New CF2H-Synthon Enables Asymmetric Radical Difluoroalkylation for Synthesis of Chiral Difluoromethylated Amines DOI Creative Commons
Xi‐Sheng Wang, Peng Liu, Yan He

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 29, 2024

Abstract The difluoromethyl group (CF₂H) is a crucial fluorinated moiety with distinctive biological properties, and the synthesis of chiral CF₂H-containing analogs has been recognized as powerful strategy in drug design screening. To date, most established method for accessing enantioenriched compounds involves enantioselective functionalization nucleophilic electrophilic CF₂H synthons. However, this approach limited by reaction scope, lower reactivity, reduced enantioselectivity. Leveraging unique fluorine effect, we designed synthesized novel radical synthon incorporating isoindolinone into alkyl halides asymmetric transformation. Here, report an efficient construction carbon stereocenters featuring via nickel-catalyzed Negishi cross-coupling. This demonstrates mild conditions, broad substrate excellent Given that optically pure difluoromethylated amines isoindolinones are key structural motifs bioactive compounds, offers practical solution drug-like molecules pharmaceutical research development.

Language: Английский

CF2H-synthon enables asymmetric radical difluoroalkylation for synthesis of chiral difluoromethylated amines DOI Creative Commons
Peng Liu, Yan He, Chenhui Jiang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 11, 2025

The difluoromethyl group is a crucial fluorinated moiety with distinctive biological properties, and the synthesis of chiral CF₂H-containing analogs has been recognized as powerful strategy in drug design. To date, most established method for accessing enantioenriched compounds involves enantioselective functionalization nucleophilic electrophilic CF₂H synthons. However, this approach limited by lower reactivity reduced enantioselectivity. Leveraging unique fluorine effect, we design synthesize radical synthon incorporating isoindolinone into alkyl halides asymmetric transformation. Here, report an efficient construction carbon stereocenters featuring via nickel-catalyzed Negishi cross-coupling. This demonstrates mild reaction conditions excellent Given that optically pure difluoromethylated amines isoindolinones are key structural motifs bioactive compounds, offers practical solution drug-like molecules. moiety, screening. authors

Language: Английский

Citations

0
Photoredox-Neutral Ni-Catalyzed Decarboxylative Fluoroalkylation via Radical Sorting Cross-Coupling DOI
Yaxing Wu, Xiuling Wang, Zhiyuan Bao

et al.

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 8140 - 8149

Published: May 1, 2025

Language: Английский

Citations

0
Nickel-catalyzed reductive cross-coupling of difluoromethylated secondary alkyl bromides with organohalides DOI
Bosheng Liu,

Jinxu Dong,

Hongyi Wang

et al.

Chemical Communications, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

We present a highly efficient and versatile nickel-catalyzed protocol for the reductive cross-coupling of unactivated CF2H-substituted electrophiles with wide variety aryl alkenyl halides. This novel approach offers high catalytic reactivity broad functional group compatibility, enabling late-stage fluoroalkylation drug molecules.

Language: Английский

Citations

0
Visible Light Catalyzed Reductive Cross‐Coupling of α‐CF3‐alkyl Bromide and Alkynyl Bromide† DOI

Yiqiang Tian,

Yi Li, Chun Zhang

et al.

Chinese Journal of Chemistry, Journal Year: 2024, Volume and Issue: 42(20), P. 2479 - 2484

Published: June 21, 2024

Comprehensive Summary Traditional reduction coupling reactions of two bromides typically rely on transition metal catalysis. Here, we introduce the development a visible‐light catalytic direct reaction between α ‐CF 3 ‐alkyl and alkynyl to access valuable organic frameworks. Our research confirms excellent compatibility this with various functional groups, which could be used modify substrate biologically active molecular fragments. Mechanistic investigations, including control experiments, fluorescence quenching studies, light‐switching have provided insights into mechanism. This study paves way for application catalysis in diverse synthetic transformations, offering sustainable efficient approach synthesis.

