Research Projects
New Sequences for the Initiation of Cationic Cascade Annulations
In 1987 the Livinghouse group disclosed that representative polyene cyclizations could be selectively initiated by novel sulfenium ion equivalents. The significance of this finding derives from the unique ability of these cyclizations to convert acyclic precursors to polycyclic products with the net incorporation of new functionalities (e.g., arylthio groups). The application of this new method to the appropriate substrates has led to syntheses for the diosphenol diterpenes(±)-totarolone and (±)-totarol as well as (±)-nimbidiol (Tetrahedron Lett.,30, 1499, 1989). This method has also been successfully applied to the synthesis of the antitumor agent taxodione (J. Chem. Soc. Chem. Commun.,502, 1992; Tetrahedron, 50, 9229, 1994) in addition to a forscolin model.
In addition to the above research, the Livinghouse group has developed an unusually flexible method for heteroannulation which relies upon acylnitrilium ion initiated cyclizations. This method has been successfully applied to the construction of highly functionalized pyrrolines and has been successfully utilized in an efficient total synthesis of the Orchidaceae alkaloid (±)-dendrobine. (J. Am. Chem. Soc.,114, 4089, 1992). It is also significant that electron-rich aromatic nuclei readily undergo \"spiroannulative\" closure onto acylnitrilium ions to provide spirocyclic tetrahydropyridine derivatives in high yield. This method has been used to synthesize an advanced intermediate en route to the irregular lycopodium alkaloid (±)-serratine (J. Chem. Soc. Perkin Transactions I, 2369, 1995). Recently, we have developed a new nucleophilic terminator, the 2-propylidene-1,3-bis(silane) group, that has proven useful for the rapid assembly of polycondensed nitrogenous heterocycles. The use of this terminator in an intramolecular cyclization onto an iminium ion has led to an efficient synthesis of the tricyclic core of stemofoline (J. Am. Chem. Soc.,118, 4200, 1996). In addition, densely functionalized pyrrolines can be prepared by the reaction of 2-propylidene-1,3-bis(silane)s with acylnitrilium ions (J. Org. Chem.,62, 805, 1997).
Personnel:
Thomas Livinghouse
Keywords:
Organic, Synthesis
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