REDOX-ACTIVE SYSTEMS FOR APPLICATIONS TO SMALL-MOLECULE ACTIVATION, ORGANIC SYNTHESIS, AND POLYMER FORMATION


Overview
     The isolation of ferrocene in 1951 represents a major landmark in chemistry. The elucidation of its unusual structure generated so much excitement that it was considered the birth of modern organometallic chemistry. Our group harnesses ferrocene's unique electronic and redox properties to impart unusual reactivity to a series of metal complexes and to generate biodegradable copolymers.

We focus on two main projects:

            (1) Redox switchable catalysis
            (2) Electrophilic metal centers for small molecule activation

    In addition, we are also interested in:

            (I) Catalysis by metal nanoparticles supported on polyaniline nanofibers
            (II) Bioorganometallic polymers


PROJECT 1: REDOX SWITCHABLE CATALYSIS



Catalysis is employed by both natural and artificial processes in order to transform readily available building blocks efficiently into molecules and materials with high value and function. Nature has evolved several mechanisms that allow enzymatic syntheses to occur in parallel within cells. In order to avoid unwanted interference from other reaction pathways, enzyme activity is controlled spatially and temporally; this control is often modulated through feedback loops and a variety of trigger-induced effects, known as allosteric control. In contrast, the reactions promoted by man-made catalysts usually occur according to carefully chosen reaction conditions. As such, research in this field has largely focused on the invention of new catalysts and the optimization of their performance to achieve high conversions and/or selectivity. Recently, however, chemists have been drawing more and more inspiration from nature and have started to look at catalytic processes that can be switched by an external stimulus. Incorporating stimuli-responsive features into artificial catalysts can confer an additional, 'bio-like' level of control over chemical transformations, with the goal that such systems will perform tasks in synthesis that are difficult or impossible to accomplish in other ways. Potential applications include using the states of multiple switchable catalysts to control sequences of transformations and producing different products from a pool of building blocks according to the order and type of stimuli applied, similar to the natural occurrence of multiple enzymatic processes in the cells.

Redox-switchable catalysis is an atom-economical method that generates multiple catalytically active species with different reactivity; because these species originate from a single precursor, the cost of chemical synthesis is reduced. Metal complexes containing redox-active groups are being increasingly studied because the electronic properties of a metal center can be altered without the need for further, extensive synthetic steps to achieve ligand modification. The goal of this research is to design a compound that exhibits orthogonal reactivity for different substrates by switching between the oxidized and reduced forms of a catalyst. Ultimately, this research project is pushing the boundaries of understanding the factors that influence catalytic activity.

The synthesis of new polymeric materials is motivated by the limitations of current materials. Interest in copolymers containing blocks that display different or complementary properties has been increasing since these materials have potential for further performance enhancements. They could also prove cost effective and competitive even against existing, inexpensive polymers.


We showed (J. Am. Chem. Soc. 2011, p. 9278) that by changing the oxidation state of iron in a ferrocene-based ligand, the reactivity of the corresponding metal complex toward various monomers was modified. Although a change in reactivity had been previously observed for systems containing ferrocene-derivatized ligands, we reported for the first time that the redox switch is dependent on the nature of the metal carrying out the polymerization reaction: yttrium experiences a decrease in reactivity toward lactide when ferrocene is oxidized, while indium shows the opposite behavior.

A cerium(III)/(IV) redox switch presented analogous behavior to the yttrium system and allowed us to study it using DFT calculations (Chem. Commun. 2011, p. 9897). Based on those results, we interpreted the difference between the two oxidation states to be the result in large changes of the binding profile to the two oxidation states, i.e., for early transition metals, cationic complexes make stronger bonds with the polar substrates of interest than their neutral counterparts. Guided by these results and because of their less Lewis acidic character than rare earths, we turned to group 4 metal complexes. This choice allowed us to test whether a better balance between the oxidized and reduced complexes exists and whether the cationic/oxidized states would still show activity toward polar substrates. Indeed, the activity of several group 4 metal alkoxide complexes supported by ferrocene-based ligands was controlled using redox reagents during the ring-opening polymerization of L-lactide and ε-caprolactone (J. Am. Chem. Soc. 2014, p. 11264). Switching in situ between the oxidized and reduced forms of a metal complex resulted in a change in the rate of polymerization of each monomer. Opposite behavior was observed for each monomer used; this result represented the first example when both the oxidized and reduced forms of a catalyst showed activity and selectivity toward different monomers. Even more importantly, we also demonstrated that one-pot copolymerization of the two monomers to give a block copolymer could be achieved.


