Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
Organocatalytic Tandem Three-Component Reaction of Aldehyde, Alkyl Vinylketone, and Amide: One-Pot Syntheses of Highly Functional Alkenes De-Wei Wang, Siang-en Syu, Yi-Ting Hung, Pei-yi Chen, Chia-Jui Lee, Ko-Wei Chen, Yu-Jhang Chen, and Wenwei Lin* Department of Chemistry, National Taiwan Normal University NO.88, Section 4, Tingchow Road, Taipei 11677, Taiwan, ROC Fax: (+886)-2-29324249; e-mail:
[email protected]
Supporting Information
Index I. General Information
S2
II. Typical procedure for a three-component reaction of aromatic aldehyde, methyl vinyl ketone, and phthalimide catalyzed by EtPPh2. (TP 1 for Table 1) S2 III. Typical procedure for a three-component reaction of aromatic aldehyde, methyl vinyl ketone, and phthalimide catalyzed by PPh3. (TP 2 for Table 1) S2 IV. Typical procedure for a One-pot syntheses of 8 and 9. (TP 3 for Table 2)
S2
V. Typical procedure for a One-pot syntheses of 10 and 11. (TP 4 for Table 3 and Scheme 3) S3 VI. Diastereomeric ratios of three-component adducts 4a-n in Table 1:
S3
VII. Spectra data of compounds 4a-n, 8a-j, 9a-b, 10a-j and 11a-c
S4
VIII. Spectra of X-ray (threo-4a, erythro-4h, (E)-8c, (E)-10f, (E)-11c) crystallography S39 IX. Spectra of 1H NMR and 13C NMR
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I. General Information: All reactions were carried out under a nitrogen atmosphere in dried glassware. All starting materials were purchased from commercial sources and used without further purification. THF was continuously refluxed and freshly distilled from sodium benzophenone ketyl under nitrogen. Yields refer to isolated yields of compounds estimated to be > 95 % pure as determined by 1H-NMR. Analytical thin layer chromatography (TLC) was performed using Merck 60 F254 precoated silica gel plate (0.2 mm thickness). Flash chromatography was performed using Merck silica gel 60. The temperature of our RT condition ranges from 27 to 30 oC.
II. Typical procedure for a three-component reaction of aromatic aldehyde, methyl vinyl ketone, and phthalimide catalyzed by EtPPh2. (TP 1 for Table 1): A dry and nitrogen-flushed 10-mL Schlenk flask, equipped with a magnetic stirring bar and a septum, was charged with a solution of aldehyde 1 (2.0 mmol) and phthalimide (3a) in dry THF (2.0 mL). Methyl vinyl ketone (2a) and EtPPh2 (5 mol%) were added, and the reaction mixture was stirred for 1-7 h at room temperature. Thereafter, the solvent was removed by evaporation in vacuo. Purification by flash chromatography furnished the adducts 4.
III. Typical procedure for a three-component reaction of aromatic aldehyde, methyl vinyl ketone, and phthalimide catalyzed by PPh3. (TP 2 for Table 1): A dry and nitrogen-flushed 10-mL Schlenk flask, equipped with a magnetic stirring bar and a septum, was charged with a solution of aldehyde 1 (1.0 mmol), phthalimide (3a) and PPh3 (20 mol%) in dry THF (1.0 mL). Methyl vinyl ketone (2a) were added, and the reaction mixture was stirred for 4-62 h at room temperature. Thereafter, the solvent was removed by evaporation in vacuo. Purification by flash chromatography furnished the adducts 4.
IV. Typical procedure for a one-pot syntheses of 8 and 9. (TP 3 for Table 2): A dry and nitrogen-flushed 10-mL Schlenk flask, equipped with a magnetic stirring bar and a septum, was charged with a solution of aldehyde 1 (2.0 mmol) and 3a or 3b in dry THF (2.0 mL). Alkyl vinyl ketone 2a or 2b and EtPPh2 (5 mol%) were added, and the reaction mixture was stirred for 1-5 h at room temperature. Then the solution of DMAP (0.1 equiv) in THF (2.0 mL), Ac2O (1.2 equiv), Et3N (2.5 equiv) were added, and the reaction mixture was stirred at 50 oC or reflux for 2-6 h. Thereafter, the solvent was removed by evaporation in vacuo. S2
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Purification by flash chromatography furnished the adducts 8 and 9.
V. Typical procedure for a One-pot syntheses of 10 and 11. (TP 4 for Table 3 and Scheme 3): A dry and nitrogen-flushed 10-mL Schlenk flask, equipped with a magnetic stirring bar and a septum, was charged with a solution of aldehyde 1 (1.0 mmol), 3c or 3d and PPh3 (20 mol%) in dry THF (1.0 mL). Alkyl vinyl ketone 2a or 2b were added, and the reaction mixture was stirred for 1-24 h at room temperature. Then the solution of DMAP (0.1 equiv) in THF (1.0 mL), Ac2O (1.2 equiv), Et3N (2.5 equiv) were added, and the reaction mixture was stirred at 50 oC or reflux for 2-6.5 h. Thereafter, the solvent was removed by evaporation in vacuo. Purification by flash chromatography furnished the adducts 10 and 11. VI. Diastereomeric ratios of three-component adducts 4a-n in Table 1: Table 1-1 Diastereomeric ratios of three-component adducts 4a-n in Table 1 Entry
Three-component adduct
d.r. (erythro : threo)
d.r. (erythro : threo)
(catalyzed by EtPPh2) (T1)
(catalyzed by PPh3) (T2)
1
4a
26:74
15:85
2
4b
25:75
18:82
3
4c
67:33
67:33
4
4d
22:78
19:81
5
4e
27:73
29:71
6
4f
34:66
33:67
7
4g
35:65
38:62
8
4h
82:18
85:15
9
4i
46:54
50:50
10
4j
--
48:52
11
4k
20:80
23:77
12
4l
33:67
35:65 S3
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
13
4m
45:55
56:44
14
4n
69:31
73:27
The diastereomeric ratios of 4a-n (determined by crude 1H NMR analysis) in different reaction conditions catalyzed by EtPPh2 or PPh3 changed in the reaction progress. In fact, we also found that the diastereomeric ratios of 4a-n changed even in the prolonged reaction time.
VII. Spectra data of compounds 4a-n, 8a-j, 9a-b, 10a-j and 11a-c: Synthesis of 2-(2-(hydroxy(4-nitrophenyl)methyl)-3-oxobutyl)isoindoline-1,3-dione (4a): OH
O
O
O2 N
N O
Prepared according to TP 1 from 4-nitrobenzaldehyde (1a) (302.2 mg, 2.0 mmol), methyl vinyl ketone (2a) (195.0 μL, 1.2 equiv), phthalimide (3a) (323.7 mg, 1.1 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 1 h], Purification by flash-chromatography (hexanes/ethyl acetate: 6/1 to 4/1), yielded 4a (yellow solid) (694.9 mg, 95%). 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.14 (d, J = 8.8 Hz) & 8.05 (d, J = 8.8 Hz) (2H+2H’), 7.84-7.69 (m, 4H+4H’), 7.54 (d, J = 8.8 Hz) & 7.48 (d, J = 8.8 Hz) (2H+2H’), 5.07 (d, J = 7.3 Hz) & 4.99 (d, J = 5.8 Hz) (1H+1H’), 4.18 (dd, 1H, J = 14.6, 5.5 Hz) & 4.12 (dd, 1H, J = 14.6, 4.0 Hz) & 4.01 (dd, 1H, J = 14.3, 5.8 Hz) & 3.91 (dd, 1H, J = 14.3, 5.8 Hz) (2H+2H’), 3.60-3.53 (m) & 3.45-3.39 (m) (1H+1H’), 2.18 (s) & 2.08 (s) (3H+3H’). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 208.9, 208.3, 168.6, 168.2, 148.5, 148.4, 147.5, 147.1, 134.4, 131.6, 131.5, 127.1, 127.0, 123.7, 123.5, 123.4, 72.5, 70.2, 57.9, 56.5, 36.7, 34.8, 32.0, 30.9. MS (20 eV, EI) m/z (%): 217 (92) [M-151]+, 173 (100), 161 (47), 151 (60). IR (CH2Cl2) ~ (cm−1): 3468 (w), 3077 (w), 2937 (w), 1771 (m), 1712 (s), 1605 (w), 1520 (m), 1399 (m), 1347 (m).
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Synthesis of threo-2-(2-(hydroxy(4-nitrophenyl)methyl)-3-oxobutyl)isoindoline-1,3-dione (threo-4a): OH
O 2N
O
N
O
O
mp.: 158.9-159.4°C. 1 H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.14 (d, 2H, J = 8.4 Hz), 7.84-7.79 (m, 2H), 7.76-7.70 (m, 2H), 7.54 (d, 2H, J = 8.8 Hz), 4.99 (pseudo t, 1H, J = 5.6 Hz), 4.01 (dd, 1H, J = 14.4, 8.4 Hz), 3.91 (dd, 1H, J = 14.0, 5.2 Hz), 3.60-3.52 (m, 2H), 2.08 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 209.0, 168.2, 148.4, 147.5, 134.4, 131.6, 127.1, 123.8, 123.6, 72.5, 56.5, 36.7, 32.1. MS (20 eV, EI) m/z (%): 350 (8) [M-18]+, 307 (10), 217 (100), 174 (82), 160 (28), 151 (23). IR (CH2Cl2) ~ (cm−1): 3468 (w), 3077 (w), 2937 (w), 1771 (m), 1712 (s), 1605 (w), 1520 (m), 1399 (m), 1347 (m). HRMS (ESI) for C19H16N2O6Na, [M+Na]+ (391.0906) found: 391.0907.
