Oxidative Coupling of 3‐Oxindoles with Indoles and Arenes

Jemison, Adriana; Nigro, Erin; Kozlowski, Marisa C.

doi:10.1002/cssc.201900438

Cited by 9 publications

(3 citation statements)

References 29 publications

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“…The above results demonstrate that indole oxidation, catalyzed by Mn-MC6*a, led to a product in which a cosolvent TFE molecule is incorporated at the C2 position of 3-oxindole. This compound is a highly interesting intermediate from a synthetic point of view as it is well suited for the construction of various synthetic targets through substitution of the trifluoroethoxy group with appropriate nucleophiles. , 2-TFE-3-oxindole is characterized by a high electrophilic character at the C2 position, similarly to 3-oxindolenine. As a proof of such reactivity, 2-TFE-3-oxindole was gradually converted into multiple reaction products when the oxidation reaction was carried out for longer times (up to 60 min) at pH 8.5 (Figure S7 and Table S1).…”

Section: Resultsmentioning

confidence: 99%

Highly Selective Indole Oxidation Catalyzed by a Mn-Containing Artificial Mini-Enzyme

et al. 2021

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Indole oxidation represents a real challenge for selectivity because it typically leads to complex mixtures of products even when highly selective enzymes are used. Here, we describe the catalytic potential of an artificial enzyme, Mn-Mimochrome VI*a (Mn-MC6*a), in promoting indole oxidation. This mini-enzyme contains a manganese−deuteroporphyrin active site within a scaffold of two synthetic small peptides covalently linked to porphyrin. Mn-MC6*a promotes the selective oxidation of indole at its C3 position, leading to a 3-oxindole derivative (2-TFE-3oxindole) with unprecedented product selectivity (86% at pH 8.5) compared to native or artificial heme-enzymes. We also suggest a possible reaction mechanism based on the effect of pH, cosolvent, and indole substitution on the reaction outcome. These studies demonstrate that Mn-MC6*a is an excellent artificial peroxygenase for the production of 3-oxindole-containing compounds as key building blocks for the synthesis of fine chemicals.

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Section: Resultsmentioning

confidence: 99%

Highly Selective Indole Oxidation Catalyzed by a Mn-Containing Artificial Mini-Enzyme

et al. 2021

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“…Screening our catalyst library rapidly led to a copper salan catalyst that was highly effective with a range of substrates (Scheme ). Mechanism studies support the formation of a copper enolate with the oxindole that undergoes facile oxidation to a captodative radical, which can reversibly dimerize. Capture of this radical by the radical cation of the second substrate leads to irreversible formation of the product upon rearomatization of the second component.…”

Section: Discussionmentioning

confidence: 99%

Catalytic Oxidative Coupling of Phenols and Related Compounds

Kozlowski

2022

ACS Catal.

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Phenols and their derivatives are the elementary building blocks for several classes of complex molecules that play essential roles in biological systems. Nature has devised methods to selectively couple phenolic compounds, and many efforts have been undertaken by chemists to mimic such coupling processes. A range of mechanisms can be involved, and with well-studied catalysts, reaction outcomes in phenol−phenol oxidative coupling reactions can be predicted with a good level of fidelity. However, reactions with catalysts that have not been studied or that do not behave similarly to known catalysts can be hard to predict and control. This Perspective provides an overview of catalytic methods for the oxidative coupling of phenols, focusing on the last 10 years, and summarizes current challenges.

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“…By contrast, no reaction was observed when indole ( 2 a ) was individually subjected to the oxidation system (Figure 3b). Given the much lower oxidation potential of 3‐hydroxyindole ( 1 a ; +0.64 V vs. Ag/AgCl) [18a] than that of indole ( 2 a ; 1.28 V vs. Ag/AgCl), [18b] it appears safe to propose that the cross‐coupling reaction commenced with the oxidation of 1 a to intermediate 5 by CueO, followed by nucleophilic addition of indole ( 2 a ) to the imine moiety of 5 . Given that the latter step requires extra acid activation [19] and the recorded excellent enantioselectivity, we speculated that CueO played a second role as an acid catalyst apart from its primary function for catalytic oxidation.…”

Section: Methodsmentioning

confidence: 99%

Expanding the Promiscuity of a Copper‐Dependent Oxidase for Enantioselective Cross‐Coupling of Indoles

et al. 2023

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Herein, we disclose the highly enantioselective oxidative cross-coupling of 3-hydroxyindole esters with various nucleophilic partners as catalyzed by copper efflux oxidase. The biocatalytic transformation delivers functionalized 2,2-disubstituted indolin-3-ones with excellent optical purity (90-99 % ee), which exhibited anticancer activity against MCF-7 cell lines, as shown by preliminary biological evaluation. Mechanistic studies and molecular docking results suggest the formation of a phenoxyl radical and enantiocontrol facilitated by a suited enzyme chiral pocket. This study is significant with regard to expanding the catalytic repertoire of natural multicopper oxidases as well as enlarging the synthetic toolbox for sustainable asymmetric oxidative coupling.

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Oxidative Coupling of 3‐Oxindoles with Indoles and Arenes

Abstract: Scheme5.Scopeo ft he cross-coupling of 3-oxindoles with simple arenes.Scheme3.Scope of the coupling of 3-oxindolesw ith indoles.[a] Reactionat 80 8C.

Cited by 9 publications

References 29 publications

Highly Selective Indole Oxidation Catalyzed by a Mn-Containing Artificial Mini-Enzyme

Highly Selective Indole Oxidation Catalyzed by a Mn-Containing Artificial Mini-Enzyme

Catalytic Oxidative Coupling of Phenols and Related Compounds

Expanding the Promiscuity of a Copper‐Dependent Oxidase for Enantioselective Cross‐Coupling of Indoles

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