A Decade of Electrochemical Dehydrogenative C,C-Coupling of Aryls

Accounts of Chemical Research, Год журнала: 2019, Номер 53(1), С. 45 - 61

Опубликована: Дек. 18, 2019

The importance of sustainable and green synthetic protocols for the synthesis fine chemicals has rapidly increased during last decades in an effort to reduce use fossil fuels other finite resources. replacement common reagents by electricity provides a cost- atom-efficient, environmentally friendly, inherently safe access novel routes. selective formation carbon-carbon bonds between two distinct substrates is crucial tool organic chemistry. This fundamental transformation enables broad variety complex molecular architectures. In particular, aryl-aryl bond high significance preparation materials, drugs, natural products. Besides well-known well-established reductive- oxidative-reagent-mediated or transition-metal-catalyzed coupling reactions, have arisen, which require fewer steps than conventional approaches. Electroorganic conversions can be categorized according nature electron transfer processes occurring. Direct transformations at inert electrode materials are benign cost-effective, whereas catalytic active electrodes mediated electrosynthesis using additional soluble reagent beneficial properties terms selectivity reactivity. general, these challenging optimization reaction parameters appropriate cell design. Galvanostatic reactions enable fast with rather simple setup, potentiostatic electrolysis may enhance selectivity. Account discusses development seminal formations over past decades, focusing on phenols leading precursors ligands in, e.g., hydroformylation reaction. A key element success electrochemical application electrochemically inert, non-nucleophilic, highly fluorinated alcohols such as 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), exhibit large potential window cross-coupling reactions. based capability HFIP stabilize radicals. Inert, carbon-based metal-free like graphite boron-doped diamond (BDD) open up electroorganic pathways. Furthermore, been developed intra- intermolecular dehydrogenative electron-rich aryls. 2,2'-biphenol derivatives ligand components catalysts requires carried out larger scale. order achieve this, continuous flow established overcome drawbacks heat transfer, overconversion, conductivity. Modular designs into processes. Recent results demonstrate electrochemistry product pharmaceutically relevant opiate alkaloids (-)-thebaine (-)-oxycodone.

Язык: Английский

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HFIP in Organic Synthesis

Chemical Reviews, Год журнала: 2022, Номер 122(15), С. 12544 - 12747

Опубликована: Июль 17, 2022

1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) is a polar, strongly hydrogen bond-donating solvent that has found numerous uses in organic synthesis due to its ability stabilize ionic species, transfer protons, and engage range of other intermolecular interactions. The use this exponentially increased the past decade become choice some areas, such as C–H functionalization chemistry. In review, following brief history HFIP an overview physical properties, literature examples reactions using or additive are presented, emphasizing effect each reaction.

Язык: Английский

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Exploiting hexafluoroisopropanol (HFIP) in Lewis and Brønsted acid-catalyzed reactions

Chemical Communications, Год журнала: 2020, Номер 56(78), С. 11548 - 11564

Опубликована: Янв. 1, 2020

Hexafluoroisopropanol (HFIP) is a solvent with unique properties that has recently gained attention for promoting wide range of challenging chemical reactions. It was initially believed HFIP almost exclusively involved in the stabilization cationic intermediates, owing to its high polarity and low nucleophilicity. However, many cases, mechanism action appears be more complex. Recent findings reveal Lewis Brønsted acid-catalyzed transformations conducted additionally involve cooperation between catalyst hydrogen-bond clusters, akin Lewis- or acid-assisted-Brønsted acid catalysis. This feature article showcases remarkable versatility reactions, an emphasis on examples yielding mechanistic insight.

Язык: Английский

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Hexafluoroisopropanol: the magical solvent for Pd-catalyzed C–H activation

Chemical Science, Год журнала: 2021, Номер 12(11), С. 3857 - 3870

Опубликована: Янв. 1, 2021

Among numerous solvents available for chemical transformations, 1,1,1,3,3,3-hexafluoro-2-propanol (popularly known as HFIP) has attracted enough attention of the scientific community in recent years.

Язык: Английский

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Alkyne Linchpin Strategy for Drug:Pharmacophore Conjugation: Experimental and Computational Realization of a Meta-Selective Inverse Sonogashira Coupling

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(8), С. 3762 - 3774

Опубликована: Янв. 7, 2020

The late-stage functionalization (LSF) of pharmaceutical and agrochemical compounds by the site-selective activation C–H bonds provides access to diverse structural analogs expands synthetically-accessible chemical space. We report a LSF strategy that hinges on use an alkyne linchpin assemble conjugates sp2-rich marketed pharmaceuticals agrochemicals with sp3-rich 3D fragments natural products. This is accomplished through template-assisted inverse Sonogashira reaction displays high levels selectivity for meta position. protocol also amenable distal modifications α-amino acids. transformation functionality other functional groups further highlights applicative potential. Computational experimental mechanistic studies shed light detailed mechanism. Turnover-limiting 1,2-migratory insertion bromoalkyne coupling partner occurs after relatively fast activation. While this unselectively, regioconvergence results from one adducts undergoing 1,2-trialkylsilyl migration form alkynylated product. A heterobimetallic Pd–Ag transition structure essential product formation in β-bromide elimination step.

