Abstract
Nitrogen heterocycles represent vital structural motifs in biologically-active natural products and pharmaceuticals. As a result, the development of new, convenient and more efficient processes to N-heterocycles is of great interest to synthetic chemists. Samarium(II) iodide (SmI₂, Kagan's reagent) has been widely used to forge challenging C-C bonds through reductive coupling reactions. Historically, the use of SmI₂ in organic synthesis has been focused on the construction of carbocycles and oxygen-containing motifs. Recently, significant advances have taken place in the use of SmI₂ for the synthesis of nitrogen heterocycles, enabled in large part by the unique combination of high reducing power of this reagent (E(1/2) of up to -2.8 V) with excellent chemoselectivity of the reductive umpolung cyclizations mediated by SmI₂. In particular, radical cross-coupling reactions exploiting SmI₂-induced selective generation of aminoketyl radicals have emerged as concise and efficient methods for constructing 2-azabicycles, pyrrolidines and complex polycyclic barbiturates. Moreover, a broad range of novel processes involving SmI₂-promoted formation of aminyl radicals have been leveraged for the synthesis of complex nitrogen-containing molecular architectures by direct and tethered pathways. Applications to the synthesis of natural products have highlighted the generality of processes and the intermediates accessible with SmI₂. In this review, recent advances involving the synthesis of nitrogen heterocycles using SmI₂ are summarized, with a major focus on reductive coupling reactions that enable one-step construction of nitrogen-containing motifs in a highly efficient manner, while taking advantage of the spectacular selectivity of the venerable Kagan's reagent.