Electronic Supplementary Information · 2012. 6. 11. · S2 1. General 1H NMR (400MHz) spectra were...

S1

Electronic Supplementary Information

A CuBr-Mediated Expedient Synthesis of 4-Bromoisoquinolones from 2-Alkynylbenzaldehydes and Primary Amines under an O2 atmosphere

Pei Chui Too and Shunsuke Chiba*

Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore

Fax: +65-67911961; E-mail: [email protected]

1. General S2 2. Synthesis of 2-alkynylbenzaldehyde derivatives 2.1. Preparation of 2-alkynylbenzaldehyde 1a-b & 1k-1s S2

2.2. Preparation of 2-arylethynylbenzaldehyde 1c-1j S6

3. CuBr-mediated synthesis of 4-bromoisoquinolones S9 3.1. A typical procedure for synthesis of 3aa S9 3.2. The reactions with CuCl and CuI S19 3.3. The reactions with !-alanine ethyl ester (2m) and propargylamine 2n S21 4. Control experiments to elucidate the reaction mechanism S22 5. 1H and 13C NMR spectrum of new compounds S24

Electronic Supplementary Material (ESI) for Chemical CommunicationsThis journal is © The Royal Society of Chemistry 2012

S2

1. General 1H NMR (400MHz) spectra were recorded on a Bruker Avance 400 spectrometers in CDCl3

[using (CH3)4Si (for 1H, ! = 0.00) as internal standard]. 13C NMR (100 MHz) spectra on a Bruker Avance 400 spectrometers in CDCl3 [using CDCl3 (for 13C, ! = 77.00) as internal standard]. The following abbreviations were used to explain the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, qn = quintet, m = multiplet, brs = broad singlet, brd = broad doublet. IR spectra were recorded on a Shimazu IR Prestige-21 FT-IR Spectrometer. High-resolution mass spectra were obtained with a Finnigan MAT 95 XP mass spectrometer (Thermo Electron Corporation). Melting points were uncorrected and were recorded on a Buchi B-54 melting point apparatus.

Flash column chromatography was performed using Merck silica gel 60 with distilled solvents. Benzene was used without further purification. CuBr!SMe2 (99%) was purchased from Sigma-Aldrich Co., Inc. All amines 2 were purchased from Sigma-Aldrich Co., Inc. except for 2f,1 2m2 and 2n3. 2. Synthesis of 2-alkynylbenzaldehyde derivatives 2.1. Preparation of 2-alkynylbenzaldehyde 1a-b & 1k-1s: a typical procedure for synthesis of 2-(2-phenylethynyl)benzaldehyde (1a).

H

O

Br

H

O

Ph

Ph

2 mol % PdCl2(PPh3)21 mol % CuI

NEt3, 50 °C, 3-6 h+

1a To a solution of 2-bromobenzaldehyde (3.70 g, 20.0 mmol), PdCl2(PPh3)2 (0.28 g, 0.40 mmol), and CuI (38 mg, 0.20 mmol) in 80 mL of NEt3 was added phenylacetylene (2.08 g, 20.4 mmol). The resulting mixture was heated under nitrogen atmosphere at 50 °C. After the reaction was completed, the reaction mixture was quenched with distilled water and extracted with ethyl acetate (50 mL " 3). The combined extracts were washed with brine and dried over MgSO4. Volatile materials were removed in vacuo and the resulting crude material was purified by flash column chromatography (Si gel, hexane : ethyl acetate = 95 : 5) to give 2-(2-phenylethynyl)benzaldehyde (1a) in 94% yield. 2-(2-Phenylethynyl)benzaldehyde (1a)4 Brown oil; 1H NMR (400 MHz, CDCl3) ! 7.36-7.40 (3H, m), 7.45 (1H, tt, J = 0.8, 7.6 Hz), 7.55-7.60 (3H, m), 7.64 (1H, dd, J = 0.8, 7.6 Hz), 7.95 (1H, dd, J = 0.8, 7.6 Hz), 10.65 (d, J = 0.4 Hz); 13C NMR (100 MHz, CDCl3) ! 84.8, 96.3, 122.3, 126.8, 127.2, 128.5, 128.6, 129.0, 131.6, 133.2, 133.7, 135.8, 191.7. 2-[2-(4-Methoxyphenyl)ethynyl]benzaldehyde (1b)5 1 R. F. Nystrom, J. Am. Chem. Soc. 1953, 75, 292. 2 A. Rayan, M. Falah, U.S. Pat. Appl. Publ. 20100284959, 2010. 3 M. Lemhadri, H. Doucet, M. Santelli, Synthesis 2005, 1359. 4 J. H. Park, S. V. Bhilare, S. W. Youn, Org. Lett. 2011, 13, 2228. 5 S. Obika, H. Kono, Y. Yasui, R. Yanada, Y. Takemoto, J. Org. Chem. 2007, 72, 4462.


S3

Prepared from 2-bromobenzaldehyde and 1-ethynyl-4-methoxybenzene, and purified by by flash column chromatography (Si gel, hexane:ethyl acetate = 95:5) in quantitative yield; White solid; 1H NMR (400 MHz, CDCl3) ! 3.84 (3H, s), 6.91 (2H, td, J = 2.4, 8.8 Hz), 7.42 (1H, dt, J = 0.4, 7.2 Hz), 7.50 (2H, td, J = 2.4, 8.8 Hz), 7.56 (1H, dt, J = 1.6, 7.6 Hz), 7.61 (1H, dd, J = 0.8, 7.2 Hz), 7.93 (1H, dd, J = 0.8, 8.0 Hz), 10.64 (1H, d, J = 0.8 Hz); 13C NMR (100 MHz, CDCl3) ! 55.3, 83.7, 96.6, 114.1, 114.3, 127.1, 127.3, 128.2, 133.0, 133.2, 133.7, 135.6, 160.2, 191.8. 2-(Hept-1-ynyl)benzaldehyde (1k)6

Prepared from 2-bromobenzaldehyde and 1-heptyne and purified by by flash column chromatography (Si gel, hexane:ethyl acetate = 95:5) in 89% yield; Yellow oil; 1H NMR (400 MHz, CDCl3) ! 0.93 (3H, t, J = 7.2 Hz), 1.32-1.49 (4H, m), 1.65 (2H, tt, J = 6.8, 7.6 Hz), 2.48 (2H, t, J = 7.2 Hz), 7.35-7.40 (1H, m), 7.48-7.55 (2H, m), 7.89 (1H, d, J = 8.0 Hz), 10.54 (1H, d, J = 0.4 Hz); 13C NMR (100 MHz, CDCl3) ! 13.9, 19.5, 22.1, 28.2, 31.1, 76.3, 98.2, 126.8, 127.8, 127.9, 133.2, 133.6, 135.9, 192.2. 2-(Cyclohexylethynyl)benzaldehyde (1l)7

Prepared from 2-bromobenzaldehyde and andcyclohexylacetylene, and purified by by flash column chromatography (Si gel, hexane:ethyl acetate = 95:5) in quantitative yield; Yellow oil; 1H NMR (400 MHz, CDCl3) ! 1.32-1.45 (3H, m), 1.46-1.61 (3H, m), 1.71-1.80 (2H, m), 1.87-1.95 (2H, m), 2.68 (1H, m), 7.35-7.40 (1H, m), 7.48-7.54 (2H, m), 7.88 (1H, d, J = 7.6 Hz), 10.56 (1H, d, J = 0.8 Hz); 13C NMR (100 MHz, CDCl3) ! 24.8, 25.8, 29.8, 32.4, 76.2, 102.1, 126.8, 127.8, 128.0, 133.2, 133.6, 135.8, 192.2. 2-(2-Cyclopropylethynyl)benzaldehyde (1m)4 6 A. Hamze, O. Provot, M. Alami, J.-D. Brion, Org. Lett. 2005, 7, 5625. 7 A. K. Verma, V. Rustagi, T. Aggarwal, A. P. Singh, J. Org. Chem. 2010, 75, 7691.


S4

Prepared from 2-bromobenzaldehyde and cyclopropylacetylene, and purified by by flash column chromatography (Si gel, hexane:ethyl acetate = 95:5) in quantitative yield; Yellow oil; 1H NMR (400 MHz, CDCl3) ! 0.83-0.90 (2H, m), 0.90-0.98 (2H, m), 1.48-1.56 (1H, m), 7.36 (1H, t, J = 7.6 Hz), 7.46-7.53 (2H, m), 7.87 (1H, d, J = 8.0 Hz), 10.49 (1H , s); 13C NMR (100 MHz, CDCl3) ! 0.3, 8.9, 71.4, 101.2, 126.9, 127.7, 127.8, 133.2, 133.6, 136.0, 192.1. 3-Methyl-2-(phenylethynyl)benzaldehyde (1n)

Prepared from 2-bromo-3-methylbenzaldehyde and phenylacetylene, and purified by by flash column chromatography (Si gel, hexane:ethyl acetate = 95:5) in 96% yield; Brown solid; mp. 48–50 °C; IR (neat) 691, 756, 1242, 1489, 1682, 1701 cm-1; 1H NMR (400 MHz, CDCl3) ! 2.59 (3H, s), 7.35 (1H, t, J = 7.6 Hz), 7.38-7.42 (3H, m), 7.50 (1H, d, J = 7.6 Hz), 7.56-7.60 (2H, m), 7.80 (1H, dd, J = 0.4, 8.0 Hz), 10.69 (1H, d, J = 0.8 Hz); 13C NMR (100 MHz, CDCl3) ! 20.5, 83.6, 100.8, 122.6, 124.6, 126.6, 128.1, 128.5, 129.0, 131.5, 134.8, 136.0, 141.5, 192.3; ESIHRMS: Found: m/z 221.0964. Calcd for C16H13O: (M+H)+ 221.0966. 4,5-Dimethoxy-2-(2-phenylethynyl)benzaldehyde (1o)4

Prepared from 6-bromo-1,3-benzodioxole-5-carboxaldehyde and phenylacetylene, and purified by flash column chromatography (Si gel, hexane:ethyl acetate = 95:5) in 93% yield; White solid; 1H NMR (400 MHz, CDCl3) ! 6.10 (2H, s), 7.03 (1H, s), 7.37 (1H, s), 7.36-7.40 (3H, m), 7.52-7.56 (2H, m), 10.49 (1H, s); 13C NMR (100 MHz, CDCl3) ! 84.7, 95.1, 102.4, 106.1, 112.0, 122.3, 123.6, 128.5, 129.0, 131.6, 132.1, 148.7, 152.4, 190.0. 5-Methoxy-2-(phenylethynyl)benzaldehyde (1p)4


S5

Prepared from 2-bromo-5-methoxybenzaldehyde and phenylacetylene, and purified by flash column chromatography (Si gel, hexane:ethyl acetate = 95:5) in 95% yield; Brown solid; 1H NMR (400 MHz, CDCl3) ! 3.88 (3H, s), 7.14 (1H, dd, J = 2.8, 8.8 Hz), 7.35-7.39 (3H, m), 7.43 (1H, d, J = 2.8 Hz), 7.53-7.58 (3H, m), 10.62 (1H, s); 13C NMR (100 MHz, CDCl3) ! 55.6, 84.8, 94.8, 109.8, 119.6, 121.7, 122.6, 128.5, 128.7, 131.5, 134.5, 137.2, 159.8, 191.6. 5-Fluoro-2-(phenylethynyl)benzaldehyde (1q)5

Prepared from 2-bromo-5-fluorobenzaldehyde and phenylacetylene, and purified by flash column chromatography (Si gel, hexane:ethyl acetate = 95:5) in 91% yield; Pale yellow solid; 1H NMR (400 MHz, CDCl3) ! 7.30 (1H, dt, J = 2.8, 8.0 Hz), 7.37-7.41 (3H, m), 7.54-7.57 (2H, m), 7.60-7.67 (2H, m), 10.60 (1H, d, J = 3.2 Hz); 13C NMR (100 MHz, CDCl3) ! 83.8, 96.0, 113.7 (d, J = 22.9 Hz), 121.3 (d, J = 22.5 Hz), 122.1, 123.0 (d, J = 3.6 Hz), 128.5, 129.1, 131.6, 135.2 (d, J = 7.6 Hz), 137.7 (d, J = 6.5 Hz), 162.3 (d, J = 251.2 Hz), 190.4. 3-(Phenylethynyl)benzofuran-2-carbaldehyde (1r)

Prepared from 3-bromobenzofuran-2-carbaldehyde and phenylacetylene, and purified by flash column chromatography (Si gel, hexane:ethyl acetate = 95:5) in 96% yield; Brown solid; mp. 99–101 °C; IR (neat) 685, 748, 881, 1294, 1339, 1667 cm-1; 1H NMR (400 MHz, CDCl3) ! 7.40-7.46 (4H, m), 7.58 (1H, dt, J = 1.2, 8.8 Hz), 7.60-7.66 (3H, m), 7.89 (1H, d, J = 8.0 Hz), 10.13 (1H, s); 13C NMR (100 MHz, CDCl3) ! 77.1, 100.1, 112.8, 115.9, 121.8, 122.5, 124.5, 127.5, 128.6, 129.6, 130.0, 131.9, 152.5, 155.4, 178.0; ESIHRMS: Found: m/z 247.0761. Calcd for C17H11O2: (M+H)+ 247.0759. 2-(Phenylethynyl)nicotinaldehyde (1s)5

Prepared from 2-bromonicotinaldehyde and phenylacetylene, and purified by flash column chromatography (Si gel, hexane:ethyl acetate = 80:20) in 88% yield; Brown solid; 1H NMR (400 MHz, CDCl3) ! 7.37-7.44 (4H, m), 7.64 (2H, d, J = 6.8 Hz), 8.20 (1H, d, J = 7.6 Hz), 8.81 (1H, d, J = 4.4 Hz), 10.66 (1H, s); 13C NMR (100 MHz, CDCl3) ! 84.6, 95.9, 121.1, 123.1, 128.4, 129.7, 131.6, 132.0, 134.6, 145.8, 154.3, 190.6.


