Regio‐Selective C−H Halogenation of 8‐Amido‐Quinolines under Transition Metal Free Conditions

Abstract

A transition metal free highly regioselective remote C−H halogenation has been developed. Oxidative halogenation (Cl, Br, I) of C5‐H of 8‐amido quinolone with inexpensive potassium persulfate as an oxidant and cheap halogenating agents like N‐halosuccinimide (NXS) or tetrabutylammonium halides (TBAX) were employed. Two reaction conditions were developed and in both routes have advantages such as C5‐selectivity, high to excellent yields (up to 98 %) and broad substrate scope. The reaction also carried out in water, open to air condition.

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

“…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)). The combination of photoredox and iron catalysis was applied by Wu, Yang, Wu and coworkers in this transformation (Scheme b (XI)) .…”

“…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.…”

“…[10] 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 CÀ H halogenation of such quinoline scaffolds by us and others. [11] Importantly, the alternative version of transition metal-free reactions of the same type have been recently realized by Watkins, [12] Xu, [13] Zhang, [14] Qiu [15] and Ghosh, [16] respectively.…”

Copper‐Catalyzed C‐4 Carboxylation of 1‐Naphthylamide Derivatives with CBr4/MeOH

“…carboxylation of styrene using cooperative Eosin-Y as photocatalyst and cobalt iodide as catalyst with CBr 4 and DMSO was reported by Tang and co-workers. [15] In continuation of our work on regioselective CÀ H bond functionalization, [16] herein, we report a simple and practical strategy for the regioselective carboxylation of 1-naphthalene amide derivatives at C-4 position by exploring bidentate chelation controlled SET strategy using carbon tetrabromide as C1-source. We began our studies using N-(naphthalene-1-yl) picolinamide (1a) as a model substrate for the carboxylation of 1naphthalne amide framework with CBr 4 and MeOH (2 mL).…”