Organic Chemistry Portal
Organic Chemistry Highlights

Microwave Chemistry

Saturday, November 15, 2008
Doris Dallinger
Karl-Franzens-University Graz

Selective Buchwald-Hartwig Amination

An extensive optimization study toward the synthesis of 6-heterocyclic substituted 2-aminoquinolines via Buchwald-Hartwig amination of 6-bromo-2-chloroquinoline with cyclic amines was conducted by the group of Simon Pyke from the University of Adelaide (J. Org. Chem. 2008, 73, ASAP. DOI: 10.1021/jo801808r). Crucial for the selective amination at the 6-position is the choice of the solvent. By changing from toluene to benzotrifluoride (BTF) not only the reaction can be performed in the microwave at 150 °C due to the better microwave absorbance characteristics of BTF compared to toluene, but also higher product yields were obtained. Under thermal heating BTF proved to be superior to toluene with respect to product yields as well.

Direct C-H Arylation of Adenines

Mouad Alami and co-workers from Université Paris-Sud have reported on the direct arylation of adenines under ligandless Pd(OH)2/C catalysis (Tetrahedron Lett. 2008, 49, ASAP. DOI: 10.1016/j.tetlet.2008.10.021). Regioselective coupling at the C8-position was obtained with a variety of aryl iodides, bromides and chlorides, although for aryl chlorides a longer reaction time (1-2 h) was necessary compared to the corresponding iodide or bromide derivatives. Advantages of this general protocol are that there is no need for protecting free NH2-substituents and that CuI is used in stoichiometric amounts. β-(E)-bromostyrene as an example for vinyl halide coupling was also successfully reacted giving exclusively the E-isomer in 55% yield.

Catalyst-free Cycloisomerization Approach to Indolizinones

The synthesis of indolizinones via a thermally induced cycloisomerization of tertiary propargylic alcohols was described by Ikyon Kim and co-workers from the Korea Research Institute of Chemical Technology (Synlett 2008, 2334. DOI: 10.1055/s-2008-1078022). Heating the starting materials in EtOH to 150 °C without the addition of a catalyst afforded the indolizinones in excellent yields. Compared to conventional heating in refluxing EtOH the reactions could be accelerated from 24-36 h to only 20-30 min (the longer reaction time is necessary when R2 = t-Bu) with similar isolated product yields.

Synthesis of Pyrroles using Magnesium Nitride as Ammonia Source

The group of Steven Ley from the University of Cambridge has reported on the synthesis of substituted pyrroles from the corresponding 1,4-dicarbonyl compounds via the Paal-Knorr reaction (Synlett 2008, 2597. DOI: 10.1055/s-0028-1083504). Magnesium nitride (Mg3N2) was used as source of ammonia which is generated in situ by the reaction of Mg3N2 with protic solvents like MeOH. Reaction times were typically 1 h, the only exception being the derivative with R1 = R2 = t-Bu where 8 h irradiation were necessary to achieve complete conversion. With respect to scale-up and library synthesis the authors prepared pyrroles under thermal heating at 80°C as well. Here, a 24 h reaction time is necessary for providing the products in good to excellent yields.


D. Dallinger, Org. Chem. Highlights 2008, November 15.