Regioselective copper(I)-NHC-catalysed allylic oxidation reactions : application towards the total syntheses of biologically active molecules

• Main Author: Ng, Sean
• Published: University of Liverpool 2011
• Subjects: 547.412
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.577144

The metal-catalysed allylic oxidation of alkenes has emerged as a powerful method for the functionalisation of Sp3 C-H bonds. This transformation has allowed for the expedient preparation of synthetically useful materials from hydrocarbon building blocks. With the development of air stable and environmentally benign copper(I)-NHC catalysts from readily available materials, it has been shown that these catalysts can participate in the allylic oxidation of alkenes in an effective manner. We have developed a powerful protocol for the functionalisation of alkenes into allylic alcohols and enones, by the use of different terminal oxidants in a divergent fashion. The highly regio- and chemoselective copper(I)-NHC-catalysed allylic oxidation has been examined in the syntheses of functionalised cyclopentenones and cyclohexenones, which has provided mechanistic insights into the oxidation. The system displays excellent tolerance of a plethora of sensitive functional groups and provides a general approach with high efficiency. It has been shown that high regioselectivity is not necessary straightforward and can depend on many factors, including stereoelectronic interactions. The studies towards the enantioselective variant via the desyrnrnetrisation of the proposed prochiral intermediate utilising a range of chiral copper(I)-NHC catalysts was unsuccessful. The synthetic utility of this transformation has been validated by the total synthesis of (±)-untenone A in the shortest and most efficient approach to date. Studies towards the total synthesis of cephalimysin A are currently ongoing, which would employ the late stage copper(I)-NHC-catalysed allylic oxidation on a densely functionalised intermediate.