Enantioselective Synthesis of Ladder Polyethers Using a Silicon-Assisted Homologation-Epoxidation-Cyclization Strategy

Organic Letters 5(13), 2339-2342, DOI: 10.1021/ol0347040

A trimethylsilyl (SiMe3) group is the basis of a strategy that emulates the three fundamental proposed processes in ladder polyether biosynthesis:  chain homologation, stereoselective epoxidation (>95% ee or >95:5 dr), and endo-selective, stereospecific (inversion) hydroxyepoxide cyclization (>95:5 endo:exo, >95% dr). A tris-THP was synthesized in 18 total operations from commercial materials using this approach.