Rhodium(II) catalysed aziridinations of homoallylic garbamates: towards a synthesis of sphingofungin F

• Main Author: Southby, Duncan P. W.
• Published: University of Nottingham 2013
• Subjects: 547.2
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604313

This thesis details an expansion of substrate scope in the intramolecular aziridination reactions of homoallylic carbamates so as to generate aziridine products containing nitrogen bearing quaternary stereocentres. The use of this methodology towards a synthesis of sphingofungin F is detailed. The Introduction identifies the reactions of nitrenoids as key methods for the installation of nitrogen bearing quaternary stereo centres and reviews the current methodologies used in the CH-insertion and aziridination reactions of nitrenoids. The involvement of the Hayes group within the field is detailed and the research aims of the project are outlined, namely the effect that an allylic stereo centre and trisubstituted alkene will have upon the reaction of a series of homoallylic carbamates under the conditions developed previously within the group. Results and Discussion details the synthesis and aziridination of a range of trisubstituted homoallylic carbamates containing an allylic stereo centre to give the product aziridines in generally high yields and as single diastereoisomers. The utility of the aziridines as synthetic intermediates is demonstrated via the preparation of a small selection of functionalised derivatives and the use of similar aziridines in a synthesis of sphingofungin F is envisaged. Introduction to the Sphingofungins details the sh'ucture and isolation of the sphingofungins and their role as inhibitors of the serine palmitoyltransferase enzyme. Some of the more recent approaches to the sphingofungins are also reviewed. 11 Towards Sphingojimgin F details our attempts towards a synthesis of sphingofungin F using the diastereoselective aziridination reaction to install the key nitrogen bearing quaternary stereocentre. Further synthetic transfonnations gave access to a protected forn1 of the polar head of sphingofungin F. A summary of this work and the future steps required to complete the synthesis of sphingofungin F are presented. The thesis concludes with the Experimental section which gIves experimental procedures and full characterisation data for all novel compounds prepared herein.