Language: Английский

Citations

2
Advances in Direct Fluoroalkylation of Organic Substrates with Partially Fluorinated Alkyl Motivs DOI
Sebastián Barata‐Vallejo, Sergio M. Bonesi, Al Postigo

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(21), P. 15879 - 15907

Published: Oct. 11, 2024

Partially fluorinated alkyl groups other than methyl are increasingly playing crucial roles in the development of drugs with diverse biological activities, thus creating an innovative chemical space within organofluorine chemistry. For studies structure–activity relationships, late-stage modification such or substituents into substrates that bear activity is essential. This perspective will study catalytic protocols for direct introduction partially monofluoroalkylated (−CHFR, –CH2CH2F), difluoroalkylated (−CF2Me, –CH2CF2H), trifluoroalkylated (−CHR(CF3), –CH2CF3, –CH2CH2CF3, –CH(Me)CF3, –C(Me)2CF3), and pentafluoropropylated (−CH2C2F5) onto (hetero)aromatic compounds, double bonds, isonitriles, halides, N, O, S atoms.

Language: Английский

Citations

2
Redox-Active α-Amino-CF3 Reagents: Developing and Applications in Ni-Catalyzed Reductive Cross-Coupling DOI

Yifan Ni,

Ying Wang, Jiyang Liu

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(35), P. 7398 - 7402

Published: Aug. 23, 2024

α-Amino-CF3 compounds are widely employed in bio- and pharmaceutical chemistry for improved stability bioactivities. Traditional methods often face challenges with functional group tolerance lack a general approach late-stage functionalization. Herein, we report new type of redox-active α-amino-CF3 reagents, easily prepared from trifluoro acetaldehyde hydrates. These reagents can serve as versatile building blocks coupling alkynyl bromides, aryl enol triflates under nickel catalysis.

Language: Английский

Citations

1
Catalyst-Free Synthesis of Novel α-Trifluoromethylated Tertiary Alcohols Bearing Azaarenes as Potential Antifungal Agents DOI
Nan Yang, Zhuang Wu, Mingxin Wang

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: unknown, P. 140042 - 140042

Published: Sept. 1, 2024

Language: Английский

Citations

1
Redox-neutral decarboxylative coupling of fluoroalkyl carboxylic acids via a dual metal photoelectrocatalysis DOI Creative Commons
Yaxing Wu, Xiuling Wang, Zhenyu Wang

et al.

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

Published: Jan. 1, 2024

Given the importance and beneficial characteristics of aliphatic CF

Language: Английский

Citations

1
Enantioconvergent C(sp3)–C(sp) Cross-Electrophile Coupling Enabled by Halogen Atom Transfer DOI
Martin Oestreich, Hendrik F. T. Klare, Nektarios Kranidiotis‐Hisatomi

et al.

Synfacts, Journal Year: 2024, Volume and Issue: 20(07), P. 0715 - 0715

Published: June 14, 2024

Key words cross-electrophile coupling - halogen atom transfer nickel catalysis photoredox trifluoromethylated alkynes

Language: Английский

Citations

0
Visible-Light-Induced Photoredox Construction of Trifluoromethylated Quaternary All-Carbon Centers and Tertiary Alcohols via C(sp3)–Si Bond Cleavage DOI
Dachang Bai,

Dandan Ma,

Lingna Chang

et al.

Synthesis, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 10, 2024

Abstract The construction of trifluoromethylated quaternary carbon centers and tertiary alcohols is realized by organo-photoredox catalysis. process proceeds via visible-light-induced C(sp3)–Si bond cleavage for the generation α-trifluoromethylated benzyl radicals, which are readily trapped electron-deficient alkenes with excellent regioselectivity all-carbon centers. α-difluoromethyl counterparts also suitable this radical conjugate addition. Furthermore, in situ oxidation these radicals O2 from air affords high yields, extends Fleming–Tamao reaction to systems.

Language: Английский

Citations

0