Metal-free C3—H Acetoxylation of Indoles Promoted by PhI(OAc)2†

doi:10.7503/cjcu20150716

Abstract

Abstract:

3-Substituted indoles are common structural motifs in a series of natural products, pharmaceuticals and biologically active compounds. Metal-free reaction was emerged as one of the most powerful tools for functionalization of indoles due to its environment friendly features. In this work, the metal-free C3—H acetoxylation of indoles and PhI(OAc)₂ was developed. The optimized reaction conditions were established by examination of the substituent, temperature and amounts of PhI(OAc)₂. A series of 3-acetoxyindoles could be obtained in HOAc at 60 ℃ without additives. The yield of product ranged from 45% to 86%. The structures were characterized by infrared(IR), nuclear magnetion resonance(NMR), high resolution mass spectra(HRMS) and X-ray diffraction techniques and a possible reaction mechanism was then proposed. Moreover, this reaction system was also feasible in a gram-scale reaction without significant decrease in the product yields.

Key words: Metal-free, Diacetoxyiodobenzene, Indole, Acetoxylation

CLC Number:

O626.1

TrendMD:

WANG Liang, QU Xing, LI Zhan, GU Changhan, HU Siqian. Metal-free C3—H Acetoxylation of Indoles Promoted by PhI(OAc)₂^†[J]. Chem. J. Chinese Universities, 2016, 37(2): 254.

Figures/Tables 7

Scheme 1 Synthetic route for C3—H acetoxylation of indoles 2a: R1=H, R2=H; 2b: R1=4-Me, R2=H; 2c: R1=4-OBn, R2=H; 2d: R1=4-Cl, R2=H; 2e: R1=4-CO2Me, R2=H; 2f: R1=5-Me, R2=H; 2g: R1=5-OMe, R2=H; 2h: R1=5-OBn, R2=H; 2i: R1=5-OPh, R2=H; 2j: R1=5-Cl, R2=H; 2k: R1=5-Br, R2=H; 2l: R1=6-Me, R2=H; 2m: R1=6-CO2Me, R2=H; 2n: R1=6-F, R2=H; 2o: R1=6-Cl, R2=H; 2p: R1=6-Br, R2=H; 2q: R1=5,6-Ph, R2=H; 2r: R1=H, R2=Me; 2s: R1=H, R2=Ph; 2t: R1=H, R2=Br

