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Supporting Information

Palladium-catalyzed Annulation of Internal Alkynes in Aqueous Medium

Wei Jie Ang, a

Chih-Hsuan Tai, b

Lee-Chiang Lo*b and Yulin Lam*

a

a Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543

b

Department of Chemistry, National Taiwan University, No. 1, Sec. 4 Roosevelt Road, Taipei 106,

Taiwan

Electronic Supplementary Material (ESI) for RSC AdvancesThis journal is © The Royal Society of Chemistry 2014

NMR and mass spectrometry characterization data

2,3-diphenyl-1-indenone (3a). Red solid. Mp 151-152 °C (lit.1 mp 152-153 °C).

1H NMR (500 MHz, CDCl3)

7.49 (d, J = 7.0 Hz, 1H), 7.33 – 7.27 (m, 6H), 7.18 – 7.14 (m, 6H), 7.05 (d, J = 7.2 Hz, 1H). 13

C NMR (126

MHz, CDCl3) 196.5, 155.3, 145.3, 133.4, 132.8, 132.4, 130.8, 130.8, 130.0, 129.3, 128.9, 128.8, 128.5,

128.1, 127.7, 123.0, 121.3. HRMS (EI): calcd for C21H14O1 282.1045, found 282.1041.


3-Phenyl-2-(trimethylsilyl)-1-indenone (3b). Orange oil. 1H NMR (500 MHz, CDCl3) 7.51 – 7.45 (m, 4H),

7.36 (dd, J = 7.6, 1.7 Hz, 2H), 7.32 – 7.23 (m, 2H), 6.88 (d, J = 7.1 Hz, 1H), 0.05 (s, 9H). 13

C NMR (126 MHz,

CDCl3) 201.8, 170.7, 147.3, 135.0, 134.8, 133.0, 132.4, 129.1, 129.1, 128.4, 127.7, 122.3, 120.8, -0.2.

HRMS (EI): calcd for C18H18O128

Si1 278.1121, found 278.1124.


2,3-Di-n-propyl-1-indenone (3c). Yellow oil. 1H NMR (500 MHz, CDCl3) 7.35 (d, J = 7.0 Hz, 1H), 7.31 (s,

1H), 7.13 (dd, J = 10.9, 3.9 Hz, 1H), 7.01 (d, J = 7.2 Hz, 1H), 2.53 – 2.48 (m, 2H), 2.25 – 2.21 (m, 2H), 1.63

(dq, J = 14.9, 7.4 Hz, 2H), 1.49 (dt, J = 15.1, 7.4 Hz, 2H), 1.02 (t, J = 7.4 Hz, 3H), 0.92 (t, J = 7.4 Hz, 3H). 13

C NMR (126 MHz, CDCl3) 198.6, 157.7, 145.7, 134.8, 133.2, 131.2, 127.9, 121.7, 119.0, 28.3, 24.9, 22.6,

21.3, 14.4, 14.2. HRMS (EI): calcd for C15H18O1 214.1358, found 214.1366.


2-Phenyl-3-methyl-1-indenone (3d). Orange solid. Mp 69-70 °C (lit.2 mp 69-71 °C).

1H NMR (500 MHz,

CDCl3) 7.49 (d, J = 7.0 Hz, 1H), 7.46 – 7.40 (m, 5H), 7.37 – 7.33 (m, 1H), 7.28 (d, J = 7.1 Hz, 1H), 7.17 (d,

J = 7.2 Hz, 1H), 2.33 (s, 3H). 13

C NMR (126 MHz, CDCl3) 196.4, 154.6, 145.9, 133.6, 133.5, 131.2, 130.4,

129.6, 128.9, 128.3, 127.7, 122.1, 119.4, 12.6. HRMS (EI): calcd for C16H12O1 220.0888, found 220.0885.


2-Methyl-3-phenyl-1-indenone (3d'). Orange solid. Mp 83-84 °C (lit.3 mp 83.5-85 °C).

1H NMR (500 MHz,

CDCl3) 7.56 – 7.42 (m, 6H), 7.29 (dd, J = 10.7, 4.2 Hz, 1H), 7.19 (t, J = 7.2 Hz, 1H), 7.06 (d, J = 7.2 Hz,

1H), 1.93 (s, 3H). 13

C NMR (126 MHz, CDCl3) 198.3, 154.7, 145.7, 133.1, 132.8, 131.2, 131.1, 129.2, 128.7,

128.1, 128.0, 122.5, 120.4, 8.6. HRMS (EI): calcd for C16H12O1 220.0888, found 220.0885.


1-Methyl-2,3-diphenyl-1H-inden-1-ol (5a). Yellow solid. Mp 122-124 °C (lit.4 mp 123-125 °C).

