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1 Supporting Information Wiley-VCH Weinheim, Germany Ruthenium-Catalyzed xidative Annulation by Cleavage of C H/ H Bonds** Lutz Ackermann,* Alexander V. Lygin, and ora Hofmann anie_ _sm_miscellaneous_information.pdf

2 Supporting Information General Remarks ptimization Studies for the Synthesis of Isoquinolone 3a Representative Procedure A: Synthesis of -thylbenzamides from Acid Chlorides Representative Procedure B: Synthesis of -thylbenzamides from Acids Preparation and Characterization of Benzamides Representative Procedure C: Ruthenium-Catalyzed Coupling of Benzamides with Alkynes Preparation and Characterization of Isoquinolones 3 Competition Experiments Deuterium-Labeling Experiments References Spectra S2 S3 S4 S4 S4 S10 S10 S26 S30 S33 S34

3 General Remarks Catalytic reactions were carried out under a 2 atmosphere using pre-dried glassware. t-amh was distilled over sodium. The following starting materials were synthesized according to previously described methods: -benzylbenzamide, 1 4-methoxy-methylbenzamide,,2-dimethylbenzamide, 3-methoxy--methylbenzamide, 2 1,2-bis(4- fluorophenyl)ethyne, 1,2-di-p-tolylethyne, 1,2-bis(4-methoxyphenyl)ethyne. 3 ther 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-MR and GC. TLC: Macherey-agel, TLC plates Alugram Sil G/UV254. Detection under UV light at 254 nm. Chromatography: Separations were carried out on rck Silica 60 ( mm, mesh ASTM). IR: measured as KBr pellets or as films between KBr plates. MS: EI-MS: Finnigan MAT 95, 70 ev, DCI-MS: Finnigan MAT 95, 200 ev, reactant gas H 3 ; ESI-MS: Finnigan LCQ. High resolution mass spectrometry (HRMS): APEX IV 7T FTICR, Bruker Daltonic. M. p.: Büchi 540 capillary melting point apparatus, values are uncorrected. MR ( 1 H, 13 C, 19 F) spectra were recorded at 300 ( 1 H), 75.5 ( 13 C, APT (Attached Proton Test)) and 283 MHz ( 19 F), respectively, on Varian Unity-300 and AMX 300 instruments for CDCl 3 solutions if not otherwise specified, chemical shifts (δ) are given in ppm. S2

4 Table S-1. ptimization Studies for the Synthesis of Isoquinolone 3a a H + Ru-catalyst (2.5 mol %) oxidant solvent, T, 22 h + H 4a Yield of 3a (%) b Remark 1a 2a 3a Catalyst xidant Solvent Temp ( C) [RuCl 2 (p-cymene)] 2 m-xylene Cu(Ac) 2 H 2 m-xylene [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 m-xylene (40) 4a (19%) Ru(H) 2 (C)(P 3 ) 3 Cu(Ac) 2 H 2 m-xylene 120 <5 Ru 3 (C) 12 Cu(Ac) 2 H 2 m-xylene [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 t-amh RuCl 3 xh 2 Cu(Ac) 2 H 2 t-amh Ru 2 Cu(Ac) 2 H 2 t-amh Grubbs-I Cu(Ac) 2 H 2 t-amh [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 DMF [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 MP 120 traces [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 DMA [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 n-bu (27) 4a 40 (15% isolated) [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 DMS [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 CH 3 CH [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 t-buch a (13%) [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 CF 3 CH 80 0 [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 PEG a (10%) [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 H(CH 2 ) 2 H [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 t-amh (50) [RuCl 2 (p-cymene)] 2 benzoquinone t-amh [RuCl 2 (p-cymene)] 2 I(Ac) 2 t-amh a (4%) [RuCl 2 (p-cymene)] 2 AgAc t-amh [RuCl 2 (p-cymene)] 2 Ag 2 C 3 t-amh [RuCl 2 (p-cymene)] 2 xone t-amh [RuCl 2 (p-cymene)] 2 K 2 S 2 8 t-amh [RuCl 2 (p-cymene)] 2 CuBr 2 t-amh [RuCl 2 (p-cymene)] 2 CuS 4 t-amh [RuCl 2 (p-cymene)] 2 Cu(acac) 2 t-amh [RuCl 2 (p-cymene)] 2 Cu(H) 2 CuC 3 t-amh [RuCl 2 (p-cymene)] 2 Cu(Tf) 2 t-amh [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 t-amh [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 t-amh under air [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 t-amh (45) + K 2 C 3 (2 equiv) [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 t-amh P 3 (10 mol %) [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 t-amh AdCK (30 mol %) [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 t-amh KPF 6 (10 mol %) [RuCl 2 (p-cymene)] 2 Cu(Ac) 2 H 2 t-amh (76) 1a:2a = 0.5 : 1.0 mmol (5 mol %) [RuCl 2 (p-cymene)] 2 (5 mol %) Cu(Ac) 2 H 2 t-amh (62) 1a:2a = 0.5 : 0.5 mmol a 1a (0.5 mmol), 2a (0.5 mmol), [RuCl 2 (p-cymene)] 2 ( mmol, 2.5 mol %), oxidant (2.0 equiv), solvent (2.0 ml), under 2. b GC yield based on the amount of 1a used; in parentheses: isolated yield. S3

5 Representative Procedure A: Synthesis of -thylbenzamides from Acid Chlorides To a solution of 4-fluorobenzoyl chloride (1.59 g, 10.0 mmol) in anhydrous Et 2 (15 ml) was added K 2 C 3 (3.45 g, 25.0 mmol) followed by H 3 Cl (1.02 g, 15.0 mmol). The mixture was stirred at ambient temperature overnight, diluted with EtAc (100 ml) and washed with H 2 (50 ml). The aqueous phase was extracted with EtAc (2 30 ml), and the combined organic phase was dried over a 2 S 4, filtrated. The solvents were removed in vacuum to give a crude product, which was purified by column chromatography on silica gel (n-hexane/etac: 1/1) to yield 4-fluoro--methylbenzamide as a colorless solid (1.18 g, 76 %). F H 4-Fluoro--methylbenzamide: M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 7.77 (m, 2H), 7.06 (t, J = 8.6 Hz, 2H), 6.51 (br s, 1H), 2.97(I)/2.96(II) (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q, J C F = 252 Hz), (C q, J C F = 3 Hz), (CH, J C-F = 9 Hz), (CH, J C F = 22 Hz), 26.8 (CH 3 ). IR (KBr): 3349 (br), 2944, 1905, 1636, 1543, 1506, 1411, 1290, 1227, 1164, 1096, 1017, 946, 848 cm 1. MS (EI) m/z (relative intensity) 153 (53) [M + ], 123 (100), 95 (48), 75 (18), 43 (18). HR-MS (EI) m/z calcd for C 8 H 8 F [M + ] , found Representative Procedure B: Synthesis of -thylbenzamides from Acids A mixture of 4-chlorobenzoic acid (1.57 g, 10.0 mmol), SCl 2 (5.0 ml) and DMF (1 drop) was heated to 80 C and stirred under 2 atmosphere for 1h. The excess of SCl 2 was distilled off, and the crude acid chloride was dissolved in anhydrous Et 2 (15 ml). K 2 C 3 (3.45 g, 25.0 mmol) was added followed by H 3 Cl (1.02 g, 15.0 mmol). The mixture was stirred at ambient temperature overnight, diluted with EtAc (100 ml) and washed with H 2 (50 ml). The aqueous phase was extracted with EtAc (2 30 ml), and the combined organic phase was dried over a 2 S 4, filtrated. The solvents were removed in vacuum to give a crude product, which was purified by column chromatography on silica gel (n-hexane/etac: 1/2) to yield 4-chloro--methylbenzamide as a colorless solid (1.51 g, 89 %). S4

