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

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Окт. 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.

Язык: Английский

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

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 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

Язык: Английский

Процитировано

1
Visible Light Catalyzed Reductive Cross‐Coupling of α‐CF3‐alkyl Bromide and Alkynyl Bromide† DOI

Yiqiang Tian,

Yi Li, Chun Zhang

и другие.

Chinese Journal of Chemistry, Год журнала: 2024, Номер 42(20), С. 2479 - 2484

Опубликована: Июнь 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.

Язык: Английский

Процитировано

3
Nickel-catalyzed reductive cross-coupling of difluoromethylated secondary alkyl bromides with organohalides DOI
Bosheng Liu,

Jinxu Dong,

Hongyi Wang

и другие.

Chemical Communications, Год журнала: 2025, Номер unknown

Опубликована: Янв. 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.

Язык: Английский

Процитировано

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

и другие.

ACS Catalysis, Год журнала: 2025, Номер unknown, С. 8140 - 8149

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0
Alkynyl Sulfide: An Unexplored yet Versatile Alkynyl Species for Chemoselective Cross-Electrophile Coupling DOI
Donghui Xing, Jinlin Liu, Liangbin Huang

и другие.

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Май 23, 2025

The development of robust and readily available carbon electrophiles for cross-electrophile coupling (XEC) is important highly desirable. Herein, we report a cobalt-catalyzed chemoselective XEC between alkynyl sulfides various alkyl halides, which tolerates otherwise widely employed handles such as series aromatic (pseudo)halogens (Ar-I/Br/Cl/OTf/OTs/SMe) provides an easy efficient method synthesizing internal alkynes (>60 examples achieving up to 96% yields). Mechanistic studies have revealed that the leaving sulfide anion adjusts reactivity alkynyl-Co intermediates, enabling excellent chemoselectivity.

Язык: Английский

Процитировано

0
cis-Diphosphine Ethene Ligand-Ni Complex Catalyzed C-P Cross-Coupling of Aryl Chlorides DOI
Yumeng Wu, Zhe Tang,

Xiaoli Li

и другие.

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Июнь 2, 2025

Nickel complexes supported by cis-diphosphine ethene ligands were synthesized and employed in the C-P coupling reaction of aryl chlorides. The rigid five-membered-ring structure formed bisphosphine with olefinic backbones nickel may be crucial for facilitating reductive elimination step catalytic cycle. steric hindrance electronic properties these have also been shown to a significant effect on rate extent reaction. A series chlorides can smoothly converted corresponding trisubstituted phosphine oxides disubstituted oxides, as well dialkyl phosphites, under mild conditions. system showed good compatibility heterocyclic structures. In addition, this air-stable easy-to-handle complex has demonstrated application potential synthesis pharmaceutical molecules.

Язык: Английский

Процитировано

0
Advances in Direct Fluoroalkylation of Organic Substrates with Partially Fluorinated Alkyl Motivs DOI
Sebastián Barata‐Vallejo, Sergio M. Bonesi, Al Postigo

и другие.

ACS Catalysis, Год журнала: 2024, Номер 14(21), С. 15879 - 15907

Опубликована: Окт. 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.

Язык: Английский

Процитировано

2
Redox-neutral decarboxylative coupling of fluoroalkyl carboxylic acids via a dual metal photoelectrocatalysis DOI Creative Commons
Yaxing Wu, Xiuling Wang, Zhenyu Wang

и другие.

Chemical Science, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Given the importance and beneficial characteristics of aliphatic CF

Язык: Английский

Процитировано

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

Yifan Ni,

Ying Wang, Jiyang Liu

и другие.

Organic Letters, Год журнала: 2024, Номер 26(35), С. 7398 - 7402

Опубликована: Авг. 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.

Язык: Английский

Процитировано

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

и другие.

Journal of Molecular Structure, Год журнала: 2024, Номер unknown, С. 140042 - 140042

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

1