Practical Synthesis of Halogenated N‐Heterocycles via Electrochemical Anodic Oxidation of Unactivated Alkenes DOI

Yanyang He,

Xiaowen Qin,

Xinxu He

et al.

European Journal of Organic Chemistry, Journal Year: 2021, Volume and Issue: 2021(42), P. 5831 - 5834

Published: Oct. 20, 2021

Abstract A general and efficient intramolecular halo‐amination of unactivated alkenes for the synthesis various halogenated N ‐heterocycles was developed via electrochemical anodic oxidation. This protocol proceeds in a simple undivided cell by employing LiI or LiBr as redox mediums halogen sources. wide range ‐heterocycles, including three‐, five‐, six‐membered were constructed moderate to good yields at room temperature. Notably, this oxidative transformation avoids utilization external oxidants strong bases, therefore represents an environmentally benign approach.

Language: Английский

HFIP in Organic Synthesis DOI
Hashim F. Motiwala,

Ahlam M. Armaly,

Jackson G. Cacioppo

et al.

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(15), P. 12544 - 12747

Published: July 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.

Language: Английский

Citations

319
Catalytic Electrophilic Halogenation of Arenes with Electron-Withdrawing Substituents DOI
Weijin Wang,

Xiaoxue Yang,

Rongheng Dai

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(29), P. 13415 - 13425

Published: July 15, 2022

The electrophilic halogenation of arenes is perhaps the simplest method to prepare aryl halides, which are important structural motifs in agrochemicals, materials, and pharmaceuticals. However, nucleophilicity weakened by electron-withdrawing substituents, whose reactions usually require harsh conditions lead limited substrate scopes applications. Therefore, containing groups (EWGs) complex bioactive compounds under mild has been a long-standing challenge. Herein, we describe Brønsted acid-catalyzed with substituents conditions, providing an efficient protocol for halides. hydrogen bonding acid protic solvent 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) enables this transformation thus solves problem.

Language: Английский

Citations

81
Zwitterionic Dual Halogen Bond-Catalyzed Electrophilic Bromination of Electron-Deficient Arenes under Mild Conditions DOI
Muyin Zhang, Zhihai Ke

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 4270 - 4279

Published: Feb. 25, 2025

Language: Английский

Citations

2
Unlocking the Friedel-Crafts arylation of primary aliphatic alcohols and epoxides driven by hexafluoroisopropanol DOI Creative Commons
Shaofei Zhang, Marie Vayer,

Florent Noël

et al.

Chem, Journal Year: 2021, Volume and Issue: 7(12), P. 3425 - 3441

Published: Nov. 17, 2021

Alcohols and epoxides are arguably ideal electrophiles for the Friedel-Crafts alkylation, since they widely available, require no pre-activation, produce stoichiometric waste beyond water. However, neither primary aliphatic alcohols nor most classes of terminal compatible with existing intermolecular methodologies, sequential reactions starting from consequently remain underexplored. Here, we report that these limitations easily overcome using Brønsted acid catalysis in hexafluoroisopropanol (HFIP) as a solvent. Electron-poor aromatic undergo stereospecific arylation to give an alcohol which, depending on reaction conditions, can partake second nucleophilic substitution different arene one pot. Phenyl ethanols react through phenonium intermediate, whereas simple participate rare SN2 process, delivering linear products exclusively. This work provides alternative metal-catalyzed cross-couplings accessing important scaffolds, widening range applications reaction.

Language: Английский

Citations

68
Difunctionalization Processes Enabled by Hexafluoroisopropanol DOI Creative Commons
Maciej Piejko, Joseph Moran, David Lebœuf

et al.

ACS Organic & Inorganic Au, Journal Year: 2024, Volume and Issue: 4(3), P. 287 - 300

Published: March 4, 2024

In the past 5 years, hexafluoroisopropanol (HFIP) has been used as a unique solvent or additive to enable challenging transformations through substrate activation and stabilization of reactive intermediates. this Review, we aim at describing difunctionalization processes which were unlocked when HFIP was involved. Specifically, focus on cyclizations additions alkenes, alkynes, epoxides, carbonyls that introduce wide range functional groups interest.