S6

2.2. Preparation of 2-arylethynylbenzaldehyde 1c-1j: a typical procedure for the synthesis of 2-[2-(4-methylphenyl)ethynyl]benzaldehyde (1c)

To a solution of 2-ethynylbenzaldehyde1 (195 mg, 1.5 mmol), PdCl2(PPh3)2 (21 mg, 0.03 mmol), and CuI (2.9 mg, 0.015 mmol) in 6 mL of NEt3 was added the 1-iodo-4-methylbenzene (393 mg, 1.8 mmol). The resulting mixture was heated under nitrogen atmosphere at 50 °C. After the reaction was completed, the reaction mixture was quenched with distilled water and extracted with ethyl acetate (50 mL " 3). Volatile materials were removed in vacuo and the crude material was purified by flash column chromatography (Si gel, hexane:ethyl acetate = 95:5) to give 2-[2-(4-methylphenyl)ethynyl]benzaldehyde (1c) in 85% yield. 2-[2-(4-Methylphenyl)ethynyl]benzaldehyde (1c)8 Yellow solid; 1H NMR (400 MHz, CDCl3) ! 2.39 (3H, s), 7.19 (2H, d, J = 8.0 Hz), 7.43 (1H, tt, J = 0.8, 7.2 Hz), 7.46 (2H, d, J = 8.0 Hz), 7.57 (1H, dt, J = 1.6, 7.6Hz), 7.63 (1H, dd, J = 0.8, 7.6 Hz), 7.94 (1H, dd, J = 0.8, 7.6 Hz), 10.65 (1H, d, J = 0.8 Hz); 13C NMR (100 MHz, CDCl3) ! 21.6, 84.3, 96.6, 119.2, 127.1, 128.4, 129.3, 131.6 (overlapped), 133.1, 133.7, 135.7, 139.4, 191.8. 2-[2-(4-Fluorophenyl)ethynyl]benzaldehyde (1d)

Prepared from 2-ethynylbenzaldehyde and 4-fluoroiodobenzene, and purified by flash column chromatography (Si gel, hexane:ethyl acetate = 95:5) in 82% yield; White solid; mp. 79–81 °C; IR (neat) 758, 829, 1233, 1506, 1591, 1684 cm-1; 1H NMR (400 MHz, CDCl3) ! 7.08 (2H, tt, J = 2.0, 8.8 Hz), 7.46 (1H, t, J = 7.6 Hz), 7.53-7.61 (3H, m), 7.63 (1H, dd, J = 0.8, 7.6 Hz), 7.95 (1H, dd, J = 0.8, 7.6 Hz), 10.62 (1H, d, J = 0.4 Hz); 13C NMR (100 MHz, CDCl3) ! 84.6, 95.2, 155.9 (d, J = 21.9 Hz), 118.4 (d, J = 3.5 Hz), 126.6, 127.4, 128.7, 133.2, 133.6 (d, J = 8.5 Hz), 133.8, 135.8, 162.9 (d, J = 249.6 Hz), 191.5; ESIHRMS: Found: m/z 225.0711. Calcd for C15H10FO: (M+H)+ 225.0716. Ethyl 4-((2-formylphenyl)ethynyl)benzoate (1e)9

8 J. D. Tovar, T. M. Swager, J. Org. Chem. 1999, 64, 6499. 9 C. P. Allen, T. Benkovics, A. K. Turek, T. P. Yoon, J. Am. Chem. Soc. 2009, 131, 12560.


S7

Prepared from 2-ethynylbenzaldehyde and ethyl 4-iodobenzoate, and purified by flash column chromatography (Si gel, hexane:ethyl acetate = 90:10) in 86% yield; Pale yellow solid; 1H NMR (400 MHz, CDCl3) ! 1.42 (3H, t, J = 7.2 Hz), 4.40 (2H, q, J = 7.2 Hz), 7.50 (1H, t, J = 7.6 Hz), 7.59-7.65 (3H, m), 7.67 (1H, dd, J = 0.8, 7.2 Hz), 7.97 (1H, dd, J = 0.8, 7.6 Hz), 8.06 (2H, td, J = 1.6, 8.4 Hz), 10.64 (1H, s); 13C NMR (100 MHz, CDCl3) ! 14.3, 61.2, 87.6, 95.3, 126.1, 126.8, 127.5, 129.1, 129.6, 130.6, 131.5, 133.4, 133.8, 135.9, 165.9, 191.3. 2-[2-(4-Trifluoromethylphenyl)ethynyl]benzaldehyde (1f)5

Prepared from 2-ethynylbenzaldehyde and 1-iodo-4-(trifluoromethyl)benzene, and purified by flash column chromatography (Si gel, hexane:ethyl acetate = 95:5) in 74% yield; Pale yellow solid; 1H NMR (400 MHz, CDCl3) ! 7.50 (1H, t, J = 7.6 Hz), 7.61 (1H, dt, J = 1.2, 7.6 Hz), 7.63-7.70 (5H, m), 7.97 (1H, dd, J = 1.2, 7.6 Hz), 10.62 (1H, d, J = 0.8 Hz); 13C NMR (100 MHz, CDCl3) ! 87.2, 94.5, 123.8 (q, J = 270.6 Hz), 125.5 (q, J = 3.7 Hz), 125.8, 126.1, 127.6, 129.2, 130.7 (q, J = 32.7 Hz), 131.9, 133.4, 133.8, 136.0, 191.2. 2-[2-(3-Methoxyphenyl)ethynyl]benzaldehyde (1g)10

Prepared from 2-ethynylbenzaldehyde and 1-bromo-3-methoxybenzene, and purified by flash column chromatography (Si gel, hexane:ethyl acetate = 90:10) in 88% yield; Brown oil; 1H NMR (400 MHz, CDCl3) ! 3.84 (3H, s), 6.95 (1H, ddd, J = 0.8, 2.4, 8.4 Hz), 7.08 (1H, q, J = 1.2 Hz), 7.16 (1H, d, J = 7.6 Hz), 7.29 (1H, t, J = 7.6 Hz), 7.45 (1H, t, J = 7.6 Hz), 7.58 (1H, dt, J = 1.2, 7.6 Hz), 7.65 (1H, d, J = 7.6 Hz), 7.95 (1H, dd, J = 0.8, 7.6 Hz), 10.65 (1H, s); 13C NMR (100 MHz, CDCl3) ! 55.3, 84.6, 96.2, 115.7, 116.3, 123.3, 124.2, 126.8, 127.2, 128.6, 129.6, 133.2, 133.8, 135.8, 159.4, 191.7. 2-[2-(2-Methoxyphenyl)ethynyl]benzaldehyde (1h)11 10 N. T. Patil, A. Konala, V. Singh, V. V. N. Reddy, Eur. J. Org. Chem. 2009, 5178.


S8

Prepared from 2-ethynylbenzaldehyde and 1-bromo-2-methoxybenzene, and purified by by flash column chromatography (Si gel, hexane:ethyl acetate = 90:10) in 87% yield; Pale yellow solid; 1H NMR (400 MHz, CDCl3) ! 3.92 (3H, s), 6.92 (1H, d, J = 8.0 Hz), 6.96 (1H, t, J = 7.2 Hz), 7.35 (1H, dt, J = 1.6, 8.0 Hz), 7.42 (1H, t, J = 7.6 Hz), 7.51 (1H, dd, J = 1.6, 7.2 Hz), 7.56 (1H, dt, J = 1.2, 7.6 Hz), 7.65 (1H, dd, J = 0.4, 8.0 Hz), 7.95 (1H, dd, J = 0.8, 7.6 Hz), 10.74 (1H, d, J = 0.8 Hz); 13C NMR (100 MHz, CDCl3) ! 55.8, 89.0, 93.0, 110.6, 111.6, 120.5, 126.9, 127.4, 128.3, 130.5, 132.9, 133.2, 133.6, 135.8, 160.4, 192.5. 2-[2-(2-Bromophenyl)ethynyl]benzaldehyde (1i)12

Prepared from 2-ethynylbenzaldehyde and 2-bromoiodobenzene, and purified by flash column chromatography (Si gel, hexane:ethyl acetate = 95:5) in 94% yield; White solid; 1H NMR (400 MHz, CDCl3) ! 7.24 (1H, dt, J = 1.6, 7.6 Hz), 7.34 (1H, dt, J = 1.2, 7.6 Hz), 7.48 (1H, t, J = 7.6 Hz), 7.58-7.63 (2H, m), 7.64 (1H, dd, J = 0.8, 8.0 Hz), 7.70 (1H, dd, J = 0.8, 8.0 Hz), 7.97 (1H, dd, J = 1.2, 8.0 Hz), 10.76 (1H, s); 13C NMR (100 MHz, CDCl3) ! 89.3, 94.6, 124.6, 125.8, 126.4, 127.1, 127.2, 129.0, 130.1, 132.6, 133.4, 133.5, 133.8, 136.1, 191.9. 2-[2-(2-Naphthyl)ethynyl]benzaldehyde (1j)

Prepared from 2-ethynylbenzaldehyde and 2-iodonaphthalene, and purified by flash column chromatography (Si gel, hexane:ethyl acetate = 95:5) in 67% yield; White solid; mp. 73–75 °C; IR (neat) 743, 758, 1263, 1506, 1591, 1653, 1690 cm-1; 1H NMR (400 MHz, CDCl3) ! 7.48 (1H, t, J = 7.6 Hz), 7.51-7.56 (2H, m), 7.58-7.64 (2H. m), 7.70 (1H, dd, J = 0.8, 8.0 Hz), 7.83-7.88 (3H, m), 7.98 (1H, dd, J = 0.8, 8.0 Hz), 8.11 (1H, s), 10.73 (1H, d, J = 0.4 Hz); 13C NMR (100 MHz, CDCl3) ! 85.2, 96.8, 119.5, 126.8, 126.9, 127.1, 127.3, 127.8, 127.9, 128.0, 128.2, 128.6, 131.9, 132.9,

11 M. Alfonsi, M. Dell’Acqua, D. Facoetti, A. Arcadi, G. Abbiati, E. Rossi, Eur. J. Org. Chem. 2009, 2852–2862 12 D. P. Iwaniuk, C. Wolf, Org. Lett. 2011, 13, 2602.


S9

133.1, 133.2, 133.8, 135.8, 191.7; ESIHRMS: Found: m/z 257.0964. Calcd for C19H13O: (M+H)+ 257.0966. 3. CuBr-mediated synthesis of 4-bromoisoquinolones: 3.1. A typical procedure for synthesis of 3aa (Table 1, entry 6).

CuBr•SMe2(2.2 equiv)

benzene-pyridine(5 : 1)

SiO2, 80 °Cunder O2 (1 atm)

H

Ph

H2N Ph+N

O

Ph

PhBr3aa1a

2a(3 equiv)

O

To a stirred solution of 2-alkynylbenzaldehyde (1a) (105.0 mg, 0.509 mmol), CuBr!SMe2 (230.2 mg, 1.12 mmol) and SiO2 (0.3 g) in 5 mL of solvent (benzene : pyridine = 5 : 1) at 80 °C under O2 atmosphere were added benzylamine (2a) [(55 µL " 3), (0.509 " 3) mmol] three times at every 1 h interval, and the reaction mixture was allowed to stir for another 1 h. After cooled to room temperature, the reaction was quenched with pH 9 buffer and extracted with ethyl acetate (20 mL " 3). The combined extracts were washed with brine and dried over MgSO4. Volatile materials were removed in vacuo, and the resulting crude material was purified by flash column chromatography (Si gel, hexane:ethyl acetate = 90:10) to give 2-benzyl-4-bromo-3-phenylisoquinolin-1(2H)-one (3aa) (158.0 mg, 0.405 mmol) in 80% yield.

2-Benzyl-4-bromo-3-phenylisoquinolin-1(2H)-one (3aa) Sticky yellow oil; IR (neat) 694, 752, 1337, 1582, 1607, 1647 cm-1; 1H NMR (400 MHz, CDCl3) ! 5.16 (2H, brs), 6.80-6.86 (2H, m), 7.06 (2H, d, J = 7.2 Hz), 7.13-7.18 (3H, m), 7.35 (2H, dd, J = 7.2, 7.6 Hz), 7.42 (1H, t, J = 7.2 Hz), 7.58 (1H, dt, J = 0.8, 7.6 Hz), 7.76 (1H, dt, J = 1.2, 7.6 Hz), 8.00 (1H, d, J = 8.0 Hz), 8.55 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 49.9, 102.8, 125.5, 126.5, 126.7, 127.0, 127.7, 128.2, 128.4, 128.5, 129.2, 129.4, 133.3, 135.5, 135.6, 137.1, 142.2, 162.1; ESIHRMS: Found: m/z 390.0490. Calcd for C22H17NO 79Br: (M+H)+ 390.0494. –Table 2– 4-Bromo-2-(4-methoxybenzyl)-3-phenylisoquinolin-1(2H)-one (3ab)

Yellow oil; IR (neat) 748, 1032, 1177, 1246, 1510, 1582, 1607, 1647 cm-1; 1H NMR (400 MHz, CDCl3) ! 3.74 (3H, s), 5.10 (2H, brs), 6.69 (2H, td, J = 1.6, 8.8 Hz), 6.76 (2H, d, J = 8.8 Hz), 7.09 (2H, d, J = 7.2 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.45 (1H, t, J = 7.6 Hz), 7.59 (1H, ddd, J = 0.8, 7.2, 8.0 Hz), 7.78 (1H, ddd, J = 1.2, 7.2, 8.0 Hz), 8.01 (1H, d, J = 8.0 Hz), 8.55 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 49.4, 55.2, 102.8, 113.6, 125.6, 126.5, 127.7, 128.35, 128.41, 128.5, 129.2, 129.3, 129.6, 133.3, 135.6, 135.7, 142.2, 158.7, 162.2; ESIHRMS: Found: m/z 420.0599. Calcd for C23H19NO2

79Br: (M+H)+ 420.0599.


S10

4-Bromo-2-(4-methylbenzyl)-3-phenylisoquinolin-1(2H)-one (3ac)

Yellow oil; IR (neat) 692, 907, 1034, 1246, 1510, 1647 cm-1; 1H NMR (400 MHz, CDCl3) ! 2.27 (3H, s), 5.11 (2H, brs), 6.73 (2H, d, J = 8.0 Hz), 6.97 (2H, d, J = 8.0 Hz), 7.09 (2H, d, J = 6.8 Hz), 7.38 (2H, dd, J = 6.8, 7.6 Hz), 7.44 (1H, tt, J = 1.2, 7.6 Hz), 7.60 (1H, ddd, J = 1.2, 7.2, 7.6 Hz), 7.78 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 8.01 (1H, d, J = 8.0 Hz), 8.55 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 21.0, 49.8, 102.7, 125.6, 126.5, 126.7, 127.7, 128.4, 128.5, 128.9, 129.2, 129.5, 133.2, 134.1, 135.5, 135.7, 136.6, 142.3, 162.1; ESIHRMS: Found: m/z 404.0650. Calcd for C23H19NO 79Br: (M+H)+ 404.0650. 4-Bromo-2-(4-fluorobenzyl)-3-phenylisoquinolin-1(2H)-one (3ad)

Yellow solid; mp. 149–151 °C; IR (neat) 750, 1219, 1335, 1508, 1582, 1638 cm-1; 1H NMR (400 MHz, CDCl3) ! 5.13 (2H, brs), 6.77-6.88 (4H, m), 7.07 (2H, d, J = 7.2 Hz), 7.39 (2H, dd, J = 7.2, 8.0 Hz), 7.46 (1H, tt, J = 1.2, 7.2 Hz), 7.61 (1H, ddd, J = 0.8, 7.2, 8.0 Hz), 7.79 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 8.02 (1H, d, J = 8.4 Hz), 8.55 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 49.2, 102.9, 115.0 (d. J = 21.4 Hz), 125.5, 126.6, 127.8, 128.4, 128.5, 128.7 (d. J = 8.0 Hz), 129.3, 129.5, 132.9 (d, J = 3.1 Hz), 133.3, 135.51, 135.53, 141.9, 161.9 (d, J = 244.2 Hz), 162.1; ESIHRMS: Found: m/z 408.0403. Calcd for C22H16NOF 79Br: (M+H)+ 408.0399. 4-Bromo-2-phenethyl-3-phenylisoquinolin-1(2H)-one (3ae)

White solid; mp. 121–123 °C; IR (neat) 754, 1223, 1337, 1508, 1584, 1609, 1651 cm-1; 1H NMR (400 MHz, CDCl3) ! 2.83-2.90 (2H, m), 3.95-4.03 (2H, m), 6.86 (2H, d, J = 6.4 Hz), 7.13-7.20 (3H, m), 7.27-7.32 (2H, m), 7.53-7.57 (3H, m), 7.60 (1H, dd, J = 7.2, 7.6 Hz), 7.78 (1H, dd, J = 7.6, 8.0 Hz), 8.00 (1H, d, J = 8.4 Hz), 8.54 (1H, d, J = 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 34.7, 49.1, 102.4, 125.6, 126.4, 126.5, 127.7, 128.1, 128.4, 128.7, 128.8, 129.3, 129.4, 133.2, 135.4, 136.0, 138.1, 142.0, 161.7; ESIHRMS: Found: m/z 404.0649. Calcd for C23H19NO 79Br: (M+H)+ 404.0650. 4-Bromo-2-(2,2-diphenylethyl)-3-phenylisoquinolin-1(2H)-one (3af)


