PhotoDeRac · Photocatalytic Deracemisation of Amines
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2020-07-01 → 2023-04-02
- Финансиране от ЕС
- 230 416 €
- Участници
- 2
- Схема
- MSCA-IF
Линиите свързват координатора с партньорите.
Накратко на български
Амините, които са част от много лекарства, се изследват чрез нови фотохимични методи за синтез и преобразуване на тяхната структура. Това помага за по-прецизното създаване на лекарствени вещества и подобрява начина, по който се синтезират сложни органични молекули.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Photocatalytic Deracemisation of Amines
Amine functional groups are of prime importance for the synthesis and application of established and emerging medicines for the betterment of humankind. Therefore, methods to synthesise these groups, particularly in a stereocontrolled manner, are always desirable. In this project, we leveraged two central properties of amines — their basicity, and their nucleophilicity — to i) discover a method for the photochemical deracemization of chiral alkyl amines, and to ii) develop a new and general annulation reaction for the synthesis of amine heterocycles through the union of photochemical reductive proton-coupled electron transfer (reductive PCET) and oxidative radical polar crossover (oxidative RPC) processes. In the course of this work, we also carried out a thorough review of documented photochemical and electrochemical applications of proton-coupled electron transfer in organic synthesis. This exercise assisted with the planning and execution of our project aims, in addition to providing a valuable and accessible practitioners guide to this emerging area of study for members of our broader research community.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
A method is proposed for the deracemisation of tertiary amines via the joint action of three distinct molecular catalysts - an Ir(III) photocatalyst, a chiral Brønsted base and a chiral thiol hydrogen-atom transfer additive. Through sequential visible-light driven electron transfer (ET), proton transfer (PT) and hydrogen-atom transfer (HAT), proximal stereocentres to amine functional groups can be selectively targeted for destruction of the undesired substrate enantiomer, and restored as the desired. An optical enrichment in the amine sample then builds over time, without other chemical change taking place. The two separate chiral catalysts work in tandem on two mechanistically distinct elementary steps, resulting in an amplification of asymmetric induction. Initial substrate activation is non-stereoselective, meaning that the total amount of substrate is capable of being processed, in stark contrast to typical chemical resolution methods. The method requires no stoichiometric reagents, produces no stoichiometric waste, is redox-neutral, and consumes only visible light photos. We believe this method will be of direct utility to the synthetic organic and medicinal chemistry communities, offering more efficient and more sustainable synthetic routes to target molecules, and going beyond the existing state-of-the-art. In the return phase of the project, the method is extended to the control of amine substrate diastereoisomers, in a tandem process involving C–N bond formation. Through appropriate catalyst selection we aim to develop complimentary methods to access either the thermodynamic or kinetic isomer – something difficult to achieve with existing epimerisation protocols. The concepts introduced here address fundamental questions of absolute and relative stereocontrol, retrosynthetic design, asymmetric autocatalysis and the utility of light as a driver of chemical change against a thermodynamic gradient, to achieve an out-of-equilibrium product distribution.
Оригинален текст от CORDIS (на английски).
Участници
- THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGEКоординаторОбединеното кралство
- TRUSTEES OF PRINCETON UNIVERSITY · Princeton, NjСъединени щати
Връзки
Данни: CORDIS, © Европейски съюз