Cu(II)-Catalyzed Unsymmetrical Dioxidation of gem-Difluoroalkenes to Generate α,α-Difluorinated-α-phenoxyketones DOI
Suvajit Koley, Kaylee Cayton, Gisela A. González‐Montiel

et al.

The Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 87(16), P. 10710 - 10725

Published: Aug. 1, 2022

A Cu-based catalyst system convergently couples gem-difluoroalkenes with phenols under aerobic conditions to deliver α,α-difluorinated-α-phenoxyketones, an unstudied hybrid fluorinated functional group. Composed of α,α-difluorinated ketone and ether moieties, these compounds have rarely been reported as a synthetic intermediate. Computational predictions later experimental corroboration suggest that the phenoxy-substituted ketone's sp3-hybridized hydrate form is energetically favored relative respective nonether variant perturbation electronic character can further encourage formation hydrate. The more facile conversion between forms suggests analogues should readily covalently inhibit proteases other enzymes. Further functionalization group enables access useful groups.

Language: Английский

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
Asymmetric Synthesis of 2,2‐Difluorotetrahydrofurans through Palladium‐Catalyzed Formal [3+2] Cycloaddition DOI
Jun Liu,

Longhui Yu,

Changwu Zheng

et al.

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(44), P. 23641 - 23645

Published: Sept. 8, 2021

The asymmetric synthesis of 2,2-difluorinated tetrahydrofurans was accomplished via enantioselective formal [3+2] cycloaddition catalyzed by palladium. reaction between gem-difluoroalkenes and racemic vinyl epoxides or vinylethylene carbonates resulted in the formation enantioenriched 2,2-difluorotetrahydrofurans with an enantioselectivity up to 98 %. Notably, used readily available (R)-BINAP as ligand at a low loading yielded wide variety difluorinated products moderate high yields. Both chiral diastereomers could be obtained single sequence.

Language: Английский

Citations

49
Catalytic oxidative dehydrogenation of N-heterocycles with nitrogen/phosphorus co-doped porous carbon materials DOI Creative Commons
Kangkang Sun,

Hongbin Shan,

Rui Ma

et al.

Chemical Science, Journal Year: 2022, Volume and Issue: 13(23), P. 6865 - 6872

Published: Jan. 1, 2022

A metal-free oxidative dehydrogenation of N-heterocycles utilizing a nitrogen/phosphorus co-doped porous carbon (NPCH) catalyst is reported. The optimal material robust against traditional poisoning agents and shows high antioxidant resistance. It exhibits good catalytic performance for the synthesis various quinoline, indole, isoquinoline, quinoxaline 'on-water' under air atmosphere. active sites in NPCH are proposed to be phosphorus nitrogen centers within network.

Language: Английский

Citations

38
Hydrogen‐Bond‐Mediated Formation of C−N or C=N Bond during Photocatalytic Reductive Coupling Reaction over CdS Nanosheets DOI
Jie He, Bo Han,

Chensheng Xian

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(26)

Published: April 19, 2024

Abstract Reductive amination of carbonyl compounds and nitro represents a straightforward way to attain imines or secondary amines, but it is difficult control the product selectivity. Herein, we report selective formation C−N C=N bond readily manipulated through solvent‐induced hydrogen bridge, facilitating swift photocatalytic reductive coupling process. The reductive‐coupling with using formic acid sodium formate as donors over CdS nanosheets selectively generates bonds in acetonitrile solvent; while taking methanol solvent, are hydrogenated via hydrogen‐bonding activation. Experimental theoretical study reveals that building hydrogen‐bond bridge between hydroxyl groups N atoms motifs facilitates transfer from surface upon illumination, resulting rapid hydrogenation give rise amines bonds. Our method provides simple selectivity by altering solvents organic transformations.

Language: Английский

Citations

8
Advances in silylation and borylation of fluoroarenes and gem-difluoroalkenes via C–F bond cleavage DOI
Juan Zhang,

Shasha Geng,

Feng Zhang

et al.

Chemical Communications, Journal Year: 2021, Volume and Issue: 57(90), P. 11922 - 11934

Published: Jan. 1, 2021

Organoboron and organosilane compounds are widely used in organic synthesis pharmaceuticals.

