Exploring Palladium-Catalyzed Cross-Coupling at Nitrile Groups

Abstract

Carbon-Carbon cross-coupling is a useful method that is used to connect carbons of different molecules to create a larger molecule. This is particularly powerful in synthesis of complicated molecules because it allows for different parts of the target molecule to be worked with separately before they are connected, which reduces the restrictions on the methods used during synthesis. One major drawback of these methods is that the number of functional motifs they work with is quite limited. The earliest reports of metal-catalyzed cross-coupling reactions were in the late 1950s1 and since then the number of different cross-coupling methods that deal with different functional motifs has steadily increased1-14. Aryl nitriles have not yet been reported as one of the viable functional motifs. In this thesis, the viability of aryl nitriles towards metal-catalyzed cross-coupling was explored, specifically regarding Palladium-catalyzed cross-coupling, and efforts towards optimizing the procedure for this reaction have been made. Conditions, reagents, and starting materials were tested to make progress toward creating an efficient reaction procedure. Aryl nitriles were shown to be reliably expected to react in the presence of some palladium catalysts, solvent and temperature were optimized, and multiple co-catalysts were shown to either interfere, promote, or not significantly affect the reaction. A reaction procedure that produced high yields was not found, but the yield of the reaction was increased in comparison to the reference reaction and suboptimal conditions were cataloged. Further avenues for the progression of the study of this reaction are discussed.