Recent Advances in Single Electron Reduction Induced Ring Opening of N-Acyl Cyclic Amines

Abstract

Cyclic amines represent ubiquitous structural motifs in organic chemistry, prominently featured in natural products and pharmaceuticals. The development of synthetic methodologies targeting cyclic amines has attracted considerable interest, given their significance in medicinal chemistry. These transformations can be broadly categorized into two main types: (1) peripheral modification and (2) skeletal remodeling. Recent advancements in late-stage C–H functionalization have showcased the synthetic potential of peripheral modification strategies. Conversely, skeletal remodeling, particularly through the ring opening of cyclic amines, has emerged as a powerful approach to access structurally diverse amines. Ring opening of cyclic amines, initiated by C–N bond cleavage, predominantly relies on two-electron mechanisms. Strained cyclic amines readily undergo such transformations, while those with a larger-membered ring, like pyrrolidines, present greater challenges. Oxidative and von Braun-type approaches have facilitated heterolytic C–N bond cleavage, offering broad applicability across various cyclic amines. In contrast, reductive approaches, which enable homolytic C–N bond cleavage, provide unique access to radical-mediated transformations. This short review highlights recent progress in single electron reduction induced ring-opening methodologies, focusing on α-aminoketyl radical generation for selective amide C–N bond cleavage. Advances in the ring opening of aziridines, azetidines, pyrrolidines, and other cyclic amines are discussed, along with their synthetic implications and future prospects.

1 Introduction

2 Ring Opening of Aziridines

2.1 Hydrogenation and Alkylation

2.2 Isomerization

2.3 Arylation

3 Ring Opening of Azetidines

4 Ring Opening of Pyrrolidines and Other Cyclic Amines

5 Conclusion and Outlook

Key words

cyclic amines - ring opening - C–N bond cleavage - single-electron reduction - skeletal remodeling

Publication History

Received: 24 December 2024

Accepted after revision: 16 January 2025

Accepted Manuscript online:
16 January 2025

Article published online:
05 March 2025

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