Language: Английский

Citations

40
Fluorine-Retentive Strategies for the Functionalization of gem-Difluoroalkenes DOI
Ryan A. Altman, Jacob P. Sorrentino

Synthesis, Journal Year: 2021, Volume and Issue: 53(21), P. 3935 - 3950

Published: July 12, 2021

gem-Difluoroalkenes are readily available fluorinated building blocks, and the fluorine-induced electronic perturbations of alkenes enables a wide array selective functionalization reactions. However, many reactions gem-difluoroalkenes result in net C─F to generate monofluorovinyl products or addition F trifluoromethyl-containing products. In contrast, fluorine-retentive strategies for remain less generally developed, is now becoming rapidly developing area. This review will present development including electrophilic, nucleophilic, radical, transition metal catalytic with an emphasis on key physical organic mechanistic aspects that enable reactivities.

Language: Английский

Citations

36
Selective and Controllable Defluorophosphination and Defluorophosphorylation of Trifluoromethylated Enones: An Auxiliary Function of the Carbonyl Group DOI

Li-Wen Sun,

Ya‐Fei Hu,

Wen-Jun Ji

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(20), P. 3745 - 3749

Published: May 11, 2023

The auxiliary function of a carbonyl group in the tunable defluorophosphination and defluorophosphorylation trifluoromethylated enones with P(O)-containing compounds was demonstrated. Controlled replacement one or two fluorine atoms while maintaining high chemo- stereoselectivity achieved under mild conditions, thus enabling diversity-oriented synthesis skeletally diverse organophosphorus libraries─(Z)-difluoro-1,3-dien-1-yl phosphinates, (1Z,3E)-4-phosphoryl-4-fluoro-buta-1,3-dien-1-yl (E)-4-phosphoryl-4-fluoro-1,3-but-3-en-1-ones─in good yields excellent functional tolerance.

Language: Английский

Citations

14
Reversal of the Regioselectivity of Iron‐Promoted Hydrogenation and Hydrohalogenation of gem‐Difluoroalkenes DOI
Yuyang Zhang, Yuchen Zhang, Xiao‐Song Xue

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(25)

Published: April 19, 2024

The reaction regioselectivity of gem-difluoroalkenes is dependent on the intrinsic polarity. Thus, reversal addition remains a formidable challenge. Herein, we described an unprecedented hydrogen atom transfer (HAT) to triggered by Fe-H species for formation difluoroalkyl radicals. Hydrogenation in situ generated radicals gave difluoromethylated products. Mechanism experiments and theoretical studies revealed that kinetic effect irreversible HAT process resulted this scenario, leading less stable α-difluoroalkyl radical regioisomer. On basis new gem-difluoroalkene, iron-promoted hydrohalogenation efficient synthesis aliphatic chlorodifluoromethyl-, bromodifluoromethyl- iododifluoromethyl-containing compounds was developed. Particularly, novel provided large-scale access various iododifluoromethylated high value synthetic application.

Language: Английский

Citations

5
Superbase-Mediated gem-Difluoroalkenylations of Sulfoximines DOI
Xianliang Wang, Chenyang Wang, Carsten Bolm

et al.

Organic Letters, Journal Year: 2022, Volume and Issue: 24(40), P. 7461 - 7464

Published: Oct. 3, 2022

At ambient temperature, deprotonated sulfoximines react with 1-trifluoromethylalkenes to provide either N- or C-gem-difluoroalkenylated products. The reaction site depends upon the N substituent of starting material. optimal conditions involve use a superbasic system NaOH in dimethyl sulfoxide. reactions are characterized by broad substrate scope and medium high yields. Scale-up experiments both C-gem-difluoroalkenylations proceeded well. Treatment N-difluoroallyl sulfoximine an aryl thiol under dioxygen afforded corresponding oxygenated addition product.

Language: Английский

Citations

19
Electrochemical Difunctionalization of gem-Difluoroalkenes: A Metal-Free Synthesis of α-Difluoro(alkoxyl/azolated) Methylated Ethers DOI

Linzi Wen,

Naifu Zhou, Zhicheng Zhang

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(18), P. 3308 - 3313

Published: May 2, 2023

A scalable electrochemical difunctionalization of gem-difluoroalkenes to structurally versatile difluoro motifs was achieved. This methodology features reagent-free conditions, good functional group tolerance, and a relatively broad substrate scope. Meanwhile, the electrolysis protocol is easy handle, products show regio- chemoselectivity. The reaction mechanism also preliminarily studied.

Language: Английский

Citations

11