Development of Copper Catalyzed Strategies for the Amination of Alkyl Halides Using Halogen-Atom Tranfer: Going Beyond SN2 Chemistry

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.