6 Cl H 4-Chloro--methylbenzamide: M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 7.67 (d, J = 8.6 Hz, 2H), 7.33 (d, J = 8.6 Hz, 2H), 6.56 (br s, 1H), 2.95(I)/2.93(II) (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (CH), (CH), 26.8 (CH 3 ). IR (KBr): 3339 (br), 3075, 2955, 1636, 1601, 1555, 1488, 1405, 1323, 1301, 1164, 1111, 1092, 1020, 1009, 959, 945, 841, 753, 722, 694, 622 cm 1. MS (EI) m/z (relative intensity) 169 (51) [M + ], 139 (100), 111 (56), 75 (27). HR-MS (EI) m/z calcd for C 8 H 8 Cl [M + ] , found: H -thyl-1-naphthamide: The representative procedure A was followed using 1-naphthoyl chloride (1.91 g, 10.0 mmol) and H 3 Cl (1.02 g, 15.0 mmol). Purification by column chromatography on silica gel (n-hexane/etac: 1/2) yielded the title compound as a colorless solid (1.36 g, 74 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = (m, 1H), (m, 2H), (m, 2H), 7.38 (d, J = 7.0 Hz, 1H), (m, 1H), 6.48 (br s, 1H), 2.88(I)/2.87(II) (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (CH), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), 26.5 (CH 3 ). IR (KBr): 3287 (br), 1652, 1541, 1409, 1259, 1218, 1075, 1048, 1015, 914, 868 cm 1. MS (EI) m/z (relative intensity) 185 (65) [M + ], 155 (100), 127 (93), 77 (12). HR-MS (EI) m/z calcd for C 12 H 11 [M + ] , found H,3-Dimethylbenzamide: The representative procedure A was followed using 2- methylbenzoyl chloride (1.55 g, 10.0 mmol) and H 3 Cl (1.02 g, 15.0 mmol). Purification by column chromatography on silica gel (n-hexane/etac: 2/1) yielded the title compound as a colorless oil (1.13 g, 76 %). 1 H-MR (300 MHz, CDCl 3 ): δ = 7.58 (s, 1H), 7.53 (m, 1H), (m, 2H) 6.39 (br s, 1H), 2.99(I)/2.97(II) (s, 3H), 2.36 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (CH), (CH), (CH), (CH), 26.7 (CH 3 ), 21.3 (CH 3 ). IR (film): 3313 (br), 1653, 1540, 1487, 1410, 1320, 1220, S5

7 1156, 1039, 890 cm 1. MS (EI) m/z (relative intensity) 149 (37) [M + ], 119 (100), 91 (64), 65 (23). HR-MS (EI) m/z calcd for C 9 H 11 [M + ] , found F 3 C H -thyl-3-(trifluoromethyl)benzamide: The representative procedure B was followed using 3-(trifluoromethyl)benzoic acid (1.90 g, 10.0 mmol) and H 3 Cl (1.02 g, 15.0 mmol). Purification by column chromatography on silica gel (n-hexane/etac: 1/2) yielded the title compound as a colorless solid (1.44 g, 71 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.02 (s, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7.51 (t, J = 7.8 Hz, 1H), 6.77 (br s, 1H), 3.00 (d, J = 4.8 Hz, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q, J C F = 33 Hz), (CH), (CH), (CH, J C F = 4 Hz), (C q, J C F = 272 Hz), (CH, J C F = 4 Hz), 26.6 (CH 3 ). IR (KBr): 3358 (br), 1639, 1554, 1491, 1447, 1408, 1337, 1072, 1023, 918, 861 cm 1. MS (EI) m/z (relative intensity) 203 (39) [M + ], 202 (38), 173 (100), 145 (78). HR-MS (EI) m/z calcd for C 9 H 8 F 3 [M + ] , found: F H 3-Fluoro--methylbenzamide: The representative procedure B was followed using 3-fluorobenzoic acid (1.40 g, 10.0 mmol) and H 3 Cl (1.02 g, 15.0 mmol). Purification by column chromatography on silica gel (n-hexane/etac: 1/1) yielded the title compound as a colorless solid (1.21 g, 79 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = (m, 2H), (m, 1H), (m, 1H), 6.49 (br s, 1H), 3.00 (I)/2.99(II) (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q, J C F = 248 Hz), (C q, J C F = 7 Hz), (CH, J C F = 8 Hz), (CH, J C F = 3 Hz), (CH, J C F = 21 Hz), (CH, J C F = 23 Hz), 26.9 (CH 3 ). IR (KBr): 3323 (br), 1557, 1411, 1331, 1271, 1153, 1080, 1024, 1001, 976, 893 cm 1. MS (EI) m/z (relative intensity) 153 (45) [M + ], 123 (100), 95 (65), 75 (22), 43 (19). HR-MS (EI) m/z calcd for C 8 H 8 F [M + ] , found S6

8 2 C H thyl 4-(methylcarbamoyl)benzoate: The representative procedure B was followed using 4-(methoxycarbonyl)benzoic acid (1.80 g, 10.0 mmol) and H 3 Cl (1.02 g, 15.0 mmol). Purification by column chromatography on silica gel (EtAc) yielded the title compound as a colorless solid (1.51 g, 78 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.05 (d, J = 8.9 Hz, 2H), 7.80 (d, J = 8.9 Hz, 2H), 6.55 (br s, 1H), 3.91 (s, 3H), 3.00(I)/2.99(II) (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (CH), (CH), 52.3 (CH 3 ), 26.9 (CH 3 ). IR (KBr): 3362, 1712, 1636, 1546, 1276, 1112, 727, 617 cm 1. MS (EI) m/z (relative intensity) 193 (48) [M + ], 178 (40), 163 (100), 135 (50), 103 (42), 76 (32). HR-MS (EI) m/z calcd for C 10 H 11 3 [M + ] , found Ac H 4-(-thylcarbamoyl)phenyl acetate: The representative procedure B was followed using 4-acetoxybenzoic acid (3.61 g, 20.0 mmol) and H 3 Cl (2.04 g, 30.0 mmol). Purification by column chromatography on silica gel (EtAc) yielded the title compound as a colorless solid (2.65 g, 68 %). M.p. = C. 1 H-MR (300 MHz, CD 3 D): δ = 7.84 (d, J = 8.9 Hz, 2H), 7.19 (d, J = 8.9 Hz, 2H), 2.90 (s, 3H), 2.28 (s, 3H). 13 C-MR (75 MHz, CD 3 D): δ = (C q ), (C q ), (C q ), (C q ), (CH), (CH), 26.9 (CH 3 ), 20.9 (CH 3 ). IR (KBr): 3300, 1752, 1630, 1554, 1217, 1162, 917 cm -1. MS (EI) m/z (relative intensity) 193 (10) [M + ], 151 (50), 121 (100), 93 (12), 65 (11), 43 (35). HR-MS (EI) m/z calcd for C 10 H 11 3 [M + ] , found D D CH D D D 2,3,4,5,6-Pentadeuteriobenzoic acid: To a stirred solution of 1-bromopentadeuteriobenzene. 4 (1.76 g, 10.8 mmol) in anhydrous THF (20 ml), a solution of n-buli in n-hexane (4.8 ml, 2.5 M, 11.9 mmol) was added dropwise at 78 C for 10 min. The mixture was stirred at the same temperature for 30 min, and then C 2 was bubbled S7

