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Content archived on 2024-06-18

Arylation and Vinylation of Enolates: New Reactivity from the Urea Linkage

Objective

Enols and enolates are among the most versatile nucleophiles in chemistry: they react well with alkylating agents or carbonyl compounds, but their coupling with aryl or alkenyl halides is usually dependent on Pd-based catalysts for enol–aryl coupling. In this proposal we aim to develop new possibilities for enolate arylation that reveal fundamental new reactivity and will have repercussions throughout the science of synthetic planning. The method builds on some arylation reactions of urea-containing organolithiums, first reported in 2007, which turn out to be general for a variety of compound classes. Preliminary experiments show that enolates also undergo this arylation, providing a simple way of introducing an Ar+ equivalent to an enolate nucleophile without the need for heavy-metal catalysis.
We propose to develop this reaction into a simple and versatile method for the challenging arylation of enolates. The resulting transformation will have broad application to the synthesis of biologically active targets, both natural and non-natural, of value to the pharmaceutical, agrochemical and related fine chemicals industries. Extension beyond the amino acids could see the method rooted among the canon of enolate-based C–C bond forming reactions.

Key objectives are:
• Arylation and vinylation of amino acids: We will optimise the enolate methodology for the synthesis of quaternary amino acid targets.
• Controlling absolute configuration: We will develop an asymmetric version of the reaction (ideally based on chiral metal ligands, but alternatively other structures) for the enantioselective synthesis of quaternary amino acids.
• Mechanistic investigation: Unravelling the remarkable mechanism of the reaction will throw light on other possible future directions for the research.
• Extending to other carboxylic acid derivatives.
• Arylation and vinylation of ketones and aldehydes.
• Synthesis of valuable target molecules.

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2013-IEF
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Funding Scheme

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MC-IEF - Intra-European Fellowships (IEF)

Coordinator

THE UNIVERSITY OF MANCHESTER
EU contribution
€ 221 606,40
Address
OXFORD ROAD
M13 9PL Manchester
United Kingdom

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Region
North West (England) Greater Manchester Manchester
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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