Due to significance of chiral epoxides as biologically active substances and as intermediates in their synthesis, efficient methods for asymmetric epoxidation are important. A good direct asymmetric catalyst route to enantiomerically enriched epoxides not containing coordinating functional groups is lacking. The absence of this methodology is exemplified by the inability to synthesize sufficient quantities of the carcinogen (+) anti- benz (a)pyrene-7,8-diol-9,10-epoxide to enable informative structural studies to be done on its DNA adducts. The current methods for synthesizing this epoxide rely on chromatographic separation of small amounts of diastereomeric derivatives and could be greatly improved be asymmetric epoxidation methods. We intend to develop a general means for obtaining unfunctionalized chiral epoxides in high enantiometric purity by utilized asymmetric organometallic catalysis. The catalysts will contain ligands designed to enable the placement of sterically different groups in an asymmetric environment about the reactive metal site. Chiral bis(cyclopentadienyl)niobium and tungsten catalysts for the asymmetric epoxidation of alkenes and for the kinetic resolution of racemic epoxides will be based on C2- symmetrical binaphtylcycopentadiene and substituted bicyclooctcyciopentadienes. Application of this epoxidation methodology will enable the enantioselective synthesis of a wide range of biologically significant compounds. We propose as an important and illustrative example, the asymmetric synthesis of mutagenic polycyclic aromatic hydrocarbon metabolites needed for DNA-adduct studies.
