Anomeric Nitroamide Enabled, Cobalt Catalyzed Alkene Hydronitration

Tertiary nitroalkanes, as well as its reduced products, α-tertiary amines, play an essential role in drug discovery either as key synthetic precursors or final incorporation in targeted molecules. Existing methods to prepare tertiary nitro compounds generally rely on polar-bond disconnections, in which strong bases or highly active electrophiles are needed. Here, we report the development of an anomeric nitroamide-based reagent that enables exquisitely selective MHAT-based Co-catalyzed alkene hydronitration for the preparation of valuable tertiary nitro compounds. This mild, scalable reaction shows broad functional group tolerance, is applied to a variety of structures. Late-stage nitration of complex contexts (9 examples) derived from drugs and natural products is also pursued. Its high prowess is further highlighted in simplifying the synthesis of a rare naturally occurring nitro sugar. Simple access to isotopically labeled 15N-containing nitro compounds is also disclosed. The anomeric nitroamide reagent was deemed safe by energetic measurements and its unique reactivity rationalized based on X-ray crystallographic analysis.