1H NMR (500

MHz, CDCl3) 7.55 (dd, J = 5.5, 2.9 Hz, 1H), 7.45 (dd, J = 7.5, 2.0 Hz, 2H), 7.37 – 7.31 (m, 5H), 7.29 (dt, J

= 7.4, 3.6 Hz, 2H), 7.24 (dd, J = 8.5, 2.8 Hz, 4H), 2.05 (s, 1H), 1.61 (s, 3H). 13

C NMR (126 MHz, CDCl3)

149.5, 147.0, 142.2, 138.7, 134.7, 134.7, 129.4, 129.3, 128.5, 128.4, 128.0, 127.6, 127.3, 126.6, 121.9, 120.8,

83.3, 24.0. HRMS (EI): calcd for C22H18O1 298.1358, found 298.1350.


1-Methyl-3-phenyl-2-(trimethylsilyl)-1H-inden-1-ol (5b). Brown solid. Mp 102-103 °C. 1H NMR (500 MHz,

CDCl3) 7.47 (d, J = 7.2 Hz, 1H), 7.41 (dt, J = 13.6, 6.8 Hz, 3H), 7.31 – 7.27 (m, 2H), 7.21 (ddt, J = 13.5, 7.4,

3.7 Hz, 2H), 6.84 (d, J = 7.1 Hz, 1H), 1.80 (s, 1H), 1.73 (s, 3H), 0.06 (s, 9H). 13


153.0, 152.0, 150.9, 143.6, 136.8, 128.8, 128.3, 128.2, 127.7, 126.7, 121.3, 120.6, 87.0, 25.2, 0.8. HRMS (EI):

calcd for C19H22O128

Si1 294.1440, found 294.1443.


1-Methyl-2,3-di-n-propyl-1H-inden-1-ol (5c). White solid. Mp 79-81 °C (lit.5 mp 74-80 °C).

1H NMR (500

MHz, CDCl3) 7.38 (d, J = 7.2 Hz, 1H), 7.23 (dd, J = 11.1, 3.8 Hz, 1H), 7.14 (t, J = 7.4 Hz, 2H), 2.44 – 2.40

(m, 2H), 2.39 – 2.32 (m, 1H), 2.28 (ddd, J = 13.8, 10.5, 5.7 Hz, 1H), 1.70 – 1.53 (m, 4H), 1.51 (s, 3H), 1.49 (s,

1H), 1.00 (dt, J = 14.9, 7.4 Hz, 6H). 13

C NMR (126 MHz, CDCl3) 149.5, 147.9, 143.0, 136.6, 128.1, 125.2,

121.2, 118.8, 82.6, 27.4, 27.2, 23.6, 23.0, 21.7, 14.8, 14.4. HRMS (EI): calcd for C16H22O1 230.1671, found

230.1677.


1,3-Dimethyl-2-phenyl-1H-inden-1-ol (5d). Brown solid. Mp 106-107 °C (lit.6 mp 106-108 °C).

1H NMR (500

MHz, CDCl3) 7.55 (d, J = 7.7 Hz, 2H), 7.48 – 7.41 (m, 3H), 7.34 (dd, J = 12.9, 7.0 Hz, 2H), 7.28 – 7.24 (m,

2H), 2.11 (s, 3H), 1.87 (s, 1H), 1.50 (s, 3H). 13

C NMR (126 MHz, CDCl3) 149.2, 146.4, 143.3, 135.2, 134.3,

129.1, 128.5, 128.2, 127.3, 126.4, 121.3, 119.3, 83.1, 23.6, 11.5. HRMS (EI): calcd for C17H16O1 236.1201,

found 236.1199.


1,2-Dimethyl-3-phenyl-1H-inden-1-ol (5d’). White solid. Mp 109-110 °C (lit.7 mp 107-109 °C).

1H NMR (500

MHz, CDCl3) 7.51 – 7.44 (m, 3H), 7.38 (dd, J = 15.0, 7.6 Hz, 3H), 7.22 (ddd, J = 15.7, 13.9, 7.4 Hz, 2H),

7.13 (d, J = 7.0 Hz, 1H), 1.99 (s, 3H), 1.65 (s, 1H), 1.58 (s, 3H). 13

C NMR (126 MHz, CDCl3) 149.1, 146.1,

142.7, 136.3, 134.5, 128.9, 128.4, 128.3, 127.4, 125.5, 121.8, 119.8, 82.0, 23.2, 9.8. HRMS (EI): calcd for

C17H16O1 236.1201, found 236.1199.


2-Amino-3,4-diphenylnaphthalene (7a). Brown solid. Mp 157-159 °C (lit.8 mp 158-160 °C).

