Synthesis of Unit A of Cryptophycin via a [2,3]-Wittig Rearrangement

The synthesis of unit A of the cryptophycins from (S)-trans-3-penten-2-ol and from (S)-trans-4-hexen-3-ol has been completed. The key stereodetermining step is a [2,3]-Wittig rearrangement of a propargyl ether. Elaboration of the rearrangement product was accomplished by means of a selective hydroboration-oxidation of a terminal alkyne, Horner-Emmons homologation of the derived aldehyde, followed by selective ozonolytic cleavage and Wittig olefination. This synthesis provides easy access to the series of cryptophycin analogues that incorporate a modified aromatic ring in unit A.