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Chirality via Cross-Coupling: New Asymmetric C-C Bond Formations Driven by Atom and Step Economy

Project description

New methods of chiral molecule synthesis could increase sustainability of drug discovery

More than half of the drugs currently in use are chiral compounds. Despite the tremendous advances made in catalysis over the past decades, the "chiral complexity" of chemical libraries in drug discovery has not followed the same upward trend. Efficient processes that directly access privileged chiral scaffolds are highly needed in the pharmaceutical industry. Cross-coupling reactions of alkenes and aryl C-H bonds circumvent "concession" steps taken by other cross-coupling reactions used in the pharmaceutical industry, thereby minimising cost, effort and waste. The EU-funded ChiCC project will develop suitable catalysts for these cross-coupling reactions that foster asymmetric C-C bond formations, with a focus on increasing step economy. Scientists will also use reactions with high atom economy, which is vital for the sustainability of chemical processes.

Objective

Over 60% of the world’s top selling small molecule drug compounds are chiral and, of these, approximately 80% are marketed as single enantiomers. Surprisingly, and despite the tremendous advances made in catalysis over the past several decades, the average “chiral complexity” of drug discovery libraries has actually decreased, while, at the same time the “chiral complexity” of marketed drugs has increased. Consequently, there is now an urgent need to provide efficient processes that access directly privileged chiral “3D” building blocks. It is our philosophy that catalysis holds the key here and new processes should be based upon atom and step economical platforms that exert control over both absolute and relative stereochemistry. Palladium catalysed cross-coupling reactions of aryl (pseudo)halides with organo-nucleophiles (esp. the Suzuki coupling) have become mainstays of the pharmaceutical industry. Here, multiple “concession” steps are usually required to prepare the reaction partners, thereby detracting from atom and step economy. Further, these processes predominantly provide planar “2D” structures and are not well suited to the production of chiral “3D” building blocks. Consequently, methods that allow feedstock precursors (e.g. alkenes and aryl C-H bonds) to be combined directly in enantioselective or enantiospecific C-C bond formations are highly desirable. Cross-couplings of this type would circumvent “concession” steps, thereby minimising cost, effort and waste; however, such processes are highly challenging because of issues associated with regio- and stereocontrol. Recently, we developed prototype catalyst systems that can address this. In the proposed ERC project, these exciting preliminary results will be developed into a wider family of processes where asymmetric C-C bond formations are achieved directly by C-H activation. The new methods, which fulfil modern reaction ideals of atom and step economy, will likely find broad use in applied settings.

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-COG - Consolidator Grant

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Call for proposal

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(opens in new window) ERC-2019-COG

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Host institution

THE UNIVERSITY OF LIVERPOOL
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.

€ 1 999 890,00
Address
BROWNLOW HILL 765 FOUNDATION BUILDING
L69 7ZX LIVERPOOL
United Kingdom

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Region
North West (England) Merseyside Liverpool
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.

€ 1 999 890,00

Beneficiaries (1)

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