Supporting Information

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1 Supporting Information Cobalt(II)-Catalyzed Acyloxylation of C- Bonds in Aromatic Amides with Carboxylic Acids Rina Ueno, Satoko atsui, and aoto Chatani* Department of Applied Chemistry, Faculty of Engineering, saka University, Suita, saka , Japan Contents I. General Information S2 II. Materials S2 III. Synthesis of Starting Materials S2-3 IV. General Procedure for the Direct Alkylation S3 V. Spectroscopic Data S3-16 VI. Deuterium Labeling Experiments S16-17 VII. Copies of 1 and 13 C MR Spectra S18-70 S1

2 I. General Information 1 MR and 13 C MR spectra were recorded on a JEL ECS-400 spectrometer in CDCl 3 with tetramethylsilane as the internal standard. Data are reported as follows: chemical shifts in ppm ( ), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, c= complex), coupling constant (z), and integration. Infrared spectra (IR) were obtained using a JASC FT/IR-4200 spectrometer; absorptions are reported in reciprocal centimeters with the following relative intensities: s (strong), m (medium), or w (weak). Mass spectra and high resolution mass spectra (RMS) were obtained using a JEL JMS-700 spectrometer. Column chromatography was performed with Si 2 (Silicycle SiliaFlash F60 ( mesh)). II. Materials 1,2-Dichloroethane (CAS ), Cyclohexanecarboxylic Acid (CAS ), Acetic Acid (CAS ), were purchased from acalai Tesque. Co(acac) 2 (CAS ), o-toluic acid (CAS ), 2,6-Dimethylbenzoic Acid(CAS ), Benzoic Acid(CAS ), Biphenyl- 2-carboxylic Acid (CAS ), 4-Chloro-2-methylbenzoic Acid (CAS ), 4-Fluoro-2- methylbenzoic Acid (CAS ), 4-Methoxy-2-methylbenzoic Acid (CAS ), 2-Bromo- 4-methylbenzoic Acid (CAS ), 2,6-Difluorobenzoic Acid (CAS ), Pivalic Acid (CAS ), o-ansic Acid (CAS ), 2-(Trifluoromethyl)benzoic Acid (CAS ), 3- Methoxy-2-methylbenzoic Acid (CAS ) and 8-Aminoquinoline (CAS ) were purchased from Tokyo Chemical Industry Co. Ag 2 C 3 (CAS ) was purchased from Wako Pure Chemical Industries, Ltd. III. Synthesis of Starting Materials All amides bearing an 8-aminoquinoline moiety were prepared by reacting the corresponding acid or acid chloride with 8-aminoquinoline. 1 General Procedure for the Preparation of Starting Amides. (1) Synthesis of amides from carboxylic acids. To a stirred solution of a carboxylic acid (15 mmol) and DMF (5 drops) in C 2 Cl 2 (10 ml), (CCl) 2 (1.5 ml, 18 mmol) was added dropwise. The solution was magnetically stirred at room temperature for 2 h. The solvent was then removed by evaporation under reduced pressure, and the resulting residue was dissolved in C 2 Cl 2 (15 ml). After cooling the reaction mixture to 0 C, a solution of 8- Aminoquinoline (17 mmol) and triethylamine (30 mmol) in 10 ml of the same solvent was added dropwise. The resulting mixture was allowed to warm to rt and stirred overnight. The solution 1 (a) Ano, Y.; Tobisu, M.; Chatani,. rg. Lett. 2012, 14, 354. (b) Aihara, Y.; Chatani,. Chem. Sci. 2012, 4, 664. (c) Shibata, K.; Chatani,. rg. Lett. 2014, 16, S2

3 containing the crude product was washed with saturated aqueous ac 3 (20 ml), and C 2 Cl 2 (3x20 ml). The combined organic phase was washed with 1 M Cl aq. (20 ml).the organic phase was dried over anhydrous a 2 S 4 and the solvent removed by evaporation. The resulting crude amide was purified by flash chromatography on silica gel (eluent: hexane/etac = 5/1). IV. Synthesis of Acyloxylation Products. (1) General Procedure for the Acyloxylation of C- Bonds in Aromatic Amides with Carboxylic Acids To a 5 ml screw-capped vial, 2-methyl--(8-quinolinyl)benzamide (1a) (39.3 mg, 0.15 mmol), Co(acac) 2 (3.9 mg, mmol), 2,6-dimethyl benzoic acid (2a) (33.8 mg, mmol), Ag 2 C 3 (55.2 mg, 0.2 mmol) and DCE (0.5 ml) were added in air. The mixture was stirred for 3 h at 100 C. The mixture was washed with saturated aqueous ac 3 (10 ml) and brine (10 ml). The organic phase was concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluent: hexane/etac= 10/1) to afford the alkylation product 3aa (49.4 mg, 80%) as a white solid. (2) A gram scale reaction To a 20 ml screw-capped vial, 2-methyl--(8-quinolinyl)benzamide (1a) (262.2 mg, 1.00 mmol), Co(acac) 2 (25.9 mg, 0.1 mmol), 2,6-dimethyl benzoic acid (2a) (225.8 mg, 1.50 mmol), Ag 2 C 3 (368.5 mg, 1.34 mmol) and DCE (3.3 ml) were added in air. The mixture was stirred for 3 h at 100 C. The mixture was washed with saturated aqueous ac 3 (15 ml) and brine (15 ml). The organic phase was concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluent: hexane/etac= 10/1) to afford the alkylation product 3aa (349.6 mg, 85%) as a white solid. V. Spectroscopic Data 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl 2,6-dimethylbenzoate (3aa) 49.4 mg, 80% yield. White solid. Mp = C. R f 0.29 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : 2.25 (s, 6), 2.50 (s, 3), 6.89 (d, J = 7.8 z, 2), 7.09 (t, J = 7.6 z, 1), (c, 2), (c, 2), (c, 2), 8.14 (dd, J = 8.2, 1.8 z, 1), 8.71 (dd, J = 4.1, 1.4 z, 1), 8.92 (dd, J = 6.9, 2.3 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 19.52, 19.83, , , , , , , , , , , , S3

