Remote C−H Functionalization of 8‐Aminoquinolinamides

Abstract

Abstract8‐Aminoquinoline, a common structural motif present in many natural products, pharmaceuticals, agrochemicals, and important drugs has always been an attractive scaffold in synthetic organic chemistry. Recent years have witnessed the development of 8‐aminoquinoline as a ligand in transition‐metal‐catalyzed C−H functionalizations. Therefore, synthesis of functionalized 8‐aminoquinolines is of great importance and rapid generation of functionalized quinolines could be achieved by direct C−H functionalization. In this regard, since the seminal report of distal C5‐H halogenations of quinoline, diverse C−X bond formation reactions have been published. This review is focused on the C5‐H functionalization of 8‐aminoquinolinamide derivatives, including not only C−C bond formation reactions but also carbon–heteroatom bond formations such as C−X (X=F, Cl, Br, I) C−S, C−Se, C−N, C−O, and C−P. In most cases, the C5 position is activated by a single electron transfer method employing either metal catalysts, photocatalysts, or metal‐free conditions.

Copper/Silver Cocatalyzed Regioselective C5–H Functionalization of 8-Aminoquinoline Amides with 1,3-Dicarbonyl Compounds

“…A plausible reaction mechanism has been proposed according to the above experiments and previous work 9, 15,20 (Scheme 4). Firstly, cationic copper coordinates with the nitrogen atoms of the 8-aminoquinoline amide 1 to generate the intermediate A, which is converted into B via a singleelectron transfer (SET) process under the action of sulfate radical anions.…”

“…sulfonation, halogenation, amination and carbon-carbon bond formation using different metal catalysts, have been rapidly explored. 15,17 1,3-Dicarbonyl compounds are important and versatile synthons that are widely used in organic synthesis, and can be utilized in CDC reactions as a powerful strategy for the construction of structurally diverse molecules. 18 In such transformations, the methylenic sp 3 C-H bond in the 1,3-dicarbonyl compound is coupled with the C-H bond of another substrate in the presence of a metal catalyst.…”

“…quinoline amides in some transformations. 15 Therefore, to study the influence of copper catalysts in our reaction, we added a catalytic amount of copper acetate as a co-catalyst in this catalytic system, with the result indicating that the presence of the copper salt improved the transformation (entry 16). Next, the use of other copper salts was investigated, with the results indicating that Cu(OTf) 2 was a better catalyst than Cu(OAc) 2 (entries 16 and 17).…”

“…12 In recent years, 8-aminoquinoline derivatives have been widely used as an N,N-bidentate directing groups for arene ortho-C-H activation/functionalization. 13 In addition, we also note that quinoline scaffolds usually have sites that are more active toward C-H functionalization, i.e., C4-H 14 and C5-H. 15 Therefore, achieving regioselective C-H functionalization of quinolines is still a challenging task. A precedent for the remote functionalization of N-(8-quinolinyl)benzamide at C5 was established by Stahl and co-workers.…”

Transition Metal‐Free C5 Tosyloxylation of 8‐Aminoquinolines with Phenyliodine Bistrifluoroacetate and Substituted 1,2‐Disulfonyl Hydrazides

“…Recently, direct C–H functionalization at C5 position of quinoline has been realized including direct construction of C–C, C–N, C–S, C–X, C–O[9e], and C–Se (Scheme ) . To the best of our knowledge, few examples are known for the direct C–H functionalization of 8‐aminoquinolines at C5 position under metal‐free conditions.…”