Cu-XAT · Development of Copper Catalyzed Strategies for the Amination of Alkyl Halides Using Halogen-Atom Tranfer: Going Beyond SN2 Chemistry
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-08-04 → 2023-08-03
- EU contribution
- €212,934
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Development of Copper Catalyzed Strategies for the Amination of Alkyl Halides Using Halogen-Atom Tranfer: Going Beyond SN2 Chemistry
The overall objectives of this project the discovery, design and development of novel catalytic methods to streamline the synthesis of high-value materials. We have completed two projects which have been published in high-quality journals with the Fellows as the co-first author. In the first project, we realized a novel strategy merging halogen-atom transfer (XAT) and Cu-catalysis for the modular Suzuki−Miyaura-type cross-coupling between alkyl Iodides and aryl organoborons. The purpose of this project was to address the problem in the cross-coupling reactions for the construction of C(sp3)–C(sp2) bonds due to the limited reactivity of palladium and nickel catalysts with alkyl halides. The approach developed here used a cooperative strategy, based on XAT for the conversion of the iodides into the corresponding radicals, and copper catalysis for C–C bond formation with the aryl organoborn. In the second project, we discovered that highly substituted phenols can be accessed through a cooperative strategy merging hydrogen-atom transfer (HAT) with Co-catalyzed desaturation using readily available cyclohexanones as materials. It is worth noting that hydrogen is the only side product, which increases the sustainability and the practicality of the reaction. Phenols are important fragments widely used in medicinal chemistry, agrochemistry and material science. Our strategy has established a platform to convert substituted cyclohexanones into value-added phenols in a highly sustainable manner.
Data: CORDIS, © European Union
Project objective
The formation of carbon–nitrogen bonds is crucial to the preparation of molecules that impact almost every aspects of our lives like drugs, agrochemicals and food additives.In text-books, creating C–N bonds is approached considering the natural nucleophilic character of N-molecules in substitution reactions with alkyl halides. In practice, these reactions are only used in the case of highly reactive substrates with low steric hinderance (e.g. primary amines + primary alkyl halides). The vast majority of substrates require forcing conditions which lead to side reactions like elimination or poly alkylation. To by-pass these issues multi-step approaches, based on extensive functional group manipulations, are still required. There is an urgent need of methods enabling to directly “plug” complex N-molecules into complex alkyl halides.This project aims at providing a conceptually novel approach to perform substitution reactions between N-nucleophiles and alkyl halides. This will be achieved by developing a radical reactivity where alpha-aminoalkyl radicals convert alkyl halides into C-radicals by halogen-atom transfer (XAT) and a copper catalyst binds the N-nucleophiles and enables amination. Upon achieving this initial goal, I aim to extend and engineer this reactivity as part of complex radical cascades leading to structurally complex chemotypes.The proposal capitalizes on recent developments of the host group that has experience in XAT and the development of catalytic reactions for the formation of C–N bonds. The development of this innovative project at the University of Manchester will create new tools in bio-organic chemistry and facilitate the preparation of high-value materials. Its implementation will be facilitated by generating, transferring, sharing and disseminating knowledge, and will enhance my future career following the training plan envisioned.
Original text from CORDIS.
Participants
- THE UNIVERSITY OF MANCHESTER · ManchesterCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union