Charge-controlled Pd catalysis enables the meta-C–H activation and olefination of arenes

Mondal, Arup; Díaz-Ruiz, Marina; Deufel, Fritz; Maseras, Feliu; Gemmeren, Manuel van

doi:10.1016/j.chempr.2022.12.019

Cited by 14 publications

(10 citation statements)

References 41 publications

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“…Soc.20211431637016376 In this study, we used the reversibility of the C–H activation step with our catalysts to (per-)deuterate drug-like molecules. Charge-controlled Pd catalysis enables the meta -C–H activation and olefination of arenesMondalA.Díaz-RuizM.DeufelF.MaserasF.van GemmerenM. Mondal, A. Díaz-Ruiz, M. Deufel, F. Maseras, F. van Gemmeren, M. Chem.2023910041016 This study details the development of a Pd-catalyzed C–H olefination reaction of arenes that, for the first time in Pd-catalyzed C–H activation, uses charge-control to enable site selectivity, thereby enabling a highly meta-selective protocol. …”

Section: Key Referencesmentioning

confidence: 99%

“…Based on these considerations we were indeed able to develop a chargecontrolled, meta-selective olefination protocol (Scheme 12). 4 Notably, in a study contemporaneous to our own work, Maiti developed a dual-ligand-enabled catalyst system that combined our general dual-ligand design with a sulfonate group on the ligand. These catalysts enabled a highly meta selective C−H olefination of protected benzylamines through charge-induced H-bonding interactions.…”

Section: Meta-selective C−h Olefination Enabled By Non-covalent Inter...mentioning

confidence: 99%

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Controlling Reactivity and Selectivity in the Nondirected C–H Activation of Arenes with Palladium

Kaltenberger,

van Gemmeren

2023

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: Aromatic structures are widespread motifs throughout organic chemistry, and C−H activation has been recognized as a major tool for enabling their sustainable and efficient functionalization. Through C−H activation, arenes can be modified without the need for prefunctionalization, leading to inherent atom-and step-economic advantages over traditional methods. However, for the development of synthetically useful methods, several hurdles have to be overcome. The strength of C−H bonds necessitates the development of sufficiently reactive catalysts, while the presence of multiple C−H bonds within a substrate poses challenges in terms of site-selectivity. Traditionally these challenges have been addressed by substrate control. By attaching different directing groups (DGs), the reactivity of the respective arene was significantly enhanced and the DG guided the metal in close proximity to specific C−H bonds, resulting in high site-selectivity. However, the introduction and removal of the DG add additional steps to the synthetic sequence, and the scope of the reaction is limited to a specific substrate class. The development of complementary nondirected methods that can be applied to a broad range of arenes without the necessity to carry a specific functional group that coordinates to Pd (referred to as simple arenes) is therefore highly desirable. However, the intrinsically lower reactivity of such substrates and the absence of a selectivity-determining DG pose significant challenges that can be solved only by the development of highly efficient catalysts. Consequently, the field of nondirected C−H activation, especially with respect to Pd-catalyzed methods, remained comparatively underdeveloped when we initiated our research program in 2017. At that time, stateof-the-art methods required the arene to be used in large excess, precluding its use in late-stage functionalization. Since organopalladium species are among the most versatile synthetic intermediates, we realized that developing a system, which can effectively and selectively activate C−H bonds in simple arenes with the arene as the limiting reagent, would be a powerful tool in synthetic organic chemistry. This account summarizes our groups' research toward the development and application of catalytic systems offering this desired reactivity and focuses explicitly on Pd-catalyzed nondirected C−H functionalization reactions of arenes, where the arene is employed as a limiting reagent. After an introduction that summarizes the state of Pd-catalyzed C−H activation of arenes before 2017 and the associated challenges, experimental and mechanistic details about the development of the first arenelimited, nondirected C−H functionalization of simple arenes with palladium will be discussed. This reactivity was enabled by the identification and combination of two complementary ligands, an N-heterocycle and an amino acid-derived ligand. Afterward we will discuss the expansion of this dual-ligand approach to further arene-limi...

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Section: Key Referencesmentioning

confidence: 99%

Section: Meta-selective C−h Olefination Enabled By Non-covalent Inter...mentioning

confidence: 99%

Controlling Reactivity and Selectivity in the Nondirected C–H Activation of Arenes with Palladium

Kaltenberger,

van Gemmeren

2023

Acc. Chem. Res.

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“…1,2 Direct C–H functionalization of aromatic amines is valuable since many drug molecules contain amine core structures. 3 To date, several meta -selective C–H functionalizations of phenethylamines, 4 benzylamines, 4 h ,5 and 2-aryl anilines 4 d ,6 have been achieved but these only involved C–C, C–B, and C–O bond formations (Scheme 1a), although a few meta -selective C–H halogenation reactions of other types of arenes have been reported. 7,8 Therefore, it is highly desirable to develop meta -selective C–H iodination of these amines considering the importance of iodo-functional group in organic synthesis.…”

Section: Introductionmentioning

confidence: 99%

Carboxyl group assisted isodesmicmeta-C–H iodination of phenethylamines, benzylamines, and 2-aryl anilines

Yang¹,

Wang²,

Zhang³

et al. 2023

Org. Chem. Front.

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“…Non‐covalent interactions have enabled the Ir‐catalyzed meta ‐C−H borylation of anilides and quaternary anilinium salts [10] . Recently, the group of van Gemmeren described one example for palladium catalyzed meta ‐C−H olefination of a quaternary anilinium salt using a similar non‐covalent approach [11] . The meta ‐C−H arylation of anilides combining a copper catalyst and diphenyliodonium salts was reported by the group of Gaunt [12] .…”

Section: Introductionmentioning

confidence: 99%

meta‐C−H Arylation of Aniline Derivatives via Palladium/ S,O‐Ligand/Norbornene Cooperative Catalysis

Sukowski,

van Borselen,

Mathew

et al. 2023

Angew Chem Int Ed

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Aromatic amines are ubiquitous moieties in organic molecules and their direct functionalization is of great interest in many research areas due to their prevalence in pharmaceuticals and organic electronics. While several synthetic tools exist for the ortho‐ and para‐functionalization of anilines, the functionalization of the less reactive meta‐position is not easy to achieve with current methods. To date, the meta‐C−H arylation of aniline derivatives has been restricted to either the use of directing groups & templates, or their transformation into anilides & quaternary anilinium salts. Herein, we report the first general and efficient meta‐C−H‐arylation of non‐directed aniline derivatives via cooperative catalysis with a palladium–S,O‐ligand–norbornene system. The reaction proceeds under mild conditions with a wide range of aniline derivatives and aryl iodides, while being operationally simple and scalable. Our preliminary mechanistic investigation–including the isolation of several palladium complexes and deuterium experiments–reveal useful insights into the substituent‐effects of both the aniline‐substrate and the norbornene‐mediator during the meta‐C−H activation step.

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Charge-controlled Pd catalysis enables the meta-C–H activation and olefination of arenes

Cited by 14 publications

References 41 publications

Controlling Reactivity and Selectivity in the Nondirected C–H Activation of Arenes with Palladium

Controlling Reactivity and Selectivity in the Nondirected C–H Activation of Arenes with Palladium

Carboxyl group assisted isodesmicmeta-C–H iodination of phenethylamines, benzylamines, and 2-aryl anilines

meta‐C−H Arylation of Aniline Derivatives via Palladium/ S,O‐Ligand/Norbornene Cooperative Catalysis

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