Decarboxylative Palladium(II)-Catalyzed Synthesis of Aryl Amidines from Aryl Carboxylic Acids: Development and Mechanistic Investigation

被引：36

作者：

Rydfjord, Jonas ^{[1
]}

Svensson, Fredrik ^{[1
]}

Trejos, Alejandro ^{[1
]}

Sjoberg, Per J. R. ^{[2
]}

Skold, Christian ^{[1
]}

Savmarker, Jonas ^{[1
]}

Odell, Luke R. ^{[1
]}

Larhed, Mats ^{[1
]}

机构：

[1] Uppsala Univ, Dept Med Chem, S-75123 Uppsala, Sweden

[2] Uppsala Univ, Dept Chem BMC, S-75123 Uppsala, Sweden

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2013年 / 19卷 / 41期

基金：

瑞典研究理事会;

关键词：

decarboxylation; density functional calculations; mass spectrometry; microwave chemistry; palladium; PALLADIUM-CATALYZED SYNTHESIS; DIELS-ALDER REACTIONS; ONE-STEP SYNTHESIS; ESI-MS; NITRILES; KETONES; INHIBITORS; DERIVATIVES; OLEFINATION; CONVERSION;

D O I：

10.1002/chem.201301809

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A fast and convenient synthesis of aryl amidines starting from carboxylic acids and cyanamides is reported. The reaction was achieved by palladium(II)-catalysis in a one-step microwave protocol using [Pd(O2CCF3)(2)], 6-methyl-2,2-bipyridyl and trifluoroacetic acid (TFA) in N-methylpyrrolidinone (NMP), providing the corresponding aryl amidines in moderate to excellent yields. The protocol is very robust with regards to the cyanamide coupling partner but requires electron-rich ortho-substituted aryl carboxylic acids. Mechanistic insight was provided by a DFT investigation and direct ESI-MS studies of the reaction. The results of the DFT study correlated well with the experimental findings and, together with the ESI-MS study, support the suggested mechanism. Furthermore, a scale-out (scale-up) was performed with a non-resonant microwave continuous-flow system, achieving a maximum throughput of 11mmolh(-1) by using a glass reactor with an inner diameter of 3mm at a flow rate of 1mLmin(-1).

引用

页码：13803 / 13810

页数：8

共 63 条

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