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

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 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.

Publication History

Received: 24 December 2024

Accepted after revision: 16 January 2025

Accepted Manuscript online:
16 January 2025