinones and aryl aldehydes was developed to prepare 3‐methyleneisoindolin‐1‐ones alkaloid .…”

Section: Figurementioning

confidence: 99%

“…[4] Wang et al described an improved synthesis of 3-alkylisoindolin-1-ones from phthalimide and organometallic reagents, through alkylation, dehydration, and with concomitant reduction by sodium cyanoborohydrate in an acidic medium. [5] In addition, a Horner reaction between phosphorylated isoindolinones and aryl aldehydes was developed to prepare 3-methyleneisoindolin-1ones alkaloid. [6] Kise and co-workers recently reported electroreductive intramolecular coupling of phthalimides with aldehydes in the presence of TMS/TEA, thus generating fused isoindolobenzazepine alkaloids in good yields.…”

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confidence: 99%

Alkali‐Metal Promoted Chemo‐ and Regioselective Cycloisomerization Reactions to (Z)‐3‐Alkylideneisoindolin‐1‐ones: Unusual Positive Role of H₂O

2018

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An alkali‐metal promoted cycloisomerization reaction of 2‐alkynylbenzamides is described for the synthesis of useful (Z)‐3‐alkylideneisoindolin‐1‐one derivatives in modest to good yields and excellent chemo‐ and regioselectivity. Superstoichiometric amounts of water was found to be crucial for this reaction, and no transition‐metal salts are necessary. This synthetically green protocol proceeds efficiently with 100% atom economy and tolerates a diverse number of functional groups.

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“…Reduction On treatment with alkyllithiums, phthalimide (68) resulted in 3-alkyl-3-hydroxy-2,3-dihydroisoindolones 69, which, on subsequent dehydration and reduction with NaBH 3 CN, afforded isoindolones 57 (Scheme 25) [46]. Reduction On treatment with alkyllithiums, phthalimide (68) resulted in 3-alkyl-3-hydroxy-2,3-dihydroisoindolones 69, which, on subsequent dehydration and reduction with NaBH 3 CN, afforded isoindolones 57 (Scheme 25) [46].…”

Section: -80%mentioning

confidence: 99%

Approaches to the Formation of Condensed Isoindolones

Csende¹,

Stájer

2005

COC

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Both direct and multistep reactions, involving the application of carbonyl compounds, e. g. oxoacids, phthalimides, 2-iodobenzamides or acylhalides, have been developed as novel synthetic routes for the preparation of 3substituted 2,3-dihydro-1H-isoindol-1-ones, which are reviewed here. Alternatively, reductive or acid-catalyzed rearrangements of certain heterocycles lead to the formation of 3-substituted isoindolones. Asymmetric syntheses too have been described. R 2 = alkyl, Bzl, Ph 17 18 48-51% Advanced Methods for the Synthesis of 3-Substituted Current

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A new synthesis of 3-alkyl-1-isoindolinones

Cited by 40 publications

References 16 publications

Nickel-Catalyzed Direct Addition of Diorganozinc Reagents to Phthalimides: Selective Formation of Gamma-Hydroxylactams

Nickel-Catalyzed Direct Addition of Diorganozinc Reagents to Phthalimides: Selective Formation of Gamma-Hydroxylactams

Alkali‐Metal Promoted Chemo‐ and Regioselective Cycloisomerization Reactions to (Z)‐3‐Alkylideneisoindolin‐1‐ones: Unusual Positive Role of H₂O

Approaches to the Formation of Condensed Isoindolones

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A new synthesis of 3-alkyl-1-isoindolinones

Cited by 40 publications

References 16 publications

Nickel-Catalyzed Direct Addition of Diorganozinc Reagents to Phthalimides: Selective Formation of Gamma-Hydroxylactams

Nickel-Catalyzed Direct Addition of Diorganozinc Reagents to Phthalimides: Selective Formation of Gamma-Hydroxylactams

Alkali‐Metal Promoted Chemo‐ and Regioselective Cycloisomerization Reactions to (Z)‐3‐Alkylideneisoindolin‐1‐ones: Unusual Positive Role of H2O

Approaches to the Formation of Condensed Isoindolones

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Alkali‐Metal Promoted Chemo‐ and Regioselective Cycloisomerization Reactions to (Z)‐3‐Alkylideneisoindolin‐1‐ones: Unusual Positive Role of H₂O