Synthesis of the North 1 Unit of the Cephalostatin Family from Hecogenin Acetate1

Hecogenin acetate (1) was converted to North 1 azidoketone 5 involving several key transformations: (1) conversion of cyclic sulfate 33b to allylic alcohol 40 via Reich iodoso olefination; (2) E-ring annulation via intermolecular oxygen alkylation of highly functionalized secondary alcohol 40 using rhodium-catalyzed decomposition of an α-diazophosphonoacetate to provide α-alkoxyphosphonoacetate 52, with subsequent intramolecular Wadsworth−Emmons reaction to provide alkoxydihydrofuran 53; and (3) establishment of the C20 stereochemistry by chromium(II) reduction of tertiary bromide 86 to a 9:1 mixture of diastereomeric spiroketals 90α/90β, separated as silyl ethers 91α/91β. Conversion of 91α to α-azidoketone 5 was uneventful.