Three-component, stereoselective C–N bond forming alkene difunctionalization

Abstract

Amines are essential functional groups in pharmaceuticals, agrochemicals, and bioactive molecules, with C(sp³)–N bonds playing a crucial role in enhancing biological activity and selectivity. Alkene difunctionalization offers a powerful strategy for constructing these bonds by introducing two distinct functional groups across a double bond in a single step. While two-component alkene difunctionalization has been widely studied, general three-component strategies for amine synthesis remain underdeveloped due to challenges in controlling regioselectivity, stereoselectivity, and competing side reactions. Recent advancements have addressed these limitations through transition-metal catalysis, directing-group-free methodologies, and radical-based mechanisms, enabling stereoselective synthesis of amines from readily available starting materials. This review discusses emerging strategies in three-component, stereoselective C–N bond-forming alkene difunctionalization, emphasizing mechanistic innovations and their impact on synthetic organic chemistry.