Photoinduced generation of alkyl and phthalimide nitrogen radicals from N-hydroxyphthalimide esters for the synthesis of benzophenone-type bioisosteres

N-Hydroxyphthalimide (NHPI) esters have emerged as powerful sources of alkyl radicals generated by single-electron transfer, but homolysis of NHPI ester to produce an alkyl radical and a phthalimide nitrogen radical is still in its infancy. In this study, we developed a light-induced method for generation of alkyl and phthalimide nitrogen radicals from NHPI esters and subsequent reactions of the radicals with [1.1.1]propellane and aryl aldehydes for rapid generation of bicycle [1.1.1]pentane ketones. This method does not require metals or photosensitizers, features a broad substrate scope (90 examples) and excellent functional group tolerance, and can be used for the functionalization of structurally complex natural products and drugs. Mechanistic investigations indicate that the reaction involves photoinduced homolytic cleavage of the Cs₂CO₃-NHPI ester complex to produce alkyl and phthalimide nitrogen radicals and subsequent hydrogen atom transfer between the phthalimide nitrogen radical and the aldehyde to generate an acyl radical.