Selective Synthesis of Indoles by Cobalt(III) Catalyzed. C H/N O Functionalization with Nitrones

Supporting Information Selective Synthesis of Indoles by Cobalt(III) Catalyzed C H/N O Functionalization with Nitrones Hui Wang, Marc Moselage, María J. González, and Lutz Ackermann* Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Tammannstraße 2, 37077 Göttingen, Germany Fax: +49 551 39-6777 E-Mail: Lutz.Ackermann@chemie.uni-goettingen.de http://www.ackermann.chemie.uni-goettingen.de/ General Remarks... S-2 Optimization for the Synthesis of Indoles 3aa... S-3 General Procedure for the Cobalt-Catalyzed C H/N O Functionalization... S-7 Intermolecular Competition Experiment... S-21 Competition Experiment between Alkynes 2... S-23 H/D Exchange Experiments... S-25 Intermolecular KIE... S-27 References... S-29 1 H-, 13 C-, and 19 F-NMR Spectra... S-30 S 1

General Remarks Catalytic reactions were carried out in Schlenk or pressure tubes under an ambient atmosphere of air. The following starting materials were synthesized according to previously described methods: Cp*CoI 2 (CO), [1] nitrones 1, [2] bisaryl alkynes 2, [3] and aryl alkyl alkynes 2. [4] [Cp*Co(MeCN) 3 ][SbF 6 ] 2 was prepared in analogy to the rhodium complex. [5] Other chemicals were obtained from commercial sources and were used without further purification. Yields refer to isolated compounds, estimated to be > 95% pure as determined by 1 H-NMR and GC-analysis. Chromatography: Merck silica gel 60 (40-63 μm). Recycling preparative HPLC (GPC) was performed on a system from JAI (LC-92XX II Series, Injection-and Control-Valve, UV and RI Detector) connected to JAIGEL HH series columns. CHCl 3 of HPLC grade was employed. NMR: Spectra were recorded on Bruker Avance 300, Varian Unity 300, Mercury 300 or Inova 500 in the solvent indicated; chemical shifts (δ) are given in ppm. All IR spectra were recorded on a Bruker FT-IR Alpha device. MS: EI-MS- and ESI-MS-spectra were recorded with Finnigan MAT 95, 70 ev; High resolution mass spectrometry (HRMS) with APEX IV 7T FTICR, Bruker Daltonic. M. p.: Stuart melting point apparatus SMP3, Barloworld Scientific, values are uncorrected. S 2

Optimization for the Synthesis of Indoles 3aa Table S1: Optimization of catalytic reaction conditions a S 3

a Reaction conditions: 1a (0.50 mmol), 2a (0.75 mmol), [Co] (xx mol %), AgSbF 6 (20 mol %), NaOAc (20 mol %), solvent (2.0 ml), under air, 100 C, 16h. b Yield of isolated product. c Cu(OAc) 2 (1.0 equiv) was used. d Without Ag salts. e HOPiv (20 mol %) used instead of NaOAc. f CsOAc (20 mol %) used instead of NaOAc. S 4

Table S2: Effect of additives a a Reaction conditions: 1a (0.50 mmol), 2a (0.75 mmol), [Co] (5.0 mol %), additive 1 (20 mol %), additive 2 (20 mol %), HFIP (2.0 ml), under air, 120 C, 16h. b Yield of isolated product. S 5

Table S3: Effect of additives a a Reaction conditions: 1a (0.50 mmol), 2a (0.75 mmol), [Co] (5.0 mol %), AgSbF 6 (20 mol %), additive (20 mol %), HFIP (2.0 ml), under air, 100 C, 16h. b Yield of isolated product. S 6

General Procedure for the Cobalt-Catalyzed C H/N O Functionalization A suspension of nitrone 1 (0.50 mmol, 1.0 equiv), alkyne 2 (0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), AgSbF 6 (34.4 mg, 20 mol %), NaOAc (8.2 mg, 20 mol %) or Piv-Leu-OH (22.1 mg, 20 mol %) was stirred at 100 C for 16 h under ambient air. After cooling to ambient temperature, the mixture was transferred into a round bottom flask with CH 2 Cl 2 (20 ml) and concentrated in vacuo. Purification by column chromatography on silica gel and optionally by GPC afforded the desired products 3. 5-Methyl-2,3-diphenyl-1H-indole (3aa) The general procedure was followed using N-(4-methoxybenzylidene)-4-methylaniline oxide 1a (121 mg, 0.50 mmol, 1.0 equiv), 1,2-diphenylethyne 2a (134 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), NaOAc (8.2 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-hexane/ch 2 Cl 2 : 3/1) yielded 3aa (130 mg, 92%) as a white solid. M. p. = 143 145 C. 1 H NMR (300 MHz, CDCl 3 ): δ = 8.11 (s, 1H), 7.58 7.37 (m, 7H), 7.36 7.19 (m, 5H), 7.09 (dd, J = 8.3, 1.6 Hz, 1H), 2.46 (s, 3H). 13 C NMR (75 MHz, CDCl 3 ): δ = 135.2 (C q ), 134.2 (C q ), 134.2 (C q ), 132.8 (C q ), 130.2 (CH), 129.7 (C q ), 129.0 (C q ), 128.6 (CH), 128.5 (CH), 128.1 (CH), 127.5 (CH), 126.1 (CH), 124.3 (CH), 119.2 (CH), 114.6 (C q ), 110.5 (CH), 21.5 (CH 3 ). IR (ATR): 3368, 3056, 1600, 1448, 1316, 1030, 780, 760, 696 cm -1. MS (ESI) m/z (relative intensity) 282 (100) [M-H] -. S 7

