Synthesis of the North 1 unit of the cephalostatin family from hecogenin acetate

Hecogenin acetate (1) was converted to North I azidoketone 5 involving seve ral key transformations: (1) conversion of cyclic sulfate 33b to allylic al cohol 40 via Reich iodoso olefination; (2) E-ring annulation via intermolec ular oxygen alkylation of highly functionalized secondary alcohol 40 using: rhodium-catalyzed decomposition of an alpha-diazophosphonoacetate to provi de alpha-alkoxyphosphonoacetate 52, with subsequent intramolecular Wadswort h-Emmons reaction to provide alkoxydihydrofuran 53; and (3) establishment o f the : C20 stereochemistry by chromium(II) reduction of tertiary bromide 8 6 to a 9:1 mixture of diastereomeric spiroketals 90 alpha/90 beta, separate d as silyl ethers 91 alpha/91 beta. Conversion of 91 alpha to alpha-azidoke tone 5 was uneventful.