Noah Setterholm

Diels-Alder modifications of TIPSO-furans

Chemistry, Dr. Bur
About My Research:

This summer I worked with Dr. Bur on more efficient ways of synthesizing the backbones of molecules found in natural products.  Of interest to many synthetic chemists are natural products isolated from plants and animals that show activity against various diseases such as HIV.  Unfortunately, only minute quantities of these complicated compounds can be isolated efficiently from natural sources. The solution to these products’ unavailability in large quantities is to produce them synthetically.  Given enough time and resources synthetic chemists can reproduce any naturally occurring molecule.  However, their methods of synthesis are not always the most efficient. This means that scaling them up to produce significant quantities of material can be very costly, especially since the majority of the chemical building blocks used today by organic chemists are derived from dwindling petroleum sources.  Our research has focused on building the core structures of these interesting molecules using specialized intramolecular Diels-Alder reactions.  We hope that by optimizing the synthesis of these core structures we can help facilitate a cost effective entrance to studying the medicinal uses of these compounds.

This research was supported by the American Chemical Society Petroleum Research Fund.

Professional Abstract:

Intramolecular Diels-Alder reactions were examined using triisopropylsilyloxy (TIPSO) furans with the goal of optimizing an efficient one-pot stereospecific synthesis of the skeletal core found in many natural products. Lithiated TIPSO-furan was added to 4-pentenal and 2-vinylbenzaldehyde. 4-pentenal was prepared via the addition of allylmagnesium chloride to glycidol affording Hex-5-ene-1,2-diol in 43% yield. Subsequent oxidation via sodium periodate yielded a product whose proton NMR was consistent with 4-pentenal. Because 4-pentenal is difficult to handle, research into its reaction with lithiated TIPSO-furan is ongoing. 2-vinylbenzaldehyde was prepared via the addition of 2-chlorostyrene to Rieke magnesium. Subsequent formylation of the Grignard with dimethylformamide yielded 2-vinylbenzaldehyde in 35% yield. Addition of lithiatedTIPSO-furan afforded a compound that fluoresces blue under ultraviolet light, consistent with the expected product 3,9-fluorenediol. The synthesis of fluorenol derivatives in this way is potentially interesting and merits further study.