An alternative mode to activate alcohols: application to the synthesis of N-heteroarene derivatives

Xiaoping Liu (1) , Jean-Marc Sotiropoulos (2) , Marc Taillefer (1, 3)

1 ENSCM - Ecole Nationale Supérieure de Chimie de Montpellier
2 IPREM - Institut des sciences analytiques et de physico-chimie pour l'environnement et les materiaux
3 ICGM - Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier

The activation of readily available but poorly reactive alcohols can be carried out solely in the presence of the tert-butoxide (KOtBu)/dimethylformamide (DMF) couple. This system allows the direct use of primary alcohols as alkylating agents to functionalize the C(sp3)–H bond of methyl azaarenes, in the absence of traditionally used transition metal-based catalysts. Various alkylated N-heteroarenes such as pyridine, quinoline, pyrazine or quinoxaline derivatives have been obtained by this method, which is supposed to proceed via the initial formation of an alkyl formate intermediate, as shown by experimental and theoretical mechanistic studies.

Keywords: Theoretical mechanistic studies; Alkylating agents; Direct use; Heteroarenes; Metal-based catalysts; Primary alcohols; Quinoxaline derivatives; Tert-butoxide

Domains: Material chemistry; Analytical chemistry; Polymers; Theoretical and/or physical chemistry

Xiaoping Liu, Jean-Marc Sotiropoulos, Marc Taillefer. An alternative mode to activate alcohols: application to the synthesis of N-heteroarene derivatives. Organic Chemistry Frontiers, 2021, 8 (18), pp.5112-5117. ⟨10.1039/d1qo00930c⟩. ⟨hal-03354966⟩