9 through the mixture at 78 C for 10 min. The mixture was allowed to warm to ambient temperature, quenched with H 2 (20 ml), acidified to ph = 1 with HCl (1M), and extracted with EtAc (5 20 ml). The combined organic phase was dried over a 2 S 4, filtered and the solvents were removed in vacuum to give the product (1.15 g, 84%). 1 H-MR (300 MHz, CDCl 3 ): δ = (br s, 1H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q, J C D = 24 Hz), (C q, J C D = 25 Hz), (C q ), (C q, J C D = 25 Hz). MS (EI) m/z (relative intensity) 127 (95) [M + ], 110 (100), 82 (84). HR-MS (EI) m/z calcd for C 7 H 2 D 5 [M + ] , found thyl 2,3,4,5,6-pentadeueriobenzamide ([D 5 ]-1a): The representative procedure B was followed using 1,2,3,4,5-pentadeuterobenzoic acid (0.92 g, 7.30 mmol) and H 3 Cl (0.75 g, 11.0 mmol). Purification by column chromatography on silica gel (n-hexane/etac: 1/2) yielded the title compound as a colorless solid (0.82 g, 81 %). M.p. = C. 1 H-MR (300 MHz, CD 3 D): δ = 2.91 (s, 3H). 13 C-MR (75 MHz, CD 3 D): δ = (C q ), (C q ), (C q, J C D = 24 Hz), (C q, J C D = 25 Hz), (C q, J C D = 25 Hz), 26.9 (CH 3 ). IR (KBr): 3307 (br), 1634, 1541, 1408, 1328, 1297, 1156, 956, 842, 804 cm 1. MS (EI) m/z (relative intensity) 140 (39) [M + ], 110 (100), 82 (81), 54 (32), 43 (34). HR-MS (EI) m/z calcd for C 8 H 4 D 5 [M + ] , found H -(4-thoxyphenyl)benzamide (1g): Benzoyl chloride (1.48 g, 10.5 mmol) was added dropwise at 0 C to a solution of 4-methoxyaniline (1.23 g, 10.0 mmol) and Et 3 (1.45 ml, 10.5 mmol) in EtAc (40 ml). The temperature was allowed to rise to ambient temperature, and then the mixture was stirred at the same temperature overnight. After dilution with EtAc (150 ml), washing with H 2 (50 ml) and brine (50 ml), the organic phase was dried over a 2 S 4, filtrated, and the solvent was removed in vacuum. The crude product was purified by recrystallization from EtAc (30 ml) to give 1.53 g (67%) of the title compound as a colorless solid. M.p. = C. 1 H-MR (300 MHz, CDCl 3 +CD 3 D): δ = 8.74 (br s, 1H), 7.80 (d, J = 7.2 Hz, 2H), (m, 5H), 6.82 (d, J = 8.9 Hz, 2H), 3.73 (s, 3H). S8

10 13 C-MR (75 MHz, CDCl 3 +CD 3 D): δ = (C q ), (C q ), (C q ), (CH), (C q ), (CH), (CH), (CH), (CH), 55.3 (CH 3 ). IR (KBr): 3333 (br), 1884, 1646, 1515, 1409, 1075, 1032, 927, 899 cm 1. MS (EI) m/z (relative intensity) 227 (65) [M + ], 105 (100), 77 (57). HR-MS (EI) m/z calcd for C 14 H 13 2 [M + ] , found F H -(4-Fluorophenyl)benzamide (1f): Benzoyl chloride (1.48 g, 10.5 mmol) was added dropwise at 0 C to a solution of 4-fluoroaniline (1.11 g, 10.0 mmol) and Et 3 (1.45 ml, 10.5 mmol) in EtAc (40 ml). The temperature was allowed to rise to ambient temperature, and then the mixture was stirred at the same temperature overnight. After dilution with EtAc (150 ml), washing with H 2 (50 ml) and brine (50 ml), the organic phase was dried over a 2 S 4, filtrated, and the solvent was removed under reduced pressure. The crude product was purified by recrystallization from EtAc (20 ml) to give the title compound (1.23 g, 57%) as a colorless solid. M.p. = C. 1 H-MR (300 MHz, CDCl 3 +CD 3 D): δ = (m, 2H), (m, 2H), (m, 3H), (m, 2H). 13 C-MR (75 MHz, CDCl 3 +CD 3 D): δ = (C q ), (d, J C F = 243 Hz, CH), (C q ), (CH), (CH), (CH), (CH), (CH, J C F = 8 Hz), (CH, J C F = 23 Hz). IR (KBr): 3347, 1653, 1614, 1509, 1406, 1247, 1157, 959, 928, 829 cm 1. MS (EI) m/z (relative intensity) 215 (32) [M + ], 105 (100), 77 (60). HR-MS (EI) m/z calcd for C 13 H 10 F [M + ] , found H n-bu -n-butylbenzamide: To a stirred mixture of benzoyl chloride (1.41g, 10.0 mmol), K 2 C 3 (2.76 g, 20.0 mmol) and anhydrous Et 2 (15 ml), n-butylamine (0.73 g, 10.0 mmol) was added dropwise at 0 C, and the mixture was stirred at ambient temperature overnight, diluted with EtAc (100 ml) and washed with H 2 (50 ml). The aqueous phase was extracted with EtAc (2 30 ml), and the combined organic phase was dried over a 2 S 4, filtrated. The solvents were removed in vacuum to give the crude product, which was purified by column chromatography on silica gel (n-hexane/etac: 1/1) to give the product (1.31 g, 74%) as a colorless oil. 1 H-MR (300 MHz, CDCl 3 ): δ = 7.76 (d, J = 7.0 Hz, 2H), (m, 3H), 6.92 (br s, 1H), 3.36 (q, J = 6.0 Hz, 2H), 1.53 (tt, J = 8.2, 7.4 Hz, 2H), 1.32 (tq, J = 7.8, 7.2 S9