Table 1 Appearance, yields, melting points, HRMS and IR data of compounds 2a—2t

Compd.	Appearance	Yield^*(%)	m. p./℃	HRMS(calcd.), m/z [M+Na⁺]	IR(KBr), $ν ˙$ /cm^-1
2a	White solid	85	123—124	276.0747(276.0743)	3195, 1743, 1573, 1458, 1428, 1369, 1316, 1208, 1158, 1124, 1073,1015
2b	Yellow solid	76	143—144	290.0925(290.0900)	3203, 2923, 2854, 1753, 1568, 1433, 1354, 1300, 1198, 1147
2c	White solid	63	127—128	382.1155(382.1162)	3210, 1738, 1573, 1499, 1448, 1362, 1271, 1232, 1160, 1096, 1064, 913
2d	White solid	73	155—156	310.0352(310.0354)	3192, 1756, 1563, 1452, 1360, 1309, 1212, 1001, 891, 770
2e	White solid	75	134—135	334.0789(334.0798)	2955, 1749, 1713, 1570, 1357, 1283, 1190, 1091, 1020, 954, 902, 740
2f	White solid	78	165—166	290.0900(290.0900)	3201, 1746, 1581, 1456, 1426, 1353, 1202, 1147, 1122, 864
2g	Yellow solid	80	166—167	306.0849(306.0849)	3209, 1744, 1536, 1436, 1366, 1210, 1075, 1020, 905, 801, 766, 747
2h	White solid	65	166—167	382.1128(382.1162)	3194, 1749, 1576, 1479, 1453, 1296, 1203, 1078, 1013, 919
2i	White solid	86	139—140	368.1009(368.1006)	3219, 1747, 1565, 1471, 1421, 1361, 1289, 1198, 1072, 965, 922
2j	Yellowish solid	83	181—182	310.0335(310.0354)	3206, 1756, 1573, 1459, 1373, 1346, 1292, 1203, 1065
2k	Yellowish solid	85	182—183	353.9846(353.9846)	3023, 1787, 1735, 1456, 1353, 1147, 1014, 919, 855, 784
2l	White solid	83	153—154	290.0875(290.0900)	3195, 2971, 2856, 1742, 1573, 1436, 1368, 1321, 1212, 1131, 789
2m	Yellow solid	63	199—200	334.0896(334.0798)	3197, 1752, 1717, 1571, 1441, 1373, 1280, 1210, 1140, 1064, 990
2n	Reddish solid	77	167—168	294.0660(294.0649)	3197, 1745, 1575, 1441, 1370, 1208, 1104, 976, 905, 855, 792
2o	White solid	70	179—180	310.0339(310.0354)	3199, 1793, 1744, 1440, 1367, 1209, 1129, 1066, 957, 792, 506
2p	White solid	80	178—179	353.9838(353.9849)	3202, 1746, 1577, 1441, 1367, 1209, 1128, 1080, 1001, 954, 786
2q	White solid	45	155—157	326.0901(326.0900)	3211, 1746, 1571, 1459, 1427, 1363, 1297, 1220, 1130, 1023, 883, 775
2r	Yellowish solid	84	158—159	290.0900(290.0900)	3207, 1745, 1598, 1556, 1444, 1366, 1317, 1207, 1008, 742
2s	White solid	81	133—134	352.1062(352.1056)	3195, 1752, 1589, 1548, 1444, 1366, 1197, 1123, 1009, 887, 746
2t	White solid	72	182—183	353.9681(353.9849)	3199, 1746, 1598, 1557, 1440, 1317, 1207, 1116, 1010, 743