1H NMR (500

MHz, CDCl3) 7.57 (d, J = 8.1 Hz, 1H), 7.28 (d, J = 7.7 Hz, 2H), 7.20 – 7.01 (m, 12H, include CDCl3), 3.66

(s, 2H). 13

C NMR (125 MHz, CDCl3) 142.3, 139.7, 139.1, 137.6, 134.4, 130.9, 130.6, 129.9, 128.3, 127.4,

127.3, 126.9, 126.9, 126.4, 125.6, 122.4, 108.3. HRMS (EI): calcd for C22H17N1 295.1361, found 295.1360.


2-Amino-4-phenyl-3-(trimethylsilyl)naphthalene (7b). Red oil. 1H NMR (500 MHz, CDCl3) 7.57 (d, J = 8.4

Hz, 2H), 7.42 (d, J = 2.6 Hz, 2H), 7.34 – 7.27 (m, 5H), 7.01 (s, 1H), 4.07 (s, 2H), 0.03 (s, 9H). 13

C NMR (125

MHz, CDCl3) 142.0, 135.0, 131.3, 131.0, 129.2, 128.3, 127.9, 127.7, 127.3, 127.0, 126.5, 125.2, 122.2,

109.3, 1.6. HRMS (EI): calcd for C19H21N128

Si1 291.1443, found 291.1435.


2-Amino-3,4-di-n-propylnaphthalene (7c). Yellow oil. 1H NMR (500 MHz, CDCl3) 7.88 (d, J = 8.5 Hz, 1H),

7.56 (d, J = 8.2 Hz, 1H), 7.30 (dd, J = 10.9, 4.0 Hz, 1H), 7.25 – 7.20 (m, 1H), 6.93 (s, 1H), 3.82 (s, 2H), 3.04

– 2.99 (m, 2H), 2.73 – 2.67 (m, 2H), 1.65 (dddd, J = 16.2, 12.9, 9.3, 6.5 Hz, 4H), 1.14 – 1.08 (m, 6H). 13

C

NMR (125 MHz, CDCl3) 142.9, 137.1, 133.7, 131.3, 127.6, 126.3, 125.0, 124.1, 122.3, 108.4, 31.0, 30.2,

24.4, 22.7, 14.8, 14.7. HRMS (EI): calcd for C16H21N1 227.1674, found 227.1678.


2-Amino-4-methyl-3-phenylnaphthalene (7d). Red oil. 1H NMR (500 MHz, CDCl3) 7.92 (d, J = 8.4 Hz, 1H),

7.63 (d, J = 8.2 Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H), 7.45 – 7.37 (m, 2H), 7.32 – 7.28 (m, 3H), 6.99 (s, 1H), 3.61

(s, 2H), 2.36 (s, 3H). 13

C NMR (125 MHz, CDCl3) 142.5, 138.5, 134.3, 132.8, 130.3, 130.0, 129.1, 127.5,



2-Amino-3-t-butyl-4-methylnaphthalene (7e). Orange oil. 1H NMR (500 MHz, CDCl3) 7.93 (d, J = 8.6 Hz,

1H), 7.50 (d, J = 8.2 Hz, 1H), 7.30 (t, J = 7.4 Hz, 1H), 7.22 (t, J = 7.7 Hz, 1H), 6.87 (s, 1H), 3.95 (s, 2H), 2.82

(s, 3H), 1.68 (s, 9H). 13

C NMR (125 MHz, CDCl3) 144.3, 135.5, 133.5, 132.7, 129.5, 125.3, 124.1, 122.4,

110.8, 37.7, 33.1, 20.2. HRMS (EI): calcd for C15H19N1 213.1517, found 213.1510.


2,3-Diphenylindole (9a). Yellow solid. Mp 121-122 °C (lit.9 mp 124-125 °C).

1H NMR (500 MHz, CDCl3)

8.25 (s, 1H), 7.70 (d, J = 7.9 Hz, 1H), 7.45 (dd, J = 11.8, 4.9 Hz, 5H), 7.39 (t, J = 7.6 Hz, 2H), 7.36 – 7.27 (m,

5H), 7.17 (t, J = 7.5 Hz, 1H). 13

C NMR (126 MHz, CDCl3) 135.9, 135.1, 134.1, 132.7, 130.2, 128.8, 128.7,

128.5, 128.2, 127.7, 126.2, 122.7, 120.4, 119.7, 115.1, 110.9. HRMS (EI): calcd for C20H15N1 269.1204, found

269.1199.


3-Phenyl-2-(trimethylsilyl)indole (9b). Yellow oil. 1H NMR (500 MHz, CDCl3) 8.17 (s, 1H), 7.59 (d, J = 8.0

Hz, 1H), 7.50 (d, J = 7.0 Hz, 2H), 7.45 (t, J = 7.6 Hz, 3H), 7.37 (t, J = 7.3 Hz, 1H), 7.25 (t, J = 7.6 Hz, 1H),

7.13 (t, J = 7.5 Hz, 1H), 0.25 (s, 9H). 13

C NMR (126 MHz, CDCl3) 137.9, 136.5, 134.0, 130.3, 128.6, 128.0,

127.8, 126.5, 122.7, 119.9, 119.5, 110.7, -0.4. HRMS (EI): calcd for C17H19N128

Si1 265.1287, found 265.1288.


