Synthesis of 2-Substituted Indoles through Cyclization and Demethylation of 2-Alkynyldimethylanilines by Ethanol

Guangkuan Zhao (1) , Christelle Roudaut (2) , Vincent Gandon (3, 4) , Mouad Alami (1) , Olivier Provot (5)

1 BioCIS - Biomolécules : Conception, Isolement, Synthèse
2 IC2MP [Poitiers] - Institut de chimie des milieux et matériaux de Poitiers [UMR 7285]
3 ICMMO - Institut de Chimie Moléculaire et des Matériaux d'Orsay
4 LCM - Laboratoire de chimie moléculaire
5 MBCIS - Molécules bioactives, conception, isolement et synthèse

Herein, we demonstrated that 2-alkynyldimethylamines easily cyclize in EtOH according to a 5-endo-dig annulation into 2substituted indoles without the aid of any additive or any metal catalyst to activate the triple bond. Thus, a variety of functionalized 2-styrylindoles, 2-arylindoles, 2-alkynylindoles, and 2-alkylindoles were prepared in high to excellent yields according to an environmentally friendly protocol. The mechanism has been explored to better understand this eco-friendly access to 2substituted indoles and DFT computations rationalized the role of the solvent in this N-annulation/dealkylation process.

Domaines: Chimie organique

Guangkuan Zhao, Christelle Roudaut, Vincent Gandon, Mouad Alami, Olivier Provot. Synthesis of 2-Substituted Indoles through Cyclization and Demethylation of 2-Alkynyldimethylanilines by Ethanol. Green Chemistry, 2019, 21 (15), pp.4204-4210. ⟨10.1039/c9gc01880h⟩. ⟨hal-03349087v2⟩