New Synthetic Methodology

The design and reduction to practice of new synthetic methodologies is an extremely important aspect of modern synthetic organic chemistry.

(i) The chemistry of thiols and sulfones

We have been exploring the synthetic utility of 2-mercaptobenzothiaziole, and we have recently developed a simple and mild method for the conversion of epoxides into alkenes, with retention of stereochemistry. Prior methods employed harsh reaction conditions that were incompatible with many functional groups. We are currently examining the scope and limitations of this new reaction and we are investigating related reactions to convert a-halo ketones to alkynes, to prepare vinyl sulfones for cycloaddition reactions, and to develop mild and efficient chemistry for malonate-type ester preparations.

Feng-Ling Wu pioneered this area during her Honours year in 2005. Feng-Ling obtained a first-class Honours degree and was awarded an Australian Postgraduate Award Scholarship to continue her PhD studies in this general area. Projects suitable for Honours and PhD students are offered in this area.

(ii) Sigmatropic Rearrangements

Other routes to developing new synthetic methodologies rely on extending the scope and utility of well-known transformations. For example, the rate of the Claisen rearrangement has been shown to be dramatically increased when the substrate has certain electron-withdrawing substituents at particular positions. Surprisingly, substrates of this type have been little studied, and there exists an excellent opportunity to further develop these synthetically important reactions.

Kelly Cosgrove has been investigating variations of the Johnson-Claisen rearrangement as part of her PhD project. Kelly has developed a number of new methodologies as part of these studies. For example, she has devised a very efficient new solvent-free way to make mixed orthoesters in high yields and purities using ketene acetals (Synlett, 2008, 2425-2428):

Kelly has further exploited these mixed orthoesters as substrates for a novel Lewis-acid-promoted Johnson-Claisen rearrangement, leading to gamma,delta-unsaturated primary alcohols (Synlett, 2009, 1749-1752):

Projects suitable for Honours and PhD students are offered in this area.