The interplay of structure and reactivity in ruthenium-catalysed alkene ring-closing metathesis

Strathclyde theses - ask staff. Thesis no. : T13194Alkene ring-closing metathesis (RCM) has fundamentally changed the way that chemists consider the construction of molecules. However, quantitative understanding has not progressed at the same rate as synthetic application. There is still not a firm quantitative understanding of the relationship between pre-catalyst and diene structure and reaction rate or efficiency; measurements reported are typically yield measurements, which are sensitive to the work-up and isolation methods employed. Work towards a detailed quantitative understanding of the interplay between structure and reactivity is presented. A variety of classical and modern physical organic chemistry tools such as spectroscopy, kinetic studies, density functional theory, and reaction simulation are employed. Kinetic studies were applied to investigate the effect of ring size on RCM rate. The order of reactivity in prototypical dienes, in reactions shown to be under thermodynamic control, was established qualitatively and some quantification of this order of reactivity is presented. Attempts to quantify kinetic EMs were unsuccessful. Additionally, 1,5-hexadiene was revealed to be a metathesis inhibitor. Reaction simulation approaches were explored for the quantification of outcomes from kinetic experiments and for comparison of substrates. An existing model for RCM was tested and several flaws were identified; overcoming these flaws allowed successful application of the model to substrate and pre-catalyst evaluation. Significant substrate isomerisation encountered in small-scale reactions was probed using kinetic experiments under a number of reaction conditions. Benzoquinone suppressed this isomerisation but reduced the rate of productive RCM. A number of potential isomerisation agents were prepared and benchmarked, and one was detected in very small quantities in a metathesis reaction. This work contributes to better quantitative understanding of RCM. In addition, the small-scale metathesis and reaction simulation approaches are excellent means by which to rapidly identify suitable reaction conditions for metathesis reactions.Alkene ring-closing metathesis (RCM) has fundamentally changed the way that chemists consider the construction of molecules. However, quantitative understanding has not progressed at the same rate as synthetic application. There is still not a firm quantitative understanding of the relationship between pre-catalyst and diene structure and reaction rate or efficiency; measurements reported are typically yield measurements, which are sensitive to the work-up and isolation methods employed. Work towards a detailed quantitative understanding of the interplay between structure and reactivity is presented. A variety of classical and modern physical organic chemistry tools such as spectroscopy, kinetic studies, density functional theory, and reaction simulation are employed. Kinetic studies were applied to investigate the effect of ring size on RCM rate. The order of reactivity in prototypical dienes, in reactions shown to be under thermodynamic control, was established qualitatively and some quantification of this order of reactivity is presented. Attempts to quantify kinetic EMs were unsuccessful. Additionally, 1,5-hexadiene was revealed to be a metathesis inhibitor. Reaction simulation approaches were explored for the quantification of outcomes from kinetic experiments and for comparison of substrates. An existing model for RCM was tested and several flaws were identified; overcoming these flaws allowed successful application of the model to substrate and pre-catalyst evaluation. Significant substrate isomerisation encountered in small-scale reactions was probed using kinetic experiments under a number of reaction conditions. Benzoquinone suppressed this isomerisation but reduced the rate of productive RCM. A number of potential isomerisation agents were prepared and benchmarked, and one was detected in very small quantities in a metathesis reaction. This work contributes to better quantitative understanding of RCM. In addition, the small-scale metathesis and reaction simulation approaches are excellent means by which to rapidly identify suitable reaction conditions for metathesis reactions