Defluorinative Carboimination of Trifluoromethyl Ketones DOI
Xiaolong Zhang, Yongquan Ning, Zhaohong Liu

et al.

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(15), P. 8802 - 8810

Published: July 8, 2022

The monofunctionalized carbodefluorination of readily accessible CF3 groups is acknowledged as an attractive approach for the preparation partially fluorinated molecules. However, their defluorinative difunctionalization remains a challenging and unmet goal. Herein, we report carboimination trifluoromethyl ketones via strategy silver carbene-initiated rearrangement, in which both C–F bond carbonyl group are functionalized simultaneously, thus providing straightforward synthetic method medicinally relevant α,α-difluoroimines. current involves intramolecular cascade process by integrating successive cleavage formation C–C C═N bonds on single molecule entity, differs relevantly from stepwise mechanism reported groups. Mechanistic studies disclose that catalysis plays critical role, particularly stages aza-Claisen rearrangement.

Language: Английский

Synthetic Advantages of Defluorinative C−F Bond Functionalization DOI Creative Commons
Leidy V. Hooker, Jeffrey S. Bandar

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(49)

Published: Aug. 22, 2023

Abstract Much progress has been made in the development of methods to both create compounds that contain C−F bonds and functionalize bonds. As such, are becoming common versatile synthetic functional handles. This review summarizes advantages defluorinative functionalization reactions for small molecule synthesis. The coverage is organized by type carbon framework fluorine attached mono‐ polyfluorinated motifs. main challenges, opportunities advances discussed each class organofluorine. Most text focuses on case studies illustrate how defluorofunctionalization can improve routes targets or properties enable unique mechanisms reactions. broader goal showcase incorporating exploiting design routes, improvement specific advent new methods.

Language: Английский

Citations

57
A review of frustrated Lewis pair enabled monoselective C–F bond activation DOI Creative Commons
Kenneth Lye, Rowan D. Young

Chemical Science, Journal Year: 2024, Volume and Issue: 15(8), P. 2712 - 2724

Published: Jan. 1, 2024

Frustrated Lewis pair (FLP) bond activation chemistry has greatly developed over the last two decades since seminal report of metal-free reversible hydrogen activation. Recently, FLP systems have been utilized to allow monoselective C-F (at equivalent sites) in polyfluoroalkanes. The problem 'over-defluorination' functionalization polyfluoroalkanes (where multiple fluoro-positions are uncontrollably functionalized) a long-standing chemical fluorocarbon for 80 years. mediated is complementary other solutions address and offers several advantages unique opportunities. This perspective highlights some these opportunities places development into context wider effort overcome 'over-defluorination'.

Language: Английский

Citations

18
Defluorinative functionalization approach led by difluoromethyl anion chemistry DOI Creative Commons
Kensuke Muta, Kazuhiro Okamoto, Hiroki Nakayama

et al.

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

Published: Jan. 7, 2025

Language: Английский

Citations

2
Photoredox-Catalyzed C–F Bond Allylation of Perfluoroalkylarenes at the Benzylic Position DOI
Naoki Sugihara, Kensuke Suzuki, Yoshihiro Nishimoto

et al.

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(25), P. 9308 - 9313

Published: June 2, 2021

Site-selective and direct C–F bond transformation of perfluoroalkylarenes was achieved with allylic stannanes via an iridium photoredox catalyst system. The present defluoroallylation proceeds exclusively at the benzylic position through perfluoroalkyl radicals generated by a single-electron transfer from excited to perfluoroalkylarenes. A variety groups are applicable: linear perfluoroalkyl-substituted arenes such as Ar–nC4F9 Ar–nC6F13 heptafluoroisopropylarenes (Ar–CF(CF3)2) underwent site-selective defluoroallylation. DFT calculation studies revealed that in situ Bu3SnF traps F– prevent retroreaction unstable radical intermediate, intermediate favorably reacts stannanes. synthesis bis(trifluoromethyl)methylene unit containing compound, which is analog useful pharmaceutical agent for prophylaxis or treatment diabetes inflammatory diseases, demonstrated utility this reaction.

Language: Английский

Citations

90
Cleavage of C(sp3)–F Bonds in Trifluoromethylarenes Using a Bis(NHC)nickel(0) Complex DOI
Hiroaki Iwamoto,

Hiroto Imiya,

Masato Ohashi

et al.