11 Hz, 2H), 0.87 (t, J = 7.3 Hz, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (CH), (CH), 39.7 (CH 2 ), 31.5 (CH 2 ), 20.0 (CH 2 ), 13.6 (CH 3 ). IR (film): 3321 (br), 1636, 1490, 1465, 1375, 1225, 1185, 1075, 976, 851 cm 1. MS (EI) m/z (relative intensity) 177 (23) [M + ], 135 (28), 134 (25), 105 (100), 77 (50). HR-MS (EI) m/z calcd for C 11 H 15 [M + ] , found Representative Procedure C: Ruthenium-Catalyzed Coupling of Benzamides with Alkynes A mixture of -methylbenzamide (67.5 mg, 0.50 mmol), diphenylacetylene (178 mg, 1.00 mmol), [RuCl 2 (p-cymene)] 2 (15.3 mg, 5.0 mol %) and Cu(Ac) 2 H 2 (200 mg, 1.00 mmol) in t-amh (2.0 ml) was stirred at 100 C under nitrogen atmosphere for 22 h. After cooling the mixture to ambient temperature, the reaction mixture was diluted with aq. H 3 solution (75 ml, 1.0 wt %) and extracted with EtAc (3 x 75 ml). The combined organic phase was washed with brine (50 ml) and dried over a 2 S 4. After filtration and evaporation of the solvents in vacuum, the crude product was purified by column chromatography on silica gel (n-hexane/etac: 4/1) to yield 3a as a colorless solid (118 mg, 76 %). 2-thyl-3,4-diphenylisoquinolin-1(2H)-one (3a) 2 : M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.57 (d, J = 4.8 Hz, 1H), 7.52 (m, 2H), (m, 11H), 3.36 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C q ), (C q ), 34.3 (CH 3 ). IR (KBr): 1646, 1604, 1552, 1489, 1414, 1176, 1074, 1025, 924, 781 cm 1. MS (EI) m/z (relative intensity) 311 (100) [M + ], 165 (7), 77 (8). HR-MS (EI) m/z calcd for C 22 H 17 [M + ] , found S10

12 (E)-2-(1,2-Diphenylvinyl)--methylbenzamide (4a): The representative procedure C was followed using -methylbenzamide (67.5 mg, 0.50 mmol), diphenylacetylene (178 mg, 1.00 mmol), and n-bu 2 (2.0 ml). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 4/1) yielded the uncyclized product 4a (24 mg, 15%) along with 3a (42 mg, 27 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = (m, 4H), (m, 10H), 6.77 (s, 1H), 6.67 (br s, 1H), 2.60(I)/2.59(II) (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH) (CH) (CH), (CH), 26.6 ppm (CH 3 ). IR (KBr): 3285, 1624, 1541, 1490, 1406, 1311, 1169, 924, 899 cm 1. MS (EI) m/z (relative intensity) 313 (77) [M + ], 282 (100), 265 (23), 252 (28), 236 (33), 178 (12), 126 (11), 77 (7). HR-MS (EI) m/z calcd for C 22 H 19 [M + ] , found ne: H H 0.11% 0.10% 6-Chloro-2-methyl-3,4-diphenylisoquinolin-1(2H)-one (3b): The representative procedure C was followed using 4-chloro--methylbenzamide (84.8 mg, 0.50 mmol) and diphenylacetylene (178 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 5/1) yielded 3b as a colorless solid (134 mg, 78 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.49 (d, J = 8.6 Hz, 1H), 7.43 (dd, J = 8.6, 2.0 Hz, 1H), (m, 11H), 3.34 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C q ), (C q ), 34.4 (CH 3 ). IR (KBr): 1649, 1597, 1443, 1416, 1360, 1190, 1070, 936, 869, S11

13 834, 784 cm 1. MS (EI) m/z (relative intensity) 347/345 (33/100) [M + ]. HR-MS (EI) m/z calcd for C 22 H 16 Cl [M + ] , found thoxy-2-methyl-3,4-diphenylisoquinolin-1(2H)-one (3c) 2 : The representative procedure C was followed using 4-methoxy--methylbenzamide (82.5 mg, 0.50 mmol) and diphenylacetylene (178 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 3/1) yielded 3c as a colorless solid (102 mg, 60 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.48 (d, J = 8.9 Hz, 1H), (m, 11H), 6.52 (d, J = 2.5 Hz, 1H), 3.69 (s, 3H), 3.32 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C q ), (C q ), (CH), (CH), 55.2 (CH 3 ), 34.1 (CH 3 ). IR (KBr): 1647, 1610, 1483, 1415, 1323, 1230, 1143, 1072, 1001, 856, 781 cm 1. MS (EI) m/z (relative intensity) 341 (100) [M + ]. HR- MS (EI) m/z calcd for C 23 H 19 2 [M + ] , found thyl-1-oxo-3,4-diphenyl-1,2-dihydroisoquinolin-6-yl acetate (3d): The representative procedure C was followed using 4-acetoxy--methylbenzamide (96.5 mg, 0.50 mmol) and diphenylacetylene (178 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 3/1) yielded 3d as a colorless solid (110 mg, 60 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.69 (d, J = 8.8 Hz, 1H), (m, 11H), 6.95 (d, J = 2.2 Hz, 1H), 3.46 (s, 3H), 2.35 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C q ), (CH), (C q ), (CH), 34.3 (CH 3 ), 21.1 (CH 3 ). IR (KBr): 1759, 1650, 1613, 1477, 1413, 1339, 1203, 1135, 1010, 970, 882, 801, 708 cm 1. MS (EI) m/z (relative intensity) 369 (82) [M + ], 326 (100). HR-MS (EI) m/z calcd for C 24 H 19 3 [M + ] , found S12

14 6-Fluoro-2-methyl-3,4-diphenylisoquinolin-1(2H)-one (3e): The representative procedure C was followed using 4-fluoro--methylbenzamide (76.5 mg, 0.50 mmol) and diphenylacetylene (178 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 5/1) yielded 3e as a colorless solid (71 mg, 43 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.56 (dd, J = 8.9, 6.0 Hz, 1H), (m, 11H), 6.78 (dd, J = 10.5, 2.5 Hz, 1H), 3.34 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q, J C F = 359 Hz), (C q ), (C q ), (C q ), (C q, J C F = 86 Hz), (CH), (CH), (CH, J C F = 10 Hz), (CH), (CH), (CH), (CH), (C q, J C F = 2 Hz), (C q, J C F = 3 Hz), (CH, J C F = 24 Hz), (CH, J C F = 23 Hz), 34.3 (CH 3 ). 19 F-MR (283 MHz, CDCl 3 ): δ = (m). IR (KBr): 1651, 1611, 1473, 1416, 1369, 1266, 1134, 1048, 1002, 875, 833, 782 cm 1. MS (EI) m/z (relative intensity) 329 (100) [M + ], 328 (100), 43 (13). HR- MS (EI) m/z calcd for C 22 H 16 F [M + ] , found thyl 2-methyl-1-oxo-3,4-diphenyl-1,2-dihydroisoquinoline-6-carboxylate (3f): The representative procedure C was followed using 4-carbomethoxy--methylbenzamide (96.5 mg, 0.50 mmol) and diphenylacetylene (178 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 2/1) yielded 3f as a colorless solid (140 mg, 76 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.58 (d, J = 8.4 Hz, 1H), 8.05 (dd, J = 8.4, 1.6 Hz, 1H), 7.85 (m, 1H), (m, 10H), 3.81 (s, 3H), 3.33 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (C q ), (CH), (CH), (CH), (C q ), 52.3 (CH 3 ), 34.4 (CH 3 ). IR (KBr): 1720, 1637, 1284, 1246, 1193, 1115, 761, 705 cm 1. MS (EI) m/z (relative intensity) 369 (100) [M + ]. HR-MS (EI) m/z calcd for C 24 H 19 3 [M + ] , found S13

