Carbomagnesium mediated reactions: A versatile tool in organic synthesis.

Abstract

Magnesium-mediated carbometallation has been employed as a route to a diverse range of organic synthons. The original carbometallation procedure has been optimized by a solvent study, which indicates that cyclohexane can be used in most cases, to improve the yields and consistency of the reaction. A wide-range of polysubstituted furans (232) were obtained when the reaction intermediate (144) was quenched with either dimethylformamide or benzonitrile. The use of carbon dioxide as an electrophile, provided a short (two-steps) synthesis of the Merck anti-inflammatory drug, Vioxx RTM (231). The reaction was also extended to a direct one-step synthesis of the ene-diyne chromophore (186). Additional research afforded a versatile route from 144 to dienophiles for intramolecular Diels-Alder reactions. An expedient route to the Taxol A/B-ring system (329) was developed. This ring system underwent a facile enone accelerated Cope rearrangement to generate a bicylco[2.2.2]octanone ring system (330). Finally, the dienophiles prepared from the carbomagnesiation reaction were employed as key steps in the preparation of tether controlled intramolecular Diels-Alder reactions. The reactions were shown to be more facile when cis-isopropylidene acetals ( 386) were employed in the tether. The trans-isopropylidene acetal tether (385b) was also prepared for a direct comparison. As anticipated the cycloaddition occurred at a much slower rate.* *Please refer to dissertation for diagrams.