Date of Thesis
Negishi cross-coupling reactions involve a transition metal-catalyzed coupling of an organohalide and an organozinc to form a new carbon-carbon bond, which is a significant accomplishment in synthetic organic chemistry. We have been optimizing a palladium catalyzed Negishi cross-coupling reaction between a β-halo α,β-unsaturated carbonyl and a monoorganozinc to form a new carbon-carbon bond at the β-position.
α,β-Unsaturated carbonyls are useful in the synthesis of human-made materials and can be used as precursors to all-carbon stereocenters (i.e., quaternary stereocenters). Although quaternary stereocenters are challenging to synthesize, they comprise important features in the structures of many natural products and pharmaceuticals. Several palladium catalysts and phosphine ligands were surveyed to identify optimal cross-coupling conditions. The choice of palladium catalyst seems to have minimal effect on efficiency or yield. However, certain electron-rich, bulky ligands, such as RuPhos, seem to inhibit undesirable pathways, allowing for higher yields and efficiency. Further work includes examination of substrate scope with the current optimized conditions through varying both the organozinc and the α,β-unsaturated carbonyl.
synthesis, reaction optimization, cross-coupling, Negishi, organozinc, α, β-Unsaturated carbonyl
Honors Thesis (Bucknell Access Only)
Bachelor of Science
Dee Ann Casteel
Berlin, Cami, "Optimization of a Negishi Cross-Coupling Reaction for the Synthesis of β,β-Disubstituted Ketones" (2020). Honors Theses. 542.