An Evaluation of the Ligand Effects on Neopentyl Phosphine Derived Precatalysts for N-Arylation Reactions and for the Cross-Coupling of Aryl Acetylenes with Propargyl Alcohols and Amides

Abstract

Palladium catalyzed cross-coupling reactions are some of the most widely employed methods for forming new C-C and C-heteroatom bonds in both academic and industrial settings. Much of the focus on developing these catalytic systems has shifted to identifying more effective ligands to facilitate these transformations. Trialkyl phosphines are a powerful class of ligands that have garnered a lot of interest in recent decades due to their ability to effectively catalyze a wide variety of cross-coupling reactions. Much of the focus in the Shaughnessy group has been on evaluating a series of neopentyl (Np) alkyl phosphine ligands and their capacity to catalyze different C-C and C-N coupling reactions. Specifically, I prepared and tested a series of air-stable [(Np3P)Pd(Ar)Br]2 and (Np3P)Pd(Ar)(amine) precatalysts for the coupling of sterically hindered aryl bromides and aniline derivatives. The amine adducts were less active than the bromine-bridged dimers, however, these precatalysts were more active than the catalyst generated in situ from Pd2(dba)3 and PNp3. We also demonstrated a positive correlation between increasing the steric bulk of the aryl group and increased catalytic activity in these N-arylation reactions. Recently the Shaughnessy group developed a method for the selective cross-coupling of terminal aryl alkynes with propargyl alcohols to afford linear (E) enynol products using a di-tert-butylneopentyl phosphine (DTBNpP) derived palladacycle. Inspired by these findings, I aimed to determine how the identity of the ligand would impact the selectivity of the cross-coupling reactions. I synthesized novel variants of the complex [Pd(μ-κ2-O,O-OAc)(κ2-C,P-(R)2PCH2C(Me)2CH2)]2 with R groups of varying size (R = cyclohexyl or isopropyl) in order to evaluate the steric effects of the phosphine ligand backbone on the outcome of the cross coupling of terminal aryl acetylenes with propargyl alcohol and N-propargylphthalimide.