We reported recently (Macromolecules 2016, p. 6768) studies of polymerization reactions showing that a reduced complex, (salfan)Zr(OtBu)2, catalyzes the polymerization of L-lactide or β-butyrolactone, while the oxidized counterpart catalyzes the polymerization of cyclohexene oxide. Several diblock (AB, BA) and triblock copolymers (ABA and BAB) of L-lactide and cyclohexene oxide were synthesized and characterized.


Current projects focus on studying the influence of the metal center on the redox switchable polymerization of cyclic esters/ethers (Al: Macromolecules 2017, p. 1847), expanding the concept of switchable polymerization to other types of monomers (Eur. J. Inorg. Chem. 2016, p. 2634), and that of redox switchable catalysis to other types of reactions (Organometallics 2016, p. 2446). The group is heavily involved in catalyst design, mechanistic studies, and polymer characterization.



PROJECT 2: ELECTROPHILIC METAL CENTERS FOR SMALL MOLECULE ACTIVATION


Activation and functionalization of inert molecules is essential to solve some of the world’s energy problems. Important examples of these molecules include aromatic compounds, as well as small molecules such as CO, CO2, CH4, and N2. Synthetic organometallic chemists have contributed majorly to advancing this field of research by designing compounds that display unusual properties and, consequently, reactivity toward these substrates. The basis of molecular design in organometallic chemistry is the study of ancillary ligands that enable specific characteristics to various metal centers.

An important new direction in ligand design is engineering direct ligand involvement in the reactions of a specific metal. This effect may be achieved through reversible processes: weak interactions (such as hydrogen bonds), protonation/deprotonation, and redox switches. Most systems that take advantage of these processes incorporate only one type of such an interaction. Our approach, however, is unique because the ligand platform can interact with the metal center through more than one process. Chelating ferrocene ligands can invoke two desirable characteristics: (i) the ligand backbone is redox active and (ii) a weak interaction of donor-acceptor type may occur between iron and an electrophilic metal center. This approach is distinct; we take advantage of weaker interactions between the metal center and iron than those delineated by others because they become important in influencing the behavior of a metal center during the course of a reaction.This stategy has led to unprecedented reactivity, as described below.


A. Reductive Cleavage of Aromatic C-H/F Bonds. The carbon-hydrogen bond is one of the most common chemical bonds. It is also one of the strongest single bonds and almost non-polar. Although it is difficult to achieve selective functionalization of C-H bonds, these processes are highly desirable from an economical point of view. Organometallic compounds have been found particularly useful in mediating C-H activation and a significant effort has been spent on understanding how such transformations work. In 1965, Chat reported the first example of C-H activation of aromatics by a low valent ruthenium complex. Since then, numerous stoichiometric and catalytic C-H bond transformations mediated by metal complexes have been discovered. Despite the fact that multiple mechanisms are available for late transition metals, σ-bond metathesis has been the only mechanism known for rare earth metals. Most noteworthy is the absence of oxidative addition for early transition metals. Oxidative addition is probably the most common pathway for carbon-element bond activation and it features prominently in C-H activation. However, oxidative addition cannot occur with early transition metals and f-elements (lanthanides and actinides), which usually have a d0 electron configuration. In this respect, the lack of redox processes for early transition metals limits their use in C-H transformations.

We reported (J. Am. Chem. Soc. 2014, p. 17410) a new type of C-H bond activation mediated by rare earth metals, reductive cleavage, which cannot be classified as σ-bond metathesis. The reaction occurs from a metal halide in the presence of a reductant and an arene and leads to the formation of a metal hydride and a metal aryl species. A detailed mechanistic study suggests that an inverse sandwich intermediate featuring a benzene dianion asymmetrically bridging two metal centers is formed prior to the C-H activation step. We consider that this reductive cleavage of C-H bonds is a counterpart for rare earth metals to the oxidative addition mechanism found with late transition metals. The discovery of reductive cleavage for redox-inert, electrophilic ions opens up new possibilities of using early transition metals in C-H bond transformations. In addition to C-H activation, we extended the reductive cleavage to C-F activation as a proof of concept to demonstrate its potential application in carbon-halide bond transformations (Organometallics 2017, p. 89).

