Regioselective ring opening of Non-Activated Aziridines using 2-Substituted Indoles as Nucleophile: A Facile Synthesis of Tryptophan Scaffold

P. Saikia; S. T. Khom; N. Sharma; N. N. Yadav* Accepted in European Journal of Organic Chemistry 2026 (https://doi.org/10.1002/ejoc.70674)

We report regio- and stereoselective ring-opening reactions of non-activated aziridines using 2-substituted indoles as nucleophiles in the presence of BF₃·OEt2 in acetonitrile at 80 °C. Under these conditions, unsubstituted indole led to dimerization, while 2-substituted indoles furnished α-amino esters in good to excellent yields. The reaction proceeds via Lewis acid activation of the aziridine, followed by indole attack at the less hindered C-3 carbon and the regioselectivity of aziridine ring opening reaction is govern by both steric and electronic factors. The resulting products serve as intermediates for the synthesis of natural and unnatural tryptophan derivatives. This method offers a concise, selective, and broadly applicable route to nitrogen-containing scaffolds with potential in medicinal chemistry.

This work is available at https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejoc.70674