Organic Chemistry Portal
Organic Chemistry Highlights

Microwave Chemistry

Monday, May 15, 2006
Doris Dallinger
Karl-Franzens-University Graz

Microwave-Assisted Suzuki Couplings with Simultaneous Cooling

Suzuki couplings using a microencapsulated palladium catalyst (Pd EnCat) under microwave heating were investigated by the group of Steven V. Ley at the University of Cambridge (Chem. Eur. J. 2006, 12, 4407. DOI: 10.1002/chem.200501400). For those compounds giving low purities under conventional microwave conditions A, higher purities could be achieved by performing the reactions at 50 W (reaction temperature did not exceed 76 °C) with simultaneous cooling (compressed air, B) by preventing otherwise occurring thermal decompositions. Even higher purities were obtained by conducting the reactions via a flow-through approach again in combination with cooling (C) due to shorter reaction times (ca. 1 min) and therefore diminished side reactions.

Microwave-Assisted Cu(II)-Mediated Cross-Couplings with Simultaneous Cooling

Erik Van der Eycken and co-workers from University of Leuven performed Cu(II)-mediated scaffold decorations on the pyrazinone core (Org. Lett. 2006, 8, 1863. DOI: 10.1021/ol060422z). N-Arylations utilizing arylboronic acids applying the Chan-Lam protocol were successfully conducted under microwave heating (300 W) with intensive simultaneous cooling at 0 °C (Coolmate). Due to prevented product decomposition, excellent yields could be achieved compared to reactions at rt or elevated temperatures, respectively. High yields could be obtained by using a mixture of Et3N/pyridine (1:2) as opposed to Et3N alone: 93% compared to 69% for R = 3-CF3.

Newman-Kwart Rearrangement

A re-evaluation of the Newman-Kwart rearrangement under microwave conditions was carried out by Jonathan D. Moseley and co-workers from AstraZeneca, Bristol (Tetrahedron 2006, 62, 4685. DOI: 10.1016/j.tet.2005.12.063). Comparisons of results obtained by microwave and thermal heating showed no significant difference which excluded any microwave effects. Additionally, a solvent rate effect has been confirmed under both microwave and thermal heating, demonstrating the stabilization of the polar transition state intermediate 1 by polar solvents like formic acid (78% compared to 23% conv. with NMP after 30 min at 140 °C).

Synthesis of N-Substituted Tetrahydroquinolinediones

The group of Shujiang Tu at the Xuzhou Normal University in China has reported on the one-pot four component reaction for the synthesis of tetrahydroquinoline-diones (Bioorg. Med. Chem. Lett. 2006, 16, 2925. DOI: 10.1016/j.bmcl.2006.03.011). By reacting aromatic aldehydes 1, dimedone 2, meldrumīs acid 3 and amines 4 under microwave conditions a new series of N-functionalized quinolone products 5 was obtained. Higher yields and shorter reaction times compared to conventional heating could be accomplished.

D. Dallinger, Org. Chem. Highlights 2006, May 15.