Organocatalytic asymmetric synthesis of Tröger’s bases

Abstract The stereochemical course of nitrogen in tertiary amines has long been overlooked because of the low energy barriers for pyramidal inversion between nitrogen-based conformers. Tröger’s base (TB) is a textbook three-dimensional (3D) molecule with N-centered chirality. Despite the major devel...

Full description

Saved in:
Bibliographic Details
Main Authors: Yu-Wei Li, Nan-Nan Mo, Han Zhang, Jian-Xiao Wu, Tian-Jiao Han, Xiao Xiao, Donghui Wei, Guang-Jian Mei
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61772-4
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract The stereochemical course of nitrogen in tertiary amines has long been overlooked because of the low energy barriers for pyramidal inversion between nitrogen-based conformers. Tröger’s base (TB) is a textbook three-dimensional (3D) molecule with N-centered chirality. Despite the major development of TB chemistry, surprisingly few general strategies are available to access enantioenriched TBs. Here, we report the organocatalytic asymmetric synthesis of TBs via the aminalization of tetrahydrodibenzodiazocines with aromatic aldehydes. This chiral phosphoric acid (CPA)-catalyzed protocol features a broad substrate scope (55 examples), high efficiency (up to 96% yield), and excellent enantioselectivity (up to >99% ee). Density functional theory (DFT) calculations are performed to reveal the reaction mechanism and the origin of the enantioselectivity. The success in preparing TB-polymers and aggregation-induced emission luminogen (AIEgen) demonstrates the potential for widespread applications, especially in the fields of materials science.
ISSN:2041-1723