Reader in Inorganic Chemistry

Tel: 0116 252 2092

email: dld3@le.ac.uk

Research Interests

C-H Activation (see refs 1-3)

Metal catalysed C-H activation followed by C-C bond formation is potentially extremely efficient in terms of atom economy and chemoselectivity and is thus a very desirable transformation from a Green Chemistry point of view. Currently the most successful strategy involves cyclometallation reactions. We have recently discovered an acetate-assisted C-H activation which provides a very mild (room temperature) route to cyclometallated half-sandwich complexes.

We are now collaborating with a computational chemistry group (Dr S. A. Macgregor, Heriot Watt University) to examine the mechanism. Our intial results on cyclometallation with palladium acetate show that the reaction goes by an electrophilic like activation, however, this occurs via an agostic intermediate rather than the traditionally assumed Wheland intermediate, with considerable intramolecular hydrogen bonding to a coordinated acetate involving a 6-membered transition state. We have subsequently shown that a similar mechanism operates for formation of Cp*Ir cyclometallated complexes (see fig below for calculated transition states).

This is the first electrophilic C-H activation for iridium and the first which doesn’t proceed via oxidative addition for a Cp*iridium species. These cyclometallations are examples of a new mechanism for C-H activation involving simultaneous activation by a Lewis acidic metal (agostic interaction) and a basic ligand (hydrogen bond) which operate in a synergistic manner to provide a low energy pathway to C-H activation. We have termed this Ambiphilic Metal Ligand Activation. The next goal of the research is to explore the mechanism in detail to define the scope of such reactions in terms of the metal-ligand combination that is required.

Bioorganometallc chemistry

 Bioorganometallc chemistry is becoming increasingly studied because of its potential in medicinal and biological chemistry. Cyclometallated iridium complexes [Ir(C~N)2(XY)]n+ (C~N = cyclometallated ligand, XY = bidentate ligand, n = 0,1] have attracted a lot of attention due to their interesting fluorescent properties. In particular, the emission wavelength and excited-state lifetime can be tuned by changing the cyclometallated ligands and the other chelate XY. The fluorescent properties of the complexes, high efficiency, due to spin orbit coupling, relatively long–lived emission and large Stokes shift and the tuneability of these properties by ligand modification make them attractive for bioanalytical applications. The main goal of this work will be to synthesise complexes which can enter cells by active or passive transport systems and then respond to a stimulus within the cell which causes a large change in fluorescence.

Cycloisomerisations for the synthesis of nucleosides and analogs

 Nucleosides and their analogues exhibit a vast array of biological activities and are of tremendous academic and industrial importance with the nucleic acid/nucleoside market worth almost £109 bn. Currently most methods of nucleoside synthesis rely on coupling a pre-formed heterocycle with an appropriate naturally occurring sugar precursor. The crucial drawbacks of these strategies include: 

Extensive functional group manipulation is required and some substituents need to be removed (particularly true for the 2,3-dideoxynucleosides), resulting in low atom- and step-economy.

Variable C1' stereoselectivity for deoxyribonucleoside analogues results in tedious chromatographic isolation of individual compounds.

We aim to establish a new approach using transition metal catalysed cycloisomerization (TMCC). TMCC reactions are highly selective, 100% atom efficient processes for formation of a variety of ring structures under mild conditions, hence are growing in utility. McDonald demonstrated the first application of TMCC methodology to nucleoside synthesis.¹ However, these W- and Mo-catalysed reactions are limited to terminal alkynes and have high catalyst loadings (40 mol %). In the last few years TMCC with Au and Pt catalysts have been reported with very low loadings, (1 mol %), which work with internal and terminal unsaturated bonds (alkynes, allenes and even alkenes), and which show exceptionally high reaction chemoselectivity, wide functional group tolerance and access to different sugar ring sizes as a function of catalyst, ligand and solvent.² Given these recent advances in TMCC catalysis a re-appraisal of the use of TMCC in nucleoside synthesis is very timely.

We will probe the mechanism of the cyclisation in order to design and then synthesise new catalysts with improved activity and selectivity.

Selected Publications

1. Room-temperature cyclometallation of amines, imines and oxazolines with [MCl2Cp* ]2 (M = Rh, Ir) and [RuCl2(p- cymene)]2  D.L. Davies, O. Al-Duaij, J. Fawcett, M. Giardiello, S.T. Hilton, and D.R. Russell, Dalton Trans., 2003, 4132-4138.
2. Computational Study of the Mechanism of Cyclometallation by Palladium Acetate D.L. Davies, S.M.A. Donald, and S.A. Macgregor, J. Amer. Chem. Soc., 2005, 127, 13754-55.
3. Electrophilic C-H Activation at {Cp*Ir}: Ancillary-Ligand Control of the Mechanism of C-H Activation  D.L. Davies, S.M.A. Donald, O. Al-Duaij, S.A. Macgregor, and M. Polleth, J. Am. Chem. Soc., 2006, 128, 4210-4211.
4. N-H versus C-H Activation of a Pyrrole Imine at {Cp*Ir}: A Computational and Experimental Study. D.L. Davies, S.M.A. Donald, O. Al-Duaij, J. Fawcett, C. Little, and S.A. Macgregor, Organometallics, 2006, 25, 5976-5978
5. Mechanistic Study of Acetate-Assisted C-H Activation of 2-Substituted Pyridines with [MCl2CP*](2) (M = Rh, Ir) and [RuCl2(p-cymene)](2). Y. Boutadla, O. Al-Duaij, D.L. Davies, G.A. Griffith, and K. Singh, Organometallics, 2009, 28, 433-440.