Total syntheses of (-)-borrelidin and (-)-doliculide and the development of the catalytic asymmetric addition of Grignard reagents to ketones

PhD ceremony: Mr. A.V.R. Madduri Venkata, 12.45 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Total syntheses of (-)-borrelidin and (-)-doliculide and the development of the catalytic asymmetric addition of Grignard reagents to ketones

Promotor(s): prof. A.J. Minnaard

Faculty: Mathematics and Natural Sciences

This thesis describes the application of copper-catalyzed asymmetric conjugate addition and ruthenium-catalyzed asymmetric hydrogenation in novel total syntheses of the macrocyclic polyketides Borrelidin and Doliculide. A second topic in the thesis comprizes the development of a novel asymmetric synthesis of chiral tertiary alcohols by copper-catalyzed addition of Grignard reagents to ketones. During the study of the latter reaction, asymmetric amplification was observed. A procedure for the copper-catalyzed conjugate addition reaction to 2-methyl cyclopentenone and 2-methyl cyclohexenone was developed as well. Finally, the already known procedure for iridium catalyzed epimerization of alcohols and amines, was extended to 1,2-amino alcohols and substrates containing multiple functional groups.