B. Isolation of a six-carbon, 10π-electron aromatic system. Aromaticity is a fundamental concept with implications spanning all the chemical sciences. Hückel's (4n+2)π-electron rule is the standard criterion to determine aromaticity and it applies well to neutral arenes as well as to charged species such as the cyclopentadienyl anion (Cp), the cyclooctatetraene dianion, and the cycloheptatrienyl cation (tropylium). In the series of all carbon aromatic compounds, no example of a benzene tetraanion, which theoretically is a 6C, 10π-electron aromatic system, had been reported prior to our work, although heteroatom analogues of such a system, known as "electron-rich aromatics", have been studied in detail for a long time. The hypothetical C6H64- was shown computationally to have the largest orbital overlap and the strongest bonds compared to its 10π-electron heteroaromatic analogues. Despite the successful synthesis of S3N3-, P64-, and Te62+, however, there had been no reports of C6H64- or its derivatives prior to our article in Nature Communications (2013), likely due to its high negative charge.


We relied on a successful strategy to stabilize benzene polyanions by using lanthanides and actinides to support the highly reduced benzene ring by coordination. The isolation of the first tetraanionic substituted benzene as a ligand coordinated to group 3 metals was achieved by taking advantage of the unique ancillary ligand employed commonly by our group. The nature of the benzene tetraanion and the aromaticity of the 6C, 10π-electron system were established by X-ray crystallographic studies, multi-nuclei nuclear magnetic resonance, X-ray absorption spectroscopy, and density functional theory calculations. The benzene tetraanionic fragment reported by us completes the series of all carbon aromatic systems. Although C6H64- in its free form may prove elusive to synthetic chemists, these examples further our understanding of aromaticity and of the ability of metal complexes to stabilize reactive fragments.

The discovery of a new C-H activation mechanism and the isolation of the benzene tetraanion described above are based on work conducted with other aromatic hydrocarbons such as naphthalene and anthracene. In 2011, we reported the synthesis and characterization of the first inverted sandwiches of these arene scandium complexes (J. Am. Chem. Soc. 2011, p. 10410). Prior to our work, the series of naphthalene and anthracene rare earth metal (group 3 metals and lanthanides) complexes was missing examples of scandium compounds. Based on structural and computational studies, we proposed that the presence of the ferrocene backbone was instrumental in stabilizing these motifs. Besides the fundamental importance of such complexes, we also showed that they exhibit rich redox chemistry, thus enabling redox-inactive metal centers (group 3 metals) to carry out electron transfer reactions (Chem. Commun. 2012, p. 2216).


C. Characterization of weak iron-metal interactions. The new bonding motifs isolated by us were possible because of the presence of the ferrocene backbone and the interaction between iron and the group 3 metal. Metal-metal bonding has been the subject of intense research and discussion, and interactions between metal centers in bimetallic complexes can give rise to interesting electronic and magnetic properties and novel reactivity. Additionally, weak metal-metal bonding is important in developing and understanding the concept of transition metal Lewis basicity, which, in turn, is of fundamental interest in understanding the reactivity of corresponding complexes. Prior to our work, only X-ray crystallography, Mössbauer, X-ray absorption spectroscopy, and computational methods were employed to determine the nature of weak metal-metal interactions. In collaboration with Professor Zink's group, we added the use of resonance Raman spectroscopy to this list (Inorg. Chem. 2013, p. 5603). Resonance Raman spectroscopy utilizes photons that are in resonance with an electronic transition of interest. When an electron is promoted from a bonding orbital to either a non-bonding or anti-bonding orbital, the change in bond order incites motion along the bond axis. This increases the Raman signal of vibrations with movement along the coordinate of the bond. Additionally, symmetric transitions are most strongly resonantly enhanced since the intensity of scattering scales with the square of the distortion. The ability to amplify the intensity of vibrations when in resonance with an electronic transition enables resonance Raman spectroscopy to assist in the assignment of these specific transitions.




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