2,3-Di-n-propylindole (9c). Pale yellow oil. 1H NMR (300 MHz, CDCl3) 7.71 (s, 1H), 7.61 – 7.55 (m, 1H),

7.32 – 7.27 (m, 1H), 7.19 – 7.08 (m, 2H), 2.79 – 2.67 (m, 4H), 1.80 – 1.63 (m, 4H), 1.02 (td, J = 7.4, 5.3 Hz,

6H). 13

C NMR (75 MHz, CDCl3) 135.2, 135.1, 128.8, 120.7, 118.8, 118.3, 112.1, 110.2, 28.1, 26.2, 24.1,

23.1, 14.2, 14.0. HRMS (EI): calcd for C14H19N1 201.1517, found 201.1521.


3-Methyl-2-phenyl-1H-indole (9d). Yellow solid. Mp 89-91 °C (lit.10

mp 88-92 °C). 1H NMR (500 MHz,

CDCl3) 7.94 (s, 1H), 7.71 (d, J = 7.9 Hz, 1H), 7.55 (dd, J = 8.2, 1.3 Hz, 2H), 7.49 (t, J = 7.8 Hz, 2H), 7.37 –

7.26 (m, 2H), 7.22 – 7.18 (m, 1H), 7.17 – 7.13 (m, 1H), 2.51 (s, 3H). 13

C NMR (126 MHz, CDCl3) 135.4,

135.2, 131.4, 129.4, 128.5, 127.8, 125.8, 121.5, 119.9, 118.8, 114.4, 110.3, 12.5. HRMS (EI): calcd for

C15H13N1 207.1048, found 207.1042.


2-tert-Butyl-3-methylindole (9e). Pale yellow oil. 1H NMR (500 MHz, CDCl3) 7.86 (s, 1H), 7.52 (d, J = 7.5

Hz, 1H), 7.30 (d, J = 7.3 Hz, 1H), 7.11 (ddt, J = 8.1, 7.1, 3.5 Hz, 2H), 2.42 (s, 3H), 1.48 (s, 9H). 13

C NMR

(126 MHz, CDCl3) 141.6, 133.7, 130.4, 120.9, 118.9, 117.7, 110.1, 105.2, 32.7, 29.9, 10.2. HRMS (EI):

calcd for C13H17N1 187.1361, found 187.1363.


1-Acetyl-3-phenyl-2-(trimethylsilyl)indole (9f). Yellow oil. 1H NMR (500 MHz, CDCl3) 7.70 (d, J = 8.3 Hz,

1H), 7.43 (t, J = 8.1 Hz, 3H), 7.36 (dd, J = 14.6, 7.3 Hz, 4H), 7.22 (dd, J = 13.4, 5.9 Hz, 1H), 2.87 (s, 3H),

0.05 (s, 9H). 13

C NMR (126 MHz, CDCl3) 169.6, 138.5, 136.5, 136.3, 135.4, 133.2, 130.6, 128.1, 127.7,

125.0, 122.8, 120.7, 113.5, 26.6, 1.7. HRMS (EI): calcd for C19H21O1N128

Si1 307.1392, found 307.1390.


1-Acetyl-2,3-di-n-propylindole (9g). Yellow oil. 1H NMR (500 MHz, CDCl3) 7.76 (dd, J = 5.7, 3.3 Hz, 1H),

7.57 – 7.46 (m, 1H), 7.24 (dd, J = 6.5, 2.9 Hz, 2H), 3.06 – 2.93 (m, 2H), 2.77 (s, 3H), 2.71 – 2.60 (m, 2H),

1.70 – 1.54 (m, 4H), 0.99 (td, J = 7.3, 5.0 Hz, 6H). 13

C NMR (126 MHz, CDCl3) 170.1, 138.2, 135.7, 130.9,

123.4, 122.6, 120.1, 118.8, 114.5, 29.0, 27.7, 26.0, 23.6, 23.4, 14.3, 14.1. HRMS (EI): calcd for C16H21N1O1

243.1623, found 243.1614.


1-Acetyl-3-methyl-2-phenylindole (9h). Pale yellow solid. Mp 81-83 °C (lit.11

mp 81-82 °C). 1H NMR (500

MHz, CDCl3) 8.45 (d, J = 8.2 Hz, 1H), 7.54 (d, J = 7.7 Hz, 1H), 7.52 – 7.48 (m, 2H), 7.46 (d, J = 7.4 Hz,

1H), 7.41 (dd, J = 8.3, 1.2 Hz, 3H), 7.35 (d, J = 7.4 Hz, 1H), 2.16 (s, 3H), 1.98 (s, 3H). 13

C NMR (126 MHz,

CDCl3) 171.0, 136.8, 134.9, 133.6, 130.2, 128.7, 128.4, 125.3, 123.4, 118.6, 118.1, 116.3, 27.6, 9.2. HRMS

(EI): calcd for C17H15N1O1 249.1154, found 249.1145.


