CHEMISTRY OF OXAZIRIDINES .18. SYNTHESIS AND ENANTIOSELECTIVE OXIDATIONS OF THE [(8,8-DIHALOCAMPHORYL)SULFONYL]OXAZIRIDINES

The synthesis and enantioselective oxidations of [(8,8-dihalocamphoryl)sulfonyl]oxaziridines [8,8-dichloro-1,7,7-trimethyl-2'-(phenylsulfonyl)spiro[bicyclo[2.2.1]heptane-2,3'-oxazinidine]] 13 are reported. These reagents are prepared in two steps from the (camphorylsulfonyl)imine 4 by treatment of the corresponding azaenolate with electrophilic halogen sources followed by biphasic oxidation of the resulting dihalo imine 6-9 with m-CPBA/K2CO3. Of these oxaziridines the dichloro reagent 13b, available on a multigram scale, affords the highest enantioselectivities for the asymmetric oxidation of sulfides to sulfoxides (42-74%) and for the hydroxylation of enolates (often better than 95% ee). In general the molecular recognition is predicted and explained in terms of minimization of nonbonded steric interactions the transition states. For the asymmetric oxidation of sulfides to sulfoxides, secondary electronic factors related to the polarity of the sulfide and oxaziridine also play a role. Definitive evidence for chelation of the metal enolate with the C-X bond in 13 is not found. The molecular recognition is interpreted in terms of the higher reactivity of the reagents and an active-site structure which is sterically complementary with the enolate. For the asymmetric hydroxylation of the Z- and E-enolates of propiophenone (16a), the Z-enolate exhibits much higher stereoselectivity than the E-enolate: >95% vs 22% ee.