Organic Chemistry Portal
Organic Chemistry Highlights

Microwave Chemistry

Tuesday, April 15, 2005
Doris Dallinger
Karl-Franzens-University Graz

Synthesis of 14-Helical β-Peptides

Justin K. Murray and Samuel H. Gellman from the University of Wisconsin-Madison have evaluated the effects of microwave heating on the solid-phase synthesis of high-purity β-peptides (Org. Lett. 2005, 7, 1517. DOI: 10.1021/ol0501727). They showed that by microwave irradiation using an automated microwave peptide synthesizer, 14-helical β-peptides, especially those containing the structure-promoting residue trans-2-aminocyclohexanecarboxylic acid (ACHC), can be obtained in a purity superior to that of both conventional heating and standard solid-phase peptide synthesis (SPPS). For shorter peptides (i.e. the hexamer) microwave heating and conventional heating gave the same results.

Retro-Reductive Aminations

Microwave-promoted direct transformations of amines to ketones have been disclosed by Akira Miyazawa and co-workers from the AIST-Institute in Japan (Chem. Commun. 2005, 2104. DOI: 10.1039/b500541h). By using water as an oxygen source and catalytic amounts of Pd/C, the retro-reductive amination of mono- or di-sec-alkylamines to the corresponding ketones was performed very efficiently. This new and “green” method provides the ketones in a high selectivity and faster rate compared to other methods which are using late transition metal oxidants (e.g. KMnO4, Pb(OAc)4) in large amounts and strong bases such as n-butyllithium.

Petasis Reactions of Electron-Poor Aromatic Amines

A recent publication of Markus Follmann and co-workers from Aventis Pharma (Synlett 2005, 1009. DOI: 10.1055/s-2005-864817) describes the rapid microwave three-component coupling reaction of an amine 1, boronic acid 2 and glyoxylic aldehyde 3, the Petasis reaction (boronic Mannich reaction). A wide range of electron-poor anilines and heterocyclic anilines, but only electron rich boronic acids can be employed to obtain the unnatural N-aryl-α-amino acids in reasonable yields. Comparison studies under conventional heating conditions (heating block, 84 C, 0.5-4 hours) gave identically results for most of the reactions.

Synthesis of Acyl Sulfonamides via Carbonylation Reactions

Mats Larhed and co-workers from Uppsala University (J. Org. Chem. 2005, 70, 3094. DOI: 10.1021/jo050080v) have reported on the palladium-catalyzed carbonylation of both aryl iodides and bromides using sulfonamides as nucleophiles. Good to excellent yields of acyl sulfonamide products were achieved by employing microwave heating for 15 minutes at 110-140 C and using Mo(CO)6 as the CO source. Utilizing this protocol, also a novel hepatitis C virus NS3 protease inhibitor including acyl sulfonamide elements was synthesized.

D. Dallinger, Org. Chem. Highlights 2005, April 15.