Table 1 Appearance, yields, melting points, HRMS and IR data of compounds 2a—2t

Compd.	Appearance	Yield^*(%)	m. p./℃	HRMS(calcd.), m/z [M+Na⁺]	IR(KBr), $ν ˙$ /cm^-1
2a	White solid	85	123—124	276.0747(276.0743)	3195, 1743, 1573, 1458, 1428, 1369, 1316, 1208, 1158, 1124, 1073,1015
2b	Yellow solid	76	143—144	290.0925(290.0900)	3203, 2923, 2854, 1753, 1568, 1433, 1354, 1300, 1198, 1147
2c	White solid	63	127—128	382.1155(382.1162)	3210, 1738, 1573, 1499, 1448, 1362, 1271, 1232, 1160, 1096, 1064, 913
2d	White solid	73	155—156	310.0352(310.0354)	3192, 1756, 1563, 1452, 1360, 1309, 1212, 1001, 891, 770
2e	White solid	75	134—135	334.0789(334.0798)	2955, 1749, 1713, 1570, 1357, 1283, 1190, 1091, 1020, 954, 902, 740
2f	White solid	78	165—166	290.0900(290.0900)	3201, 1746, 1581, 1456, 1426, 1353, 1202, 1147, 1122, 864
2g	Yellow solid	80	166—167	306.0849(306.0849)	3209, 1744, 1536, 1436, 1366, 1210, 1075, 1020, 905, 801, 766, 747
2h	White solid	65	166—167	382.1128(382.1162)	3194, 1749, 1576, 1479, 1453, 1296, 1203, 1078, 1013, 919
2i	White solid	86	139—140	368.1009(368.1006)	3219, 1747, 1565, 1471, 1421, 1361, 1289, 1198, 1072, 965, 922
2j	Yellowish solid	83	181—182	310.0335(310.0354)	3206, 1756, 1573, 1459, 1373, 1346, 1292, 1203, 1065
2k	Yellowish solid	85	182—183	353.9846(353.9846)	3023, 1787, 1735, 1456, 1353, 1147, 1014, 919, 855, 784
2l	White solid	83	153—154	290.0875(290.0900)	3195, 2971, 2856, 1742, 1573, 1436, 1368, 1321, 1212, 1131, 789
2m	Yellow solid	63	199—200	334.0896(334.0798)	3197, 1752, 1717, 1571, 1441, 1373, 1280, 1210, 1140, 1064, 990
2n	Reddish solid	77	167—168	294.0660(294.0649)	3197, 1745, 1575, 1441, 1370, 1208, 1104, 976, 905, 855, 792
2o	White solid	70	179—180	310.0339(310.0354)	3199, 1793, 1744, 1440, 1367, 1209, 1129, 1066, 957, 792, 506
2p	White solid	80	178—179	353.9838(353.9849)	3202, 1746, 1577, 1441, 1367, 1209, 1128, 1080, 1001, 954, 786
2q	White solid	45	155—157	326.0901(326.0900)	3211, 1746, 1571, 1459, 1427, 1363, 1297, 1220, 1130, 1023, 883, 775
2r	Yellowish solid	84	158—159	290.0900(290.0900)	3207, 1745, 1598, 1556, 1444, 1366, 1317, 1207, 1008, 742
2s	White solid	81	133—134	352.1062(352.1056)	3195, 1752, 1589, 1548, 1444, 1366, 1197, 1123, 1009, 887, 746
2t	White solid	72	182—183	353.9681(353.9849)	3199, 1746, 1598, 1557, 1440, 1317, 1207, 1116, 1010, 743

