News and Publications
The Skaggs Institute for Chemical Biology
Scientific Report 1998-1999
Organic and Organometallic Chemistry and Catalysis
M.G. Finn, J. Guo, S. Maddock, M. Dintzner, C. Averbuj
Transition metals are found at the sites of action in many chemical and biological
processes. We seek to uncover and use the unique patterns of reactivity of transition
metals in a multidisciplinary approach for the development of new reagents, catalysts,
and synthetic processes.
Polymer-Supported Chiral Lewis Acid Catalysts
Our long-range goal is the development of true combinatorial methods for the
synthesis and rapid screening of chiral catalysts for a variety of organic transformations.
We start with the assembly and analysis of multidentate chiral ligands covalently
bound to polystyrene resins and other support materials and use electron-deficient
metal complexes of these ligands as chiral Lewis acid catalysts. An important
theme is the relationship between the properties of the polymeric support and
the chemistry of the attached catalyst species.
For example, electron-deficient early transition-metal complexes often aggregate
in the solution phase. We are testing the abilities of various solid supports
to control the interaction of attached Lewis acidic species, thereby shifting
such equilibria toward specific aggregates or to monomeric species. We recently
developed several tools necessary for this enterprise, including a family of
thermally cleavable linkage units, which enable us to control the identity and
concentration of active ligand sites on a polymer, and a method for the rapid
analysis of enantiomeric excess on an extremely small scale (Fig. 1). Combinatorial
methods for discovery of new reactions and asymmetric catalytic processes will
also be aided by a collaborative project with G. Siuzdak, The Scripps Research
Institute, on new mass spectrometry assays.
Catalytic Antibodies: Selection and Metal-Based Reactivity
In collaboration with R. Lerner and C. Barbas, the Skaggs Institute, we are
enlarging the scope of enantioselective reactions that can be performed by catalytic
antibody systems. The strong association of ß-diketones with the active
sites of aldolase antibodies enables us to import nonbiological reactivity engines
into chiral binding pockets on the back of diketone carriers. We are attempting
this step with several catalytically active metal complexes and are using the
phage display technique to evolve antibodies specifically adapted for the role
of catalyst "host." New selection methods are also being used for the discovery
of catalytic function.
Metal-Mediated Diradical Cycloaromatization Reactions
Several years ago we pioneered the use of the organometallic rearrangement
of terminal acetylenes to vinylidenes in the enediyne cycloaromatization process.
This strategy converts a high-energy Bergman-type process into a lower-energy
Myers-style cycloaromatization, with the production of a metal-centered radical
and a carbon σ-radical (Fig. 2). We recently returned to this process to
expand its scope and explore its catalytic variations. Water-soluble versions
are of interest for their potential ability to cleave polynucleotide or protein
Boring, E., Sabat, M., Finn, M.G., Grimes, R.N. Alkene and alkyne insertion
reactions with tantalum metallacarborane complexes: The Et2C2B4H42 carborane
ligand as spectator and participant. Organometallics 17:3865, 1998.
Brody, M.S., Finn, M.G. Palladium-catalyzed coupling of functionalized
bromoarenes to a polystyrene-bound aryl tributylstannane. Tetrahedron Lett. 40:415,
Curtis, M.A., Finn, M.G., Grimes, R.N. A hydridotantalum(V)-carborane
analogue of Schwartz's reagent: Synthesis and reactivity. J. Organomet. Chem.
Dopico, P.G., Finn, M.G. Synthesis and cycloaromatization kinetics
of aromatic allene enynes. Tetrahedron 55:29, 1999.
Finn, M.G., Lerner, R.A., Barbas, C.F. Cofactor induced refinement
of catalytic antibody activity: A metal-specific allosteric effect. J. Am. Chem.
Soc. 120:2963, 1998.
Guo, J., Wu, J., Siuzdak, G., Finn, M.G. Measurement of enantiomeric
excess by kinetic resolution and mass spectrometry. Angew. Chem. Int. Ed. 38:1755,
McCleland, B.W., Nugent, W.A., Finn, M.G. Mechanistic studies of the
zirconium-triisopropanolamine catalyzed enantioselective addition of azide to
cyclohexene oxide. J. Org. Chem. 63:6656, 1998.
Nugent, W.A., Licini, G., Bonchio, M., Borolini, O., Finn, M.G., McCleland,
B.W. Homogeneous catalysis as a tool for organic synthesis. Pure Appl. Chem.