Language: Английский

Citations

14
Iron-Catalyzed Csp2–Csp3 Cross-Coupling via Double Decarboxylation: One Step Synthesis of Remote Polar Alkenes DOI

Ni Xiong,

Chengxiang Zhou,

Shiyi Li

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(10), P. 2029 - 2033

Published: March 4, 2024

Herein, we report an efficient photoinduced iron-catalyzed strategy for cross-couplings of alkyl carboxylic and acrylic acids, which provides a powerful tool the synthesis variety alkenes with polar functional groups. This novel synthetic methodology can also be applied to preparation ketones by using α-keto acids. Mechanistic experiments revealed preliminary mechanistic details. Diverse functionalization could achieved, may help streamline complex analogues drug discovery.

Language: Английский

Citations

7
Controlling the regioselectivity of the bromolactonization reaction in HFIP DOI Creative Commons
Tuong Anh To, Nhu T. A. Phan, Binh Khanh

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(19), P. 7187 - 7197

Published: Jan. 1, 2024

The halolactonization reaction provides rapid access to densely functionalized lactones from unsaturated carboxylic acids. endo/exo regioselectivity of this cyclization is primarily determined by the electronic stabilization alkene substituents, thus making it inherently dependent on substrate structures. Therefore method often affords one type halolactone regioisomer only. Herein, we introduce a simple and efficient for regioselectivity-switchable bromolactonization reactions mediated HFIP solvent. Two sets conditions were developed, each forming endo-products or exo-products in excellent regioselectivity. A combination computational experimental mechanistic studies not only confirmed crucial role HFIP, but also revealed formation under kinetic control thermodynamic control. This study paves way future work use perfluorinated solvents dictate outcomes organic synthesis.

Language: Английский

Citations

7
Late-Stage Halogenation of Complex Substrates with Readily Available Halogenating Reagents DOI
Weijin Wang, Song Song, Ning Jiao

et al.

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(21), P. 3161 - 3181

Published: Sept. 20, 2024

ConspectusLate-stage halogenation, targeting specific positions in complex substrates, has gained significant attention due to its potential for diversifying and functionalizing molecules such as natural products pharmaceutical intermediates. Utilizing readily available halogenating reagents, hydrogen halides (HX), N-halosuccinimides (NXS), dichloroethane (DCE) reagents late-stage halogenation shows great promise expanding the toolbox of synthetic chemists. However, reactivity haleniums (X

Language: Английский

Citations

7
Hexafluoroisopropanol‐Promoted or Brønsted Acid‐Mediated Photochemical [2+2] Cycloadditions of Alkynes with Maleimides DOI

Ierasia Triandafillidi,

Nikolaos F. Nikitas,

Petros L. Gkizis

et al.

ChemSusChem, Journal Year: 2022, Volume and Issue: 15(4)

Published: Jan. 3, 2022

Although the use of light stimulating organic transformations has been known for more than a century, there is an increasing research interest on expanding established knowledge. While [2+2] cycloadditions are promoted photochemically, literature precedent reaction between alkynes and maleimides limited only handful examples exist, focusing mainly N-aliphatic maleimides. Herein, differences in reactivity N-alkyl N-aryl were identified, hexafluoroisopropanol (HFIP) or trifluoroacetic acid (TFA) as viable solutions was proposed order to achieve high yields. In case maleimides, both HFIP-mediated TFA-promoted reactions using LED 370 nm irradiation, without external photocatalyst. thioxanthone (THX) employed energy transfer photocatalyst along with 427 irradiation HFIP. Mechanistic studies performed, supporting pivotal role HFIP TFA, acquiring good yields classes

Language: Английский

Citations

27
Synthesis of Unprotected β‐Arylethylamines by Iron(II)‐Catalyzed 1,2‐Aminoarylation of Alkenes in Hexafluoroisopropanol DOI Creative Commons
Valentyn Pozhydaiev, Marie Vayer, Claire Fave

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(9)

Published: Dec. 21, 2022

β-Arylethylamines are prevalent structural motifs in molecules exhibiting biological activity. Here we report a sequential one-pot protocol for the 1,2-aminoarylation of alkenes with hydroxylammonium triflate salts and (hetero)arenes. Unlike existing methods, this reaction provides direct entry to unprotected β-arylethylamines remarkable functional group tolerance, allowing key drug-oriented groups be installed two-step process. The use hexafluoroisopropanol as solvent combination an iron(II) catalyst proved essential reaching high-value nitrogen-containing molecules.

Language: Английский

Citations

26