HR-MS (ESI) m/z calcd for C 21 H 17 N [M-H] - : 282.1288, found: 282.1292. The analytical data were in accordance with those reported in the literature. [6] 2,3-Diphenyl-1H-indole (3da) The general procedure was followed using N-(4-methoxybenzylidene)aniline oxide 1d (113.6 mg, 0.50 mmol, 1.0 equiv), 1,2-diphenylethyne 2a (134 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), NaOAc (8.2 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-hexane/ch 2 Cl 2 : 3/1) yielded 3da (102.3 mg, 76%) as a white solid. M. p. = 98 100 C. 1 H NMR (300 MHz, CDCl 3 ): δ = 8.18 (s, 1H), 7.71 (d, J = 7.9 Hz, 1H), 7.55 7.38 (m, 7H), 7.38 7.22 (m, 5H), 7.17 (t, J = 7.5 Hz, 1H). 13 C NMR (75 MHz, CDCl 3 ): δ = 135.8 (C q ), 135.0 (C q ), 134.0 (C q ), 132.6 (C q ), 130.1 (CH), 128.7 (C q ), 128.6 (CH), 128.5 (CH), 128.1 (CH), 127.7 (CH), 126.2 (CH), 122.7 (CH), 120.4 (CH), 119.7 (CH), 115.0 (C q ), 110.7 (CH). IR (ATR): 3389, 3039, 1601, 1455, 1151, 1008, 748, 694, 606, 515 cm -1. MS (ESI) m/z (relative intensity) 269 (100), 296 (85), 381 (20) [M] +. HR-MS (ESI) m/z calcd for C 20 H 15 N [M] + : 269.1199, found: 269.1197. The analytical data were in accordance with those reported in the literature. [6] 5-Fluoro-2,3-diphenyl-1H-indole (3ea) The general procedure was followed using 4-fluoro-N-(4-methoxybenzylidene)aniline oxide 1e (122.6 mg, 0.50 mmol, 1.0 equiv), 1,2-diphenylethyne 2a (134 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), NaOAc (8.2 mg, 20 mol %). S 8

Purification by coloumn chromatography on silica gel (n-hexane/ch 2 Cl 2 : 3/1) yielded 3ea (101 mg, 70%) as a white solid. M. p. = 124 126 C. 1 H NMR (300 MHz, CDCl 3 ): δ = 8.13 (s, 1H), 7.50 7.37 (m, 7H), 7.36 7.26 (m, 5H), 7.01 (td, J = 9.0, 2.5 Hz, 1H). 13 C NMR (75 MHz, CDCl 3 ): δ = 158.4 (d, 1 J = 235.3 Hz, C q ), 135.8 (C q ), 134.6 (C q ), 132.3 (C q ), 132.3 (C q ), 129.9 (CH), 129.2 (d, 3 J = 10.1 Hz, C q ), 128.7 (CH), 128.6 (CH), 128.1 (CH), 127.9 (CH), 126.4 (CH), 115.2 (d, 4 J = 4.7 Hz, C q ), 111.6 (d, 3 J = 9.8 Hz, CH), 111.0 (d, 2 J = 26.5 Hz, CH), 104.6 (d, 2 J = 24.1 Hz, CH). 19 F NMR (283 MHz, CDCl 3 ): δ = -123.44 (td, J = 9.5, 4.4 Hz). IR (ATR): 3423, 1600, 1474, 1069, 951, 859, 754, 692, 604, 465 cm -1. MS (ESI) m/z (relative intensity) 286 (100) [M-H] -. HR-MS (ESI) m/z calcd for C 20 H 14 NF [M-H] - : 286.1038, found: 286.1040. The analytical data were in accordance with those reported in the literature. [6] 5-Chloro-2,3-diphenyl-1H-indole (3fa) The general procedure was followed using 4-chloro-N-(4-methoxybenzylidene)aniline oxide 1f (131 mg, 0.50 mmol, 1.0 equiv), 1,2-diphenylethyne 2a (134 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), Piv-Leu-OH (22.1 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-hexane/ch 2 Cl 2 : 3/1) yielded 3fa (115 mg, 76%) as a pale yellow solid. M. p. = 110 112 C. 1 H NMR (300 MHz, CDCl 3 ): δ = 8. 20 (s, 1H), 7.63 (d, J = 2.0 Hz, 1H), 7.50 7.34 (m, 6H), 7.34 7.25 (m, 5H), 7.18 (dd, J = 8.6, 2.0 Hz, 1H). 13 C NMR (76 MHz, CDCl 3 ): δ = 135.4 (C q ), 134.3 (C q ), 134.2 (C q ), 132.1 (C q ), 130.0 (CH), 129.9 (C q ), 128.7 (CH), 128.6 (CH), 128.1 (CH), 128.0 (CH), 126.5 (CH), 126.1 (C q ), 122.9 (CH), 119.1 (CH), 114.7 (C q ), 111.9 (CH). IR (ATR): 3438, 3420, 1506, 1458, 762, 694, 607, 505, 476 cm -1. MS S 9

