Copper-Catalyzed Regioselective C–H Sulfonylation of 8-Aminoquinolines

Abstract

Copper(I)-catalyzed 5-sulfonation of quinolines via bidentate-chelation assistance has been developed. The reaction is compatible with a wide range of quinoline substrates and arylsulfonyl chlorides. Experimental and theoretical (DFT) investigation implicated that a single-electron-transfer process is involved in this sulfonylation transformation.

One‐pot reactions for the synthesis of 5‐sulfonyl quinolines via domino N‐acylation and remote C‐H sulfonylation

“…3‐Methyl‐ N ‐(5‐tosylquinolin‐8‐yl)butanamide ( 4d ) . Colorless liquid; 1 H NMR (400 MHz, CDCl 3 ): δ = 10.01 (s, 1 H), 9.04 (d, 1 H, J = 8.0 Hz), 8.89 (d, 1 H, J = 8.0 Hz), 8.81 (d, 1 H, J = 4.0 Hz), 8.49 (d, 1 H, J = 8.0 Hz), 7.81 (d, 2 H, J = 8.0 Hz), 7.56‐7.53 (m, 1 H), 7.25 (d, 2 H, J = 8.0 Hz), 2.45 (d, 2 H, J = 8.0 Hz), 2.35 (s, 3 H), 2.31‐2.26 (m, 1 H), 1.05 (d, 6 H, J = 4.0 Hz); 13 C NMR (100 MHz, CDCl 3 ): δ = 171.7, 148.5, 144.0, 139.8, 138.9, 138.0, 133.4, 132.0, 129.8, 129.0, 127.2, 124.2, 123.1, 114,1, 47.4, 26.2, 22.5, 21.5; ESI‐MS (M + H) + : 383.…”

“…N‐(5‐Tosylquinolin‐8‐yl)propionamide ( 4i ) . White solid; mp 137‐138°C; 1 H NMR (400 MHz, CDCl 3 ): δ = 10.07 (s, 1H), 9.07 (dd, J = 8.8, 1.6 Hz, 1H), 8.89 (d, J = 8.4 Hz, 1H), 8.82 (dd, J = 4.2, 1.6 Hz, 1H), 8.49 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 8.3 Hz, 2H), 7.56 (dd, J = 8.8, 4.2 Hz, 1H), 7.26 (d, J = 5.4 Hz, 3H), 2.63 (q, J = 7.6 Hz, 2H), 2.36 (s, 3H), 1.33 (t, J = 7.6 Hz, 3H).…”

“…Yet on the other hand, the sulfonylation of the C5‐H bond in the quinoline ring directed by the amide fragment has in recently years emerged as a highly useful tool in providing sulfonylated quinolines (B, Scheme ). Predominantly, the selective C5‐H sulfonylation of N ‐acyl 8‐aminoquinolines by employing sulfonyl chlorides as sulfonylating reagents has been reported by several groups via copper catalysis . Later on, sulfinate salts and sulfonyl hydrazides were also successfully utilized as the sulfonyl sources for the synthesis of these products, respectively.…”

“…Predominantly, the selective C5-H sulfonylation of N-acyl 8-aminoquinolines by employing sulfonyl chlorides as sulfonylating reagents has been reported by several groups via copper catalysis. [31][32][33] Later on, sulfinate salts [34,35] and sulfonyl hydrazides [36] were also successfully utilized as the sulfonyl sources for the synthesis of these products, respectively.…”

C–H Functionalization of Aromatic Amides

“…One year later, Zeng and co‐workers developed another method for the highly regioselective C‐5–H sulfonylation of 8‐aminoquinoline amides (Scheme ) . Compared with the former protocol, the reaction systems of the two methods are very similar.…”