Table 2 1H NMR and 13C NMR data of compounds 2a—2t

Compd.	¹H NMR(400 MHz, CDCl₃), δ	¹³C NMR(100 MHz, CDCl₃), δ
2a	8.81(d,J=8.4 Hz, 1H), 8.67(d, J=4.8 Hz, 2H), 8.43(s, 1H), 7.56(d, J=7.8 Hz, 1H), 7.37(t, J=7.5 Hz, 1H), 7.29—7.25(m, 1H), 7.02(t, J=4.8 Hz, 1H), 2.40(s, 3H)	168.2, 158.1, 157.8, 133.5, 132.8, 124.6, 124.0, 122.2, 117.5, 116.4, 116.1, 114.6, 21.1
2b	8.73—8.59(m, 3H), 8.36(s, 1H), 7.24(dd, J=10.3, 5.1 Hz, 1H), 7.02—6.92(m, 2H), 2.63(s, 3H), 2.37(s, 3H)	168.7, 158.1, 157.7, 134.3, 133.2, 129.4, 124.5, 123.9, 122.7, 116.0, 114.8, 114.1, 29.7, 21.3, 18.8
2c	8.66(d,J=4.8 Hz, 2H), 8.44(d, J=8.4 Hz, 1H), 8.06(s, 1H), 7.54—7.48(m, 2H), 7.40(dd, J=9.7, 5.6, 1.4 Hz, 3H), 7.25(d, J=4.6 Hz, 1H), 7.02(t, J=4.8 Hz, 1H), 6.74(d, J=7.9 Hz, 1H), 5.11(s, 2H), 1.91(s, 3H)	169.8, 158.1, 157.7, 152.0, 136.9, 135.1, 133.2, 128.5, 128.4, 128.2, 125.4, 116.2, 114.5, 114.2, 110.0, 104.1, 70.4, 20.4
2d	8.79—8.72(m, 1H), 8.66—8.61(m, 2H), 8.27(d, J=2.0 Hz, 1H), 7.20(t, J=7.7 Hz, 2H), 7.02(t, J=4.8, 3.4 Hz, 1H), 2.39(s, 3H)	169.5, 158.1, 157.2, 134.6, 132.2, 125.0, 124.2, 123.3, 121.4, 116.9, 116.6, 115.3, 21.1
2e	9.12(d,J=8.5 Hz, 1H), 8.66(d, J=4.7 Hz, 2H), 8.31(s, 1H), 7.82(d, J=7.5 Hz, 1H), 7.37(t, J=8.0 Hz, 1H), 7.05(t, J=4.6 Hz, 1H), 3.91(d, J=13.3 Hz, 3H), 2.41(s, 3H)	170.1, 167.2, 158.2, 157.3, 134.5, 132.8, 125.4, 123.5, 123.0, 122.5, 120.7, 118.7, 116.7, 52.2, 21.0
2f	8.69—8.59(m, 3H), 8.36(s, 1H), 7.33(s, 1H), 7.18(d, J=8.5 Hz, 1H), 6.97(t, J=4.2 Hz, 1H), 2.47(s, 3H), 2.39(s, 3H)	168.2, 158.1, 157.7, 133.3, 131.7, 131.2, 126.1, 124.2, 117.2, 116.2, 115.9, 114.6, 21.4, 21.1
2g	8.66(dd,J=22.8, 6.8 Hz, 3H), 8.39(s, 1H), 6.98(d, J=8.2 Hz, 3H), 3.89(s, 3H), 2.40(s, 3H)	168.1, 158.1, 157.6, 155.6, 133.4, 127.8, 124.7, 117.5, 115.8, 115.1, 114.0, 99.4, 55.7, 21.1
2h	8.70(d,J=8.7 Hz, 1H), 8.63(d, J=4.7 Hz, 2H), 8.40(s, 1H), 7.49(d, J=7.5 Hz, 2H), 7.40(t, J=7.3 Hz, 2H), 7.36—7.30(m, 1H), 7.06(d, J=9.8 Hz, 2H), 6.98(t, J=4.6 Hz, 1H), 5.13(s, 2H), 2.39(s, 3H), 5.13(s, 2H), 2.39(s, 3H)	168.1, 158.1, 157.6, 154.8, 137.3, 133.4, 128.6, 127.9, 127.7, 124.7, 117.6, 115.9, 115.2, 114.5, 101.0, 70.6, 21.1
2i	8.83—8.76(m, 1H), 8.67(d, J=4.8 Hz, 2H), 8.46(s, 1H), 7.38—7.29(m, 2H), 7.20(d, J=2.4 Hz, 1H), 7.14—6.99(m, 5H), 2.35(s, 3H)	168.1, 158.6, 158.1, 157.6, 152.0, 133.3, 129.7, 129.5, 125.0, 122.5, 117.8, 117.6, 116.1, 115.7, 107.9, 21.0