CCDC number: 778973
Synthesis of 2-(2-(hydroxy(3-nitrophenyl)methyl)-3-oxobutyl)isoindoline-1,3-dione (4b) :
Prepared according to TP 1 from 3-nitrobenzaldehyde (1b) (302.2 mg, 2.0 mmol), methyl vinyl ketone (2a) (195.0 μL, 1.2 equiv), phthalimide (3a) (323.7 mg, 1.1 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 1 h], Purification by flash-chromatography (hexanes/ethyl acetate: 6/1 to 4/1), yielded 4b (yellow solid) (657.3 mg, 89%).
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1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.23 (s, 1H+1H’), 8.06 (d, J = 8.0 Hz) & 7.99 (d, J = 8.0 Hz) (1H+1H’), 7.84-7.59 (m, 5H+5H’), 7.50 (t, J = 8.0 Hz) & 7.40 (t, J = 8.0 Hz) (1H+1H’), 5.07-4.98 (m, 1H+1H’), 4.23-3.36 (m, 4H+4H’), 2.17 (s) & 2.11 (s) (3H+3H’). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 209.1, 208.2, 168.7, 168.1, 148.3, 143.5, 143.4, 134.4, 134.3, 132.7, 132.4, 131.6, 131.5, 129.6, 129.2, 123.6, 123.5, 122.9, 122.5, 121.3, 121.2, 72.4, 70.1, 58.2, 56.6, 36.7, 35.0, 32.0, 31.0. MS (20 eV, EI) m/z (%): 350 (8) [M-18]+, 217 (88), 174 (100), 160 (64), 151 (62), 105 (15). IR (CH2Cl2) ~ (cm−1): 3466 (w), 3077 (w), 2937 (w), 1771 (m), 1713 (s), 1530 (m), 1398 (m), 1352 (m). HRMS (ESI) for C19H16N2O6Na, [M+Na]+ (391.0906) found: 391.0911.
Synthesis of 2-(2-(hydroxy(2-nitrophenyl)methyl)-3-oxobutyl)isoindoline-1,3-dione (4c):
Prepared according to TP 1 from 2-nitrobenzaldehyde (1c) (302.2 mg, 2.0 mmol), methyl vinyl ketone (2a) (195.0 μL, 1.2 equiv), phthalimide (3a) (323.7 mg, 1.1 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 1.5 h], Purification by flash-chromatography (hexanes/ethyl acetate: 6/1 to 4/1), yielded 4c (yellow solid) (645.1 mg, 88%). 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.01 (d, J = 8.0 Hz) & 7.93 (d, J = 8.0 Hz) (1H+1H’), 7.89-7.52 (m, 6H+6H’), 7.43 (t, J = 8.0 Hz) & 7.33 (t, J = 8.0 Hz) (1H+1H’), 5.74-5.48 (m, 1H+1H’), 4.24-3.91 (m, 3H+3H’), 3.72-3.49 (m, 1H+1H’), 2.30 (s) & 1.97 (s) (3H+3H’). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 209.8, 209.2, 168.5, 168.2, 147.4, 147.1, 137.3, 136.2, 134.3, 134.1, 133.9, 133.3, 131.8, 131.6, 128.8, 128.7, 128.4, 125.0, 123.6, 123.4, 68.1, 67.5, 55.5, 54.9, 36.6, 34.7, 31.8, 30.4. MS (20 eV, EI) m/z (%): 369 (11) [M+1]+, 307 (16), 291 (43), 217 (100), 174 (62), 160 (88), 121 (43). IR (CH2Cl2) ~ (cm−1): 3468 (w), 3070 (w), 2937 (w), 1771 (m), 1713 (s), 1525 (m), 1398 (m), 1348 (m). HRMS (ESI) for C19H16N2O6Na, [M+Na]+ (391.0906) found: 391.0909. S6
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Synthesis of 4-(2-((1,3-dioxoisoindolin-2-yl)methyl)-1-hydroxy-3-oxobutyl)benzonitrile (4d): OH
O
O
NC
N O
Prepared according to TP 1 from 4-cyanobenzaldehyde (1d) (262.3 mg, 2.0 mmol), methyl vinyl ketone (2a) (195.0 μL, 1.2 equiv), phthalimide (3a) (323.7 mg, 1.1 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 1.5 h], Purification by flash-chromatography (hexanes/ethyl acetate: 6/1 to 4/1), yielded 4d (white solid) (626.1 mg, 90%). 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 7.83-7.70 (m, 4H+4H’), 7.57 (d, J = 8.4 Hz) & 7.52-7.46 (m) & 7.41 (d, J = 8.0 Hz) (4H+4H’), 5.01 (d, J = 7.0 Hz) & 4.93 (d, J = 6.2 Hz) (1H+1H’), 4.18-4.06 (m) & 3.95 (dd, 1H, J = 14.2, 8.0 Hz) & 3.89 (dd, 1H, J = 14.2, 5.8 Hz) (2H+2H’), 3.58-3.51 (m) & 3.43-3.36 (m) (1H+1H’), 2.16 (s) & 2.07 (s) (3H+3H’). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 209.0, 208.3, 168.6, 168.1, 146.5, 146.4, 134.4, 132.3, 132.1, 131.6, 131.5, 127.0, 126.9, 123.5, 118.4, 118.3, 111.8, 111.2, 72.7, 70.4, 57.8, 56.4, 36.7, 34.8, 32.0, 30.8. MS (20 eV, EI) m/z (%): 348 (2) [M]+, 217 (100), 188 (18), 174 (93), 160 (32), 131 (39). IR (CH2Cl2) ~ (cm−1): 3468 (m), 3062 (w), 2944 (w), 2228 (m), 1771 (m), 1712 (s), 1609 (w), 1399 (m), 1365 (w). HRMS (ESI) for C20H16N2O4Na, [M+Na]+ (371.1008) found: 371.1011.
Synthesis of 2-(2-(hydroxy(4-(trifluoromethyl)phenyl)methyl)-3-oxobutyl)isoindoline-1,3 -dione (4e):
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Prepared according to TP 1 from 4-(trifluoromethyl)benzaldehyde (1e) (274.0 μL, 2.0 mmol), methyl vinyl ketone (2a) (195.0 μL, 1.2 equiv), phthalimide (3a) (323.7 mg, 1.1 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 1.5 h], Purification by flash-chromatography (hexanes/ethyl acetate: 6/1 to 4/1), yielded 4e (white solid) (730.5 mg, 95%). 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 7.73-7.63 (m, 4H+4H’), 7.49-7.35 (m, 4H+4H’), 5.01 (d, J = 7.0 Hz) & 4.91 (d, J = 6.9 Hz) (1H+1H’), 4.15-3.25 (m, 4H+4H’), 2.10 (s, 3H+3H’). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 209.3, 208.3, 168.5, 168.0, 145.2, 134.2, 131.4, 130.0 (quartet, J = 32.0 Hz), 129.5 (quartet, J = 32.0 Hz), 126.7, 126.3, 125.4 (quartet, J = 4.0 Hz), 125.1 (quartet, J = 4.0 Hz), 123.8 (quartet, J = 270.0 Hz), 123.7 (quartet, J = 270.0 Hz), 123.3, 123.2, 73.1, 70.7, 57.5, 56.3, 36.7, 34.9, 31.8, 30.6. MS (20 eV, EI) m/z (%): 391 (1) [M]+, 231 (74), 217 (69), 174 (100), 160 (22), 148 (7). IR (CH2Cl2) ~ (cm−1): 3470 (w), 3063 (w), 2944 (w), 1774 (m), 1713 (s), 1399 (m), 1363 (m), 1326 (s), 1165 (m), 1124 (m), 1068 (m). HRMS (ESI) for C20H16F3NO4Na, [M+Na]+ (414.0929) found: 414.0937.
Synthesis of 2-(2-((4-bromophenyl)(hydroxy)methyl)-3-oxobutyl)isoindoline-1,3-dione (4f):
Prepared according to TP 1 from 4-bromobenzaldehyde (1f) (370.0 mg, 2.0 mmol), methyl vinyl ketone (2a) (325.0 μL, 2.0 equiv), phthalimide (3a) (382.5 mg, 1.3 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 2 h],
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Purification by flash-chromatography (hexanes/ethyl acetate: 6/1 to 4/1), yielded 4f (white solid) (699.3 mg, 87%). 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 7.82-7.67 (m, 4H+4H’), 7.39 (d, J = 8.0 Hz) & 7.33 (d, J = 8.4 Hz) (2H+2H’), 7.22 (d, J = 8.4 Hz) & 7.16 (d, J = 8.0 Hz) (2H+2H’), 4.93-4.80 (m, 1H+1H’), 4.17-3.13 (m, 4H+4H’), 2.10 (m, 3H+3H’). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 209.5, 208.4, 168.7, 168.1, 140.2, 140.1, 134.3, 134.2, 131.7, 131.6, 131.5, 128.0, 127.9, 123.5, 123.4, 122.0, 121.5, 73.1, 70.8, 57.9, 56.4, 36.8, 35.1, 32.0, 31.0. MS (20 eV, EI) m/z (%): 401 (2) [M]+, 243 (63), 241 (59), 217 (83), 174 (100), 160 (36). IR (CH2Cl2) ~ (cm−1): 3468 (w), 3063 (w), 2944 (w), 1771 (m), 1712 (s), 1399 (m), 1363 (m), 1074 (w), 1008 (w). HRMS (ESI) for C19H16BrNO4Na, [M+Na]+ (424.0160) found: 424.0168.