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(45), P. 19360 - 19367

Published: Oct. 28, 2020

The first example of the oxidative addition a C(sp3)-F bond in trifluoromethylarenes to nickel(0) complex is described. A that bears two N-heterocyclic carbene (NHC) ligands low steric demand able cleave bonds afford corresponding trans-difluorobenzyl nickel(II) fluoride complexes. Isolation and characterization studies suggested cleavage proceeds via an η2-arene complex. Taking advantage reactivity these complexes, we developed catalytic hydrodefluorination using hydrosilanes. computational study indicated electron-rich center supported by relatively small NHC cleaves syn-SN2' mechanism.

Language: Английский

Citations

76
C–F bond functionalizations of trifluoromethyl groups via radical intermediates DOI
Tesfaye Tebeka Simur,

Ye Tian,

You‐Jie Yu

et al.

Chinese Chemical Letters, Journal Year: 2021, Volume and Issue: 33(3), P. 1193 - 1198

Published: Aug. 12, 2021

Language: Английский

Citations

75
Recent advances in radical enabled selective Csp3–F bond activation of multifluorinated compounds DOI
Sifan Li, Wei Shu

Chemical Communications, Journal Year: 2021, Volume and Issue: 58(8), P. 1066 - 1077

Published: Dec. 24, 2021

Fluorine-containing molecules have found broad applications in pharmaceutical and agrochemical industries as introducing fluorine into a molecule could significantly tune the biological activities of parent molecules. Thus, synthesis fluorine-containing has received substantial attention over past few decades. As complementary strategy for fluorinated compounds through new Csp3-F bonds formation, selective cleavage inert from easily-available cost-effective multifluorinated molecules, such fluoroalkylaromatics, α-trifluoromethyl alkenes α-multifluorinated carbonyl compounds, been emerging an attractive alternative to access Moreover, inherent nature radical reactions offers opportunity functionalizations occur under mild conditions. In this regard, development photoredox catalysis, transition-metal or electrochemistry enable species generation via gained progress made recent years. This highlight summerizes advances single-electron-transfer enabled pathways.

Language: Английский

Citations

65
A Base-Promoted Reductive Coupling Platform for the Divergent Defluorofunctionalization of Trifluoromethylarenes DOI

Shawn E. Wright,

Jeffrey S. Bandar

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(29), P. 13032 - 13038

Published: July 14, 2022

We report a trifluoromethylarene reductive coupling method that dramatically expands the scope of difluorobenzylic substructures accessible

Language: Английский

Citations

54
Organoboron Reagent‐Controlled Selective (Deutero)Hydrodefluorination DOI
Zhengjia Shen, Chen Zhu, Xiao Zhang

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(7)

Published: Dec. 16, 2022

(Deuterium-labeled) CF2 H- and CFH2 -moieties are of high interest in drug discovery. The demand for the incorporation these fluoroalkyl moieties into molecular structures has witnessed significant synthetic progress, particularly (deutero)hydrodefluorination CF3 -containing compounds. However, controllable replacement fluorine atoms while maintaining chemoselectivity remains challenging. Herein, we describe development a selective reaction via electrolysis. exhibits remarkable control, which is enabled by addition different organoboron sources. procedure operationally simple scalable, provides access one step to high-value building blocks application medicinal chemistry. Furthermore, density functional theory (DFT) calculations have been carried out investigate mechanism rationalize observed.

Language: Английский

Citations

45
Construction of C–X (X = S, O, Se) Bonds via Lewis Acid-Promoted Functionalization of Trifluoromethylarenes DOI
Jun Xu, Jiawei Liu,

Rui Wang

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(11), P. 7339 - 7346

Published: May 16, 2023

The conversion of easily available trifluoromethylarenes through C–F bond activation provides an attractive pathway for rapid access to difluorobenzylic substructures in producing pharmaceuticals and agrochemicals. However, recent advances this area have been confined C–C(H) construction, thus limiting the diversity accessible motifs. In contrast, selective formation a carbon–heteroatom via functionalization, which enable fast convenient diverse fluorine-containing motifs with high chemical diversity, remains formidable synthetic challenge. Herein, we disclosed Lewis acid promoted photoredox-catalyzed strategy construction C–X (X = S, O or Se) bonds by single C(sp3)–F trifluoromethylarenes, direct synthesis medicinally interesting aryldifluoromethyl ether [ArCF2X– O, Se)] scaffolds. This method relies on readily reagents can tolerate range thiol, phenol, selenol nucleophiles. Its utility was exemplified late-stage modifications several pharmaceutical ingredients. Preliminary studies suggest two parallel pathways: photocatalytic electron-transfer (SET), electron donor–acceptor (EDA) process.

Language: Английский

Citations

33