Highly Regioselective Copper-Catalyzed C5- Sulfonylation Of 8-Aminoquinolines

Selective functionalization of C-H bonds is the goal of researchers for a long time in organic synthesis. Combination of transition metals and directing groups has been successfully transformed sp2-hybridized ortho- selective C-H bonds to C-O, C-X, C-C and C-N bonds. However, selective catalytic remote C-H bond activation methods for C-S bond formation remain relatively undeveloped. Besides, aryl sulfones are widely applied in synthetic chemistry. Therefore, it is necessary for organic methodology to synthesis aryl sulfones through selective remote C-H activation which is farther away from the directing group.This paper systematically studied an approach for copper-catalyzed regioselective C5-H sulfonylation of 8-aminoquinolines via bidentate-chelation assistance. The bidentate-chelation assisted cyclometalation could also possibly induce an unusual remote C5-H bond sulfonylation. 8-aminoquinoline derivatives and readily available and inexpensive sulfonyl chlorides were employed in DCE. It showed that CuBr(10 mol%)/K2CO3(1.0 equiv) catalytical system could obtain chelation-induced C5-sulfonation of quinolines in moderate to good yield. All of the C5-sulfonation products were confirmed by 1H NMR、13C NMR、HR-MS and X-ray crystallographic analysis. We could get designed product with different substituent groups of reaction substrates. The reactivity of arylsulfonyl chlorides was partly dependent on the electronic effect, but it produced moderate to excellent yield. And the yield is almost not affected by quinoline coupling partners. The reaction tolerated a broad range of the type of substitutes and substituted position in 8-aminequinolines to provide the corresponding C5-arylsulfonyl quinolines with good conversions. Importantly, we further studied the regioselectivity of sulfonylation. We found it could still smoothly convert to the corresponding product even if the position of the substituent is in C4- and C6- of quinoline or there is a sensitive groups in the C2- quinoline.In this paper, it shown that the probable mechanism is a free radical process, and we captured the sulfonyl free radical. In addition, according to the results of the control experiment, we considered it would form the Cu(II)-bidentate chelation. And theoretical investigation implicated that a single electron transfer process is involved in this sulfonylation transformation.