Organic Chemistry Portal
Organic Chemistry Highlights

Microwave Chemistry

Saturday, January 15, 2006
C. Oliver Kappe
Karl-Franzens-University Graz

Ring Closing Metathesis for Guaianolide Synthesis

Oliver Reiser and his group from the University of Regensburg, Germany have reported on the ring-closing metathesis (RCM) of a sterically demanding substrate in the context of the total synthesis of tricyclic 5.7.5-sesquiterpene lactones of the guaianolide type (Adv. Synth. Catal. 2005, 347, 1869. DOI: 10.1002/adsc.200505137). Key to the success for the formation of the tetrasubstituted double bond system by RCM was the combination of microwave heating and sparging an inert gas through the solution in order to remove the formed ethylene. An optimized 98% isolated product yield was obtained by irradiating the bisolefin precursor in the presence of 15 mol% of Grubbs II catalyst in toluene for 90 min at reflux temperature (110 C), while passing a gentle stream of argon through the solution. Importantly, under sealed vessel microwave irradiation the RCM failed completely, and starting material was recovered almost quantitatively.

Direct Reductive Amination of Aldehydes

A team from Medivir Ltd. in the United Kingdom has described (Org. Lett. 2005, 7, 5653. DOI: 10.1021/ol0522844) a fast protocol for the direct reductive amination of aldehydes which uses dibutyltin dichloride as catalyst in the presence of phenylsilane as reductant. Best results are obtained utilizing 10 mol% of dibutyltin dichloride as a catalyst and 2 equivalents of phenylsilane as the reducing agent, employing THF as solvent and sealed vessel microwave heating at 100 C for 7 minutes. Suitable reactants for this novel protocol include aliphatic and aromatic aldehydes building blocks on the one hand, and anilines, secondary and primary amines on the other. Work-up typically involves extraction or cation exchange methods.

Synthesis of Quinazolinobenzodiazepines

The one-pot total synthesis of the quinazolinobenzodiazepine alkaloid sclerotigenin via a novel microwave-assisted domino reaction was reported by Ji-Feng Liu and colleagues from ArQule Inc, Woburn, Massachusetts (J. Org. Chem. 2005, 70, 10488. DOI: 10.1021/jo051876x). The alkaloid was obtained in 55% yield by condensation of two equivalents of anthranilic acid with N-Boc-glycine in the presence of triphenyl phosphite using pyridine as solvent and microwave heating at 230 C for 20 minutes. Related products were obtained employing substituted anthranilic acids and other amino acids as starting materials (R1 ≠ H). The authors also developed a three-component, one-pot sequential modification that allowed the preparation of related alkaloids having different substituents on the aromatic rings, starting from two different anthranilic acid derivatives.

Rapid Deprotection of N-Boc Amines

A. Ganesan and his group from the University of Southampton have demonstrated a rapid method for the deprotection of N-Boc-protected amines using microwave irradiation (Mol. Diversity 2005, 9, 291. DOI: 10.1007/s11030-005-4386-8). The procedure utilizes 5 equivalents of trifluoroacetic acid (TFA) and dichloromethane as solvent. The protected amines are heated at 60 C for 30 minutes in the cleavage cocktail. The freebase amines can be rapidly isolated by scavenging the crude reaction mixture with basic Amberlyst A-221 ion exchange resin.

C. O. Kappe, Org. Chem. Highlights 2006, January 15.