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Enantioselective Photochemical Reactions of Cyclopropene

Project description

Light-driven chemical synthesis for drug discovery

Many biologically active molecules exist as mirror-image pairs. However, typically only one form produces the desired therapeutic effect. Producing a single mirror-image form, known as an enantiomer, with high efficiency remains a central challenge in pharmaceutical chemistry. Light-driven chemical reactions offer a powerful but underexplored strategy for achieving this selectivity. With the support of the Marie Skłodowska-Curie Actions programme, the EnphoCypro project will exploit light to control the chemistry of a class of small ring-shaped molecules, steering reactions towards a single mirror-image product using specialised catalysts. Researchers will develop two complementary light-based approaches to build complex molecular structures. These methods will expand the toolkit available for synthesising chiral building blocks relevant to drug discovery.

Objective

In this proposal, we aim to explore the photochemistry of cyclopropene derivatives to access enantioenriched cyclopropenes and polycyclic fused rings with multiple stereocenters. Cyclopropenes can be photochemically excited to form intermediates, depending on the mode of excitation: triplet excitation leads to a diradical intermediate, while singlet excitation leads to a vinyl carbene intermediate. This project is divided into two parts.
In the first part, we will utilize deracemization through selective singlet excitation of cyclopropenes using chiral Lewis acid catalysts. Deracemization converts a racemic mixture into a single enantiomer with 100% efficiency, unlike classical resolution techniques. Cyclic deracemization involves selectively racemizing one enantiomer, leading to the accumulation of the opposite enantiomer. The chiral Lewis acid, coordinated to the ester group of the cyclopropene via two-point binding, will enable selective excitation of one enantiomer into a singlet state. This excited singlet state will collapse into an achiral vinyl carbene, which can cyclize to reform the racemic starting material, driving the mixture toward enantioenriched cyclopropene.
In the second part, we will explore the triplet excitation of cyclopropenes. Triplet excitation activates the olefin rather than the σ-bond, forming a triplet (1,2-diradical) intermediate. We plan to generate this intermediate using a chiral thioxanthone catalyst developed by the Bach group. The chiral environment provided by the catalyst will block one face, allowing selective reaction from one face, leading to enantioenriched bicyclo[2.1.0]pentanes.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

TECHNISCHE UNIVERSITAET MUENCHEN
Net EU contribution
€ 217 965,12
Address
Arcisstrasse 21
80333 Muenchen
Germany
Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost
No data