Synthesis of 2-(2-((4-chlorophenyl)(hydroxy)methyl)-3-oxobutyl)isoindoline-1,3-dione (4g):
Prepared according to TP 1 from 4-chlorobenzaldehyde (1g) (281.1 mg, 2.0 mmol), methyl vinyl ketone (2a) (325.0 μL, 2.0 equiv), phthalimide (3a) (382.5 mg, 1.3 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 3 h], Purification by flash-chromatography (hexanes/ethyl acetate: 6/1 to 4/1), yielded 4g (white solid) (593.2 mg, 83%). 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 7.82-7.68 (m, 4H+4H’), 7.31-7.15 (4H+4H’), 4.91 (d, J = 8.0 Hz) & 4.85 (d, J = 6.4 Hz) (1H+1H’), 4.16-3.82 (m, 2H+2H’), 3.59-3.35 (m, 1H+1H’), 2.10 (s) & 2.08 (s) (3H+3H’). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 209.4, 208.4, 168.5, 168.0, 139.7, 139.6, 134.1, 134.0, 133.7, 133.2, 131.5, 131.4, 128.6, 128.4, 127.7, 127.5, 123.3, 123.2, 73.0, 70.9, 57.8, 56.5, 36.7, 35.2, 31.6, 30.8. MS (20 eV, EI) m/z (%): 357 (4) [M]+, 217 (100), 174 (91), 160 (51), 140 (77).
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IR (CH2Cl2) ~ (cm−1): 3468 (w), 3062 (w), 2944 (w), 1772 (m), 1715 (s), 1398 (m), 1362 (m), 1089 (m). HRMS (ESI) for C19H16ClNO4Na, [M+Na]+ (380.0666) found: 380.0660.
Synthesis of erythro-2-(2-((2-chlorophenyl)(hydroxy)methyl)-3-oxobutyl)isoindoline-1,3dione (erythro-4h): Cl
OH
O
O N O
Prepared according to TP 2 from 2-chlorobenzaldehyde (1h) (225.0 μL, 2.0 mmol), methyl vinyl ketone (2a) (325.0 μL, 2.0 equiv), phthalimide (3a) (382.5 mg, 1.3 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 5 h], Purification by flash-chromatography (hexanes/ethyl acetate: 6/1 to 4/1), yielded erythro-4h (white solid) (646.4 mg, 91%). mp.:150.6-151.3°C. 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 7.78-7.72 (m, 2H), 7.70-7.64 (m, 2H), 7.59-7.54 (m, 1H), 7.30-7.25 (m, 1H), 7.21-7.14 (m, 1H), 7.12-7.06 (m, 1H), 5.39 (t, 1H, J = 4.0 Hz), 4.09 (dd, 1H, J = 14.3, 7.0 Hz), 3.97 (dd, 1H, J = 14.3, 5.1 Hz), 3.88-3.82 (m, 1H), 3.42 (pseudo t, J = 3.5 Hz), 2.27 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 209.5, 168.2, 137.8, 134.0, 131.8, 131.6, 129.7, 128.8, 128.0, 127.0, 123.3, 68.9, 53.6, 34.6, 30.3. MS (20 eV, EI) m/z (%): 357 (4) [M]+, 304 (17), 217 (67), 197 (100), 174 (57), 160 (45). IR (CH2Cl2) ~ (cm−1): 3466 (w), 3062 (w), 2934 (w), 1772 (m), 1715 (s), 1398 (m), 1362 (m), 1071 (w), 1010 (w). HRMS (ESI) for C19H16ClNO4Na, [M+Na]+ (380.0666) found: 380.0675.
CCDC number: 778974
Synthesis of 2-(2-(hydroxy(phenyl)methyl)-3-oxobutyl)isoindoline-1,3-dione (4i):
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Prepared according to TP 1 from benzaldehyde (1i) (202 μL, 2.0 mmol), methyl vinyl ketone (2a) (195.0 μL, 1.2 equiv), phthalimide (3a) (323.7 mg, 1.1 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 7 h], Purification by flash-chromatography (hexanes/ethyl acetate: 6/1 to 4/1), yielded 4i (white solid) (349.4 mg, 54%). 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 7.77-7.63 (m, 4H+4H’), 7.35-7.08 (m, 5H+5H’), 4.89 (d, J = 8.0 Hz) & 4.85 (d, J = 7.3 Hz) (1H+1H’), 4.11-3.70 (m, 2H+2H’), 3.61-3.40 (m, 1H+1H’), 2.08 (s) & 1.98 (s) (3H+3H’). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 209.7, 208.5, 168.5, 168.0, 141.1, 141.0, 134.0, 131.7, 131.6, 128.5, 128.3, 127.9, 127.6, 126.2, 126.1, 123.3, 123.2, 73.8, 71.9, 57.9, 56.7, 36.9, 35.5, 31.6, 30.9. MS (20 eV, EI) m/z (%): 323 (4) [M]+, 217 (65), 174 (59), 163 (100), 105 (13). IR (CH2Cl2) ~ (cm−1): 3483 (w), 2922 (w), 1771 (m), 1712 (s), 1395 (m), 1362 (m). HRMS (ESI) for C19H17NO4Na, [M+Na]+ (346.1055) found: 346.1061.
Synthesis of 2-(2-(hydroxy(p-tolyl)methyl)-3-oxobutyl)isoindoline-1,3-dione (4j): OH
O
O N O
Prepared according to TP 1 from benzaldehyde (1j) (118.0 μL, 1.0 mmol), methyl vinyl ketone (2a) (162.0 μL, 2.0 equiv), phthalimide (3a) (220.7 mg, 1.5 equiv), and triphenylphosphine (52.5 mg, 20 mol%) in THF (1.0 mL) [reaction condition: RT for 62 h], Purification by flash-chromatography (hexanes/ethyl acetate: 6/1), yielded 4j (white solid) (210.0 mg, 62%).
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Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 7.73-7.58 (m, 4H+4H’), 7.16 (d, J = 8.0 Hz) & 7.11 (d, J = 8.0 Hz) (2H+2H’), 6.97 (t, 2H+2H’, J = 8.4 Hz), 4.87-4.82 (m, 1H+1H’), 4.10-3.50 (m, 3H+3H’), 3.46-3.20 (m, 1H+1H’), 2.17-1.94 (m, 6H+6H’). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 209.7, 208.5, 168.4, 167.8, 138.0, 137.9, 137.6, 137.1, 133.9, 133.8, 131.5, 131.4, 129.0, 128.9, 126.1, 125.8, 123.2, 123.0, 73.8, 71.7, 57.6, 56.4, 36.7, 35.4, 31.4, 30.7, 20.8, 20.7. MS (20 eV, EI) m/z (%): 337 (8) [M]+, 320 (15), 217 (73), 177 (100), 120 (14). IR (CH2Cl2) ~ (cm−1): 3476 (w), 2930 (w), 1771 (m), 1712 (s), 1399 (m), 1358 (m). HRMS (ESI) for C20H19NO4Na, [M+Na]+ (360.1212) found: 360.1214.
Synthesis of 2-(2-(hydroxy(pyridin-4-yl)methyl)-3-oxobutyl)isoindoline-1,3-dione (4k):
Prepared according to TP 1 from 4-pyridylbenzaldehyde (1k) (188.0 μL, 2.0 mmol), methyl vinyl ketone (2a) (325.0 μL, 2.0 equiv), phthalimide (3a) (382.5 mg, 1.3 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 1 h], Purification by flash-chromatography (hexanes/ethyl acetate: 4/1 to 1/1), yielded 4k (brown solid) (630.0 mg, 97%). 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.47 (d, J = 4.8 Hz) & 8.37 (d, J = 4.8 Hz) (2H+2H’), 7.83-7.67 (m, 4H+4H’), 7.29 (d, J = 5.1 Hz) & 7.22 (d, J = 4.8 Hz) (1H+1H’), 4.96 (d, J = 7.0 Hz) & 4.85 (d, J = 5.5 Hz) (1H+1H’), 4.11 (d, J = 5.1 Hz) & 3.94 (d, J = 7.0 Hz) (2H+2H’), 3.56-3.34 (m, 2H+2H’), 2.15 (s) & 2.05 (s) (3H+3H’). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 209.0, 208.1, 168.6, 168.2, 150.6, 150.5, 149.8, 149.5, 134.3, 131.6, 131.5, 123.5, 121.2, 121.1, 71.8, 69.9, 57.6, 56.3, 36.8, 34.9, 32.0, 30.8. MS (20 eV, EI) m/z (%): 325 (6) [M+1]+, 217 (60), 174 (43), 164 (100), 160 (15), 109 (17). IR (CH2Cl2) ~ (cm−1): 3461 (w), 2944 (w), 1772 (w), 1713 (s), 1604 (w), 1398 (m), 1364 (m). HRMS (ESI) for C18H17N2O4, [M+H]+ (325.1188) found: 325.1192.
Synthesis of 2-(2-(hydroxy(pyridin-3-yl)methyl)-3-oxobutyl)isoindoline-1,3-dione (4l): S12
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
Prepared according to TP 1 from 3-pyridylbenzaldehyde (1l) (188.0 μL, 2.0 mmol), methyl vinyl ketone (2a) (325.0 μL, 2.0 equiv), phthalimide (3a) (382.5 mg, 1.3 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 1 h], Purification by flash-chromatography (hexanes/ethyl acetate: 4/1 to 1/1), yielded 4l (brown solid) (632.9 mg, 98%). 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.58-8.51 (m, 1H+1H’), 8.44-8.36 (m, 1H+1H’), 7.84-7.66 (m, 5H+5H’), 7.29-7.18 (m, 1H+1H’), 4.98-4.92 (m, 1H+1H’), 4.24-3.32 (m, 4H+4H’), 2.15 (s) & 2.10 (s) (3H+3H’). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 209.2, 208.1, 168.7, 168.0, 148.9, 148.4, 147.7, 137.4, 134.7, 134.5, 134.3, 134.2, 131.6, 123.7, 123.6, 123.5, 123.4, 71.3, 69.3, 58.5, 56.8, 36.7, 35.4, 31.7, 31.0. MS (20 eV, EI) m/z (%): 325 (20) [M+1]+, 281 (100), 218 (89), 174 (91), 164 (100), 160 (65), 107 (58). IR (CH Cl ) ~ (cm−1): 3461 (w), 2937 (w), 1772 (m), 1715 (s), 1398 (m), 1361 (m). 2
2
HRMS (ESI) for C18H17N2O4, [M+H]+ (325.1188) found: 325.1190.