2j	8.84—8.61(m, 3H), 8.44(s, 1H), 7.52(s, 1H), 7.36—7.24(m, 1H), 7.05(s, 1H), 2.39(s, 3H)	168.0, 158.2, 157.5, 132.6, 131.1, 127.9, 125.1, 124.8, 117.7, 117.1, 116.4, 115.9, 21.0
2k	8.67(t,J=7.2 Hz, 3H), 8.42(s, 1H), 7.68(s, 1H), 7.43(d, J=8.9 Hz, 1H), 7.04(t, J=4.7 Hz, 1H), 2.39(s, 3H)	168.0, 158.2, 157.4, 132.4, 131.4, 127.4, 125.6, 120.2, 118.1, 116.4, 115.7, 115.5, 21.0
2l	8.81—8.55(m, 3H), 8.34(s, 1H), 7.42(d, J=7.9 Hz, 1H), 7.09(d, J=7.8 Hz, 1H), 6.98(t, J=4.7 Hz, 1H), 2.53(s, 3H), 2.38(s, 3H)	168.2, 158.1, 157.8, 134.7, 133.6, 133.2, 123.8, 121.9, 117.1, 116.5, 115.9, 113.9, 22.2, 21.1
2m	9.50(s, 1H), 8.72(d,J=4.6 Hz, 2H), 8.58(s, 1H), 7.95(d, J=8.3 Hz, 1H), 7.59(d, J=8.3 Hz, 1H), 7.08(t, J=4.6 Hz, 1H), 3.98(s, 3H), 2.41(s, 3H)	168.1, 168.0, 167.9, 158.3, 157.4, 133.1, 132.1, 127.3, 126.3, 123.2, 118.6, 117.7, 117.2, 116.6, 52.2, 29.7, 21.0
2n	8.66(d,J=4.6 Hz, 2H), 8.57(d, J=11.0 Hz, 1H), 8.39(s, 1H), 7.52—7.38(m, 1H), 7.02(dd, J=11.8, 6.6 Hz, 2H), 2.39(s, 3H)	168.0, 162.3, 158.1, 157.5, 133.2, 132.8, 132.7, 120.5, 118.2, 118.1, 116.3, 114.7, 114.7, 110.7, 110.5, 103.9, 103.6
2o	8.86(s, 1H), 8.66(d,J=4.5 Hz, 2H), 8.40(s, 1H), 7.45(d, J=8.3 Hz, 1H), 7.24(t, J=8.2 Hz, 1H), 7.04(t, J=4.4 Hz, 1H), 2.38(s, 3H)	168.0, 158.1, 157.4, 133.2, 132.9, 130.5, 122.7, 122.5, 118.3, 116.6, 116.4, 115.0, 21.0
2p	9.03(s, 1H), 8.68(t,J=3.6 Hz, 2H), 8.41(s, 1H), 7.39(q, J=8.4 Hz, 2H), 7.14—6.96(m, 1H), 2.39(s, 3H)	168.1, 168.0, 158.2, 157.4, 133.2, 125.4, 122.9, 119.5, 118.6, 118.4, 116.5, 115.0, 21.0
2q	9.00(dd,J=9.2, 2.5 Hz, 1H), 8.70—8.73(m, 2H), 8.59(d, J=8.8 Hz, 2H), 7.94(d, J=8.0 Hz, 1H), 7.75(d, J=9.2 Hz, 1H), 7.62—7.56(m, 1H), 7.52—7.46(m, 1H), 7.06(s, 1H), 2.53(s, 3H)	168.0, 158.2, 157.8, 135.4, 130.3, 129.9, 128.4, 127.0, 126.1, 125.1, 124.3, 123.7, 117.1, 116.7, 116.6, 113.8, 21.6
2r	8.77(d,J=8.4 Hz, 1H), 8.47(s, 2H), 8.39(s, 1H), 7.55(d, J=7.8 Hz, 1H), 7.36(t, J=7.8 Hz, 1H), 7.24(t, J=7.5 Hz, 1H), 2.39(s, 3H), 2.27(s, 3H)	168.2, 158.0, 156.1, 133.1, 132.7, 125.1, 124.4, 123.8, 121.9, 117.4, 116.2, 114.7, 21.0, 15.0
2s	8.89—8.81(m, 3H), 8.47(s, 1H), 7.57(d, J=6.3 Hz, 3H), 7.50(t, J=7.5 Hz, 2H), 7.46—7.36(m, 2H), 7.27(t, J=8.1 Hz, 1H), 2.40(s, 3H)	168.1, 156.8, 156.0, 134.4, 133.6, 132.8, 129.4, 129.0, 128.4, 126.5, 124.7, 124.0, 122.3, 117.5, 116.4, 114.6, 21.0
2t	8.73—8.60(m, 3H), 8.34(s, 1H), 7.55(d, J=7.8 Hz, 1H), 7.36(t, J=7.8 Hz, 1H), 7.26(t, J=6.3 Hz, 1H), 2.39(s, 3H)	168.0, 158.5, 155.9, 133.9, 132.7, 124.9, 124.1, 122.5, 117.6, 116.4, 114.4, 113.0, 21.1

