Recent Advances in Pd‐Catalyzed Suzuki‐Miyaura Cross‐Coupling Reactions with Triflates or Nonaflates

Degli Innocenti, Maria; Schreiner, Till; Breinbauer, Rolf

doi:10.1002/adsc.202301124

Cited by 6 publications

(3 citation statements)

References 119 publications

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“…Taking advantage of the exceptional tunability of molecular Pd catalysts and the significant advancements in phosphine ligand development over the years [47][48] , this methodology exhibited excellent flexibility for reaction optimizations. In situations where transformations were initially unsuccessful, they could be effectively enabled through simple ligand modification and the addition of an inorganic base.…”

Section: Deuteration Of Pharmaceuticalsmentioning

confidence: 99%

Homogenous Palladium-Catalyzed Dehalogenative Deuteration and Tritiation of Aryl Halides with D2/T2 Gas

Li,

Lin,

Dungan

et al. 2024

Preprint

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Catalytic dehalogenative deuteration and tritiation with D2/T2 gas is a widely employed method for precisely introducing hydrogen isotopes into specific positions within organic molecules. While palladium(0) based heterogeneous catalysts, such as Pd/C, are commonly used for this purpose, challenges related to functional group tolerance and incomplete iso-tope incorporation are often encountered, particularly with respect to aryl bromides and chlorides. These long-standing issues pose a hurdle to achieving optimal results in tracer synthesis. The limited incorporation of isotopes for aryl bro-mides and chlorides presents a significant obstacle to the application of this method in the preparation of high specific activity tritium tracers. Herein, we present a novel palladium catalytic system using Zn(OAc)2 as an additive, which ena-bles homogeneous dehalogenative deuteration and tritiation using D2/T2 gas. Under mild reaction conditions, a wide range of drug-like aryl halides and pseudohalides undergo selective deuteration with complete isotope incorporation. The reaction displays excellent compatibility with diverse functional groups, including multiple bonds, O/N-benzyl, and cy-ano groups, which are frequently problematic in Pd/C reactions. Furthermore, this method was successfully applied to the tritiation of four halogenated pharmaceutically relevant molecules, resulting in predictable high specific activity per halogen atom (26.5-27.7 Ci/mmol). Notably, the developed system allows gram-scale preparation of a deuterium-containing intermediate, a crucial step in synthesizing a deuterium-labeled drug molecule. A reaction pathway involving a key intermediate, Pd(Ar)OAc, was proposed to activate hydrogen gas during dehalogenative deuteration and tritiation. This innovative method has potential to change the practice of dehalogenative deuteration and tritiation in the realm of hydrogen isotope labeling.

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Section: Deuteration Of Pharmaceuticalsmentioning

confidence: 99%

Homogenous Palladium-Catalyzed Dehalogenative Deuteration and Tritiation of Aryl Halides with D2/T2 Gas

Li,

Lin,

Dungan

et al. 2024

Preprint

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“…[1][2][3][4][5] Of these reactions, Suzuki-Miyaura coupling stands out as the most widely applied technique for producing a diverse array of industrial chemicals, encompassing pharmaceuticals, agrochemicals, functional materials, and other fine chemicals. [6][7][8][9] Conventionally, in Suzuki-Miyaura couplings, an organic halide reacts with an organoboron nucleophile in a batch reactor using homogeneous or heterogeneous Pd catalysts. While homogeneous Pd catalysts have been extensively studied for their high activity and selectivity, they face challenges in catalyst recovery and reuse.…”

Section: Introductionmentioning

confidence: 99%

“…Since the initial studies in the early 1970s, Pd‐catalyzed cross‐coupling reactions have evolved into one of the most powerful methodologies for forming carbon−carbon (C−C) bonds in organic compounds [1–5] . Of these reactions, Suzuki‐Miyaura coupling stands out as the most widely applied technique for producing a diverse array of industrial chemicals, encompassing pharmaceuticals, agrochemicals, functional materials, and other fine chemicals [6–9] . Conventionally, in Suzuki‐Miyaura couplings, an organic halide reacts with an organoboron nucleophile in a batch reactor using homogeneous or heterogeneous Pd catalysts.…”

Section: Introductionmentioning

confidence: 99%

Recent Advancements in Continuous‐Flow Suzuki‐Miyaura Coupling Utilizing Immobilized Molecular Palladium Complexes

Zhang,

Yamada

2024

Chemistry A European J

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Immobilized Pd‐catalyzed Suzuki–Miyaura coupling under continuous‐flow conditions using a packed‐bed reactor, representing an efficient, automated, practical, and safe technology compared to conventional batch‐type reactions. The core objective of this study is the development of an active and durable catalyst. In contrast to supported Pd nanoparticles, the attachment of Pd complexes onto solid supports through well‐defined coordination sites is considered a favorable approach for preparing highly dispersed and stabilized Pd species. These species can be directly employed in various flow reactions without the need for pre‐treatment. This concept paper explores recent achievements involving the application of immobilized Pd complexes as precatalysts for continuous‐flow Suzuki–Miyaura coupling. Our focus is to elucidate the significance of the designed catalyst structures in relation to their catalytic performance under flow conditions. Additionally, we highlight various reaction systems and catalyst packing methods, emphasizing their crucial roles in establishing a practical synthesis process.

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Palladium(II) complexes of amino acid derived ONO-tridentate enamine ligand for Suzuki-Miyaura cross-coupling reaction

Şenocak,

Fırıncı,

Sevinçek

et al. 2024

Inorganic Chemistry Communications

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Recent Advances in Pd‐Catalyzed Suzuki‐Miyaura Cross‐Coupling Reactions with Triflates or Nonaflates

Cited by 6 publications

References 119 publications

Homogenous Palladium-Catalyzed Dehalogenative Deuteration and Tritiation of Aryl Halides with D2/T2 Gas

Homogenous Palladium-Catalyzed Dehalogenative Deuteration and Tritiation of Aryl Halides with D2/T2 Gas

Recent Advancements in Continuous‐Flow Suzuki‐Miyaura Coupling Utilizing Immobilized Molecular Palladium Complexes

Palladium(II) complexes of amino acid derived ONO-tridentate enamine ligand for Suzuki-Miyaura cross-coupling reaction

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