Renewable Electricity Enables Green Routes to Fine Chemicals and Pharmaceuticals DOI Creative Commons
Ayesha Murtaza,

Muhammad Awais Qamar,

Kaynat Saleem

et al.

The Chemical Record, Journal Year: 2022, Volume and Issue: 22(5)

Published: Feb. 1, 2022

Abstract Syntheses of chemicals using renewable electricity and when generating high atom economies are considered green sustainable processes. In the present state affairs, electrochemical manufacturing fine pharmaceuticals is not as common place it could be therefore, merits more attention. There also a need to turn attention toward synthesis valuable from recyclable greenhouse gases that can accelerate process circular economy. CO 2 emissions major contributor human‐induced global warming. conversion into application its utilisation will contribute economy while maintaining environmental sustainability. Herein, we an overview electro‐carboxylation, including mechanistic aspects, which forms carboxylic acids molecular carbon dioxide. We discuss fluorination, methoxylation amide formation reactions.

Language: Английский

Divergent, Stereospecific Mono‐ and Difluoromethylation of Boronic Esters DOI
Valerio Fasano,

Nils Winter,

Adam Noble

et al.

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(22), P. 8502 - 8506

Published: Feb. 28, 2020

There is considerable interest in incorporating fluorine into agrochemicals and pharmaceuticals to improve their biological properties. Whilst a number of methods have been reported for installing CH2 F CHF2 groups, they are mainly limited radical reactions, which invariably racemic. Herein, we report the divergent, stereospecific reaction fluoroiodomethyllithium with boronic esters give α-fluoro-boronic esters. These unique intermediates can be readily transformed corresponding mono- or difluoromethylated compounds through proto- fluorodeboronation, respectively. The use highly unstable was key allowing rapid 1,2-migration over competing decomposition carbanion. DFT calculations informed supported experimental findings.

Language: Английский

Citations

42
Copper-catalyzed carbo-difluoromethylation of alkenes via radical relay DOI Creative Commons
Aijie Cai, Wenhao Yan,

Xiaojun Zeng

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: June 1, 2021

Abstract Organic molecules that contain alkyl-difluoromethyl moieties have received increased attention in medicinal chemistry, but their synthesis a modular and late-stage fashion remains challenging. We report herein an efficient copper-catalyzed radical relay approach for the carbo-difluoromethylation of alkenes. This simultaneously introduces CF 2 H groups along with complex alkyl or aryl into alkenes regioselectivity opposite to traditional addition. demonstrate broad substrate scope wide functional group compatibility. scalable protocol is applied functionalization analogues bioactive molecules. Mechanistic studies density theory calculations suggest unique ligand effect on reactivity Cu-CF species.

Language: Английский

Citations

39
Visible-Light-Mediated Tandem Difluoromethylation/Cyclization of Alkenyl Aldehydes toward CF2H-Substituted Chroman-4-one Derivatives DOI
Liu‐Liang Mao, An‐Xi Zhou,

Xianhong Zhu

et al.

The Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 87(18), P. 12414 - 12423

Published: Aug. 25, 2022

An efficient and facile visible-light-mediated tandem difluoromethylation/cyclization of alkenyl aldehydes, with easily accessible air-stable [Ph3PCF2H]+Br- as the difluoromethylation reagent, has been established. A range CF2H-substituted chroman-4-one skeletons their derivatives, such 2,3-dihydroquinolin-4(1H)-ones, chroman, 3,4-dihydronaphthalen-1(2H)-one, 2,3-dihydrobenzofuran, 2,3-dihydro-1H-inden-1-one, are efficiently produced in moderate to good yields excellent chemoselectivity under mild reaction conditions.

Language: Английский

Citations

24
Photocatalytic α-Trifluoromethylthiolation of N-Acyl Amines DOI
Floriane Doche, Thomas Poisson, Tatiana Besset

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(21), P. 14112 - 14120

Published: Oct. 19, 2023

A photocatalytic approach for the C(sp3)–H trifluoromethylthiolation of amides under mild reaction conditions is reported. We have developed a protocol that tolerates large range functional groups and allows functionalization aromatic aliphatic in high yields (26 examples, up to 83% yield) by using low catalytic loading an organophotocatalyst. With this approach, synthesis original fluorinated acyclic thioaminals successfully achieved. Detailed mechanistic studies are conducted enable deciphering oxidative quenching cycle via proton-coupled electron transfer (PCET), allowing formation primary radical at α-position nitrogen.

Language: Английский

Citations

16
Aurones: A Promising Scaffold to Inhibit SARS-CoV-2 Replication DOI
Guilherme S. Caleffi, Alice dos Santos Rosa, Luana G. de Souza

et al.