Table 2 1H NMR and 13C NMR data of compounds 2a—2t

Compd.	¹H NMR(400 MHz, CDCl₃), δ	¹³C NMR(100 MHz, CDCl₃), δ
2a	8.81(d,J=8.4 Hz, 1H), 8.67(d, J=4.8 Hz, 2H), 8.43(s, 1H), 7.56(d, J=7.8 Hz, 1H), 7.37(t, J=7.5 Hz, 1H), 7.29—7.25(m, 1H), 7.02(t, J=4.8 Hz, 1H), 2.40(s, 3H)	168.2, 158.1, 157.8, 133.5, 132.8, 124.6, 124.0, 122.2, 117.5, 116.4, 116.1, 114.6, 21.1
2b	8.73—8.59(m, 3H), 8.36(s, 1H), 7.24(dd, J=10.3, 5.1 Hz, 1H), 7.02—6.92(m, 2H), 2.63(s, 3H), 2.37(s, 3H)	168.7, 158.1, 157.7, 134.3, 133.2, 129.4, 124.5, 123.9, 122.7, 116.0, 114.8, 114.1, 29.7, 21.3, 18.8
2c	8.66(d,J=4.8 Hz, 2H), 8.44(d, J=8.4 Hz, 1H), 8.06(s, 1H), 7.54—7.48(m, 2H), 7.40(dd, J=9.7, 5.6, 1.4 Hz, 3H), 7.25(d, J=4.6 Hz, 1H), 7.02(t, J=4.8 Hz, 1H), 6.74(d, J=7.9 Hz, 1H), 5.11(s, 2H), 1.91(s, 3H)	169.8, 158.1, 157.7, 152.0, 136.9, 135.1, 133.2, 128.5, 128.4, 128.2, 125.4, 116.2, 114.5, 114.2, 110.0, 104.1, 70.4, 20.4
2d	8.79—8.72(m, 1H), 8.66—8.61(m, 2H), 8.27(d, J=2.0 Hz, 1H), 7.20(t, J=7.7 Hz, 2H), 7.02(t, J=4.8, 3.4 Hz, 1H), 2.39(s, 3H)	169.5, 158.1, 157.2, 134.6, 132.2, 125.0, 124.2, 123.3, 121.4, 116.9, 116.6, 115.3, 21.1
2e	9.12(d,J=8.5 Hz, 1H), 8.66(d, J=4.7 Hz, 2H), 8.31(s, 1H), 7.82(d, J=7.5 Hz, 1H), 7.37(t, J=8.0 Hz, 1H), 7.05(t, J=4.6 Hz, 1H), 3.91(d, J=13.3 Hz, 3H), 2.41(s, 3H)	170.1, 167.2, 158.2, 157.3, 134.5, 132.8, 125.4, 123.5, 123.0, 122.5, 120.7, 118.7, 116.7, 52.2, 21.0
2f	8.69—8.59(m, 3H), 8.36(s, 1H), 7.33(s, 1H), 7.18(d, J=8.5 Hz, 1H), 6.97(t, J=4.2 Hz, 1H), 2.47(s, 3H), 2.39(s, 3H)	168.2, 158.1, 157.7, 133.3, 131.7, 131.2, 126.1, 124.2, 117.2, 116.2, 115.9, 114.6, 21.4, 21.1
2g	8.66(dd,J=22.8, 6.8 Hz, 3H), 8.39(s, 1H), 6.98(d, J=8.2 Hz, 3H), 3.89(s, 3H), 2.40(s, 3H)	168.1, 158.1, 157.6, 155.6, 133.4, 127.8, 124.7, 117.5, 115.8, 115.1, 114.0, 99.4, 55.7, 21.1
2h	8.70(d,J=8.7 Hz, 1H), 8.63(d, J=4.7 Hz, 2H), 8.40(s, 1H), 7.49(d, J=7.5 Hz, 2H), 7.40(t, J=7.3 Hz, 2H), 7.36—7.30(m, 1H), 7.06(d, J=9.8 Hz, 2H), 6.98(t, J=4.6 Hz, 1H), 5.13(s, 2H), 2.39(s, 3H), 5.13(s, 2H), 2.39(s, 3H)	168.1, 158.1, 157.6, 154.8, 137.3, 133.4, 128.6, 127.9, 127.7, 124.7, 117.6, 115.9, 115.2, 114.5, 101.0, 70.6, 21.1
2i	8.83—8.76(m, 1H), 8.67(d, J=4.8 Hz, 2H), 8.46(s, 1H), 7.38—7.29(m, 2H), 7.20(d, J=2.4 Hz, 1H), 7.14—6.99(m, 5H), 2.35(s, 3H)	168.1, 158.6, 158.1, 157.6, 152.0, 133.3, 129.7, 129.5, 125.0, 122.5, 117.8, 117.6, 116.1, 115.7, 107.9, 21.0