15 2-thyl-3,4-diphenylbenzo[h]isoquinolin-1(2H)-one (3g): The representative procedure C was followed using -methyl-1-naphthamide (92.5 mg, 0.50 mmol) and diphenylacetylene (178 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 4/1) yielded 3g as a colorless solid (132 mg, 73 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = (d, J = 8.7 Hz, 1H), 7.88 (d, J = 8.9 Hz, 2H), 7.78 (t, J = 7.8 Hz, 1H), 7.62 (t, J = 7.4 Hz, 1H), (m, 11H), 3.49 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (C q ), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C q ), (C q ), 35.1 (CH 3 ). IR (KBr): 1641, 1602, 1487, 1416, 1367, 1249, 1137, 1021, 920, 834, 733 cm 1. MS (EI) m/z (relative intensity) 361 (100) [M + ]. HR-MS (EI) m/z calcd for C 26 H 19 [M + ] , found S H + [RuCl 2 (p-cymene)] 2 (5.0 mol %) Cu(Ac) 2 H 2 t-amh, 100 C, 22 h 1h 2a 3h: 42% S + S H 4h: 38% (4ha/4hb=21/17) 6-thyl-4,5-diphenylthieno[2,3-c]pyridin-7(6H)-one (3h) and 3-(1,2-Diphenylvinyl)--methylthiophene-2-carboxamide (4h): The representative procedure C was followed using -methylthiophene-2-carboxamide (70.5 mg, 0.50 mmol) and diphenylacetylene (178 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 5/1) yielded 3h (67 mg, 42%) and 4h (E/Z isomers 4ha/4hb, 61 mg, 38%) as colorless solids. S14

16 6-thyl-4,5-diphenylthieno[2,3-c]pyridin-7(6H)-one (3h): M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 7.60 (d, J = 5.9 Hz, 1H), (m, 3H), (m, 5H), (m, 2H), 6.90 (d, J = 5.2 Hz, 1H), 3.39 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (C q ), (CH), (CH), (CH), (CH), (CH), (C q ), 34.2 (CH 3 ). IR (KBr): 1640, 1577, 1490, 1440, 780, 760, 700 cm 1. MS (EI) m/z (relative intensity) 317 (90) [M + ], 316 (100), 77 (10). HR-MS (EI) m/z calcd for C 20 H 15 S [M + ] , found (1,2-Diphenylvinyl)--methylthiophene-2-carboxamide Isomer 4ha: Isolated yield: 33 mg (21%). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = (m, 13H), 5.71 (br s, 1H), 2.76(I)/2.74(II) (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), 26.7 (CH 3 ). IR (KBr): 3240, 1618, 1558, 1406, 1326, 1160, 842, 798, 766, 705 cm 1. MS (EI) m/z (relative intensity) 319 (100) [M + ], 289 (26), 261 (96), 228 (34), 202 (24). HR-MS (EI) m/z calcd for C 20 H 17 S [M + ] , found Isomer 4hb: Isolated yield: 28 mg (17%). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 7.36 (d, J = 5.1 Hz, 1H), (m, 11H), 6.88 (d, J = 4.1 Hz, 1H), 6.86 (s, 1H), 6.43 (br s, 1H), 2.77(I)/2.75(I) (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), 26.6 (CH 3 ). IR (KBr): 3230, 1620, 1560, 1406, 1330, 1164, 842 cm 1. MS (EI) m/z (relative intensity) 319 (100) [M + ], 289 (21), 261 (94), 228 (28), 202 (10). HR-MS (EI) m/z calcd for C 20 H 17 S [M + ] , found S15

17 2-n-Butyl-3,4-diphenylisoquinolin-1(2H)-one (3i) 5 : The representative procedure C was followed using -(n-butyl)benzamide (88.5 mg, 0.50 mmol) and diphenylacetylene (178 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 5/1) yielded 3i as a colorless solid (80 mg, 45 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.55 (d, J = 7.6 Hz, 1H), 7.48 (m, 2H), (m, 11H), 3.85 (m, 2H), 1.57 (m, 2H), 1.12 (m, 2H), 0.71 (t, J = 7.3 Hz, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C q ), (C q ), 46.0 (CH 2 ), 30.7 (CH 2 ), 20.0 (CH 2 ), 13.4 (CH 3 ). IR (KBr): 2960, 2863, 1651, 1611, 1588, 1480, 1381, 1281, 1141, 1028, 819, 760 cm 1. MS (EI) m/z (relative intensity) 353 (82) [M + ], 336 (63), 310 (35), 297 (100), 278 (16), 252 (12), 165 (14). HR-MS (EI) m/z calcd for C 25 H 23 [M + ] , found Benzyl-3,4-diphenylisoquinolin-1(2H)-one (3j) 2 : The representative procedure C was followed using -benzylbenzamide (105.5 mg, 0.50 mmol) and diphenylacetylene (178 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 4/1) yielded 3j as a colorless solid (122 mg, 63 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = (m, 1H), (m, 2H), (m, 12H), 6.92 (m, 4H), 5.24 (s, 2H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C q ), (C q ), 49.1 (CH 2 ). IR (KBr): 1950, 1652, 1613, 1588, 1489, 1422, 1327, 1120, 1029, 922, 803, 762 cm 1. MS (EI) m/z (relative intensity) 387 (100) [M + ], 386 (100), 308 (29), 165 (27), 91 (53). HR-MS (EI) m/z calcd for C 23 H 19 2 [M + ] , found S16

18 F 2-(4-Fluorophenyl)-3,4-diphenylisoquinolin-1(2H)-one (3k): The representative procedure C was followed using -(4-fluorophenyl)benzamide (107.5 mg, 0.50 mmol) and diphenylacetylene (178 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 4/1) yielded 3k as a colorless solid (121 mg, 62 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.57 (dd, J = 7.6, 1.4 Hz, 1H), (m, 2H), (m, 8H), (m, 7H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q, J C F = 255 Hz), (C q ), (C q ), (C q ), (C q, J C F = 3 Hz), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH, J C F = 30 Hz), (CH), (CH), (CH), (C q ), (C q ), (CH, J C F = 23 Hz). 19 F-MR (283 MHz, CDCl 3 ): δ = (m). IR (KBr): 1899, 1661, 1587, 1554, 1442, 1328, 1227, 1090, 1012, 923, 854, 784, 747 cm 1. MS (EI) m/z (relative intensity) 391 (100) [M + ], 280 (8), 198 (12), 95 (13). HR-MS (EI) m/z calcd for C 27 H 18 F [M + ] , found (4-thoxyphenyl)-3,4-diphenylisoquinolin-1(2H)-one (3l): The representative procedure C was followed using -(4-methoxyphenyl)benzamide (113.5 mg, 0.50 mmol) and diphenylacetylene (178 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 3/1) yielded 3l as a colorless solid (99 mg, 49 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.57 (dd, J = 7.6, 1.5 Hz, 1H), (m, 2H), (m, 6H), 7.02 (d, J = 9.0 Hz, 2H), (m, 5H), 6.73 (d, J = 9.0 Hz, 2H), 3.71 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C q ), (C q ), (CH), 55.3 (CH 3 ). IR (KBr): 1654, 1605, 1508, 1323, 1249, 1030, 813, 762 cm 1. MS (EI) m/z (relative intensity) 403 (100) [M + ], 280 (12), 210 (8), 77 (7). HR-MS (EI) m/z calcd for C 28 H 21 2 [M + ] , found S17