(ESI) m/z (relative intensity) 302 (100), 304 (30) [M-H] -. HR-MS (ESI) m/z calcd for C 20 H 14 NCl [M-H] - : 302.0742, found: 302.0743. The analytical data were in accordance with those reported in the literature. [6] 5-Bromo-2,3-diphenyl-1H-indole (3ga) The general procedure was followed using 4-bromo-N-(4-methoxybenzylidene)aniline oxide 1g (153 mg, 0.50 mmol, 1.0 equiv), 1,2-diphenylethyne 2a (134 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), NaOAc (8.2 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-hexane/ch 2 Cl 2 : 3/1) yielded 3ga (158 mg, 91%) as a pale yellow solid. M. p. = 133 135 C. 1 H NMR (300 MHz, CDCl 3 ): δ = 8.19 (s, 1H), 7.78 (d, J = 1.8 Hz, 1H), 7.49 7.36 (m, 6H), 7.35 7.21 (m, 6H). 13 C NMR (75 MHz, CDCl 3 ): δ = 135.2 (C q ), 134.4 (C q ), 134.3 (C q ), 132.0 (C q ), 130.5 (C q ), 130.0 (CH), 128.7 (CH), 128.6 (CH), 128.1 (CH), 128.0 (CH), 126.5 (CH), 125.4 (CH), 122.1 (CH), 114.6 (C q ), 113.7 (C q ), 112.3 (CH). IR (ATR): 3451, 1449, 1306, 1286, 760, 696, 648, 586, 508, 445 cm -1. MS (ESI) m/z (relative intensity) 346 (100) [M-H] -. HR-MS (ESI) m/z calcd for C 20 H 14 NBr [M-H] - : 346.0237, found: 346.0231. The analytical data were in accordance with those reported in the literature. [6] 6-Methyl-2,3-diphenyl-1H-indole (3ha) The general procedure was followed using N-(4-methoxybenzylidene)-3-methylaniline oxide 1h (121 mg, 0.50 mmol, 1.0 equiv), 1,2-diphenylethyne 2a (134 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 S 10

mol %), Piv-Leu-OH (22.1 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-hexane/ CH 2 Cl 2 : 3/1) yielded 3ha (126 mg, 89%) as a white solid. M. p. = 95 97 C. 1 H NMR (300 MHz, CDCl 3 ): δ = 8.07 (s, 1H), 7.56 (d, J = 8.2 Hz, 1H), 7.48 7.36 (m, 5H), 7.35 7.24 (m, 5H), 7.22 7.19 (m, 1H), 6.99 (dd, J = 8.2, 0.9 Hz, 1H), 2.49 (s, 3H). 13 C NMR (75 MHz, CDCl 3 ): δ = 136.3 (C q ), 135.2 (C q ), 133.3 (C q ), 132.8 (C q ), 132.6 (C q ), 130.1 (CH), 128.6 (CH), 128.5 (CH), 128.0 (CH), 127.5 (CH), 126.6 (C q ), 126.1 (CH), 122.2 (CH), 119.3 (CH), 114.9 (C q ), 110.8 (CH), 21.7 (CH 3 ). IR (ATR): 3406, 1601, 1502, 1449, 1439, 1250, 914, 804, 763, 697 cm -1. MS (ESI) m/z (relative intensity) 282 (100) [M-H] -. HR-MS (ESI) m/z calcd for C 21 H 17 N [M-H] - : 282.1288, found: 282.1289. The analytical data were in accordance with those reported in the literature. [6] Ethyl 2,3-diphenyl-1H-indole-5-carboxylate (3ia): The general procedure was followed using nitrone 1i (150 mg, 0.50 mmol, 1.0 equiv), diphenylacetylene 2a (134 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), NaOAc (8.2 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-hexane/etoac: 20/1) yielded 3ia (113 mg, 67%) as an off-white solid. M.p. = 178-180 C. 1 H NMR (500 MHz, DMSO-d 6 ): δ = 11.98 (s, 1H), 8.15 (d, J = 1.6 Hz, 1H), 7.82 (dd, J = 8.5, 1.6 Hz, 1H), 7.53 (d, J = 8.5 Hz, 1H), 7.48-7.42 (m, 4H), 7.38-7.32 (m, 6H), 4.29 (q, J = 7.1 Hz, 2H), 1.30 (t, J = 7.1 Hz, 3H). 13 C NMR (125 MHz, DMSO-d 6 ): δ = 166.3 (C q ), 138.4 (C q ), 135.5 (C q ), 134.3 (C q ), 131.6 (C q ), 129.6 (CH), 128.5 (CH), 128.3 (CH), 127.9 (CH), 127.6 (CH), 127.5 (C q ), 126.3 (CH), 122.7 (CH), 121.3 (C q ), 120.8 (CH), 114.3 (C q ), 111.1 (CH), 60.0 (CH 2 ), 14.2 (CH 3 ). IR (ATR): 3310, 1684, 1306, 1235, 1102, 1083, 756, 694, 654, 608. MS (ESI) m/z (relative intensity) 342.2 (20) [M+H] +, 364.1 (100) [M+Na] +. HR-MS (ESI) m/z calcd for C 23 H 19 NO 2 Na [M+Na] + : 364.1313, found: 364.1301. S 11

