Anionic and Radical Cyclization of Unsaturated Hydrazones: Application to the Synthesis of Chiral Polycyclic Compounds

• Applicant: Professor Dr. Dieter Enders (†)
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2002 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5383692

To date, numerous radical reactions performed either under thermal or photochemical activation have been deviced, but few of them have been conducted in an asymmetric manner. Moreover, tandem cyclizations (radical or anionic) represent now the methods of choice to built complex natural product skeleton. The aim of the project is to combine highly stereoselective methodologies using the well-known SAMP/RAMP hydrazones and tandem cyclization processes in order to obtain chiral polycyclic structures. By selective a-functionnalization (halogenation, phenylselenation) of hydrazones and subsequent transformation of the substrates into unsaturated compounds, a further radical process could be performed and lead to cyclized products. The stereoselective C-X bond formation and/or the presence of the chiral hydrazone moiety are expected to control the stereoselectivity of the overall process. The memory effect could be also studied by conducting the radical reaction on the carbonyl derivatives after removal of the hydrazone functionality. In a parallel manner, deprotonation of unsaturated SAMP hydrazones and treatment with an halogen or phenylselenium derivatives could deliver compounds resulting from an asymmetric anionic cyclization process. In order to enhance the structural complexity, it should be noted that cross-metathesis reactions could be performed on the unsaturated starting material with various alkenes before the key-cyclization step. These two approaches should afford chiral compounds with similar skeleton and also complexity. Therefore, it will be interesting to compare them before to investigate an application toward the asymmetric synthesis of natural compounds.

• DFG Programme: Research Grants
• International Connection: France
• Participating Person: Professor Dr. Olivier Piva