19 2,7-Dimethyl-3,4-diphenylisoquinolin-1(2H)-one (3m): The representative procedure C was followed using 3-methyl--methylbenzamide (74.5 mg, 0.50 mmol) and diphenylacetylene (178 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 5/1) yielded 3m as a colorless solid (132 mg, 81 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.37 (s, 1H), 7.36 (d, J = 8.3 Hz, 1H), (m, 11H), 3.35 (s, 3H), 2.50 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C q ), (C q ), 34.3 (CH 3 ), 21.4 (CH 3 ). IR (KBr): 1645, 1499, 1340, 1145, 948, 830, 769, 730 cm 1. MS (EI) m/z (relative intensity) 325 (100) [M + ]. HR-MS (EI) m/z calcd for C 23 H 19 [M + ] , found (Trifluoromethyl)-2-methyl-3,4-diphenyl-isoquinolin-1(2H)-one (3n): The representative procedure C was followed using 3-(trifluoromethyl)--methylbenzamide (101.5 mg, 0.50 mmol) and diphenylacetylene (178 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 5/1) yielded 3n as a colorless solid (120 mg, 63 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.85 (s, 1H), 7.70 (dd, J = 8.6, 2.0 Hz, 1H), (m, 11H), 3.37 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q, J C F = 90 Hz), (CH), (CH), (C q ), (CH), (CH), (CH), (CH, J C F = 3 Hz), (CH), (CH), (C q ), (CH, J C F = 4 Hz), (C q ), (C q, J C F = 272 Hz), (C q ), 34.5 (CH 3 ). 19 F-MR (283 MHz, CDCl 3 ): δ = (s). IR (KBr): 1653, 1592, 1491, 1409, 1313, 1171, 1070, 1008, 838, 785, 740 cm 1. MS (EI) m/z (relative intensity) 379 (100) [M + ]. HR-MS (EI) m/z calcd for C 23 H 16 F 3 [M + ] , found S18

20 2-thyl-3,4-dip-tolylisoquinolin-1(2H)-one (3o): The representative procedure C was followed using -methylbenzamide (66.6 mg, 0.49 mmol) and 1,2-dip-tolylethyne (207.1 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 4/1) yielded 3o as a colorless solid (118 mg, 71 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.54 (ddd, J = 6.4, 1.8, 1.0 Hz, 1H), (m, 2H), 7.15 (ddd, J = 7.4, 1.7, 1.0 Hz, 1H), (m, 8H), 3.30 (s, 3H), 2.26 (s, 3H), 2.26 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C q ), (C q ), 34.3 (CH 3 ), 21.2 (CH 3 ), 21.2 (CH 3 ). IR (neat): 1640, 1592, 1509, 1480, 1411, 1328, 1284, 1022, 817, 773 cm 1. MS (EI) m/z (relative intensity) 339 (100) [M + ], 246 (8), 178 (12), 132 (17), 91 (13). HR-MS (EI) m/z calcd for C 24 H 21 + [M + ] , found ,4-Bis(4-methoxyphenyl)-2-methylisoquinolin-1(2H)-one (3p) 2 : The representative procedure C was followed using -methylbenzamide (67.5 mg, 0.50 mmol) and 1,2-bis(4- methoxyphenyl)ethyne (194.8 mg, 0.82 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 3/1) yielded 3p as an orange solid (104 mg, 56 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.54 (dd, J = 7.8, 1.7 Hz, 1H), (m, 2H), (m, 1H), (m, 4H), (m, 4H), 3.76 (s, 3H), 3.76 (s, 3H), 3.34 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (C q ), (CH), (C q ), (CH), (CH), (C q ), (C q ), (CH), (CH), 55.1 (CH 3 ), 55.1 (CH 3 ), 34.3 (CH 3 ). IR (neat): 1788, 1730, 1644, 1605, 1506, 1463, 1328, 1242, 1108, S19

21 862, 808, 731 cm 1. MS (EI) m/z (relative intensity) 371 (100) [M + ], 355 (11), 267 (9), 239 (16), 165 (12), 135 (16). HR-MS (EI) m/z calcd for C 24 H [M + ] , found F F 3,4-Bis(4-fluorophenyl)-2-methylisoquinolin-1(2H)-one (3q): The representative procedure C was followed using -methylbenzamide (66.6 mg, 0.49 mmol) and 1,2-bis(4- fluorophenyl)ethyne (217.1 mg, 1.01 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 4/1) yielded 3q as a colorless solid (107 mg, 61 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.54 (d, J = 7.2 Hz, 1H), (m, 2H), 6.99 (m, 9H), 3.33 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q, J C F = 248 Hz), (C q, J C F = 244 Hz), (C q ), (C q ), (CH, J C F = 8 Hz), (C q ), (CH, J C F = 9 Hz), (C q, J C F = 3 Hz), (CH), (CH), (CH), (CH), (C q ), 118.2(C q ), (CH, J C-F = 21 Hz), (CH, J C F = 20 Hz), 34.3 (CH 3 ). 19 F-MR (283 MHz, CDCl 3 ): δ = (m), (m). IR (neat): 1639, 1603, 1505, 1482, 1331, 1159, 1054, 817, 771, 728 cm 1. MS (EI) m/z (relative intensity) 346 [M-H + ], 303 (8), 250 (10), 183 (14), 136 (12), 95 (13). HR- MS (EI) m/z calcd for C 22 H 14 F 2 - [M-H + ] , found thyl-3,4-di-n-propylisoquinolin-1(2H)-one (3r): The representative procedure C was followed using -methylbenzamide (67.5 mg, 0.50 mmol) and 4-octyne (110 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 5/1) yielded 3r as a colorless solid (71 mg, 58 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.45 (ddd, J = 8.0, 1.2, 0.8 Hz, 1H), 7.63 (dd, J = 4.2, 0.8 Hz, 2H), 7.41 (tt, J = 7.8, 5.2 Hz, 1H), 3.66 (s, 3H), (m, 4H), (m, S20

