Spirodiepoxides: Synthesis of Epoxomicinoids

Abstract

Three closely related analogues of epoxomicin have been synthesized. Allene-derived spirodiepoxides were key intermediates. Spirodiepoxide formation and stereochemical dependence on solvent, oxidant, and allene structure were cataloged. The facial selectivity of the first epoxidation of 1,3-disubstituted and trisubstituted allenes was found to be >20:1 with dimethyldioxirane in chloroform. For stereogenic allenes, the facial selectivity of the second oxidation is dependent primarily on allene structure and secondarily on solvent and oxidant. For the acyclic systems evaluated this ratio was as high as 8:1. A conformational model is advanced to account for these observations.