A Two-Directional Approach to a (−)-Dictyostatin C11−C23 Segment: Development of a Highly Diastereoselective, Kinetically-Controlled Meerwein−Ponndorf−Verley Reduction

A three-step synthesis of a precursor to the C11−C23 segment of (−)-dictyostatin is described. The sequence features a sonication-assisted, enantioselective double hetero Diels−Alder (HDA) reaction catalyzed by Jacobsen's Cr(III) Schiff base catalyst, followed by a novel, highly diastereoselective Meerwein−Ponndorf−Verley (MPV) reduction of the hydropyranone subunits under kinetic control to yield the bis(axial alcohol) 4. Generalized studies of both the HDA and MPV methodologies are also described.