Date of Thesis
β,β-disubstituted α,β-unsaturated ketones (enones) are an important class of organic compounds commonly used in various types of reactions such as cycloadditions, conjugate additions, and direct nucleophilic additions for the synthesis of more complex molecules such as natural products and pharmaceuticals. A versatile method to prepare derivatives is therefore desirable. Current methods employ highly reactive Grignard reagents which introduce chemoselectivity limitations.
We have developed a method involving cross-coupling reactions with vinylogous anhydride and vinylogous halide substrates utilizing mild functionalized organozinc reagents in which electrophilic functional groups can be incorporated to increase the structural diversity. Reaction screening was performed by varying the vinylogous substrate, catalyst identity and quantity, additives (e.g., Lewis acids), and organozinc reagent. Optimization has led to high yields of β,β-disubstituted enone products (5 examples, 15-79% yields) utilizing a simple copper catalyst with easily synthesized functionalized organozinc reagents. The observation of a second, undesired organozinc addition was leveraged to use two non-equivalent organozinc reagents in the one-pot synthesis of ketones with β-quaternary stereocenters.
cross-coupling, organozinc, unsaturated ketone, chemoselectivity
Masters Thesis (Bucknell Access Only)
Master of Science
Rensch, Heather R., "Cross-Coupling Reactions of Functionalized Organozinc Reagents for the Synthesis of β,β-Disubstituted α,β-Unsaturated Ketones" (2017). Master’s Theses. 276.