Visible‐Light‐Induced Pyridylation of Remote C(sp³)−H Bonds by Radical Translocation of N‐Alkoxypyridinium Salts

Abstract

Metal-free,v isible-light-induced site-selective heteroarylation of remote C(sp 3 ) À Hb onds has been accomplished through the design of N-alkoxyheteroarenium salts serving as both alkoxy radical precursors and heteroaryl sources.T he transient alkoxy radical can be generated by the single-electron reduction of an N-alkoxypyridinium substrate by ap hotoexcited quinolinone catalyst. Subsequent radical translocation of the alkoxy radical forms an ucleophilic alkylr adical intermediate,w hich undergoes addition to the substrate to achieve remote C(sp 3 ) À Hh eteroarylation. This cascade strategy provides ap owerful platform for remote C(sp 3 ) À H heteroarylation in ac ontrollable and selective manner and is well suited for late-stage functionalization of complex bioactive molecules.

Pyridinium Salts as Redox‐Active Functional Group Transfer Reagents

“…Hong and co-workers have designed N-alkoxy pyridinium 32,which serves as both an alkoxy radical precursor as well as ah eteroaryl source for subsequent radical trapping (Scheme 19). [84] After generation of the transient alkoxy radical mediated by ap hotoexcited quinolinone catalyst 33, radical translocation of the alkoxy radical 34 by 1,5-HAT generates an ucleophilic alkyl radical intermediate 35.A lkyl radical 35 undergoes addition to pyridinium 32 to achieve remote C(sp 3 ) À Hh eteroarylation while generating an ew oxygen-centered radical 34.Notably,ifthe substrate contains an olefinic bond in the 5-position, radical ring-closure and subsequent pyridination is observed. [85] Scheme 16.…”

Visible‐Light‐Active Coumarin‐ and Quinolinone‐Based Photocatalysts and Their Applications in Chemical Transformations

“…In 2018, we reported a metal‐free, visible‐light‐induced site‐selective remote C(sp 3 )−H bond heteroarylation reaction based on the use of photocatalyst Q 1 (Scheme 22), [35] where in the N ‐alkoxyheteroarenium salt was used as both an alkoxy radical source and a heteroarene source. During this process, it was determined that the photoexcited Q 1 * enables the production of the alkoxy radical via a single‐electron reduction of the N ‐alkoxyheteroarenium salt.…”

Radical Functionalization of Remote C(sp 3 )–H Bonds Mediated by Unprotected Alcohols and Amides

“…These surrogates are then harnessed to deliver alkoxy radicals under ultraviolet irradiation or heat. [13][14][15][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] Formation of alkoxy radicals direct from free alcohols would extend the generality and scope of alkoxy radical-mediated site-selective C(sp 3 )-H bond transformation and significantly improve the atom and step economy of the method. However, while not affecting other chemical bonds with lower BDEs (e.g., BDEs of common alkyl C-H bonds < 101 kcal/mol), transformation of alcoholic O-H bonds to alkoxy radicals by using simple oxidation conditions remains elusive.…”