Synthetic Diversity from a Versatile and Radical Nitrating Reagent

Abstract

We leverage the slow liberation of nitrogen dioxide from a newly discovered, inexpensive succinimide-derived reagent to allow for the C-H diversification of alkenes and alkynes. Beyond furnishing a library of aryl β-nitroalkenes, this reagent provides unparalleled access to β-nitrohydrins and β-nitroethers. Detailed mechanistic studies strongly suggest that a mesolytic N-N bond fragmentation liberates a nitryl radical. Using in situ photo-sensitized, electron paramagnetic resonance spectroscopy, we observed direct evidence of a nitryl radical in solution by nitrone spin-trapping. To further exhibit versatility of N-nitrosuccinimide under photoredox conditions, the late-stage diversification of an extensive number of C-H partners to prepare isoxazolines and isoxazoles is presented. This approach allows for the formation of an in situ nitrile oxide from a ketone partner, the presence of which is detected by the formation of the corresponding furoxan when conducted in the absence of a dipolarophile. This 1,3-dipolar cycloaddition with nitrile oxides and alkenes or alkynes proceeds in a single-operational step using a mild, regioselective, and general protocol with broad chemoselectivity.

Keywords: C−H nitration; alkenes; photoredox; radicals; reaction mechanisms.