Professor Steve Marsden This proposal is representative of the projects currently on offer in the group. For more details of active research projects, please visit the Research and Publications sections of our webpages at: www.chem.leeds.ac.uk/SPM Direct arylation of carboxylates by C-H activation (Industrial CASE with AstraZeneca) As part of our general interest in methods for the efficient construction of quaternary asymmetric centres,1 we have recently developed routes to the synthesis of quaternary 3-alkoxy2 and 3-aminooxindoles3 by palladium-catalysed enolate arylation, including highly effective asymmetric variants (in collaboration with the Kundig group in Geneva).4 These are now being applied in target synthesis studies towards, for example, the structurally unique tryptamine trimer psychotrimine.
α-Arylated carbonyl compounds in general are fundamentally important building blocks for the pharmaceutical industry. The subunit itself is prominent in Non-Steroidal Anti-Inflammatory drugs such as simple α-arylacetic acid derivatives (eg Indomethacin) and higher homologues such as Naproxen and Ibuprofen; it also occurs in oxindoles such as the anti-inflammatory drug Tenidap. Additionally, they are valuable templates for cyclocondensation reactions to generate heteroaromatic skeleta such as indoles. In a new departure, we are interested extending our work on enolate arylation to the use of simple arenes (rather than aryl halides) as reaction partners by C-H activation chemistry. Such an oxidative coupling process will greatly broaden the scope and chemical efficiency of the arylation approach to α-arylated carbonyl compounds. This project will be of interest to students who wish to work on a project combining catalysis, synthetic organic chemistry and target synthesis.
References 1. (a) R. Newton, S. P. Marsden, Synthesis, 2005, 3263-3270; (b) D. Lertpibulpanya, S. P. Marsden, I. Rodriguez Garcia, C. Kilner, Angew. Chem. Int. Ed., 2006, 45, 5000-5002; (c) D. Lertpibulpanya, S. P. Marsden, Org. Biomol. Chem., 2006, 4, 3498-3504; (d) M. C. Jones, S. P. Marsden, D. M. Muñoz-Subtil, Org. Lett., 2006, 8, 5509-5512; (e) C. E. Headley, S. P. Marsden, J. Org. Chem., 2007, 72, 7185-7189; (f) S. P. Marsden, R. Newton, J. Am. Chem. Soc., 2007, 129, 12600-12601; (g) M. C. Jones, S. P. Marsden, Org. Lett., 2008, 10, 4125-4128. 2. J. M. Hil gren, S. P. Marsden, J. Org. Chem., 2008, 73, 6459-6461 3. (a) E. L. Watson, S. P. Marsden, S. A. Raw, Org. Lett., 2008, 10, 2905-2908; (b) E.L. Watson, S. P. Marsden, S. A. Raw, Tetrahedron Lett., 2009, 50, 3318-3320. 4. Y. Jia, J. M. Hil gren, E. L. Watson, S. P. Marsden, E. P. Kundig, Chem. Commun., 2008, 4040-4042.
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