A HAT process of N-pyridyl radical cations for the synthesis of benzophenone-type bioisosteres†

N-Pyridyl radical cations are versatile synthetic intermediates, and interest in developing novel strategies for generating them and exploring their inherent reactivity is long-standing. Although Katritzky salts are powerful reagents for the generation of alkyl radicals via single-electron transfer and fragmentation, an alternative fragmentation pathway, that is, cleavage of the C–N bonds to afford alkyl radicals and nitrogen-centered pyridyl radical cations, would offer new synthetic opportunities and facilitate a process in N-pyridyl radical cation chemistry. In this study, we developed a photochemical method for generating alkyl radicals and N-pyridyl radical cations from Katritzky salts and reported the application of these radicals in novel functionalization reactions of [1.1.1]propellane to rapidly generate benzophenone-type bioisosteres. Mechanistic investigations indicate the light-induced, K₂HPO₄ promoted homolytic cleavage of the Katritzky salt C–N bond to produce an alkyl radical and an N-pyridyl radical cation and subsequent hydrogen atom transfer between the N-pyridyl radical cation and the aldehyde to generate an acyl radical. This mild method does not require a metal or photosensitizer and tolerates a broad range of functional groups. We demonstrated its utility by modifying a series of peptide feedstocks and drugs.