Microfluidic electrochemistry for single-electron transfer redox-neutral reactions

Science, Journal Year: 2020, Volume and Issue: 368(6497), P. 1352 - 1357

Published: June 18, 2020

Electrochemistry offers opportunities to promote single-electron transfer (SET) redox-neutral chemistries similar those recently discovered using visible-light photocatalysis but without the use of an expensive photocatalyst. Herein, we introduce a microfluidic electrochemistry (μRN-eChem) platform that has broad applicability SET chemistry, including radical-radical cross-coupling, Minisci-type reactions, and nickel-catalyzed C(sp2)-O cross-coupling. The cathode anode simultaneously generate corresponding reactive intermediates, selective transformation is facilitated by rapid molecular diffusion across channel outpaces decomposition intermediates. μRN-eChem was shown enable two-step gram-scale electrosynthesis nematic liquid crystal compound, demonstrating its practicality.

Language: Английский

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Cross-Electrophile Coupling: Principles, Methods, and Applications in Synthesis

Chemical Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Cross-electrophile coupling (XEC), defined by us as the cross-coupling of two different σ-electrophiles that is driven catalyst reduction, has seen rapid progression in recent years. As such, this review aims to summarize field from its beginnings up until mid-2023 and provide comprehensive coverage on synthetic methods current state mechanistic understanding. Chapters are split type bond formed, which include C(sp

Language: Английский

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Sulfonate Versus Sulfonate: Nickel and Palladium Multimetallic Cross-Electrophile Coupling of Aryl Triflates with Aryl Tosylates

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(24), P. 10634 - 10640

Published: June 2, 2020

While phenols are frequent and convenient aryl sources in cross-coupling, typically as sulfonate esters, the direct cross-Ullmann coupling of two different esters is unknown. We report here a general solution to this challenge catalyzed by combination Ni Pd with Zn reductant LiBr an additive. The reaction has broad scope, demonstrated 33 examples (65% ± 11% average yield). Mechanistic studies show that strongly prefers triflate, catalyst small preference for tosylate, transfer between catalysts mediated Zn, improves yields consuming arylzinc intermediates.

Language: Английский

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Stereoselective gem-Difluorovinylation of gem-Difluorinated Cyclopropanes Enabled by Ni/Pd Cooperative Catalysis

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(19), P. 11960 - 11965

Published: Sept. 13, 2021

A cross-electrophile coupling between gem-difluorinated cyclopropanes and 2,2-difluorovinyl tosylate via dual Ni/Pd cooperative catalysis under mild reaction conditions is presented. Various structurally unique organofluorine compounds bearing both monofluoroalkene gem-difluoroalkene moieties can be effectively afforded in good yields with a high (Z)-selectivity. The synthetic utility of this protocol has been successfully demonstrated by the late-stage modification series complex bioactive molecules.

Language: Английский

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Homogeneous Organic Electron Donors in Nickel-Catalyzed Reductive Transformations

The Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 87(12), P. 7589 - 7609

Published: June 7, 2022

Many contemporary organic transformations, such as Ni-catalyzed cross-electrophile coupling (XEC), require a reductant. Typically, heterogeneous reductants, Zn

Language: Английский

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Zinc and manganese redox potentials in organic solvents and their influence on nickel-catalysed cross-electrophile coupling

Nature Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 6, 2024

Language: Английский

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Direct dehydrogenative alkyl Heck-couplings of vinylarenes with umpolung aldehydes catalyzed by nickel

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Feb. 12, 2019

Abstract Alkenes are fundamental functionalities in nature and highly useful intermediates organic synthesis, medicinal chemistry material sciences. Transition-metal-catalyzed Heck couplings with halides as electrophiles have been established a powerful protocol for the synthesis of this valuable building block. However, requirement generation stoichiometric hazardous halide wastes may cause significant sustainable concerns. The halide-free oxidative alkenylations involving organometallics or arenes coupling partners provide facile alternative pathway. Nonetheless, amounts extra oxidant essential most cases. Herein, we present direct dehydrogenative alkyl Heck-coupling reaction under oxidant-free conditions, liberating hydrogen, nitrogen water side products. Excellent regioselectivity is achieved via neighboring oxygen atom coordination. Broad substrate scope, great functional group (ketone, ester, phenol, free amine, amide etc) tolerance modification pharmaceutical candidates biological molecules exemplified its generality practicability.

Language: Английский

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Nickel-Catalyzed Cross-Electrophile Coupling Reactions for the Synthesis of gem-Difluorovinyl Arenes

ACS Catalysis, Journal Year: 2020, Volume and Issue: 10(22), P. 13616 - 13623

Published: Nov. 10, 2020

A nickel-catalyzed cross-electrophile coupling reaction between (hetero)aryl bromides and 2,2-difluorovinyl tosylate is presented. This protocol provides facile incorporation of the gem-difluorovinyl moiety in organic molecules. The method features mild conditions, good functional group tolerance, excellent yields. Furthermore, mechanistic experiments DFT studies indicate a Ni(0)/Ni(II) catalytic cycle, thus differing from currently accepted cycle for C(sp2)–C(sp2) reactions.

Language: Английский

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A Widely Applicable Dual Catalytic System for Cross-Electrophile Coupling Enabled by Mechanistic Studies

ACS Catalysis, Journal Year: 2020, Volume and Issue: 10(21), P. 12642 - 12656

Published: Sept. 29, 2020

A dual catalytic system for cross-electrophile coupling reactions between aryl halides and alkyl that features a Ni catalyst, Co cocatalyst, mild homogeneous reductant is described. Mechanistic studies indicate the catalyst activates halide, while cocatalyst halide. This allows to be rationally optimized variety of substrate classes by simply modifying loadings catalysts based on reaction product profile. For example, bromides iodides with bromides, iodides, benzyl chlorides demonstrated using same under similar conditions but different optimal in each case. Our tolerant numerous functional groups capable heteroaryl halides, di-ortho-substituted pharmaceutically relevant druglike diverse range halides. Additionally, platform facilitates series selective one-pot three-component bromo(iodo)arenes two distinct demonstrates unique level control provides enables rapid generation molecular complexity. The can readily utilized wide applications as all components are commercially available, scalable, toxic amide-based solvents not required. It anticipated this strategy, well underlying mechanistic framework, will generalizable other reactions.

Language: Английский

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A General, Multimetallic Cross-Ullmann Biheteroaryl Synthesis from Heteroaryl Halides and Heteroaryl Triflates

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(51), P. 21484 - 21491

Published: Dec. 17, 2021

Despite their importance to medicine and materials science, the synthesis of biheteroaryls by cross-coupling remains challenging. We describe here a new, general approach biheteroaryls: Ni- Pd-catalyzed multimetallic cross-Ullmann coupling heteroaryl halides with triflates. An array 5-membered, 6-membered, fused bromides chlorides, as well aryl triflates derived from heterocyclic phenols, proved be viable substrates in this reaction (62 examples, 63 ± 17% average yield). The generality was further demonstrated 96-well plate format at 10 μmol scale. 96 possible products provided >90% hit rate under single set conditions. Further, low-yielding combinations could rapidly optimized "Toolbox Plate" ligands, additives, reductants.

Language: Английский

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