1. Acyl Anions in Bottle: Thiazolium Carbinol Methodology
Karl Scheidt, Department of Chemistry, Northwestern University
The ability to access unconventional reactivity patterns is a useful strategy in organic synthesis. Polarity reversal (Umpolung) is the inversion of electrophilic reactivity to generate an atypical nucleophile. The prototypical Umpolung species is the acyl anion, which has been studied for over a century. In our studies, we have discovered that O-silyl thaizolium carbinols are isolable and stable compounds that undergo acyl anion reactivity when exposed to a fluoride ion. This unique property has advantages over standard acyl anion chemistry since the desired nucleophile is accessed without the use of medium/strong bases. This mild new protocol is the key characteristic in the addition to nitroalkenes. Yields for the -keto nitro products from this reaction would otherwise undergo elimination. We have used thiazolium carbinols in the presence of silylated phenols in a new synthesis of -aryl ketones. In this process, both the nucleophile (acyl anion) and electrophile (o-quinone methide) are generated in situ. Lastly, a general Umploung approach to a-hydroxy ketones has been developed using a cross-acyloin reaction between our thiazolium carbinols and enolizable aldehydes.
extension to incorporate other reactive electrophiles
mechanistic studies to understand the interaction of fluoride and the carbinols
development of catalytic, asymmetric variants
Easily prepared, storable