Recent Advances on the C-H Bond Functionalization on C(5) Position of 8-Aminoquinolines

Abstract

8-Aminoquinolines are important nitrogen-containing heterocycles widely existing in the natural products, bio-active molecules and agrochemicals. It has been developed as significant bidentate directing groups or as ligand auxiliary in various kinds of organic reactions, especially in the area of C-H bond functionalization. Therefore, the synthesis of such motifs, especially those with substituted quinolines is of great significance. This review focuses on the remote C-H bond functionalizaitons of 8-aminoquinolines on the C(5) position, including the advantages and disadvantages as well as an outlook in this field.

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

“…Recent years have witnessed much progress in halogenation reactions of the quinoline ring in the C2–C7 positions [ 8 – 9 ]. Among them, the synthesis of important C5-halogenated products gained particular attention since Stahl et al reported the first chlorination example using LiCl as the halogen source [ 10 ].…”

Copper-catalyzed selective C5-H bromination and difluoromethylation of 8-aminoquinoline amides using ethyl bromodifluoroacetate as the bifunctional reagent

“… 11 Since Stahl et al 12 reported the first instance of cuprous-catalyzed chlorination using lithium chloride in an oxygen atmosphere, remote C5-functionalization has garnered particular interest. 13 Recent efforts have been focused on C–C, 14 C–N, 15 C–P, 16 C–O, 17 C–S 18 and C–X 19 bond construction through direct C5-H functionalization via transition-metal-catalyzed reactions as well as by employing metal-free conditions.…”

Carbon–Carbon Bond Formation of Trifluoroacetyl Amides with Grignard Reagents via C(O)–CF3 Bond Cleavage

“…Herein, as part of our continuous works on the development of cross-coupling reaction utilizing Grignard reagents as key coupling partner as well as on the functionalization of aminoquinoline, we disclose an efficient protocol for site-selective cleavage of C­(O)–CF 3 bond of a wide range of trifluoroacetyl amides by Grignard reagents (Scheme b2). Trifluoroacetanilides, 2,2,2-trifluoro- N -(quinolin-8-yl)­acetamide and N -alkyl-2,2,2-trifluoroacetamide are well tolerated in this protocol.…”