2,3-Diphenyl-5-(thiophen-2-yl)-1H-indole (3ja): The general procedure was followed using nitrone 1j (155 mg, 0.50 mmol, 1.0 equiv), diphenylacetylene 2a (134 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), NaOAc (8.2 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-hexane/etoac: 30/1) and GPC yielded 3ja (144 mg, 82%) as an off-white solid. M.p. = 186-188 C. 1 H NMR (500 MHz, DMSO-d 6 ): δ = 11.71 (s, 1H), 7.69 (d, J = 1.2 Hz, 1H), 7.50 (d, J = 1.3 Hz, 2H), 7.48-7.46 (m, 2H), 7.44-7.35 (m, 8H), 7.33-7.29 (m, 2H), 7.08 (dd, J = 5.1, 3.5 Hz, 1H). 13 C NMR (75 MHz, DMSO-d 6 ): δ = 145.3 (C q ), 135.7 (CH), 135.1 (C q ), 134.9 (C q ), 132.2 (C q ), 129.8 (CH), 128.7 (CH), 128.5 (CH), 128.4 (C q ), 128.3 (C q ), 128.1 (CH), 127.7 (C q ), 126.3 (CH), 126.0 (CH), 124.0 (CH), 122.1 (CH), 120.6 (CH), 115.3 (CH), 113.6 (C q ), 112.1 (CH). IR (ATR): 3399, 798, 761, 703, 693, 630, 608, 515, 494, 431. MS (ESI) m/z (relative intensity) 350.1 (100) [M-H] -, 386.1 (3) [M+Cl] -. HR-MS (ESI) m/z calcd for C 24 H 16 NS [M-H] - : 350.1009, found: 350.1009. 5-Methyl-2,3-di-p-tolyl-1H-indole (3ab) The general procedure was followed using N-(4-methoxybenzylidene)-4-methylaniline oxide 1a (121 mg, 0.50 mmol, 1.0 equiv), 1,2-di-p-tolylethyne 2b (155 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), Piv-Leu-OH (22.1 mg, 20 mol %). Purification by coloumn chromatography S 12

on silica gel (n-pentane/etoac: 30/1) yielded 3ab (115.2 mg, 74%) as a white solid. M. p. = 157 160 C. 1 H NMR (300 MHz, CDCl 3 ): δ = 8.05 (s, 1H), 7.44 (s, 1H), 7.35-7.28 (m, 5H), 7.23 7.17 (m, 2H), 7.16 7.09 (m, 2H), 7.05 (dd, J = 8.4, 1.6 Hz, 1H), 2.44 (s, 3H), 2.41 (s, 3H), 2.35 (s, 3H). 13 C NMR (125 MHz, CDCl 3 ): δ = 137.2 (C q ), 135.5 (C q ), 134.0 (C q ), 132.2 (C q ), 130.0 (C q ), 129.9 (CH), 129.9 (C q ) 129.4 (C q ), 129.2 (CH), 129.1 (CH), 129.1 (C q ), 127.8 (CH), 123.9 (CH), 119.1 (CH), 114.1 (C q ), 110.4 (CH), 21.6 (CH 3 ), 21.3 (CH 3 ), 21.3 (CH 3 ). IR (ATR): 3379, 2917, 1510, 1439, 821, 798, 723, 517 cm -1. MS (EI) m/z (relative intensity): 327 (17), 311 (100), 298 (15), 91.1 (9). HR-MS (ESI) m/z calcd for C 23 H 21 N [M] + : 311.1674, found: 311.1665. The analytical data were in accordance with those reported in the literature. [7] 2,3-Bis(4-methoxyphenyl)-5-methyl-1H-indole (3ac) The general procedure was followed using N-(4-methoxybenzylidene)-4-methylaniline oxide 1a (121 mg, 0.50 mmol, 1.0 equiv), 1,2-bis(4-methoxyphenyl)ethyne 2c (178 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), Piv-Leu-OH (22.1 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-pentane/etoac: 10/1) yielded 3ac (122 mg, 71%) as a yellow solid. M. p. = 147 150 C. 1 H NMR (500 MHz, CDCl 3 ): δ = 8.03 (s, 1H), 7.40 (s, 1H), 7.37 7.30 (m, 4H), 7.27 (d, J = 8.2 Hz, 1H), 7.03 (s, 1H), 6.93 (d, J = 8.7 Hz, 2H), 6.84 (d, J = 8.9 Hz, 2H), 3.85 (s, 3H), 3.80 (s, 3H), 2.43 (s, 3H). 13 C NMR (125 MHz, CDCl 3 ): δ = 159.0 (C q ), 157.9 (C q ), 134.0 (C q ), 133.8 (C q ), 131.1 (CH), 129.4 (C q ), 129.2 (CH), 127.7 (C q ), 125.4 (C q ), 123.8 (CH), 119.0 (CH), 114.3 S 13

(C q ), 114.1 (CH), 114.0 (CH), 113.3 (C q ) 110.4 (CH), 55.2 (CH 3 ), 55.2 (CH 3 ), 21.5 (CH 3 ). IR (ATR): 3362, 2928, 2835, 1510, 1455, 1231, 1172, 1023, 829, 791 cm -1. MS (EI) m/z (relative intensity): 343 (100), 328 (50), 268 (9) 171 (5). HR-MS (ESI) m/z calcd for C 23 H 21 NO 2 [M] + : 343.1572, found: 343.1572. 5-Methyl-2,3-bis[4-(trifluoromethyl)phenyl]-1H-indole (3ad) The general procedure was followed using N-(4-methoxybenzylidene)-4-methylaniline oxide 1a (121 mg, 0.50 mmol, 1.0 equiv), 1,2-bis[4-(trifluoromethyl)phenyl]ethyne 2d (236 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), Piv-Leu-OH (22.1 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-hexane/ch 2 Cl 2 : 3/1) yielded 3ad (153 mg, 73%) as a yellow solid. M. p. = 149 150 C. 1 H NMR (300 MHz, CDCl 3 ): δ = 8.21 (s, 1H), 7.68-7.54 (m, 4H), 7.49 (t, J = 8.7 Hz, 4H), 7.42 (s, 1H), 7.35 (d, J = 8.3 Hz, 1H), 7.13 (dd, J = 8.3, 1.6 Hz, 1H), 2.45 (s, 3H). 13 C NMR (75 MHz, CDCl 3 ): δ = 138.7 (C q ), 135.8 (C q ), 134.6 (C q ), 133.1 (C q ), 130.7 (C q ), 129.8 (q, 2 J = 33.1 Hz, C q ), 130.3 (CH), 128.5 (q, 2 J = 31.9 Hz, C q ), 128.5 (C q ), 128.3 (CH), 125.9 (q, 3 J = 3.8 Hz, CH), 125.6 (q, 3 J = 3.8 Hz, CH), 125.4 (CH), 124.3 (q, 1 J = 272.0 Hz, C q ), 124.0 (q, 1 J =273.0 Hz, C q ), 119.1 (CH), 114.7 (C q ), 111.0 (CH), 21.5 (CH 3 ). 19 F NMR (282 MHz, CDCl 3 ): δ = -62.34, -62.67. IR (ATR): 3474, 2922, 1617, 1319, 1154, 1090, 1060, 840, 793 cm -1. MS (EI) m/z (relative intensity): 343 (100), 328 (50), 268 (9) 171 (5). HR-MS (ESI) m/z calcd for C 23 H 15 F 6 N [M] + : 419.1109, found: 419.1120. S 14

