The Highly Regioselective Halogenation of N‐(8‐quinolinyl)amides on the C‐5 Position with Cuprous Halides Under Mild Conditions

Abstract

Regioselective halogenation of heteroaromatics via C−H activation is a challenge in organic synthesis. In this paper, we described a simple, mild and highly selective protocol for halogenating C‐5 of N‐(8‐quinolinyl) amides with cuprous halides in the presence of NFSI (N‐Fluorobenzenesulfonimide) at room temperature. The different chloro‐, bromo‐ and iodo‐ substituted N‐(8‐quinolinyl) amides on C‐5 position were obtained respectively in good yields with excellent substrates tolerance.

Iron(III)-Catalyzed Highly Regioselective Halogenation of 8-Amidoquinolines in Water

“…Based on our work, as well as existing literatures [20,21,22,23,24,25,26,27], a plausible reaction pathway was proposed, as shown in Scheme 9. At first, substrate 1 and Fe(III) species formed complex A, which was transformed to be complex B after deprotonation [41,47].…”

“…Similarly, Zhang, Li, Huang, etc. described copper-catalyzed C5 C-H halogenation of 8-amidoquinolines (Scheme 2a) [21,22,23,24,25,26,27]. Meanwhile, Li and other groups also reported transition metal-free C5 halogenation of 8-amidoquinolines (Scheme 2b) [28,29,30,31].…”

Visible Light Mediated External Oxidant Free Selective C5 Bromination of 8‐Aminoquinoline Amides under Ambient Conditions

“…Since this research focused on the C5 bromination of 8‐aminoquinoline amides, the previous achievements on this area were summarized in Scheme b . Using CuBr as bromine source and NFSI ( N ‐Fluorobenzenesulphonimide) as oxidant, Li group and Zhu, Xu et al . reported this transformation nearly at the same time (Scheme b(I)&(II)).…”

Recent Strategies for Carbon−Halogen Bond Formation Using Nickel

“…[35] Based on their previous studies using stoichiometric copper salts to induce the C À Xbond formation, the authors hypothesized that NFSI could also be used as an electrophilic fluorine source in an ickel-catalyzed CÀHf luorination process (Scheme 10, top). [36] Following the reaction optimization studies using different transition metal catalysts and fluorinating agents, NFSI and NiSO 4 were found to give the highest product yields (Scheme 10, bottom). Thes ubstrate scope illustrated tolerance of sterically bulky aliphatic substituents and electronwithdrawing aryl substituents,h eterocyclic substituents,a s well as aliphatic substituents on the quinoline ring.…”