Chemo- and Stereoselective Synthesis of Fluorinated Enamides from Ynamides in HF/Pyridine: Second-Generation Approach to Potent Ureas Bioisosteres

被引：56

作者：

Metayer, Benoit ^{[1
]}

Compain, Guillaume ^{[1
]}

Jouvin, Kevin ^{[2
]}

Martin-Mingot, Agnes ^{[1
]}

Bachmann, Christian ^{[3
]}

Marrot, Jerome ^{[2
]}

Evano, Gwilherm ^{[4
]}

Thibaudeau, Sebastien ^{[1
]}

机构：

[1] Univ Poitiers, CNRS, UMR 7285, Superacid Grp Organ Synth Team,IC2MP, F-86073 Poitiers 09, France

[2] Univ Versailles St Quentin Yvelines, CNRS, UMR 8180, Inst Lavoisier Versailles, F-78035 Versailles, France

[3] Univ Poitiers, CNRS, UMR 7285,IC2MP, Computat Chem Grp Catalysis & Renewable Carbon Te, F-86073 Poitiers 09, France

[4] Univ Libre Bruxelles, Serv Chim & PhysicoChim Organ, Lab Chim Organ, B-1050 Brussels, Belgium

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2015年 / 80卷 / 07期

关键词：

PROTEIN-KINASE INHIBITORS; ELECTROPHILIC REARRANGEMENTS; FLUORIDE) COMPLEXES; HYDROGEN-FLUORIDE; 1,1-DIBROMO-1-ALKENES; DISCOVERY; AMIDES; HF; CONVENIENT; PYRIDINE;

D O I：

10.1021/jo502699y

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

(E)- and (Z)-alpha-fluoroenamides could be easily prepared with high levels of chemo- and regioselectivities by hydrofluorination of readily available ynamides with HF/pyridine. The scope and limitations of this new process for the hydrofluorination of ynamides, as well as the stability of the resulting alpha-fluoroenamides, have been extensively studied. Theoretical calculations at the MP2 and B3LYP levels of theory showed that the resulting fluoroenamides exhibit geometrical and electronic properties that partially mirror those of ureas, therefore demonstrating that the hydrofluorination of ynamides provides a general, straightforward, and user-friendly approach to bioisosteres of ureas, potent building blocks for biological studies and medicinal chemistry.

引用

页码：3397 / 3410

页数：14

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[11] The origin of the conformational preference of N,N′-diaryl-N,N′-dimethyl ureas [J].