Organic Chemistry Portal
Organic Chemistry Highlights

Microwave Chemistry

Saturday, June 15, 2004
C. Oliver Kappe
Karl-Franzens-University Graz

Vinyl Cyclobutane Rearrangements

A recent publication by the group of Phil S. Baran from the Scripps Research Institute (Angew. Chem. Int. Ed. 2004, 43, 2674. DOI: 10.1002/anie.200453937) reports the total synthesis of ageliferin, an antiviral agent with interesting molecular architecture. Just one minute (!) of microwave irradiation of sceptrin, another natural product, for 195 C under sealed vessel conditions provides ageliferin in 40% yield, along with 52% of recovered starting material. Remarkably, if the reaction is performed without microwaves at the same temperature only starting material and decomposition products are observed.

Diels-Alder Cycloaddition Chemistry

Christopher J. Moody and co-workers from the University of Exeter have employed (Chem. Commun. 2004, 946. DOI: 10.1039/b401580k) a "biomimetic" hetero-Diels-Alder-aromatization sequence for the construction of the pyridine ring in amythiamicin D. The key cycloaddition reaction between the azadiene and enamine component was carried out by microwave irradiation at 120 C for 12 hours (see also Chem. Commun. 2002, 1760. DOI: 10.1039/b204868j) and gave the required 2,3,6-tris(thiazolyl)pyridine intermediate in moderate yield. Coupling of the remaining building blocks then completed the first total synthesis of the thiopeptide antibiotic amythiamicin D.

Suzuki-Miyaura Cross-Coupling Reactions

A series of air- and moisture-stable (N-heterocyclic carbene)Pd(allyl)Cl complexes has been shown by Steven P. Nolan and coworkers (J. Org. Chem. 2004, 69, 3173. DOI: 10.1021/jo035834p) to catalyze Suzuki-Miyaura cross coupling reactions of aryl chlorides with boronic acids. This catalytic system is compatible to microwave conditions and rapid couplings were observed within 1.5 min at 120 C. The conventionally heated reactions (60 C) required several hours to reach completion. The same article also reports on microwave-assisted dehalogenations of aryl chlorides using the same catalytic system.

Solid-Phase Synthesis of Indol-2-ones via Radical Cyclization

Koichi Fukase and coworkers from Osaka University have reported (Synlett 2004, 1049. DOI: 10.1055/s-2004-820052) the solid-phase synthesis of indol-2-ones (4 diversity points) via a radical cyclization pathway. The key cyclization step was carried out by using Bu3SnH and AIBN in DMF under microwave irradiation conditions, providing a small library of 40 compounds. Interestingly, the related radical cyclization in solution phase was considerable less effective.

Review and Feature Articles

Two recent review articles highlight the importance of microwave chemistry for carbohydrate chemistry:

S. K. Das, "Application of Microwave Irradiation in the Synthesis of Carbohydrates", Synlett 2004, 915-932. DOI: 10.1055/s-2004-820034

A. Corsaro, U. Chiacchio, V. Pistara, G. Romeo, "Microwave-Assisted Chemistry of Carbohydrates", Curr. Org. Chem. 2004, 8, 511-538. Available for free

(Reproduced by permission of Bentham Science Publishers)

C. O. Kappe, Org. Chem. Highlights 2004, June 15.