4 132.59, , , , , , , , , IR (ATR): 3337 w, 3018 w, 2978 w, 1749 m, 1681 m, 1524 s, 1484 m, 1424 w, 1386 w, 1327 w, 1263 w, 1217 s, 1103 w, 1054 w, 772 s. MS, m/z (relative intensity, %): 410 (M +, 13), 134 (10), 133 (100), 105 (22). RMS Calcd for C , found methyl-2-(quinolin-8-ylcarbamoyl)phenyl 2-methyl benzoate (3ab) 38.1 mg, 64% yield. White solid. R f 0.29 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : δ 2.48 (s, 3), 2.53 (s, 3), 6.93 (t, J = 7.6 z, 1), 7.08 (d, J = 7.8 z, 1), (c, 2), (c, 2), (c, 2), 7.98 (dd, J = 8.0, 1.1 z, 1), 8.12 (dd, J = 8.3, 1.8 z, 1), 8.73 (dd, J = 4.1, 1.8 z, 1), 8.88 (dd, J = 6.9, 2.3 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 19.64, 21.75, , , , , , , , , , , , , , , , , , , , , , , RMS Calcd for C , found This compound has been reported previously. 2 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl benzoate (3ac) 19.2 mg, 33% yield. White solid. R f 0.29 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : δ 2.51 (s, 3), (c, 3), (c, 3), (c, 2), 8.01 (dd, J = 8.3, 1.4 z, 2), 8.11 (dd, J = 8.3, 1.8 z, 1), 8.74 (dd, J = 4.4, 1.6 z, 1), 8.85 (dd, J = 6.4, 2.3 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 19.69, , , , , , , , , , , , , , , , , , , , IR (ATR): 3348 w, 3025 w, 2933 w, 1677 m, 1582 w, 1520 s, 1481 m, 1385 w, 1325 w, 1269 m, 1096 w, 1044 w, 907 w, 825 w, 791 w, 755 w, 699 w. MS, m/z (relative intensity, %): 396 (M +, 2 Wang, F.; u, Q.; Shu, C.; Lin, Z.; Win, D.; Shi, T.; Zhang, W. rg. Lett. 2017, 19, S4

5 45), 305 (26), 254 (12), 253 (70), 252 (100), 175 (21), 147 (13), 145 (11), 144 (78), 135 (11), 91 (14). RMS Calcd for C , found This compound has been reported previously. 2 3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl [1,1'-biphenyl]-2-carboxylate (3ad) 52.5 mg, 76% yield. White solid. Mp = C. R f 0.14 (hexane/etac = 5/1). 1 MR (CDCl 3, 400 Mz) : 2.46 (s, 3), 6.82 (d, J = 7.8 z, 1), 7.04 (td, J = 7.7, 1.2 z, 1), 7.13 (d, J = 7.8 z, 1), (m, 7), 7.37 (td, J = 7.6, 1.2 z, 1), 7.42 (q, J = 4.1 z, 1), (m, 2), 7.67 (dd, J = 7.8, 1.4 z, 1), 8.15 (dd, J = 8.5, 1.6 z, 1), 8.72 (q, J = 2.0 z, 1), 8.91 (dd, J = 6.9, 2.3 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : 19.62, , , , , , , , , , , , , , , , , , (two overlapping peaks), , , , , , , , IR (ATR): 3334 w, 3014 w, 2968 w, 2925 w, 2850 w, 2359 w, 1740 s, 1679 w, 1523 m, 1483 w, 1457 w, 1423 w, 1368 m, 1218 s, 1040 s, 772 s. MS, m/z (relative intensity, %): 380 (M +, 22), 238 (18), 237 (100), 236 (59), 179 (12), 159 (19), 145 (13), 144 (91), 131 (17), 91 (12). RMS Calcd for C , found methyl-2-(quinolin-8-ylcarbamoyl)phenyl 4-fluoro-2-methylbenzoate (3ae) 35.6 mg, 57% yield. White solid. Mp = C. R f 0.29 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : δ 2.48 (s, 3), 2.53 (s, 3), 6.58 (td, J = 8.4, 2.4 z, 1), 6.77 (dd, J = 9.6, 2.8 z, 1), (c, 2), (c, 2), (c, 2), 8.01 (dd, J = 8.7, 6.0 z, 1), 8.13 (dd, J = 8.3, 1.4 z, 1), 8.73 (dd, J = 4.4, 1.6 z, 1), 8.87 (dd, J = 6.4, 2.8 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : 19.60, 21.98, , , , , , , , , , , , , , , , , , , , S5