S11

Yellow solid; mp. 159–161 °C; IR (neat) 698, 756, 1508, 1636, 1645, 1653 cm-1; 1H NMR (400 MHz, CDCl3) ! 4.52 (2H, brs), 4.60 (1H, t, J = 7.2 Hz), 6.72 (2H, brs), 6.90-6.97 (4H, m), 7.13-7.20 (6H, m), 7.36 (2H, dd, J = 7.2, 8.0 Hz), 7.44 (1H, tt, J = 1.2, 7.6 Hz), 7.57 (1H, ddd, J = 1.2, 6.8, 8.0 Hz), 7.75 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 7.95 (1H, d, J = 8.0 Hz), 8.50 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 48.0, 52.0, 102.6, 125.6, 126.5, 126.6, 127.6, 128.2, 128.35, 128.43, 128.5, 129.1, 129.8, 133.1, 135.4, 135.6, 141.2, 142.3, 162.2; ESIHRMS: Found: m/z 480.0963. Calcd for C29H23NO 79Br: (M+H)+ 480.0963. 4-Bromo-2-pentyl-3-phenylisoquinolin-1(2H)-one (3ag)

Yellow oil; IR (neat) 762, 1092, 1339, 1474, 1582, 1647, 2930, 2955 cm-1; 1H NMR (400 MHz, CDCl3) ! 0.77 (3H, t, J = 6.8 Hz), 1.02-1.17 (4H, m), 1.56 (2H, tt, J = 7.2, 8.0 Hz), 3.79 (2H, t, J = 8.0 Hz), 7.33-7.37 (2H, m), 7.50-7.56 (3H, m), 7.57 (1H, ddd, J = 0.8, 7.2, 8.0 Hz), 7.75 (1H, ddd, J = 1.6, 7.2, 8.4 Hz), 7.98 (1H, d, J = 8.4 Hz), 8.50 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 13.8, 21.9, 28.3, 28.8, 47.4, 102.3, 125.7, 126.4, 127.5, 128.2, 128.7, 129.25, 129.28, 133.0, 135.4, 136.2, 142.2, 161.6; ESIHRMS: Found: m/z 370.0814. Calcd for C20H21NO 79Br: (M+H)+ 370.0807. 4-Bromo-2-(2-(cyclohex-1-en-1-yl)ethyl)-3-phenylisoquinolin-1(2H)-one (3ah)

White solid; mp. 107–109 °C; IR (neat) 752, 1578, 1609, 1636, 1647, 2859, 2924 cm-1; 1H NMR (400 MHz, CDCl3) ! 1.40-1.52 (4H, m), 1.66 (2H, brs), 1.85 (2H, brs), 2.15 (2H, t, J = 8.0 Hz), 3.86 (2H, t, J = 8.0 Hz), 5.21 (1H, brs), 7.34-7.38 (2H, m), 7.51-7.58 (4H, m), 7.74 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 7.97 (1H, d, J = 8.0 Hz), 8.49 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 22.1, 22.7, 25.1, 27.8, 36.9, 46.5, 102.3, 123.4, 125.6, 126.4, 127.5, 128.1, 128.7, 129.27, 129.34, 133.0, 134.1, 135.3, 136.0, 142.0, 161.6; ESIHRMS: Found: m/z 408.0964. Calcd for C23H23NO 79Br: (M+H)+ 408.0963. 4-Bromo-2-(cyclohexylmethyl)-3-phenylisoquinolin-1(2H)-one (3ai)


S12

Mixture Rotational isomer (1.00 : 0.22) at room temperature; White solid; mp. 140–145 °C; IR (neat) 1335, 1506, 1578, 1645, 1717, 2849, 2926 cm-1; 1H NMR (400 MHz, CDCl3, the major isomer’s spectra was shown) ! 0.73-0.84 (2H, m), 1.01-1.12 (3H, m), 1.37-1.43 (2H, m), 1.52-1.70 (4H, m), 3.78 (2H, brs), 7.30-7.36 (2H, m), 7.48-7.55 (3H, m), 7.57 (1H, ddd, J = 1.2, 6.8, 8.0 Hz), 7.75 (1H, ddd, J = 1.6, 7.2, 8.4 Hz), 7.99 (1H, d, J = 8.0 Hz), 8.50 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3, the major isomer’s spectra was shown) ! 25.8, 26.1, 30.7, 37.5, 52.6, 102.6, 125.6, 126.4, 127.5, 128.3, 128.5, 129.1, 129.9, 133.0, 135.4, 136.0, 142.4, 162.1; ESIHRMS: Found: m/z 396.0956. Calcd for C22H23NO 79Br: (M+H)+ 396.0963. 4-Bromo-2-(cyclopropylmethyl)-3-phenylisoquinolin-1(2H)-one (3aj)

Orange solid; mp. 102–104 °C; IR (neat) 694, 764, 1474, 1607, 1645, 2851, 2924 cm-1; 1H NMR (400 MHz, CDCl3) ! 0.16-0.22 (2H, m), 0.33-0.38 (2H, m), 0.92-1.03 (1H, m), 3.82 (2H, d, J = 6.8 Hz), 7.33-7.40 (2H, m), 7.48-7.56 (3H, m), 7.55 (1H, t, J = 7.2 Hz), 7.74 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 7.97 (1H, d, J = 8.0 Hz), 8.50 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 4.2, 10.7, 50.8, 102.4, 125.7, 126.4, 127.5, 128.2, 128.6, 129.2, 129.7, 133.0, 135.4, 136.2, 142.0, 162.1; ESIHRMS: Found: m/z 354.0498. Calcd for C19H17NO 79Br: (M+H)+ 354.0494. 4-Bromo-2-(2-methoxyethyl)-3-phenylisoquinolin-1(2H)-one (3ak)

Yellow oil; IR (neat) 692, 760, 1103, 1115, 1580, 1647, 3003 cm-1; 1H NMR (400 MHz, CDCl3) ! 3.18 (3H, s), 3.54 (2H, t, J = 6.0 Hz), 4.06 (2H, t, J = 6.0 Hz), 7.32-7.37 (2H, m), 7.50-7.55 (3H, m), 7.57 (1H, ddd, J = 1.2, 7.2, 8.0 Hz), 7.77 (1H, ddd, J = 1.2, 7.2, 8.0 Hz), 7.99 (1H, d, J = 8.0 Hz), 8.49 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 46.4, 58.7, 69.4, 102.6, 125.5, 126.5, 127.6, 128.1, 128.7, 129.3, 129.7, 133.2, 135.6, 136.1, 142.4, 161.9; ESIHRMS: Found: m/z 358.0445. Calcd for C18H17NO2 79Br: (M+H)+ 358.0443. 4-Bromo-2-methyl-3-phenylisoquinolin-1(2H)-one (3al)


S13

White solid; mp. 132–134 °C; IR (neat) 745, 756, 1117, 1339, 1474, 1636, 1645 cm-1; 1H NMR (400 MHz, CDCl3) ! 3.32 (3H, s), 7.31-7.35 (2H, m), 7.50-7.59 (4H, m), 7.75 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 7.98 (1H, d, J = 8.4 Hz), 8.50 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 35.1, 101.9, 125.3, 126.4, 127.6, 128.1, 128.98, 129.03, 129.3, 133.0, 135.4, 136.4, 142.2, 162.2; ESIHRMS: Found: m/z 314.0178. Calcd for C16H13NO 79Br: (M+H)+ 314.0181.

2-Methyl-3-phenylisoquinolin-1(2H)-one (4al)13

White solid; 1H NMR (400 MHz, CDCl3) ! 3.43 (3H, s), 6.46 (1H, s), 7.39-7.43 (2H, m), 7.45-7.51 (6H, m), 7.63 (1H, dd, J = 7.2, 7.6 Hz), 8.46 (1H, d, J = 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 34.1, 107.5, 124.9, 125.8, 126.6, 127.8, 128.6, 128.7, 128.9, 132.2, 136.2, 136.3, 143.9, 163.3.

–Table 3– 2-Benzyl-4-bromo-3-(4-methoxyphenyl)isoquinolin-1(2H)-one (3ba)

Sticky yellow oil; IR (neat) 750, 1032, 1173, 1248, 1508, 1609, 1645 cm-1; 1H NMR (400 MHz, CDCl3) ! 3.85 (3H, s), 5.18 (2H, brs), 6.84-6.90 (4H, m), 6.99 (2H, d, J = 8.4 Hz), 7.15-7.20 (3H, m), 7.59 (1H, ddd, J = 1.2, 7.2, 8.0 Hz), 7.78 (1H, ddd, J = 1.2, 7.2, 8.0 Hz), 8.01 (1H, d, J = 8.0 Hz), 8.55 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 50.0, 55.3, 103.5, 113.8, 125.5, 126.6, 126.7, 127.0, 127.7, 128.1, 128.2, 128.6, 130.8, 133.3, 135.6, 137.3, 142.2, 160.0, 162.3; ESIHRMS: Found: m/z 420.0605. Calcd for C23H19NO2 79Br: (M+H)+ 420.0599. 2-Benzyl-4-bromo-3-(4-methylphenyl)isoquinolin-1(2H)-one (3ca)

13 A. Couture, H. Cornet, P. Grandclaudon, J. Organomet. Chem. 1992, 440, 7.


S14

Sticky yellow oil; IR (neat) 1456, 1474, 1508, 1582, 1607, 1647, 3010 cm-1; 1H NMR (400 MHz, CDCl3) ! 2.40 (3H, s), 5.16 (2H, brs), 6.84-6.89 (2H, m), 6.97 (2H, d, J = 8.0 Hz), 7.14-7.19 (3H, m), 7.56 (1H, ddd, J = 1.2, 7.2, 8.0 Hz), 7.77 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 8.01 (1H, d, J = 8.0 Hz), 8.54 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 21.4, 50.0, 102.9, 125.5, 126.5, 126.7, 127.0, 127.6, 128.2, 128.5, 129.1, 129.3, 132.8, 133.2, 135.6, 137.2, 139.2, 142.4, 162.2; ESIHRMS: Found: m/z 404.0656. Calcd for C23H19NO 79Br: (M+H)+ 404.0650. 2-Benzyl-4-bromo-3-(4-fluorophenyl)isoquinolin-1(2H)-one (3da)

White solid; mp. 131–133 °C; IR (neat) 1223, 1238, 1373, 1506, 1636, 1717, 1734 cm-1; 1H NMR (400 MHz, CDCl3) ! 5.17 (2H, brs), 6.80-6.85 (2H, m), 7.00-7.08 (4H, m), 7.16-7.20 (3H, m), 7.61 (1H, ddd, J = 1.2, 7.2, 8.0 Hz), 7.80 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 8.01 (1H, d, J = 8.0 Hz), 8.56 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 49.9, 103.3, 115.6 (d, J = 21.7 Hz), 125.6, 126.59, 126.62, 127.2, 127.9, 128.3, 128.6, 131.5 (d, J = 8.4 Hz), 131.6 (d, J = 3.8 Hz), 133.4, 135.4, 137.0, 141.2, 162.1, 162.9 (d, J = 248.6 Hz); ESIHRMS: Found: m/z 408.0392. Calcd for C22H16NOF 79Br: (M+H)+ 408.0399. Ethyl 4-(2-benzyl-4-bromo-1-oxo-1,2-dihydroisoquinolin-3-yl)benzoate (3ea)

Yellow oil; IR (neat) 760, 1022, 1099, 1271, 1506, 1653, 1717 cm-1; 1H NMR (400 MHz, CDCl3) ! 1.42 (3H, t, J = 7.2 Hz), 4.42 (2H, q, J = 7.2 Hz), 5.15 (2H, brs), 6.78-6.83 (2H, m), 7.12-7.20 (5H, m), 7.62 (1H, ddd, J = 0.8, 7.2, 8.0 Hz), 7.80 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 8.01 (1H, d, J = 8.0 Hz), 8.04 (2H, d, J = 8.4 Hz), 8.57 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 14.3, 49.9, 61.3, 102.6, 125.6, 126.6 (overlapped), 127.2, 128.1, 128.4, 128.6, 129.6, 129.7, 131.2, 133.4, 135.4, 136.8, 139.7, 141.2, 162.1, 165.8; ESIHRMS: Found: m/z 462.0703. Calcd for C25H21NO3 79Br: (M+H)+ 462.0705. 2-Benzyl-4-bromo-3-(4-trifluoromethylphenyl)isoquinolin-1(2H)-one (3fa)

Yellow oil; IR (neat) 760, 1067, 1128, 1167, 1321, 1647 cm-1; 1H NMR (400 MHz, CDCl3) ! 5.14 (2H, brs), 6.75-6.81 (2H, m), 7.13-7.20 (5H, m), 7.59-7.66 (3H, m), 7.80 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 8.01 (1H, d, J = 8.0 Hz), 8.57 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 49.9,


S15

102.8, 123.7 (q, J = 270.6 Hz), 125.4 (q, J = 3.7 Hz), 125.7, 126.56, 126.63, 127.3, 128.2, 128.4, 128.7, 130.1, 131.3 (q, J = 32.6 Hz), 133.5, 135.3, 136.8, 139.0, 140.6, 162.1; ESIHRMS: Found: m/z 458.0359. Calcd for C23H16NOF3 79Br: (M+H)+ 458.0367. 2-Benzyl-4-bromo-3-(3-methoxyphenyl)isoquinolin-1(2H)-one (3ga)

Sticky oil; IR (neat) 1040, 1215, 1261, 1456, 1489, 1578, 1651 cm-1; 1H NMR (400 MHz, CDCl3) ! 3.56 (3H, s), 4.94 (1H, brd, J = 14.8 Hz), 5.38 (1H, brd. J = 15.2 Hz), 6.46 (1H, s), 6.73 (1H, d, J = 7.6 Hz), 6.83-6.90 (2H, m), 6.96 (1H, ddd, J = 0.8, 2.4, 8.4 Hz), 7.16-7.21 (3H, m), 7.31 (1H, t, J = 8.0 Hz), 7.60 (1H, ddd, J = 1.2, 7.6, 8.4 Hz), 7.79 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 8.02 (1H, d, J = 8.0 Hz), 8.56 (1H, dd, J = 1.2, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 50.0, 55.0, 102.6, 114.3, 115.7, 121.5, 125.5, 126.5, 126.7, 127.0, 127.7, 128.3, 128.5, 129.6, 133.3, 135.6, 136.6, 137.4, 142.0, 159.2, 162.2; ESIHRMS: Found: m/z 420.0602. Calcd for C23H19NO2 79Br: (M+H)+ 420.0599. 2-Benzyl-4-bromo-3-(2-methoxyphenyl)isoquinolin-1(2H)-one (3ha)