Synthesis of 2-(2-(hydroxy(pyridin-2-yl)methyl)-3-oxobutyl)isoindoline-1,3-dione (4m):
Prepared according to TP 1 from 2-pyridylbenzaldehyde (1m) (191.0 μL, 2.0 mmol), methyl vinyl ketone (2a) (325.0 μL, 2.0 equiv), phthalimide (3a) (382.5 mg, 1.3 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 5 h], Purification by flash-chromatography (hexanes/ethyl acetate: 4/1 to 1/1), yielded 4m (brown solid) (605.9 mg, 94%). S13
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.48 (d, J = 4.8 Hz) & 8.35 (d, J = 4.8 Hz) (1H+1H’), 7.85-7.52 (m, 5H+5H’), 7.48 (d, J = 8.0 Hz) & 7.41 (d, J = 7.7 Hz) (1H+1H’), 7.19-6.95 (m, 1H+1H’), 5.10 (d, J = 5.5 Hz) & 4.94 (d, J = 4.0 Hz) (1H+1H’), 4.60 (brs) & 4.35 (brs) (1H+1H’), 4.11-3.70 (m, 1H+1H’), 2.32 (s) & 2.02 (s) (3H+3H’). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 209.6, 208.5, 168.3, 168.2, 159.7, 159.0, 148.5, 148.1, 136.9, 136.6, 134.1, 133.9, 131.8, 131.7, 123.4, 123.2, 122.7, 122.3, 121.4, 121.2, 73.0, 71.5, 55.9, 55.7, 36.8, 34.6, 31.2, 30.0. MS (20 eV, EI) m/z (%): 217 (70) [M-107]+, 174 (100), 160 (45), 79 (49). IR (CH2Cl2) ~ (cm−1): 3464 (w), 3062 (w), 2944 (w), 1772 (m), 1713 (s), 1398 (m),. HRMS (ESI) for C18H17N2O4, [M+H]+ (325.1188) found: 325.1189.
Synthesis of 2-(2-(furan-2-yl(hydroxy)methyl)-3-oxobutyl)isoindoline-1,3-dione (4n):
Prepared according to TP 1 from 2-furaldehyde (1n) (166.0 μL, 2.0 mmol), methyl vinyl ketone (2a) (325.0 μL, 2.0 equiv), phthalimide (3a) (382.5 mg, 1.3 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 5 h], Purification by flash-chromatography (hexanes/ethyl acetate: 6/1 to 4/1), yielded 4n (white solid) (484.6 mg, 77%). 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 7.81-7.65 (m, 4H+4H’), 7.27-7.19 (m, 1H+1H’), 6.35-6.14 (m, 2H+2H’), 4.95 (d, J = 7.7 Hz) & 4.90 (d, J = 6.6 Hz) (1H+1H’), 4.18-3.84 (m, 2H+2H’), 3.69-3.52 (m, 1H+1H’), 2.18 (s, 3H+3H’). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 209.3, 207.6, 168.7, 168.0, 153.6, 153.5, 142.2, 142.0, 134.2, 134.1, 131.6, 123.4, 123.3, 110.4, 110.3, 107.8, 107.1, 67.4, 65.8, 55.3, 54.4, 36.4, 35.1, 31.1, 30.2. MS (20 eV, EI) m/z (%): 313 (5) [M]+, 217 (18), 174 (28), 153 (100). IR (CH2Cl2) ~ (cm−1): 3466 (w), 3121 (w), 2944 (w), 1772 (m), 1714 (s), 1398 (m), 1362 (m), 1010 (w). HRMS (ESI) for C17H15NO5Na, [M+Na]+ (336.0848) found: 336.0850.
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Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
Synthesis of (E)-2-(2-(4-nitrobenzylidene)-3-oxobutyl)isoindoline-1,3-dione ((E)-8a):
O
O O 2N
N O
Prepared according to TP 3 from 4-nitrobenzaldehyde (1a) (302.2 mg, 2.0 mmol), methyl vinyl ketone (2a) (210.9 μL, 1.3 equiv.), phthalimide (3a) (297.2 mg, 1.01 equiv.), and ethyl diphenylphosphine (20.4 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 1 h]; triethylamine (0.70 mL, 2.5 equiv), acetic anhydride (0.23 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (24.4 mg, 0.1 equiv) and THF (2.0 mL) [reaction condition: 50℃ for 3 h]. Purification by recrystallization with CH2Cl2 and hexane yielded (E)-8a (yellow solid) (E:Z= 92:8, 567.5 mg, 81%). (E)-8a (yellow solid) mp.: 203.1-203.8 °C. 1 H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.17 (d, 2H, J = 8.6 Hz), 7.77-7.69 (m, 3H), 7.69-7.63 (m, 2H), 7.59 (d, 2H, J = 8.5 Hz), 4.65 (s, 2H), 2.49 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 198.1, 167.7, 147.5, 141.2, 139.4, 138.2, 134.0, 131.7, 129.4, 123.7, 123.2, 35.1, 26.1. MS (20 eV, EI) m/z (%): 351 (17) [M+1]+, 307 (2), 203 (100), 161 (4), 148 (11). IR (CH2Cl2) ~ (cm−1): 1770 (w), 1705 (s), 1518 (m), 1391 (w), 1349 (m). HRMS (ESI) for C19H14N2O5Na, [M+Na]+ (373.0800) found: 373.0802. Anal. Calcd. for C19H14N2O5: C, 65.14; H, 4.03; N, 8.00. found: C, 65.32; H, 3.96; N, 8.07. Synthesis of (Z)-2-(2-(4-nitrobenzylidene)-3-oxobutyl)isoindoline-1,3-dione ((Z)-8a):
O N
O 2N
O
S15
O
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
The compound (Z)-8a can be carefully purified by flash-chromatography (hexanes/ethyl acetate: 4/1) as yellow solid. 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.18 (d, 2H, J = 8.5 Hz), 7.93-7.85 (m, 2H), 7.80-7.73 (m, 2H), 7.38 (d, 2H, J = 8.4 Hz), 6.86 (s, 1H), 4.62 (s, 2H), 2.11 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 203.5, 167.7, 147.6, 141.6, 141.0, 134.4, 131.9, 130.9, 129.4, 123.8, 123.7, 40.6, 30.5. MS (20 eV, EI) m/z (%): 351 (2) [M+1]+, 203 (100), 148 (9). IR (CH2Cl2) ~ (cm−1): 1770 (w), 1705 (s), 1518 (m), 1391 (w), 1349 (m). HRMS (ESI) for C19H13N2O5, [M-H]+ (349.0824) found: 349.0820.
Synthesis of (E)-2-(2-(3-nitrobenzylidene)-3-oxobutyl)isoindoline-1,3-dione ((E)-8b): O
O N NO2
O
Prepared according to TP 3 from 3-nitrobenzaldehyde (1b) (302.2 mg, 2.0 mmol), methyl vinyl ketone (2a) (210.9 μL, 1.3 equiv.), phthalimide (3a) (297.2 mg, 1.01 equiv.), and ethyl diphenylphosphine (20.4 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 1 h]; triethylamine (0.70 mL, 2.5 equiv), acetic anhydride (0.23 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (24.4 mg, 0.1 equiv) and THF (2.0 mL) [reaction condition: 50℃ for 3 h]. Purification by flash-chromatography (hexanes/dichloromethane: 1/4) yielded 8b (yellow solid) (E:Z= 91:9, 579.5 mg, 83%). yellow solid mp.: 147.8-148.4 °C. 1 H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.27 (s, 1H), 8.08 (d, 1H, J = 8.0 Hz), 7.80 (d, 1H, J = 7.6 Hz), 7.75-7.68 (m, 3H), 6.68-6.62 (m, 2H), 7.53 (t, 1H, J = 8.0 Hz), 4.63 (s, 2H), 2.47 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 198.1, 167.6, 148.1, 139.4, 137.9, 136.2, 134.4, 133.9, 131.6, 129.6, 123.5, 123.2, 123.1, 34.8, 26.0. MS (20 eV, EI) m/z (%): 351 (5) [M+1]+, 332 (13), 287 (51), 260 (8), 203 (100), 156 (13), 128 (12). S16
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
IR (CH2Cl2) ~ (cm−1): 2918 (w), 1774 (w), 1718 (m), 1533 (w), 1396 (w), 1354 (w), 1266 (s). HRMS (MALDI) for C19H15N2O5, [M+H]+ (351.0981) found: 351.0992. Anal. Calcd. for C19H14N2O5: C, 65.14; H, 4.03; N, 8.00. found: C, 64.86; H, 3.99; N, 7.91. Synthesis of (Z)-2-(2-(3-nitrobenzylidene)-3-oxobutyl)isoindoline-1,3-dione ((Z)-8b):
O N
O
O 2N O
1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.19-8.13 (m, 1H), 8.09 (s, 1H), 7.92-7.85 (m, 2H), 7.79-7.73 (m, 2H), 7.56-7.47 (m, 2H), 6.86 (s, 1H), 4.62 (s, 2H), 2.12 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 203.3, 167.7, 148.3, 140.3, 136.7, 134.3, 131.9, 130.9, 129.6, 123.6, 123.4, 123.3, 123.2, 40.5, 30.4. MS (20 eV, EI) m/z (%): 351 (4) [M+1]+, 287 (38), 203 (100), 148 (10). IR (CH2Cl2) ~ (cm−1): 2918 (w), 1774 (w), 1718 (m), 1533 (w), 1396 (w), 1354 (w), 1266 (s). HRMS (ESI) for C19H13N2O5, [M-H]+ (349.0824) found: 349.0821.
