Copper-Catalyzed Direct Acyloxylation of C(sp 2 ) H Bonds. in Aromatic Amides

Supporting Information for Copper-Catalyzed Direct Acyloxylation of C(sp 2 ) H Bonds in Aromatic Amides Feifan Wang, Qiyan Hu, Chao Shu, Zhiyang Lin, Dewen Min, Tianchao Shi and Wu Zhang* Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Laboratory of Molecule-Based Materials, College of Chemistry and Materials Science, Anhui ormal University, Wuhu 241000, China. Table of Contents General Information...S2 General Procedures...S2 General Procedure for Copper-Catalyzed C H Acyloxylation...S2 Copper-Catalyzed C H Acyloxylation of 1a with benzoic acid (2 mmol scale)...s2 Characterization Data of Products 3aa-7a...S3 S23 X-ray Crystal Structure of the compound 5ba...S24 The hydrolyzation of 5ba...S24 Mechanistic Investigation.........S25 Radical Experiments......S25 Deuteration Experiments........S26 KIE Studies...S27 Copies of 1 H and 13 C MR Spectra...S28 S72 S1

General Information All starting materials and reagents were commercially available and used directly without further purification. All carboxamides were synthesized by the reactions between the corresponding acyl chlorides or acids and 8-aminoquinolines according to the literature procedures. 1 All known products gave satisfactory analytical data by MR spectra, corresponding to the reported literature values. In addition, unknown compounds were confirmed by HRMS. Melting points were determined using X-4 micro melting point apparatus and are uncorrected. MR spectra were recorded at room temperature on a Bruker Avance-300 or Bruker Avance-500 at 300 MHz or 500 MHz with tetramethylsilane (TMS) as an internal standard. Chemical shifts are given in δ relative to TMS, the coupling constants J are given in Hz. High-resolution mass spectra (HRMS) were recorded on Agilent 6200 LC/MS TF using APCI or ESI in positive mode. General Procedures General Procedure for Copper-Catalyzed C H Acyloxylation To a 10 ml reaction tube was added amide 1a (0.2 mmol), acid (0.3 mmol), CuBr (5.7 mg, 20 mol %), Ag 2 C 3 (110.3 mg, 2 equiv), and toluene/dmf (1.5 ml/0.5 ml) in air. The mixture was stirred at 130 for 15 h. The reaction mixture was then cooled to room temperature, diluted with ethyl acetate and quenched with saturated sodium chloride. The aqueous phase was extracted with ethyl acetate (3 10 ml). The organic layer was dried over a 2 S 4. After concentration, the resulting residue was purified by flash chromatography to afford the product. Copper-Catalyzed C H Acyloxylation of 1a with benzoic acid (2 mmol scale) To a 50 ml reaction tube was added amide 1a (524 mg, 2 mmol), benzoic acid 2a (366 mg, 3 mmol), CuBr (57 mg, 20 mol %), Ag 2 C 3 (1103 mg, 2 equiv), and toluene/dmf (15 ml/5 ml) in air. The mixture was stirred at 130 for 15 h. The reaction mixture was then cooled to room temperature, diluted with ethyl acetate and quenched with saturated sodium chloride. The aqueous phase was extracted with ethyl acetate (3 40 ml). The organic layer was dried over a 2 S 4. After concentration, the resulting residue was purified by flash chromatography on silica gel (eluent: petroleum ether/ethyl acetate = 12/1) to afford the desired alkylated product 3aa (581 mg, 76%) as a white solid. 1 (a) Grigorjeva, L.; Daugulis,. rg. Lett. 2014, 16, 4684. (b) Khan, B; Kant, R.; Koley, D.; Adv. Synth. Catal. 2016, 358, 2352. (c) Roane, J.; Daugulis,. J. Am. Chem. Soc. 2016, 138, 4601. S2

Characterization Data of Products 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl benzoate 3aa H The compound 3aa was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3aa as a white solid (68 mg, 89% yield). Mp = 135.6-136.1. 1 H MR (300 MHz, CDCl 3 ): δ 10.12 (s, 1H), 8.86 (dd, J = 6.3, 1.8 Hz, 1H), 8.74 (d, J = 3.6 Hz, 1H), 8.11 (d, J = 8.1 Hz, 1H), 8.01 (d, J = 7.8 Hz, 2H), 7.54-7.37 (m, 5H), 7.25-7.16 (m, 4H), 2.53 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 165.04, 164.87, 148.21, 147.68, 138.31, 137.71, 136.26, 134.21, 133.42, 130.72, 130.18, 130.13, 128.95, 128.20, 127.85, 127.30, 122.01, 121.60, 120.33, 116.82, 19.60. HRMS (APCI): Calcd for C 24 H 19 2 3 [M + H] + 383.1396, found 383.1391. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl-4-methylbenzoate 3ab The compound 3ab was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3ab as a white solid (69.7 mg, 88% yield). Mp = 99.5-101.2. 1 H MR (300 MHz, CDCl 3 ): δ 10.11 (s, 1H), 8.86 (dd, J = 6.3, 2.4 Hz, 1H), 8.74 (d, J = 3.0 Hz, 1H), 8.11 (d, J = 8.1 Hz, 1H), 7.90 (d, J = 8.1 Hz, 2H), 7.54-7.47 (m, 2H), 7.44-7.38 (m, 2H), 7.26-7.20 (m, 2H), 6.98 (d, J = 7.8 Hz, 2H), 2.53 (s, 3H), 2.26 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 165.06, 164.92, 148.20, 147.76, 144.20, 138.37, 137.64, 136.16, 134.29, 130.78, 130.23, 130.06, 128.91, 128.05, 127.86, 127.30, 126.23, 121.92, 121.57, 120.38, 116.79, 21.61, 19.56; HRMS (APCI): Calcd for C 25 H 21 2 3 [M + H] + 397.1552, found 397.1559. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl-3-methylbenzoate 3ac S3

The compound 3ac was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3ac as a white solid (68.9 mg, 87% yield). Mp = 118.4-119.2. 1 H MR (300 MHz, CDCl 3 ): δ 10.14 (s, 1H), 8.88 (dd, J = 6.3, 2.4 Hz, 1H), 8.75 (d, J = 2.7 Hz, 1H), 8.14 (d, J = 8.1 Hz, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.77 (s, 1H), 7.56-7.40 (m, 4H), 7.26-7.18 (m, 3H), 7.11-7.06 (m, 1H), 2.53 (s, 3H), 2.07 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 165.10, 164.90, 148.18, 147.75, 138.00, 137.71, 136.29, 134.27, 134.13, 130.59, 130.07, 128.93, 128.07, 127.90, 127.37, 121.94, 121.56, 120.29, 116.87, 20.87, 19.55; HRMS (APCI): Calcd for C 25 H 21 2 3 [M + H] + 397.1552, found 397.1556. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl-2-methylbenzoate 3ad H The compound 3ad was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3ad as a white solid (66.5 mg, 84% yield). Mp = 94.4-95.3. 1 H MR (300 MHz, CDCl 3 ): δ 10.04 (s, 1H), 8.79 (dd, J = 6.6, 1.8 Hz, 1H), 8.63 (s, 1H), 8.00 (d, J = 8.1 Hz, 1H), 7.88 (d, J = 7.8 Hz, 1H), 7.45-7.27 (m, 4H), 7.16-7.08 (m, 3H), 6.97 (d, J = 7.5 Hz, 1H), 6.83 (m, 1H), 2.43 (s, 3H), 2.38 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 164.64, 163.99, 147.15, 146.66, 140.26, 137.30, 136.51, 135.15, 133.20, 131.49, 130.51, 130.25, 130.01, 129.05, 127.07, 126.86, 126.22, 124.49, 120.98, 120.55, 119.43, 115.75, 20.59, 18.47; HRMS (APCI): Calcd for C 25 H 21 2 3 [M + H] + 397.1552, found 397.1546. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl-4-methoxybenzoate 3ae H S4

