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Photocatalytic Reductive Coupling of Imines: A New Platform for Chiral Amine Synthesis

Objective

Chiral α-branched amines and their derivatives are commonplace in pharmaceuticals, agrochemicals and biologically relevant natural products. Accordingly, the development of new synthetically powerful methods for their synthesis, and/or further functionalisation, through new carbon-carbon bond forming processes is both important and timely from academic and industrial perspectives. Such chiral α-branched amine motifs can be accessed from electrophilic imine substrates, through direct addition of carbon-centered nucleophiles such as organometallic reagents and electron rich π-nucleophiles. This traditional approach takes advantage of the easy formation of imines and their natural polarity and has led to numerous developments over the years. Whilst nucleophilic addition reactions dominate the chemistry of imines, polarity reversal is possible but requires the careful design of imine precursors able to stabilise anionic intermediates following deprotonation. Free radical chemistry offers the possibility to reverse the polarity of imine derivatives; the formal addition of a hydrogen atom to the C=N π-bond can generate a nucleophilic α-amino radical able to react with alkenes and alkynes. However, to date these approaches have been limited by the way the radical is generated. Here we propose a new and broadly applicable ‘umpolung’ approach to access chiral α-branched amine motifs directly from imine substrates. Our plan is to design and develop a new reductive photochemical system that will allow the direct generation of ‘free’ nucleophilic α-amino radical species capable of undergoing a broad range of synthetically useful carbon-carbon bond forming processes. This non-classical umpolung strategy has a wealth of untapped synthetic potential and will allow the development of new modes of reactivity each in turn rendering new suites of synthetic methodologies including catalytic asymmetric versions.

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2017

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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
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.

€ 183 454,80
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
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.

€ 183 454,80
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