Inorganic Stereochemistry and Asymmetric Synthesis Professor Bruce Wild

We study the synthesis of new types of chiral molecules. Chiral molecules exist as pairs of mirror-image arrangements of atoms that are not superimposable on one another, like pairs of hands in which one is left and the other right. Each one of these molecular configurations is called an enantiomer. The biological activity of one enantiomer of a chiral compound can differ completely from that of the mirror-image substance. Since many drugs are chiral, careful work is required to separate and purify the required enantiomer for clinical use.

Catalysts can be used to transmit chiral information to compounds as they are synthesised. We are particularly interested in synthesising enantiomerically pure phosphorus compounds as these are used in catalysts for a number of industrial processes, including the synthesis of chiral drugs. Our group has pioneered the use of a special method for the separation of the enantiomers of chiral phosphines that gives each enantiomer in very high purity. The enantiomerically pure phosphines, in turn, can be used to develop chiral catalysts for the production of new chiral drugs in enantiomerically pure form.

Current research activities

Metal helicates

An enantiomerically pure hexaphosphine that contains four left-handed phosphorus centres has been shown to react with a copper salt to spontaneously self-assemble a protein-like double α-helix complex containing three copper ions. We are synthesising related phosphines in an attempt to stabilise DNA-like, double α-helix conformers of these inorganic helicates. The gold analogues of the complexes are potent and relatively non-toxic anti-tumour agents.

Asymmetric synthesis

Chiral phosphine-transition metal complexes are used as catalysts for the synthesis of pharmaceuticals. There are few satisfactory methods available for the synthesis of the chiral phosphines. We have discovered that an enantiomerically pure 7-membered heterocyclic phosphine forms stable salts with certain phosphorus and arsenic substrates. These salts can be converted into new chiral phosphines and arsines in high enantiomeric purity. We are using this new method to develop a general method for the synthesis of a variety of important chiral phosphines and arsines in enantiomerically pure form.

Inorganic asymmetric synthesis

The synthesis of enantiomerically pure chiral inorganic complexes has developed little in the last 100 years, despite the importance of left- and right-handed inorganic metal complexes in biology. Enterobactin, which is responsible for the uptake of iron in bacteria, contains an iron centre that resembles a right-handed, three-bladed propeller. We are developing a method for the inorganic asymmetric synthesis of chiral, two- and three-bladed propeller metal complexes. The method uses an enantiomerically pure, organic auxiliary molecule to direct the asymmetric synthesis of the chiral iron complex.

Annual Research Report   (PDF format)

Group members

Academic Staff:
Professor Bruce Wild (Leader)   |   Dr Joerg Steinback   |   Dr Xiangting Zhou

Technical and General Staff:
Paul Gugger

PhD Students:
Nathan Kilah   |   Heather Kitto   |   Elizabeth Krenske   |   Rebecca Warr   |   Kerri Wells

Honours Students:
Michelle Wier

Key publications

1. Pabel, M., Willis, A. C., and Wild, S. B. First Resolution of a Free Fluorophosphine Chiral at Phosphorus. Resolution and Reactions of Free and Coordinated (±)-Fluorophenylisopropylphosphine. Inorg. Chem., 1996, 35, 1244–1249.
2. Bader, A., Pabel, M., Willis, A. C., and Wild, S. B. First Resolution of a Free Secondary Phosphine Chiral at Phosphorus and Stereospecific Formation and Structural Characterization of a Homochiral Secondary Phosphine–Borane Complex. Inorg. Chem.1996, 35, 3874–3877.
3. Hockless, D. C. R., McDonald, M. A., Pabel, M., and Wild, S. B. Facile Syntheses and Interconversions Between Simple Phosphiranium and Phosphirenium Salts. J. Organometal. Chem., 1997, 529, 189–196. (Invited paper – Special issue on Organophosphorus Chemistry edited by Francois Mathey)
4. Airey, A. L., Swiegers, G. F., Willis, A. C., and Wild, S. B. Self-Assembly of Homochiral Double Helix and Side-by-Side Helix Conformers of Double-Stranded Disilver(I)- and Digold(I)–Tetra(tertiary phosphine) Helicates. Inorg. Chem., 1997, 36, 1588–1597.
5. Bowyer, P. K., Cook, V. C., Gharib-Naseri, N., Gugger, P. A., Rae, A. D., Swiegers, G. F., Willis, A. C., Zank, J., and Wild, S. B. Configurationally Homogeneous Diastereomers of a Linear Hexa(tertiary Phosphine): Enantioselective Self-Assembly of a Double-Stranded Parallel Helicate of the Type (P)-[Cu₃(hexaphos)₂](PF₆)₃. Proc. Natl. Acad. Sci. (USA), 2002, 99, 4877–4882. (Invited Paper – Special issue on Supramolecular Chemistry and Self-Assembly edited by J. Halpern).

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Dr Wild is a Senior Fellow in the Research School of Chemistry.

group photos

Professor S B Wild Research School of Chemistry, Building 35 Australian National University Canberra ACT 0200 AUSTRALIA Ph: +61 2 6125 4236 Fx: +61 2 6125 3216 E-mail: sbw@rsc.anu.edu.au