Copper-mediated divergent synthesis of halogenated 1-pyrrolines, 3-azabicyclo[3.1.0]hex-2-enes and α,α-dibromo imines from N-allyl enamines†

Abstract

By varying the halide type and its addition rate, the divergent synthesis of dibromo 1-pyrrolines, 3-azabicyclo[3.1.0]hex-2-enes, and α,α-dibromo imines from N-allyl enamines was successfully achieved. 1-Pyrrolines and 3-azabicyclo[3.1.0]hex-2-enes are important building blocks in organic synthesis and pharmaceutical chemistry. Herein, we disclose a chemodivergent protocol for the Cu-mediated, halide-controlled annulation of N-allyl enamines, enabling straightforward access to these valuable scaffolds with good yields and high selectivity. The type of halogen reagent, its addition rate, and the solvent are critical for controlling reaction selectivity. A reaction mechanism is proposed, which involves X-transfer/radical cyclization to construct pyrrolines or 3-azabicyclo[3.1.0]hex-2-enes. It is worth mentioning that N-allyl enamine serves as both a bromine acceptor and donor in this transformation. This strategy employs readily available starting materials, mild conditions, and a simple protocol and exhibits good functional group compatibility, demonstrating that N-allyl enamines are versatile building blocks for constructing nitrogen-containing heterocycles.