Mechanistic Insights into Metal Carbene Catalysis

Metal carbenes have a rich history in catalysis, the 2005 Nobel prize awarded to Schrock, Grubbs, and Yves Chauvin was for the alkene metathesis reaction, a key intermediate during which is a metal carbene. The chemistry or metal carbenes in catalysis is ever growing with a multitude of synthetic studies of a variety of reactions. However, metathesis reaction aside, mechanistic insight is lagging behind. The vast majority of papers in the field simply focus on synthetic scope or limitations and product yield and there are very few experimental studies investigating catalytic mechanisms of the reactions published.
We aim to address these shortcomings using a complimentary combined experimental and computational approach to studying reaction mechanisms. Approaching a problem experimentally by first studying reaction kinetics allows behaviour predicted by computational models of the catalytic cycle to be validated, giving much needed confidence in the model. Developing an understanding of the reaction kinetics and catalyst behaviour has the potential to underscore improvements in existing processes. This can lead to much lower catalyst loadings, increased scope by allowing previously unreactive substrates to be employed, and insights which allow the rational design of new catalysts. Experimental understanding can be augmented by the computational models, where theories for improving selectivity or reactivity using newly designed catalysts can be tested before time and material intensive commitment in the lab.
The large volumes of novel synthetic chemistry published has generated an enormous number of important mechanistic questions which we could profitably investigate. This project will focus on two highly useful transformations which diazo compounds as carbene precursors: palladium catalysed cross coupling and copper catalysed enantioselective allenylation. With the exception of computational studies and stoichiometric insertion reactions with preformed carbenes, no direct experimental evidence for the widely assumed mechanisms for either reaction exists. The transformations can suffer from high catalyst and ligand loadings, the requirement for a large excess of diazo substrates, and issues of product selectivity. Studying the mechanism of this reaction should allow us to shed light on the veracity of the proposed mechanistic models, allow us to rationally improve reaction conditions, and provide understanding on issues of selectivity
As well as usefully improving existing synthetic methodology through rigorous mechanistic analysis, a more speculative aim of the project will seek new possibilities for photochemical transformations involving metal carbenes. The photochemical generation of free carbenes directly from diazo compounds has been documented recently. These are updated examples of classic chemistry seen in a new light using light. However, these transformations lack the control and selectivity afforded by transition metal catalysis. As of yet, there have been no reports of metal carbenes generated in this straightforward manner. This offers an additional avenue to explore and new mechanistic considerations for which to account.