Rapid ?-Amination Of N-Substituted Indoles By Using DBU-Activated N-Bromoimides As Nitrogen Sources

2-Amino-substituted indoles are widely existed as they constitute a key component of many natural products and pharmaceutical molecules such as physostigmine, (-)-Chaetominine, cheese penicillin C. In view of the importance of 2-amino-substituted indoles, synthetic routes to achieve them have received researchers' much attention.In our work, we demonstrated that N-bromoimide can be used as nitrogen source by using DBU-activation strategy. With this strategy, we achieved direct ?-amination N-substituted indoles in high efficiency. We found that the optimal conditions for the amination reaction are:1 equivalents of N-methylindole as a substrate,2.2 equiv of N-halogenated imides,2.2 equiv of DBU,6.6 equiv of H2O,2 mL of dry DMF as solvent, stirred at room temperature for 3 min. The results showed that:N-methyl indole, N-allyl indole, N-benzyl indole compounds with various substituents on the phenyl ring can afford the corresponding imidated products in high yields within a very short time. The structure of the products is identified by 1H NMR, 13C NMR and HRMS. Mechanistic study indicates that DBU-activated N-bromogenated imides can produce a more electrophilic bromine and a more nucleophilic nitrogen atom. The process involves tandem bromonium ion formation, nucleophilic substitution by imide anion, elimination of HBr. The protocol provides a novel, efficient, green, and complimentary access to ?-imidated indoles under mild conditions, without the necessity of external nitrogen sources.