The organometallic chemistry of transition metals has grown explosively in the last twenty years, but still only a small fraction of the potential for use in organic synthesis has been exploited.
We are interested in developing new synthetic methods and strategies for organic synthesis which use the unique reactivity of organotransition metal complexes, and applying these to the synthesis of natural products and potentially bioactive targets. Much of our work to date has used the early transition metal zirconium.
In developing novel synthetic methods using transition metals it is important to carry out transformations which are not readily achieved using ‘conventional' reagents. It is also important to make full use of the metal, particularly when it is used stoichiometrically i.e. to use it in several bond forming process. Zirconium is unusual for a transition metal in preferring a 16 electron configuration - a characteristic which gives it exceptional reactivity. The two main starting points for its use in synthesis are hydrozirconation, for example to give alkenylzirconocene 1, and the zirconocene induced co-cyclisation of two unsaturated species to afford a 5-member zirconacycle such as 5. We have developed further elaborations of intermediates 1 and 5 using the insertion of carbenoids such as 2 and 6. These species donate an electron pair to the empty orbital on zirconium to give a 18 electron metallate intermediates 3 and 7 which undergo a 1,2-migratory insertion to afford elaborated products 4 and 8 respectively.1,2 An important feature of carbenoid insertion is that the product retains the carbon-zirconium bond of the precursor so the process is both inherently iterative, and the products are well suited to further elaboration.
Insertion of 1-chloro-1-lithioalkenes into organozirconocenes. A versatile synthesis of stereodefined unsaturated systems, Kasatkin, A.; Whitby, R. J. J. Am. Chem. Soc. 1999, 121, 7039-7049.
Ring expansion of 5-to 6-member zirconacycles by carbenoid insertion, Dixon, S.; Fillery, S. M.; Kasatkin, A.; Norton, D.; Thomas, E.; Whitby, R. J. Tetrahedron 2004, 60, 1401-1416.