2,3-Diphenyl-5-azaindole (9i). White solid. Mp 225-227 °C (lit.12

mp 228 °C). 1H NMR (500 MHz, CDCl3)

10.98 (s, 1H), 8.95 (s, 1H), 8.33 (d, J = 5.5 Hz, 1H), 7.53 – 7.49 (m, 2H), 7.47 – 7.43 (m, 2H), 7.42 – 7.35 (m,

3H), 7.34 – 7.29 (m, 4H). 13

C NMR (126 MHz, CDCl3) 142.5, 140.7, 140.1, 135.6, 134.0, 132.0, 130.0,

128.7, 128.6, 128.5, 128.1, 126.7, 125.7, 114.1, 106.6. HRMS (EI): calcd for C19H14N2 270.1157, found

270.1148.


3-Phenyl-2-(trimethylsilyl)-5-azaindole (9j). Brown solid. Mp 193-195 °C. 1H NMR (500 MHz, CDCl3)

9.09 (s, 1H), 8.86 (s, 1H), 8.31 (d, J = 5.8 Hz, 1H), 7.49 – 7.43 (m, 3H), 7.39 – 7.36 (m, 2H), 7.30 (d, J = 5.8

Hz, 1H), 0.24 (s, 9H). 13

C NMR (125 MHz, CDCl3) 143.1, 141.5, 141.2, 135.7, 135.2, 131.5, 130.2, 128.4,

128.2, 127.1, 106.1, -0.5. HRMS (EI): calcd for C16H18N228

Si1 266.1239, found 266.1236.


2,3-Di-n-propyl-5-azaindole (9k). Brown solid. Mp 59-60 °C. 1H NMR (300 MHz, CDCl3) 9.79 (s, 1H),

8.83 (s, 1H), 8.21 (d, J = 5.5 Hz, 1H), 7.20 (d, J = 5.6 Hz, 1H), 2.73 (dt, J = 7.6, 5.9 Hz, 4H), 1.79 – 1.61 (m,

4H), 0.97 (td, J = 7.3, 2.4 Hz, 6H). 13

C NMR (126 MHz, CDCl3) 140.9, 139.5, 139.4, 136.9, 125.8, 111.6,



3-Methyl-2-phenyl-5-azaindole (9l). Brown solid. Mp 167-169 °C. 1H NMR (300 MHz, CDCl3) 10.25 (s,

1H), 8.90 (s, 1H), 8.27 (s, 1H), 7.67 – 7.58 (m, 2H), 7.47 (t, J = 7.5 Hz, 2H), 7.38 (d, J = 7.3 Hz, 1H), 7.29 (d,

J = 5.4 Hz, 1H), 2.51 (s, 3H). 13

C NMR (75 MHz, CDCl3) 141.8, 140.5, 139.8, 135.4, 132.5, 129.2, 128.8,

128.6, 128.0, 127.7, 107.9, 106.2, 9.5. HRMS (EI): calcd for C14H12N2 208.1000, found 208.0991.


2-t-Butyl-3-methyl-5-azaindole (9m). Red solid. Mp 155-157 °C. 1H NMR (300 MHz, CDCl3) 9.20 (s, 1H),

8.81 (s, 1H), 8.22 (d, J = 5.5 Hz, 1H), 7.17 (d, J = 5.6 Hz, 1H), 2.45 (s, 3H), 1.48 (s, 9H). 13

C NMR (75 MHz,

CDCl3) 143.0, 140.8, 139.8, 137.9, 127.3, 105.7, 104.9, 33.0, 30.0, 10.0. HRMS (EI): calcd for C12H16N2

188.1313, found 188.1310.


3,4-Diphenylisoquinoline (11a). White solid. Mp 153-155 °C (lit.13

mp 154-155 °C). 1H NMR (500 MHz,

CDCl3) 9.27 (s, 1H), 7.93 (dd, J = 6.1, 3.2 Hz, 1H), 7.57 (dd, J = 6.6, 2.8 Hz, 1H), 7.52 – 7.45 (m, 2H), 7.31

– 7.20 (m, 5H), 7.14 (dd, J = 7.6, 1.7 Hz, 2H), 7.12 – 7.05 (m, 3H). 13

C NMR (125 MHz, CDCl3) 151.7,

150.6, 140.7, 137.2, 135.9, 131.1, 130.5, 130.4, 130.2, 128.2, 127.6, 127.5, 127.3, 127.3, 127.0, 126.8, 125.5.

HRMS (EI): calcd for C21H15N1 281.1204, found 281.1200.


