Dual Photoredox/Copper Catalysis for the Remote C(sp³)−H Functionalization of Alcohols and Alkyl Halides by N‐Alkoxypyridinium Salts

Abstract

Under mild dual photoredox/copper catalysis, the reaction of N‐alkoxypyridinium salts with readily available silyl reagents (TMSN3, TMSCN, TMSNCS) afforded δ‐azido, δ‐cyano, and δ‐thiocyanato alcohols in high yields. The reaction went through a domino process involving alkoxy radical generation, 1,5‐hydrogen atom transfer (1,5‐HAT) and copper‐catalyzed functionalization of the resulting C‐centered radical. Conditions for catalytic enantioselective δ‐C(sp3)−H cyanation were also documented.

Pyridinium Salts as Redox‐Active Functional Group Transfer Reagents

“…Bao and Zhu recently combined similar 1,5-HATp rocesses with copper-catalyzed cross-coupling reactions (Scheme 20). [86] This dual catalytic system enabled the remote introduction of azido,c yano,a nd thiocyanato groups from readily available N-alkoxy pyridinium salts 37.Notably, the transformation can be rendered enantioselective through the use of acopper co-catalyst bearing ac hiral ligand.…”

Organophotocatalytic Remote Thiocyanation Reaction via Ring‐Opening Functionalization of Cycloalkanols

“…Recently, the development of radical thiocyanation reactions has greatly enriched the synthesis methodology of remote alkyl thiocyanates (Scheme 1C). In 2019, Zhu and co‐workers [9c] developed a remote C(sp 3 )−H thiocyanation by N ‐alkoxypyridinium salts under dual photoredox/copper catalysis. In 2020, Zhang's [9a] and Liu's [9b] group independently disclosed an intermolecular C(sp 3 )−H site‐selective thiocyanation of aliphatic sulfonamides catalysed by Cu(I) complexes.…”

Remote C(sp3)−H Arylation and Vinylation of N‐Alkoxypyridinium Salts to δ‐Aryl and δ‐Vinyl Alcohols

“…[12] However,i nm ost of the cases,over stoichiometric amounts of oxidantare generally required to derivatize in situ the hydroxyl group to aw eaker OÀXb ond, with Zou'sc onditions being an otable exception. [11] On the other hand, N-alkoxyphthalimides [13][14][15] and N-alkoxypyr-idinium [16][17][18] have recently been shown to be excellent precursors of the alkoxyl radicals under reductivec onditions. Besides classica tom/group transfer reactions, [19] other interesting transformationsh ave been developed for the synthesis of d-functionalized alcohols.…”

“…The arylation of easily availablea nd bench-stable N-alkoxypyridiniums alt 1a (Ar = Ph)u sing 4-(tert-butyl)phenylboronic acid (2a)w as chosen as at est reaction( Scheme 2). Under the conditions developed previously for the azidation of 1a [fac-Ir(ppy) 3 (0.02 equiv), CuOAc (0.2 equiv), 1,10-phenanthroline (0.3 equiv), Blue LEDs, RT], [18] the reactiono f1a with 2a failed to produce the coupled product 3aa.A dding ad ifferentb ase into the reactionm ixture had no positive effect. In most of the cases, 2-phenyltetrahydrofuran was formeda st he main product.…”