The compound 3ae was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3ae as a white solid (58.5 mg, 71% yield). Mp = 147.6-148.2. 1 H MR (300 MHz, CDCl 3 ): δ 10.10 (s, 1H), 8.86 (dd, J = 6.3, 2.1 Hz, 1H), 8.74 (d, J = 2.7 Hz, 1H), 8.11 (d, J = 7.2 Hz, 1H), 7.96 (d, J = 8.7 Hz, 2H), 7.55-7.39 (m, 4H), 7.24-7.20 (m, 2H), 6.65 (d, J = 9.0 Hz, 2H), 3.74 (s, 3H), 2.52 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 164.97, 164.69, 163.65, 148.22, 147.80, 138.40, 137.63, 136.12, 134.32, 132.33, 130.04, 127.98, 127.85, 127.28, 121.92, 121.57, 121.28, 120.43, 116.72, 113.44, 55.36, 19.56. HRMS (APCI): Calcd for C 25 H 21 2 4 [M + H] + 413.1501, found 413.1498. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl-3-chlorobenzoate 3af H Cl The compound 3af was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3af as a white solid (57.4 mg, 69% yield). Mp = 108.1-108.9. 1 H MR (300 MHz, CDCl 3 ): δ 10.16 (s, 1H), 8.87 (dd, J = 6.0, 2.7 Hz, 1H), 8.77 (d, J = 3.3 Hz, 1H), 8.16 (d, J = 7.8 Hz, 1H), 7.96 (s, 1H), 7.88 (d, J = 7.5 Hz, 1H), 7.57-7.52 (m, 2H), 7.46-7.41 (m, 2H), 7.35 (d, J = 7.8 Hz, 1H), 7.29-7.23 (m, 2H), 7.17-7.11 (m, 1H), 2.54 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 163.58, 162.75, 147.33, 146.45, 137.27, 136.86, 135.19, 133.33, 133.09, 132.36, 129.65, 129.53, 129.14, 129.02, 128.45, 127.39, 127.23, 126.24, 121.05, 120.62, 119.11, 115.70, 114.71, 18.55. HRMS (ESI): Calcd for C 24 H 18 2 3 Cl [M + H] + 417.1006, found 417.1003. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl-2-chlorobenzoate 3ag The compound 3ag was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3ag as a white solid (51.6 mg, 62% yield). Mp = 97.6-98.2. 1 H MR (300 MHz, CDCl 3 ): δ 10.11 (s, 1H), 8.90 (d, J = 5.1 Hz, 1H), 8.73 (d, J = 2.7 Hz, 1H), 8.13 (d, J = 7.8 Hz, 1H), 7.81 (d, J = 7.5 Hz, 1H), 7.56-7.23 (m, 8H), 7.01-6.96 (m, 1H), 2.53 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 164.83, 163.78, 148.34, 147.40, 138.39, 137.57, 136.16, 134.39, 134.24, 132.99, 131.95, 130.99, 130.18, 128.61, 128.41, 127.84, 127.27, S5

126.35, 122.38, 122.09, 121.65, 120.33, 116.81, 19.53; HRMS (ESI): Calcd for C 24 H 18 2 3 Cl [M + H] + 417.1006, found 417.1007. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl-4-chlorobenzoate 3ah H Cl The compound 3ah was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3ah as a white solid (63.2 mg, 76% yield). Mp = 88.4-89.3. 1 H MR (300 MHz, CDCl 3 ): δ 10.08 (s, 1H), 8.85 (dd, J = 6.3, 2.7 Hz, 1H), 8.72 (d, J = 3.0 Hz, 1H), 8.11 (d, J = 7.5 Hz, 1H), 7.92 (d, J = 8.4 Hz, 2H), 7.50-7.39 (m, 4H), 7.25-7.11 (m, 4H), 2.53 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 163.71, 163.10, 147.16, 146.51, 138.86, 137.23, 136.72, 135.27, 133.10, 130.46, 129.59, 129.11, 127.49, 127.29, 126.84, 126.38, 126.28, 121.07, 120.60, 119.18, 115.75, 18.51; HRMS (APCI): Calcd for C 24 H 18 2 3 Cl [M + H] + 417.1006, found 417.1003. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl-4-bromobenzoate 3ai The compound 3ai was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3ai as a white solid (69.0 mg, 75% yield). Mp = 96.7-97.4. 1 H MR (300 MHz, CDCl 3 ): δ 10.07 (s, 1H), 8.84 (d, J = 3.3 Hz, 1H), 8.73 (d, J = 3.0 Hz, 1H), 8.14 (d, J = 7.5 Hz, 1H), 7.84 (d, J = 8.4 Hz, 2H), 7.51-7.40 (m, 4H), 7.31 (d, J = 8.1 Hz, 2H), 7.25-7.22 (m, 2H), 2.53 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 164.71, 164.31, 148.21, 147.53, 138.28, 137.76, 136.28, 134.14, 131.59, 131.52, 130.61, 130.15, 128.64, 128.33, 127.86, 127.32, 122.10, 121.64, 120.20, 116.76, 109.99, 19.56; HRMS (ESI): Calcd for C 24 H 18 2 3 Br [M + H] + 461.0500, found 461.0508. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl-4-fluorobenzoate 3aj S6

The compound 3aj was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3aj as a white solid (68.8 mg, 86% yield). Mp = 144.1-146.6. 1 H MR (300 MHz, CDCl 3 ): δ 10.09 (s, 1H), 8.85 (dd, J = 6.0, 2.7 Hz, 1H), 8.73 (dd, J = 2.7, 1.2 Hz, 1H), 8.13 (d, J = 7.2 Hz, 1H), 8.01 (dd, J = 8.4, 5.4 Hz, 2H), 7.55-7.39 (m, 4H), 7.25-7.22 (m, 2H), 6.87-6.81 (m, 2H), 2.53 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 165.92 (d, J C-F = 253.3 Hz), 164.80, 163.99, 148.18, 147.59, 138.27, 137.74, 136.32, 134.17, 132.79 (d, J C-F = 9.5 Hz), 130.66, 130.14, 128.27, 127.87, 127.33, 125.22 (d, J C-F = 2.5 Hz), 122.06, 121.61, 120.26, 116.82, 115.38 (d, J C-F = 21.9 Hz), 19.56; HRMS (APCI): Calcd for C 24 H 18 2 3 F [M + H] + 401.1301, found 401.1309. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl-3-(trifluoromethyl)benzoate 3ak The compound 3ak was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3ak as a white solid (53.1 mg, 59% yield). Mp = 113.5-114.1. 1 H MR (300 MHz, CDCl 3 ): δ 10.10 (s, 1H), 8.84 (dd, J = 6.0, 3.0 Hz, 1H), 8.73 (dd, J = 4.2, 1.2 Hz, 1H), 8.23 (s, 1H), 8.18 (d, J = 7.8 Hz, 1H), 8.12-8.09 (m, 1H), 7.64 (d, J = 7.8 Hz, 1H), 7.54-7.24 (m, 7H), 2.55 (s, 3H); 13 C MR (125 MHz, CDCl 3 ): δ 164.60, 163.78, 148.31, 147.43, 138.24, 137.88, 136.22, 134.04, 133.28, 130.88 (q, 2 J C-F = 32.8 Hz), 130.60, 130.22, 129.88, 129.85, 128.91, 128.54, 127.85, 127.23, 126.95 (q, 3 J C-F = 3.8 Hz), 123.30 (q, 1 J C-F = 271.3 Hz), 122.11, 121.64, 120.15, 116.68, 19.57; HRMS (ESI): Calcd for C 25 H 18 2 3 F 3 [M + H] + 451.1269, found 451.1271. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl[1,1'-biphenyl]-4-carboxylate 3al S7

The compound 3al was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3al as a white solid (70.5 mg, 77% yield). Mp = 187.0-187.4. 1 H MR (300 MHz, CDCl 3 ): δ 10.13 (s, 1H), 8.88 (dd, J = 7.2, 1.5 Hz, 1H), 8.75 (dd, J = 2.7, 1.5 Hz, 1H), 8.11-8.05 (m, 3H), 7.55-7.36 (m, 11H), 7.27-7.22 (m, 2H), 2.54 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 164.89, 148.19, 147.77, 146.07, 139.80, 138.34, 137.72, 136.21, 134.27, 130.69, 130.11, 128.87, 128.19, 128.17, 127.86, 127.69, 127.32, 127.20, 126.84, 121.97, 121.57, 120.36, 116.82, 19.57; HRMS (APCI): Calcd for C 30 H 23 2 3 [M + H] + 459.1708, found 459.1707. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl-2-naphthoate 3am The compound 3am was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3am as a white solid (63.1 mg, 73% yield). Mp = 148.9-149.2. 1 H MR (300 MHz, CDCl 3 ): δ 10.18 (s, 1H), 8.87 (dd, J = 7.2, 1.2 Hz, 1H), 8.74 (dd, J = 4.2, 1.2 Hz, 1H), 8.54 (s, 1H), 8.05 (d, J = 7.8 Hz, 1H), 8.00 (dd, J = 8.1, 0.9 Hz, 1H), 7.72 (d, J = 8.1 Hz, 1H), 7.63 (d, J = 8.7 Hz, 1H), 7.51-7.30 (m, 9H), 7.25-7.23 (m, 1H), 2.55 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 165.12, 164.92, 148.23, 147.82, 138.33, 137.77, 136.17, 135.58, 134.25, 132.16, 132.00, 130.72, 130.14, 129.27, 128.43, 128.17, 127.98, 127.85, 127.58, 127.30, 126.46, 126.20, 125.41, 121.98, 121.57, 120.33, 116.77, 19.59; HRMS (APCI): Calcd for C 28 H 21 2 3 [M + H] + 433.1552, found 433.1551. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl thiophene-2-carboxylate 3an S8

The compound 3an was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3an as a white solid (54.3 mg, 70% yield). Mp = 123.2-123.6. 1 H MR (300 MHz, CDCl 3 ): δ 10.09 (s, 1H), 8.87 (dd, J = 6.3, 2.1 Hz, 1H), 8.75 (d, J = 2.4 Hz, 1H), 8.12 (d, J = 7.8 Hz, 1H), 7.77 (d, J = 3.6 Hz, 1H), 7.55-7.38 (m, 6H), 7.23-7.20 (m, 1H), 6.89-6.86 (m, 1H), 2.52 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 163.70, 159.29, 147.23, 146.29, 137.38, 136.61, 135.12, 133.78, 133.27, 132.56, 131.25, 129.68, 129.02, 127.20, 126.65, 126.24, 120.93, 120.58, 119.23, 115.73, 18.50; HRMS (ESI): Calcd for C 22 H 17 2 3 S [M + H] + 389.0960, found 389.0955. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl isobutyrate 3ao The compound 3ao was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3ao as a yellow liquid (42.4 mg, 61% yield). 1 H MR (300 MHz, CDCl 3 ): δ 10.00 (s, 1H), 8.93 (dd, J = 6.6, 1.5 Hz, 1H), 8.77 (d, J = 3.9 Hz, 1H), 8.16 (d, J = 7.5 Hz, 1H), 7.61-7.56 (m, 2H), 7.44 (dd, J = 8.4, 4.2 Hz, 1H), 7.39-7.33 (m, 1H), 7.17 (d, J = 7.5 Hz, 1H), 7.03 (d, J = 8.1 Hz, 1H), 2.69-2.55 (m, 1H), 2.48 (s, 3H), 1.02 (d, J = 7.2 Hz, 6H); 13 C MR (75 MHz, CDCl 3 ): δ 174.50, 163.89, 147.35, 146.45, 137.35, 136.27, 135.19, 133.28, 131.51, 129.88, 128.92, 126.93, 126.30, 121.01, 120.68, 119.19, 115.68, 32.98, 18.33, 17.58; HRMS (ESI): Calcd for C 21 H 21 2 3 [M + H] + 349.1552, found 349.1552. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl 2-phenylbutanoate 3ap The compound 3ap was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3ap as a white solid (44.9 mg, 53% yield). Mp = 112.8-113.6. 1 H MR (500 MHz, CDCl 3 ): δ 9.88 (s, 1H), 8.80-8.78 (m, 1H), 8.74-8.73 (m, 1H), 8.18 (d, J = 7.0 Hz, 1H), 7.56 (d, J = 3.0 Hz, 2H), 7.46 (dd, J = 7.0, 2.0 Hz, 1H), 7.34-7.30 (m, 1H), 7.15 (d, J = 7.5 Hz, 1H), 7.09-7.08 (m, 2H), 6.95 (d, J = 8.0 Hz, 1H), 6.85-6.84 (m, 3H), 3.53 (t, J = 7. 0 S9

Hz, 1H), 2.44 (s, 3H), 2.05-2.01 (m, 1H), 1.70-1.64 (m, 1H), 0.70 (t, J = 7.5 Hz, 3H); 13 C MR (125 MHz, CDCl 3 ): δ 172.51, 164.68, 148.19, 147.33, 138.30, 137.81, 137.44, 136.35, 134.24, 130.87, 129.91, 128.12, 128.04, 128.00, 127.76, 127.40, 126.86, 121.95, 121.65, 120.02, 117.04, 53.36, 26.45, 19.45, 11.87; HRMS (ESI): Calcd for C 27 H 25 2 3 [M + H] + 425.1865, found 425.1869. 2-(quinolin-8-ylcarbamoyl)phenyl-4-methylbenzoate 3bb H The compound 3bb was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3bb as a white solid (29.8 mg, 39% yield). Mp = 126.5-127.3. 1 H MR (300 MHz, CDCl 3 ): δ 10.89 (s, 1H), 8.91 (dd, J = 7.2, 1.2 Hz, 1H), 8.37 (dd, J = 4.2, 1.2 Hz, 1H), 8.19-8.14 (m, 3H), 8.11 (dd, J = 8.1, 1.2 Hz, 1H), 7.62-7.41 (m, 4H), 7.37-7.31 (m, 2H), 7.18 (d, J = 7.8 Hz, 2H), 2.38 (s, 3H); 13 C MR (125 MHz, CDCl 3 ): δ 165.12, 163.46, 148.66, 147.76, 144.60, 138.47, 136.27, 134.67, 132.32, 131.01, 130.78, 129.09, 128.59, 127.88, 127.43, 126.39, 126.33, 123.56, 121.81, 121.46, 117.20, 21.74; HRMS (APCI): Calcd for C 24 H 19 2 3 [M + H] + 383.1396, found 383.1394. 2-(quinolin-8-ylcarbamoyl)-1,3-phenylene bis(4-methylbenzoate) 3bb The compound 3bb was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3bb as a white solid (26.8 mg, 26% yield). Mp = 188.2-188.8. 1 HMR (300 MHz, CDCl 3 ): δ 10.27 (s, 1H), 8.73-8.71 (m, 2H), 8.08 (d, J = 8.1 Hz, 1H), 7.98 (d, J = 8.1 Hz, 4H), 7.62-7.33 (m, 6H), 7.07 (d, J = 8.1 Hz, 4H), 2.31 (s, 6H); 13 C MR (125 MHz, CDCl 3 ): δ 164.67, 160.99, 148.96, 148.09, S10

144.43, 138.31, 135.97, 134.32, 130.71, 130.43, 129.04, 127.75, 127.24, 126.09, 124.54, 121.82, 121.48, 120.75, 116.73, 21.67; HRMS (APCI): Calcd for C 32 H 24 2 5 [M + H] + 517.1763, found 517.1762. 2-(quinolin-8-ylcarbamoyl)phenyl-4-bromobenzoate 3bi The compound 3bi was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3bi as a white solid (33.9 mg, 38% yield). Mp = 119.5-120.2. 1 H MR (300 MHz, CDCl 3 ): δ 10.74 (s, 1H), 8.89 (d, J = 6.9 Hz, 1H), 8.45 (d, J = 4.2 Hz, 1H), 8.12 (d, J = 7.8 Hz, 4H), 7.63-7.32 (m, 8H). 13 C MR (75 MHz, CDCl 3 ): δ 163.36, 162.35, 147.30, 146.79, 137.40, 135.31, 133.49, 131.31, 131.07, 130.70, 129.76, 127.94, 127.70, 127.02, 126.87, 126.39, 125.58, 122.40, 120.91, 120.56, 115.98; HRMS (APCI): Calcd for C 23 H 16 2 3 Br [M + H] + 447.0344, found 447.0341. 2-(quinolin-8-ylcarbamoyl)-1,3-phenylene bis(4-bromobenzoate) 3bi The compound 3bi was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3bi as a white solid (10.3 mg, 8% yield). Mp = 186.3-187.5. 1 H MR (300 MHz, CDCl 3 ): δ 10.27 (s, 1H), 8.70 (d, J = 3.9 Hz, 2H), 8.14 (d, J = 7.8 Hz, 1H), 7.95 (d, J = 8.1 Hz, 4H), 7.65-7.60 (m, 1H), 7.49-7.35 (m, 9H); 13 C MR (75 MHz, CDCl 3 ): δ 163.94, 160.76, 148.76, 147.97, 137.94, 136.54, 133.93, 131.82, 131.71, 131.01, 128.95, 127.87, 127.69, 127.42, 122.21, 121.62, 120.91, 117.02; HRMS (APCI): Calcd for C 30 H 19 2 5 Br 2 [M + H] + 644.9661, found 644.9666. S11

4-methyl-2-(quinolin-8-ylcarbamoyl)phenyl 4-methylbenzoate 3cb The compound 3cb was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3cb as a white solid (32.5 mg, 41% yield). Mp = 149.1-149.8. 1 H MR (300 MHz, CDCl 3 ): δ 10.88 (s, 1H), 8.91 (d, J = 6.6 Hz, 1H), 8.35-8.34 (m, 1H), 8.17 (d, J = 7.5 Hz, 2H), 8.10 (d, J = 7.8 Hz, 1H), 7.96 (s, 1H), 7.56-7.36 (m, 4H), 7.20-7.16 (m, 3H), 2.46 (s, 3H), 2.38 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 165.29, 163.60, 156.92, 147.73, 146.39, 144.47, 138.50, 136.21, 134.74, 132.97, 131.32, 130.75, 129.04, 128.09, 127.86, 127.42, 126.51, 123.27, 121.73, 121.41, 117.17, 21.72, 20.88; HRMS (APCI): Calcd for C 25 H 21 2 3 [M + H] + 397.1552, found 397.1544. 4-methoxy-2-(quinolin-8-ylcarbamoyl)phenyl-4-methylbenzoate 3db The compound 3db was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3db as a white solid (14.8 mg, 18% yield). Mp = 143.4-143.9. 1 H MR (300 MHz, CDCl 3 ): δ 10.95 (s, 1H), 8.91 (d, J = 7.2 Hz, 1H), 8.33 (d, J = 3.9 Hz, 1H), 8.18 (d, J = 8.1 Hz, 2H), 8.12 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 3.0 Hz, 1H), 7.57-7.48 (m, 2H), 7.53 (dd, J = 8.4, 4.2 Hz, 1H), 7.23-7.10 (m, 4H), 3.92 (s, 3H), 2.38 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 165.48, 163.20, 157.42, 147.79, 144.54, 142.03, 138.51, 136.16, 134.64, 130.77, 129.06, 127.85, 127.36, 126.42, 124.58, 121.87, 121.47, 118.97, 117.16, 114.51, 109.99, 55.85, 21.74; HRMS (APCI): Calcd for C 25 H 21 2 4 [M + H] + 413.1501, found 413.1497. 2-methoxy-6-(quinolin-8-ylcarbamoyl)phenyl-4-methylbenzoate 3db S12

The compound 3db was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3db as a white solid (15.7 mg, 19% yield). Mp = 157.0-157.8. 1 H MR (300 MHz, CDCl 3 ): δ 11.06 (s, 1H), 8.92 (dd, J = 7.5, 0.9 Hz, 1H), 8.25-8.22 (m, 3H), 8.09 (d, J = 8.4 Hz, 1H), 7.79 (dd, J = 7.8, 0.6 Hz, 1H), 7.55-7.31 (m, 5H), 7.24-7.16 (m, 2H), 3.85 (s, 3H), 2.42 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 164.49, 163.09, 151.53, 147.76, 144.37, 138.62, 138.55, 136.13, 134.81, 130.92, 129.48, 129.09, 127.85, 127.37, 126.59, 126.39, 122.36, 121.76, 121.45, 117.19, 115.16, 56.43, 21.78; HRMS (APCI): Calcd for C 25 H 21 2 4 [M + H] + 413.1501, found 413.1496. 4-methoxy-2-(quinolin-8-ylcarbamoyl)-1,3-phenylene bis(4-methylbenzoate) 3db The compound 3db was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ ethyl acetate = 8/1 gave 3db as a yellow solid (25.1 mg, 23% yield). Mp = 189.1-190.5. 1 H MR (300 MHz, CDCl 3 ): δ 10.30 (s, 1H), 8.74 (d, J = 3.6 Hz, 1H), 8.70 (dd, J = 6.0, 2.1 Hz, 1H), 8.08 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 7.8 Hz, 2H), 7.98 (d, J = 7.8 Hz, 2H), 7.42-7.29 (m, 4H), 7.17-7.09 (m, 5H), 3.88 (s, 3H), 2.33 (s, 3H), 2.32 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 165.09, 164.16, 160.73, 149.78, 148.01, 144.26, 141.42, 138.27, 136.06, 134.29, 130.56, 130.36, 129.01, 127.75, 127.23, 126.30, 126.00, 125.79, 121.81, 121.46, 121.08, 116.90, 113.55, 56.58, 21.67; HRMS (APCI): Calcd for C 33 H 27 2 6 [M + H] + 547.1869, found 547.1861. S13

5-methyl-2-(quinolin-8-ylcarbamoyl)phenyl-4-methylbenzoate 3eb The compound 3eb was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 3eb as a white solid (36.4 mg, 46% yield). Mp = 132.5-133.2. 1 H MR (300 MHz, CDCl 3 ): δ 10.91 (s, 1H), 8.90 (d, J = 7.2 Hz, 1H), 8.29 (d, J = 3.9 Hz, 1H), 8.19 (d, J = 7.8 Hz, 2H), 8.08 (d, J = 8.1 Hz, 2H), 7.54-7.44 (m, 2H), 7.32 (dd, J = 8.4, 4.2 Hz, 1H), 7.25-7.17 (m, 3H), 7.11 (s, 1H), 2.44 (s, 3H), 2.38 (s, 3H); 13 C MR (125 MHz, CDCl 3 ): δ 165.25, 163.41, 148.63, 147.67, 144.56, 143.37, 138.44, 136.23, 134.75, 131.01, 130.78, 129.08, 127.84, 127.40, 127.22, 126.47, 125.51, 123.94, 121.66, 121.40, 117.14, 21.75, 21.37; HRMS (APCI): Calcd for C 25 H 21 2 3 [M + H] + 397.1552, found 397.1551. 5-methyl-2-(quinolin-8-ylcarbamoyl)-1,3-phenylene bis(4-methylbenzoate) 3eb The compound 3eb was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether /ethyl acetate = 10/1 gave 3eb as a white solid (15.9 mg, 15% yield). Mp = 173.2-174.1. 1 H MR (300 MHz, CDCl 3 ): δ 10.28 (s, 1H), 8.70 (d, J = 3.6 Hz, 2H), 8.07 (d, J = 8.1 Hz, 1H), 7.99 (d, J = 7.8 Hz, 4H), 7.42-7.36 (m, 3H), 7.14 (s, 2H), 7.07 (d, J = 7.5 Hz, 4H), 2.47 (s, 3H), 2.31 (s, 6H); 13 C MR (125 MHz, CDCl 3 ): δ 164.80, 161.08, 148.78, 147.99, 144.36, 141.83, 138.26, 135.99, 134.40, 130.41, 129.01, 127.74, 127.26, 126.17, 121.67, 121.41, 116.66, 21.67, 21.56; HRMS (APCI): Calcd for C 33 H 26 2 5 [M + H] + 531.1920, found 531.1922. 5-methyl-2-(quinolin-8-ylcarbamoyl)phenyl-4-bromobenzoate 3ei S14

The compound 3ei was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ethyl acetate = 10/1 gave 3ei as a white solid (32.2 mg, 35% yield). Mp = 173.2-174.1. 1 H MR (300 MHz, CDCl 3 ): δ 10.75 (s, 1H), 8.89 (d, J = 7.2 Hz, 1H), 8.38 (d, J = 3.6 Hz, 1H), 8.15-8.10 (m, 3H), 8.04 (d, J = 8.1 Hz, 1H), 7.55-7.47 (m, 4H), 7.37 (dd, J = 8.1, 4.2 Hz, 1H), 7.27-7.24 (m, 1H), 7.12 (s, 1H), 2.46 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 164.52, 163.38, 148.33, 147.71, 143.44, 138.43, 136.36, 134.64, 132.13, 131.73, 130.80, 128.93, 128.18, 127.91, 127.47, 125.68, 123.84, 121.79,121.54, 117.05, 21.39; HRMS (APCI): Calcd for C 24 H 18 2 3 Br [M + H] + 461.0500, found 461.0497. 5-methyl-2-(quinolin-8-ylcarbamoyl)-1,3-phenylene bis(4-bromobenzoate) 3ei Br H Br The compound 3ei was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ethyl acetate = 10/1 gave 3ei as a white solid (6.6 mg, 5% yield). Mp = 186.2-187.6. 1 H MR (300 MHz, CDCl 3 ): δ 10.31 (s, 1H), 8.69 (d, J = 3.9 Hz, 2H), 8.16 (d, J = 7.5 Hz, 1H), 7.95 (d, J = 8.4 Hz, 4H), 7.48-7.46 (m, 3H), 7.41 (d, J = 8.4 Hz, 4H), 7.16 (s, 2H), 2.49 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 164.05, 160.84, 148.62, 147.87, 142.22, 137.98, 136.47, 131.81, 131.69, 128.87, 127.86, 127.84, 127.42, 124.71, 122.03, 121.55, 116.90, 116.84, 21.58; HRMS (APCI): Calcd for C 31 H 21 2 5 Br 2 [M + H] + 658.9817, found 658.9817. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl cinnamate 5aa S15

H The compound 5aa was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 5aa as a white solid (49.8 mg, 61% yield). Mp = 143.2-144.0. 1 H MR (300 MHz, CDCl 3 ): δ 10.11 (s, 1H), 8.92 (dd, J = 7.2, 1.2 Hz, 1H), 8.78 (dd, J = 3.9, 1.2 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 7.66 (d, J = 16.2 Hz, 1H), 7.60-7.38 (m, 4H), 7.31-7.17 (m, 7H), 6.41 (d, J = 15.9 Hz, 1H), 2.52 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 165.18, 164.93, 148.31, 147.58, 146.75, 138.45, 137.65, 136.25, 134.35, 133.92, 130.73, 130.52, 130.08, 128.72, 128.12, 127.96, 127.38, 122.02, 121.62, 120.27, 116.87, 116.77, 19.57; HRMS (APCI): Calcd for C 26 H 21 2 3 [M + H] + 409.1552, found 409.1551. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl (E)-3-(4-methoxyphenyl)acrylate 5ab The compound 5ab was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 5ab as a white solid (62.2 mg, 71% yield). Mp = 104.6-105.4. 1 H MR (300 MHz, CDCl 3 ): δ 10.10 (s, 1H), 8.92 (d, J = 6.9 Hz, 1H), 8.79 (d, J = 2.4 Hz, 1H), 8.12 (d, J = 8.1 Hz, 1H), 7.61 (d, J = 15.9 Hz, 1H), 7.54-7.37 (m, 4H), 7.19-7.16 (m, 4H), 6.77 (d, J = 8.1 Hz, 2H), 6.28 (d, J = 15.9 Hz, 1H), 3.79 (s, 3H), 2.51 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 165.51, 165.01, 161.57, 148.32, 147.68, 146.45, 138.51, 137.59, 136.18, 134.41, 130.77, 130.04, 129.87, 127.98, 127.35, 126.70, 121.97, 121.61, 120.33, 116.81, 114.15, 55.35, 19.56; HRMS (APCI): Calcd for C 27 H 23 2 4 [M + H] + 439.1657, found 439.1652. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl (E)-3-(3-methoxyphenyl)acrylate 5ac S16