3-Phenylisoquinoline (11b). Beige solid. Mp 101-102 °C (lit.14

mp 102-103 °C). 1H NMR (500 MHz, CDCl3)

9.35 (s, 1H), 8.18 – 8.10 (m, 2H), 8.08 (s, 1H), 8.00 (d, J = 8.2 Hz, 1H), 7.88 (d, J = 8.2 Hz, 1H), 7.77 –

7.67 (m, 1H), 7.59 (t, J = 7.5 Hz, 1H), 7.52 (t, J = 7.7 Hz, 2H), 7.42 (t, J = 7.4 Hz, 1H). 13

C NMR (125 MHz,

CDCl3) 152.4, 151.3, 139.6, 136.7, 130.5, 128.8, 128.5, 127.8, 127.6, 127.1, 127.0, 126.9, 116.5. HRMS

(EI): calcd for C15H11N1 205.0891, found 205.0886.


4-Methyl-3-phenylisoquinoline (11c). White solid. Mp 102-103 °C (lit.13

mp 101-102 °C). 1H NMR (500 MHz,

CDCl3) 9.21 (s, 1H), 8.06 (d, J = 8.5 Hz, 1H), 7.99 (d, J = 8.1 Hz, 1H), 7.80 – 7.72 (m, 1H), 7.65 – 7.56 (m,

3H), 7.49 (t, J = 7.6 Hz, 2H), 7.41 (t, J = 7.4 Hz, 1H), 2.66 (s, 3H). 13

C NMR (125 MHz, CDCl3) 151.8,

150.1, 141.2, 136.1, 130.3, 129.8, 128.0, 128.0, 127.5, 127.2, 126.6, 124.0, 123.5, 15.5. HRMS (EI): calcd for

C16H13N1 219.1048, found 219.1043.


6,7-Dimethoxy-3,4-di-n-propylisoquinoline (11d). Yellow solid. Mp 88-90 °C (lit.15

mp 85.5-89.5 °C). 1H

NMR (500 MHz, CDCl3) 8.84 (s, 1H), 7.11 (s, 2H), 4.00 (s, 3H), 3.97 (s, 3H), 2.94 – 2.84 (m, 4H), 1.80 –

1.71 (m, 2H), 1.65 (m, 2H), 1.06 (t, J = 7.4 Hz, 3H), 1.01 (t, J = 7.3 Hz, 3H). 13


152.4, 151.6, 148.9, 147.4, 131.7, 126.8, 123.1, 105.6, 101.4, 55.8 (2), 37.2, 29.9, 23.7, 23.5, 14.6, 14.3.

HRMS (EI): calcd for C17H23N1O2 273.1729, found 273.1727.


6,7-Dimethoxy-4-methyl-3-phenylisoquinoline (11e). White solid. Mp 154-155 °C (lit.15

mp 155-156 °C). 1H

NMR (500 MHz, CDCl3) 8.97 (s, 1H), 7.55 (d, J = 7.1 Hz, 2H), 7.44 (t, J = 7.6 Hz, 2H), 7.36 (t, J = 7.4 Hz,

1H), 7.20 (s, 1H), 7.17 (s, 1H), 4.03 (s, 3H), 4.01 (s, 3H), 2.56 (s, 3H). 13

C NMR (125 MHz, CDCl3) 152.8,

150.8, 149.7, 147.5, 141.5, 132.6, 129.7, 127.9, 127.2, 123.3, 122.6, 105.7, 101.9, 55.9, 15.6. HRMS (EI):

calcd for C18H17N1O2 279.1259, found 279.1252.


6,7-Dimethoxy-3-methyl-4-phenylisoquinoline (11e’). Yellow oil. 1H NMR (500 MHz, CDCl3) 9.01 (s, 1H),

7.58 – 7.51 (m, 2H), 7.49 – 7.45 (m, 1H), 7.32 – 7.28 (m, 2H), 7.23 (s, 1H), 6.65 (s, 1H), 4.03 (s, 3H), 3.75 (s,

3H), 2.46 (s, 3H). HRMS (EI): calcd for C18H17N1O2 279.1259, found 279.1252.


3,4-diphenylisocoumarin (13a). White solid. Mp 168-169 °C (lit.16

mp 169-171 °C). 1H NMR (500 MHz,

CDCl3) 8.32 (dd, J = 7.9, 1.3 Hz, 1H), 7.57 – 7.52 (m, 1H), 7.46 – 7.41 (m, 1H), 7.35 – 7.30 (m, 3H), 7.27 –

7.23 (m, 2H), 7.19 – 7.16 (m, 2H), 7.11 (tdd, J = 10.4, 5.2, 3.6 Hz, 4H). 13

C NMR (126 MHz, CDCl3) 162.2,

150.9, 138.8, 134.6, 134.3, 132.9, 131.2, 129.5, 129.2, 129.0, 128.9, 128.1, 128.1, 127.8, 125.31, 120.4, 116.9.