2,3-Bis(3-chlorophenyl)-5-methyl-1H-indole (3ae) The general procedure was followed using N-(4-methoxybenzylidene)-4-methylaniline oxide 1a (121 mg, 0.50 mmol, 1.0 equiv), 1,2-bis(3-chlorophenyl)ethyne 2e (185 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), NaOAc (8.2 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-hexane/ch 2 Cl 2 : 3/1) yielded 3ae (146 mg, 83%) as a yellow oil. 1 H NMR (400 MHz, CDCl 3 ): δ = 8.10 (s, 1H), 7.46 7.39 (m, 3H), 7.34 7.28 (m, 3H), 7.28 7.18 (m, 4H), 7.10 (dd, J = 8.5, 1.4 Hz, 1H), 2.45 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ = 136.7 (C q ), 134.6 (C q ), 134.3 (C q ), 134.2 (C q ), 134.1 (C q ) 132.9 (C q ), 130.3 (C q ), 129.9 (CH), 129.8 (CH), 129.8 (CH), 128.5 (C q ), 128.3 (CH), 127.8 (CH), 127.7 (CH), 126.5 (CH), 126.4 (CH), 125.0 (CH), 119.0 (CH), 114.1 (C q ), 110.7 (CH), 21.5 (CH 3 ). IR (ATR): 3399, 2917, 1594, 1562, 1485, 1458, 1077, 883, 784, 733 cm -1. MS (EI) m/z (relative intensity): 351 (100), 315 (11), 381 (10), 178 (7). HR-MS (ESI) m/z calcd for C 23 H 21 NO 2 [M] + : 351.0582, found: 351.0588. 2,3-Bis(4-chlorophenyl)-5-methyl-1H-indole (3af): The general procedure was followed using nitrone 1a (121 mg, 0.50 mmol, 1.0 equiv), 1,2-bis(4-chlorophenyl)ethyne 2f (185 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 S 15

mg, 5.0 mol %), Piv-Leu-OH (22.1 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-hexane/ch 2 Cl 2 : 3/1) yielded 3af (99 mg, 56%) as a pale yellow solid. M. p. = 131-132 C. 1 H NMR (300 MHz, CDCl 3 ): δ = 8.08 (s, 1H), 7.40 (s, 1H), 7.39 7.31 (m, 9H), 7.08 (d, J = 9.4 Hz, 1H), 2.43 (s, 3H). 13 C NMR (125 MHz, CDCl 3 ): δ = 134.2 (C q ), 133.6 (C q ), 133.3 (C q ), 133.1 (C q ), 132.1 (C q ), 131.2 (CH), 130.9 (C q ), 130.1 (C q ), 129.2 (CH), 128.9 (CH), 128.8 (CH), 128.6 (C q ), 124.7 (CH), 118.9 (CH), 113.8 (C q ), 110.6 (CH), 21.6 (CH 3 ). IR (ATR): 3452, 3390, 1498, 1471, 1086, 1013, 833, 784, 529, 504. MS (ESI) m/z (relative intensity) 350 (100), 351 (20), 352 (60) [M-H] -. HR-MS (ESI) m/z calcd for C 21 H 15 NCl 2 [M-H] - : 350.0509, found: 350.0508. 2-(4-Fluorophenyl)-5-methyl-3-pentyl-1H-indole (3ag): The general procedure was followed using nitrone 1a (121 mg, 0.50 mmol, 1.0 equiv), 1-fluoro-4-(hept-1-yn-1-yl)benzene 2g (143 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), Piv-Leu-OH (22.1 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-hexane/etoac: 10/1) and GPC yielded 3ag (114 mg, 77%) as a pale yellow solid. M. p. = 118 120 C. 1 H NMR (300 MHz, DMSO-d 6 ): δ = 10.98 (s, 1H), 7.65-7.58 (m, 2H), 7.35 (d, J = 8.9 Hz, 2H), 7.31 (d, J = 1.8 Hz, 1H), 7.24 (d, J = 8.1 Hz, 1H), 6.92 (dd, J = 8.2, 1.6 Hz, 1H), 2.78 (t, J = 7.8 Hz, 2H), 2.39 (s, 3H), 1.62 (p, J = 7.2 Hz, 2H), 1,35-1.25 (m, 4H), 0.83 (t, J = 7.1 Hz, 3H). 13 C NMR (75 MHz, DMSO-d 6 ): δ = 161.3 (d, 1 J C-F = 245 Hz, C q ), 134.3 (C q ), 132.9 (C q ), 129.5 (d, 3 J C-F = 8.1 Hz, CH), 128.9 (C q ), 127.0 (C q ), 123.0 (CH), 119.9 (C q ), 118.1 (CH), 115.6 (d, 2 J C-F = 21.5 Hz, CH), 111.7 (C q ), 110.8 (CH), 31.4 (CH 3 ), 30.3 (CH 2 ), 24.0 (CH 2 ), 22.0 (CH 3 ), 21.3 (CH 2 ), 13.9 (CH 2 ). 19 F NMR (282 MHz, DMSO-d 6 ): δ = S 16

