Enantioselective Zinc-Catalyzed [3+2] Azomethine Ylide Cycloaddition: Developing Planar Chiral [2.2]Paracyclophane-Imidazoline N,O-Ligands

Abstract

Asymmetric catalysis constitutes a key strategy for the enantioselective synthesis of natural products and bioactive compounds. Chiral ligands are crucial for achieving the required reactivity and enantioselectivity in asymmetric catalytic reactions. Consequently, the rational design of chiral ligands is central to the development of new asymmetric transition-metal-catalyzed reactions. Our group has been actively engaged for many years in the development of chiral ligands for a wide range of asymmetric transformations. This Account presents our recent efforts in the design of chiral ligands specifically for the asymmetric [3+2] azomethine ylide cycloaddition, an important transformation for the asymmetric synthesis of pyrrolidines. We detail their application in Zn-catalyzed [3+2] cycloadditions, discuss the underlying transition states responsible for the observed selectivity, and highlight synthetic applications of this important reaction.

1 Introduction

2 Metal-Catalyzed Azomethine Ylide Cycloaddition

3 Ligand Design: UCD-Imphanol Ligands

4 Application of UCD-Imphanol Ligands in Zn(II)-Catalyzed Azomethine Ylide [3+2] Cycloaddition

5 Synthetic Applications

6 Conclusions

Key words

asymmetric catalysis - chiral ligand design - planar chiral ligands - paracyclophanes - azomethine ylides - [3+2] cycloaddition

Publication History

Received: 09 February 2025

Accepted after revision: 12 March 2025

Accepted Manuscript online:
12 March 2025

Article published online:
24 April 2025

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