22 4H), (m, 6H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (CH), (CH), (CH), (C q ), (CH), (C q ), 31.8 (CH 2 ), 31.3 (CH 3 ), 29.8 (CH 2 ), 23.6 (CH 2 ), 22.6 (CH 2 ), 14.4 (CH 3 ), 14.2 (CH 3 ). IR (KBr): 1646, 1587, 1557, 1457, 1372, 1173, 1057, 898, 740 cm 1. MS (EI) m/z (relative intensity) 243 (30) [M + ], 214 (100). HR-MS (EI) m/z calcd for C 16 H 21 [M + ] , found ,4-Dimethyl-3-phenylisoquinolin-1(2H)-one (3s): The representative procedure C was followed using -methylbenzamide (67.5 mg, 0.50 mmol) and 1-phenylpropyne (116 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 5/1) yielded 3s as a colorless solid (75 mg, 60 %). M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.53 (d, J = 8.7 Hz, 1H), (m, 2H), (m, 4H), 7.26 (d, J = 8.0 Hz, 2H), 3.26 (s, 3H), 2.01 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (C q ), (CH), (C q ), 34.1 (CH 3 ), 14.7 (CH 3 ). IR (KBr): 1641, 1485, 1409, 1186, 1062, 1007, 840, 787, 704 cm 1. MS (EI) m/z (relative intensity) 249 (85) [M + ], 248 (100), 233 (30), 77 (23). HR-MS (EI) m/z calcd for C 17 H 15 [M + ] , found ne: 3-(4-thoxyphenyl)-2,4-dimethylisoquinolin-1(2H)-one (3t): The representative procedure C was followed using -methylbenzamide (70.0 mg, 0.52 mmol) and 1-(4- methoxyphenyl)propyne (144.6 mg, 0.99 mmol). After 22 h, purification by column S21

23 chromatography on silica gel (n-hexane/etac: 3/1) yielded 3t as a yellow oil (93 mg, 66 %). 1 H-MR (300 MHz, CDCl 3 ): δ = 8.50 (d, J = 8.0 Hz, 1H), (m, 2H), (m, 1H), (m, 2H), (m, 2H), 3.84 (s, 3H), 3.25 (s, 3H), 2.01 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (C q ), (CH), (C q ), (CH), (CH), (C q ), 55.2 (CH 3 ), 34.1 (CH 3 ), 14.8 (CH 3 ). IR (neat): 1642, 1611, 1510, 1484, 1411, 1288, 1180, 1029, 763 cm 1. MS (EI) m/z (relative intensity) 278 (100) [M-H + ], 263 (53), 248 (20), 220 (11), 178 (10), 165 (11), 148 (19), 86 (15), 77 (16). HR-MS (EI) m/z calcd for C 18 H [M + ] , found ne: 2.5 % 0.4 % 3-Cyclohex-1-enyl-2,4-dimethylisoquinolin-1(2H)-one (3u): The representative procedure C (with 10.0 mol % of [RuCl 2 (p-cymene)] 2 ) was followed using -methylbenzamide (69.0 mg, 0.51 mmol) and 1-(prop-1-ynyl)cyclohex-1-ene (126.0 mg, 1.05 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 4/1) yielded 3u as an orange oil (72 mg, 56 %). 1 H-MR (300 MHz, CDCl 3 ): δ = 8.47 (d, J = 8.3 Hz, 1H), (m, 2H), (m, 1H), (m, 1H), 3.52 (s, 3H), (m, 5H), (m, 2H), 1.76 (m, 4H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (CH), (C q ), (CH), (C q ), 32.7 (CH 3 ), 29.1 (CH 2 ), 25.2 (CH 2 ), 22.5 (CH 2 ), 21.7 (CH 2 ), 14.2 (CH 3 ). IR (neat): 2925, 2858, 2836, 1639, 1588, 1486, 1414, 1323, 1030, 765, 694 cm 1. MS (EI) m/z (relative intensity) 253 (100) [M + ], 238 (22), 224 (38), 210 (59), 196 (27), 165 (10), 128 (8), 115 (10), 77 (16). HR-MS (EI) m/z calcd for C 17 H 19 + [M + ] , found S22

24 ne: 0.7 % 1b H + 2a [RuCl 2 (p-cymene)] 2 (5.0 mol %) Cu(Ac) 2 H 2 t-amh, 100 C, 22 h + 3v: 40% 3w: 33% 7-thoxy-2-methyl-3,4-diphenylisoquinolin-1(2H)-one (3v) and 5-thoxy-2-methyl-3,4-diphenylisoquinolin-1(2H)-one (3w): The representative procedure C was followed using 3-methoxy--methylbenzamide (82.5 mg, 0.50 mmol) and diphenylacetylene (178 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 4/1) yielded 3v (69 mg, 40%) and 3w (56 mg, 33%) as colorless solids. 7-thoxy-2-methyl-3,4-diphenylisoquinolin-1(2H)-one (3v): M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 7.96 (d, J = 2.5 Hz, 1H), (m, 12H), 3.95 (s, 3H), 3.37 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (C q ), (CH), (C), (CH), 55.7 (CH 3 ), 34.5 (CH 3 ). IR (KBr): 2946, 1641, 1606, 1589, 1497, 1352, 1253, 1146, 1052, 949, 833, 727 cm 1. MS (EI) m/z (relative intensity) 341 (100) [M + ], 326 (16). HR-MS (EI) m/z calcd for C 23 H 19 2 [M + ] , found thoxy-2-methyl-3,4-diphenylisoquinolin-1(2H)-one (3w): M.p. = C. 1 H- MR (300 MHz, CDCl 3 ): δ = 8.23 (dd, J = 8.1, 1.1 Hz, 1H), 7.44 (dd, J = 8.0, 8.0 Hz, 1H), S23

25 (m, 3H), (m, 8H), 3.30 (s, 3H), 3.29 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (CH), (C q ), (CH), (C q ), (CH), (CH), (CH), (C q ), (CH), 55.9 (CH 3 ), 34.4 (CH 3 ). IR (KBr): 1630, 1602, 1583, 1556, 1492, 1417, 1266, 1156, 1027, 882, 825, 773 cm 1. MS (EI) m/z (relative intensity) 341 (100) [M + ], 249 (15), 43 (15). HR-MS (EI) m/z calcd for C 23 H 19 2 [M + ] , found F + H 1c 2a [RuCl 2 (p-cymene)] 2 (5.0 mol %) Cu(Ac) 2 H 2 t-amh, 100 C, 22 h F + F 3x: 17% 3y: 66% 7-Fluoro-2-methyl-3,4-diphenylisoquinolin-1(2H)-one (3x) and 5-Fluoro-2-methyl-3,4-diphenylisoquinolin-1(2H)-one (3y): The representative procedure C was followed using 3-fluoro--methylbenzamide (76.5 mg, 0.50 mmol) and diphenylacetylene (178 mg, 1.00 mmol). After 22 h, purification by column chromatography on silica gel (n-hexane/etac: 5/1) yielded 3x (28 mg, 17%) and 3y (108 mg, 66%) as colorless solids. 7-Fluoro-2-methyl-3,4-diphenylisoquinolin-1(2H)-one (3x): M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.19 (dd, J = 9.3, 2.8 Hz, 1H), (m, 12H), 3.35 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q ), (C q, J C F = 248 Hz), (C q ), (C q ), (C q ), (C q ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C q, J C F = 8 Hz), (CH, J C F = 23 Hz), (C q ), (CH, J C F = 23 Hz), 34.5 (CH 3 ). 19 F-MR (283 MHz, CDCl 3 ): δ = (m). IR (KBr): 1646, 1592, 1559, 1489, 1442, 1348, 1136, 1074, 958, 846, 795, 734 cm 1. MS (EI) m/z (relative intensity) 329 (100) [M + ], 250 (8), 183 (7), 77 (10). HR-MS (EI) m/z calcd for C 22 H 16 F [M + ] , found S24