Synthesis of (E)-2-(3-oxo-2-(4-(trifluoromethyl)benzylidene)butyl)isoindoline-1,3-dione ((E)-8c): O O F3 C
N O
Prepared according to TP 2 from 4-(trifluoromethyl)benzaldehyde (1c) (273.1 μL, 2.0 mmol), methyl vinyl ketone (2a) (243.4 μL, 1.5 equiv.), phthalimide (3a) (297.2 mg, 1.01 equiv.), and ethyl diphenylphosphine (20.4 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 1.5 h]; triethylamine (0.70 mL, 2.5 equiv), acetic anhydride (0.23 mL, 1.2 equiv), S17
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4-(Dimethylamino)pyridine (24.4 mg, 0.1 equiv) and THF (2.0 mL) [reaction condition: 50℃ for 4.5 h]. Purification by flash-chromatography (hexanes/dichloromethane: 2/3) yielded 8c (white solid) (E:Z= 93:7, 604.8 mg, 81%). white solid mp.: 132.7-133.3 °C. 1 H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 7.75-7.67 (m, 3H), 7.66-7.59 (m, 2H), 7.57-7.46 (m, 4H), 4.64 (s, 2H), 2.46 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 198.3, 167.7, 140.5, 138.2, 137.3, 133.8, 131.7, 130.3(quartet, J = 33 Hz), 128.7, 125.3(quartet, J = 3 Hz), 123.7(quartet, J = 271 Hz), 123.0, 35.0, 26.0. MS (20 eV, EI) m/z (%): 374 (12) [M+1]+, 330 (2), 226 (100), 148 (7). IR (CH2Cl2) ~ (cm−1): 2917 (s), 1772 (w), 1710 (s), 1393 (m), 1322 (s), 1120 (m). HRMS (MALDI) for C18H12F3NO2, [M+H]+ (374.1004) found: 374.1011. Anal. Calcd. for C20H14F3NO3: C, 64.34; H, 3.78; N, 3.75. found: C, 64.65; H, 3.73; N, 3.99.
CCDC number: 769605 Synthesis of (Z)-2-(3-oxo-2-(4-(trifluoromethyl)benzylidene)butyl)isoindoline-1,3-dione ((Z)-8c):
O N
F3C
O
O
1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 7.92-7.84 (m, 2H), 7.79-7.71 (m, 2H), 7.58 (d, 2H, J = 8.1 Hz), 7.32 (d, 2H, J = 8.0 Hz), 6.87 (s, 1H), 4.61 (s, 2H), 2.06 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 203.8, 167.7, 139.6, 138.8, 134.3, 132.1, 132.0, 130.6(quartet, J = 32 Hz), 128.9, 125.5(quartet, J = 3 Hz), 123.8(quartet, J = 270 Hz), 123.6, 40.5, 30.5. MS (20 eV, EI) m/z (%): 374 (2) [M+1]+, 330 (2), 226 (100), 148 (5). IR (CH2Cl2) ~ (cm−1): 2917 (s), 1772 (w), 1710 (s), 1393 (m), 1322 (s), 1120 (m). HRMS (ESI) for C20H14F3NO3Na, [M+Na]+ (396.0823) found: 396.0831.
Synthesis of (E)-2-(2-(4-chlorobenzylidene)-3-oxobutyl)isoindoline-1,3-dione ((E)-8d): S18
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
Prepared according to TP 3 from 4-chlorobenzaldehyde (1g) (281.2 mg, 2.0 mmol), methyl vinyl ketone (2a) (325.0 μL, 2.0 equiv), phthalimide (3a) (382.5 mg, 1.3 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 3 h]; triethylamine (695.0 μL, 2.5 equiv), acetic anhydride (225.0 μL, 1.2 equiv), 4-(Dimethylamino)pyridine (24.4 mg, 0.1 equiv) and additional THF (2.0 mL) [reaction condition: 50℃ for 5 h], Purification by flash-chromatography (hexanes/ethyl acetate: 6/1) for twice, yielded 8d (E/Z = 94/6, 520.0 mg, 77%). white solid mp.: 137.5-138.0 °C. 1 H-NMR of (E)-8d (400 MHz, CDCl3, 25 °C) δ/ppm: 7.76-7.71 (m, 2H), 7.67-7.62 (m, 3H), 7.37 (d, 2H, J = 8.4 Hz), 7.30 (d, 2H, J = 8.4 Hz), 4.66 (s, 2H), 2.44 (s, 3H). 13
C-NMR of (E)-8d (100 MHz, CDCl3, 25 °C) δ/ppm: 198.5, 167.8, 141.2, 136.2, 134.8, 133.8, 132.9, 131.8, 130.1, 128.8, 123.0, 35.1, 25.9. MS (20 eV, EI) m/z (%): 340 (7) [M+1]+, 194 (46), 192 (100), 148 (7). IR (CH2Cl2) ~ (cm−1): 3063 (w), 1772 (m), 1713 (s), 1670 (m), 1394 (m), 1334 (w), 1240 (w), 1120 (w), 1090 (w). HRMS (ESI) for C19H13ClNO3, [M-H]- (338.0584) found: 338.0579. 1
H-NMR of (E)-8d+(Z)-8d (400 MHz, CDCl3, 25 °C) δ/ppm: 7.88-6.80 (m, 9H+9H’), 4.66 (s, 2H) & 4.56 (s, 2H’), 2.44 (s, 3H) & 2.04 (s, 3H’). 13
C-NMR of (E)-8d+(Z)-8d (100 MHz, CDCl3, 25 °C) δ/ppm: 204.2, 198.5, 167.8, 167.7, 141.2, 138.2, 136.2, 134.8, 134.7, 134.1, 133.8, 133.6, 132.9, 132.7, 131.9, 131.8, 130.1, 129.9, 128.8, 128.7, 123.5, 123.0, 40.5, 35.1, 30.4, 25.9.
Synthesis of (E)-2-(2-(2-chlorobenzylidene)-3-oxobutyl)isoindoline-1,3-dione ((E)-8e):
S19
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
Prepared according to TP 3 from 2-chlorobenzaldehyde (1h) (225.0 μL, 2.0 mmol), methyl vinyl ketone (2a) (325.0 μL, 2.0 equiv), phthalimide (3a) (382.5 mg, 1.3 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 5 h]; triethylamine (695.0 μL, 2.5 equiv), acetic anhydride (225.0 μL, 1.2 equiv), 4-(Dimethylamino)pyridine (24.4 mg, 0.1 equiv) and additional THF (2.0 mL) [reaction condition: reflux for 4 h], Purification by flash-chromatography (hexanes/ethyl acetate: 6/1) for twice, yielded 8e as white solid (E/Z = 97/3, 514.3 mg, 76%). white solid mp.: 62.3-62.9 °C. 1 H-NMR of (E)-8e (400 MHz, CDCl3, 25 °C) δ/ppm: 7.76-7.70 (m, 3H), 7.67-7.62 (m, 2H), 7.55-7.51 (m, 1H), 7.36-7.31 (m, 1H), 7.28-7.18 (m, 2H), 4.56 (s, 2H), 2.48 (s, 3H). 13
C-NMR of (E)-8e (100 MHz, CDCl3, 25 °C) δ/ppm: 198.4, 167.6, 139.7, 137.1, 133.7, 133.4, 133.2, 131.9, 130.0, 129.9, 129.5, 126.8, 123.0, 35.0, 26.0. MS (20 eV, EI) m/z (%): 340 (5) [M+1]+, 304 (100), 192 (32), 157 (12). IR (CH2Cl2) ~ (cm−1): 3063 (w), 1772 (m), 1715 (s), 1674 (m), 1395 (m), 1334 (w), 1240 (w), 1120 (w). HRMS (ESI) for C19H14ClNO3Na, [M+Na]+ (362.0560) found: 362.0556.
Synthesis of (Z)-2-(2-(2-chlorobenzylidene)-3-oxobutyl)isoindoline-1,3-dione ((Z)-8e):
O Cl
N
O
O
The compound (Z)-8e can be carefully purified by recrystallization with hexane and dichloromethane as white solid.
S20
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
1
H-NMR of (Z)-8e (400 MHz, CDCl3, 25 °C) δ/ppm: 7.91-7.85 (m, 2H), 7.77-7.71 (m, 2H), 7.39 (d, 1H, J = 8.0 Hz), 7.30-7.14 (m, 3H), 7.00 (s, 1H), 4.63 (s, 2H), 1.95 (s, 3H). 13
C-NMR of (Z)-8e (100 MHz, CDCl3, 25 °C) δ/ppm: 203.0, 167.7, 138.6, 134.1, 133.1, 132.3, 132.0, 130.7, 130.0, 129.6, 126.9, 123.5, 40.2, 30.3. MS (20 eV, EI) m/z (%): 304 (100) [M-35]+, 246 (22), 160 (5). IR (CH2Cl2) ~ (cm−1): 3063 (w), 1772 (m), 1715 (s), 1674 (m), 1395 (m), 1334 (w), 1240 (w), 1120 (w). HRMS (ESI) for C19H15ClNO3, [M+H]+ (340.0740) found: 340.0747.
