Electrochemical and Scalable Dehydrogenative C(sp<sup>3</sup>)−H Amination via Remote Hydrogen Atom Transfer in Batch and Continuous Flow

Nikolaienko, Pavlo; Jentsch, Marc; Kale, Ajit Prabhakar; Cai, Yunfei; Rueping, Magnus

doi:10.1002/chem.201806092

Cited by 39 publications

(31 citation statements)

References 88 publications

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“…Thus, as model reaction the cross coupling was conducted using photovoltaic panels as an alternative source of electricity (Figure 3e). [17] The reaction pattern remained the same and desired product 3a was isolated in good yield. In order to prove practicability, a multigram scale reaction was also performed (see SI).…”

Section: Accepted Manuscriptmentioning

confidence: 76%

Nickel‐Catalyzed Chain‐Walking Cross‐Electrophile Coupling of Alkyl and Aryl Halides and Olefin Hydroarylation Enabled by Electrochemical Reduction

et al. 2020

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The first electrochemical approach for nickel‐catalyzed cross‐electrophile coupling was developed. This method provides a novel route to 1,1‐diarylalkane derivatives from simple and readily available alkyl and aryl halides in good yields and excellent regioselectivity under mild conditions. The procedure shows good tolerance for a broad variety of functional groups and both primary and secondary alkyl halides can be used. Furthermore, the reaction was successfully scaled up to the multigram scale, thus indicating potential for industrial application. Mechanistic investigation suggested the formation of a nickel hydride in the electroreductive chain‐walking arylation, which led to the development of a new nickel‐catalyzed hydroarylation of styrenes to provide a series of 1,1‐diaryl alkanes in good yields under mild reaction conditions.

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Section: Accepted Manuscriptmentioning

confidence: 76%

Nickel‐Catalyzed Chain‐Walking Cross‐Electrophile Coupling of Alkyl and Aryl Halides and Olefin Hydroarylation Enabled by Electrochemical Reduction

et al. 2020

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“…In sharp contrast, electrochemical studies based on NCRs have been limited thus far . Two strategies have been employed to stabilize the aromatic aminyl radicals, namely, the use of captodative effects in the presence of a strong electron‐withdrawing group such as an amide or a sulfamide group (Scheme a, A ) and delocalization effects originating from diaryl amine motifs (Scheme a, B ). Considering the intriguing structure of pyridine, both the captodative effect and the delocalization effect might be achieved in one molecule.…”

Section: Introductionmentioning

confidence: 99%

Tunable Electrochemical C−N versus N−N Bond Formation of Nitrogen‐Centered Radicals Enabled by Dehydrogenative Dearomatization: Biological Applications

Han

Wang

et al. 2020

Angewandte Chemie

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Herein, an environmentally friendly electrochemical approach is reported that takes advantage of the captodative effect and delocalization effect to generate nitrogen‐centered radicals (NCRs). By changing the reaction parameters of the electrode material and feedstock solubility, dearomatization enabled a selective dehydrogenative C−N versus N−N bond formation reaction. Hence, pyrido[1,2‐a]benzimidazole and tetraarylhydrazine frameworks were prepared through a sustainable transition‐metal‐ and exogenous oxidant‐free strategy with broad generality. Bioactivity assays demonstrated that pyrido[1,2‐a]benzimidazoles displayed antimicrobial activity and cytotoxicity against human cancer cells. Compound 21 exhibited good photochemical properties with a large Stokes shift (approximately 130 nm) and was successfully applied to subcellular imaging. A preliminary mechanism investigation and density functional theory (DFT) calculations revealed the possible reaction pathway.

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“…Accurate control of residence time in flow reactions generating gases is difficult, since the formation of gas bubbles (slugs) decreases the residence time during the reaction. Hence, a back-pressure regulator was included in the system to solubilize the majority of hydrogen formed at the cathode (1 to 5 bar), allowing the synthesis of the tosylpyrrolidine compound methyl 4-methyl-1-tosylpyrrolidine-2-carboxylate in 76% yield with a productivity of 0.37 mmol h − 1 (Scheme 68) [226].…”

Section: − N Bond Formationmentioning

confidence: 99%

Pushing the boundaries of C–H bond functionalization chemistry using flow technology

2020

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C-H functionalization chemistry is one of the most vibrant research areas within synthetic organic chemistry. While most researchers focus on the development of small-scale batch-type transformations, more recently such transformations have been carried out in flow reactors to explore new chemical space, to boost reactivity or to enable scalability of this important reaction class. Herein, an up-to-date overview of C-H bond functionalization reactions carried out in continuous-flow microreactors is presented. A comprehensive overview of reactions which establish the formal conversion of a C-H bond into carbon-carbon or carbonheteroatom bonds is provided; this includes metal-assisted C-H bond cleavages, hydrogen atom transfer reactions and C-H bond functionalizations which involve an S E-type process to aromatic or olefinic systems. Particular focus is devoted to showcase the advantages of flow processing to enhance C-H bond functionalization chemistry. Consequently, it is our hope that this review will serve as a guide to inspire researchers to push the boundaries of C-H functionalization chemistry using flow technology.

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Electrochemical and Scalable Dehydrogenative C(sp³)−H Amination via Remote Hydrogen Atom Transfer in Batch and Continuous Flow

Cited by 39 publications

References 88 publications

Nickel‐Catalyzed Chain‐Walking Cross‐Electrophile Coupling of Alkyl and Aryl Halides and Olefin Hydroarylation Enabled by Electrochemical Reduction

Nickel‐Catalyzed Chain‐Walking Cross‐Electrophile Coupling of Alkyl and Aryl Halides and Olefin Hydroarylation Enabled by Electrochemical Reduction

Tunable Electrochemical C−N versus N−N Bond Formation of Nitrogen‐Centered Radicals Enabled by Dehydrogenative Dearomatization: Biological Applications

Pushing the boundaries of C–H bond functionalization chemistry using flow technology

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Electrochemical and Scalable Dehydrogenative C(sp3)−H Amination via Remote Hydrogen Atom Transfer in Batch and Continuous Flow

Cited by 39 publications

References 88 publications

Nickel‐Catalyzed Chain‐Walking Cross‐Electrophile Coupling of Alkyl and Aryl Halides and Olefin Hydroarylation Enabled by Electrochemical Reduction

Nickel‐Catalyzed Chain‐Walking Cross‐Electrophile Coupling of Alkyl and Aryl Halides and Olefin Hydroarylation Enabled by Electrochemical Reduction

Tunable Electrochemical C−N versus N−N Bond Formation of Nitrogen‐Centered Radicals Enabled by Dehydrogenative Dearomatization: Biological Applications

Pushing the boundaries of C–H bond functionalization chemistry using flow technology

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Electrochemical and Scalable Dehydrogenative C(sp³)−H Amination via Remote Hydrogen Atom Transfer in Batch and Continuous Flow