The compound 5ac was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 5ac as a white solid (56.9 mg, 65% yield). Mp = 120.4-121.0. 1 H MR (300 MHz, CDCl 3 ): δ 10.12 (s, 1H), 8.93 (dd, J = 6.9, 1.5 Hz, 1H), 8.78 (dd, J = 2.7, 1.2 Hz, 1H), 8.13 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 15.9 Hz, 1H), 7.58-7.38 (m, 4H), 7.24-7.15 (m, 3H), 6.87-6.80 (m, 2H), 6.76 (s, 1H), 6.41 (d, J = 15.9 Hz, 1H), 3.75 (s, 3H), 2.52 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 165.17, 164.95, 159.72, 148.26, 147.56, 146.68, 137.63, 136.35, 135.27, 134.30, 130.73, 130.10, 129.72, 128.13, 127.97, 127.40, 122.06, 121.63, 120.92, 120.27, 117.04, 116.95, 116.62, 112.69, 55.26, 19.57; HRMS (APCI): Calcd for C 27 H 23 2 4 [M + H] + 439.1657, found 439.1650. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl (E)-3-(2-methoxyphenyl)acrylate 5ad H The compound 5ad was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 5ad as a white solid (49.1 mg, 56% yield). Mp = 157.1-158.5. 1 H MR (300 MHz, CDCl 3 ): δ 10.11 (s, 1H), 8.92 (d, J = 6.9 Hz, 1H), 8.78 (d, J = 2.4 Hz, 1H), 8.11 (d, J = 8.4 Hz, 1H), 7.97 (d, J = 16.2 Hz, 1H), 7.54-7.37 (m, 4H), 7.30-7.16 (m, 4H), 6.85-6.79 (m, 2H), 6.53 (d, J = 16.2 Hz, 1H), 3.74 (s, 3H), 2.51 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 165.82, 165.02, 158.44, 148.25, 147.76, 142.40, 138.47, 137.57, 136.20, 134.40, 131.72, 130.82, 130.01, 129.33, 127.94, 127.34, 122.98, 121.91, 121.51, 120.49, 120.37, 117.32, 116.98, 111.00, 55.32, 19.56; HRMS (APCI): Calcd for C 27 H 23 2 4 [M + H] + 439.1657, found 439.1652. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl (E)-3-(p-tolyl)acrylate 5ae S17

The compound 5ae was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 5ae as a white solid (55.7 mg, 66% yield). Mp = 119.1-119.6. 1 H MR (300 MHz, CDCl 3 ): δ 10.11 (s, 1H), 8.92 (dd, J = 6.9, 1.5 Hz, 1H), 8.78 (dd, J = 4.2, 1.5 Hz, 1H), 8.12 (dd, J = 8.4, 1.2 Hz, 1H), 7.63 (d, J = 15.9 Hz, 1H), 7.57-7.31 (m, 4H), 7.21-7.05 (m, 6H), 6.37 (d, J = 16.2 Hz, 1H), 2.52 (s, 3H), 2.31 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 165.38, 164.98, 148.30, 147.62, 146.80, 141.05, 138.44, 137.61, 136.28, 134.35, 131.22, 130.74, 130.07, 129.47, 128.15, 128.05, 127.96, 127.38, 122.02, 121.63, 120.30, 116.89, 115.64, 21,47, 19.58; HRMS (APCI): Calcd for C 27 H 23 2 3 [M + H] + 423.1708, found 423.1715. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl (E)-3-(4-chlorophenyl)acrylate 5af The compound 5af was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 5af as a white solid (53.9 mg, 61% yield). Mp = 128.2-129.1. 1 H MR (300 MHz, CDCl 3 ): δ 10.14 (s, 1H), 8.93 (d, J = 6.9 Hz, 1H), 8.76-8.81 (m, 1H), 8.16 (d, J = 7.8 Hz, 1H), 7.60 (d, J = 16.2 Hz, 1H), 7.60-7.39 (m, 4H), 7.25-7.12 (m, 6H), 6.38 (d, J = 15.6 Hz, 1H), 2.52 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 164.94, 164.88, 148.32, 147.53, 145.21, 138.44, 137.67, 136.45, 136.27, 134.34, 132.40, 130.66, 130.10, 129.24, 129.00, 128.17, 127.96, 127.40, 122.03, 121.64, 120.19, 117.38, 116.86, 19.55; HRMS (APCI): Calcd for C 26 H 20 2 3 Cl [M + H] + 443.1162, found 443.1160. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl (E)-3-(3-chlorophenyl)acrylate 5ag S18

The compound 5ag was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 5ag as a white solid (52.2 mg, 59% yield). Mp = 135.2-136.5. 1 H MR (300 MHz, CDCl 3 ): δ 10.11 (s, 1H), 8.93 (dd, J = 7.2, 1.5 Hz, 1H), 8.79 (dd, J = 4.5, 1.5 Hz, 1H), 8.14 (d, J = 8.1 Hz, 1H), 7.56 (d, J = 15.9 Hz, 1H), 7.56-7.38 (m, 4H), 7.28-7.16 (m, 4H), 7.09-7.07 (m, 1H), 7.04 (s, 1H), 2.53 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 164.83, 164.64, 148.33, 147.48, 144.99, 138.39, 137.78, 136.36, 135.67, 134.71, 134.30, 130.56, 130.33, 130.12, 129.94, 128.22, 127.98, 127.87, 127.40, 126.08, 122.11, 121.70, 120.17, 118.29, 116.86, 19.58; HRMS (APCI): Calcd for C 26 H 20 2 3 Cl [M + H] + 443.1162, found 443.1164. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl (E)-3-(2-chlorophenyl)acrylate 5ah The compound 5ah was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 5ah as a white solid (46.9 mg, 53% yield). Mp = 113.2-114.1. 1 H MR (300 MHz, CDCl 3 ): δ 10.10 (s, 1H), 8.92 (d, J = 7.2 Hz, 1H), 8.78 (d, J = 3.0 Hz, 1H), 8.11-8.04 (m, 2H), 7.58-7.14 (m, 10H), 6.41 (d, J = 15.9 Hz, 1H), 2.52 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 164.83, 164.77, 148.32, 147.50, 142.45, 138.46, 137.69, 136.15, 134.98, 134.33, 132.25, 131.22, 130.06, 130.01, 128.18, 127.92, 127.67, 127.33, 126.89, 121.98, 121.60, 120.24, 119.39, 116.87, 19.54. HRMS (APCI): Calcd for C 26 H 20 2 3 Cl [M + H] + 443.1162, found 443.1160. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl (E)-3-(4-fluorophenyl)acrylate 5ai S19