Synthesis of (E)-2-(3-oxo-2-(pyridin-4-ylmethylene)butyl)isoindoline-1,3-dione ((E)-8f):
Prepared according to TP 3 from 4-pyridylbenzaldehyde (1k) (188.0 μL, 2.0 mmol), methyl vinyl ketone (2a) (325.0 μL, 2.0 equiv), phthalimide (3a) (382.5 mg, 1.3 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 1 h]; triethylamine (695.0 μL, 2.5 equiv), acetic anhydride (225.0 μL, 1.2 equiv), 4-(Dimethylamino)pyridine (24.4 mg, 0.1 equiv) and additional THF (2.0 mL) [reaction condition: 50℃ for 2 h], Purification by flash-chromatography (hexanes/ethyl acetate: 4/1 to 2/1), yielded 8f as brown solid (E/Z = 92/8, 586.2 mg, 96%). brown solid mp.: 105.2-105.9 °C. 1 H-NMR of (E)-8f (400 MHz, CDCl3, 25 °C) δ/ppm: 8.56 (d, 2H, J = 4.7 Hz), 7.76-7.70 (m, 2H), 7.68-7.63 (m, 2H), 7.59 (s, 1H), 7.32 (d, 2H, J = 5.5 Hz), 4.62 (s, 2H), 2.45 (s, 3H). 13
C-NMR of (E)-8f (100 MHz, CDCl3, 25 °C) δ/ppm: 198.1, 167.7, 149.8, 142.7, 138.9, 138.3, 134.0, 131.6, 123.1, 122.9, 35.0, 26.0. MS (20 eV, EI) m/z (%): 307 (19) [M+1]+, 263 (20), 159 (100), 144 (30), 117 (48). IR (CH2Cl2) ~ (cm−1): 3047 (w), 1772 (w), 1713 (s), 1674 (m), 1594 (w), 1396 (m), 1249 (m), 1120 (m). HRMS (ESI) for C18H15N2O3, [M+H]+ (307.1083) found: 307.1089. Anal. Calcd. for C18H14N2O3: C, 70.58; H, 4.61; N, 9.15. found: C, 70.34; H, 4.56; N, 9.16.
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Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
Synthesis of (Z)-2-(3-oxo-2-(pyridin-4-ylmethylene)butyl)isoindoline-1,3-dione ((Z)-8f):
O N
N
O
O
The compound (Z)-8f can be carefully purified by recrystallization with hexane and dichloromethane as white solid. 1
H-NMR of (Z)-8f (400 MHz, CDCl3, 25 °C) δ/ppm: 8.56 (d, 2H, J = 4.7 Hz), 7.76-7.70 (m, 2H), 7.68-7.63 (m, 2H), 7.59 (s, 1H), 7.32 (d, 2H, J = 5.5 Hz), 4.62 (s, 2H), 2.45 (s, 3H). 13
C-NMR of (Z)-8f (100 MHz, CDCl3, 25 °C) δ/ppm: 198.1, 167.7, 149.8, 142.7, 138.9, 138.3, 134.0, 131.6, 123.1, 122.9, 35.0, 26.0. MS (20 eV, EI) m/z (%): 307 (5) [M+1]+, 263 (4), 159 (100), 117 (9). IR (CH2Cl2) ~ (cm−1): 3047 (w), 1772 (w), 1713 (s), 1674 (m), 1594 (w), 1396 (m), 1249 (m), 1120 (m). HRMS (ESI) for C18H15N2O3, [M+H]+ (307.1083) found: 307.1081.
Synthesis of (E)-2-(3-oxo-2-(pyridin-3-ylmethylene)butyl)isoindoline-1,3-dione ((E)-8g):
Prepared according to TP 3 from 3-pyridylbenzaldehyde (1l) (188.0 μL, 2.0 mmol), methyl vinyl ketone (2a) (325.0 μL, 2.0 equiv), phthalimide (3a) (382.5 mg, 1.3 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 1 h]; triethylamine (695.0 μL, 2.5 equiv), acetic anhydride (225.0 μL, 1.2 equiv), 4-(Dimethylamino)pyridine (24.4 mg, 0.1 equiv) and additional THF (2.0 mL) [reaction condition: 50℃ for 3 h], Purification by flash-chromatography (hexanes/ethyl acetate: 4/1 to 2/1), yielded 8g (E/Z = 91/9, 611.4 mg, 99%).
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Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
brown solid mp.: 107.1-107.8 °C. 1 H-NMR of (E)-8g (400 MHz, CDCl3, 25 °C) δ/ppm: 8.66 (s, 1H), 8.53 (d, 1H, J = 4.4 Hz), 7.87 (d, 1H, J = 7.7 Hz), 7.79-7.74 (m, 2H), 7.70-7.64 (m, 3H), 7.34-7.29 (m, 1H), 4.67 (s, 2H), 2.47 (s, 3H). 13
C-NMR of (E)-8g (100 MHz, CDCl3, 25 °C) δ/ppm: 198.2, 167.9, 149.7, 138.7, 137.8, 136.0, 134.0, 131.8, 130.6, 123.3, 123.2, 35.0, 26.0. MS (20 eV, EI) m/z (%): 307 (19) [M+1]+, 263 (71), 159 (100), 144 (42), 117 (11). IR (CH2Cl2) ~ (cm−1): 3055 (w), 1772 (w), 1713 (s), 1674 (m), 1396 (m), 1247 (w), 1120 (w). HRMS (ESI) for C18H15N2O3, [M+H]+ (307.1083) found: 307.1081. Anal. Calcd. for C18H14N2O3: C, 70.58; H, 4.61; N, 9.15. found: C, 70.73; H, 4.56; N, 9.14. 1
H-NMR of (E)-8g+(Z)-8g (400 MHz, CDCl3, 25 °C) δ/ppm: 8.68-8.43 (m, 2H+2H’), 7.91-6.78 (m, 7H+7H’), 4.66 (s, 2H) & 4.61 (s, 2H’), 2.47 (s, 3H) & 2.10 (s, 3H’). 13
C-NMR of (E)-8g+(Z)-8g (100 MHz, CDCl3, 25 °C) δ/ppm: 203.4, 198.1, 167.7, 167.6, 149.6, 149.5, 149.4, 139.8, 138.5, 137.6, 135.9, 135.5, 134.2, 133.9, 131.8, 131.7, 130.9, 130.6, 130.0, 123.5, 123.2, 123.1, 40.5, 35.0, 30.3, 26.0.
Synthesis of (E)-2-(3-oxo-2-(pyridin-2-ylmethylene)butyl)isoindoline-1,3-dione ((E)-8h):
Prepared according to TP 3 from 2-pyridylbenzaldehyde (1m) (191.0 μL, 2.0 mmol), methyl vinyl ketone (2a) (325.0 μL, 2.0 equiv), phthalimide (3a) (382.5 mg, 1.3 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 5 h]; triethylamine (695.0 μL, 2.5 equiv), acetic anhydride (225.0 μL, 1.2 equiv), 4-(Dimethylamino)pyridine (24.4 mg, 0.1 equiv) and additional THF (2.0 mL) [reaction condition: reflux for 6 h], Purification by flash-chromatography (hexanes/ethyl acetate: 4/1 to 2/1), yielded (E)-8h (brown solid) (E/Z = 98/2, 549.9 mg, 90%). mp.: 158.4-159.0 °C.
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Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
1
H-NMR of (E)-8h (400 MHz, CDCl3, 25 °C) δ/ppm: 8.63 (d, 1H, J = 4.4 Hz), 7.79-7.68 (m, 3H), 7.67-7.62 (m, 2H), 7.55 (s, 1H), 7.50 (d, 1H, J = 7.7 Hz), 7.23-7.19 (m, 1H), 5.19 (s, 2H), 2.51 (s, 3H). 13
C-NMR of (E)-8h (100 MHz, CDCl3, 25 °C) δ/ppm: 199.2, 168.0, 153.8, 149.7, 139.2, 138.3, 136.5, 133.7, 132.1, 126.2, 123.2, 123.0, 34.7, 26.2. MS (20 eV, EI) m/z (%): 306 (27) [M]+, 291 (48), 263 (49), 159 (100), 144 (18). IR (CH2Cl2) ~ (cm−1): 3055 (w), 1770 (m), 1710 (s), 1673 (m), 1393 (m), 1334 (w), 1250 (m), 1120 (w). HRMS (ESI) for C18H15N2O3, [M+H]+ (307.1083) found: 307.1088.
Synthesis
of
(E)-4-(2-((1,3-dioxoisoindolin-2-yl)methyl)-3-oxopent-1-enyl)benzonitrile
((E)-8i):
O
O NC
N O
Prepared according to TP 3 from 4-cyanobenzaldehyde (1d) (262.3 mg, 2.0 mmol), ethyl vinyl ketone (2b) (262.9 μL, 1.3 equiv.), phthalimide (3a) (297.2 mg, 1.01 equiv.), and ethyl diphenylphosphine (20.4 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 1.5 h]; triethylamine (0.70 mL, 2.5 equiv), acetic anhydride (0.23 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (24.4 mg, 0.1 equiv) and THF (2.0 mL) [reaction condition: reflux for 5 h]. Purification by flash-chromatography (hexanes/ethyl acetate: 4/1) yielded 8i (E:Z= 92:8, 534.3 mg, 76%). white solid mp.: 149.8-150.4 °C. 1 H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 7.76-7.70 (m, 2H), 7.69-7.64 (m, 3H), 7.62-7.49 (m, 4H), 4.62 (s, 2H), 2.83 (quartet, 2H, J = 7.2 Hz), 1.11 (t, 3H, J = 7.2 Hz). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 200.8, 167.6, 139.4, 138.5, 137.4, 134.0, 132.1, 131.7, 129.2, 123.1, 118.2, 112.0, 35.2, 31.0, 8.2. MS (20 eV, EI) m/z (%): 345 (2) [M+1]+, 315 (8), 197 (100), 168 (17), 148 (8). IR (CH2Cl2) ~ (cm−1): 2919 (m), 2230 (m), 1773 (m), 1715 (s), 1394 (m). HRMS (MALDI) for C21H16N2O3Na, [M+Na]+ (367.1059) found: 367.1063. S24
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
Anal. Calcd. for C21H16N2O3: C, 73.24; H, 4.68; N, 8.13. found: C, 73.25; H, 4.67; N, 8.09.