115.01. IR (ATR): 3381, 2923, 2857, 1506, 1441, 1225, 838, 797, 516, 477 cm -1. MS (ESI) m/z (relative intensity) 295 (6) [M] +, 312 (100), 334 (34), 350 (24). HR-MS (ESI) m/z calcd for C 20 H 22 FN [M] + : 295.1736, found: 295.1727. 3-Butyl-5-methyl-2-(4-nitrophenyl)-1H-indole (3ah): The general procedure was followed using nitrone 1a (121 mg, 0.50 mmol, 1.0 equiv), 1-(hex-1-yn-1-yl)-4-nitrobenzene 2h (152 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), Piv-Leu-OH (22.1 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-hexane/etoac: 30/1) and GPC yielded 3ah (84 mg, 54%) as a yellow solid. M. p. = 126-128 C. 1 H NMR (300 MHz, DMSO-d 6 ): δ = 11.23 (s, 1H), 8.34 (d, J = 8.9 Hz, 2H), 7.87 (d, J = 8.9 Hz, 2H), 7.37 (d, J = 1.6 Hz, 1H), 7.29 (d, J = 8.2 Hz, 1H), 7.00 (dd, J = 8.4, 1.5 Hz, 1H), 2.89 (dd, J = 8.7, 6.8 Hz, 2H), 2.40 (s, 3H), 1.62 (tt, J = 8.0, 6.2 Hz, 2H), 1.39 (tt, J = 7.3, 7.3 Hz, 2H), 0.90 (t, J = 7.3 Hz, 3H). 13 C NMR (75 MHz, DSMO-d 6 ): δ = 145.5 (C q ), 139.7 (C q ), 135.1 (C q ), 131.3 (C q ), 128.3 (C q ), 127.7 (CH), 127.5 (C q ), 124.5 (CH), 123.9 (CH), 118.5 (CH), 115.2 (C q ), 111.1 (CH), 32.6 (CH 2 ), 23.9 (CH 2 ), 22.0 (CH 2 ), 21.2 (CH 3 ), 13.7 (CH 3 ). IR (ATR): 3313, 1684, 1306, 1234, 1106, 755, 693, 654, 608, 590. MS (ESI) m/z (relative intensity) 331.2 (100) [M+Na] +, 356.2 (25). HR-MS (ESI) m/z calcd for C 19 H 20 N 2 O 2 Na [M+Na] + : 331.1422, found: 331.1410. Ethyl 5-methyl-2-phenyl-1H-indole-3-carboxylate (3ai): S 17

The general procedure was followed using nitrone 1a (121 mg, 0.50 mmol, 1.0 equiv), ethyl 3-phenylpropiolate 2i (131 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), Piv-Leu-OH (22.1 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-hexane/etoac: 10/1) and GPC yielded 3ai (86.6 mg, 63%) as a colourless solid. M. p. = 145-147 C. 1 H NMR (300 MHz, DMSO-d 6 ): δ = 11.97 (s, 1H), 7.86 (d, J = 1.0 Hz, 1H), 7.68-7.65 (m, 2H), 7.52-7.45 (m, 3H), 7.33 (d, J = 8.2 Hz, 1H), 7.44 (dd, J = 8.2, 1.1 Hz, 1H), 4.19 (q, J = 7.1 Hz, 2H), 2.43 (s, 3H), 1.21 (t, J = 7.1 Hz, 3H). 13 C NMR (125 MHz, DMSO-d 6 ): δ = 164.5 (C q ), 144.3 (C q ), 133.9 (C q ), 132.0 (C q ), 129.9 (C q ), 129.8 (CH), 128.6 (CH), 127.7 (CH), 127.5 (C q ), 124.0 (CH), 120.8 (CH), 111.4 (CH), 102.4 (C q ), 58.8 (CH 2 ), 21.4 (CH 3 ), 14.1 (CH 3 ). IR (ATR): 3232, 1652, 1476, 1451, 1268, 1218, 1145, 1049, 777, 696 cm -1. MS (ESI) m/z (relative intensity) 234 (3) [M-OEt] +, 280 (6) [M+H] +, 302 (100) [M+Na] +. HR-MS (ESI) m/z calcd for C 18 H 17 NNaO 2 [M+Na] + : 302.1157, found: 302.1159. The analytical data were in accordance with those reported in the literature. [8] Ethyl 6-methyl-2-phenyl-1H-indole-3-carboxylate (3hj): The general procedure was followed using nitrone 1h (121 mg, 0.50 mmol, 1.0 equiv), ethyl 3-phenylpropiolate 2j (131 mg, 0.75 mmol, 1.5 equiv), Cp*Co(CO)I 2 (12 mg, 5.0 mol %), Piv-Leu-OH (22.1 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-hexane/etoac: 10/1) and GPC yielded 3hj (94.9 mg, 68%) as a colorless solid. M. p. = 144-146 C. 1 H-NMR (300 MHz, DMSO-d 6 ): δ = 11.94 (s, 1H), 7.92 (d, J = 8.2 Hz, 1H), 7.94-7.91 (m, 2H), 7.51-7.45 (m, 3H), 7.23 (d, J = 1.4 Hz, 1H), 7.02 (dd, J = 8.2, 1.6 Hz, 1H), 4.18 (q, J = 7.1 Hz, 2H), 2.42 (s, 3H), 1.22 (t, J = 7.1 Hz, 3H). 13 C-NMR (75 MHz, DMSO-d 6 ): δ = 164.5 (C q ), 143.9 (C q ), S 18