6 138.42, , , (d, J = z), , , IR (ATR): 3340 w, 3059 w, 3025 w, 2926 w, 2860 w, 2359 w, 1738 s, 1676 s, 1607 w, 1581 w, 1521 s, 1482 s, 1461 m, 1424 m, 1384 m, 1325 m, 1262 w, 1217 s, 1111 m, 1051 m, 960 w, 897 w, 826 m, 761 m, 682 w. MS, m/z (relative intensity, %): 384 (M +, 21), 241 (24), 240 (52), 163 (16), 145 (14), 144 (100), 135 (14), 91 (13). RMS Calcd for C F , found methyl-2-(quinolin-8-ylcarbamoyl)phenyl 4-chloro-2-methylbenzoate (3af) The compound 3af was prepared according to general procedure (the amount of Co(acac) 2 was increased to 20 mol%) mg, 54% yield. White solid. Mp = C. R f 0.29 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : δ 2.45 (s, 3), 2.53 (s, 3), 6.88 (dd, J = 8.5, 2.1 z, 1), 7.06 (d, J = 1.8 z, 1), (c, 1), (c, 2), (c, 2), 7.91 (d, J = 8.3 z, 1), 8.14 (dd, J = 8.3, 1.4 z, 1), 8.72 (dd, J = 4.1, 1.8 z, 1), 8.86 (dd, J = 6.0, 3.2 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 19.66, 21.69, 76.85, 77.16, 77.37, 77.47, , , , , , , , , , , , , , , , , , , , , , , IR (ATR): 3342 w, 3016 w, 2968 w, 2360 w, 2333 w, 1739 s, 1677 m, 1595 w, 1522 s, 1482 m, 1425 m, 1382 m, 1325 m, 1218 s, 1104 s, 1051 w, 897 w, 827 w, 769 m, 680 w. MS, m/z (relative intensity, %): 444 (M +, 6), 303 (10), 302 (18), 301 (12), 300 (17), 145 (13), 144 (100), 91 (12). RMS Calcd for C Cl , found methyl-4-phenethyl-3-(quinolin-8-ylcarbamoyl)phenyl acetate (3ag) 49.7 mg, 77% yield. White solid. Mp = C. R f 0.14 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : 2.49 (s, 3), 2.52 (s, 3), 3.73 (s, 3), 6.42 (dd, J = 8.7, 2.7 z, 1), 6.57 (d, J = 2.7 z, 1), 7.20 (dd, J = 12.1, 8.0 z, 2), (c, 2), (c, 2), 8.01 (d, J = 8.7 S6

7 z, 1), 8.13 (dd, J = 8.2, 1.8 z, 1), 8.75 (dd, J = 4.4, 1.6 z, 1), 8.89 (dd, J = 6.9, 2.3 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 19.64, 22.40, 55.34, , , , , , , , , , , , , , , , , , , , , , , IR (ATR): 3334 w, 3012 w, 2969 w, 2924 w, 2360 w, 2341 w, 1739 s, 1678 w, 1605 w, 1523 m, 1483 w, 1425 w, 1368 m, 1325 w, 1218 s, 1122 w, 1036 w, 898 w, 827 w, 770 s, 685 w. MS, m/z (relative intensity, %): 424 (M +, 13), 281 (21), 239 (41), 238 (52), 161 (14), 145 (13), 144 (100), 91 (16). RMS Calcd for C , found methyl-6-phenethyl--(quinolin-8-yl)-3-(trifluoromethyl)benzamide (3ah) The compound 3ah was prepared according to general procedure (the amount of Co(acac) 2 was increased to 20 mol%) mg, 72% yield. White solid. Mp = C. R f 0.29 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : δ 2.33 (s, 3), 2.53 (s, 3), 6.91 (t, J = 7.8 z, 1), (c, 3), (c, 3), (c, 2), 8.13 (dd, J = 8.2, 1.8 z, 1), 8.72 (dd, J = 4.1, 1.8 z, 1), 8.92 (dd, J = 7.3, 1.8 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 19.63, 23.78, , , , , , , , , , , , , , , , , , , , , , , IR (ATR): 3337 w, 3009 w, 2969 w, 2925 m, 2850 w, 1744 s, 1678 m, 1523 s, 1482 m, 1424 m, 1380 m, 1326 w, 1266 w, 1220 s, 1174 w, 1122 w, 1100 m, 1053 w, 753 m. MS, m/z (relative intensity, %): 434 (M +, 9), 291 (15), 290 (21), 213 (12), 185 (19), 145 (12), 144 (100), 91 (21). RMS Calcd for C Br , found ,6-dimethyl-2-phenethyl--(quinolin-8-yl)benzamide (3ai) 49.0 mg, 78% yield. White solid. Mp = C. R f 0.29 (hexane/etac = 3/1). 1 MR (CDCl 3, S7

8 400 Mz) : δ 2.52 (s, 3), 6.77 (t, J = 8.2 z, 2), 7.24 (t, J = 7.3 z, 2), (c, 1), (c, 2), (c, 2), 8.14 (dd, J = 8.2, 1.8 z, 1), 8.72 (dd, J = 4.4, 1.6 z, 1), 8.92 (dd, J = 6.9, 1.8 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 19.60, (t, J = 66.0 z), , (d, J = z).06, , (d, J = z), , , , , , (t, J = 41.2 z), , , , , , , , (d, J = 20.6 z), , (d, J = 24.8 z), IR (ATR): 3339 w, 3012 w, 2969 w, 2925 w, 2850 w, 2359 w, 2337 w, 1742 s, 1679 w, 1624 w, 1523 m, 1469 m, 1425 w, 1368 m, 1326 m, 1218 s, 1092 w, 1053 w, 1015 w, 898 w, 771 s. MS, m/z (relative intensity, %): 418 (M +, 9), 401 (12), 284 (67), 275 (29), 260 (18), 171 (12), 141 (100), 113 (17). RMS Calcd for C F , found phenethyl--(quinolin-8-yl)-1-naphthamide (3aj) 36.6 mg, 67% yield. White solid. Mp = C. R f 0.57 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : δ 1.09 (s, 9), 2.48 (s, 3), 7.02 (d, J = 7.8 z, 1), 7.18 (d, J = 7.8 z, 1), 7.37 (t, J = 8.0 z, 1), 7.46 (dd, J = 8.2, 4.6 z, 1), (c, 2), 8.18 (dd, J = 8.2, 1.8 z, 1), 8.79 (dd, J = 4.1, 1.4 z, 1), 8.95 (dd, J = 6.9, 1.8 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 19.43, 26.96, 39.11, , , , , , , , , , , , , , , , , IR (ATR): 2955 m, 2925 m, 2902 w, 1720 m, 1681 s, 1597 s, 1525 s, 1483 w, 1384 w, 1325 m, 1219 w, 1168 m, 1114 s, 826 w, 771 s. MS, m/z (relative intensity, %): 402 (M +, 32), 260 (19), 259 (100), 258 (92), 244 (10), 215 (19), 181 (24), 153 (20), 145 (10), 144 (83), 141 (11), 140 (16), 139 (11), 91 (27). RMS Calcd for C , found methyl-2-(quinolin-8-ylcarbamoyl)phenyl cyclohexanecarboxylate (3ak) 29.2 mg, 50% yield. White solid. Mp = C. R f 0.29 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : (m, 3), (m, 2), (m, 3), 1.76 (dd, J = 13.3, S8

9 3.2 z, 2), 2.37 (tt, J = 11.0, 3.7 z, 1), 2.48 (s, 3), 7.03 (d, J = 7.8 z, 1), 7.17 (d, J = 7.8 z, 1), 7.36 (t, J = 8.0 z, 1), 7.46 (q, J = 4.1 z, 1), (m, 2), 8.18 (dd, J = 8.2, 1.4 z, 1), 8.78 (q, J = 2.0 z, 1), 8.93 (dd, J = 6.9, 1.8 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 19.54, 25.16, 25.59, 28.68, 43.06, , , , , , , , , , (two overlapping peaks), , , , , , IR (ATR): 3015 w, 2970 w, 2941 w, 1739 s, 1523 w, 1482 w, 1425 m, 1367 m, 1216 m, 1116 w, 772 m. MS, m/z (relative intensity, %): 402 (M +, 32), 260 (19), 259 (100), 258 (92), 244 (10), 215 (19), 181 (24), 153 (20), 145 (10), 144 (83), 141 (11), 140 (16), 139 (11), 91 (27). RMS Calcd for C , found methyl-2,6-diphenethyl--(quinolin-8-yl)benzamide (3al) The compound 3al was prepared according to general procedure (the amount of Co(acac) 2 was increased to 20 mol%) mg, 43% yield. White solid. R f 0.43 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : 2.10 (s, 3), 2.50 (s, 3), 7.05 (d, J = 8.2 z, 1), 7.19 (d, J = 7.8 z, 1), 7.37 (t, J = 7.8 z, 1), 7.45 (q, J = 4.3 z, 1), (m, 2), 8.18 (dd, J = 8.2, 1.4 z, 1), 8.78 (q, J = 1.8 z, 1), 8.94 (dd, J = 6.9, 1.8 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 19.70, 20.95, , , , , , , , , , , , , , , , , RMS Calcd for C , found This compound has been reported previously. 3 4-methoxy-3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl 2,6-dimethylbenzoate (3ba) The compound 3ba was prepared according to general procedure (the amount of Co(acac) 2 was increased to 40 mol%) mg, 76% yield. White solid. Mp = C. R f 0.43 (hexane/etac 3 Zhang, M. J. Chem. Res. 2013, 37, 606. S9

