Improving Practicality and Scope of Nickel-Catalyzed Coupling Reactions.

Abstract

Efficient organic synthesis in medicinal chemistry and in complex molecule preparation often requires expedient and inexpensive processes. Nickel-catalyzed reductive coupling reactions from our group fulfill these requirements by a swift union of two simple unsaturated π-fragments via C-C bond formations. The focus of this thesis is to qualitatively elucidating the role and influence of reducing agents in these nickel-catalyzed reductive coupling reactions and to apply the mechanistic insights learned to related reaction classes. Common reducing agents in nickel-catalyzed reductive coupling reactions are metallic, flammable, expensive or highly mass intensive. Low molecular weight alcohols are mild and inexpensive reagents. The introduction of alcohols as reducing agents in reductive coupling reactions has been achieved in our work. Through ligand effects studies, incorporation of the alcohol reducing reagent as part of the final product has been accomplished in an internal redox reaction. This internal redox reaction make the nickel-catalyzed coupling processes even more practical and atom economical. Two regioselecitvity control strategies have been applied to the addition of functional groups to allenes. The application of these strategies resulted in highly regioselective allene addition processes that broaden the scope of products that can be obtained using existing methods. Through these studies, mechanistic insights in nickel-catalyzed coupling reactions have been gained and applied to other reaction classes.