Issue 17, 2025

Transforming 2D azolium salts to 3D caged tertiary amines via stereoselective dearomative cascade annulation

Abstract

Three-dimensional fused-ring frameworks, especially those incorporating heteroatoms, are fundamental to expanding chemical space and unlocking unique properties critical for drug discovery and functional materials, yet their synthesis remains a formidable challenge. Herein, we report for the first time the union of two distinct azolium salts as an efficient synthetic platform to access tertiary amine-caged frameworks under mild conditions. The strategy combines the masked nucleophilic and electrophilic properties of isoquinolinium and pyridinium salts, and avails double dearomatization guided inverse electron demand (4 + 2) or (3 + 2) annulation in a highly regio- and diastereoselective manner to construct the nitrogen caged motifs. Our methodology creates two new rings and four new bonds in a single operation and transforms flat-aromatic compounds into structurally unprecedented three-dimensional architectures with contiguous stereocenters in very high yields. DFT studies have shed light on the reaction mechanism, indicating that the annulation step is rate-limiting, with (4 + 2) annulation proceeding stepwise and (3 + 2) annulation following a concerted pathway.

Graphical abstract: Transforming 2D azolium salts to 3D caged tertiary amines via stereoselective dearomative cascade annulation

Supplementary files

Article information

Article type
Edge Article
Submitted
26 Feb 2025
Accepted
25 Mar 2025
First published
26 Mar 2025
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2025,16, 7551-7559

Transforming 2D azolium salts to 3D caged tertiary amines via stereoselective dearomative cascade annulation

K. Patra, S. Deb, V. S. Kumar Choutipalli, S. Mulani, S. Mallik, V. Subramanian and M. Baidya, Chem. Sci., 2025, 16, 7551 DOI: 10.1039/D5SC01527H

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements