1. New Chemoselective Functionalization of Nitriles and Vinylogous Esters
Jared T. Shaw, Department of Chemistry, University of California, Davis
New synthetic methods that enable chemoselective functionalization of simple starting materials into complex products are useful for the assembly of organic compounds for medicinal chemistry, materials and other applications. We have pursued two new methods to achieve this end. We have discovered several new catalysts for the addition of alpha silylnitriles to aldehydes, specifically quaternary ammonium acetates and BINOL-Ti(Oi-Pr)4. In each case, co-catalysis with CuOAc enhances the reactivity significantly. No reaction is observed when the silyl group is absent, which indicates that the reaction is selective for the alpha-silyl nitrile. Having demonstrated this new reactivity, we are now pursuing new approaches to achieving stereoselectivity. In a parallel study, we have shown that beta-alkoxy enones and related carbonyl compounds undergo substitution reactions with Grignard reagents. Striking chemoselectivity is observed, as there is no addition to the ketone and no displacement of sulfonate esters on related substrates. This method has proven to be general and has been demonstrated on more than 30 substrates. We are now developing new methods for accessing non-aromatic substrates that will provide easy access to previously unavailable frameworks in a single step.
catalytic synthesis of functionalized nitriles
chemoselective displacement of aryl and vinyl ethers