Synthesis of (E)-2-(2-acetyl-4-oxo-4-phenylbut-2-enyl)isoindoline-1,3-dione ((E)-8j):
O O
O N O
Prepared according to TP 2 from phenylglyoxal monohydrate (1n) (156.9 mg, 1.0 mmol), methyl vinyl ketone (2a) (121.7 μL, 1.5 equiv.), phthalimide (3a) (176.6 mg, 1.2 equiv.), and triiphenylphosphine (52.5 mg, 20 mol%) in THF (1.0 mL) [reaction condition: RT for 4.5 h]; triethylamine (0.35 mL, 2.5 equiv), acetic anhydride (0.11 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (12.2 mg, 0.1 equiv) and THF (1.0 mL) [reaction condition: reflux for 2 h]. Purification by flash-chromatography (hexanes/ethyl acetate: 3/1) yielded 8j (E:Z= 93:7, 230.1 mg, 69%). white solid mp.: 180.6-181.4 °C. 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 7.96 (d, 2H, J = 7.2 Hz), 7.92-7.86 (m, 2H), 7.81-7.75 (m, 2H), 7.61 (s, 1H), 7.55 (t, 1H, J = 7.4 Hz ), 7.44 (t, 2H, J = 7.6 Hz ), 4.28 (s, 2H), 2.56 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 197.3, 195.9, 165.6, 136.7, 134.9, 132.9, 132.0, 131.6, 129.6, 128.4, 128.1, 124.1, 37.9, 26.0. MS (20 eV, EI) m/z (%): 334 (2) [M+1]+, 290 (5), 186 (100), 105 (42). IR (CH2Cl2) ~ (cm−1): 2918 (w), 1786 (w), 1730 (s), 1675 (m), 1350 (m), 1266 (m). HRMS (ESI) for C20H15NO4Na, [M+Na]+ (356.0899) found: 356.0904.
Synthesis of (E)-1-(2-(4-nitrobenzylidene)-3-oxobutyl)pyrrolidine-2,5-dione ((E)-9a):
O
O2N
N O
S25
O
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
Prepared according to TP 3 from 4-nitrobenzaldehyde (1a) (302.2 mg, 2.0 mmol), methyl vinyl ketone (2a) (210.9 μL, 1.3 equiv), succinimide (3b) (200.1 mg, 1.01 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 1 h]; triethylamine (695.0 μL, 2.5 equiv), acetic anhydride (225.0 μL, 1.2 equiv), 4-(Dimethylamino)pyridine (24.4 mg, 0.1 equiv) and additional THF (2.0 mL) [reaction condition: 50 °C for 3 h], Purification by short flash-chromatography (CH2Cl2) then recrystallized with CH2Cl2 and hexanes, yielding (E)-9a as yellow solid (E/Z = 88/12, 460.1 mg, 76%). mp: 159.7-160.5 °C 1
H-NMR of (E)-9a (400 MHz, CDCl3, 25 °C) δ/ppm: 8.27 (d, 2H, J = 8.6 Hz), 7.67 (s, 1H), 7.62 (d, 2H, J= 8.6 Hz), 4.45 (s, 2H), 2.56 (s, 4H), 2.46 (s, 3H). 13
C-NMR of (E)-9a (100 MHz, CDCl3, 25 °C) δ/ppm: 198.0, 176.5, 147.6, 141.1, 139.6, 137.5, 129.7, 123.7, 35.8, 27.9, 26.0. MS (20 eV, EI) m/z (%): 302.0 (2) [M]+, 202.9 (100), 99.9 (7). IR (CH2Cl2) ~ (cm−1): 3058 (m), 1705 (s), 1676 (s), 1523 (s), 1350 (s), 1266 (s). HRMS (MALDI) for C15H15N2O5, [M+H]+ (303.0981) found: 303.0993.
Synthesis ((E)-9b):
of
(E)-4-(2-((2,5-dioxopyrrolidin-1-yl)methyl)-3-oxobut-1-enyl)benzonitrile
O
N
NC
O
O
Prepared according to TP 3 from 4-cyanobenzaldehyde (1b) (262.3 mg, 2.0 mmol), methyl vinyl ketone (2a) (210.9 μL, 1.3 equiv), succinimide (3b) (200.1 mg, 1.01 equiv), and ethyl diphenylphosphine (20.5 μL, 5 mol%) in THF (2.0 mL) [reaction condition: RT for 1.5 h]; triethylamine (695.0 μL, 2.5 equiv), acetic anhydride (225.0 μL, 1.2 equiv), 4-(Dimethylamino)pyridine (24.4 mg, 0.1 equiv) and additional THF (2.0 mL) [reaction condition: 50 °C for 4.5 h], Purification by short flash-chromatography (CH2Cl2) then recrystallized with CH2Cl2 and hexane, yielding (E)-9b as white solid (E/Z = 90/10, 387.4 mg, 68%).
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Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
mp: 152.2-152.9 °C 1
H-NMR of (E)-9b (400 MHz, CDCl3, 25 °C) δ/ppm: 7.70 (d, 2H, J = 8.1 Hz), 7.63 (s, 1H), 7.55 (d, 2H, J= 8.1 Hz), 4.45 (s, 2H), 2.55 (s, 4H), 2.45 (s, 3H). 13
C-NMR of (E)-9b (100 MHz, CDCl3, 25 °C) δ/ppm: 197.9, 176.3, 139.6, 139.0, 136.8, 131.9, 129.2, 118.0, 111.9, 35.4, 27.7, 25.7. MS (20 eV, EI) m/z (%): 283 (12) [M+1]+, 183 (100), 141 (8), 100 (6). IR (CH2Cl2) ~ (cm−1): 3058 (m), 2231 (w), 1704 (s), 1674 (s), 1266 (s). HRMS (MALDI) for C16H14N2O3Na, [M+Na]+ (305.0902) found: 305.0913.
Synthesis of (E)-1-methyl-3-(2-(4-nitrobenzylidene)-3-oxobutyl)imidazolidine-2,4-dione ((E)-10a): O O O 2N
N O
N
Prepared according to TP 4 from 4-nitrobenzaldehyde (1a) (151.1 mg, 1.0 mmol), methyl vinyl ketone (2a) (113.6 μL, 1.4 equiv.), 1-methylhydantoin (3c) (119.8 mg, 1.05 equiv.), and triphenylphosphine (52.5 mg, 20 mol%) in THF (1.0 mL) [reaction condition: RT for 3 h]; triethylamine (0.35 mL, 2.5 equiv.), acetic anhydride (0.11 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (12.2 mg, 0.1 equiv.) and additional THF (1.0 mL) [reaction condition: 50℃ for 3.5 h], Purification by flash-chromatography (dichloromethane/methanol: 400/1 to 200/1) yielded 10a (E/Z = 84/16, 266.0 mg, 84%). yellow solid mp.: 145.5-146.1 °C. 1 H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.18 (d, 2H, J = 8.5 Hz), 7.63 (d, 2H, J = 7.4 Hz), 7.60 (s, 1H), 4.39 (s, 2H), 3.67 (s, 2H), 2.85 (s, 3H), 2.42 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 198.0, 169.1, 156.1, 147.4, 141.1, 139.5, 137.5, 129.7, 123.5, 51.2, 35.8, 29.3, 25.9. MS (20 eV, EI) m/z (%): 318 (13) [M+1]+, 257 (5), 203 (100), 160 (4), 115 (83). IR (CH2Cl2) ~ (cm−1): 3100 (m), 2945 (s), 2918 (s), 2849 (s), 1771 (m), 1709 (s), 1679 (s), 1345 (s). HRMS (MALDI) for C15H16 N3O5, [M+H]+ (318.1090) found: 318.1103.
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Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
Synthesis of (E)-1-methyl-3-(2-(3-nitrobenzylidene)-3-oxobutyl)imidazolidine-2,4-dione ((E)-10b): O O N NO 2
O
N
Prepared according to TP 4 from 3-nitrobenzaldehyde (1b) (151.1 mg, 1.0 mmol), methyl vinyl ketone (2a) (113.6 μL, 1.4 equiv.), 1-methylhydantoin (3c) (119.8 mg, 1.05 equiv.), and triphenylphosphine (52.5 mg, 20 mol%) in THF (1.0 mL) [reaction condition: RT for 3 h]; triethylamine (0.35 mL, 2.5 equiv.), acetic anhydride (0.11 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (12.2 mg, 0.1 equiv.) and additional THF (1.0 mL) [reaction condition: 50℃ for 3.5 h], Purification by flash-chromatography (dichloromethane/methanol: 400/1 to 200/1) yielded 10b (E/Z = 83/17, 280.0 mg, 88%). yellow solid mp.: 148.3-148.8 °C. 1 H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.27 (s, 1H), 8.16 (d, 1H, J = 7.7 Hz), 7.80 (d, 1H, J = 7.2 Hz), 7.65 (s, 1H), 7.62-7.51 (m, 1H), 4.41 (s, 2H), 3.69 (s, 2H), 2.87 (s, 3H), 2.44 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 198.1, 169.1, 156.1, 148.1, 139.4, 137.3, 136.2, 134.6, 129.6, 123.7, 123.2, 51.3, 35.7, 29.4, 26.0. MS (20 eV, EI) m/z (%): 318 (2) [M+1]+, 300 (4), 256 (13), 238 (31), 203 (100), 114 (58). IR (CH2Cl2) ~ (cm−1): 3057 (m), 2986 (s), 2918 (s), 2851 (m), 1775 (m), 1727 (s), 1716 (s), 1678 (s), 1533(s), 1266(s). HRMS (MALDI) for C15H16 N3O5, [M+H]+ (318.1090) found: 318.1103. Anal. Calcd. for C15H15 N3O5: C, 56.78; H, 4.76; N, 13.24. found: C, 56.84; H, 4.73; N, 12.96.
