Asymmetric Catalysis: Intramolecular Hydroamination of Alkenes

Abstract:

Intramolecular hydroamination of alkenes stands as one of the most direct and atomeconomical strategies for the construction of nitrogen-containing heterocycles. However, its efficient asymmetric catalysis through this transformation remains a persistent and formidable challenge in the field of organic synthesis chemistry. This review summarizes the significant progress in asymmetric intramolecular hydroamination of alkenes during the past five years (2022–2026), centering upon two predominant catalytic paradigms: organometallic catalysis and metal-free catalysis. It emphasizes novel catalytic mechanisms exhibited by transition metal catalysts, which are fundamentally different from the traditional coordination activation mode; the metal-free catalysis section separately evaluates organic small-molecule catalysis, s-block catalysis, and Frustrated Lewis Pairs (FLPs) catalysis. Through the analysis and comparison of representative examples of various catalytic systems, the advantages and disadvantages of different catalytic systems in terms of stereochemical control mechanisms, substrate scope expansion, reaction parameter optimization, and side reaction suppression were summarized, thereby revealing the inherent patterns and essential characteristics of distinct activation modes in achieving stereoselective control. Looking forward, this article outlines corresponding research directions to address these limitations and explores emerging methodological approaches that warrant further investigation, furnishing theoretical underpinnings and methodological frameworks of this field.