Inter and intramolecular N-conjugate addition reactions using cinchona derived primary amines

• Main Author: Ball, Anthony
• Published: University of Nottingham 2015
• Subjects: 547; QD241 Organic chemistry
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.680257

This thesis describes the conjugate addition of nitrogen nucelophiles to alpha,beta-unsaturated enones using cinchona derived amines. Two separate projects are outlined within, intermolecular and intramolecular N-conjugate addition reactions. The first project involves the investigation of a range of nitrogen nucleophiles in their intermolecular additions to alpha,beta-unsaturated ketones. The reactions were performed using either 9-deoxy-9-epi-aminoquinine or 9-deoxy-9-epi-aminoquinidine as the catalyst with phenylacetic acid as a co-catalyst. These catalysts were found to promote conjugate addition of a range of nitrogen heterocycles to acyclic alpha,beta-unsaturated ketones. In particular, the addition of pyrazoles was found to proceed in high yield and enantioselectivity. In contrast, addition of these nucleophiles to cyclic ketones gave low enantioselectivity. The second project involves the investigation of intramolecular N-conjugate addition processes. In this case, the reactions were performed using 9-deoxy-9-epi-aminoquinine and trifluoroacetic acid as the catalyst system. Several different groups on nitrogen were investigated and the reaction conditions optimised for each group. The ring size and substitution around the ring system formed were also investigated with high yields and enantioselectivites obtained.