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Development and mechanistic investigations of efficient Fe-catalysed asymmetric C–H activation

Project description

Development of efficient Fe-catalysed asymmetric C–H activation

Chirality in bioactive molecules is well established with only one enantiomer exhibiting the specific biological activity. Metal-catalysed enantioselective inner sphere C–H activation relies on precious and toxic metals (Pd and Ru), limiting the reaction’s applicability. The EU-funded AsymFeCH project aims to develop non-toxic, sustainable and inexpensive Fe-catalysed enantioselective C–H activation reactions. For this purpose, Fe complexes with chiral phosphines will be used as precatalysts in the catalytic hydroarylation of allenes or alkenes with aromatic ketones. The obtained mechanistic understanding will be used for further reaction development with different substrates (imines and 1,1-diphenylketone derivatives), providing foundations for the advancement of the field of asymmetric Fe-catalysed C–H activation.

Objective

The importance of chirality in bioactive molecules is well established with only one enantiomer exhibiting the desired biological activity. To date, more than 90% of chiral drugs on the market are supplied as racemates potentially causing side-effects or of uncertain bioactivity. The enantioselective synthesis of chemicals has risen to address such issues with enantioselective catalytic C–H activation standing out due to its atom economy, step efficiency, and avoidance of substrate pre-functionalization. So far, metal-catalysed enantioselective inner sphere C–H activation relies mainly on precious and/or toxic metals, such as Pd and Ru, limiting the reaction’s applicability. Therefore, efforts are currently being made to replace such metals with more benign 3rd row transition metals. Nevertheless, only one report of such transformation has been reported with Fe despite Fe being extremely desirable due to its low cost, toxicity and high natural abundance. The AsymFeCH project will address this issue through the development of non-toxic, sustainable and inexpensive Fe-catalysed enantioselective C–H activation reactions. For this purpose, low valent Fe complexes with chiral phosphines will be used as precatalysts in the catalytic hydroarylation of allenes or alkenes with aromatic ketones. The mechanism and origin of enantioselectivity of the developed reactions will then be delineated through a unique combination of spectroscopies and kinetic studies. Subsequently, the acquired mechanistic understanding will be used for further reaction development with more challenging substrates (imines and 1,1-diphenylketone derivatives) setting the foundations for the scientific and industrial communities to advance the field of asymmetric Fe-catalysed C-H activation. This will not only lead to the sustainable and greener synthesis of pure chiral products affecting the pharmaceutical and materials sectors but will also make Europe less dependent on Pd, an imported precious metal.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

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

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Call for proposal

(opens in new window) H2020-MSCA-IF-2019

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Coordinator

GEORG-AUGUST-UNIVERSITAT GOTTINGEN STIFTUNG OFFENTLICHEN RECHTS
Net EU contribution
€ 162 806,40
Address
WILHELMSPLATZ 1
37073 Gottingen
Germany
Region
Niedersachsen Braunschweig Göttingen
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 162 806,40