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

A metal and light-free Minisci-type acylation approach of 8-aminoquinoline amides with general primary alcohols was demonstrated under (Bu4NCl)-Bu-t/K2S2O8 system. Simultaneously, the C2-H alkylation can be realized by accident for special benzyl alcohols bearing strong electron-donating groups. Most N-heterocycles were also compatible to afford corresponding acylated products. Furthermore, the mechanism investigation reveals that chlorine radical induced the original ketyl radical generation through abstracting the alpha-C-H from the alcohols, then underwent nucleophilic carbon-centered radicals addition, deprotonation, and oxidation to provide the target acylation products.

Automated summary

A metal and light-free Minisci-type acylation approach was developed for 8-aminoquinoline amides with general primary alcohols under (Bu4NCl)-Bu-t/K2S2O8 system. Unexpected C2-H alkylation can occur for specific benzyl alcohols with strong electron-donating groups. Most N-heterocycles are also compatible for the formation of acylated products. Mechanistic investigation reveals the involvement of chlorine radical in generating ketyl radical from alcohols, followed by nucleophilic carbon-centered radicals addition, deprotonation, and oxidation to form the desired acylation products.