Synthesis of 2-hydroxy-3-indolinones and 3-hydroxy-2-indolinones by anionic cyclization, in situ oxidation and rearrangement

Coldham, Iain; Adams, Harry; Ashweek, Neil J.; Barker, Thomas A.; Reeder, Andrew T.; Skilbeck, Melanie C.

doi:10.1016/j.tetlet.2010.02.159

Cited by 17 publications

(7 citation statements)

References 48 publications

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“…Air-stable indoxyl derivatives like intermediate E are reported in the literature . Therefore, aerial oxidation of intermediate E takes place under the reaction conditions to provide the desired 2-hydroxyindoxyls 3 as previously reported. , We presume that intermediate E can suffer ready enolization due to extensive conjugation and exist as indole intermediate D . The stability of intermediate D may be attributed to the presence of acidic C2-hydrogen and activated carbonyl group, and therefore, no Grignard addition product to the C3-carbonyl group of the intermediate E is detected.…”

supporting

confidence: 51%

“…Other reported approaches for the synthesis of 2-hydroxyindoxyls involve base-mediated ring contraction of 3-hydroxy-2,4(1 H ,3 H )-quinolinediones, acidic hydrolysis of a 3-acetoxy-2-phenylindole precursor, butyllithium-promoted tandem cyclization, and autoxidation of 2-(benzylamino)benzamide derivatives (Scheme ). Recently, Zhu and co-workers reported the synthesis of a 2-hydroxyindoxyl derivative by using a Cu(I)-catalyzed intramolecular C (sp3)–H amidation of 2-aminoacetophenone utilizing O 2 as the oxidant at high temperature (Scheme ). Later, Yang et al developed an oxidative cyclization of 2-aminophenyl-1,3-dione using CAN and TEMPO as oxidants for the synthesis of 2-hydroxyindoline-3-ones (Scheme ).…”

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confidence: 99%

“…We propose that the reaction of 3-hydroxy-2-oxindoles 1 initiates with the formation of the intermediate A . ,, The Grignard addition to the intermediate A provides the intermediate B , which subsequently generates the indolinium ion intermediate C (Scheme ). Then aromatization-driven C3-hydrogen abstraction provides indole intermediate D that tautomerizes by capturing the proton lost during the aromatization to generate indoxyl intermediate E .…”

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confidence: 99%

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Domino Grignard Addition and Oxidation for the One-Pot Synthesis of C2-Quaternary 2-Hydroxyindoxyls