The compound 5ai was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 5ai as a white solid (53.7 mg, 63% yield). Mp = 132.7-133.4. 1 H MR (300 MHz, CDCl 3 ): δ 10.10 (s, 1H), 8.93 (d, J = 6.6 Hz, 1H), 8.78 (d, J = 3.0 Hz, 1H), 8.13 (d, J = 8.1 Hz, 1H), 7.60 (d, J = 16.2 Hz, 1H), 7.55-7.38 (m, 4H), 7.21-7.17 (m, 4H), 6.97-6.92 (m, 2H), 6.33 (d, J = 15.9 Hz, 1H), 2.52 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 164.98, 164.92, 163.98 (d, J C-F = 250.8 Hz), 148.28, 147.57, 145.35, 138.43, 137.64, 136.26, 134.36, 130.69, 130.20 (d, J C-F = 3.8 Hz), 130.07, 129.95, 128.11, 127.96, 127.39, 121.99, 121.61, 120.22, 116.88, 116.56 (d, J C-F = 1.7 Hz), 116.02, 115.73, 19.53; HRMS (APCI): Calcd for C 26 H 20 2 3 F [M + H] + 427.1458, found 427.1457. 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl (E)-3-(4-bromophenyl)acrylate 5aj The compound 5aj was prepared according to general procedure. A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 5aj as a white solid (57.3 mg, 59% yield). Mp = 145.0-145.6. 1 H MR (300 MHz, CDCl 3 ): δ 10.11 (s, 1H), 8.92 (dd, J = 6.9, 1.5 Hz, 1H), 8.78 (d, J = 3.0 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 7.57 (d, J = 16.2 Hz, 1H), 7.59-7.38 (m, 6H), 7.22-7.17 (m, 2H), 7.06-7.04 (m, 2H), 6.39 (d, J = 15.9 Hz, 1H), 2.52 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 165.02, 164.86, 148.30, 147.52, 145.26, 138.42, 137.67, 136.30, 134.33, 132.83, 131.97, 130.65, 130.10, 129.44, 128.17, 127.96, 127.41, 124.84, 122.04, 121.64, 120.19, 117.50, 116.88, 19.54; HRMS (APCI): Calcd for C 26 H 20 2 3 Br [M + H] + 487.0657, found 487.0656. 2-(quinolin-8-ylcarbamoyl)phenyl cinnamate 5ba H S20

The compound 5ba was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 5ba as a white solid (43.3 mg, 55% yield). Mp = 107.8-109.5. 1 H MR (300 MHz, CDCl 3 ): δ 11.06 (s, 1H), 8.98 (d, J = 7.2 Hz, 1H), 8.76 (d, J = 3.0 Hz, 1H), 8.19 (d, J = 7.8 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 15.9 Hz, 1H), 7.61-7.51 (m, 3H), 7.46-7.35 (m, 8H), 6.84 (d, J = 15.9 Hz, 1H); 13 C MR (75 MHz, CDCl 3 ): δ 164.94, 163.31, 148.35, 148.12, 147.31, 138.76, 136.42, 134.86, 134.06, 132.34, 131.17, 130.78, 128.91, 128.28, 128.04, 127.95, 127.57, 126.30, 123.33, 121.88, 121.50, 117.20, 117.15. HRMS (APCI): Calcd for C 25 H 19 2 3 [M + H] + 395.1396, found 395.1394. 4-chloro-2-(quinolin-8-ylcarbamoyl)phenyl cinnamate 5fa The compound 5fa was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 5fa as a white solid (35.1 mg, 41% yield). Mp: 192.3-193.2 ; 1 H MR (300 MHz, CDCl 3 ): δ 11.09 (s, 1H), 8.95 (d, J = 6.3 Hz, 1H), 8.76 (d, J = 2.7 Hz, 1H), 8.18-8.14 (m, 2H), 7.89 (d, J = 15.9 Hz, 1H), 7.61-7.53 (m, 3H), 7.40-7.31 (m, 7H), 6.83 (d, J = 16.2 Hz, 1H); 13 C MR (75 MHz, CDCl 3 ): δ 163.65, 160.80, 147.17, 146.76, 141.11, 137.70, 135.43, 133.56, 132.90, 131.15, 130.86, 130.08, 129.93, 128.90, 127.94, 127.86, 127.30, 127.03, 126.52, 123.74, 121.15, 120.65, 120.54, 116.33, 115.72. HRMS (APCI): Calcd for C 25 H 18 2 3 Cl [M + H] + 429.1006, found 429.1014. 5-methyl-2-(quinolin-8-ylcarbamoyl)phenyl cinnamate 5da The compound 5da was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 5da as a white solid (35.1 mg, 43% yield). Mp = 107.5-108.8. 1 H MR (300 MHz, CDCl 3 ): δ 11.07 (s, 1H), 8.97 (d, J = 7.2 Hz, 1H), 8.74 (d, J = 2.7 Hz, 1H), 8.14-8.09 (m, 2H), 7.89 (d, J = 16.2 Hz, 1H), 7.59-7.49 S21

(m, 2H), 7.41-7.37 (m, 6H), 7.26-7.22 (m, 1H), 7.15 (s, 1H), 6.86 (d, J = 16.2 Hz, 1H), 2.46 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 165.04, 163.28, 148.30, 148.05, 147.19, 143.37, 138.77, 136.37, 134.99, 134.09, 131.16, 130.76, 128.92, 128.27, 128.03, 127.57, 127.18, 124.90, 123.75, 121.71, 121.44, 117.28, 117.13, 21.42. HRMS (APCI): Calcd for C 26 H 21 2 3 [M + H] + 409.1552, found 409.1542. 5-fluoro-2-(quinolin-8-ylcarbamoyl)phenyl cinnamate 5ga The compound 5ga was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 5ga as a white solid (29.7 mg, 36% yield). Mp = 141.3-142.6. 1 H MR (300 MHz, CDCl 3 ): δ 11.09 (s, 1H), 8.96 (d, J = 7.2 Hz, 1H), 8.74 (d, J = 2.7 Hz, 1H), 8.26-8.21 (m, 1H), 8.15 (d, J = 5.1 Hz, 1H), 7.90 (d, J = 15.9 Hz, 1H), 7.61-7.52 (m, 2H), 7.42-7.36 (m, 6H), 7.17-7.11 (m, 2H), 6.85 (d, J = 15.9 Hz, 1H); 13 C MR (75 MHz, CDCl 3 ): δ 164.41, 164.31 (d, J C-F = 252.2 Hz), 162.33, 148.14, 147.95, 138.73, 136.47, 134.77, 133.90, 133.11 (d, J C-F = 9.9 Hz), 130.99, 128.96, 128.35, 128.06, 127.58, 121.96, 121.52, 117.25, 116.71, 113.59 (d, J C-F = 21.2 Hz), 111.00 (d, J C-F = 24.9 Hz). HRMS (APCI): Calcd for C 25 H 18 2 3 F [M + H] + 413.1301, found 413.1302. 2-(quinolin-8-ylcarbamoyl)phenyl (E)-3-(4-bromophenyl)acrylate 5bj The compound 5bj was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ethyl acetate = 12/1 gave 5bj as a white solid (54.8 mg, 58% yield). Mp = 175.9-177.2. 1 H MR (300 MHz, CDCl 3 ): δ 10.99 (s, 1H), 8.97 (d, J = 7.2 Hz, 1H), 8.75 (d, J = 3.0 Hz, 1H), 8.16 (d, J = 8.1 Hz, 2H), 7.80 (d, J = 15.9 Hz, 1H), 7.59-7.23 (m, 10H), 6.80 (d, J =15.9 Hz, 1H); 13 C MR (75 MHz, CDCl 3 ): δ 164.69, 163.31, 148.04, 145.80, 138.73, 136.49, 134.79, 132.96, 132.35, 132.18, 131.07, 129.58, 128.05, 128.01, 127.61, 126.39, 125.12, 123.28, 121.91, 121.52, 117.84, S22