2j	8.84—8.61(m, 3H), 8.44(s, 1H), 7.52(s, 1H), 7.36—7.24(m, 1H), 7.05(s, 1H), 2.39(s, 3H)	168.0, 158.2, 157.5, 132.6, 131.1, 127.9, 125.1, 124.8, 117.7, 117.1, 116.4, 115.9, 21.0
2k	8.67(t,J=7.2 Hz, 3H), 8.42(s, 1H), 7.68(s, 1H), 7.43(d, J=8.9 Hz, 1H), 7.04(t, J=4.7 Hz, 1H), 2.39(s, 3H)	168.0, 158.2, 157.4, 132.4, 131.4, 127.4, 125.6, 120.2, 118.1, 116.4, 115.7, 115.5, 21.0
2l	8.81—8.55(m, 3H), 8.34(s, 1H), 7.42(d, J=7.9 Hz, 1H), 7.09(d, J=7.8 Hz, 1H), 6.98(t, J=4.7 Hz, 1H), 2.53(s, 3H), 2.38(s, 3H)	168.2, 158.1, 157.8, 134.7, 133.6, 133.2, 123.8, 121.9, 117.1, 116.5, 115.9, 113.9, 22.2, 21.1
2m	9.50(s, 1H), 8.72(d,J=4.6 Hz, 2H), 8.58(s, 1H), 7.95(d, J=8.3 Hz, 1H), 7.59(d, J=8.3 Hz, 1H), 7.08(t, J=4.6 Hz, 1H), 3.98(s, 3H), 2.41(s, 3H)	168.1, 168.0, 167.9, 158.3, 157.4, 133.1, 132.1, 127.3, 126.3, 123.2, 118.6, 117.7, 117.2, 116.6, 52.2, 29.7, 21.0
2n	8.66(d,J=4.6 Hz, 2H), 8.57(d, J=11.0 Hz, 1H), 8.39(s, 1H), 7.52—7.38(m, 1H), 7.02(dd, J=11.8, 6.6 Hz, 2H), 2.39(s, 3H)	168.0, 162.3, 158.1, 157.5, 133.2, 132.8, 132.7, 120.5, 118.2, 118.1, 116.3, 114.7, 114.7, 110.7, 110.5, 103.9, 103.6
2o	8.86(s, 1H), 8.66(d,J=4.5 Hz, 2H), 8.40(s, 1H), 7.45(d, J=8.3 Hz, 1H), 7.24(t, J=8.2 Hz, 1H), 7.04(t, J=4.4 Hz, 1H), 2.38(s, 3H)	168.0, 158.1, 157.4, 133.2, 132.9, 130.5, 122.7, 122.5, 118.3, 116.6, 116.4, 115.0, 21.0
2p	9.03(s, 1H), 8.68(t,J=3.6 Hz, 2H), 8.41(s, 1H), 7.39(q, J=8.4 Hz, 2H), 7.14—6.96(m, 1H), 2.39(s, 3H)	168.1, 168.0, 158.2, 157.4, 133.2, 125.4, 122.9, 119.5, 118.6, 118.4, 116.5, 115.0, 21.0
2q	9.00(dd,J=9.2, 2.5 Hz, 1H), 8.70—8.73(m, 2H), 8.59(d, J=8.8 Hz, 2H), 7.94(d, J=8.0 Hz, 1H), 7.75(d, J=9.2 Hz, 1H), 7.62—7.56(m, 1H), 7.52—7.46(m, 1H), 7.06(s, 1H), 2.53(s, 3H)	168.0, 158.2, 157.8, 135.4, 130.3, 129.9, 128.4, 127.0, 126.1, 125.1, 124.3, 123.7, 117.1, 116.7, 116.6, 113.8, 21.6
2r	8.77(d,J=8.4 Hz, 1H), 8.47(s, 2H), 8.39(s, 1H), 7.55(d, J=7.8 Hz, 1H), 7.36(t, J=7.8 Hz, 1H), 7.24(t, J=7.5 Hz, 1H), 2.39(s, 3H), 2.27(s, 3H)	168.2, 158.0, 156.1, 133.1, 132.7, 125.1, 124.4, 123.8, 121.9, 117.4, 116.2, 114.7, 21.0, 15.0
2s	8.89—8.81(m, 3H), 8.47(s, 1H), 7.57(d, J=6.3 Hz, 3H), 7.50(t, J=7.5 Hz, 2H), 7.46—7.36(m, 2H), 7.27(t, J=8.1 Hz, 1H), 2.40(s, 3H)	168.1, 156.8, 156.0, 134.4, 133.6, 132.8, 129.4, 129.0, 128.4, 126.5, 124.7, 124.0, 122.3, 117.5, 116.4, 114.6, 21.0
2t	8.73—8.60(m, 3H), 8.34(s, 1H), 7.55(d, J=7.8 Hz, 1H), 7.36(t, J=7.8 Hz, 1H), 7.26(t, J=6.3 Hz, 1H), 2.39(s, 3H)	168.0, 158.5, 155.9, 133.9, 132.7, 124.9, 124.1, 122.5, 117.6, 116.4, 114.4, 113.0, 21.1