10 = 31). 1 MR (CDCl 3, 400 Mz) : δ 2.22 (s, 6), 3.89 (s, 3), 6.88 (d, J = 7.8 z, 2), (c, 2), (c, 1), 7.33 (d, J = 8.7 z, 1), (c, 2), 7.71 (d, J = 3.2 z, 1), 7.98 (dd, J = 4.4, 1.6 z, 1), 8.06 (dd, J = 8.2, 1.8 z, 1), 8.93 (dd, J = 7.3, 1.4 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 20.11, 55.99, , , , , , , , , , , , , , , , , , , , , IR (ATR): 3344 w, 3056 w, 3026 w, 2959 w, 2863 w, 1675 m, 1596 w, 1579 w, 1521 s, 1482 m, 1424 w, 1386 w, 1326 m, 1261 w, 1169 w, 1126 m, 1080 w, 899 w, 825 w, 791 w, 756 w, 699 w. MS, m/z (relative intensity, %): 420 (M +, 12), 276 (13), 171 (12), 145 (13), 144 (100), 91 (13). RMS Calcd for C , found (quinolin-8-ylcarbamoyl)-[1,1'-biphenyl]-3-yl 2,6-dimethylbenzoate (3ca) The compound 3ca was prepared according to general procedure (the amount of Co(acac) 2 was increased to 20 mol%) mg, 56% yield. White solid. Mp = C. R f 0.29 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : δ 2.33 (s, 6), 6.94 (d, J = 7.8 z, 2), 7.13 (tt, J = 7.6, 1.7 z, 2), (c, 3), 7.32 (dd, J = 8.2, 4.1 z, 1), 7.37 (dd, J = 8.2, 0.9 z, 1), (c, 3), (c, 3), 8.05 (dd, J = 8.2, 1.4 z, 1), 8.58 (dd, J = 4.1, 1.8 z, 1), 8.71 (dd, J = 6.9, 1.8 z, 1), 9.85 (s, 1). 13 C MR (CDCl 3, 100 Mz) : δ 19.91, , , , , , , , , , , , , , , , , , (two overlapping peaks), , , , , , IR (ATR): 3017 w, 2970 w, 2948 w, 2924 w, 1739 s, 1680 w, 1523 w, 1424 w, 1367 m, 1217 s, 1102 w, 1046 w, 771 s. MS, m/z (relative intensity, %): 380 (M +, 3), 237 (18), 236 (18), 145 (32), 144 (100), 117 (12), 105 (15). RMS Calcd for C , found (quinolin-8-ylcarbamoyl)-3-(trifluoromethyl)phenyl 2,6-dimethylbenzoate (3da) S10

11 62.9 mg, 90% yield. White solid. Mp = C. R f 0.29 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : δ 2.26 (s, 6), 6.91 (d, J = 7.3 z, 2), 7.12 (t, J = 7.6 z, 1), 7.41 (dd, J = 8.5, 4.4 z, 1), (c, 3), (c, 2), 8.14 (dd, J = 8.2, 1.8 z, 1), 8.72 (dd, J = 4.4, 1.6 z, 1), 8.87 (dd, J = 5.0, 3.7 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) :δ 19.88, , , , , (q, J = 16.4 z), (d, J = 82.4 z), , , , , , , , , , , (d, J = z), , , , , IR (ATR): 3333 w, 3007 w, 2955 w, 2925 w, 2852 w, 1750 m, 1712 s, 1686 m, 1581 w, 1524 s, 1486 m, 1463 m, 1424 m, 1360 m, 1318 s, 1262 w, 1220 s, 1173 m, 1132 m, 1099 w, 1081 w, 1028 m. MS, m/z (relative intensity, %): 422 (M +, 2), 263 (11), 223 (16), 145 (18), 144 (100), 57 (10). RMS Calcd for C , found methoxy-3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl 2,6-dimethylbenzoate (3ea) 61.2 mg, 92% yield. White solid. Mp = C. R f 0.43 (hexane/etac = 31). 1 MR (CDCl 3, 400 Mz) : δ 2.23 (s, 6), 2.34 (s, 3), 3.91 (s, 3), 6.91 (d, J = 7.3 z, 2), 6.99 (d, J = 9.2 z, 1), (c, 2), 7.42 (dd, J = 8.2, 4.1 z, 1), (c, 2), 8.15 (dd, J = 8.2, 1.8 z, 1), 8.73 (dd, J = 4.4, 1.6 z, 1), 8.93 (dd, J = 6.9, 1.8 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 13.22, 19.79, 56.12, , , , , , , , , , , , , (two overlapping peaks), , , , , , , IR (ATR): 3338 w, 3012 w, 2928 w, 2834 w, 1745 m, 1679 m, 1595 w, 1523 w, 1479 s, 1425 m, 1385 m, 1326 m, 1302 w, 1272 m, 1220 s, 1146 w, 1098 s, 1052 s, 827 s. MS, m/z (relative intensity, %): 420 (M +, 12), 276 (13), 171 (12), 145 (13), 144 (100), 91 (13). RMS Calcd for C , found acetoxy-3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl 2,6-dimethylbenzoate (3fa) S11

