Development of C-H functionalization methodology on non-aromatic and aromatic azaheterocycles.

Development of efficient and versatile synthetic approaches to construct carbon-carbon and carbon-nitrogen bonds via direct C (sp2)-H functionalization of the imine or aldonitrone moiety in azaheterocyclic compounds are of importance with respect to the development of more sustainable organic syntheses in a PASE way (= Pot, Atom, Step Economical). C(sp2)-H functionalizations of the nucleophilic substitution of hydrogen (SNH) type are inherently very attractive versus other synthetic methods considering they do not require transition metal catalysis, though still rather limitedly explored and developed in azaheterocyclic substrates. This gives access to novel substituted scaffolds with a variety of potential applications. SNH reactions are two-step processes: the addition of the nucleophilic reactants to pi-deficient azaheterocyclic substrate (formation sigma Н-adduct intermediates) followed by reformation of the imine moiety via either an elimination [«Addition - Elimination»] (built-in oxidant) or an oxidation reaction [«Addition - Oxidation»]. The sigma Н-adducts will also be transformed in other manners, allowing to achieve di rather than mono functionalization. Development of efficient SNH protocols will require an understanding of the factors which promote sigma Н-adduct formation and the search for sustainable oxidants to transform them. Insight will be obtained through mechanistic studies involving both experimental techniques and computational chemistry (DFT).

Keywords:ORGANIC SYNTHESIS

Disciplines:Organic chemical synthesis

Project type:Collaboration project