Asymmetric synthesis of functionalised Pyrrolidines and their application in Total Synthesis

The intramolecular aza-Michael reaction has been used effectively in the synthesis of nitrogen
heterocycles, with several efforts made in recent years to do so asymmetrically. The selection
of the Michael acceptor can play an important role in both the rate and enantioselectivity of
the reaction. The research in this thesis demonstrates how the use of a chiral phosphoric acid
can catalyse the intramolecular asymmetric aza-Michael reaction of a protected amine with
an α,β- unsaturated thioester. The scope of the reaction was demonstrated in the synthesis
of 2,2- and 3,3-spirocyclic pyrrolidines in high yields and enantioselectivity. The
synthesis of an unsubstituted pyrrolidine provided the core of two natural products (R)-
bgugaine and (R)-irnidine and both succumbed to total synthesis. (R)-Bgugaine was
synthesized in a 33% overall yield in 6 steps while (R)-irnidine was synthesized for the first
time in an overall yield of 18% over 6 steps.