135.9 (C q ), 132.0 (C q ), 131.7 (C q ), 129.9 (CH), 128.7 (CH), 127.7 (CH), 125.1 (C q ), 123.1 (CH), 120.9 (CH), 111.5 (CH), 102.7 (C q ), 58.9 (CH 2 ), 21.3 (CH 3 ), 14.2 (CH 3 ). IR (ATR): 3251, 1661, 1452, 1269, 1214, 1123, 1046, 805, 766, 688 cm -1. MS (ESI) m/z (relative intensity) 280 (27) [M+H] +, 302 (100) [M+Na] +, 318 (3) [M+K] +. HR-MS (ESI) m/z calcd for C 18 H 18 NO 2 [M+H] + : 280.1338, found: 280.1332. The analytical data were in accordance with those reported in the literature. [9] 5-Methyl-2-(4-nitrophenyl)-3-phenyl-1H-indole (3ak): The general procedure was followed using nitrone 1a (121 mg, 0.50 mmol, 1.0 equiv), 1-nitro-4-(phenylethynyl)benzene 2k (175 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), Piv-Leu-OH (22.1 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-hexane/etoac: 10/1) and GPC yielded 3ak (105 mg, 64%) as a red solid. M. p. = 153-155 C. 1 H NMR (500 MHz, DMSO-d 6 ): δ = 11.68 (s, 1H), 8.19 (d, J = 9.0 Hz, 2H), 7.66 (d, J = 9.1 Hz, 2H), 7.47-7.42 (m, 2H), 7.37-7.33 (m, 4H), 7.25 (d, J = 1.4 Hz, 1H), 7.66 (dd, J = 8.3, 1.5 Hz, 1H), 2.36 (s, 3H). 13 C NMR (75 MHz, DMSO-d 3 ): δ = 145.8 (C q ), 139.1 (C q ), 135.1 (C q ), 134.6 (C q ), 131.4 (C q ), 129.8 (CH), 128.8 (CH), 128.8 (C q ), 128.3 (CH), 128.2 (C q ), 126.6 (CH), 124.9 (CH), 123.6 (CH), 118.5 (CH), 115.9 (C q ), 111.5 (CH), 21.1 (CH 3 ). IR (ATR): 3266, 1595, 1504, 1336, 1107, 1008, 849, 754, 705, 439. MS (ESI) m/z (relative intensity) 329.1 (12) [M+H] +, 351.1 (100) [M+Na] +. HR-MS (ESI) m/z calcd for C 21 H 16 N 2 O 2 Na [M+Na] + : 351.1109, found: 351.1095. S 19

1-[3-Ethyl-2-(4-methoxyphenyl)-5-methyl-3H-indol-3-yl]propan-1-one (4al): The general procedure was followed using nitrone 1a (121 mg, 0.50 mmol, 1.0 equiv), 3-hexyne 2l (61.6 mg, 0.75 mmol, 1.5 equiv), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), Piv-Leu-OH (22.1 mg, 20 mol %). Purification by coloumn chromatography on silica gel (n-hexane/etoac: 10/1) and GPC yielded 4al (74 mg, 46%) as a colorless solid. M. p. = 96-98 C. 1 H NMR (300 MHz, CDCl 3 ): δ = 7.87 (d, J = 8.9 Hz, 2H), 7.60 (d, J = 7.9 Hz, 1H), 7.24 (ddd, J = 8.0, 1.7, 0.8 Hz, 1H), 6.99 (d, J = 0.8 Hz, 1H), 6.96 (d, J = 9.0 Hz, 2H), 3.86 (s, 3H), 2.53-2.27 (m, 2H), 2.40 (s, 3H), 2.03-1.75 (m, 2H), 0.8 (t, J = 7.2 Hz, 3H), 0.24 (t, J = 7.4 Hz, 3H). 13 C NMR (75 MHz, CDCl 3 ): δ = 207.3 (C q ), 175.8 (C q ), 162.2 (C q ), 155.0 (C q ), 139.1 (C q ), 136.3 (C q ), 129.9 (CH), 129.7 (CH), 125.7 (C q ), 122.7 (CH), 120.4 (CH), 114.6 (CH), 75.4 (C q ), 55.6 (CH 3 ), 31.3 (CH 3 ), 26.6 (CH 2 ), 21.7 (CH 2 ), 8.3 (CH 3 ), 7.3 (CH 3 ). IR (ATR): 2967, 3935, 1706, 1603, 1505, 1459, 1254, 1174, 1033, 836. MS (ESI) m/z (relative intensity) 306.2 (70) [M-Me] +, 322.2 (41) [M+H] +, 344.2 (100) [M+Na] +. HR-MS (ESI) m/z calcd for C 21 H 23 NO 2 Na [M+Na] + : 344.1626, found: 344.1624. S 20