Yellow solid; mp. 108–110 °C; IR (neat) 758, 1256, 1495, 1578, 1599, 1636, 2965 cm-1; 1H NMR (400 MHz, CDCl3) ! 3.55 (3H, s), 4.93 (1H, brd, J = 15.2 Hz), 5.33 (1H, brd. J = 15.2 Hz), 6.82-6.88 (2H, m), 6.88-6.95 (3H, m), 7.11-7.16 (3H, m), 7.40-7.46 (1H, m), 7.58 (1H, ddd, J = 1.2, 7.6, 8.4 Hz), 7.77 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 8.00 (1H, d, J = 8.0 Hz), 8.56 (1H, dd, J = 1.2, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 49.8, 55.2, 103.3, 110.9, 120.4, 124.5, 125.6, 126.4, 126.9, 127.1, 127.5, 128.0, 128.5, 131.1, 131.3, 133.1, 135.7, 137.2, 139.7, 156.5, 162.4; ESIHRMS: Found: m/z 420.0598. Calcd for C23H19NO2 79Br: (M+H)+ 420.0599. 2-Benzyl-4-bromo-3-(2-bromophenyl)isoquinolin-1(2H)-one (3ia)

Yellow oil; IR (neat) 692, 752, 1026, 1327, 1472, 1607, 1647 cm-1; 1H NMR (400 MHz, CDCl3) ! 4.49 (1H, d, J = 15.2 Hz), 5.80 (1H, d, J = 15.6 Hz), 6.80-6.87 (3H, m), 7.11-7.20 (4H, m), 7.30 (1H, dt, J = 1.6, 8.0 Hz), 7.62 (1H, ddd, J = 1.2, 7.6, 8.4 Hz), 7.69 (1H, dd, J = 1.2, 8.0 Hz), 7.79 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 8.01 (1H, d, J = 8.0 Hz), 8.59 (1H, dd, J = 1.2, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 49.7, 103.4, 123.9, 125.8, 126.6, 127.0, 127.18, 127.22, 128.1, 128.2, 128.6,


S16

130.9, 132.1, 132.7, 133.3, 135.4, 136.4, 136.9, 140.8, 162.2; ESIHRMS: Found: m/z 469.9583. Calcd for C22H16NO 79Br 81Br: (M+H)+ 469.9578. 2-Benzyl-4-bromo-3-(2-naphthyl)isoquinolin-1(2H)-one (3ja)

Yellow oil; IR (neat) 748, 1337, 1506, 1582, 1647 cm-1; 1H NMR (400 MHz, CDCl3) ! 5.02 (1H, brd, J = 15.2 Hz), 5.33 (1H, brd, J = 15.2 Hz), 6.77 (2H, d, J = 6.8 Hz), 7.07-7.20 (4H, m), 7.48-7.59 (3H, m), 7.62 (1H, ddd, J = 0.8, 7.2, 8.0 Hz), 7.68 (1H, d, J = 8.0 Hz), 7.80 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 7.85 (1H, d, J = 8.4 Hz), 7.89 (1H, d, J = 8.0 Hz), 8.03 (1H, d, J = 8.4 Hz), 8.59 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 50.1, 103.1, 125.6, 126.4, 126.57, 126.62, 126.8, 127.07, 127.13, 127.76, 127.81, 128.22, 128.24, 128.4, 128.6, 129.4, 132.6, 132.8, 133.1, 133.3, 135.6, 137.2, 142.1, 162.2; ESIHRMS: Found: m/z 440.0654. Calcd for C26H19NO 79Br: (M+H)+ 440.0650. 2-Benzyl-4-bromo-3-pentylisoquinolin-1(2H)-one (3ka)

N

O

Ph

n-C5H11Br

X-ray of 3ka

Colorless crystal; mp. 109–111 °C; IR (neat) 764, 1456, 1506, 1558, 1645, 1717 cm-1; 1H NMR (400 MHz, CDCl3) ! 0.91 (3H, t, J = 6.8 Hz), 1.30-1.42 (4H, m), 1.56-1.64 (2H, m), 2.90 (2H, t, J = 8.0 Hz), 5.50 (2H, brs), 7.14 (2H, d, J = 7.2 Hz), 7.25 (1H, t, J = 7.2 Hz), 7.31 (2H, dd, J = 6.8, 7.6 Hz), 7.51 (1H, ddd, J = 1.2, 7.2, 8.0 Hz), 7.74 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 7.98 (1H, d, J = 8.4 Hz), 8.46 (1H, dd, J = 1.2, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 13.9, 22.2, 27.9, 31.7, 33.6, 48.1, 102.3, 124.6, 125.9, 126.1, 127.0, 127.3, 128.5, 128.8, 133.2, 135.8, 137.0, 142.4, 162.5; ESIHRMS: Found: m/z 384.0969. Calcd for C21H23NO 79Br: (M+H)+ 384.0963. 2-Benzyl-4-bromo-3-cyclohexylisoquinolin-1(2H)-one (3la)

White solid; mp. 126–128 °C; IR (neat) 1339, 1456, 1506, 1576, 1607, 1636, 1653cm-1; 1H NMR (400 MHz, CDCl3) ! 0.92-1.50 (4H, m), 1.55-1.90 (4H, m), 2.53 (2H, dtd, J = 3.6, 12.4, 12.8 Hz), 3.06 (1H, tt, J = 3.2, 12.0 Hz), 5.57 (2H, brs), 7.19 (2H, d, J = 7.2 Hz), 7.23-7.28 (1H, m), 7.32 (2H, dd, J = 7.2, 7.6 Hz), 7.51 (1H, ddd, J = 1.2, 7.2, 8.0 Hz), 7.72 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 8.06


S17

(1H, d, J = 8.0 Hz), 8.47 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 25.4, 26.8, 27.9, 43.1, 48.6, 101.9, 124.6, 125.8, 126.2, 127.2, 127.3, 128.4, 128.7, 133.0, 136.2, 137.6, 145.2, 163.0; ESIHRMS: Found: m/z 396.0961. Calcd for C22H23NO 79Br: (M+H)+ 396.0963. 2-Benzyl-4-bromo-3-cyclopropylisoquinolin-1(2H)-one (3ma)

White solid; mp. 120–122 °C; IR (neat) 696, 764, 1456, 1506, 1576, 1645, 1717 cm-1; 1H NMR (400 MHz, CDCl3) ! 0.95-1.00 (2H, m), 1.23-1.29 (2H, m), 1.65 (1H, tt, J = 6.0, 8.4 Hz), 5.81 (2H, brs), 7.14 (2H, d, J = 7.2 Hz), 7.20-7.30 (3H, m), 7.52 (1H, ddd, J = 0.8, 7.2, 8.0 Hz), 7.73 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 8.02 (1H, d, J = 8.4 Hz), 8.46 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 12.1, 15.3, 47.5, 105.5, 125.1, 126.0, 126.3, 127.0, 127.3, 128.3, 128.6, 133.0, 135.8, 137.6, 141.3, 162.5; ESIHRMS: Found: m/z 354.0497. Calcd for C19H17NO 79Br: (M+H)+ 354.0494. 2-Benzyl-4-bromo-5-methyl-3-phenylisoquinolin-1(2H)-one (3na)

Yellow solid; mp. 141–143 °C; IR (neat) 694, 760, 1327, 1456, 1506, 1578, 1639 cm-1; 1H NMR (400 MHz, CDCl3) ! 2.96 (3H, s), 5.11 (2H, brs), 6.78-6.84 (2H, m), 7.04 (2H, d, J = 7.2 Hz), 7.13-7.18 (3H, m), 7.32-7.42 (3H, m), 7.45 (1H, dd, J = 7.6, 8.0 Hz), 7.57 (1H, d, J = 7.2 Hz), 8.54 (1H, d, J = 8.0 Hz) ; 13C NMR (100 MHz, CDCl3) ! 25.6, 50.2, 100.1, 126.8, 127.0, 127.30, 127.33, 127.6, 128.2, 128.5, 128.9, 129.5, 134.2, 135.3, 136.7, 137.1, 137.5, 142.7, 162.3; ESIHRMS: Found: m/z 404.0647. Calcd for C23H19NO 79Br: (M+H)+ 404.0650. 6-Benzyl-8-bromo-7-phenyl-[1,3]dioxolo[4,5-g]isoquinolin-5(6H)-one (3oa)

Sticky yellow oil; IR (neat) 696, 1036, 1231, 1406, 1472, 1568, 1645 cm-1; 1H NMR (400 MHz, CDCl3) ! 5.13 (2H, brs), 6.14 (2H, s), 6.79-6.85 (2H, m), 7.05 (2H, d, J = 6.8 Hz), 7.14-7.19 (3H, m), 7.35 (2H, dd, J = 6.8, 8.0 Hz), 7.42 (1H, s), 7.42 (1H, tt, J = 1.2, 8.0 Hz), 7.90 (1H, s); 13C NMR (100 MHz, CDCl3) ! 50.0, 102.1, 102.4, 105.1, 106.3, 121.2, 126.7, 127.0, 128.2, 128.4, 129.1, 129.5, 133.2, 135.8, 137.2, 141.0, 148.4, 152.8, 161.3; ESIHRMS: Found: m/z 434.0389. Calcd for C23H17NO3 79Br: (M+H)+ 434.0392.


S18

2-Benzyl-4-bromo-7-methoxy-3-phenylisoquinolin-1(2H)-one (3pa)

Yellow solid; mp. 161–163 °C; IR (neat) 698, 939, 1038, 1406, 1474, 1645 cm-1; 1H NMR (400 MHz, CDCl3) ! 3.97 (3H, s), 5.16 (2H, brs), 6.80-6.87 (2H, m), 7.07 (2H, d, J = 7.2 Hz), 7.14-7.19 (3H, m), 7.32-7.39 (3H, m), 7.42 (1H, t, J = 7.2 Hz), 7.94 (1H, d, J = 9.2 Hz), 7.96 (1H, d, J = 2.4 Hz); 13C NMR (100 MHz, CDCl3) ! 50.1, 55.8, 102.7, 108.4, 123.6, 126.7, 127.0, 128.2, 128.37, 128.40 (overlapped), 129.1, 129.6, 129.8, 135.7, 137.2, 139.7, 159.4, 161.9; ESIHRMS: Found: m/z 420.0599. Calcd for C23H19NO2 79Br: (M+H)+ 420.0599. 2-Benzyl-4-bromo-7-fluoro-3-phenylisoquinolin-1(2H)-one (3qa)

Yellow solid; mp. 104–106 °C; IR (neat) 696, 752, 941, 1341, 1489, 1585, 1647 cm-1; 1H NMR (400 MHz, CDCl3) ! 5.15 (2H, brs), 6.79-6.85 (2H, m), 7.06 (2H, d, J = 6.8 Hz), 7.14-7.20 (3H, m), 7.37 (2H, dd, J = 7.2, 8.0 Hz), 7.44 (1H, tt, J = 1.2, 7.2 Hz), 7.51 (1H, ddd, J = 2.8, 8.0, 8.8 Hz), 8.04 (1H, dd, J = 4.8, 8.8 Hz), 8.21 (1H, d, J = 1.2, 9.2 Hz); 13C NMR (100 MHz, CDCl3) ! 50.2, 102.1, 113.7 (d, J = 23.2 Hz), 121.8 (d, J = 23.4 Hz), 126.8, 127.1 (d, J = 7.8 Hz), 127.2, 128.3, 128.5, 129.3, 129.4 (d, J = 8.2 Hz), 129.5, 132.2 (d, J = 2.2 Hz), 135.4, 136.9, 141.5 (d, J = 2.8 Hz), 161.4 (d, J = 4.2 Hz), 162.0 (d, J = 247.9 Hz); ESIHRMS: Found: m/z 408.0405. Calcd for C22H16NOF 79Br: (M+H)+ 408.0399. 2-benzyl-4-bromo-3-phenylbenzofuro[2,3-c]pyridin-1(2H)-one (3ra)

White solid; mp. 182–184 °C; IR (neat) 743, 1038, 1456, 1474, 1647, 1668 cm-1; 1H NMR (400 MHz, CDCl3) ! 5.28 (2H, brs), 6.79-6.85 (2H, m), 7.05 (2H, d, J = 7.2 Hz), 7.13-7.19 (3H, m), 7.39 (2H, t, J = 7.6 Hz), 7.42-7.49 (2H, m), 7.62 (1H, ddd, J = 1.2, 7.2, 8.4 Hz), 7.75 (1H, d, J = 8.8 Hz), 8.45 (1H, dd, J = 0.4, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 50.0, 95.5, 112.8, 123.4, 123.5, 123.6, 127.0, 127.3, 128.29, 128.32, 128.6, 129.3, 129.5, 129.8, 134.4, 136.7, 142.7, 143.3, 154.1, 156.9; ESIHRMS: Found: m/z 430.0437. Calcd for C24H17NO2 79Br: (M+H)+ 430.0443. 6-Benzyl-8-bromo-7-phenyl-1,6-naphthyridin-5(6H)-one (3sa)


S19

Yellow solid; mp. 138–140 °C; IR (neat) 698, 1435, 1456, 1541, 1558, 1638 cm-1; 1H NMR (400 MHz, CDCl3) ! 5.17 (2H, brs), 6.80-6.87 (2H, m), 7.10 (2H, d, J = 7.2 Hz), 7.15-7.21 (3H, m), 7.39 (2H, dd, J = 6.8, 7.6 Hz), 7.46 (1H, tt, J = 1.2, 7.2 Hz), 7.54 (1H, dd, J = 4.8, 8.0 Hz), 8.81 (1H, dd, J = 1.6, 8.0 Hz), 9.09 (1H, dd, J = 1.6, 4.8 Hz); 13C NMR (100 MHz, CDCl3) ! 50.0, 104.7, 121.4, 122.6, 126.7, 127.2, 128.3, 128.5, 129.0, 129.4, 135.0, 136.6, 137.1, 146.2, 150.2, 155.1, 162.1; ESIHRMS: Found: m/z 391.0443. Calcd for C21H16N2O 79Br: (M+H)+ 391.0446.

6-Benzyl-7-phenyl-1,6-naphthyridin-5(6H)-one (4sa)

Yellow solid; mp. 113–115 °C; IR (neat) 704, 839, 1358, 1437, 1506, 1558, 1653 cm-1; 1H NMR (400 MHz, CDCl3) ! 5.24 (2H, brs), 6.72 (1H, s), 6.87-6.93 (2H, m), 7.15-7.20 (3H, m), 7.23 (2H, d, J = 7.2 Hz), 7.36 (2H, dd, J = 7.2, 8.0 Hz), 7.41-7.46 (2H, m), 8.74 (1H, dd, J = 1.2, 8.0 Hz), 8.93 (1H, dd, J = 1.6, 4.8 Hz); 13C NMR (100 MHz, CDCl3) ! 48.6, 109.8, 120.9, 121.7, 126.8, 127.1, 128.3 (overlapped), 128.8, 129.2, 135.2, 136.6, 137.1, 147.8, 152.9, 154.8, 163.1; ESIHRMS: Found: m/z 313.1335. Calcd for C21H17N2O: (M+H)+ 313.1341.

3.2. The reactions with CuCl and CuI It was found that CuCl and CuI also showed the reactivity in the present reaction conditions, giving 4-chloro- and 4-iodoisoquinolones 3aa’ and 3aa”, respectively, while lower yields were observed.

Scheme S1.

