| Floris P.J.T. Rutjes1, Sape S. Kinderman2, Koen F.W. Hekking1, Floris L. van Delft1, and Hans E. Schoemaker3. (1) Department of Organic Chemistry, University of Nijmegen, Toernooiveld 1, Nijmegen, 6525 ED, Netherlands, (2) Organic Chemistry, University of Amsterdam, Amsterdam, Netherlands, (3) Department Advanced Synthesis and Catalysis, DSM, PO Box 18, Geleen, 6160 MD, Netherlands |
Efficient sequences for the construction of oxygen and nitrogen heterocyclic natural products will be detailed. A first approach consists of the formation of reactive acetals, followed by different types of cyclization reactions. More specifically, Pd-catalyzed coupling of alkoxy allenes to alcohols or sulfonamides provides stable O,O- or N,O-acetals, that can be efficiently elaborated using ring-closing metathesis or acid-mediated cyclization to highly functionalized heterocycles such as vincantril. A second approach involves the use of á-alkoxy acrylates as novel substrates for ring-closing metathesis reactions. Beside the scope and limitations of this conversion, a new one-pot synthesis for the conversion of alcohols into the corresponding á-alkoxy acrylates will be described. The viability of this sequence has been illustrated with the shortest total synthesis of KDO and 2-deoxy KDO.  |