Natural Product Synthesis, Organometallic Chemistry, Homogeneous Catalysis

livinghousechemistry.montana.edu

The primary focus of Professor Livinghouse\'s research involves the discovery of new carbon-carbon and carbon-heteroatom bond forming reactions with particular emphasis on the application of these to the synthesis of biologically active compounds. The aforementioned goals are being pursued on three major experimental fronts. A summary of these appears below.

Keywords:
Organic, Synthesis

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).

Keywords:
Organic, Synthesis

Within the last several years, the Livinghouse group has become heavily engaged in the development and application of synthetic methods involving low valent group IV and group V metals. The first synthetically practical zirconocene equivalent was discovered in our laboratory. This reagent, [(Cp)2Zr(DMAP)2], possesses sequentially displaceable dimethylaminopyridine ligands which permit its use in intermolecular two component coupling reactions involving unsymmetri-cal partners (Tetrahedron Lett.,30, 3495, 1989). Moreover, this species and related complexes have proven to be exceptionally versatile reagents for promoting enyne macrocyclization reactions (Tetrahedron,50, 4421, 1995) as well as the cocylization of hydrazone moieties with carbon-carbon multiple bonds (J. Am. Chem. Soc.,111, 4495, 1989). In addition, the Livinghouse group has reported the first synthetically practical examples of intramolecular [2+2] cycloadditions involving group IV metal-imido complexes and alkynes (J. Am. Chem. Soc.,114, 5459, 1992). The synthetic viability of this new methodolo-gy was subsequently demonstrated by us in a concise total synthesis of the indolizidine alkaloid (±)-monomorine (J. Org. Chem.,57, 1323, 1992) and the potent antifungal (+)-preussin (J. Am. Chem. Soc.,115, 11485, 1993). In addition, we have shown that a wide variety of functionally differentiated heterocycles can be synthesized using this methodology (Organometallics,16, 1523, 1997).

Keywords:
Organic, Synthesis

On going efforts in our laboratories have culminated in the development of novel procedures for effecting the catalysis of representative intramolecular [4+2] and [2+2+2] cycloaddition reactions on Rh(I) templates (J. Am. Chem. Soc.,112, 4965, 1990). Significantly, we have discovered that highly enantioselective variations of these transforma-tions can be achieved by the use of rhodium catalysts modified by specifically designed chiral bisphosphine ligands which differentiate the metal center both spatially and electronically (Tetrahedron,50, 6155, 1994). These new chiral rhodium complexes are currently being exploited in asymmetric variations of the Rh(I) catalyzed [4+2] cycloaddition reaction (Tetrahedron,50, 6145, 1994) and the hydroboration of alkenes. Recently, we have discovered a new protocol for effecting [2 + 2 + 1] cyclopentenone annulations that are catalyzed by cobalt complexes (J. Am. Chem. Soc.,118, 2285, 1996; Tetrahedron Lett.,39, 7637 and 7641, 1998). This remarkable catalytic reaction is currently being exploited in an efficient synthetic approach to the alkaloid magellanenone as well as several other natural products and bioactive molecules.

Keywords:
Organic, Synthesis