Versatile, tunable method for NaNO2/HX (Cl or Br)–mediated radical dihalogenation or nitration of olefins

Abstract

We have developed a versatile, tunable method for NaNO2/HX (Cl or Br)–mediated radical nitration or vicinal dihalogenation of olefins. The method allowed us to synthesize high-added-value vicinal dihalides by using inexpensive, low-molecular-weight HCl or HBr as a chloride or bromide source and commercially available NaNO2 under irradiation with blue LEDs without the need for a photocatalyst or metal catalyst. In the absence of light, reactions of the olefins with NaNO2 and HCl gave nitration products in a controllable fashion. This highly tunable reaction system was compatible with a diverse array of olefin substrates, showed good functional group tolerance, and was successfully used for late-stage dihalogenation and nitration of dozens of derivatives of natural products and active pharmaceutical ingredients. Mechanistic studies showed that in the dihalogenation reactions, a nitrosyl halide (X–N=O) generated in situ by reaction of NaNO2 and aqueous HX not only delivered a halogen radical upon photoirradiation to initiate olefin dihalogenation but also underwent halogen-atom transfer (XAT) process with a carbon radical intermediate to form the vicinal dihalogenation product. In the nitration reactions, a nitric oxide (NO or NO2) that was formed in situ from NaNO2 and the same equivalent of HCl selectively triggered olefin nitration.