+N

O

Ph

PhX

3aa' (X = Cl); 23%3aa" (X = l); 39%**

1a(0.5 mmol)

2a(3 equiv)

CuX(2.2 equiv)



**Pydirine was used as a sole solvent.

2-Benzyl-4-chloro-3-phenylisoquinolin-1(2H)-one (3aa’)


S20

Synthesized from 2.2 equiv of CuCl; Yellow oil; IR (neat) 696, 752, 1477, 1495, 1585, 1611, 1647 cm-1; 1H NMR (400 MHz, CDCl3) ! 5.15 (2H, brs), 6.80-6.86 (2H, m), 7.09 (2H, d, J = 6.8 Hz), 7.14-7.18 (3H, m), 7.36 (2H, dd, J = 6.8, 7.6 Hz), 7.43 (1H, t, J = 7.6 Hz), 7.61 (1H, dt, J = 0.8, 7.6 Hz), 7.79 (1H, dt, J = 1.2, 7.6 Hz), 8.00 (1H, d, J = 8.0 Hz), 8.57 (1H, dd, J = 0.8, 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 49.5, 111.8, 123.8, 125.5, 126.8, 127.1, 127.8, 128.3, 128.5, 128.6,129.2, 129.6, 133.1, 133.6, 134.7, 137.2, 140.5, 162.0; ESIHRMS: Found: m/z 346.1003. Calcd for C22H17NOCl: (M+H)+ 346.0999. 2-Benzyl-4-iodo-3-phenylisoquinolin-1(2H)-one (3aa’’)

Synthesized from 2.2 equiv of CuI in pyridine (0.1 M); White solid; IR (neat) 696, 762, 1030, 1339, 1587, 1603, 1647 cm-1; mp. 86–88 °C; 1H NMR (400 MHz, CDCl3) ! 5.20 (2H, brs), 6.80-6.86 (2H, m), 7.02 (2H, d, J = 7.6 Hz), 7.14-7.18 (3H, m), 7.35 (2H, dd, J = 7.2, 7.6 Hz), 7.42 (1H, t, J = 7.2 Hz), 7.57 (1H, t, J = 7.6 Hz), 7.75 (1H, t, J = 7.6 Hz), 7.96 (1H, d, J = 8.0 Hz), 8.51 (1H, d, J = 8.0 Hz); 13C NMR (100 MHz, CDCl3) ! 50.8, 79.9, 125.2, 126.7, 127.0, 127.8, 128.2, 128.4, 128.6, 129.3, 129.5, 131.7, 133.6, 137.2, 137.4, 139.3, 145.7, 162.5; ESIHRMS: Found: m/z 438.0354. Calcd for C22H17NOI: (M+H)+ 438.0355.


S21

3.3. The reactions with !-alanine ethyl ester (2m) and propargylamine 2n The reaction of !-alanine ethyl ester (2m) (as a hydrochloride salt) with 1a under the standard reaction conditions provided 4-bromoisoquinoline 5 and protonated isoquinoline 6 in 42% and 28% yields, respectively, with certain C-N bond cleavage, and no desired 4-bromoisoquinolone was formed at all (Scheme S2). Similarly, 3-phenylprop-2-yn-1-amine (2n) also delivered 4-bromoisoquinoline 5 without forming 4-bromoisoquinolone 3. It is noted that aromatic amines (anilines) did not work at all to provide any cyclized product under the present reaction conditions.

Scheme S2.

O

H

Ph

H2N




2 h

N

XPh

+

1a(0.5 mmol)

2m(1.2 equiv)

5 (X = Br); 42%6 (X = H); 28%

CO2EtCl–

O

H

Ph

H2N




4 h

N

BrPh

+

1a(0.5 mmol)

2n(3 equiv)

5 30%

Ph

4-Bromo-3-phenylisoquinoline (5)14

White solid; 1H NMR (400 MHz, CDCl3) ! 7.41-7.53 (3H, m), 7.66 (1H, ddd, J = 0.8, 7.2, 8.0 Hz), 7.71-7.76 (2H, m), 7.82 (1H, ddd, J = 1.2, 6.8, 8.4 Hz), 7.98 (1H, d, J = 8.0 Hz), 8.31 (1H, dd, J = 0.8, 8.8 Hz), 9.22 (1H, s); 13C NMR (100 MHz, CDCl3) ! 118.2, 126.9, 127.7, 127.8, 127.9, 128.3, 128.5, 129.8, 131.8, 135.9, 140.7, 151.0, 152.3. 3-Phenylisoquinoline (6)15

White solid; 1H NMR (400 MHz, CDCl3) ! 7.41 (1H, tt, J = 1.2, 7.6 Hz), 7.48-7.53 (2H, m), 7.57 (1H, ddd, J = 1.2, 6.8, 8.0 Hz), 7.68 (1H, ddd, J = 1.2, 6.8, 8.0 Hz), 7.86 (1H, d, J = 8.0 Hz), 7.97

14 H.-P. Zhang, S.-C. Yu, Y. Liang, P. Peng, B.-X. Tang, J.-H. Li, Synlett 2011, 982. 15 Y.-N. Niu, Z.-Y. Yan, G.-L. Gao, H.-L. Wang, X.-Z. Shu, K.-G. Ji, Y.-M. Liang, J. Org. Chem. 2009, 74, 2893.


S22

(1H, d, J = 8.0 Hz), 8.06 (1H, s), 8.10-8.15 (2H, m), 9.33 (1H, s); 13C NMR (100 MHz, CDCl3) ! 116.5, 126.8, 126.9, 127.0, 127.5, 127.7, 128.4, 128.7, 130.4, 136.5, 139.5, 151.2, 152.3. 4. Control experiments to elucidate the reaction mechanism To elucidate the reaction mechanism for the formation of 4-bromoisoquinolone derivatives 3, especially pertaining to how N-C bond forming cyclization as well as formation of C=O and C-Br bonds could occur, several control experiments were conducted (Scheme S3). The reaction of N-benzylaldimines 7 under the standard reaction conditions afforded 4-bromoisoquinolone 3aa (Scheme S3-a), while cyclization of N-benzylamide 8 did not proceed at all (Scheme S3-b). With the fact that the reaction of benzaldehyde (9) and benzylamine (2a) under the present conditions gave only aldimine 10 derived from condensation of 9 and 2a as well as dimerization of 2a (Scheme S3-c), it could be expected that the N-C bond forming cyclization onto alkyne might occur prior to the C=O bond formation. Stahl reported a CuBr-catalyzed aerobic bromination of arenes in the presence of LiBr as a stoichiometric bromine atom source, where molecular bromine generated in situ underwent an electrophilic bromination. 16 On the contrary, treatment of cyclooctene (11) under the present reaction conditions (2.2 equiv of CuBr•SMe2, SiO2, in benzene-pyridine under an O2 atmosphere) did not afford any electrophilic bromination product (Scheme S3-d). This suggested that molecular bromine (or a precursor of bromonium cation) is not likely involved in the present 4-bromoisoquinolone formation. It is also noted that vinylic C-H bromination of isoquinolone 4aa did not proceed under the present reaction conditions (Scheme S3-e).

Scheme S3.

N

Ph

PhN

O

PhBr

Ph(a)

NH

Ph

Ph

O

3aa 36%

no reaction(recovery of 8 in 81% yield)

(b)

H N Ph

O

+ H2N Ph

standardconditions

standardconditions

standardconditions

(c)

**standard conditions: CuBr•SMe2 (2.2 equiv) in benzene-pyridine (5:1), SiO2 80 °C, under an O2 atmosphere (1 atm).

7

8

9 2a (3 equiv) 10 116% based on 9

standardconditions Br

X0%11

(d)

N

O

PhBr

Ph

3aa 0%

standardconditionsN

O

PhH

Ph

4aa

(e)

16 L. Yang, Z. Lu and S. S. Stahl, Chem. Commun. 2009, 6460.


S23

Preparation of N-benzyl-2-(2-phenylethynyl)benzaldimine (7):

Ph

H

O

+ H2N PhMS 4A

CH2Cl2, rt24 h Ph

N Ph

1a2a

7 To a solution of 2-(2-phenylethynyl)benzaldehyde (1a) (206 mg, 1.0 mmol) in 1 mL of CH2Cl2 were added benzylamine (2a) (107 mg, 1.0 mmol) and MS 4Å (20 mg). The reaction mixture was allowed to stir at room temperature for 24 h. After the completion of reaction, the mixture was filtered and volatile materials were removed in vacuo and the crude material was used for next reaction without further purification. N-Benzyl-2-(2-phenylethynyl)benzaldimine (7)5 Brown oil; 1H NMR (400 MHz, CDCl3) ! 4.90 (2H, s), 7.36-7.40 (10H, m), 7.50-7.57 (3H, m), 8.14 (1H, d, J = 6.8 Hz), 8.99 (1H, s); 13C NMR (100 MHz, CDCl3) ! 65.1, 86.4, 94.9, 122.9, 124.1, 126.4, 127.0, 128.1, 128.4, 128.5, 128.58, 128.63, 130.3, 131.5, 132.5, 136.7, 139.1, 160.5. N-Benzyl-2-(phenylethynyl)benzamide (8)17

NH

O

Ph

Ph Prepared from N-benzyl-2-bromobenzamide and phenylacetylene by the same procedure with the section 2.1., and purified by flash column chromatography (Si gel, hexane:ethyl acetate = 80:20) in 95% yield; White solid; 1H NMR (400 MHz, CDCl3) ! 4.70 (2H, d, J = 5.6 Hz), 7.13 (2H, d, J = 7.2 Hz), 7.22-7.29 (5H, m), 7.30-7.40 (3H, m), 7.42-7.48 (2H, m), 7.56-7.61 (1H, m), 7.80 (1H, brs), 8.12-8.17 (1H, m); 13C NMR (100 MHz, CDCl3) ! 44.5, 87.5, 95.8, 119.6, 121.8, 127.5, 128.2, 128.4, 128.75, 128.86, 128.92, 130.2, 130.6, 131.4, 133.6, 135.0, 137.8, 166.1. Both imine 10 and isoquinolone 4aa were known compounds (see the references). N-Benzyl-benzaldimine (10)18

2-Benzyl-3-phenylisoquinolin-1(2H)-one (4aa)19

N

O

PhH

Ph

17 G. Liu, Y. Zhou, D. Ye, D. Zhang, X. Ding, H. Jiang, H. Liu, Adv. Synth. Catal. 2009, 351, 2605. 18 L. G. Marinescu, C. M. Pedersen, M. Bols, Tetrahedron 2004, 61, 123. 19 N. Sakai, K. Annaka, A. Fujita, A. Sato, T. Konakahara, J. Org. Chem. 2008, 73, 4160.


4. 1H and 13C NMR spectrum of new compounds

S24

1H NMR spectrum of 1d (400 MHz, CDCl3)

11 10 9 8 7 6 5 4 3 2 1 ppm

7.062

7.067

7.079

7.084

7.089

7.101

7.106

7.263

7.442

7.461

7.477

7.479

7.480

7.535

7.540

7.548

7.552

7.557

7.566

7.570

7.586

7.589

7.604

7.607

7.624

7.626

7.643

7.646

7.939

7.941

7.958

7.960

10.623

10.624

2.06

1.05

3.15

1.03

1.03

1.00

7.17.27.37.47.57.67.77.87.98.0 ppm

7.06

27.

067

7.07

97.

084

7.08

97.

101

7.10

6

7.26

3

7.44

27.

461

7.47

77.

479

7.48

07.

535

7.54

07.

548

7.55

27.

557

7.56

67.

570

7.58

67.

589

7.60

47.

607

7.62

47.

626

7.64

37.

646

7.93

97.

941

7.95

87.

960

2.06

5

1.05

2

3.15

2

1.02

9

1.02

6

10.6010.65 ppm

10.6

2310

.624

1.00

0

!

H

O

F



S25

13C NMR spectrum of 1d (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm76.68

77.00

77.32

84.65

95.16

115.77

115.99

118.40

118.43

126.59

127.37

128.66

133.15

133.59

133.68

133.78

135.78

161.66

164.16

191.54

!

H

O

F



S26

1H NMR spectrum of 1j (400 MHz, CDCl3)

11 10 9 8 7 6 5 4 3 2 1 ppm

7.259

7.459

7.478

7.497

7.520

7.528

7.536

7.544

7.553

7.590

7.594

7.597

7.613

7.615

7.632

7.635

7.687

7.689

7.707

7.708

7.831

7.839

7.846

7.854

7.862

7.967

7.969

7.987

7.989

8.107

10.726

10.727

1.03

1.99

2.00

1.01

2.99

0.97

0.99

1.00

10.7210.74 ppm

10.7

2610

.727

1.00

0

6.97.07.17.27.37.47.57.67.77.87.98.08.18.28.38.4 ppm

7.25

9

7.45

97.

478

7.49

77.

520

7.52

87.

536

7.54

47.

553

7.59

07.

594

7.59

77.

613

7.61

57.

632

7.63

57.

687

7.68

97.

707

7.70

87.

831

7.83

97.

846

7.85

47.

862

7.96

77.

969

7.98

77.

989

8.10

7

1.03

3

1.98

9

2.00

0

1.01

0

2.99

0

0.97

0

0.99

0

!

H

O



S27

13C NMR spectrum of 1j (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm76.68

77.00

77.32

85.20

96.75

119.54

126.76

126.86

127.09

127.30

127.80

127.87

128.03

128.24

128.61

131.87

132.89

133.10

133.22

133.79

135.84

191.69

!

H

O



S28

1H NMR spectrum of 1n (400 MHz, CDCl3)

11 10 9 8 7 6 5 4 3 2 1 ppm

2.589

7.259

7.332

7.351

7.371

7.388

7.393

7.396

7.404

7.413

7.491

7.509

7.510

7.566

7.570

7.573

7.576

7.580

7.582

7.590

7.787

7.787

7.806

7.807

10.689

10.691

3.00

4.34

1.07

2.12

1.00

0.95

10.7 ppm

10.689

10.691

0.946

7.17.27.37.47.57.67.77.87.98.0 ppm

7.259

7.332

7.351

7.371

7.388

7.393

7.396

7.404

7.413

7.491

7.509

7.510

7.566

7.570

7.573

7.576

7.580

7.582

7.590

7.787

7.787

7.806

7.807

4.336

1.072

2.119

1.000

!

H

O

PhMe



S29

13C NMR spectrum of 1n (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

20.48

76.68

77.00

77.32

83.61

100.81

122.55

124.65

126.61

128.06

128.52

128.98

131.53

134.84

135.99

141.54

192.25

!

H

O

PhMe



S30

1H NMR spectrum of 1r (400 MHz, CDCl3)

11 10 9 8 7 6 5 4 3 2 1 ppm

7.260

7.402

7.405

7.411

7.414

7.422

7.425

7.436

7.440

7.452

7.552

7.555

7.574

7.577

7.590

7.593

7.603

7.628

7.635

7.639

7.647

7.652

7.883

7.903

10.126

4.19

4.36

1.07

1.00

10.1210.14 ppm

10.1

26

1.00

0

7.37.47.57.67.77.87.9 ppm

7.26

0

7.40

27.

405

7.41

17.

414

7.42

27.

425

7.43

67.

440

7.45

2

7.55

27.

555

7.57

47.

577

7.59

07.

593

7.60

37.

628

7.63

57.

639

7.64

77.

652

7.88

37.

903

4.19

3

4.35

8

1.07

3

!

H

O

Ph

O



S31

13C NMR spectrum of 1r (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm76.68

77.00

77.32

100.07

112.83

115.87

121.78

122.55

124.52

127.48

128.61

129.59

130.01

131.93

152.48

155.37

178.01

!

H

O

Ph

O



S32

1H NMR spectrum of 3aa (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

5.157

6.815

6.824

6.833

6.838

7.052

7.070

7.143

7.148

7.153

7.159

7.169

7.239

7.327

7.345

7.364

7.398

7.416

7.432

7.435

7.559

7.562

7.580

7.598

7.600

7.742

7.745

7.763

7.781

7.784

7.988

8.008

8.542

8.544

2.03

2.04

2.03

3.09

2.08

1.10

1.09

1.05

1.02

1.00

5.05.56.06.57.07.58.08.5 ppm

5.15

7

6.81

56.