HRMS (EI): calcd for C21H14O2 298.0994, found 298.0996.


4-phenyl-3-(trimethylsilyl)isocoumarin (13b). White solid. Mp 160-161 °C (lit.15

mp 159-160 °C). 1H NMR

(300 MHz, CDCl3) 8.36 (ddd, J = 7.7, 1.5, 0.5 Hz, 1H), 7.63 – 7.49 (m, 2H), 7.47 (dd, J = 4.1, 2.4 Hz, 3H),

7.28 (dd, J = 6.5, 3.1 Hz, 2H), 7.00 – 6.90 (m, 1H), -0.00 (s, 9H). 13

C NMR (126 MHz, CDCl3) 163.4, 160.7,

137.6, 134.5, 134.2, 131.3, 129.2, 128.9, 128.5, 128.5, 128.4, 124.9, 121.2, -1.4. HRMS (EI): calcd for

C18H18O228

Si1 294.1076, found 294.1075.


3,4-di-n-propylisocoumarin (13c). Yellow oil. 1H NMR (500 MHz, CDCl3) 8.32 (d, J = 7.9 Hz, 1H), 7.72 (t,

J = 7.6 Hz, 1H), 7.52 (d, J = 8.1 Hz, 1H), 7.46 (t, J = 7.6 Hz, 1H), 2.62 – 2.54 (m, 4H), 1.80 – 1.69 (m, 2H),

1.61 (dt, J = 15.5, 7.6 Hz, 2H), 1.02 (dt, J = 19.1, 7.4 Hz, 6H). 13

C NMR (126 MHz, CDCl3) 162.9, 154.2,

138.0, 134.5, 129.9, 127.0, 122.6, 120.9, 112.2, 32.7, 28.2, 22.9, 21.2, 14.1, 13.8. HRMS (EI): calcd for

C15H18O2 230.1307, found 230.1304.


4-methyl-3-phenylisocoumarin (13d). Orange solid. Mp: 114-115 °C (lit.17

mp 116-117.5 °C). 1H NMR (500

MHz, CDCl3) 8.39 (dd, J = 7.9, 1.3 Hz, 1H), 7.86 – 7.77 (m, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.60 (dd, J = 8.0,

1.6 Hz, 2H), 7.56 (t, J = 7.6 Hz, 1H), 7.49 – 7.43 (m, 3H), 2.32 (s, 3H). 13

C NMR (126 MHz, CDCl3) 162.5,

151.2, 138.8, 134.7, 133.3, 129.7, 129.5, 129.3, 128.2, 127.9, 123.3, 120.8, 109.1, 13.6. HRMS (EI): calcd for

C16H12O2 236.0837, found 236.0845.


3-t-Butyl-4-methylisocoumarin (13e). White solid. Mp 94-95 °C (lit.16

mp 94-96 °C). 1H NMR (500 MHz,

CDCl3) 8.33 – 8.27 (m, 1H), 7.77 – 7.69 (m, 1H), 7.57 (d, J = 8.2 Hz, 1H), 7.46 (dd, J = 11.1, 4.0 Hz, 1H),

2.34 (s, 3H), 1.45 (s, 9H). 13

C NMR (126 MHz, CDCl3) 162.6, 159.4, 139.9, 134.42, 129.3, 127.1, 122.5,

120.3, 107.4, 37.2, 29.7, 13.1. HRMS (EI): calcd for C14H16O2 216.1150, found 216.1159.


1,1-Dimethyl-3,4-diphenylisochromene (15a). White solid. Mp 92-93 °C (lit.18

mp 90-91 °C). 1H NMR (500

MHz, CDCl3) 7.37 (t, J = 7.3 Hz, 2H), 7.34 – 7.27 (m, 5H), 7.24 (d, J = 4.0 Hz, 2H), 7.19 – 7.14 (m, 4H),

6.93 (d, J = 7.8 Hz, 1H), 1.83 (s, 6H). 13

C NMR (125 MHz, CDCl3) 148.1, 137.1, 136.3, 136.0, 132.0, 131.7,

128.8, 128.5, 127.7, 127.4, 127.2, 126.9, 126.9, 123.6, 122.2, 115.7, 77.7, 27.1. HRMS (EI): calcd for

C23H20O1 312.1514, found 312.1519.


1,1-Dimethyl-4-phenyl-3-(trimethylsilyl)isochromene (15b). Orange oil. 1H NMR (300 MHz, CDCl3) 7.43 –

7.32 (m, 3H), 7.29 – 7.24 (m, 2H), 7.20 – 7.04 (m, 3H), 6.64 (dd, J = 7.6, 0.6 Hz, 1H), 1.66 (s, 6H), -0.12 (s,

9H). 13

C NMR (75 MHz, CDCl3) 156.2, 137.4, 136.7, 131.7, 130.7, 128.2, 128.1, 127.3, 127.2, 127.0, 122.9,

122.2, 75.7, 27.0, -1.6. HRMS (EI): calcd for C20H24O128

Si1 308.1596, found 308.1587.