12 63.4 mg, 90% yield. White solid. Mp = C. R f 0.34 (exane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : δ 2.25 (s, 6), 2.31 (s, 3), 2.38 (s, 3), 6.90 (d, J = 7.8 z, 2), 7.10 (t, J = 7.8 z, 1), 7.24 (s, 2), 7.42 (dd, J = 8.2, 4.1 z, 1), (c, 2), 8.15 (dd, J = 8.2, 1.8 z, 1), 8.74 (dd, J = 4.1, 1.4 z, 1), 8.90 (dd, J = 6.0, 2.7 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 13.59, 19.86, 20.96, , , , , , , , , , , , , , , , , , , , , , IR (ATR): 3015 w, 2970 w, 2943 w, 1738 s, 1437 w, 1368 m, 1214 m, 772 m. MS, m/z (relative intensity, %): 342 (M +, 100), 313 (16), 297 (13), 251 (35), 223 (14), 197 (12), 171 (25), 144 (51), 141 (11), 91 (14). RMS Calcd for C , found ,4-dimethyl-2-(quinolin-8-ylcarbamoyl)phenyl 2,6-dimethylbenzoate (3ga) 60.4 mg, 94% yield. White solid. Mp = C. R f 0.43 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : δ 2.23 (s, 6), 2.34 (s, 3), 2.36 (s, 3), 6.89 (d, J = 7.8 z, 2), (c, 2), 7.31 (d, J = 8.2 z, 1), 7.41 (dd, J = 8.2, 4.1 z, 1), (c, 2), 8.14 (dd, J = 8.2, 1.8 z, 1), 8.72 (dd, J = 4.4, 1.6 z, 1), 8.93 (dd, J = 7.1, 2.1 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 16.86, 19.78, 20.00, , , , , , , , , , , , , , , , , , , , , IR (ATR): 3335 w, 3014 w, 2970 w, 2925 w, 1739 s, 1679 w, 1523 m, 1483 w, 1424 w, 1368 m, 1219 s, 1102 w, 1053 w, 771 s. MS, m/z (relative intensity, %): 356 (19), 355 (M +, 74), 264 (44), 213 (11), 212 (75), 211 (50), 210 (11), 197 (14), 185 (16), 184 (48), 183 (18), 182 (20), 172 (12), 171 (100), 170 (13), 144 (40), 94 (89), 93 (18). RMS Calcd for C , found (quinolin-8-ylcarbamoyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl 2,6-dimethylbenzoate (3ha) The compound 3ha was prepared according to general procedure (the amount of Co(acac) 2 and S12

13 Ag 2 C 3 were increased to 20 mol% and 0.30 mmol, respectively).30.8 mg, 45% yield. White solid. Mp = C. R f 0.14 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : δ 2.29 (s, 6), (c, 4), 6.82 (d, J = 9.2 z, 1), 6.92 (d, J = 7.8 z, 2), 7.03 (d, J = 8.7 z, 1), 7.11 (t, J = 7.6 z, 1), 7.41 (dd, J = 8.2, 4.1 z, 1), (c, 2), 8.13 (dd, J = 8.5, 1.6 z, 1), 8.74 (dd, J = 4.4, 1.6 z, 1), 8.92 (dd, J = 6.9, 1.8 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 19.90, 64.10, 64.75, , , , , , , , , , , , , , , , , , , , , IR (ATR): 3016 w, 2955 w, 2925 w, 2852 w, 1742 s, 1679 w, 1525 m, 1481 m, 1377 m, 1328 w, 1299 w, 1263 m, 1219 s, 1078 m, 1048 w, 766 s. MS, m/z (relative intensity, %): 454 (M +, 19), 134 (10), 133 (100), 105 (15). RMS Calcd for C , found methoxy-2-(quinolin-8-ylcarbamoyl)phenyl 2,6-dimethylbenzoate (3ia) 34.7 mg, 55% yield. White solid. Mp = C. R f 0.43 (hexane/etac = 31). 1 MR (CDCl 3, 400 Mz) : δ 2.32 (s, 6), 3.90 (s, 3), 6.95 (t, J = 7.6 z, 4), 7.13 (t, J = 7.6 z, 1), 7.41 (dd, J = 8.2, 4.1 z, 1), (c, 3), 8.14 (dd, J = 8.2, 1.4 z, 1), 8.75 (dd, J = 4.1, 1.8 z, 1), 8.93 (dd, J = 7.3, 1.4 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 20.11, 55.99, , , , , , , , , , , , , , , , , , , , , IR (ATR): 3005 w, 2957 w, 2922 w, 2852 w, 1745 m, 1679 m, 1605 w, 1525 s, 1468 m, 1423 m, 1383 w, 1327 w, 1261 w, 1219 s, 1080 s, 770 s. MS, m/z (relative intensity, %): 426 (M +, 11), 134 (10), 133 (100), 105 (16). RMS Calcd for C , found fluoro-3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl 2,6-dimethylbenzoate (3ja) 55.2 mg, 87% yield. White solid. Mp = C. R f 0.43 (hexane/etac = 31). 1 MR S13