117.17. HRMS (APCI): Calcd for C 25 H 18 Br 2 3 [M + H] + 473.0500, found 473.0498. 2-(quinolin-8-ylcarbamoyl)phenyl (E)-3-(4-methoxyphenyl)acrylate 5bb The compound 5bb was prepared according to general procedure (the reaction time was extended to 30 h). A purification by flash chromatography in petroleum ether/ethyl acetate = 10/1 gave 5bb as a white solid (37.3 mg, 44% yield). Mp = 135.7-137.2. 1 H MR (300 MHz, CDCl 3 ): δ 11.10 (s, 1H), 8.97 (d, J = 7.2Hz, 1H), 8.75 (d, J = 3.0 Hz, 1H), 8.19 (d, J = 7.2 Hz, 1H), 8.13 (d, J = 8.1 Hz, 1H), 7.83 (d, J = 15.9 Hz, 1H), 7.59-7.35 (m, 8H), 6.85 (d, J = 8.7 Hz, 2H), 6.69 (d, J = 15.9 Hz, 1H), 3.82 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): δ 164.21, 162.31, 160.78, 147.51, 147.01, 145.98, 137.68, 135.45, 133.86, 131.27, 130.17, 129.02, 127.03, 126.85, 126.55, 125.80, 125.10, 122.36, 120.82, 120.44, 116.29, 113.48, 113.34, 54.38. HRMS (APCI): Calcd for C 26 H 21 2 4 [M + H] + 425.1501, found 425.1502. 2-hydroxy--(quinolin-8-yl)benzamide 7a The compound 7a was prepared according to the hydrolyzation of 5ba. A purification by flash chromatography in petroleum ether/ethyl acetate = 8/1 gave 7a as a white solid (47.0 mg, 89% yield). Mp = 134.2-135.0. 1 H MR (300 MHz, CDCl 3 ): δ 12.31 (s, 1H), 10.97 (s, 1H), 8.87 (d, J = 3.0 Hz, 1H), 8.81 (dd, J = 5.7, 3.0 Hz, 1H), 8.20 (d, J = 5.1 Hz, 1H), 7.85 (d, J = 7.8 Hz, 1H), 7.62-7.45 (m, 4H), 7.07-6.98 (m, 2H); 13 C MR (75 MHz, CDCl 3 ): δ 167.40, 161.06, 147.43, 137.72, 135.43, 133.55, 132.51, 126.94, 126.28, 125.03, 121.23, 120.81, 117.99, 117.75, 115.92, 114.14. HRMS (APCI): Calcd for C 16 H 13 2 2 [M + H] + 265.0977, found 265.0975. S23

X-ray crystal structure of the compound 5ba Figure S1. RTEP view of 5ba. [2] The hydrolyzation of 5ba Scheme S1 The compound 5ba was prepared according to general procedure (the reaction time was extended to 30 h). To a 10 ml reaction tube was added amide 5ba (0.2 mmol) and aqueous ah (2 ml). The mixture was stirred at 110 for 24 h in air, and reflux. The reaction mixture was then cooled to room temperature and added aqueous HCl, adjusted the ph of the solution to 6~7. The aqueous phase was extracted with ethyl acetate (3 10 ml) and the organic layer was dried over a 2 S 4. After concentration, the resulting residue was purified by flash chromatography to afford the product 7a. [2] CCDC-1526975 (for 5ba) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. S24

Radical Experiments Scheme S2 S25

Deuteration Experiments Scheme S3 To a 10 ml reaction tube was added amide (0.2 mmol), acid (0.3 mmol), CuBr (5.7 mg, 20 mol %), Ag 2 C 3 (110.3 mg, 2 equiv), and toluene/dmf (1.5 ml/0.5 ml) in air. The mixture was stirred at 130 for 24 h. The reaction mixture was then cooled to room temperature, diluted with ethyl acetate and quenched with saturated sodium chloride. The aqueous phase was extracted with ethyl acetate (3 10 ml). The organic layer was dried over a 2 S 4. After concentration, the resulting residue was purified by flash chromatography to afford the product. The product was analyzed by 1 H MR. 1 H MR (300 MHz, CDCl 3 ): δ 10.89 (s, 1H), 8.91 (d, J = 7.2 Hz, 1H), 8.34 (d, J = 3.3 Hz, 1H), 8.29 (d, J =7.8 Hz, 2H), 8.12 (d, J = 8.4 Hz, 1H), 7.61-7.46 (m, 3H), 7.42-7.33 (m, 3H). D D D D H Figure S2 S26

KIE Studies Scheme S4 To a 10 ml reaction tube was added amide 1 (0.2 mmol), d 5-1 (0.2 mmol), acid (0.6 mmol), CuBr (11.4 mg, 0.08 mmol), Ag 2 C 3 (220.6 mg, 0.8 mmol), and toluene/dmf (3 ml/1 ml) in air. The mixture was stirred at 130 for 24 h. The reaction mixture was then cooled to room temperature, diluted with ethyl acetate and quenched with saturated sodium chloride. The aqueous phase was extracted with ethyl acetate (3 10 ml). The organic layer was dried over a 2 S 4. After concentration, the resulting residue was purified by flash chromatography to afford the product. 1 H MR analysis of the mixture showed a modest value of k H /k D = 1.4 (see the attached spectrum). 1 H MR (300 MHz, CDCl 3 ): δ 10.88 (s, 1H), 8.91 (d, J = 6.3 Hz, 1H), 8.32-8.28 (m, 3H), 8.17 (dd, J = 7.5, 1.2 Hz, 0.58H), 8.09 (dd, J = 8.1, 0.9 Hz, 1H), 7.60-7.45 (m, 5H), 7.41-7.31 (m, 4H). Figure S3 S27

Copies of 1 H and 13 C MR Spectra S28

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H 3bi Br H 3bi Br S46

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