A beta-Oxyanionic Organolithium-Weinreb Amide Coupling Strategy Towards the Syntheses of Aculeatins A, B, D and Strevertene A

The main part of this dissertation details the coupling reaction between beta-oxyanionic organolithiums and Weinreb amides. These organolithiums are prepared by the lithium di-tert-butylbiphenylide (LiDBB) mediated reductive lithiation of phenylthio alcohols. Optimization of this coupling with model substrates revealed that only 1.5 equivalents of the phenylthio alcohol were needed for product yields up to 90%. Since the products are enantiopure beta-hydroxy ketones, this coupling is a good alternative to diastereoselective aldol reactions. An application of this coupling was demonstrated in the highly convergent syntheses of aculeatins A, B, D, and 6-epi-D. In the next phase, efforts were made towards the double coupling between two beta-oxyanionic organolithiums and Weinreb/morpholine diamides. The double coupling will be applied to the first total synthesis of strevertene A.