Conventional ligand design in transition metal catalysis capitalizes on the ability of phosphorous, nitrogen, carbon, oxygen, and sulfur-based donors to modify the steric and electronic properties of a reactive metal center. Heterobimetallic transition metal complexes that contain a dative metal-metal bond provide a unique approach to ligand design where the reactivity of the metal center can be modified by metal-metal electronic communication. Our laboratory is interested in using the unique properties of heterobimetallic complexes to address significant limitations in current transition metal catalysis. My PhD work has focused on the ability of early/late transition metal heterobimetallic complexes to facilitate catalysis by speeding up reductive processes that occur at the late transition metal center. My initial studies were aimed at understanding the importance of the metal-metal interaction to catalysis in allylic amination reactions catalyzed by Pd–Ti heterobimetallic complexes and the potential of these catalysts to enable reactivity with challenging nitrogen nucleophiles. We also explored the substrate scope of the allylic amination with a variety of hindered amines and allylic chloride substrates under mild conditions. Aminations of this type have previously been shown to require harsh reaction conditions and tend to give low yields. A variety of sterically hindered secondary amine nucleophiles were able to readily undergo allylic substitution. Many of these aminations were complete within ten minutes. A series of allylic electrophiles were also shown to undergo the reaction. We have also looked at the ability of hindered amines to undergo intramolecular cyclizations to produce pyrrolidine and piperidine products. My continuing efforts in the laboratory are focused on developing chiral titanium-phosphinoamide ligands for enantioselective heterobimetallic catalysis. We have synthesized a series of chiral diamine-based phosphinoamide-titanium ligands in order to investigate enantioselective intramolecular aminations. Importantly, each of these new Ti-ligands enables room temperature catalysis in intramolecular aminations with hindered amines, suggesting contributions by the Ti center. Similar reactivity has not been achieved with monometallic chiral Pd catalysts in our lab. Importantly, many of these ligands enable modest enantioselectivity in the allylic aminations.

Heterobimetallic complexes present a unique approach to catalyzing challenging reactions. By having two metals in close proximity to each other, the metals are able to interact and alter their electronics in a way that simple organic ligands (carbon, nitrogen, sulfur etc.) cannot. Our studies of heterobimetallic complexes focus on a Pd–Ti complex. The complex features a dative interaction between the palladium and the titanium held together by a phosphonamide scaffold. This interaction increases the electrophilicity of the palladium and makes it a very suitable catalyst for allylic amination reactions. We have conducted extensive studies of this catalyst in allylic aminations, the results of which will be discussed. Our first studies with heterobimetallic Pd–Ti complexes focused on their potential to catalyze challenging allylic amination reactions. These studies showed that the Pd–Ti complex was effective at catalyzing allylic aminations with sterically hindered secondary amines, a reaction which had heretofore proved challenging. We then developed a method for synthesizing the catalyst in situ, greatly simplifying the procedure by which the catalyst is used and making it that much more accessible. We also tested the substrate scope and varied the structure of both the amine and chloride substrates. Our results demonstrated the high catalytic activity of heterobimetallic catalysts with most substrates, in spite of steric hindrance of notoriously challenging substrates. Next, investigated the origin of the fast catalysis we had observed with heterobimetallic Pd–Ti complexes. We confirmed the catalytic cycle and determined the activation barrier for the rate-determining step. We computationally investigated the reactivity of various control catalysts in which the Pd–Ti interaction was severed. These results were compared with the reactivity of the heterobimetallic catalyst. We found that the activation barrier for turnover-limiting reductive amine addition was lowered with the bimetallic complex because of an increased electrophilicity at palladium. We further supported our claim by synthesizing a phosphinoamide palladium complex lacking a titanium atom and testing it in the allylic amination reaction. Our findings in the lab corroborated our calculations. We also ensured that the Pd–Ti catalyst was not transformed prior to catalysts by examining various decomposition pathways and determining that they all resulted in higher energy pathways. We discovered that the Pd–Ti interaction is made possible only by the steric interaction provided by N-tert-butyl groups on the amines which sterically reinforce the Pd–Ti interaction. Lastly, we tested the catalytic activity of the complex with allylic acetates and found them to be ineffective due to catalyst decomposition. It is our hope that these findings can serve as guiding principles when designing heterobimetallic complexes for future catalytic applications.

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