Around 95% of pharmaceuticals rely on the use of an organolithium reagent at one point in their synthesis.1 One of their major uses is in the metallation reaction, which is the conversion of a C-H bond to a more useful C-M bond. In particular, Directed ortho-Metallation (DoM) is one of the most widely used protocols to ortho-functionalise aromatic systems.2However, organolithium reagents exhibit poor functional group tolerance, react with solvents and generally require cryogenic temperature reaction conditions.The utilisation of alkali metal magnesiates in synthetic protocols has emerged as a leading alternative to organolithiums in a series of regioselective deprotonations (metal-hydrogen exchange) and metal-halogen exchanges.3This presentation details the chemistry of selected potassium and sodium magnesiates which exhibit novel reactivity and selectively activate one or two C�H bonds of the substrate respectively. Ultimately, the organometallic reagents isolated in these reactions are mixed-metal amide-containing macrocyclic complexes known as inverse crown complexes.4 We have recently reported inverse crown precursors5 which has allowed us to develop a new general metallation strategy to regioselectively 2,5- or 3,5-dimetallate selected aromatic systems while tolerating a wide range of functional groups without the need for cryogenic temperatures.61 Collum, D.; Acc. Chem. Res. 1993 , 26, 227.2 Whisler, M.; MacNeil, S.; Snieckus, V.; Beak, P.; Angew. Chem. Int. Ed. 2004 , 43, 2206.3 Mulvey, R.; Mongin, F.; Uchiyama, M.; Kondo, Y.; Angew. Chem. Int. Ed. 2007  , 46, 3802; Haag B.; Mosrin M.; Ila H.; Malakhov V.; Knochel P.; Angew. Chem. Int. Ed. 2011 , 50, 9794.4 Armstrong, D.; Kennedy, A.; Mulvey, R.; Rowlings, R.; Angew. Chem. Int. Ed. 1999 , 38, 131.5 Mart�nez-Mart�nez, A.; Armstrong D.; Conway, B.; Fleming, B.; Klett, J.; Kennedy, A.; Mulvey, R.; Robertson, S.; O'Hara, C.; Chem. Sci. 2014 , 4, 771.6 Mart�nez-Mart�nez, A.; Kennedy, A.; Mulvey, R.; O'Hara, C.; Unpublished results.

Co-operative effects between magnesium and alkali metals: Development of a powerful deprotonation method to override the classical directed <i>ortho</i>-metallation chemistry

248th National Meeting (2014)

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Co-operative effects between magnesium and alkali metals: Development of a powerful deprotonation method to override the classical directed ortho-metallation chemistry