Stereoselective oxidative cyclisations of 1,5,9-trienes : synthetic studies towards eurylene

• Main Author: Sheikh, Nadeem Sadiq
• Published: University of Southampton 2008
• Subjects: 547.59
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.484954

A novel synthetic route towards the stereoselective formation of trans-THF rings by permanganate promoted oxidative cyclisation of 1,5-diene precursors was developed. This methodology was applied to 1,5-dienoates and 1,5,9-trienoates to afford trans-THF regions of the natural products, (+)-linalool oxide and eurylene respectively. Synthesis of trans-THF aldehyde fragment 2.47 of eurylene was accomplished, using (+)-transcumylcyclohexanol as a chiral auxiliary to direct the stereoselective oxidative cyclisation of 1,5,9-triene 4.35 by permanganate. An efficient synthesis of cis-THF trial fragment 2.38 of eurylene was also achieved by permanganate mediated oxidative cyclisation of 1,5,9-triene 3.9, bearing (2S)-10,2camphorsultam as a chiral auxiliary. Trans-THF aldehyde 2.47 and cis-THF triol 2.38 intersect with a reported synthesis of eurylene, hence achieving a formal synthesis of the natural product. Seven, out of eight, stereogenic centres present in eurylene were established by two permanganate induced stereoselective oxidative cyclisations. Several coupling strategies were investigated to complete a total synthesis eurylene. Successful formation of the complete carbon skeleton 6.56 was achieved, although it was not possible to attain selective reduction of the triple bond in 6.56. The knowledge gained will be used to devise a revised end game, which ultimately a total synthesis to be achieved.