Aerobic Catalyzed Oxidative Cross-Coupling of <i>N</i>,<i>N</i>-Disubstituted Anilines and Aminonaphthalenes with Phenols and Naphthols

Paniak, Thomas J.; Kozlowski, Marisa C.

doi:10.1021/acs.orglett.0c00046

“…An optimized protocol with 40 mol% of BF 3 ⋅ OEt 2 as additive and air as oxidant afforded compound 3 a in 66 % yield (entry 5). In comparison, the recently reported oxidative coupling of 2‐(dimethylamino)naphthalene ( 1 a ) with various phenols using a chromium−salen catalyst under aerobic conditions afforded mixtures of C−C and C−O coupling products [21] . Variation of the reaction conditions given in entry 5 of Table 1 gave no further improvement.…”

Section: Resultsmentioning

confidence: 85%

“…In comparison, the recently reported oxidative coupling of 2-(dimethylamino)naphthalene (1 a) with various phenols using a chromiumÀ salen catalyst under aerobic conditions afforded mixtures of CÀ C and CÀ O coupling products. [21] Variation of the reaction conditions given in entry 5 of Table 1 gave no further improvement. For example, the very slow reaction in ethanol as solvent afforded 3 a in only 17 % yield after 24 h (entry 6) and the reaction at 0 °C provided 3 a in only 36 % yield (entry 7).…”

Section: Resultsmentioning

confidence: 97%

Iron‐Catalyzed Oxidative C−O and C−N Coupling Reactions Using Air as Sole Oxidant**

Purtsas

¹

,

Rosenkranz

²

,

Dmitrieva

³

et al. 2022

Chemistry A European J

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We describe the oxygenation of tertiary arylamines, and the amination of tertiary arylamines and phenols. The key step of these coupling reactions is an iron-catalyzed oxidative CÀ O or CÀ N bond formation which generally provides the corresponding products in high yields and with excellent regioselectivity. The transformations are accomplished using hexadecafluorophthalocyanineÀ iron(II) (FePcF 16 ) as catalyst in the presence of an acid or a base additive and require only ambient air as sole oxidant.

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“…21,[32][33][34] Numerous metal catalysts and metal-free oxidants have been reported for the dimerization and cross-coupling of phenolic substrates; however, the application of these methods is commonly restricted to electron-rich phenols or those bearing only mildly electron-withdrawing groups such as halides. [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] When general reactivity can be achieved, controlling the selectivity of the oxidative coupling reaction presents several additional layers of difficulty with the need to exert control over chemo-, site-, and atroposelectivity to form sterically hindered biaryl bonds (Figure 1c). Extensive investigation over the last two decades has provided insight into the selectivity outcomes of phenolic oxidative cross-couplings, leading to the development of computational tools and predictive models based on mechanistic investigation of select catalysts and the electronics of each phenol to better understand the chemoselectivity outcomes of these reactions .…”

