Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 1:  Synthetic Strategy and Preparation of a Common Precursor

The synthetic strategy for producing multigram quantities of (+)-discodermolide (<BO>1</BO>) using a hybridized Novartis−Smith−Paterson synthetic route via common precursor <BO>3</BO> is described. In the first part of this five-part series, we present a multikilogram preparation of α-methyl aldehyde <BO>10</BO> from Roche ester, its syn-aldol reaction with Evans boron enolate, removal of the chiral auxiliary, and the preparation of Weinreb amide <BO>3</BO> (Smith common precursor). The common precursor was produced without any chromatography.