Brønsted Acid-Catalyzed [3 + 2] Cycloaddition of Indoles with Azabicyclobutanes: Access to Indole-Fused 1-Azabicyclo[2.1.1]hexanes

Organic Letters 2026

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Authors: Debasis Aich, Arpan Naskar, Subrata Hazra, Suchandrima Banerjee, Boudhayan Bandyopadhyay, Santanu Panda
DOI: 10.1021/acs.orglett.6c02421
Cited by: 1
References: 27

Abstract

1-Azabicyclo[2.1.1]hexanes are valuable nitrogen-rich scaffolds with growing importance in medicinal chemistry. We report a Brønsted acid-catalyzed formal cycloaddition of N-substituted indoles with azabicyclobutane (ABB) ketones, providing a mild, transition-metal-free, and highly stereoselective route to aza-bicyclohexanes. Using pTSA·H2O in HFIP, the reaction proceeds at room temperature in up to 93% yield and 99:1 d.r. Mechanistic studies suggest cooperative activation by pTSA and HFIP via hydrogen-bond-assisted proton transfer. The synthesized scaffolds also exhibited promising antimicrobial activity.

Fields of Study & Subjects

Radical Photochemical Reactions Synthesis and Catalytic Reactions Catalytic C–H Functionalization Methods

Publication details

Journal / source
Organic Letters
Publisher
American Chemical Society (ACS)
Volume
28
Issue
32
Pages
10163–10168
Publication date
1 August 2026
Language
EN