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Alkali-Metal-Mediated Metallation

Final Report Summary - MEDIATED METALLATION (Alkali-Metal-Mediated Metallation)

The metal-hydrogen exchange reaction (metallation) is one of the most fundamental synthetic tools. Professor Mulvey's group have shown that special synergic effects can be induced by mixing an alkali metal base with certain magnesium or zinc reagents, leading to revolutionary new mixed-metal reagents that can perform reactions impossible with traditional single metal reagents (R. E. Mulvey, Acc. Chem. Res., 2009, 42, 743-755). Recently, this novel chemistry has been extended to a transition metal (manganese). This project investigated, among other objectives, the extension of this synergic methodology to other transition metals (cobalt, chromium, iron and nickel). Some of these synergic complexes have been described as 'inverse crowns', most of them involving alkali metal-magnesium partnerships. New chemical opportunities can be opened (redox chemistry, catalysis, magnetochemistry and anion complexation) if inverse crowns could be synthesised in which magnesium is replaced by any divalent transition metal.

Project main results:
The reactions of mixed alkali-metal reagents of Cr(II) and Fe(II) with benzene formed the first chromium and iron host inverse crowns and their magnetic properties were studied. This work was published as a front cover article in Angew. Chem. Int. Ed., 2009, 48, 3317. Turbo-Grignard reagents have wholly revolutionised aromatic molecule functionalisation chemistry (P. Knochel, Eur. J. Org. Chem. 2009, 1781. See also http://www.sigmaaldrich.com/chemistry/chemical-synthesis/technology-spotlights/chemetall.html online), but until our work, these had been mysterious 'black-box' reagents, with unknown constitutions and structures.

Using diffusion-ordered NMR spectroscopy (DOSY) and X-ray crystallography, two kinds of turbo-Grignard bases were fully structurally characterised rationalising their contrasting reactivities. This represented the first ever study of its kind for this type of reagent, which was recognised in two prestigious papers: Angew. Chem. Int. Ed., 2008, 47, 8079 (VIP status and inside cover); and Angew. Chem. Int. Ed., 2010, 49, 3185.

The elucidation of the TMP derivative's X-ray structure indicated a way to synthesise this base in a cheaper way than the one previously reported by Knochel. This is by metathesis (exchange) between LiTMP and the inexpensive metal halide salt MgCl2. Following the successful work with Li/Mg halogen based systems a systematic study of the metathesis reaction of ZnCl2 with variable amounts of the Grignard tBuMgCl was realised. The Mg-Zn hybrids characterised offered valuable information about the organic synthetic processes in which they are used, for example in Negishi cross-coupling transformations. This work was published in P.N.A.S. 2010, 107, 5294.

Socioeconomic impact:
The quantity and quality of the publications under this Marie-Curie program (40 % of the work is still unpublished) have been highly important for the scientific community as they cover such topical areas as main-group chemistry and metallation. Also the fellow researcher has improved his expertise and CV in such a way to allow him to get a new position for three years (Juan de la Cierva fellowship) in his country of origin, with high expectations of a longer-term position in the Spanish University system. This reintegration and knowledge exchange between two European Member States, is a main objective of this Marie-Curie program.

From an economic point of view, as with fundamental research generally, its benefits will only be seen in the long term; however, the results obtained for the turbo-Grignard reagents research are already of direct application for these new reagents for selective functionalisation. This shows the great importance that templated structural studies, a main focal point of the Mulvey group, have in modern chemistry, which established a cheaper way to synthesise such an important reagent ['(TMP)MgCl.LiCl' is recently comercialised by Aldrich].

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