mentioning

confidence: 99%

Biaryl bond formation through biocatalytic oxidative cross-coupling reactions

Zetzsche

¹

,

Yazarians

²

,

Chakrabarty

³

et al. 2021

Preprint

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Biocatalysis offers compelling advantages in synthesis, often becoming the method of choice based on sustainability, safety, and selectivity considerations. Despite these advantages, enzymes in synthesis are typically dedicated to functional group intercon versions in linear synthetic sequences and have not been broadly integrated into the retrosynthetic logic for carbon skeleton assembly. In this article, we disclose a biocatalytic platform for fragment coupling to assemble target molecules convergently. Specifically, we report a strategy for biocatalytic phenolic cross-coupling through oxidative C-C bond formation. Using cytochrome P450 enzymes, we demonstrate the ability to catalyze cross-coupling reactions on a panel of phenolic substrates and further demonstrate the ability to tune these catalysts to possess the desired reactivity, site-, and atroposelectivity. This streamlined method for constructing sterically-hindered biaryl bonds provides an engineerable platform for assembling molecules with programmable catalyst-controlled reactivity and selectivity unprecedented with small molecule catalysts.Convergent synthetic strategies enable the efficient construction of carbon frameworks, quickly generating complexity by stitching individual building blocks together. 1 Chemists depend on transformations, such as cross-coupling reactions, that can reliably be programmed into synthetic routes for convergent approaches. 2 Ideally, reactions planned for the assembly phase of a convergent synthesis are both perfectly selective and tolerate a breadth of functional groups to minimize the production of undesired products, installation of protecting groups, or unnecessary redox manipulations. 3 These qualities are common in biocatalytic reactions due to the catalyst-controlled selectivity possible with large molecule catalysts; 4 however, the enzymatic transformations most commonly applied in synthesis are confined to functional group interconversions, not convergent steps within a synthetic route. [5][6][7][8][9][10][11] To enable convergent biocatalytic strategies, a handful of biocatalytic methods have recently been developed, [12][13][14][15] foreshadowing the potential of convergent biocatalysis in synthesis. Based on the paucity of enzyme-mediated methods for uniting substantial fragments, we developed an intense interest in expanding the repertoire of biocatalysts capable of convergent fragment couplings. As a first step toward this goal, we sought to develop a platform for the biocatalytic assembly of carbon frameworks through oxidative cross-coupling reactions, thus providing a solution for this transformation's outstanding reactivity and selectivity challenges through biocatalysis and enabling convergent synthetic routes (Figure 1a).We chose to target biaryl bond formation as a model transformation for convergent cross-coupling reactions, given the ubiquitous nature of biaryl scaffolds in drugs, materials, and ligands for asymmetric catalysis (Figure 1b) and the fundamental synthetic challenges presented by the...

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“…21,[32][33][34] Numerous metal catalysts and metal-free oxidants have been reported for the dimerization and cross-coupling of phenolic substrates; however, the application of these methods is commonly restricted to electron-rich phenols or those bearing only mildly electron-withdrawing groups such as halides. [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] When general reactivity can be achieved, controlling the selectivity of the oxidative coupling reaction presents several additional layers of difficulty with the need to exert control over chemo-, site-, and atroposelectivity to form sterically hindered biaryl bonds (Figure 1c). Extensive investigation over the last two decades has provided insight into the selectivity outcomes of phenolic oxidative cross-couplings, leading to the development of computational tools and predictive models based on mechanistic investigation of select catalysts and the electronics of each phenol to better understand the chemoselectivity outcomes of these reactions .…”

mentioning

confidence: 99%

Biaryl bond formation through biocatalytic oxidative cross-coupling reactions

Zetzsche

¹

,

Yazarians

²

,

Chakrabarty

³

et al. 2021

Preprint

0

View full text Add to dashboard Cite

Biocatalysis offers compelling advantages in synthesis, often becoming the method of choice based on sustainability, safety, and selectivity considerations. Despite these advantages, enzymes in synthesis are typically dedicated to functional group interconversions in linear synthetic sequences and have not been broadly integrated into the retrosynthetic logic for carbon skeleton assembly. In this article, we disclose a biocatalytic platform for fragment coupling to assemble target molecules convergently. Specifically, we report a strategy for biocatalytic phenolic cross-coupling through oxidative C–C bond formation. Using cytochrome P450 enzymes, we demonstrate the ability to catalyze cross-coupling reactions on a panel of phenolic substrates and further demonstrate the ability to tune these catalysts to possess the desired reactivity, site-, and atroposelectivity. This streamlined method for constructing sterically-hindered biaryl bonds provides an engineerable platform for assembling molecules with programmable catalyst-controlled reactivity and selectivity unprecedented with small molecule catalysts.

show abstract

Aerobic Catalyzed Oxidative Cross-Coupling of N,N-Disubstituted Anilines and Aminonaphthalenes with Phenols and Naphthols

Cited by 24 publications

References 52 publications

Iron‐Catalyzed Oxidative C−O and C−N Coupling Reactions Using Air as Sole Oxidant**

Iron‐Catalyzed Oxidative C−O and C−N Coupling Reactions Using Air as Sole Oxidant**

Biaryl bond formation through biocatalytic oxidative cross-coupling reactions

Biaryl bond formation through biocatalytic oxidative cross-coupling reactions

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