Intermolecular Competition Experiment A suspension of N-(4-methoxybenzylidene)-4-methylaniline oxide (1a) (121 mg, 0.5 mmol), 4-fluoro-N-(4-methoxybenzylidene)aniline oxide (1e) (123 mg, 0.5 mmol), diphenylacetylene (2a) (89 mg, 0.5 mmol), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), AgSbF 6 (34.4 mg, 20 mol %) and NaOAc (8.2 mg, 20 mol %) in HFIP (2.0 ml) was stirred under air at 100 C for 16 h. After cooling to ambient temperature, the mixture was transferred into a round bottom flask with CH 2 Cl 2 (20 ml) and concentrated in vacuo. Purification by flash column chromatography on silica gel (n-hexane/ch 2 Cl 2 : 3/1) yielded the products 3aa and 3ea (120 mg) and the conversions were determined by 1 H NMR spectroscopy. S 21

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Competition Experiment between Alkynes 2 A suspension of 1,2-bis(4-methoxyphenyl)ethyne (2c) (119 mg, 0.5 mmol), 1,2-bis[4-(trifluoromethyl)phenyl]ethyne (2d) (157 mg, 0.5 mmol), N-(4-methoxybenzylidene)-4-methylaniline oxide (1a) (121 mg, 0.5 mmol), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), AgSbF 6 (34.4 mg, 20 mol %) and NaOAc (8.2 mg, 20 mol %) in HFIP (2.0 ml) was stirred at 100 C for 16 h under air. After cooling to ambient temperature, the mixture was filtered through a short pad of celite, rinsed with CH 2 Cl 2 (20 ml) and concentrated in vacuo. The crude 1 H NMR was measured to determine the conversions to the products 3ac (62%) and 3ad (17%) using the 1,3,5-trimethoxybenzene as the internal standard. S 23

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H/D Exchange Experiments N-(4-methoxybenzylidene)-4-methylaniline oxide 1a (121 mg, 0.5 mmol), Cp*CoI 2 (CO) (12 mg, 5 mol %), AgSbF 6 (34.4 mg, 20 mol %) and NaOAc (8.2 mg, 20 mol %), HFIP (1.8 ml) and CD 3 OD (0.2 ml) were placed in a 25 ml Schlenk tube under air and the mixture was stirred at 100 C for 2 h. After cooling to ambient temperature, the mixture was transferred into a round bottom flask with CH 2 Cl 2 (20 ml) and concentrated in vacuo. Purification by flash column chromatography on silica gel (n-hexane/etoac: 3/1) yielded 1a (80 mg, 66%). N-(4-methoxybenzylidene)-4-methylaniline oxide (1a) (121 mg, 0.5 mmol), diphenylacetylene (2a) (89 mg, 0.5 mmol), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), AgSbF 6 (34.4 mg, 20 mol %) and NaOAc (8.2 mg, 20 mol %), HFIP (1.8 ml) and D 3 COD (0.2 ml) were placed in a 25 ml Schlenk tube under air and the mixture was stirred at 100 C for 2 h. After cooling to ambient temperature, the mixture was transferred into a round bottom flask with CH 2 Cl 2 (20 ml) and concentrated in vacuo. Purification by flash column chromatography on silica gel (n-hexane/ch 2 Cl 2 : 3/1) yielded the product 3aa (80 mg, 21%) and 1a (31 mg, 25%) (n-hexane/etoac: 3/1). S 25

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yield / % Intermolecular KIE Two parallel reactions of 2a with 1d or [D] 5-1d were performed to determine the corresponding KIE value. 1d (113.6 mg, 0.5 mmol) or [D] 5-1d (116.2 mg, 0.5 mmol), diphenylacetylene (2a) (134 mg, 0.75 mmol), Cp*CoI 2 (CO) (12 mg, 5.0 mol %), AgSbF 6 (34.4 mg, 20 mol %), NaOAc (8.2 mg, 20 mol %), 1,3,5-trimethoxybenzene (28 mg, 0.17 mmol) as internal standard and HFIP (2.0 ml) were placed in a 25 ml Schlenk tube. The mixture was stirred at 100 C, a periodic aliquot (0.05 ml) was removed by syringe and analyzed by GC to determine the following conversions: 60 50 40 30 20 10 y = 0,8569x 1a [D] 5-1a y = 0,3186x 0 0 10 20 30 40 50 60 70 t / min S 27

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References [1] Sun, B.; Yoshino, T.; Matsunaga, S.; Kanai, M. Adv. Synth. Catal. 2014, 356, 1491 1495. [2] Evans, D. A.; Song, H.-J.; Fandrick, K. R. Org. Lett. 2006, 8, 3351 3354. [3] Mio, M. J.; Kopel, L. C.; Braun, J. B.; Gadzikwa, T. L.; Hull, K. L.; Brisbois, R. G.; Markworth, C. J.; Grieo, P. A. Org. Lett. 2002, 4, 3199 3202. [4] Lu, B.; Li, C.; Zhang, L.; J. Am. Chem. Soc. 2010, 132, 14070 14072. [5] Chen, K.; Li, H.; Lei, Z.-Q.; Li, Y.; Ye, W.-H.; Zhang, L.-S.; Sun, J.; Shi, Z.-J. Angew. Chem. Int. Ed. 2012, 51, 9851 9855. [6] Zhou, Z.; Liu, G.; Chen, Y.; Lu, X. Adv. Synth. Catal. 2015, 357, 2944 2950. [7] He, P; Du, Y.; Liu, G.; Cao, C.; Shi, Y.; Zhanga, J.; Pang, G. RSC Adv. 2013, 3, 18345 18350. [8] Nguyen, H. H.; Kurth, M. J. Org. Lett. 2013, 15, 362 365. [9] Jia, Z.; Nagano, T.; Li, X.; Chan, A. S. C. Eur. J. Org. Chem. 2013, 858 861. S 29

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