Synthesis of Nitrogen Heterocycles Using Samarium(II) Iodide

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 (SmI(2), Kagan’s reagent) has been widely used to forge challenging C–C bonds through reductive coupling reactions. Historically, the use of SmI(2) 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 SmI(2) 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 SmI(2). In particular, radical cross-coupling reactions exploiting SmI(2)-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 SmI(2)-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 SmI(2). In this review, recent advances involving the synthesis of nitrogen heterocycles using SmI(2) 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.