Journal of Natural Products, Journal Year: 2023, Volume and Issue: 86(6), P. 1536 - 1549

Published: May 31, 2023

Aurones are a small subgroup of flavonoids in which the basic C6–C3–C6 skeleton is arranged as (Z)-2-benzylidenebenzofuran-3(2H)-one. These compounds structural isomers flavones and flavonols, natural products reported potent inhibitors SARS-CoV-2 replication. Herein, we report design, synthesis, anti-SARS-CoV-2 activity series 25 aurones bearing different oxygenated groups (OH, OCH3, OCH2OCH3, OCH2O, OCF2H, OCH2C6H4R) at A- and/or B-rings using cell-based screening assays. We observed that 12 exhibit EC50 < 3 μM (8e, 8h, 8j, 8k, 8l, 8m, 8p, 8q, 8r, 8w, 8x, 8y), five presented 1 (8h, 8w) without evident cytotoxic effect Calu-3 cells. The substitution B-ring with OCF2H seems beneficial for antiviral activity, while corresponding phenolic derivatives showed significant decrease activity. most compound series, aurone 8q (EC50 = 0.4 μM, SI 2441.3), 2 to times more effective than polyphenolic myricetin (2) baicalein (1), respectively. Investigation active 3CLpro based on molecular dynamic calculations suggested these should detach from site 3CLpro, and, probably, they could bind another protein target (either receptor or enzyme).

Language: Английский

Citations

14
Visible Light-Induced Radical Cascade Difluoromethylation/Cyclization of Unactivated Alkenes: Access to CF2H-Substituted Polycyclic Imidazoles DOI Creative Commons
S.J. Lin, Yuanyuan Deng,

Hanxun Zhong

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(26), P. 28129 - 28143

Published: June 19, 2024

An efficient and mild protocol for the visible light-induced radical cascade difluoromethylation/cyclization of imidazoles with unactivated alkenes using easily accessible bench-stable difluoromethyltriphenylphosphonium bromide as precursor -CF

Language: Английский

Citations

5
Silver-Catalyzed C–H Aryloxydifluoromethylation and Arylthiodifluoromethylation of Heteroarenes DOI
Xiaolei Zhu, Yangen Huang, Xiu‐Hua Xu

et al.

Organic Letters, Journal Year: 2020, Volume and Issue: 22(14), P. 5451 - 5455

Published: July 9, 2020

The oxidative C–H aryloxydifluoromethylation and arylthiodifluoromethylation of heteroaromatic compounds through the decarboxylation easily accessible aryloxydifluoroacetic acids arylthiodifluoroacetic acids, respectively, are disclosed. These reactions promoted by combination catalytic AgNO3 Selectfluor or K2S2O8 to give ArOCF2- ArSCF2-substituted in moderate high yields.

Language: Английский

Citations

39
Organocatalytic Three-Component Acyldifluoromethylation of Vinylarenes via N-Heterocyclic Carbene-Catalyzed Radical Relay DOI

Kun She,

Liang Feng,

Shichao Tian

et al.

Organic Letters, Journal Year: 2022, Volume and Issue: 24(26), P. 4840 - 4844

Published: June 27, 2022

We herein describe an N-hetercyclic carbene-catalyzed three-component acyldifluoromethylation of vinylarenes, aldehydes, and NaSO2CF2H. This organocatalytic approach provides a practical route for the synthesis pharmaceutically relevant α-aryl-β-difluormethyl ketones without need transition metals or photocatalysts. The late-stage drug analogues was also demonstrated. reaction design employs NaSO2CF2H as source CF2H radical in presence oxidant relay.

Language: Английский

Citations

20
Copper-Catalyzed Visible-Light-Induced Allylic Difluoromethylation of Unactivated Alkenes Using Difluoroacetic Acid DOI

Jinlian Wang,

Ziwei Luo,

Yili Wu

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(6), P. 1045 - 1049

Published: Feb. 8, 2023

We herein describe a straightforward allylic difluoromethylation reaction of unactivated alkenes. Compared to cross-couplings prefunctionalized substrates for the construction CF2H bonds, this employs readily available alkenes as under mild conditions. Difluoroacetic acid is used an inexpensive and easy-to-handle source radical visible light irradiation with PIDA. The copper catalyst plays important role diverting pathway toward opposed previously found hydrodifluoromethylation.

Language: Английский

Citations

13
Nickel‐Catalyzed Markovnikov‐Selective Hydrodifluoromethylation of Alkynes Using BrCF2H DOI
Shiwei Pan,

Fan Chen,

Yanyan Zhang

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(31)

Published: June 9, 2023

A Markovnikov-selective hydrodifluoromethylation of alkynes with BrCF2 H via nickel catalysis is described. This protocol proceeds a migratory insertion hydride to alkyne followed by CF2 H-coupling, enabling straightforward access diverse branched H-alkenes high efficiency and exclusive regioselectivity. The mild condition applies wide array aliphatic aryl good functional group compatibility. Mechanistic studies are presented support the proposed pathway.

Language: Английский

Citations

10