Metal-free site-selective C–H cyanoalkylation of 8-aminoquinoline and aniline-derived amides with azobisisobutyronitrile

Abstract

An efficient metal-free cyanoalkylation of 8-aminoquinoline and aniline-derived amides was achieved in the presence of K2S2O8. The method showed good substrate tolerance and also suitable for bromination and dimerization reactions.

FeIII/TBHP mediated remote C–O bond construction of 8-aminoquinolines: access to methoxylation and cyanomethoxylation

“…Notably, different from our previous work on the activation of 8-aminoquinoline through the N-radical pathway, no N-radical species are detected, demonstrating a different mechanism from our previous studies. 22 On the basis of the exploration and previous literature reports, 15,18b,c a tentative mechanism for the Fe III /TBHP system involved methoxylation and cyanoalkoxylation reactions was proposed as shown in Scheme 5. Initially, TBHP is induced by Fe 3+ to generate t BuOO • and the Fe 3+ is reduced to Fe 2+ at the same time (eqn (1)).…”

“…Notably, different from our previous work on the activation of 8-aminoquinoline through the N-radical pathway, no N-radical species are detected, demonstrating a different mechanism from our previous studies. 22…”

tBu4NCl/K2S2O8 System Induced C‐2 Functionalization of 8‐Aminoquinoline Amides with Primary Alcohols

“…The proposed mechanisms were depicted on the basis of above experimental observations and previous literature (Scheme 6). [15d,16] Initially, K 2 S 2 O 8 and Cl anion generated chlorine radical through a SET process. The chlorine radical then acts as a HAT reagent, extracting the α‐C−H from the alcohol to provide the ketyl radical along with a molecule of hydrogen chloride (equation 1).…”

Recent Advances on Radical-Mediated Cyanoalkylation/Cyanation using AIBN and Analogues as the Radical Sources

“…In 2021, Li and co-workers developed a metal-free siteselective C-H cyanoalkylation protocol of 8-aminoquinoline initiated by AIBN (Scheme 41 Electron-donating substitution groups on the 8-aminoquinoline ring increased the yields, while electron-withdrawing groups decreased the yields. Desired product was gained in moderate to excellent yields according to different substitution groups.…”