Development of Highly Active and Selective Copper Catalysts for New ATRP Initiating Systems

Reversible deactivation radical polymerization (RDRP) techniques have revolutionized polymer chemistry for the controlled synthesis of functional polymers with predefined
molecular weights, narrow molecular weight distributions and with high chain-end functionality. One of these techniques, atom transfer radical polymerization (ATRP), makes use of a catalytic system, most commonly copper complexed by a nitrogen-based ligand, in which the L/CuI activator species cleaves a (macro)alkyl halide bond generating a carbon-centered radical and the oxidized L/CuII-X deactivator species. The radical propagates by adding to a few monomer units before being quickly deactivated by the L/CuII-X complex. As with any radical
process, irreversible termination reactions are unavoidable and thus a gradual buildup of L/CuIIX is observed according to the persistent radical effect (PRE), leading to a suppressed rate of polymerization. Various systems with activator regeneration, also known as “low ppm Cu
ATRP,” have been developed to overcome the PRE, but these require the use of highly active catalysts. At the forefront of ATRP research has been the development of new externally regulated systems as well as mechanistic understanding of the processes in order to select the
best catalytic system. My contribution to the field was primarily focused on: (1) the development and understanding of new initiating systems for low ppm ATRP using light and
zero-valent metals such as Ag⁰ and Cu⁰, (2) the synthesis and characterization the highly active catalysts based on ligand design and (3) quantification and mechanistic understanding of radical termination processes in both conventional free radical polymerization and ATRP with highly active catalysts. Chapter 1 overviews the progressive development of catalytic systems in ATRP. Since ATRP’s discovery in 1995, various kinetic and thermodynamic parameters have been quantified in order to better understand this system. The first catalysts involved the use of relatively simple bidentate bipyridine (bpy)-based ligand and required catalyst loadings of greater than 10,000 ppm. Through rational ligand design, structure vs. reactivity relationships between activity and N-atom donor type, denticity, geometry were understood. This allowed the
synthesis of more complex and robust ligands which greatly increased the efficiency of ATRP. The activity of catalysts in ATRP has now increased over 1,000,000,000 times compared to seminal bpy-based catalysts and allow for ATRP to be conducted using catalyst loadings as low
as 5 ppm. This chapter encompasses almost 25 years of ATRP catalytic systems and discusses potential opportunities for future development. Chapter 2 discusses mechanistic studies for the newly developed photochemically mediated ATRP. Photochemical control over ATRP with ppm amounts of copper was first
achieved in 2012, however, there was significant mechanistic debate over how the polymerization operated, namely the mechanism of photochemical reduction of L/CuII-X. Using
both experimental and simulation techniques, the mechanism of photoATRP was elucidated. It was found that the main method of radical (re)generation occurs via a reductive quenching process between excited state deactivator complex, [L/CuII-X]* and excess amines acting as electron donors. By using model studies and kinetic simulations, other photochemical processes were studied and quantified. The effect of light irradiation on other methods of low ppm ATRP such as initiators for continuous activator regeneration (ICAR) ATRP was also quantified.
Chapter 3 discusses ATRP in the presence of zero-valent metals. This is an attractive method because the reactions are easy to operate and it opens up the possibility for catalyst recycling. ATRP was first conducted in the presence of Cu0 in 1997, however, a vigorous mechanistic debate was ongoing for over a decade. Specifically, two mechanisms, supplemental activator and reducing agent (SARA) ATRP and single electron transfer living
radical polymerization (SET-LRP), both using the same species, were debated. It was found that the SARA mechanism holds true in both aqueous and organic media. Both activation of alkyl halides by Cu⁰, ka⁰, and comproportionation between Cu⁰ and L/CuII, kcomp, were quantified in a variety of solvents for different ligands and alkyl halides. In-depth mechanistic studies attempted to elucidate the surface reactions occurring in SARA ATRP. Finally, a new system employing the use of Ag⁰ wire as a reducing agent for L/CuII-X was used in ATRP and exhibited
one of the highest degrees of “living” control in any ATRP system reported thus far. Chapter 4 overviews in-depth kinetics of both normal and low ppm ATRP systems such
as ICAR ATRP and SARA ATRP. Recent reports have made inaccurate claims about reaction mechanisms due to the misunderstanding that the rate of polymerization in ATRP is not directly related to the rate of alkyl halide activation. This chapter aims to rectify the claims made by others and to present a much clearer and accurate picture of the kinetics of ATRP. Chapter 5 discusses the recent advancements in catalytic design in ATRP. Specifically, the tetradentate tripodal ligand tris(2-pyridylmethyl)amine (TPMA) was systematically modified to include methyl (-Me) and methoxy (-OMe) electron donating groups to decrease the redox potential, E₁/₂, of the L/Cu^I/^II couple. Substitution of each pyridine arm lead to a catalyst that was 10, 100 and 1000 times more active than the unsubstituted ligand. Structural studies of both the L/Cu^I and L/Cu^II-X species were also conducted. The catalysts were characterized in
solution using UV-Vis, electrochemistry and low-temperature ¹H NMR spectroscopy and also used as catalysts in activators regenerated by electron transfer (ARGET) ATRP. In order to increase the activity further, the TPMA scaffold was substituted with even more electron donating dimethylamino (-NMe2) groups. Characterization of this complex, [Cu^II(TPMA^NMe2)Br][Br], revealed the most active ATRP catalyst to date with rates of activation approaching diffusion controlled-limits (k_a > 10⁶ M^-1s^-1) and KATRP values approaching unity for ethyl α-bromoisobutyrate (EBiB) in acetonitrile (MeCN) at ambient temperatures. ICAR and Ag⁰-mediated ARGET ATRP exhibited a well-controlled polymerization with >99% chain-end
functionality using as little as 10 ppm of catalyst.
Chapter 6 discusses the recent research efforts to understand how acrylate radicals terminate in both conventional radical polymerization (RP) and ATRP. It is known that active L/Cu^I catalysts can catalyze the termination of acrylate radicals, the mechanism, however,
remains elusive. It has been concluded that un-catalyzed radical termination of acrylatesnoccurs predominately via combination while CRT gives saturated chain-ends. We aimed tondetermine the effects that ligand geometry and electronics has on this reaction as well as elucidate the mechanism of non-catalyzed radical termination. The intimate mechanism of the CRT reaction is currently being studied. Throughout the process, a novel reaction between
organotellanyl radicals (TeR) and propagating carbon-based radicals was discovered. Finally, Chapter 7 provides a summary with an emphasis on future directions.