Multicomponent Tandem Triple Functionalization of Indoles via a Directing‐group‐free Strategy

Abstract

The position-selective functionalization of the poorly reactive benzenoid nucleus of indoles has remained a great challenge in organic chemistry.Here we describe a directing-group-free, threecomponent tandem C3-acylation/C5,6-H disulfenylation of indoles via an iodine-, Lewis acid-and Brønsted acid-cooperated mediated strategy. This protocol is remarkable for its exceptional regio-and chemo-selectivity, broad substrate scope, good functional group tolerance and mild reaction conditions. Advantageously, the present protocol offers great potential for the development of general siteselective functionalization at the benzenoid nucleus of indoles, removing the requirement for neighbouring activating groups.

Directing-group-free strategy for the iodine-mediated regioselective dichalcogenation of indolines: understanding the full catalytic cycles

“…The present study combined our experimental results with previous reports to demonstrate that disulfide 2a undergoes a radical process with I 2 to generate intermediate 2a-1 in C5–H functionalization of indoline. 8 Notably, the formation of the relatively unstable intermediate PhSI is a prerequisite for all reactions. The comparable electronegativities of sulfur and iodine suggest that the S–I bond in PhSI may undergo homolytic cleavage leading to radicals PhS˙ and I˙, or heterolytic cleavage resulting in PhS + and I − species.…”

“…intermediate 2a-1 in C5-H functionalization of indoline 8. Notably, the formation of the relatively unstable intermediate PhSI is a prerequisite for all reactions.…”

Recent advances in selective mono-/dichalcogenation and exclusive dichalcogenation of C(sp2)–H and C(sp3)–H bonds

“…161 Very recently, Liang and coworkers described an unprecedented directing-group-free, three-component tandem C3-acylation/C5,6-dithiolation of indoles 76 with various anhydrides 85 and diaryl disulfides 33 under air atmosphere via an iodine-, Lewis acid- and Brønsted acid-cooperated mediated strategy (Scheme 25). 162 It is notable that electron-rich acyl substrates (R 5 = Ph, t Bu, OMe) failed to participate in the desired reactions due to their low electrophilicity ( 8h–j ). Moreover, the reaction of 3-cyanoindole led to an unexpected C2,5,6-trithiolated indole product 86 in an acceptable yield (17%).…”

Iron-Catalyzed Friedel–Crafts-type 3,5-Diacylation of Indoles

“…Light yellow solid (34 mg, 39% yield); mp 157.1− 157.8 °C; 1 H NMR (600 MHz,: δ 8.51 (d, J = 6.6 Hz, 1H), 7.97 (d, J = 1.1 Hz, 1H), 7.82 (d,J = 7.7 Hz,2H), 7.59 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 7.15 (d, J = 9.7 Hz, 1H), 3.93 (s, 3H). 13 C{ 1 H} NMR (151 MHz, Chloroform-d): δ 193.5, 174.8 (q, J = 35.7 Hz), 159.4, 157.8, 139.9 (q, J = 6.1, 5.6 Hz), 139.1 (d,J = 11.6 Hz),137.8,133.5,130.0,128.6,125.2 (d,J = 4.1 Hz), 124.2 (d, J = 17.0 Hz), 122.7, 116.9 (q, J = 290.8 Hz), 110.2, 98.1, 97.9, 34.4. 19 1-(5-Benzoyl-6-chloro-1-methyl-1H-indol-3-yl)-2,2,2-trifluoroethan-1-one (4maa).…”

“…Petroleum ether and ethyl acetate (7:1) were used as eluents. Yellow liqiud (16 mg, 20% yield); 1 H NMR (600 MHz,Chloroformd): δ 8.91 (d,J = 1.2 Hz,1H),7.91 (dd,J = 8.6,1.6 Hz,1H),7.86 (s,1H),2H),7.56 (t,J = 7.4 Hz,1H), 7.48 (t, J = 7.6 Hz, 2H), 7.42 (d, J = 8.6 Hz, 1H), 3.91 (s, 3H), 1.39 (s, 9H). 13 C{ 1 H} NMR (151 MHz, Chloroform-d): δ 202.…”