Copper-Promoted N-Arylation of 8-Acylaminoquinoline Compounds

Abstract

A copper-promoted N-arylation of 8-acylaminoquinolines has been developed. The N-arylation of 8-acylaminoquinoline with triaryl bismuth generated the target products in moderate to high yields under 40 mol% Cu(OAc) 2 , 2.0 equiv. of NaHCO 3 in 1,4-dioxane at 100 ℃ for 12 h. The reaction is compatible with a wide range of quinoline substrates, which provides a new method for synthesis of N-arylamide compounds.

Copper-Catalyzed Base-Free N-Arylation of 8-Aminoquinoline Amides through Chelation Assistance

“…5 Li and co-workers recently realized a copper-promoted N-arylation of 8-acylaminoquinolines with triarylbismuth reagents. 6 During the preparation of our manuscript, the Yin group reported a copper(0)-induced arylation of phosphinamides with arylboronic acids. 7 Consequently, the development of an efficiently alternative synthetic route for the functionalization of the N-H bond of 8-aminoquinolines remains of utmost importance.…”

“…Finally, the influence of the iodonium counterion was investigated, and the triflate and tetrafluoroborate both failed to cause reaction under the standard conditions (entries 20 and 21). When mesityl(phenyl)iodonium hexafluorophosphate was used instead of its diphenyl analogue, a lower yield (63%) was obtained (entry 22), showing that [PhI + Ph]PF 6 is more active than [PhI + Mes]PF 6 in this transformation. With the best reaction conditions in hand (Table 1, entry 7), we examined the scope of the reaction for the phenylation of 8-aminoquinoline amides 1 with the iodonium salt 2a (Figure 1).…”