Synthesis and properties of chiral pyrazolidines derived from (+)-pulegone

Several enantiomerically pure N(2)-substituted octahydroindazoles were prepared as bicyclic pyrazolidine derivatives of (+)-pulegone. Condensation of pulegone with hydrazine delivered a hexahydroindazole intermediate, which underwent N(2)-substitution with various electrophiles (alkyl halides, acyl chlorides, phenyl isocyanate). The resulting N(2)-substituted hexahydroindazoles could be reduced with LiBEt₃H in THF to the target compounds. In addition, a N(2)- thiobenzoyl and some N(2)-carbamoyl derivatives as well as a N(1)-substituted octahydroindazole were synthesized. The compounds showed medium activity as iminium ion catalysts promoting quantitatively the Michael addition of nitroethane to cinnamaldehyde in up to 82% ee for the resulting syn-diaste-reoisomer and 78% ee for the anti-dia-stereoisomer. Unexpectedly, the N(2)-acyloctahydroindazoles were readily oxidized under aerobic conditions. Moreover, it was shown that an oxidation of methyl phenyl sulfide to the corresponding sulfoxide is promoted by an N(2)-acyloctahydroindazole in deuterochloroform as solvent. It is proposed that the oxidation of N(2)-acyloctahydroindazoles proceeds by in situ generation of hydrogen peroxide, which in turn can act as an oxidant.