Fast or slow: Delivery of reagents to catalysis

Transition metal coupling of suitably functionalized organic reactants has revolutionized organic synthesis. Understanding the mechanism of such processes is a key component in their successful design, application and development in academia and industry.

Catalytic cycles offer interesting but challenging vehicles for mechanistic study and one area that has fascinated us is the local and global deviation of systems, via bypass or poisoning, from ideal steady-state behavior. These features, in particular focusing on the liberation1 and delivery of reactants from precursor reagents, will be the major topic of the presentation.

Selected examples from mechanistic studies into the catalysis of C-C bond forming reactions-2-5 using strategic combinations of isotopic labelling, NMR, kinetics, mass spectrometry calorimetry, computation, X-ray crystallography, and small-angle neutron scattering, will be presented.

What has emerged from these studies, and been of particular interest to us, is the way in which a variety of subtle chemical and physical changes and unanticipated consequences of these changes can conspire to facilitate a useful reaction, or to inhibit undesired ones. A recurring theme is that the controlled delivery4,6 or release5 of reactants can be a key part of the success of the overall chemical process.

References:

[1] A. J. J. Lennox and G. C. Lloyd-Jones J. Am. Chem. Soc., 2012, 134, 7431-7441
[2] L. T. Ball, G. C. Lloyd-Jones and C. A. Russell J. Am. Chem. Soc. 2014,136, 254–264
[3] C. Poree and G. C. Lloyd-Jones, unpublished results
[4] T. Corrie, A. Cresswell, and G. C. Lloyd-Jones, unpublished results
[5] J. Gonzalez, M. D Burke and G. C. Lloyd-Jones, unpublished results
[6] L. T. Ball and G. C. Lloyd-Jones, Science, 2014, 345, 381-382