Table 3 Optimization of the reaction conditionsa

Entry	R	T/℃	Molar fraction(%)	Yield^b(%)	Entry	R	T/℃	Molar fraction(%)	Yield^b(%)
1	H	50	150	0	10	2-Pyrimidyl	25	150	0
2	Me	50	150	0	11	2-Pyrimidyl	40	150	45
3	Bn	50	150	0	12	2-Pyrimidyl	60	150	85
4	Ph	50	150	40	13	2-Pyrimidyl	70	150	83
5	2-Py	50	150	65	14	2-Pyrimidyl	80	150	80
6	2-Pyrimidyl	50	150	78	15	2-Pyrimidyl	60	110	83
7	Ac	50	150	0	16	2-Pyrimidyl	60	120	85
8	Boc	50	150	0	17	2-Pyrimidyl	60	200	80
9	PhSO₂	50	150	0	18	2-Pyrimidyl	60	250	76

Table 4 Substrate scope of the C3—H acetoxylation of indoles

Entry	Product	R¹	R²	Yield^*(%)	Entry	Product	R¹	R²	Yield^*(%)
1	2a	H	H	85	11	2k	5-Br	H	85
2	2b	4-Me	H	76	12	2l	6-Me	H	83
3	2c	4-OBn	H	63	13	2m	6-CO₂Me	H	63
4	2d	4-Cl	H	73	14	2n	6-F	H	77
5	2e	4-CO₂Me	H	75	15	2o	6-Cl	H	70
6	2f	5-Me	H	78	16	2p	6-Br	H	80
7	2g	5-OMe	H	80	17	2q	5,6-Ph	H	45
8	2h	5-OBn	H	65	18	2r	H	Me	84
9	2i	5-OPh	H	86	19	2s	H	Ph	81
10	2j	5-Cl	H	83	20	2t	H	Br	72

Fig.1 Crystal structure of compound 2a

Scheme 2 Proposed mechanism of the C3—H acetoxylation of indoles

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Metal-free C3—H Acetoxylation of Indoles Promoted by PhI(OAc)₂^†

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