Prostaglandin endoperoxide model compounds. Part 2. Stereospecific synthesis of isomeric 5-bromo-2,3-dioxabicyclo[2.2.1]heptanes and 2-bromo-6,7-dioxabicyclo[3.2.1]octanes

Abstract

Cyclopent-3-enyl hydroperoxide (9) has been prepared from cyclopentadiene via hydroboration and autoxidation, and converted by bromination into trans-3,cis-4-dibromocyclopentyl hydroperoxide (10). Reaction of compound (10) with silver oxide has afforded endo-5-bromo-2,3-dioxabicyclo[2.2.1]heptane (11)(42%), whereas treatment of compound (10) with silver trifluoroacetate has provided exo-5-bromo-2,3-dioxabicyclo[2.2.1]heptane (15)(6%) and exo-5-trifluoroacetoxy-2,3-dioxabiclo[2.2.1]heptane (16)(14%). The exo-bromide (15)(11%) has also been prepared from cyclopent-3-enyl bromide by trans-hydroperoxybromination and ring closure with silver oxide. The configurations of the [2.2.1]peroxides have been confirmed by catalytic hydrogenation.

Cyclohex-3-enyl hydroperoxide (26) has been prepared from anisole by a 5-step procedure ending with oxidation ofN-cyclohex-3-enyl-N′-tosylhydrazide, and converted by bromination into a mixture of two diastereoisomeric 3,4-dibromocyclohexyl hydroperoxides. Treatment of the trans-3,cis-4-dibromide (27) with silver oxide has afforded endo-bromo-6,7-dioxabicyclo[3.2.1]octane (29)(40%), whereas reaction of the cis-3,trans-4-dibromide (28) with silver trifluoroacetate has provided exo-2-bromo-6,7-dioxabicyclo[3.2.1]octane (30)(18%). Treatment of compound (27) with silver trifluoroacetate yielded a 9 : 1 mixture of peroxides (30) and (29)(19%), but compound (28) did not react with silver oxide.

It is suggested that the silver oxide-induced dioxabicyclizations proceed by an S_N2 mechanis wheras the silver trifluoroacetate reactions involve a bromonium ion intermediate.