1,1-Dimethyl-3-t-butyl-4-methylisochromene (15c). Yellow oil. 1H NMR (500 MHz, CDCl3) 7.22 (t, J = 7.5

Hz, 1H), 7.18 – 7.11 (m, 2H), 7.07 (d, J = 6.5 Hz, 1H), 2.12 (s, 3H), 1.53 (s, 6H), 1.27 (s, 9H). 13

C NMR (125

MHz, CDCl3) 155.8, 136.9, 134.2, 127.0, 125.6, 121.5, 120.9, 104.0, 75.6, 36.3, 29.0, 26.1, 13.7. HRMS

(EI): calcd for C16H22O1 230.1671, found 230.1665.


3,4-Diphenyl-1H-isochromene (15d). Orange solid. Mp 79-81 °C. 1H NMR (500 MHz, CDCl3) 7.36 (ddd, J

= 14.5, 7.7, 3.6 Hz, 3H), 7.28 (dd, J = 6.6, 5.0 Hz, 4H), 7.22 – 7.15 (m, 6H), 6.89 – 6.86 (m, 1H), 5.32 (s, 2H). 13

C NMR (125 MHz, CDCl3) 151.2, 136.8, 135.3, 133.7, 131.6, 129.0, 128.6, 128.1, 128.0, 127.9, 127.5,

127.0, 126.6, 123.6, 123.0, 117.0, 68.7. HRMS (EI): calcd for C21H16O1 284.1201, found 284.1198.


4-Phenyl-3-(trimethylsilyl)-1H-isochromene (15e). Orange oil. 1H NMR (500 MHz, CDCl3) 7.43 – 7.35 (m,

3H), 7.31 – 7.25 (m, 2H), 7.15 (dt, J = 19.3, 7.4 Hz, 2H), 7.07 (d, J = 7.0 Hz, 1H), 6.67 (d, J = 7.5 Hz, 1H),

5.00 (s, 2H), -0.11 (s, 9H). 13

C NMR (125 MHz, CDCl3) 159.5, 136.9, 132.3, 131.7, 129.7, 128.7, 128.1,

127.9, 127.4, 126.9, 123.7, 122.2, 67.7, -1.2. HRMS (EI): calcd for C18H20O128

Si1 280.1283, found 280.1276.


3-t-Butyl-4-methyl-1H-isochromene (15f). Yellow oil. 1H NMR (500 MHz, CDCl3) 7.27 (dd, J = 11.3, 3.8

Hz, 2H, CDCl3 overlap), 7.20 – 7.10 (m, 2H), 7.03 (d, J = 7.3 Hz, 1H), 4.80 (s, 2H), 2.15 (s, 3H), 1.30 (s, 9H). 13

C NMR (125 MHz, CDCl3) 159.9, 135.8, 129.1, 127.8, 125.3, 123.0, 120.4, 101.2, 68.5, 37.0, 29.6, 13.8.

HRMS (EI): calcd for C14H18O1 202.1358, found 202.1359.


2-t-Butyl-3-methylbenzofuran (15g). Yellow oil. 1H NMR (500 MHz, CDCl3) 7.47 – 7.41 (m, 1H), 7.38 (dd,

J = 6.8, 1.7 Hz, 1H), 7.23 – 7.17 (m, 2H), 2.32 (s, 3H), 1.45 (s, 9H). 13

C NMR (125 MHz, CDCl3) 159.8,

152.8, 131.5, 123.0, 121.7, 118.4, 110.4, 107.3, 34.3, 29.5, 9.0. HRMS (EI): calcd for C13H16O1 188.1201,

found 188.1206.


NOE spectra

For compound 5b, irradiation of the methyl protons (1.73 ppm) resulted in a positive NOE for the

trimethylsilyl (TMS) group (0.06 ppm). This verified that the TMS group is on the 2-position.

For compound 9b, irradiation of the NH proton (8.17 ppm) resulted in a positive NOE for the trimethylsilyl

(TMS) group (0.25 ppm). This verified that the TMS group is on the 2-position.

Compound 9b

Compound 5b


Irradiation of the NH proton (9.20 ppm) in compound 9m gave a positive NOE for the t-butyl group (1.48

ppm) but no positive NOE was observed for the methyl group (2.45 ppm). (Top spectrum)

For the same compound 9m, irradiation of the methyl proton (2.45 ppm), did not give a positive NOE for the

NH proton (9.20 ppm), concluding the structure of the compound. (Bottom spectrum)

Compound 9m

Compound 9m


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