I. Lewis base-catalyzed aldol reaction in the total synthesis of erythronolide B II. Efforts towards the total synthesis of amphidinolide H

Lewis base (trimethylsilylquinine and trimethylsilylquinidine) catalyzed acyl halide-aldehyde cyclocondensation (AAC) reactions have been developed to prepare synthetically important bispropionate units previously by the Nelson group. A new Lewis base-catalyzed diastereoselective Mukaiyama aldol reaction has extended this bispropionate unit preparation methodology to all- syn bispropionates which widely occurred in polypropionate natural products. By using phenoxides as Lewis base catalysts, enol silanes were activated and underwent a Felkin attack on an aldehyde through an antiperiplanar transition state to generate all-syn bispropionate product in high yields and excellent diastereoselectivities.*;All-syn bispropionate prepared from the Lewis base-catalyzed diastereoselective Mukaiyama aldol reaction has been untilized in natural product synthesis of erythronolide B establishing "syn,syn,syn " stereochemical relationships from C2-C5.*;Studies towards the total synthesis of the cytotoxic marine macrolide amphidinolide H (89) have been disclosed. By exploiting AAC methodology, several key stereochemical relationships present in major fragments 198 and 199 were established. A highly enantioselective synthesis of methyl ketone 200 was realized from commercially available (S)-(-)-glycidol. Iodide 198 was coupled with boronic ester 199 via an efficient Suzuki reaction to form a C7-C20 fragment.*;*Please refer to dissertation for diagrams.