Blue LED-Mediated N–H Insertion of Indoles into Aryldiazoesters at Room Temperature in Batch and Flow: Reaction Kinetics, Density Functional Theory, and Mechanistic Study

Mild blue light-mediated N–H insertion of indole and its derivatives into aryldiazoesters has been reported in a batch and flow strategy to afford the corresponding N-alkylated product in moderate-to-excellent yield. Detailed high-performance liquid chromatography-based reaction kinetics measurements, control experiments, and kinetic isotope effect reveal that 3-substituted indoles with electron-withdrawing groups such as −CN and −CHO facilitated the product formation, whereas the electron-donating group retarded the process. The neutral indole performed in between them. Furthermore, Hammett plot and density functional theory-based transition-state optimization studies showed substantial correlation of the electronic nature of the substituents at the C3 position of indoles with the rate of the N–H insertion reaction. The strategy was utilized to synthesize a key intermediate for the natural product (−)-psychotrimine.