Dual‐Catalysed Intermolecular Reductive Coupling of Dienes and Ketones**

Angewandte Chemie International Edition, Год журнала: 2023, Номер 63(2)

Опубликована: Ноя. 10, 2023

Abstract We report a mild, catalytic method for the intermolecular reductive coupling of feedstock dienes and styrenes with ketones. Our conditions allow concomitant formation cobalt hydride species single‐electron reduction Subsequent selective hydrogen‐atom transfer from generates an allylic radical which can selectively couple persistent radical‐anion ketone. This radical‐radical negates unfavourable steric interactions ionic pathways avoids unstable alkoxy previous olefin‐carbonyl couplings, were limited, as result, to aldehydes. Applications this novel straightforward approach include efficient synthesis drug molecules, key intermediates in site‐selective late‐stage functionalisation.

Язык: Английский

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Radical Decyanations of Unactivated Carbon‐CN Bonds: Recent Achievements and Mechanistic Studies

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(13), С. 2058 - 2091

Опубликована: Май 17, 2023

Abstract Decyanation is an important process in the synthesis of aromatic molecules studies pharmaceutical research, medical and materials sciences. In late‐stage modifications privileged carbo/heterocyclic scaffolds, radical‐type decyanation techniques have been devised to date. As a result, chemistry cyano‐involved conversions, hotly debated subject over past few decades, has advanced significantly. The cyano group (CN), on other hand, rarely acknowledged as good reaction site due its thermodynamic robustness. most recent advancements catalytic radical protocols that CN behaved leaving made are surveyed this article. Following introduction number different modes, reactions used activate C−CN bonds primarily categorized, text herein divided into three groups: (1) photo‐catalyzed transformations, (2) electro‐catalyzed (3) transition‐metal‐catalyzed or metal‐free transformations. With emphasis systems synthetic applications bond activation, review will provide readers with overview reactions.

Язык: Английский

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Electrochemically Generated Carbanions Enable Isomerizing Allylation and Allenylation of Aldehydes with Alkenes and Alkynes

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(25), С. 14143 - 14154

Опубликована: Июнь 15, 2023

The direct coupling of aldehydes with petrochemical feedstock alkenes and alkynes would represent a practical streamlined approach for allylation allenylation chemistry. However, conventional approaches commonly require preactivated substrates or strong bases to generate allylic propargylic carbanions only afford branched propargylation products. Developing mild selective access synthetically useful linear products is highly desirable, albeit formidable challenges. We report strategy using hydrogen evolution reaction (HER) carbanion from weakly acidic sp3 C-H bonds (pKa ∼ 35-40) under conditions, obviating the use bases, Schlenk techniques, multistep procedures. cathodically generated reverses typical selectivity unconventional isomerizing (125 examples). generation was monitored identified by in situ ultraviolet-visible (UV-vis) spectroelectrochemistry. Furthermore, we extended this protocol other their application reactions between alcohols carbanions. appealing features include excellent functional group tolerance, chemo- regioselectivity, diverse utility products, which includes offering diene luminophores bioactive scaffolds. also performed cyclic voltammetry, control experiments, density theory (DFT) calculations rationalize observed mechanism.

Язык: Английский

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Unraveling Hydrogen Atom Transfer Mechanisms with Voltammetry: Oxidative Formation and Reactivity of Cobalt Hydride

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(32), С. 17665 - 17677

Опубликована: Авг. 2, 2023

The utility of transition metal hydride catalyzed hydrogen atom transfer (MHAT) has been widely demonstrated in organic transformations such as alkene isomerization and hydrofunctionalization reactions. However, the highly reactive nature radical intermediates hindered mechanistic insight into this pivotal reaction. Recent advances electrochemical MHAT have opened up possibility for new analytical approaches diagnosis. Here, we report a voltammetric interrogation Co-based reactivity, describing detail oxidative formation reactivity key Co–H intermediate its reaction with aryl alkenes. Insights from cyclic voltammetry finite element simulations help elucidate rate-limiting step formation, which show to be tunable based on ligand design. Voltammetry is also suggestive Co–alkyl dynamic equilibrium neutral radical. These studies provide information design future reactions, catalyst silane choice, relative stability metal–alkyl species, how reactions utilize intermediates. In summary, these establish an important template studying perspective kinetic frameworks.

Язык: Английский

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A Scalable Solution to Constant-Potential Flow Electrochemistry

Organic Process Research & Development, Год журнала: 2024, Номер 28(5), С. 1877 - 1885

Опубликована: Март 1, 2024

The burgeoning interest in new electrochemical methods holds promise to provide a plethora of strategic disconnections for pharmaceutical compounds that are safer, less wasteful, and more streamlined than traditional chemical strategies. use organic electrochemistry the commercial production pharmaceuticals is exceedingly rare due lack modular infrastructure. Herein we describe cascading continuous stirred tank reactors with individual cell potential control applied over reaction "stages" which demonstrate balance between high selectivity throughput necessary be viable strategy space. Using degree afforded by this reactor design, 1 kg demonstration was achieved 9 h yield (2.6 kg/day throughput).

Язык: Английский

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