In this collaborative project, the catalytic behavior of cationic octahedral iridium(III) complexes will be investigated in C-C bond-forming reactions. First, thorough investigation of the mechanism of Nazarov cyclization will be conducted, using Ir(III) complexes as a tool to study the complex sequence of steps involved in the reaction. Second, selective methods to conduct new tandem sequences and new methods for enol alkylation using Lewis acidic Ir(III) complexes will be developed. Finally, chiral catalysts for asymmetric Nazarov cyclizations and multi-step sequences based on cationic Ir(III) systems will be synthesized and studied, including new C2 symmetric complexes closely related to the known catalysts possessing adjacent labile binding sites on the catalyst metal center.
With this award, the Organic and Macromolecular Chemistry Program is supporting the research collaboration of Professor Alison Frontier and Professor Richard Eisenberg of the Department of Chemistry at the University of Rochester. Research in the catalysis of electrophilic Ir(III) complexes aids in the development of new synthetic methodologies needed for the preparation of commodity and fine chemicals. Increasing molecular complexity through catalysis represents a key means of creating new useful compounds of potential impact beyond the research laboratory.
We have designed, prepared and studied the reactivity of three new catalysts (1-3) that trigger two novel ring-forming reactions. A fourth class of catalysts (4) was examined in the context of a third type of ring-forming reaction (Figure 1). Catalyst 1 is an asymmetric iridium(III) catalyst that is able to promote difficult cyclization reactions. A new type of cyclization also became possible with this catalyst, which had not been reported before. The two cyclizations provide rings with five and six carbons, and demonstrate reactivity not previously reported (Scheme 1). Palladium (II) complexes 2 and 3 and several copper(II) complexes of type 4 have also been developed to catalyze cyclizations like the reaction on the left (above), as well as another type of reaction that both forms a ring and installs new carbon-carbon bonds at specific positions around the ring. The intellectual merit of this work lay in our ability to achieve a high level of control over the reaction, and pinpoint the factors that were most important in achieving this control. Before our research in this area, it was mot possible to use these reactions to obtain, with selectivity, five-membered rings with specific carbon branching patterns (Scheme 2). A complete study focused on the mechanism of these carbon-carbon bond-forming reactions has been completed, which improves our ability to predict the outcome of reactions and put them to practical use. The broader impacts of this work pertain to the preparation of compounds of therapeutic importance: small bioactive molecules that are difficult to obtain contain ring systems of the three types we are able to build using the new catalytic reaction chemistry developed in this research program. The educational activities carried out focused on the Not Voodoo website developed by the PI, which is a tool for all students studying synthetic organic chemistry in the laboratory. Improvements were made to protect the integrity of the site (anti-spam programming) and the redesign of key sections of the website. Traffic to the site improved as a result of this work, and the PI continues to get positive feedback on the value of the content for both beginning and advanced research students.