824

6.83

36.

838

7.05

27.

070

7.14

37.

148

7.15

37.

159

7.16

97.

239

7.32

77.

345

7.36

47.

398

7.41

67.

432

7.43

57.

559

7.56

27.

580

7.59

87.

600

7.74

27.

745

7.76

37.

781

7.78

47.

988

8.00

8

8.54

28.

544

8.56

28.

564

2.03

3

2.04

0

2.03

03.

088

2.08

31.

104

1.08

7

1.04

6

1.02

0

1.00

0

!

N

O

Ph

PhBr



S33

13C NMR spectrum of 3aa (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

49.92

76.68

77.00

77.32

102.76

125.52

126.51

126.72

127.02

127.71

128.20

128.37

128.53

129.16

129.44

133.26

135.54

135.60

137.11

142.20

162.12

!

N

O

Ph

PhBr



S34

1H NMR spectrum of 3aa’ (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm5.146

6.820

6.829

6.838

6.843

7.080

7.097

7.150

7.152

7.155

7.160

7.166

7.176

7.252

7.345

7.362

7.381

7.412

7.415

7.418

7.433

7.449

7.452

7.590

7.592

7.610

7.628

7.630

7.775

7.778

7.796

7.798

7.813

7.817

7.993

1.98

2.03

2.03

3.06

2.29

1.19

1.09

1.16

1.04

1.00

5.05.56.06.57.07.58.08.59.0 ppm

5.14

6

6.82

06.

829

6.83

86.

843

7.08

07.

097

7.15

07.

152

7.15

57.

160

7.16

67.

176

7.25

27.

345

7.36

27.

381

7.41

27.

415

7.41

87.

433

7.44

97.

452

7.59

07.

592

7.61

07.

628

7.63

07.

775

7.77

87.

796

7.79

87.

813

7.81

77.

993

8.01

38.

558

8.56

08.

578

8.58

0

1.98

4

2.02

7

2.03

53.

063

2.29

11.

193

1.09

5

1.16

0

1.03

8

1.00

0

!

N

O

Ph

PhCl



S35

13C NMR spectrum of 3aa’ (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

49.52

76.68

77.00

77.32

111.83

123.85

125.52

126.79

127.08

127.76

128.26

128.46

128.60

129.25

129.59

133.13

133.62

134.71

137.15

140.54

161.98

!

N

O

Ph

PhCl



S36

1H NMR spectrum of 3aa’’ (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

5.198

6.812

6.821

6.830

7.007

7.025

7.150

7.159

7.164

7.250

7.333

7.352

7.370

7.404

7.422

7.440

7.547

7.565

7.585

7.729

7.747

7.749

7.768

7.945

7.966

8.500

8.520

2.08

2.07

2.05

3.08

2.15

1.02

1.11

1.06

1.04

1.00

5.56.06.57.07.58.08.5 ppm

5.19

8

6.81

26.

821

6.83

07.

007

7.02

57.

150

7.15

97.

164

7.25

07.

333

7.35

27.

370

7.40

47.

422

7.44

07.

547

7.56

57.

585

7.72

97.

747

7.74

97.

768

7.94

57.

966

8.50

08.

520

2.07

9

2.06

8

2.04

5

3.07

8

2.15

31.

020

1.10

7

1.06

2

1.03

6

1.00

0

!

N

O

Ph

PhI



S37

13C NMR spectrum of 3aa’’ (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

50.79

76.68

77.00

77.32

79.88

125.22

126.71

127.04

127.77

128.23

128.41

128.60

129.26

129.52

131.71

133.60

137.22

137.43

139.27

145.70

162.53

!

N

O

Ph

PhI



S38

1H NMR spectrum of 3ab (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm3.742

5.097

6.671

6.678

6.684

6.695

6.700

6.707

6.751

6.773

7.078

7.096

7.258

7.370

7.374

7.391

7.410

7.430

7.433

7.437

7.452

7.467

7.470

7.572

7.574

7.590

7.592

7.594

7.610

7.612

7.756

7.759

7.774

7.777

7.779

7.794

7.798

3.10

1.95

2.01

2.02

1.96

2.09

1.04

1.05

1.03

1.01

1.00

6.46.66.87.07.27.47.67.88.08.28.48.68.8 ppm

6.67

16.

678

6.68

46.

695

6.70

06.

707

6.75

16.

773

7.07

87.

096

7.25

87.

370

7.37

47.

391

7.41

07.

430

7.43

37.

437

7.45

27.

467

7.47

07.

572

7.57

47.

590

7.59

27.

594

7.61

07.

612

7.75

67.

759

7.77

47.

777

7.77

97.

794

7.79

87.

995

8.01

5

8.54

28.

545

8.56

38.

565

2.01

42.

019

1.96

2

2.08

61.

040

1.04

8

1.03

4

1.00

6

1.00

0

!

N

O

PhBr

OMe



S39

13C NMR spectrum of 3ab (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

49.42

55.18

76.68

77.00

77.32

102.79

113.57

125.63

126.53

127.71

128.35

128.41

128.55

129.20

129.29

129.60

133.26

135.58

135.71

142.24

158.67

162.22

!

N

O

PhBr

OMe



S40

1H NMR spectrum of 3ac (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

2.270

5.108

6.721

6.741

6.956

6.976

7.082

7.086

7.103

7.260

7.359

7.362

7.379

7.398

7.422

7.425

7.428

7.444

7.462

7.573

7.576

7.594

7.596

7.611

7.614

7.762

7.766

7.780

7.783

7.786

7.801

7.804

8.004

8.023

8.024

3.08

2.02

2.00

2.00

2.10

2.00

1.06

1.00

0.99

0.98

1.00

6.66.87.07.27.47.67.88.08.28.48.68.89.0 ppm

6.72

16.

741

6.95

66.

976

7.08

27.

086

7.10

37.

260

7.35

97.

362

7.37

97.

398

7.42

27.

425

7.42

87.

444

7.46

27.

573

7.57

67.

594

7.59

67.

611

7.61

47.

762

7.76

67.

780

7.78

37.

786

7.80

17.

804

8.00

48.

023

8.02

48.

539

8.54

18.

559

8.56

1

2.00

2

2.00

2

2.10

0

2.00

01.

063

0.99

8

0.99

4

0.97

8

1.00

0

!

N

O

PhBr

Me



S41

13C NMR spectrum of 3ac (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

21.02

49.79

76.68

77.00

77.32

102.71

125.57

126.49

126.75

127.67

128.39

128.53

128.87

129.15

129.49

133.22

134.07

135.54

135.66

136.64

142.27

162.12

!

N

O

PhBr

Me



S42

1H NMR spectrum of 3ad (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

5.127

6.780

6.785

6.794

6.802

6.809

6.815

6.823

6.830

6.835

6.846

6.851

6.857

6.868

6.873

7.061

7.079

7.260

7.369

7.372

7.389

7.409

7.434

7.438

7.441

7.456

7.472

7.475

7.478

7.589

7.591

7.607

7.609

7.627

7.630

7.774

7.778

7.793

7.795

7.798

2.01

4.07

2.00

2.09

1.10

1.05

1.05

1.02

1.00

6.66.87.07.27.47.67.88.08.28.48.6 ppm

6.78

06.

785

6.79

46.

802

6.80

96.

815

6.82

36.

830

6.83

56.

846

6.85

16.

857

6.86

86.

873

7.06

17.

079

7.26

07.

369

7.37

27.

389

7.40

97.

434

7.43

87.

441

7.45

67.

472

7.47

57.

478

7.58

97.

591

7.60

77.

609

7.62

77.

630

7.77

47.

778

7.79

37.

795

7.79

87.

813

7.81

68.

008

8.02

88.

029

8.54

18.

543

8.56

18.

564

4.06

9

1.99

6

2.08

91.

100

1.05

5

1.04

9

1.02

1

1.00

0

!

N

O

PhBr

F



S43

13C NMR spectrum of 3ad (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

49.20

76.68

77.00

77.32

102.93

114.94

115.15

125.45

126.56

127.80

128.45

128.49

128.62

128.70

129.27

129.49

132.87

132.90

133.35

135.51

135.53

141.94

160.65

162.13

163.09

!

N

O

PhBr

F



S44

1H NMR spectrum of 3ae (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

2.852

2.871

2.893

3.985

4.005

4.026

6.855

6.871

7.152

7.168

7.187

7.202

7.208

7.255

7.282

7.290

7.300

7.305

7.547

7.556

7.562

7.572

7.580

7.598

7.617

7.758

7.778

7.797

7.994

8.015

8.527

8.547

2.07

2.02

2.04

3.03

2.07

4.05

1.05

1.02

1.00

6.66.87.07.27.47.67.88.08.28.48.68.8 ppm

6.85

56.

871

7.15

27.

168

7.18

77.

202

7.20

87.

255

7.28

27.

290

7.30

07.

305

7.54

77.

556

7.56

27.

572

7.58

07.

598

7.61

77.

758

7.77

87.

797

7.99

48.

015

8.52

78.

547

2.04

5

3.03

2

2.07

4

4.05

0

1.05

5

1.02

0

1.00

0

!

N

O

PhBr

Ph



S45

13C NMR spectrum of 3ae (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

34.71

49.06

76.68

77.00

77.32

102.44

125.61

126.44

126.48

127.70

128.11

128.43

128.71

128.84

129.32

129.40

133.16

135.43

135.98

138.08

141.97

161.67

!

N

O

PhBr

Ph



S46

1H NMR spectrum of 3af (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

4.521

4.578

4.597

4.615

6.724

6.922

6.930

7.136

7.146

7.156

7.161

7.169

7.173

7.183

7.192

7.196

7.244

7.343

7.361

7.381

7.418

7.421

7.424

7.440

7.455

7.458

7.461

7.548

7.551

7.569

7.586

7.589

7.724

7.728

7.742

7.745

7.748

7.763

7.766

2.90

1.97

4.00

6.08

2.07

0.97

1.04

1.02

1.01

1.00

6.46.66.87.07.27.47.67.88.08.28.48.68.8 ppm

6.72

46.

922

6.93

07.

136

7.14

67.

156

7.16

17.

169

7.17

37.

183

7.19

27.

196

7.24

47.

343

7.36

17.

381

7.41

87.

421

7.42

47.

440

7.45

57.

458

7.46

17.

548

7.55

17.

569

7.58

67.

589

7.72

47.

728

7.74

27.

745

7.74

87.

763

7.76

67.

940

7.94

07.

960

8.49

18.

493

8.51

18.

513

1.97

5

4.00

3

6.08

0

2.07

30.

968

1.04

4

1.01

9

1.01

0

1.00

0

!

N

O

PhBr

Ph

Ph



S47

13C NMR spectrum of 3af (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

48.04

52.05

76.68

77.00

77.32

102.61

125.57

126.55

126.64

127.63

128.21

128.35

128.43

128.52

129.06

129.82

133.15

135.44

135.59

141.20

142.28

162.21

!

N

O

PhBr

Ph

Ph



S48

1H NMR spectrum of 3ag (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

0.753

0.771

0.788

1.041

1.048

1.060

1.079

1.086

1.098

1.101

1.117

1.135

1.537

1.555

1.576

1.595

1.617

2.174

3.773

3.793

3.813

7.262

7.331

7.336

7.343

7.348

7.355

7.511

7.517

7.523

7.527

7.535

7.537

7.539

7.541

7.546

7.549

7.553

7.560

7.564

7.567

7.569

7.585

7.587

7.732

7.735

7.750

7.753

7.756

7.770

7.774

7.970

7.971

7.991

3.10

4.09

2.16

2.09

2.07

4.11

1.06

1.03

1.00

7.07.27.47.67.88.08.28.48.6 ppm

7.26

27.

331

7.33

67.

343

7.34

87.

355

7.51

17.

517

7.52

37.

527

7.53

57.

537

7.53

97.

541

7.54

67.

549

7.55

37.

560

7.56

47.

567

7.56

97.

585

7.58

77.

732

7.73

57.

750

7.75

37.

756

7.77

07.

774

7.97

07.

971

7.99

1

8.48

78.

489

8.50

78.

509

2.07

1

4.11

4

1.06

2

1.02

7

1.00

0

!

N

O

PhBr



S49

13C NMR spectrum of 3ag (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

13.80

21.90

28.28

28.81

47.36

76.68

77.00

77.32

102.26

125.67

126.38

127.55

128.16

128.71

129.25

129.28

132.99

135.43

136.16

142.15

161.64

!

N

O

PhBr



S50

1H NMR spectrum of 3ah (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

0.000

1.425

1.432

1.438

1.447

1.451

1.463

1.478

1.482

1.494

1.497

1.506

1.520

1.620

1.659

1.839

2.131

2.151

2.172

3.843

3.863

3.884

5.210

7.261

7.349

7.353

7.361

7.366

7.372

7.523

7.530

7.534

7.541

7.548

7.557

7.566

7.584

7.586

7.730

7.733

7.751

7.769

7.772

7.970

7.991

8.482

8.484

8.502

8.504

4.17

2.06

2.04

2.05

1.97

0.99

2.11

4.20

1.07

1.01

1.00

7.07.27.47.67.88.08.28.48.68.8 ppm

7.26

17.

349

7.35

37.

361

7.36

67.

372

7.52

37.

530

7.53

47.

541

7.54

87.

557

7.56

67.

584

7.58

67.

730

7.73

37.

751

7.76

97.

772

7.97

07.

991

8.48

28.

484

8.50

28.

504

2.10

5

4.20

3

1.07

4

1.01

1

1.00

0

!

N

O

PhBr



S51

13C NMR spectrum of 3ah (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

22.10

22.75

25.12

27.82

36.94

46.60

76.68

77.00

77.32

102.31

123.48

125.69

126.41

127.59

128.13

128.73

129.32

129.39

133.01

134.12

135.42

136.05

142.09

161.63

!

N

O

PhBr



S52

1H NMR spectrum of 3ai (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

0.743

0.751

0.773

0.780

0.803

0.832

1.010

1.033

1.053

1.074

1.080

1.087

1.385

1.416

1.570

1.589

1.595

1.605

1.615

1.625

1.634

1.643

1.652

1.662

3.773

3.785

7.262

7.313

7.317

7.322

7.325

7.331

7.337

7.500

7.509

7.512

7.518

7.527

7.535

7.540

7.546

7.548

7.566

7.583

7.586

7.730

7.733

7.748

7.751

7.754

7.768

7.772

7.975

7.995

8.484

8.486

8.504

8.506

2.09

3.09

2.07

4.65

1.99

2.01

4.01

1.04

0.99

0.98

7.07.27.47.67.88.08.28.48.68.8 ppm

7.26

27.

313

7.31

77.

322

7.32

57.

331

7.33

77.

500

7.50

97.

512

7.51

87.

527

7.53

57.

540

7.54

67.

548

7.56

67.

583

7.58

67.

730

7.73

37.

748

7.75

17.

754

7.76

87.

772

7.97

57.

995

8.48

48.

486

8.50

48.

506

2.00

8

4.01

4

1.03

5

0.98

7

0.97

6

!

N

O

PhBr



S53

13C NMR spectrum of 3ai (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

25.81

26.11

30.66

37.48

52.57

76.69

77.00

77.21

77.32

102.56

125.63

126.41

127.54

128.29

128.47

129.14

129.85

132.97

135.42

136.04

142.38

162.15

!

