Application of the Stereodivergent Oxy-Michael Cyclisation to the Synthesis of Natural Products and Organocatalytic Asymmetric Aldol Reactions in Water

This work outlines two different projects. The first project was the study of a stereodivergent oxy-Michael cyclisation and its application towards the synthesis of natural products, diospongin A, diospongin B and psymberin/ircinistatin A. The α,β-unsaturated thioesters under TBAF-mediated conditions gave the 2,6-trans-tetrahydropyran; under acid-mediated conditions gave the 2,6-cis-tetrahydropyran. The 4-hydroxyl group is crucial for the stereodivergence; when the hydroxyl group was removed or protected the stereodivergence vanished. The second project was the study of (L)-proline benzyl ester-catalysed asymmetric aldol reactions in water. The reaction was carried out in a pH 7 buffered aqueous solution of cyclohexanone and a series of aryl aldehydes to provide anti aldol products in 7-89% ee. The aldol reaction between various ketone donors with 4-nitrobenzaldehyde under the same conditions were also developed to provide products in 13-61% ee