Organocatalysis with N-heterocyclic carbenes via new reactive intermediates
Final Report Abstract
This summary comprises of two separate projects carried out in collaboration with Prof. Dr. David Lupton (host) and Dr. Joel Hooper from the School of Chemistry at the Monash University. The first topic was focused on studying the potential of sulfonyl and sulfinyl azolium derivatives under N-heterocyclic carbene (NHC) catalysis. The proof-of-principle of the reaction protocol was discovered in 2015 by Lupton et al. by utilizing sulfonyl fluorides. My project specific studies began with the exploration and synthesis of new reactive precursors bearing the α,β-unsaturated sulfonyl and sulfinyl ester as well as the sulfinyl fluoride scaffold. The demonstrated molecules exhibit a high reactivity and potential to engage in NHC-catalysed reactions for the synthesis of e.g. sultones and sultines. The high reactivity and tendency for decomposition of the sulfinyl scaffold had a significant impact on the applicability of these structures in the NHC catalysed reactions. While aromatic sulfonyl esters showed no reactivity in NHC catalysis, for the sulfinyl surrogates decomposition was the predominant reaction pathway. For the second project, my studies were carried out in the field of Reversible Addition Fragmentation Chain Transfer (RAFT) polymerisation, focused on polymer functionalization via cross-coupling reactions with boronic acids. RAFT polymerisation is a powerful method for the synthesis of narrow polydispersity polymers. Applicable to most monomers, RAFT is increasingly being deployed in sophisticated applications, such as in biomedical science, to prepare robust narrow dispersity polymer conjugates. In collaboration with Dr. Hooper, studies on coupling reactions between low and high molecular weight RAFT polymers with key functional groups were undertaken. The copper(I) promoted coupling reaction between RAFT polymer end groups and aryl boronic acids was discovered recently and studies began in exploring the cross-coupling of small molecule polystyrene surrogates with aryl boronic acids. This method allowed complete end group conversion of small (Mn ~ 4.000) and large (Mn ~ 38.000) molecular weight polystyrene, polyacrylate and polymethylmethacrylates bearing the phenyl-thiocarbonylthio or dimethylpyrazole end-group. As a demonstration of the utility of this method two key functional building blocks, biotin and a borodipyrrin (Bodipy) fluorescent dye, were chosen to extend the variability of functionalization by coupling with diverse RAFT polymers. The biotin functionalization of a water soluble polymethacrylate bearing a triethylene glycol methyl ether (TEGOMe) group was also demonstrated.
Publications
- Chemical Science 2018:“RAFT polymer cross-coupling with boronic acids”
Hartwig Golf, Riley O’Shea, Carl Braybrook, Oliver Hutt, David W. Lupton and Joel F. Hooper
(See online at https://doi.org/10.1039/c8sc01862f)