2019

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We herein delineate an unexplored reactivity of 3-hydroxyoxindoles toward Grignard addition enabling a rapid access to a broad range of unnatural C2-quaternary 2-hydroxyindoxyls in high yields. The reaction proceeds via a mechanistically intriguing one-pot 1,2-hydride shift followed by autoxidation pathway. The utility of this method is demonstrated by the synthesis of a new class of bis-indoxyl spirofuran derivatives.T he oxindole moiety is present in a large number of natural products and biologically active molecules. 1 The motif has also been used as a versatile synthetic intermediate for various organic transformations. 1,2 On the contrary, 2hydroxyindoxyl, a pseudooxindole moiety, has remained less explored. The indoxyl ring system bearing a C2-quaternary center is a privileged structural unit present in various natural products like brevianamide A and B, 3 rupicoline, 4 iboluteine, 5 austamide, 6 phytoaliexin, erucalexin, 7 and matemone, 8 as well as biologically active compounds (Figure 1). For instance, 2hydroxyindoxyl alkaloid melochicorin, isolated from the plant Melochia corchorifolia, 9 shows hepatoprotective and antioxidant activity. 10 While 3-substituted 3-hydroxy-2-oxindoles can be easily synthesized by reported methods, 11 the preparation of unnatural 2-substituted 2-hydroxyindoxyls remains a synthetic challenge. Until now, only a few convenient methods are available for the synthesis of pseudooxindole 2-hydroxyindoxyls. Generally, oxidation of indoles using m-CPBA, 12 monoperphthalic acid, 13 and DMDO 14 produces 2-hydroxyindoxyls as byproducts. Davis' reagent has been used to improve the yield of 2-hydroxyindoxyls. 15 Sakamoto et al. 16 reported oxidation of 2-substituted N-acylindoles by MoO 5 • HMPA to directly obtain 1-acetyl-2-hydroxyindoxyls. Later, Jimenez et al. used oxodiperoxo molybdenum complexes to improve the yield. 17 The oxidation of 2,3,6-trimethyl-4-(1H)quinolinone by NaOCl 18 and 2-methyl-3-phenylquinolinone by acidic potassium permanganate 19 has also been used to access the corresponding indoxyls. However, long reaction times and low yields render such approaches less attractive. Other reported approaches for the synthesis of 2-hydroxyindoxyls involve base-mediated ring contraction of 3-hydroxy-2,4(1H,3H)-quinolinediones, 20 acidic hydrolysis of a 3acetoxy-2-phenylindole precursor, 21 butyllithium-promoted tandem cyclization, and autoxidation of 2-(benzylamino)benzamide derivatives (Scheme 1). 22 Recently, Zhu and coworkers reported the synthesis of a 2-hydroxyindoxyl derivative by using a Cu(I)-catalyzed intramolecular C (sp3)−H amidation of 2-aminoacetophenone utilizing O 2 as the oxidant at high temperature (Scheme 1). 23 Later, Yang et al. developed an oxidative cyclization of 2-aminophenyl-1,3-dione using CAN and TEMPO as oxidants for the synthesis of 2hydroxyindoline-3-ones (Scheme 1). 24 Nevertheless, the synthesis of 2-hydroxyindoxyls from readily available starting materials with high flexibility in their substitution pattern is yet to be addressed. Therefore, an e...

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Domino Grignard Addition and Oxidation for the One-Pot Synthesis of C2-Quaternary 2-Hydroxyindoxyls

2019

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“…Compounds containing the 2-hydroxyindol-3-one substructure are important intermediates in the total syntheses of some natural products including (+)-isatisine A, (±)mersicarpine, hinckdentine A, mitomycin and others (Karadeolian & Kerr, 2010;Magolan et al, 2008;Higuchi et al, 2009;Colandrea et al, 2003;Kawasaki et al, 2004). New synthetic approaches towards 2-hydroxyindol-3-ones have been reported recently (Coldham et al, 2010;Higuchi et al, 2010;Cariou et al, 2007;Hewitt & Shao, 2006; Altinis Kiraz et al, 2004). A related 2-hydroxyindol-3-one compound, alkaloid melochicorine, was found in the plant Melochicoria corchorifolia (Bhakuni et al, 1991) In the crystal structure of (I) two molecules are connected by two intermolecular O-H Table 1).…”

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confidence: 99%

2-Hydroxy-2-methyl-1-phenylindolin-3-one

2011

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“…Thus, the importance of indoxyls has inspired wide interest in creating methodologies for their synthesis. Several reported methods for the preparation of 2,2‐disubstituted indol‐3‐ones have utilized acid‐induced, base‐induced, or thermal‐induced rearrangements of 2,3‐dihydroxyindolines and 3 H ‐indol‐3‐ols , oxidative rearrangement of 2,3‐disubstituted indoles , alkylation of 2‐substituted indol‐3‐ones , cyclization of o ‐nitrogenated acetophenones , ring contraction of 3‐hydroxy‐2,4(1 H ,3 H )‐quinolinediones , acid‐mediated substitution of 2‐alkoxyindol‐3‐one , the recent oxidation of indoles by m ‐CPBA , and so on . Still, general and efficient methods for the synthesis of indoxyls from simple and readily available precursors are of great value.…”

Section: Introductionmentioning

confidence: 99%