Enantioselective organocatalytic ammonium enolate mediated transformations and studies towards the total synthesis of (-)-galanthamine

• Main Author: Johansson, C. C. C.
• Published: University of Cambridge 2006
• Subjects: 547.6
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.605611

(1) An enantioselective organocatalytic ammonium enolate mediated intramolecular cyclopropanation reaction has been developed. Studies towards an asymmetric intramolecular epoxidation reaction as well as an organocatalytic cycloisomerisation reaction have also been undertaken. These processes are catalysed by cinchona alkaloid derivatives, of which a novel class, bearing an alkyl substituent in the 2-position of the quinoline moiety, has been developed. The intramolecular cyclopropanation reaction provided bicycle[4.1.0]alkanes in good yields (> 80%) and excellent e.e.’s (> 93%). The unoptimised e.e. for the intramolecular epoxidation was 40%, and e.e’s up to 95% were observed in the cycloisomerisation reaction. (Fig. 566397A) (2) Two novel concepts; trans-annular ring closure and “zip-up” strategy have been applied towards a synthesis of (-)-galanthamine. The racemic syntheses of advanced intermediates 212 and 226 were accomplished in few steps from commercially available starting materials.