26 5-Fluoro-2-methyl-3,4-diphenylisoquinolin-1(2H)-one (3y): M.p. = C. 1 H-MR (300 MHz, CDCl 3 ): δ = 8.41 (d, J = 8.1 Hz, 1H), (m, 1H), (m, 4H), (m, 7H), 3.32 (s, 3H). 13 C-MR (75 MHz, CDCl 3 ): δ = (C q, J C F = 3 Hz), (C q, J C F = 255 Hz), (C q ), (C q ), (C q ), (C q ), (CH, J C F = 4 Hz), (CH), (CH), (CH), (CH), (CH), (CH), (C q, J C F = 9 Hz), (CH, J C F = 4 Hz), (CH, J C F = 22 Hz), (C q ), 34.5 (CH 3 ). 19 F-MR (283 MHz, CDCl 3 ): δ = (dd, J = 12, 5 Hz). IR (KBr): 1650, 1588, 1547, 1443, 1359, 1256, 1162, 917, 845, 821, 763 cm 1. MS (EI) m/z (relative intensity) 329 (100) [M + ], 250 (9), 183 (7), 118 (7), 77 (9). HR-MS (EI) m/z calcd for C 22 H 16 F [M + ] , found S25

27 Intermolecular Competition Experiments with Substituted Benzamides 1d and 1e F H 1d 2.0 equiv H 1e 2.0 equiv + 2a [RuCl 2 (p-cymene)] 2 (5.0 mol %) Cu(Ac) 2 H 2 t-amh, 100 C, 22 h 3e/3c =63/37 ( 1 HMR) F 3e 3c The mixture of 4-fluoro--methylbenzamide (1d) (153 mg, 1.00 mmol), 4-methoxy-methylbenzamide (1e) (165 mg, 1.00 mmol), diphenylacetylene (2a) (89 mg, 0.50 mmol), [RuCl 2 (p-cymene)] 2 (15.3 mg, 5.0 mol %) and Cu(Ac) 2 H 2 (200 mg, 0.50 mmol) in t-amh (2.0 ml) was stirred at 100 C under nitrogen atmosphere for 22 h. After cooling the mixture to ambient temperature, the reaction mixture was diluted with aq. H 3 (75 ml, 1.0 wt %) and extracted with EtAc (3 x 75 ml). The combined organic phase was washed with brine (50 ml) and dried over a 2 S 4. After filtration and evaporation of the solvents in vacuum, the mixture was analyzed by GC-MS to show complete conversion of diphenylacetylene (2a). The ratio of isoquinolin-1(2h)-ones 3e/3c of the same crude mixture was determined to be 63/37 by 1 H MR. S26

28 Intermolecular Competition Experiments with Substituted Benzamides 1f and 1g H 1f 2.0 equiv F + [RuCl 2 (p-cymene)] 2 (5.0 mol %) Cu(Ac) 2 H 2 t-amh, 100 C, 22 h 3k + F H 1g 2.0 equiv 2a 3k/3l = 71/29 ( 1 HMR) 3l The mixture of -(4-fluorophenyl)benzamide (1f) (215 mg, 1.00 mmol), -(4-methoxyphenyl)benzamide (1g) (227 mg, 1.00 mmol), diphenylacetylene (2a) (89 mg, 0.50 mmol), [RuCl 2 (p-cymene)] 2 (15.3 mg, 5.0 mol %) and Cu(Ac) 2 H 2 (200 mg, 1.00 mmol) in t-amh (2.0 ml) was stirred at 100 C under nitrogen atmosphere for 22 h. At ambient temperature, the reaction mixture was diluted with aq. H 3 (75 ml, 1.0 wt %) and extracted with EtAc (3 x 75 ml). The combined organic phase was washed with brine (50 ml) and dried over a 2 S 4. After filtration and evaporation of the solvents in vacuum, the mixture was analyzed by GC-MS to show complete conversion of diphenylacetylene (2a). The ratio of isoquinolin-1(2h)-ones 3k/3l in the crude mixture of products was determined to be 71/29 by 1 H MR. S27

29 Intermolecular Competition Experiments with Alkynes 2a and 2b 1a H + + 2a 2.0 equiv Et Et 2b 2.0 equiv [RuCl 2 (p-cymene)] 2 (5.0 mol %) Cu(Ac) 2 H 2 t-amh, 100 C, 22 h 3a: 49% single product The mixture of -methylbenzamide (1a), (67.5 mg, 0.50 mmol), diphenylacetylene (2a), (178 mg, 1.00 mmol), 3-hexyne (2b), (82 mg, 1.00 mmol), [RuCl 2 (p-cymene)] 2 (15.3 mg, 5.0 mol %) and Cu(Ac) 2 H 2 (200 mg, 1.00 mmol) in t-amh (2.0 ml) was stirred at 100 C under nitrogen atmosphere for 22 h. At ambient temperature, the reaction mixture was diluted with aq. H 3 (75 ml, 1.0 wt %) and extracted with EtAc (3 x 75 ml). The combined organic phase was washed with brine (50 ml) and dried over a 2 S 4. After filtration and evaporation of the solvents in vacuum, the crude product was purified by column chromatography on silica gel to give isoquinolin-1(2h)-one 3a (76 mg, 49%) as a single product (analysis of the reaction mixture after the reaction by GC-MS showed no formation of the product derived from 3-hexyne). S28

30 Intermolecular Competition Experiments with Alkynes 2c and 2d F 1a H + + [RuCl 2 (p-cymene)] 2 (5.0 mol %) Cu(Ac) 2 H 2 t-amh, 100 C, 22 h 3o 17% + 2c 2.0 equiv F 2d 2.0 equiv F F 3q 68% A mixture of -methylbenzamide (1a) (33.8 mg, 0.25 mmol), 1,2-di-p-tolylethyne (2c), (103 mg, 0.50 mmol), 1,2-bis(4-fluorophenyl)ethyne (2d) (107 mg, 0.50 mmol), [RuCl 2 (p-cymene)] 2 (7.7 mg, 5.0 mol %) and Cu(Ac) 2 H 2 (100 mg, 0.50 mmol) in t-amh (1.0 ml) was stirred at 100 C under nitrogen atmosphere for 22 h. At ambient temperature, the reaction mixture was diluted with aq. H 3 (75 ml, 1.0 wt %) and extracted with EtAc (3 x 75 ml). The combined organic phase was washed with brine (50 ml) and dried over a 2 S 4. After filtration and evaporation of the solvents in vacuum, the crude product was purified by column chromatography on silica gel to give isoquinolin-1(2h)-one 3o (14 mg, 17%) and isoquinolin-1(2h)-one 3q (59 mg, 68%). S29