Nickel‐Catalyzed Defluorinative Asymmetric Cyclization of Fluoroalkyl‐Substituted 1,6‐Enynes for the Synthesis of Seletracetam DOI

Kuai Wang,

Jiachang Chen, Wenfeng Liu

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(46)

Published: Sept. 23, 2022

Abstract The introduction of fluorine‐containing groups into organic molecules can significantly affect their physical and chemical properties has long been used as an effective strategy for drug discovery development. Consequently, the development catalytic asymmetric methods synthesis heterocycles is highly desirable sought after. Herein, we describe a nickel‐catalyzed defluorinative cyclization fluoroalkyl‐substituted 1,6‐enynes, providing expedient access to synthetically attractive 4‐fluorovinyl‐substituted 2‐pyrrolidones in good yields with remarkable high levels chemo‐, regio‐, enantioselectivities (90–99 % ee,>35 examples). This protocol features readily available starting materials excellent functional group compatibility, exhibits complementary regioselectivity. utility this was demonstrated enantioselective antiepileptic Seletracetam.

Language: Английский

Recent advance in the C–F bond functionalization of trifluoromethyl-containing compounds DOI
Guobing Yan,

Kaiying Qiu,

Ming Guo

et al.

Organic Chemistry Frontiers, Journal Year: 2021, Volume and Issue: 8(14), P. 3915 - 3942

Published: Jan. 1, 2021

The C–F bond is the strongest single in organic compounds.

Language: Английский

Citations

153
Recent Advances in the Synthesis of Difluorinated Architectures from Trifluoromethyl Groups DOI
Feng Zhao, Wenlong Zhou,

Zuo Zuo

et al.

Advanced Synthesis & Catalysis, Journal Year: 2021, Volume and Issue: 364(2), P. 234 - 267

Published: Nov. 29, 2021

Abstract Fluorine‐containing moieties are widely used in the pharmaceutical, agrochemical, and material fields. Thus, these structures of immense interest fields organic synthesis medicinal chemistry. Among various fluorinated groups, difluoromethyl unit has drawn increasing attention due to its unique pharmaceutical properties. In recent years, several methods for difluoromethylated compounds have been rapidly developed. However, most treat aromatic with excess difluoromethylating reagents, which often contain organometallic compounds, so transformations generally less environmentally friendly atom‐economical. this review, we summarize development new motifs or difluoroalkenes from trifluoromethylated trifluoromethyl alkenes via single C( sp 3 )−F bond cleavage. magnified image

Language: Английский

Citations

122
Synthesis of gem-Difluoroalkenes via Nickel-Catalyzed Allylic Defluorinative Reductive Cross-Coupling DOI
Yun Lan,

Feiyan Yang,

Chuan Wang

et al.

ACS Catalysis, Journal Year: 2018, Volume and Issue: 8(10), P. 9245 - 9251

Published: Sept. 4, 2018

In this protocol, we report an allylic defluorinative reductive cross-coupling reaction for C–C bond formation. Under the Ni-catalysis challenging C(sp3)–F cleavage of trifluoromethyl-substituted alkenes was achieved with easily accessible primary, secondary and tertiary alkyl halides as coupling partners Zn-powder reducing agent. This process provides efficient convenient entry to gem-difluoroalkenes bearing various sensitive functional groups under mild conditions. Moreover, method proves be suitable late-stage functionalization multifunctional complex molecules.

Language: Английский

Citations

160
Copper-Catalyzed Asymmetric Defluoroborylation of 1-(Trifluoromethyl)Alkenes DOI Creative Commons
Pan Gao,

Chengkai Yuan,

Yue Zhao

et al.

Chem, Journal Year: 2018, Volume and Issue: 4(9), P. 2201 - 2211

Published: July 26, 2018

Language: Английский

Citations

152
Activation of C–F bonds α to C–C multiple bonds DOI
Jean‐Denys Hamel, Jean‐François Paquin

Chemical Communications, Journal Year: 2018, Volume and Issue: 54(73), P. 10224 - 10239

Published: Jan. 1, 2018

A closer look is given to the successful approaches C(sp3)–F activation of benzylic, allylic, propargylic and allenylic fluorides.

Language: Английский

Citations

149
NiH‐Catalyzed Migratory Defluorinative Olefin Cross‐Coupling: Trifluoromethyl‐Substituted Alkenes as Acceptor Olefins to Form gem‐Difluoroalkenes DOI
Fenglin Chen,

Xianfeng Xu,

Yuli He

et al.

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(13), P. 5398 - 5402

Published: Jan. 17, 2020

We report a NiH-catalyzed migratory defluorinative coupling between two electronically differentiated olefins. A broad range of unactivated donor olefins can be joined directly to acceptor containing an electron-deficient trifluoromethyl substituent in both intra- and intermolecular fashion form gem-difluoroalkenes. This shows site- chemoselectivity under mild conditions, with the formation tertiary or quaternary carbon center.

