Vanadium(II)-Promoted Cyclization of 5,6-Enals or 5,6-Ynals. A Stereoselective Approach to trans-2-Alkyl or 2-Alkylidenecyclopentanols

Inokuchi, T.; Kawafuchi, H.; Torii, S. J. Org. Chem. 1991, 56, 4983.

Reductive cyclization of 5,6-enals to the corresponding trans-2-substituted cyclopentanols has been achieved by treatment with the V(II) reagent, [V₂Cl₃(THF)₆]₂[Zn₂Cl₆], prepared from VCl₃(THF)₃ and zinc. This intramolecular enal coupling reaction may involve the initial activation of the formyl group by the V(II) reagent to generate the corresponding V(III)-aldehyde ketyl and its ensuing addition to the olefinic moiety. The stereochemical outcome of this reaction turned out to be considerably influenced by the kinds of internal olefins and their geometries. For instance, (E)-7-oxo-2-heptenoate 1a is smoothly converted to the corresponding 2-alkylcyclopentanol with a trans:cis ratio of 24~50:1, while its Z-isomer 1b predominantly yields pinacol product by an intermolecular homo-coupling process. The method is applicable to a synthesis of a key intermediate for isocarbacyclin from the corresponding precursor with an 5,6-ynal array.