Development of New Methods in Organocatalysis and the Enantioselective Total Synthesis of (-)-Minovincine

Abstract

New methods in organocatalysis and their application towards the total synthesis of natural products are discussed. This dissertation aims to detail efforts to advance the field of chemical synthesis through the discovery of novel asymmetric transformations.

The design and development of a new strategy to achieve the direct intramolecular α-arylation of aldehydes via singly occupied molecular orbital (SOMO) activation is described. This novel protocol allows the generation of α-methine stereocenters under mild conditions that prevent post-reaction epimerization and produces α-arylated aldehydes in high yield and with excellent levels of enantioselectivity.

Furthermore, the first asymmetric total synthesis of (-)-minovincine was accomplished in nine linear steps via organocascade catalysis. An organocatalytic Diels- Alder/β-elimination/Michael addition cascade allowed rapid access to the central spiroindoline core of the natural product in an enantioselective fashion.

Finally, a new method to effect the enantioselective 1,4-addition of arylboronic acids into α,β-unsaturated aldehydes via the productive merger of organo- and transition metal catalysis is explored. Preliminary experiments suggest that the transformation is accelerated by the presence of an amine. The observed enantioselectivity is believed to result from the selective addition of an intermediate arylrhodium species into an activated chiral iminium ion.