14 (CDCl 3, 400 Mz) : δ 2.28 (s, 6), 2.46 (s, 3), 6.92 (d, J = 7.8 z, 2), 7.12 (t, J = 7.6 z, 1), (c, 3), 7.43 (dd, J = 8.2, 4.1 z, 1), (c, 2), 8.16 (dd, J = 8.2, 1.4 z, 1), 8.73 (dd, J = 4.1, 1.8 z, 1), 8.91 (dd, J = 6.0, 3.2 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 18.98, 19.88, , , , (d, J = z), , , , (d, J = 28.8 z), , , (d, J = 12.4 z), , , , , , , , , , , (d, J = 8.4 z), IR (ATR): 3337 w, 3014 w, 2970 w, 2925 w, 1740 s, 1680 w, 1523 m, 1484 m, 1424 w, 1367 m, 1326 w, 1255 w, 1219 s, 1100 w, 1049 w, 1008 w, 777 s. MS, m/z (relative intensity, %): 393 (30), 392 (M +, 100), 301 (37), 249 (14), 248 (27), 247 (17), 219 (33), 171 (56), 145 (15), 144 (88), 131 (16), 102 (10), 91 (17). RMS Calcd for C F , found bromo-3-methyl-2-(quinolin-8-ylcarbamoyl)phenyl 2,6-dimethylbenzoate (3ka) 46.9 mg, 64% yield. White solid. Mp = C. R f 0.29 (hexane/etac = 31). 1 MR (CDCl 3, 400 Mz) : δ 2.42 (s, 6), 2.44 (s, 3), 6.91 (d, J = 7.8 z, 2), (c, 2), 7.40 (dd, J = 8.2, 4.1 z, 1), (c, 2), 7.64 (d, J = 8.2 z, 1), 8.12 (dd, J = 8.2, 1.8 z, 1), 8.73 (dd, J = 4.1, 1.8 z, 1), 8.87 (dd, J = 6.2, 2.5 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 19.23, 21.17, , , , , , , , , , , , , , , , , , , , , IR (ATR): 3017 w, 2970 w, 2943 w 1739 s, 1678 w, 1524 w, 1481 w, 1425 w, 1367 m, 1217 s, 1094 w, 1050 w, 771 s. MS, m/z (relative intensity, %): 396 (M +, 2), 252 (11), 145 (23), 144 (100), 121 (34). RMS Calcd for C Br , found ,6-difluoro-2-(quinolin-8-ylcarbamoyl)phenyl 2,6-dimethylbenzoate (3la) 33.4 mg, 52% yield. White solid. Mp = C. R f 0.29 (hexane/etac = 3/1). 1 MR S14

15 (CDCl 3, 400 Mz) : δ 2.36 (s, 6), 6.97 (d, J = 7.3 z, 2), (c, 2), 7.34 (td, J = 9.2, 4.6 z, 1), 7.43 (dd, J = 8.3, 4.1 z, 1), 7.57 (d, J = 4.6 z, 2), 8.16 (dd, J = 8.5, 1.6 z, 1), 8.74 (dd, J = 4.4, 1.6 z, 1), 8.87 (t, J = 4.4 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 20.06, (dd, J = 28.8 z, 99.2 z), , (dd, J = 86.8 z, 37.2 z), (d, J = 37.2 z), , , , (d, J = 24.8 z), , , , , , , , , (d, J = 12.0 z), , , (d, J = 8.4 z), , IR (ATR): 3015 w, 2970 w, 2944 w, 1739 s, 1546 w, 1437 w, 1437 m, 1367 m, 1217 w, 1088 w, 772 s. MS, m/z (relative intensity, %): 442 (M +, 2), 167 (23), 145 (23), 144 (100). RMS Calcd for C , found fluoro-5-methoxy-2-(quinolin-8-ylcarbamoyl)phenyl 2,6-dimethylbenzoate (3ma) The compound 3ma was prepared according to general procedure (the amount of Co(acac) 2 was increased to 20 mol%) mg, 72% yield. White solid. Mp = C. R f 0.23 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : δ 2.36 (s, 6), 3.88 (s, 3), (c, 2), 6.95 (d, J = 7.8 z, 2), 7.14 (t, J = 7.6 z, 1), 7.40 (dd, J = 8.2, 4.1 z, 1), (c, 2), 8.13 (dd, J = 8.2, 1.4 z, 1), 8.70 (dd, J = 4.1, 1.8 z, 1), 8.88 (dd, J = 6.6, 2.1 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 20.16, 56.12, 99.84, , , , , , , (d, J = z), , , , , (d, J = 30.4 z), , , , , (d, J = 16.0 z), , , , IR (ATR): 3017 w, 2970 w, 2945 w, 2925 w, 1739 s, 1628 w, 1527 w, 1425 w, 1367 m, 1218 s, 1150 w, 1102 w, 1056 w, 771 s. MS, m/z (relative intensity, %): 384 (M +, 15), 241 (41), 240 (42), 145 (34), 144 (100), 117 (17), 109 (16). RMS Calcd for C F , found (quinolin-8-ylcarbamoyl)naphthalen-2-yl 2,6-dimethylbenzoate (3na) S15

