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Mechanistic Studies of NHC Organocatalysis – Quantifying the Reactivity of the Breslow Intermediate

Project description

Enhancing understanding of a key intermediate in organocatalysis

N-heterocyclic carbenes (NHCs) are the most versatile class of organocatalysts, allowing access to a variety of catalytic intermediates for constructing complex targets from simple starting materials. Despite advances in the field, the reason why product distributions of NHC-catalysed processes often differ dramatically is still poorly understood. Funded by the Marie Skłodowska-Curie Actions programme, the NHC2Breslow project aims to improve mechanistic understanding of the Breslow intermediate; first characterised in 2012, its reactivity is key to a multitude of synthetic transformations. Therefore, it is regarded as the cornerstone of modern NHC-mediated catalysis.

Objective

N-heterocyclic carbenes (NHCs) are the most versatile class of organocatalyst, allowing access to a variety of catalytic intermediates for the construction of complex targets from simple starting materials under mild conditions. Despite many individual conceptual advances in this field, it is not understood (or even commonly acknowledged by practitioners) why product distributions of NHC-catalysed processes often differ dramatically with catalyst scaffold or with subtle substituent variation within an NHC-catalyst family. Following the many synthetic innovations over the past decade, future transformative benefits will rely on the careful, quantitative and detailed analysis and understanding of all aspects of reactions mechanisms in order to make informed choice of catalyst for a given transformation, rather then relying on brute force screening. To break from this traditional, time-intensive screening approach and fully realize the potential of NHCs, a quantitative mechanistic understanding is required. Central to this state-of-the-art field is the catalytically competent “Breslow intermediate” (BI) that is regarded as the cornerstone of modern NHC-mediated catalysis. First characterised in 2012, its reactivity is key to a multitude of synthetic transformations. Despite its importance, a quantitative understanding of the behaviour of this transiently formed species has yet to be defined. This proposal will deliver quantitative underpinning knowledge of this key intermediate that will (i) be used to develop a fundamental scale to quantify BI reactivity with a range of electrophilic species and (ii) be applied to answer unresolved mechanistic and chemoselectivity questions in contemporary NHC-based catalysis.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

THE UNIVERSITY COURT OF THE UNIVERSITY OF ST ANDREWS
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 212 933,76
Address
NORTH STREET 66 COLLEGE GATE
KY16 9AJ ST ANDREWS
United Kingdom

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Region
Scotland Eastern Scotland Clackmannanshire and Fife
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.

€ 212 933,76
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