60th Annual Report on Research 2015

During the funding period of this New Directions Award, significance advances were made in the solidification of our efforts toward identifying and optimizing performance attributes of task-specific ionic liquids and related small molecules. The results of this study have established a framework by which future work will focus on designing a high-throughput synthetic approach that will allow access to multiple structural motifs with the modular flexibility necessary for point modifications. The main objectives for this project included 1) the design and synthesis of various nitrogen and phosphorus containing cyclic and acyclic frameworks that will react with carbon dioxide in an efficient and reversible fashion, 2) the installation of a molecular “switch” to moderate CO₂ binding energies, and 3) the discovery of new chemistries based on the synthesis of novel heterocyclic motifs. Efforts toward achieving each of these objectives led to results establishing a long-term program in my group toward the synthesis and evaluation of soft materials for energy related applications (e.g., carbon capture, energy storage, sensing, diagnostics, etc.). This report provides a detailed overview of our findings and how I envision this work to have a long-term impact on the future of my research program.

New Approaches to Heteroatomic Small Molecule Design and Synthesis.

During this funding period, successfully addressed considerable roadblocks to diversity-oriented synthesis by introducing a versatile strategy that combines two distinct molecular entities through the formation of cation-anion pair combinations using advanced parallel synthesis capabilities. This initial work will focus on the preparation of various N-heterocyclic scaffolds, including aryl- and cycloalkylamines, which will allow for flexible modular tuning, thereby enabling us to examine substituent stereoelectronic effects on the capture and utilization of CO₂. To increase the variety of chemical entities, we had to first develop the technology that will allow greater access to these under-explored areas. To achieve these aims we will use both well-established and newly developed synthetic methods to rapidly assemble chemically diverse sets of orthogonal structural frameworks for the development of new task-specific ILs. Two exciting areas of discovery that resulted from these efforts include the assembly of designed bifunctional N-heterocycles containing a frustrated acid-base pair for two-point CO₂ complexation that will simultaneously transfer electron density away from the resulting carboxylate carbon, thereby rendering the bound carbonyl carbon susceptible to further functionalization, and the reaction between strained 4-membered rings with electron rich phosphines to construct caged phosphorus hetereocycles with applications in diagnostics.

A Formal Au/Ag-Catalyzed [3+2] Cycloaddition Toward Substituted Imidazoles.

The ability to site-selectively functionalize various N-heterocyclic frameworks, in particular those related to an imidazole core, remains a significant challenge in organic synthesis. The imidazole ring constitutes one of the most versatile N-heteroaromatics in organic synthesis, is a well-established precursors to stable N-heterocyclic carbenes (NHCs), and are exceptionally useful in the construction of ionic liquids. Our efforts toward the development of a transition metal-catalyzed [3+2] cycloaddition strategy in the construction of 5-membered nitrogen heterocycles, with a focus on the imidazole framework, led to the formulation of mechanistic hypothesis that which future reaction designs can be based. Our initial goal was to develop a flexible approach toward imidazole construction that would enable the maximum amount of structural diversity at C4 and C5. To that end, we designed and implemented a Au/Ag-catalyzed [3+2] cycloaddition approach involving an amidine and propargyl bromide. These efforts led to a streamlined method involving the alkylation of an amidine with a propargyl halide followed by an in situ Au(I)/Ag(I)-catalyzed 5-endo-dig cyclization to directly assemble the desired substituted imidazoles (eq 1). Most notably, we discovered that the reaction tolerates the use of formamidines as substrates to directly construct C2-unsubstituted imidazoles as N-heterocyclic carbene precursors. Deuterium labeling and competition experiments led to our proposed catalytic cycle, which was crucial for evaluating future reaction designs. A manuscript detailing these efforts is in the advanced stages of preparation, and will be submitted in the near future. Subsequent work will focus on the design of new π-Lewis acid catalyzed heterocyclization strategies based on our mechanistic findings for the convergent of assembly of other ionic liquid relevant molecular architectures (e.g., pyrazoles, tetrazoles, pyrroles, etc.).

Conformational Switches for Low Energy Carbon Separation.

The second objective delineated in our proposal focused on the design and synthesis of properly functionalized heterocyclic frameworks that are susceptible to a conformational change upon exposure to an outside stimulant. We were able to synthesize an imidazolide ionic liquid and N-heterocyclic carbene as the warhead functionality in carbon capture, each bearing a 2,5-dimethylthienyl ethene group susceptible to a UV light initiated 6π electrocyclization. We established through UV-Vis spectroscopy that this conformational change weakened the newly formed C–C bond with carbon dioxide, and thereby resulting in a decrease of the energy penalty required for carbon desorption. The bis(thienyl)imidazole was synthesized in two steps from commercially available 2,5-dimethylthiophene, and converted into either the corresponding ionic liquid or N-hetereocyclic carbene. Exposure to 1 atm of CO₂ yielded the the carboxylated adduct in near quantitative yield. Rapid electrocyclic ring opening upon exposure to ambient light validated the recyclable nature of this unique design, and demonstrated the efficacy of this approach toward future applications in carbon capture and utilization. The support for these efforts was critical to establishing a base for future efforts aimed at providing a working fluid for advanced industrial applications.

In summary, we are exceedingly grateful for the ACS PRF support of this work that has established an exhilarating and vibrant addition to my research program. The support has had a significant impact on the training of students in materials design and synthesis, and in the establishment of multiple avenues of hetereocycle construction and applications. Students involved on these projects obtained additional skills associated with small molecule synthesis and their subsequent evaluation as new carbon capture agents.