Copper-catalyzed C–N cross-coupling for construction of alkylated N-cyanamide derivatives via nitrogen umpolung

The cyano group is found in numerous bioactive compounds. Although cyano groups are easily introduced into target molecules by the formation of C–CN, the coupling of CN to nitrogen is more challenging because of the high electronegativity of that element. We have developed an efficient one-pot two-step method of preparing alkylated N-acyl cyanamides and cyanoformamides through a nitrogen-umpolung strategy. The strategy involves a Cu-nitrene transfer and a Cu-catalyzed N-alkylation, with various dioxazolones, trimethylsilyl cyanide (TMSCN), and halides. This transformation exhibits broad substrate scope and excellent functional-group tolerance by a straightforward procedure under mild conditions. Our reaction can also carry out the late-stage functionalization of complex natural products and pharmaceuticals.