Language: Английский

Citations

126
New Radical Borylation Pathways for Organoboron Synthesis Enabled by Photoredox Catalysis DOI
Jing Qi, Feng‐Lian Zhang, Ji‐Kang Jin

et al.

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(31), P. 12876 - 12884

Published: March 31, 2020

Radical borylation using N-heterocyclic carbene (NHC)-BH3 complexes as boryl radical precursors has emerged an important synthetic tool for organoboron assembly. However, the majority of reported methods are limited to reaction modes involving carbo- and/or hydroboration specific alkenes and alkynes. Moreover, generation NHC-boryl radicals relies principally on hydrogen atom abstraction with aid initiators. A distinct method is reported, well pathways enabled by photoredox catalysis. generated via a single-electron oxidation subsequently undergo cross-coupling in-situ-generated anions yield gem-difluoroallylboronates. photoredox-catalyzed arylboration was achieved cyanoarenes arylating components from which elaborated organoborons were accessed. Mechanistic studies verified oxidative formation through single-electron-transfer pathway.

Language: Английский

Citations

120
Catalytic Enantioselective Boryl and Silyl Substitution with Trifluoromethyl Alkenes: Scope, Utility, and Mechanistic Nuances of Cu–F β-Elimination DOI
Paulo H. S. Paioti, Juan del Pozo,

Malte S. Mikus

et al.

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(50), P. 19917 - 19934

Published: Dec. 6, 2019

Catalytic enantioselective methods are introduced that allow access to a variety of allyl boronates and silanes contain difluoroalkene unit; the resulting products may be used for preparation organofluorine compounds in high enantiomeric purity. Furthermore, number key mechanistic aspects transformations have been investigated analyzed. Thus, first, an NHC–Cu-catalyzed method boryl substitution with F3C-substituted alkenes is introduced. These processes, unlike previously reported strategies, applicable alkyl as well aryl substituted substrates, afford bearing moiety (up 98% yield 95:5 er). Second, corresponding silyl substitutions, first cases their kind, presented 94% 97:3 Third, experimental computational (DFT) investigations described shed light on catalytic processes. Evidence (X-ray structures Cu–alkyl intermediates kinetic studies) put forth illustrating initial Cu–boryl Cu–silyl addition significantly faster than ensuing Cu–F elimination, latter step can facilitated by either mild Lewis acid (e.g., Li or Na cation) nucleophilic promoter alkoxide). findings together DFT studies demonstrate β-elimination probably proceeds anti-stereochemistry. Representative ways through which new understanding rationalize disclosed findings, improve transformation, develop diastereo- provided. For example, explanation provided regarding why bisphosphine–Cu complexes do not efficiently promote substitutions aryl-substituted but facile, how size ligand impact regioselectivity efficiency.

Language: Английский

Citations

118
gem-Difluoroallylation of Aryl Diazoesters via Catalyst-Free, Blue-Light-Mediated Formal Doyle–Kirmse Reaction DOI
Jianhua Yang,

Jiazhuang Wang,

Hongtai Huang

et al.

Organic Letters, Journal Year: 2019, Volume and Issue: 21(8), P. 2654 - 2657

Published: March 29, 2019

A first example of low-energy blue-light-mediated formal Doyle–Kirmse reaction for gem-difluoroallylation aryl diazoesters has been developed. variety highly functionalized gem-difluoroallyl containing esters bearing transformable sulfur and bromine groups were efficiently assembled with broad substrate scope under mild, catalyst-free, additive-free conditions. The represents a practical environmentally friendly approach C–CF2 bond formation based on rearrangement strategy, which will find potential applications among drug discovery development.

Language: Английский

Citations

112
Beyond Carbon: Enantioselective and Enantiospecific Reactions with Catalytically Generated Boryl- and Silylcopper Intermediates DOI Creative Commons
Weichao Xue, Martin Oestreich

ACS Central Science, Journal Year: 2020, Volume and Issue: 6(7), P. 1070 - 1081

Published: July 9, 2020

Catalytic asymmetric C–C bond formation with alkylcopper intermediates as carbon nucleophiles is now textbook chemistry. Related chemistry boron and silicon where the boryl- accordingly silylcopper are catalytically regenerated from bench-stable pronucleophiles had been underdeveloped for years or did not even exist until recently. Over past decade, copper catalysis employing those main-group elements rapidly transformed into a huge field in its own right an impressive breadth of enantioselective C–B C–Si bond-forming reactions, respectively. Its current state art does have to shy away comparison that boron's silicon's common neighbor periodic table, carbon. This Outlook meant be detailed summary manifold advances. It rather aims at providing brief conceptual what forms basis latest exciting progress, especially area three-component reactions cross-coupling reactions.

Language: Английский

Citations

97