Язык: Английский

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Photoinduced Proton‐Transfer Reactions for Mild O‐H Functionalization of Unreactive Alcohols

Angewandte Chemie International Edition, Год журнала: 2019, Номер 59(14), С. 5562 - 5566

Опубликована: Дек. 27, 2019

Hexafluoroisopropanol is typically considered as an unreactive solvent and not a reagent in organic synthesis. Herein, we report on mild efficient photochemical reaction of aryl diazoacetates with hexafluoroisopropanol that enables, under stoichiometric conditions, the synthesis fluorinated ethers excellent yield. Mechanistic studies indicate there preorganization diazoalkane acts hydrogen-bonding complex. Only after photoexcitation does this complex undergo protonation-substitution to product. Investigations applicability transformation show broad variety acidic alcohols can be subjected thus demonstrate feasibility concept for O-H functionalization reactions (54 examples, up 98 % yield).

Язык: Английский

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Emerging unconventional organic solvents for C–H bond and related functionalization reactions

Chemical Society Reviews, Год журнала: 2020, Номер 49(6), С. 1643 - 1652

Опубликована: Янв. 1, 2020

Recognizing and classifying the recently appeared reactivity enabling unconventional solvents is main objective of this tutorial review, for applications in field C–H bond functionalization reactions.

Язык: Английский

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Palladium-Catalyzed meta-C–H Allylation of Arenes: A Unique Combination of a Pyrimidine-Based Template and Hexafluoroisopropanol

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(28), С. 12453 - 12466

Опубликована: Июнь 4, 2020

Controlling remote selectivity and delivering novel functionalities at distal positions in arenes are an important endeavor contemporary organic synthesis. In this vein, template engineering mechanistic understanding of new functionalization strategies essential for enhancing the scope such methods. Herein, meta-C–H allylation has been achieved with aid a palladium catalyst, pyrimidine-based auxiliary, allyl phosphate. 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) was found as critical solvent transformation. The role HFIP throughout catalytic cycle systematically studied. A broad substrate phenethyl ether, phenol, benzylsulfonyl ester, phenethylsulfonyl phenylacetic acid, hydrocinnamic 2-phenylbenzoic acid derivatives demonstrated. Interestingly, conformationally flexible have also selectively allylated meta-position using combination 1H NMR, 31P ESI-MS, kinetic experiments, density functional theory (DFT) computations suggested that reaction proceeds through ligand-assisted activation, addition forming Pd-π-allyl complex which is then followed by turnover determining C–C bond formation step leading to meta-allylated product.

Язык: Английский

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Lewis Acid/Hexafluoroisopropanol: A Promoter System for Selective ortho-C-Alkylation of Anilines with Deactivated Styrene Derivatives and Unactivated Alkenes

ACS Catalysis, Год журнала: 2020, Номер 10(18), С. 10794 - 10802

Опубликована: Авг. 26, 2020

Aniline derivatives are frequently encountered in molecules of industrial relevance such as dyes or antioxidants, which make the development synthetic methods for functionalization these privileged structures highly sought-after. A general protocol hydroarylation electronically diverse alkenes with anilines would be ideal to provide densely functionalized compounds. However, this transformation has been underexplored compared more traditional unactivated because significant challenges associated control selectivity and its substrate tolerance. Herein, we describe a selective, versatile, user-friendly ortho-C-alkylation that hinges on beneficial combination Lewis acid (Ca(II)) hexafluoroisopropanol solvent. This allows extension deactivated styrenes demonstrates remarkable improved reactivity regarding aliphatic alkenes, styrene derivatives, dienes. In addition, DFT computations were performed which, combined experimental observations, suggest nearly concerted mechanism impart ortho-selectivity.

Язык: Английский

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Late-Stage β-C(sp³)–H Deuteration of Carboxylic Acids

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(29), С. 10895 - 10901

Опубликована: Июль 19, 2021

Carboxylic acids are highly abundant in bioactive molecules. In this study, we describe the late-stage β-C(sp3)-H deuteration of free carboxylic acids. On basis finding that C-H activation with our catalysts is reversible, de-deuteration process was first optimized. The resulting method uses ethylenediamine-based ligands and can be used to achieve desired when using a deuterated solvent. reported allows for functionalization wide range diverse substitution patterns, as well molecules related frameworks enables nonactivated methylene bonds time.

Язык: Английский

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