Organocatalytic and Stereoselective Synthesis of Bipyrazolidin-3-ones

Significance

A stereoselective [3+2] dipolar cyclo­addition of azomethine imines with α,β-unsaturated aldehydes provides a reasonably general route to bipyrazolidin-3-ones. The reaction is catalyzed by α,α-diarylprolinol salt 1 and proceeds in high exo selectivity and enantioinduction. The scope of the reaction has been adequately tested for aromatic substitution on the reaction partners but less so for aliphatic derivatives. Bipyrazolidin-3-one derivatives are biologically significant compounds; in particular, high anti-bacterial activity has been associated with this ring system (e.g., L. N. Jungheim, S. K. Sigmund J. Org. Chem. 1987, 52, 4007-4013; J. M. Indelicato, C. E. Pasini J. Med. Chem. 1988, 31, 1227-1230; R. E. Holmes, D. A. Neel Tetrahedron Lett. 1990, 31, 5567-5570). An X-ray crystallographic structure to prove the formation of the exo product is given, as well as some possible reaction models for the [3+2] cycloaddition.