Under Construction!!
N. Soldermann, R. Neier*
Université de Neuchâtel,
Institut de chimie, Bellevaux, CH-2000 Neuchâtel
The length of a synthesis is determinated
by the increase of complexity achieved per synthetic operation. Combining
several transformations into a one-pot reaction has proven to be the an
excellent strategy to increase the efficiency of organic synthesis [1].
Developing novel tandem reaction has steadily gained in importance in recent
years [2, 3].
In our group a new tandem process Diels-Alder reaction/Ireland-Claisen rearrangement starting from O-butadienyl-ketene-acetals as been developed [4].
A total of three C-C bonds were formed in one single transformation and three chiral center, two cyclic and one exocyclic were formed. This process shows a high diastereoselectivity for the Ireland-Claisen rearrangement starting from the endo-product of the Diels-Alder reaction. A mechanistic study of our process was done to understand and improve the selectivity of the reaction and finally apply it to the synthesis of natural products.
(+)-Juvabione is a sesquiterpene-derived cyclohexenylester isolated from balsam plants[5], which can modify the metamorphosis in insects and shows therefore juvenile hormone activity. Based on our mechanistic knowledge of the tandem process, the novel tandem-reaction was applied to a short synthesis of (rac.)-juvabione 3 with good overall yield [6].
Several chiral auxiliaries are studied
to obtain a diastereoselective synthesis. If high diastereoselectivity
will be observed, an enantioselective Diels-Alder reaction followed by
the suprafacial Ireland-Claisen rearrangement should allow to synthesize
(+)-juvabione enantioselectively.
[1] P.A.Wender, in ‘Organic Synthesis: Theory and Applications, volume 2’, Ed. T. Hudlicky, JAI Press Inc., Greenwich, London, 1993, p.27.
[2] P.V. Fish, W.S. Johnson, J.Org.Chem. 1994, 59, 2324.
[3] L.F. Tietze, J. Bachmann, J. Wichmann, O. Burchhardt, Angew.Chem. 1988, 100, 983.
[4] J.Velker, J-P. Roblin, A. Neels, H. Stoeckli-Evans, F-G. Klaerner, J-S.Gehrke, R. Neier, Synlett1999, 925.
[5] W.S. Bowers, H.M. Fales, M.J. Thompson, Science 1966, 154, 1020.
[6] N.Soldermann, J. Velker, O.Vallat, H. Stoecki-Evans, R. Neier, Helv.Chim.Acta.2000, 2266-2276.
