Organic Chemistry Portal
Organic Chemistry Highlights

Microwave Chemistry

Friday, February 15, 2008
Doris Dallinger
Karl-Franzens-University Graz

Gold(I)-Catalyzed Intramolecular [4+2] Cycloadditions

The intramolecular [4+2] cycloaddition of alkenyl- (1) and aryl-substitued 1,6-enynes 2 was described by the group of Antonio Echavarren from the Institute of Chemical Research of Catalonia (ICIQ), Spain, (J. Am. Chem. Soc. 2008, 130, 269. DOI: 10.1021/ja075794x). The transformations proceed via catalysis involving cationic Au(I)-complexes and furnish bicyclic products from 1 and tricyclic derivatives from 2. Heating under microwave conditions leads to reduced reaction times (h vs. min) and improved yields. Precatalyst 4 proved to be more reactive than 3 especially under room temperature conditions. Substrates 2 with m-substituents at the aryl moiety gave mixtures of regioisomers, whereas other minor by-product formation was observed via a 6-endo cyclization pathway.

One-Pot Three-Component Isoxazole Synthesis

The group of Thomas Müller from Heinrich-Heine-Universität Düsseldorf, Germany, has developed the synthesis of 3,4,5-substituted isoxazoles via a one-pot three-component reaction pathway (Synthesis 2008, 293. DOI: 10.1055/s-2007-1000856). In the first sequence, alkynones 1 are obtained by Sonogashira coupling of acid chlorides with terminal alkynes at room temperature. After addition of hydroximinoyl chlorides 2 and Et3N to the same reaction vessel, alkynones 1 reacted further to the corresponding isoxazoles via a 1,3-dipolar cycloaddition with in situ generated aromatic nitrile oxides from 2. By employing microwave heating for the cycloaddition step, reaction times could be reduced from three days to 30 min, while increased yields of the final products and less by-product formation (dimerization of nitrile oxides to furoxan oxides) were observed.

Synthesis of Substituted 2-Aminoimidazoles

The synthesis of mono- and disubstituted 2-aminoimidazoles by the reaction of diverse α-haloketones with N-acetylguanidine was reported by Yulin Lam and co-workers from the National University of Singapore (J. Comb. Chem. 2008, 10, 118. DOI: 10.1021/cc700143n). In the first reaction step, the corresponding imidazol-2-acetamides were obtained in excellent yields. Further deacylation with H2SO4 and MeOH/H2O (1:1) or EtOH, respectively, and subsequent formation of the free amine with 5 M KOH in MeOH furnished the 2-aminoimidazole products, again in high yields. The overall reaction time could be cut down to only 20 min compared to several days under conventional room temperature conditions.

Suzuki-Miyaura Coupling/Aldol Condensation Cascade Reaction

Jung-Nyoung Heo and co-workers from the Korea Research Institute of Chemical Technology have disclosed a cascade reaction of o-substituted aryl halides and o-formyl or o-acetyl-arylboronic acids - involving first a Suzuki-Miyaura coupling and a subsequent intramolecular aldol condensation - for the synthesis of phenanthrene derivatives (J. Org. Chem. 2008, 73, 495. DOI: 10.1021/jo702001n). Crucial for obtaining the phenanthrenes in high yields is the ratio of the solvent mixture, with toluene/EtOH 2:1 leading to optimum results. When a ketone is employed as aldol acceptor (R4 = Me) DavePhos as ligand has to be used, and a lower temperature of 120 °C for 5 min for the Suzuki coupling was necessary followed by an additional 10 min at 150 °C for the aldol condensation. The same is true for some aryl halide building blocks (R1 = CO2Et, CN; X = Cl), where either DavePhos or SPhos has to be applied in order to prevent side reactions and to receive the phenanthrene products in good yields. The reversed approach was possible as well where boronate esters are reacted with 2-bromoaryl carboxaldehydes.


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