The Chemical Catalysis Program supports Professors Steven T. Diver and Jerome B. Keister at the State University of New York (SUNY) at Buffalo who have proposed a research program that will focus on studying enyne metathesis, which offers a direct catalytic synthesis of 1,3-dienes from simple unsaturated reactants. There is a substantial lack of information concerning the mechanism of the reaction and the structural parameters in the alkyne and alkene substrates affecting the outcome of the process. The proposal is focused on understanding the intimate steps of the catalytic cycle and the role of each reagent in influencing the reaction rate. The study is intended to be systematic and carried out under a variety of conditions. The study is based on chemical kinetics that will be performed using in-situ Fourier Transform Infrared Spectroscopy (FT-IR), thus allowing the continuous monitoring of the reaction. Special attention will be given to the functional group tolerance in the substrates, a point that is not well understood due to the lack of a systematic study of this reaction. Understanding this reaction and the development of more practical enyne metathesis may lead to industrial applications especially in fine chemical synthesis in the pharmaceutical industry.
With the support of the Chemical Catalysis Program in the Chemistry Division at the National Science Foundation, Dr. Steven T. Diver and Jerome B. Keister will perform detailed mechanistic studies that are likely to shed light on fundamental pathways that could lead to the design of more robust and efficient catalysts. A better understanding of enyne metathesis could provide reagents for chemical biology that may help in the study of human diseases and lead to new drugs and more cost effective syntheses. This contribution to the lower the cost of pharmaceuticals could help alleviate the high cost of healthcare on the US economy. The research will involve students at all levels and provide a collaborative learning environment. The PIs will continue to involve high school students, females and persons from underrepresented groups in their research.
Optimizing the efficiency and utility of an organic reaction depends on how well we chemically understand the reaction. Modern organic chemistry employs metal-catalyzed reactions because of their ability to make otherwise difficult or impossible reactions possible. Because they are metal catalysts, they react more than once for maximum efficiency. To react faster means being in the cycle for productive reactions, and time spent outside the cycle is wasteful and can lead to unwanted side reactions. In this NSF-Sponsored research project, we investigated the mechanism of ene-yne metathesis, to identify reactive intermediates in this reaction and determine how the catalyst spends its time. The ene-yne metathesis is a highly effective way to join simple reactants in order to make useful products known as 1,3-dienes. These products are valued building blocks for organic synthesis. In the metathesis field, new catalysts are continually being created and become adopted by other scientists for other applications. The newest catalysts are "phosphine-free" catalysts that are highly active. How these new catalysts promote ene-yne metathesis is not clearly understood. Last, despite the popularity of the Grubbs catalysts and metal catalysis in general, the metal must be removed and ideally deactivated, at the end of the desired chemical reaction. There is no general and effective way to do this. There were several important outcomes of this project. This was a collaborative research project between Dr. Steven Diver and Dr. Jerome Keister, both at the University at Buffalo, the State University of New York. Importantly, federally-supported research projects like this one train young people to become scientists. These students gain knowledge from research-based inquiry, learn to write reports and papers and to learn how to organize and present their data in an intelligible way. Central to this project was use of a technique called in situ IR which can monitor the rates of fast chemical reactions. We found: (1) certain phosphine-free catalysts have unique resting states—non-catalytically-active species that can enter the catalytic cycle only at particular points; (2) that ethylene-alkyne metathesis is inhibited by higher concentrations of ethylene; (3) that some phosphine-free catalysts that promote ene-yne metathesis lack resting states and catalyze metathesis faster than their rate of initiation; (4) rate profiling gives insight about a catalyst’s effectiveness, providing for a rational means for catalyst selection; (5) solid-supported reagents can be used to quench and effectively remove metals from chemical reactions and processes; gold(I)-promoted cyclization of alkynes can be used to access vinyl carbene intermediates. As research products, we have disseminated our results by publication in peer-reviewed journals. Overall, this has greatly contributed to our understanding of the catalysts that promote this important catalytic reaction. The broader impacts of this investigation were achieved primarily through training young scientists in a collaborative learning environment. Students from the undergraduate to graduate levels were involved with this project. The synthetic and critical skills acquired in a project that unravels reaction mechanism prepare undergraduate students for success in graduate or professional schools. The development of more practical enyne metathesis may lead to industrial applications in fine chemical synthesis and in the pharmaceutical industry. Incomplete understanding of the mechanism of enyne metathesis, unidentified side reactions and low catalyst efficiency are stumbling blocks that prevent more widespread use and limit efficiency. Detailed mechanistic studies shed light on fundamental pathways that may help lead to the design of more robust and efficient catalysts. Metathesis may further provide reagents for chemical biology that may help to study human disease. Improved efficiency in pharmaceutical applications may lead to new drugs and more cost effective chemical synthesis. This could help lower the cost of pharmaceuticals which might help alleviate the cost of healthcare on the US economy.