N

O

PhBr



S54

1H NMR spectrum of 3aj (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

0.355

0.366

0.370

0.382

0.941

0.946

0.952

0.959

0.961

0.967

0.978

0.987

0.991

0.996

1.008

1.016

3.816

3.833

7.262

7.351

7.355

7.363

7.368

7.374

7.504

7.511

7.515

7.522

7.529

7.536

7.542

7.554

7.572

7.717

7.721

7.738

7.756

7.759

7.964

7.973

7.984

8.487

8.489

8.507

8.509

2.04

2.07

1.09

2.08

2.14

4.22

1.06

1.03

1.00

7.17.27.37.47.57.67.77.87.98.08.18.28.38.48.58.68.78.8 ppm

7.26

27.

351

7.35

57.

363

7.36

87.

374

7.50

47.

511

7.51

57.

522

7.52

97.

536

7.54

27.

554

7.57

27.

717

7.72

17.

738

7.75

67.

759

7.96

47.

973

7.98

4

8.48

78.

489

8.50

78.

509

2.13

8

4.21

9

1.06

2

1.02

7

1.00

0

!

N

O

PhBr



S55

13C NMR spectrum of 3aj (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

4.16

10.68

50.80

76.68

77.00

77.32

102.35

125.71

126.35

127.48

128.23

128.60

129.24

129.67

132.98

135.44

136.17

142.03

162.07

!

N

O

PhBr



S56

1H NMR spectrum of 3ak (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

3.183

3.519

3.535

3.550

4.041

4.057

4.073

7.263

7.335

7.339

7.345

7.347

7.352

7.359

7.503

7.508

7.516

7.519

7.526

7.530

7.534

7.543

7.547

7.554

7.557

7.572

7.574

7.592

7.595

7.745

7.748

7.763

7.765

7.768

7.783

7.786

7.982

8.002

8.482

3.05

2.08

2.07

2.03

2.96

1.17

1.07

1.02

1.00

7.27.47.67.88.08.28.48.6 ppm

7.26

37.

335

7.33

97.

345

7.34

77.

352

7.35

97.

503

7.50

87.

516

7.51

97.

526

7.53

07.

534

7.54

37.

547

7.55

47.

557

7.57

27.

574

7.59

27.

595

7.74

57.

748

7.76

37.

765

7.76

87.

783

7.78

67.

982

8.00

2

8.48

28.

484

8.50

28.

504

2.03

2

2.95

71.

166

1.07

0

1.01

7

1.00

0

!

N

O

PhBr

OMe



S57

13C NMR spectrum of 3ak (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

46.39

58.71

69.36

76.68

77.00

77.32

102.60

125.49

126.50

127.63

128.14

128.68

129.32

129.73

133.19

135.56

136.05

142.40

161.89

!

N

O

PhBr

OMe



S58

1H NMR spectrum of 3al (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

3.318

7.262

7.316

7.319

7.330

7.335

7.339

7.510

7.512

7.519

7.523

7.527

7.531

7.548

7.561

7.568

7.570

7.586

7.588

7.732

7.735

7.752

7.755

7.770

7.773

7.973

7.994

8.489

8.491

8.509

3.14

2.06

4.22

1.06

1.03

1.00

7.47.67.88.08.28.48.6 ppm

7.26

27.

316

7.31

97.

330

7.33

57.

339

7.51

07.

512

7.51

97.

523

7.52

77.

531

7.54

87.

561

7.56

87.

570

7.58

67.

588

7.73

27.

735

7.75

27.

755

7.77

07.

773

7.97

37.

994

8.48

98.

491

8.50

98.

511

2.06

0

4.22

0

1.05

8

1.02

6

1.00

0

!

N

OMe

PhBr



S59

13C NMR spectrum of 3al (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

35.11

76.68

77.00

77.32

101.94

125.34

126.41

127.61

128.13

128.98

129.03

129.30

133.02

135.43

136.36

142.17

162.17

!

N

OMe

PhBr



S60

1H NMR spectrum of 3ba (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm3.851

5.178

6.853

6.859

6.863

6.867

6.877

6.885

6.975

6.996

7.165

7.172

7.176

7.181

7.260

7.570

7.573

7.590

7.608

7.611

7.761

7.764

7.779

7.781

7.784

7.799

7.802

8.005

8.025

8.535

8.537

8.555

8.557

3.07

2.00

4.01

2.03

3.00

1.05

1.05

1.01

1.00

6.87.07.27.47.67.88.08.28.48.68.8 ppm

6.85

36.

859

6.86

36.

867

6.87

76.

885

6.97

56.

996

7.16

57.

172

7.17

67.

181

7.26

0

7.57

07.

573

7.59

07.

608

7.61

17.

761

7.76

47.

779

7.78

17.

784

7.79

97.

802

8.00

58.

025

8.53

58.

537

8.55

58.

557

4.01

3

2.03

3

2.99

8

1.05

1

1.04

7

1.01

1

1.00

0

!

N

O

Ph

BrOMe



S61

13C NMR spectrum of 3ba (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

49.96

55.28

76.68

77.00

77.32

103.46

113.75

125.55

126.57

126.73

127.03

127.67

128.08

128.24

128.55

130.79

133.26

135.62

137.26

142.16

159.99

162.25

!

N

O

Ph

BrOMe



S62

1H NMR spectrum of 3ca (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

2.404

5.155

6.848

6.854

6.862

6.871

6.955

6.975

7.147

7.157

7.164

7.173

7.176

7.248

7.557

7.560

7.577

7.595

7.598

7.747

7.750

7.768

7.771

7.785

7.789

7.995

8.015

8.529

8.531

8.549

8.551

3.11

2.00

2.03

2.05

5.15

1.06

1.05

1.02

1.00

6.87.07.27.47.67.88.08.28.48.68.8 ppm

6.84

86.

854

6.86

26.

871

6.95

56.

975

7.14

77.

157

7.16

47.

173

7.17

67.

248

7.55

77.

560

7.57

77.

595

7.59

87.

747

7.75

07.

768

7.77

17.

785

7.78

97.

995

8.01

5

8.52

98.

531

8.54

98.

551

2.03

1

2.05

2

5.14

6

1.06

4

1.04

8

1.02

2

1.00

0

!

N

O

Ph

BrMe



S63

13C NMR spectrum of 3ca (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

21.42

49.98

76.68

77.00

77.32

102.93

125.54

126.53

126.72

127.00

127.65

128.22

128.54

129.10

129.27

132.81

133.25

135.63

137.22

139.20

142.41

162.18

!

N

O

Ph

BrMe



S64

1H NMR spectrum of 3da (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

5.166

6.814

6.823

6.832

6.837

7.024

7.034

7.044

7.067

7.169

7.178

7.185

7.194

7.259

7.593

7.596

7.614

7.631

7.634

7.774

7.778

7.795

7.798

7.813

7.816

8.000

8.020

8.551

8.553

8.571

8.574

2.00

2.05

4.06

3.03

1.04

1.05

1.03

1.00

6.66.87.07.27.47.67.88.08.28.48.68.8 ppm

6.81

46.

823

6.83

26.

837

7.02

47.

034

7.04

47.

067

7.16

97.

178

7.18

57.

194

7.25

9

7.59

37.

596

7.61

47.

631

7.63

47.

774

7.77

87.

795

7.79

87.

813

7.81

6

8.00

08.

020

8.55

18.

553

8.57

18.

574

2.04

6

4.05

8

3.02

6

1.03

9

1.05

4

1.03

2

1.00

0

!

N

O

Ph

BrF



S65

13C NMR spectrum of 3da (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

49.85

76.68

77.00

77.32

103.33

115.45

115.67

125.58

126.59

126.62

127.18

127.93

128.34

128.61

131.48

131.56

131.60

131.63

133.37

135.42

136.98

141.15

161.64

162.14

164.13

!

N

O

Ph

BrF



S66

1H NMR spectrum of 3ea (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

1.403

1.421

1.439

4.389

4.407

4.425

4.442

5.147

6.797

6.806

6.815

6.820

7.140

7.162

7.166

7.175

7.180

7.261

7.600

7.602

7.620

7.638

7.640

7.779

7.782

7.800

7.818

7.821

7.997

8.017

8.029

8.050

8.554

8.556

8.574

8.576

3.11

2.18

1.97

2.03

5.05

1.14

1.15

3.11

1.00

6.87.07.27.47.67.88.08.28.48.6 ppm

6.79

76.

806

6.81

56.

820

7.14

07.

162

7.16

67.

175

7.18

07.

261

7.60

07.

602

7.62

07.

638

7.64

07.

779

7.78

27.

800

7.81

87.

821

7.99

78.

017

8.02

98.

050

8.55

48.

556

8.57

48.

576

2.02

6

5.04

8

1.13

9

1.14

8

3.10

9

1.00

0

!

N

O

Ph

BrCO2Et



S67

13C NMR spectrum of 3ea (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.28

49.88

61.31

76.68

77.00

77.32

102.63

125.60

126.59

127.24

128.06

128.40

128.65

129.60

129.70

131.15

133.44

135.39

136.78

139.71

141.18

162.06

165.84

!

N

O

Ph

BrCO2Et



S68

1H NMR spectrum of 3fa (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

5.142

6.767

6.773

6.787

7.144

7.148

7.157

7.171

7.175

7.184

7.255

7.595

7.609

7.615

7.626

7.644

7.646

7.781

7.785

7.802

7.820

7.823

7.995

8.015

8.557

8.559

8.578

8.579

2.06

2.01

4.86

3.14

1.24

1.03

1.00

6.57.07.58.08.59.0 ppm

6.76

76.

773

6.78

77.

144

7.14

87.

157

7.17

17.

175

7.18

47.

255

7.59

57.

609

7.61

57.

626

7.64

47.

646

7.78

17.

785

7.80

27.

820

7.82

37.

995

8.01

5

8.55

78.

559

8.57

88.

579

2.00

7

4.85

7

3.14

1

1.24

2

1.03

0

1.00

0

!

N

O

Ph

BrCF3



S69

13C NMR spectrum of 3fa (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

49.86

76.68

77.00

77.32

102.85

119.63

122.34

125.05

125.32

125.36

125.40

125.43

125.65

126.56

126.63

127.31

127.79

128.19

128.44

128.69

130.15

130.82

131.14

131.47

131.80

133.50

135.32

136.77

138.97

140.64

162.06

!

N

O

Ph

BrCF3



S70

1H NMR spectrum of 3ga (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

3.563

4.923

4.960

5.367

5.405

6.462

6.724

6.743

6.845

6.854

6.860

6.869

6.878

6.890

6.949

6.951

6.955

6.957

6.970

6.972

6.976

6.978

7.162

7.172

7.178

7.186

7.188

7.193

7.197

7.259

7.288

7.308

7.328

7.582

7.585

7.601

7.603

7.621

7.623

7.770

7.774

7.789

7.791

3.07

1.00

0.98

1.00

1.00

2.01

1.04

3.00

1.04

1.04

1.04

1.01

1.00

6.46.66.87.07.27.47.67.88.08.28.48.68.8 ppm

6.46

26.

724

6.74

36.

845

6.85

46.

860

6.86

96.

878

6.89

06.

949

6.95

16.

955

6.95

76.

970

6.97

26.

976

6.97

87.

162

7.17

27.

178

7.18

67.

188

7.19

37.

197

7.25

97.

288

7.30

87.

328

7.58

27.

585

7.60

17.

603

7.62

17.

623

7.77

07.

774

7.78

97.

791

7.79

47.

809

7.81

28.

011

8.03

1

8.54

88.

551

8.56

88.

571

0.99

5

1.00

1

2.01

0

1.03

6

3.00

5

1.03

6

1.03

8

1.03

5

1.01

0

1.00

0

!

N

O

Ph

Br

OMe



S71

13C NMR spectrum of 3ga (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

50.02

55.02

76.68

77.00

77.32

102.55

114.33

115.70

121.51

125.51

126.54

126.67

127.00

127.75

128.26

128.55

129.58

133.30

135.55

136.59

137.42

142.04

159.23

162.16

!

N

O

Ph

Br

OMe



S72

1H NMR spectrum of 3ha (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

3.545

4.915

4.953

5.310

5.348

6.829

6.838

6.840

6.847

6.853

6.889

6.898

6.910

6.921

6.931

7.124

7.129

7.134

7.141

7.150

7.259

7.404

7.414

7.417

7.425

7.427

7.435

7.437

7.448

7.562

7.565

7.583

7.600

7.603

7.744

7.748

7.762

7.765

7.768

7.783

3.08

1.01

1.02

2.07

3.06

3.08

1.09

1.06

1.04

1.03

1.00

6.66.87.07.27.47.67.88.08.28.48.68.8 ppm

6.82

96.

838

6.84

06.

847

6.85

36.

889

6.89

86.

910

6.92

16.

931

7.12

47.

129

7.13

47.

141

7.15

07.

259

7.40

47.

414

7.41

77.

425

7.42

77.

435

7.43

77.

448

7.56

27.

565

7.58

37.

600

7.60

37.

744

7.74

87.

762

7.76

57.

768

7.78

37.

786

7.99

08.

010

8.54

98.

551

8.56

98.

571

2.07

1

3.05

7

3.07

7

1.08

7

1.05

7

1.04

2

1.02

6

1.00

0

!

N

O

Br

Ph

OMe



S73

13C NMR spectrum of 3ha (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

49.82

55.21

76.68

77.00

77.32

103.33

110.89

120.35

124.54

125.63

126.44

126.86

127.12

127.50

127.98

128.48

131.08

131.26

133.03

135.75

137.24

139.68

156.47

162.45

!

N

O

Br

Ph

OMe



S74

1H NMR spectrum of 3ia (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

4.471

4.509

5.784

5.823

6.815

6.820

6.834

6.837

6.852

6.856

7.115

7.119

7.123

7.129

7.137

7.141

7.150

7.155

7.168

7.173

7.176

7.192

7.195

7.254

7.280

7.284

7.300

7.304

7.319

7.323

7.601

7.604

7.619

7.621

7.623

7.639

7.642

7.674

7.677

7.694

7.697

7.772

7.776

1.01

1.00

3.03

4.11

1.06

1.05

1.02

1.04

1.02

1.00

6.66.87.07.27.47.67.88.08.28.48.68.8 ppm

6.81

56.

820

6.83

46.

837

6.85

26.

856

7.11

57.

119

7.12

37.

129

7.13

77.

141

7.15

07.

155

7.16

87.

173

7.17

67.

192

7.19

57.

254

7.28

07.

284

7.30

07.

304

7.31

97.

323

7.60

17.

604

7.61

97.

621

7.62

37.

639

7.64

27.

674

7.67

77.

694

7.69

77.

772

7.77

67.

790

7.79

37.

796

7.81

17.

814

8.00

58.

024

8.02

5

8.57

48.

576

8.59

48.

596

3.03

0

4.11

3

1.06

5

1.04

5

1.02

2

1.03

7

1.01

7

1.00

0

!

N

O

Br

Ph

Br



S75

13C NMR spectrum of 3ia (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

49.72

76.68

77.00

77.32

103.40

123.89

125.80

126.64

127.02

127.18

127.22

128.05

128.23

128.64

130.90

132.05

132.72

133.30

135.42

136.35

136.90

140.80

162.22

!

N

O

Br

Ph

Br



S76

1H NMR spectrum of 3ja (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

5.005

5.043

5.310

5.348

6.760

6.777

7.083

7.087

7.104

7.123

7.138

7.149

7.155

7.165

7.169

7.186

7.189

7.253

7.493

7.514

7.531

7.534

7.544

7.547

7.564

7.567

7.581

7.584

7.597

7.599

7.617

7.635

7.637

7.670

7.690

7.706

7.780

7.783

7.800

7.818

1.00

1.00

1.98

4.08

2.12

1.05

1.16

1.16

1.07

2.18

1.06

1.00

6.66.87.07.27.47.67.88.08.28.48.68.89.0 ppm

6.76

06.

