Metal-free C5-selective halogenation of quinolines under aqueous conditions

Abstract

An efficient and convenient method of C5-selective halogenation of quinoline derivatives was developed.

A general method for the metal-free, regioselective, remote C–H halogenation of 8-substituted quinolines

“…These results are in good agreement with previous reports of C5 halogenation reactions via radical mechanisms. 12h , 12i , 13c , 13f , 13g , 15 , 16 Based on the above results and literature reports, 19 a plausible mechanism via a radical pathway is proposed (see ESI † ).…”

“… 17 Although these halogenations of quinoline have been reported, a facile and metal-free reaction for C5-halogenation is still rare. 18 , 19 Additionally, the reported methods have several limitations. For instance, to the best of our knowledge in the reported examples the substrate scope is largely restricted to 8- NH -amides of quinolines.…”

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

“…C5 and C7 dibromination was achieved by Zhang, Zhou and Shen et al., and only C5 bromination could be attained when the amount of NaBr and PhI(OAc) 2 were reduced from 4 to 2 equivalents (Scheme b (VI)) . Highly efficient C5 bromination was developed by Xu, Wang and coworkers just by using NBS under aqueous conditions in 15 mins (Scheme b (VII)) . Using K 2 S 2 O 8 as oxidant and bromide as bromine source, Zhang group (NaBr), Ghosh group (TBAB) and Sun group (LiBr) reported this reaction almost simultaneously (Scheme b (VIII), (IX)&(X)).…”

“…Based on the results of previous reports, the proposed mechanism of this transformation was illustrated in Scheme . The excited photoredox catalyst PTH* can be oxidative quenched by CBr 4 .…”

Transition‐Metal‐free C5, C7‐Dihalogenation and the Switchable C5 Halogenation of 8‐Hydroxyquinolines

“…Later on, a series of other transition metal catalysts, including different copper, palladium, nickel and iron reagents have been successfully employed to catalyze the remote C−H halogenation of such quinoline scaffolds by us and others . Importantly, the alternative version of transition metal‐free reactions of the same type have been recently realized by Watkins, Xu, Zhang, Qiu and Ghosh, respectively. Regardless these notable advances in the quinoline C−H halogenation reactions, the reliance on the amide substitution as directing group (DG) is a severe restriction to the molecular diversity of the synthesized haloquinolines by these methods.…”