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

Defluoroalkylation of Trifluoromethylarenes with Hydrazones: Rapid Access to Benzylic Difluoroarylethylamines DOI Creative Commons
Cecilia M. Hendy, Cameron J. Pratt, Nathan T. Jui

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(9), P. 1397 - 1402

Published: Feb. 27, 2023

Here, we report an efficient and modular approach toward the formation of difluorinated arylethylamines from simple aldehyde-derived N,N-dialkylhydrazones trifluoromethylarenes (CF3-arenes). This method relies on selective C-F bond cleavage via reduction CF3-arene. We show that a diverse set CF3-arenes CF3-heteroarenes react smoothly with range aryl alkyl hydrazones. The β-difluorobenzylic hydrazine product can be selectively cleaved to form corresponding benzylic difluoroarylethylamines.

Language: Английский

Citations

26
Photoinduced copper-catalyzed C–N coupling with trifluoromethylated arenes DOI Creative Commons
Jun Huang, Qi Gao, Zhong Tao

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Dec. 14, 2023

Selective defluorinative functionalization of trifluoromethyl group (-CF3) is an attractive synthetic route to the pharmaceutically privileged fluorine-containing moiety. Herein, we report a strategy based on photoexcited copper catalysis activate C-F bond di- or trifluoromethylated arenes for divergent radical C-N coupling with carbazoles and aromatic amines. The use different ligands can tune reaction products diversity. A range substituted, structurally diverse α,α-difluoromethylamines be obtained from via carbazoles, while interesting double ready difluoromethylated arenes. Based this success, carbazole-centered PNP ligand designed optimal ligand, enabling copper-catalyzed construction imidoyl fluorides amines through functionalization. Interestingly, 1,2-difluoroalkylamination styrenes also developed, delivering γ,γ-difluoroalkylamines, bioisostere β-aminoketones, in synthetically useful yields. DFT studies reveal inner-sphere electron transfer mechanism Cu-catalyzed selective activation C(sp3)-F bonds.

Language: Английский

Citations

26
Asymmetric Defluoroallylation of 4‐Trifluoromethylpyridines Enabled by Umpolung C−F Bond Activation** DOI

Fei‐Yu Zhou,

Lei Jiao

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(21)

Published: March 11, 2022

Carbon-fluorine bond activation of the trifluoromethyl group represents an important approach to fluorine-containing molecules. While selective defluorinative functionalization reactions CF3 -containing substrates have been achieved by invoking difluorocarbocation, difluorocarboradical, or difluoroorganometallic species as key intermediates, transformations via fluorocarbanion mechanism only limited success. Furthermore, enantioselective transformation remained a formidable challenge. Here we report reaction 4-trifluoromethylpyridines involving difluoro(pyrid-4-yl)methyl anion intermediate, which was developed based upon our previous studies on N-boryl pyridyl chemistry. In particular, asymmetric defluoroallylation and -pyrimidines could be using Ir-catalysis forge difluoroalkyl-substituted chiral center.

Language: Английский

Citations

35
Carbodefluorination of fluoroalkyl ketones via a carbene-initiated rearrangement strategy DOI Creative Commons
Linxuan Li, Xinyu Zhang, Yongquan Ning

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 25, 2022

The C-F bond cleavage and C-C formation (i.e., carbodefluorination) of readily accessible (per)fluoroalkyl groups constitutes an atom-economical efficient route to partially fluorinated compounds. However, the selective mono-carbodefluorination trifluoromethyl (CF

Language: Английский

Citations

33
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

Citations

31