777

7.08

37.

087

7.10

47.

123

7.13

87.

149

7.15

57.

165

7.16

97.

186

7.18

97.

253

7.49

37.

514

7.53

17.

534

7.54

47.

547

7.56

47.

567

7.58

17.

584

7.59

77.

599

7.61

77.

635

7.63

77.

670

7.69

07.

706

7.78

07.

783

7.80

07.

818

7.82

17.

838

7.85

97.

878

7.89

88.

022

8.04

3

8.57

78.

595

8.59

7

1.98

1

4.08

3

2.11

91.

051

1.16

51.

161

1.07

42.

178

1.06

2

1.00

0

!

N

O

Ph

Br



S77

13C NMR spectrum of 3ja (400 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

50.11

76.68

77.00

77.32

103.06

125.61

126.45

126.57

126.62

126.82

127.07

127.13

127.76

127.81

128.22

128.36

128.60

129.43

132.59

132.81

133.11

133.34

135.61

137.21

142.19

162.24

!

N

O

Ph

Br



S78

1H NMR spectrum of 3ka (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

0.893

0.910

0.928

1.318

1.335

1.352

1.360

1.368

1.378

1.398

1.406

1.571

1.589

1.613

1.629

1.647

2.876

2.897

2.917

5.501

7.135

7.153

7.229

7.247

7.258

7.265

7.292

7.311

7.328

7.490

7.492

7.510

7.527

7.530

7.716

7.719

7.737

7.739

7.754

7.758

7.965

7.986

8.450

8.452

8.470

8.472

3.07

4.14

2.55

2.04

1.93

2.04

1.46

1.99

1.05

1.04

1.00

1.00

7.07.27.47.67.88.08.28.48.6 ppm

7.13

57.

153

7.22

97.

247

7.25

87.

265

7.29

27.

311

7.32

87.

490

7.49

27.

510

7.52

77.

530

7.71

67.

719

7.73

77.

739

7.75

47.

758

7.96

57.

986

8.45

08.

452

8.47

08.

472

2.03

9

1.46

01.

994

1.05

1

1.04

0

0.99

9

1.00

0

!

N

O

Ph

n-C5H11Br



S79

13C NMR spectrum of 3ka (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

22.10

22.74

25.12

27.82

36.93

46.59

76.68

77.00

77.32

102.30

123.47

125.68

126.40

127.58

128.12

128.73

129.31

129.39

133.01

134.11

135.41

136.03

142.08

161.62

!

N

O

Ph

n-C5H11Br



S80

1H NMR spectrum of 3la (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

0.000

1.010

1.179

1.187

1.195

1.211

1.219

1.228

1.252

1.408

1.577

1.610

1.687

1.713

1.778

1.845

2.039

2.485

2.507

2.516

2.539

2.548

2.570

2.579

3.025

3.047

3.056

3.064

5.566

6.998

7.017

7.183

7.201

7.229

7.247

7.251

7.265

7.302

7.321

7.339

7.491

7.494

7.511

7.529

7.531

7.697

7.701

7.716

7.718

7.721

7.736

7.739

8.047

8.067

8.464

8.466

8.484

8.486

1.92

1.70

2.06

1.24

2.80

1.02

2.05

1.03

0.27

2.09

0.45

2.27

1.62

2.05

0.25

1.05

1.27

1.24

0.22

1.00

7.07.27.47.67.88.08.28.48.68.8 ppm

6.99

87.

017

7.18

37.

201

7.22

97.

247

7.25

17.

265

7.28

27.

302

7.32

17.

339

7.43

57.

454

7.47

37.

491

7.49

47.

511

7.52

97.

531

7.69

77.

701

7.71

67.

718

7.72

17.

736

7.73

9

8.04

78.

067

8.33

38.

353

8.46

48.

466

8.48

48.

486

0.45

3

2.26

8

1.62

2

2.05

3

0.25

1

1.04

6

1.26

5

1.24

4

0.22

2

1.00

0

!

N

O

Ph

Br



S81

13C NMR spectrum of 3la (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

25.39

26.75

27.91

43.08

48.62

76.68

77.00

77.32

101.92

124.57

125.82

126.16

127.16

127.26

128.36

128.75

133.04

136.22

137.56

145.18

162.98

!

N

O

Ph

Br



S82

1H NMR spectrum of 3ma (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

0.963

0.975

0.978

0.990

1.237

1.248

1.252

1.269

1.273

1.286

1.590

1.609

1.624

1.630

1.639

1.645

1.651

1.660

1.666

1.681

5.806

7.129

7.147

7.201

7.212

7.219

7.225

7.237

7.260

7.276

7.279

7.293

7.297

7.300

7.502

7.504

7.522

7.540

7.542

7.712

7.716

7.731

7.733

7.736

7.751

7.754

8.012

8.033

8.445

8.447

8.465

1.96

1.98

1.06

2.02

2.01

3.93

1.06

1.06

1.00

1.00

7.07.27.47.67.88.08.28.48.68.8 ppm

7.12

97.

147

7.20

17.

212

7.21

97.

225

7.23

77.

260

7.27

67.

279

7.29

37.

297

7.30

07.

502

7.50

47.

522

7.54

07.

542

7.71

27.

716

7.73

17.

733

7.73

67.

751

7.75

4

8.01

28.

033

8.44

58.

447

8.46

58.

467

2.00

7

3.93

2

1.06

1

1.06

1

0.99

8

1.00

0

!

N

O

Ph

Br



S83

13C NMR spectrum of 3ma (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

12.07

15.25

47.49

76.68

77.00

77.32

105.53

125.06

126.04

126.25

127.03

127.32

128.33

128.61

133.01

135.77

137.60

141.29

162.49

!

N

O

Ph

Br



S84

1H NMR spectrum of 3na (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

2.957

5.111

6.800

6.808

6.818

7.035

7.053

7.148

7.157

7.162

7.256

7.334

7.352

7.370

7.394

7.411

7.433

7.452

7.472

7.557

7.575

8.531

8.551

3.21

2.01

2.07

2.05

3.11

2.12

1.03

1.22

1.08

1.00

6.66.87.07.27.47.67.88.08.28.48.6 ppm

6.80

06.

808

6.81

8

7.03

57.

053

7.14

87.

157

7.16

27.

256

7.33

47.

352

7.37

07.

394

7.41

17.

433

7.45

27.

472

7.55

77.

575

8.53

18.

551

2.06

9

2.04

8

3.10

7

2.12

31.

032

1.22

0

1.08

3

1.00

0

!

N

O

Ph

Me BrPh



S85

13C NMR spectrum of 3na (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

25.62

50.20

76.69

77.00

77.32

100.11

126.78

127.02

127.30

127.33

127.56

128.19

128.48

128.94

129.51

134.23

135.32

136.75

137.11

137.54

142.69

162.29

!

N

O

Ph

Me BrPh



S86

1H NMR spectrum of 3oa (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

5.134

6.144

6.805

6.814

6.823

6.829

7.043

7.060

7.154

7.160

7.163

7.170

7.180

7.261

7.330

7.347

7.367

7.399

7.402

7.405

7.422

7.436

7.439

7.900

2.06

2.11

2.14

2.05

3.16

1.43

2.24

2.17

1.00

5.56.06.57.07.58.0 ppm

5.13

4

6.14

4

6.80

56.

814

6.82

36.

829

7.04

37.

060

7.15

47.

160

7.16

37.

170

7.18

07.

261

7.33

07.

347

7.36

77.

399

7.40

27.

405

7.42

27.

436

7.43

9

7.90

0

2.05

8

2.10

6

2.14

4

2.04

7

3.15

6

1.43

22.

238

2.17

2

1.00

0

!

N

O

Ph

PhBr

O

O



S87

13C NMR spectrum of 3oa (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

50.04

76.68

77.00

77.32

102.11

102.44

105.11

106.33

121.21

126.70

127.02

128.22

128.38

129.14

129.54

133.19

135.76

137.22

141.03

148.36

152.80

161.29

!

N

O

Ph

PhBr

O

O



S88

1H NMR spectrum of 3pa (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm3.970

5.160

6.822

6.831

6.840

6.845

7.063

7.081

7.154

7.163

7.170

7.253

7.330

7.348

7.352

7.359

7.367

7.375

7.382

7.400

7.418

7.924

7.947

7.961

7.967

2.93

1.96

1.98

2.00

3.17

3.21

1.09

1.97

6.66.87.07.27.47.67.88.08.2 ppm

6.82

26.

831

6.84

06.

845

7.06

37.

081

7.15

47.

163

7.17

07.

253

7.33

07.

348

7.35

27.

359

7.36

77.

375

7.38

27.

400

7.41

8

7.92

47.

947

7.96

17.

967

1.98

1

2.00

0

3.16

9

3.20

7

1.08

6

1.96

6

!

N

O

Ph

PhBr

MeO



S89

13C NMR spectrum of 3pa (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

50.14

55.79

76.68

77.00

77.32

102.74

108.37

123.56

126.74

127.04

128.24

128.37

128.40

129.12

129.62

129.76

135.67

137.20

139.72

159.43

161.87

!

N

O

Ph

PhBr

MeO



S90

1H NMR spectrum of 3qa (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm5.149

6.808

6.819

6.827

6.832

7.056

7.073

7.153

7.162

7.166

7.174

7.180

7.189

7.262

7.348

7.366

7.386

7.420

7.423

7.426

7.441

7.457

7.460

7.482

7.489

7.502

7.504

7.509

7.511

7.524

7.531

8.018

8.031

8.041

8.053

2.04

2.01

1.96

3.00

2.05

1.06

1.06

1.03

1.00

6.66.87.07.27.47.67.88.08.28.4 ppm

6.80

86.

819

6.82

76.

832

7.05

67.

073

7.15

37.

162

7.16

67.

174

7.18

07.

189

7.26

27.

348

7.36

67.

386

7.42

07.

423

7.42

67.

441

7.45

77.

460

7.48

27.

489

7.50

27.

504

7.50

97.

511

7.52

47.

531

8.01

88.

031

8.04

18.

053

8.19

78.

204

8.22

08.

227

2.00

5

1.95

9

3.00

4

2.04

7

1.05

6

1.05

9

1.03

3

1.00

0

!

N

O

Ph

PhBr

F



S91

13C NMR spectrum of 3qa (400 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

50.16

76.68

77.00

77.32

102.09

113.58

113.82

121.72

121.95

126.76

127.05

127.13

127.18

128.29

128.47

129.32

129.40

129.52

132.22

135.39

136.89

141.50

141.52

160.77

161.38

161.42

163.25

!

N

O

Ph

PhBr

F



S92

1H NMR spectrum of 3ra (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

5.282

6.803

6.809

6.815

6.823

6.827

7.036

7.054

7.131

7.135

7.140

7.144

7.153

7.162

7.168

7.171

7.179

7.184

7.260

7.367

7.386

7.405

7.419

7.422

7.440

7.444

7.448

7.451

7.458

7.460

7.466

7.482

7.485

7.488

7.596

7.599

7.614

7.617

7.620

1.99

2.01

1.96

3.02

2.23

1.85

1.04

0.99

1.00

6.46.66.87.07.27.47.67.88.08.28.48.68.8 ppm

6.80

36.

809

6.81

56.

823

6.82

77.

036

7.05

47.

131

7.13

57.

140

7.14

47.

153

7.16

27.

168

7.17

17.

179

7.18

47.

260

7.36

77.

386

7.40

57.

419

7.42

27.

440

7.44

47.

448

7.45

17.

458

7.46

07.

466

7.48

27.

485

7.48

87.

596

7.59

97.

614

7.61

77.

620

7.63

57.

638

7.73

77.

759

8.43

58.

436

8.45

58.

456

2.01

2

1.96

1

3.01

7

2.23

1

1.84

6

1.03

9

0.99

5

1.00

0

!

NO

O

PhBr

Ph



S93

13C NMR spectrum of 3ra (400 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

49.97

76.68

77.00

77.32

95.48

112.83

123.39

123.49

123.62

126.98

127.29

128.29

128.32

128.58

129.31

129.53

129.83

134.35

136.72

142.70

143.32

154.08

156.92

!

NO

O

PhBr

Ph



S94

1H NMR spectrum of 3sa (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

5.172

6.821

6.831

6.840

6.845

7.085

7.088

7.106

7.165

7.175

7.179

7.187

7.192

7.263

7.371

7.374

7.391

7.410

7.439

7.442

7.445

7.461

7.476

7.479

7.482

7.523

7.535

7.543

7.555

8.801

8.805

8.821

8.825

2.08

1.99

2.00

3.10

2.26

1.27

1.21

1.01

1.00

6.66.87.07.27.47.67.88.08.28.48.68.89.09.2 ppm

6.82

16.

831

6.84

06.

845

7.08

57.

088

7.10

67.

165

7.17

57.

179

7.18

77.

192

7.26

37.

371

7.37

47.

391

7.41

07.

439

7.44

27.

445

7.46

17.

476

7.47

97.

482

7.52

37.

535

7.54

37.

555

8.80

18.

805

8.82

18.

825

9.08

49.

088

9.09

59.

100

1.99

3

1.99

6

3.09

7

2.25

8

1.26

51.

207

1.01

2

1.00

0

!

N

N

PhBr

O

Ph



S95

13C NMR spectrum of 3sa (400 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

50.04

76.68

77.00

77.32

104.68

121.38

122.63

126.67

127.25

128.29

128.51

129.05

129.42

135.02

136.57

137.05

146.18

150.24

155.08

162.15

!

N

N

PhBr

O

Ph



S96

1H NMR spectrum of 4sa (400 MHz, CDCl3)

10 9 8 7 6 5 4 3 2 1 ppm

5.244

6.724

6.884

6.889

6.898

6.907

7.166

7.175

7.181

7.189

7.192

7.197

7.201

7.218

7.221

7.239

7.263

7.342

7.344

7.362

7.381

7.409

7.413

7.416

7.420

7.429

7.434

7.440

7.450

7.453

8.726

8.729

8.730

8.746

1.95

1.00

1.93

2.92

1.97

2.08

2.04

0.96

1.01

6.66.87.07.27.47.67.88.08.28.48.68.89.09.2 ppm

6.72

46.

884

6.88

96.

898

6.90

77.

166

7.17

57.

181

7.18

97.

192

7.19

77.

201

7.21

87.

221

7.23

97.

263

7.34

27.

344

7.36

27.

381

7.40

97.

413

7.41

67.

420

7.42

97.

434

7.44

07.

450

7.45

3

8.72

68.

729

8.73

08.

746

8.74

98.

922

8.92

68.

933

8.93

8

1.00

0

1.92

9

2.91

91.

965

2.07

92.

044

0.95

9

1.00

7

!

N

N

PhH

O

Ph



S97

13C NMR spectrum of 4sa (400 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

48.65

76.68

77.00

77.32

109.81

120.85

121.65

126.75

127.09

128.33

128.84

129.20

135.19

136.56

137.08

147.78

152.88

154.84

163.15

!

N

N

PhH

O

Ph


Date post:	16-Aug-2021
Category:	Documents
Upload:	others
View:	2 times
Download:	0 times

Electronic Supplementary Information · 2012. 6. 11. · S2 1. General 1H NMR (400MHz) spectra were...

Documents