16 56.7 mg, 86% yield. White solid. Mp = C. R f 0.43 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) : δ 2.30 (s, 6), 6.92 (d, J = 7.3 z, 2), 7.11 (t, J = 7.6 z, 1), 7.38 (dd, J = 8.2, 4.1 z, 1), 7.47 (d, J = 8.7 z, 1), (m, 4), 7.94 (dd, J = 6.2, 3.4 z, 1), 8.03 (d, J = 8.7 z, 1), 8.09 (dd, J = 6.2, 3.4 z, 1), 8.14 (dd, J = 8.5, 1.6 z, 1), 8.63 (dd, J = 4.1, 1.4 z, 1), 9.05 (dd, J = 7.3, 1.4 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz): δ 19.90, 76.84, 77.16, 77.36, 77.47, , , , , , , , , , , , , , , , , , , , , , , , IR (ATR): 3015 w, 2970 w, 2947 w, 1739 s, 1674 w, 1522 w, 1425 w, 1367 s, 1217 m, 1100 w, 1048 w, 772 s. MS, m/z (relative intensity, %): 444 (M +, 6), 303 (14), 302 (14), 301 (15), 300 (13), 145 (26), 144 (100). RMS Calcd for C , found (quinolin-8-ylcarbamoyl)thiophen-3-yl 2,6-dimethylbenzoate (3na) The compound 3na was prepared according to general procedure (the amount of Co(acac) 2 was increased to 20 mol%) mg, 77% yield. White solid. Mp = C. R f 0.23 (hexane/etac = 3/1). 1 MR (CDCl 3, 400 Mz) :δ 2.40 (s, 6), 7.12 (d, J = 7.8 z, 2), 7.19 (dd, J = 8.2, 4.6 z, 1), 7.35 (t, J = 7.6 z, 1), 7.41 (d, J = 5.5 z, 1), 7.45 (dd, J = 8.2, 1.4 z, 1), (m, 2), 7.58 (d, J = 5.3 z, 1), 8.03 (dd, J = 8.2, 1.8 z, 1), 8.86 (dd, J = 7.3, 1.4 z, 1), (s, 1). 13 C MR (CDCl 3, 101 Mz) : δ 20.50, , , , , , , , , , , , , , , , , , , IR (ATR): 3016 w, 2970 w, 2943 w, 2924 w, 2852 w, 1739 s, 1654 w, 1531 w, 1431 w, 1367 m, 1217 s, 1096 w, 1043 w, 771 s. MS, m/z (relative intensity, %): 456 (M +, 50), 314 (16), 313 (100), 312 (70), 144 (20), 132 (15). RMS Calcd for C S , found VI. Deuterium Labeling Experiments S16

17 D D CD 3 D D 1a-d mmol ArC (2a) mmol cat. Co(acac) 2 10 mol% Ag 2 C mmol DCE 0.5 ml 100 C, 30 min under air D D CD 3 D D 1a-d 7 68% 98% (D) + D D CD 3 2 CAr D 3aa-d 6 19% S17

18 VII. Copies of 1 and 13 C MR Spectra S18

19 S19

20 S20

21 3ab S21

22 3ab S22

23 3ac S23

24 3ac S24

25 Ph 3ad S25

26 Ph 3ad S26

27 F 3ae S27

28 F 3ae S28

29 Cl 3af S29

30 Cl 3af S30

31 S31

32 S32

33 Br 3ah S33

34 Br 3ah S34

35 F F 3ai S35

36 F F 3ai S36

37 3aj S37

38 S38

39 3ak S39

40 3ak S40

41 C3 3al S41

42 C3 3al S42

43 Me 3ba S43

44 Me 3ba S44

45 Ph 3ca S45

46 Ph 3ca S46

47 CF 3 3da S47

48 CF 3 3da S48

49 Me 3ea S49

50 Me 3ea S50

51 Ac 3fa S51

52 Ac 3fa S52

53 3ga S53

54 3ga S54

55 3ha S55

56 3ha S56

57 Me 3ia S57

58 Me 3ia S58

59 F 3ja S59

60 F 3ja S60

61 Br 3ka S61

62 Br 3ka S62

63 F F 3la S63

64 F F 3la S64

65 F Me 3ma S65

66 F Me 3ma S66

67 3na S67

68 3na S68

69 S 3oa S69

70 S 3oa S70