Synthesis of (E)-1-methyl-3-(2-(2-nitrobenzylidene)-3-oxobutyl)imidazolidine-2,4-dione ((E)-10c):
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Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
NO2
O O N O
N
Prepared according to TP 4 from 2-nitrobenzaldehyde (1c) (151.1 mg, 1.0 mmol), methyl vinyl ketone (2a) (113.6 μL, 1.4 equiv.), 1-methylhydantoin (3c) (119.8 mg, 1.05 equiv.), and triphenylphosphine (52.5 mg, 20 mol%) in THF (1.0 mL) [reaction condition: RT for 15 h]; triethylamine (0.35 mL, 2.5 equiv.), acetic anhydride (0.11 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (12.2 mg, 0.1 equiv.) and additional THF (1.0 mL) [reaction condition: reflux for 6.0 h], Purification by flash-chromatography (dichloromethane/methanol: 400/1 to 200/1) yielded 10c (E/Z = 92/8, 292.0 mg, 92%). yellow solid mp.: 110.7-110.9 °C. 1 H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.14 (d, 1H, J = 8.0 Hz), 8.00 (s, 1H), 7.71-7.61 (m, 1H), 7.61-7.47 (m, 2H), 4.20 (s, 2H), 3.56 (s, 2H), 2.80 (s, 3H), 2.44 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 198.0, 168.9, 155.8, 146.7, 139.8, 135.2, 133.7, 130.6, 130.5, 129.4, 124.7, 51.2, 35.3, 29.2, 25.9. MS (20 eV, EI) m/z (%): 318 (2) [M+1]+, 270 (17), 257 (25), 227 (6), 187 (13), 161 (23), 127 (36), 120 (100), 99 (12). IR (CH Cl ) ~ (cm−1): 3059 (s), 2926 (s), 2853 (s), 1775 (s), 1713 (s), 1608 (m), 1526 (s), 2
2
1243 (s). HRMS (MALDI) for C15H16 N3O5, [M+H]+ (318.1090) found: 318.1101. Anal. Calcd. for C15H15 N3O5: C, 56.78; H, 4.76; N, 13.24. found: C, 56.93; H, 4.73; N, 12.95.
Synthesis of (E)-4-(2-((3-methyl-2,5-dioxoimidazolidin-1-yl)methyl)-3-oxobut-1-enyl) benzonitrile ((E)-10d): O O NC
N O
S29
N
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
Prepared according to TP 4 from 4-cyanobenzaldehyde (1d) (133.8 mg, 1.0 mmol), methyl vinyl ketone (2a) (113.6 μL, 1.4 equiv.), 1-methylhydantoin (3c) (119.8 mg, 1.05 equiv.), and triphenylphosphine (52.5 mg, 20 mol%) in THF (1.0 mL) [reaction condition: RT for 4.5 h]; triethylamine (0.35 mL, 2.5 equiv.), acetic anhydride (0.11 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (12.2 mg, 0.1 equiv.) and additional THF (1.0 mL) [reaction condition: 50℃ for 3.5 h], Purification by flash-chromatography (dichloromethane/methanol: 400/1 to 200/1) yielded 10d (E/Z = 89/11, 276.0 mg, 92%). white solid mp.: 112.0-112.5 °C. 1 H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 7.67 (d, 2H, J = 8.2 Hz), 7.62 (s, 1H), 7.57 (d, 2H, J = 8.1 Hz), 4.42 (s, 2H), 3.67 (s, 2H), 2.89 (s, 3H), 2.44 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 198.0, 169.0, 156.0, 139.8, 139.1, 137.0, 132.0, 129.3, 118.1, 112.0, 51.2, 35.7, 29.3, 25.9. MS (20 eV, EI) m/z (%): 298 (5) [M+1]+, 183 (100), 168 (5), 115 (73). IR (CH2Cl2) ~ (cm−1): 3057 (s), 2986 (s), 2918 (s), 2851 (s), 2231(m), 1775 (s), 1716 (s), 1677 (s), 1606 (m), 1266 (s). HRMS (MALDI) for C16H16 N3O3, [M+H]+ (298.1191) found: 298.1203.
Synthesis of (E)-1-methyl-3-(3-oxo-2-(4-(trifluoromethyl)benzylidene)butyl) imidazolidine-2,4-dione ((E)-10e): O O F3C
N O
N
Prepared according to TP 4 from 4-(trifluromethyl)benzaldehyde (1e) (140 μL, 1.0 mmol), methyl vinyl ketone (2a) (113.6 μL, 1.4 equiv.), 1-methylhydantoin (3c) (119.8 mg, 1.05 equiv.), and triphenylphosphine (52.5 mg, 20 mol%) in THF (1.0 mL) [reaction condition: RT for 23 h]; triethylamine (0.35 mL, 2.5 equiv.), acetic anhydride (0.11 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (12.2 mg, 0.1 equiv.) and additional THF (1.0 mL) [reaction condition: 50℃ for 6.5 h], Purification by flash-chromatography (dichloromethane/methanol: 400/1 to 200/1) yielded 10e (E/Z = 90/10, 304.7 mg, 90%). white solid S30
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
mp.: 106.5-107.0 °C. 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 7.68-7.56 (m, 3H), 7.56-7.45 (m, 2H), 4.42 (s, 2H), 3.56 (s, 2H), 2.81 (s, 3H), 2.42 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 198.3, 169.1, 156.1, 140.3, 138.2, 136.6, 130.3 (quartet, J = 32 Hz), 128.9, 125.2 (quartet, J = 4 Hz), 123.7 (quartet, J = 270 Hz), 51.2, 36.0, 29.2, 25.9. MS (20 eV, EI) m/z (%): 340 (2) [M]+, 227 (12), 225 (100), 183 (2), 115 (36). IR (CH2Cl2) ~ (cm−1): 3058 (m), 2986 (s), 2918 (s), 2851 (m), 1732 (s), 1717 (s), 1676 (s), 1617 (m), 1267 (s), 1245 (s). HRMS (MALDI) for C16H16 F3N2O3, [M+H]+ (341.1113) found: 341.1121. Anal. Calcd. for C16H15 F3N2O3: C, 56.47; H, 4.76; N, 8.23. found: C, 56.77; H, 4.43; N, 8.22.
Synthesis of (E)-3-(2-(4-bromobenzylidene)-3-oxobutyl)-1-methylimidazolidine-2,4-dione ((E)-10f): O O Br
N O
N
Prepared according to TP 4 from 4-bromobenzaldehyde (1f) (186.9 mg, 1.0 mmol), methyl vinyl ketone (2a) (113.6 μL, 1.4 equiv.), 1-methylhydantoin (3c) (119.8 mg, 1.05 equiv.), and triphenylphosphine (52.5 mg, 20 mol%) in THF (1.0 mL) [reaction condition: RT for 24 h]; triethylamine (0.35 mL, 2.5 equiv.), acetic anhydride (0.11 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (12.2 mg, 0.1 equiv.) and additional THF (1.0 mL) [reaction condition: reflux for 5 h], Purification by flash-chromatography (dichloromethane/methanol: 400/1 to 200/1) yielded 10f (E/Z = 89/11, 290.5 mg, 83%). white solid mp.: 97.0-98.0 °C. 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 7.59 (s, 1H), 7.52 (d, 2H, J = 8.2 Hz), 7.30 (d, 2H, J = 8.2 Hz), 4.48 (s, 2H), 3.64 (s, 2H), 2.88 (s, 3H), 2.44 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 198.5, 169.2, 156.3, 141.1, 135.7, 133.4, 131.7, 130.4, 123.1, 51.4, 36.1, 29.5, 26.0. MS (20 eV, EI) m/z (%): 352 (2) [M+2]+, 351 (3) [M+1]+, 236 (100), 223 (5), 115 (17). S31
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
IR (CH2Cl2) ~ (cm−1): 3059 (m), 2928 (s), 1773 (s), 1709 (s), 1671 (s), 1632 (m), 1242 (s), 591 (s). HRMS (ESI) for C15H16N2O3Br, [M+H]+ (351.0344) found: 351.0336.
CCDC number: 770519
Synthesis of (E)and (Z)-1-methyl-3-(3-oxo-2-(pyridin-4-ylmethylene)butyl) imidazolidine-2,4-dione ((E)-10g and (Z)-10g): O O
N N O
N
Prepared according to TP 4 from nicotinaldehyde (1j) (97.0 μL, 1.01 equiv.), methyl vinyl ketone (2a) (113.6 μL, 1.4 equiv.), 1-methylhydantoin (3c) (114.1 mg, 1.0 mmol), and triphenylphosphine (52.5 mg, 20 mol%) in THF (1.0 mL) [reaction condition: RT for 12 h]; triethylamine (0.35 mL, 2.5 equiv.), acetic anhydride (0.11 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (12.2 mg, 0.1 equiv.) and additional THF (1.0 mL) [reaction condition: 50℃ for 4 h], Purification by flash-chromatography (dichloromethane/methanol: 400/1 to 200/1) yielded 10g (E/Z = 89/11, 251.3 mg, 92%). white oil 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.63 (d, 2H, J = 5.6 Hz), 8.56 (d, 2H’, J = 5.7 Hz), 7.55 (s, 1H), 7.32 (d, 2H, J = 5.7 Hz), 7.10 (d, 2H’, J = 5.8 Hz), 6.70 (s, 1H’), 4.44 (s, 2H), 4.39 (s, 2H’), 3.91 (s, 2H’), 3.61 (s, 2H), 3.00 (s, 3H’), 2.90 (s, 3H), 2.45 (s, 3H), 2.10 (s, 3H’). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 203.4, 198.1, 169.2, 169.1, 156.0, 155.9, 149.9, 149.8, 142.6, 142.4, 140.6, 138.6, 137.6, 130.3, 122.8, 122.3, 51.5, 51.2, 41.3, 35.9, 30.3, 29.6, 29.3, 25.9. MS (20 eV, EI) m/z (%): 274 (5) [M+1]+, 159 (100), 144 (11), 115 (17). IR (CH2Cl2) ~ (cm−1): 3044 (m), 2930 (s), 1770 (s), 1703 (s), 1596 (s), 1249 (s), 1155 (s). HRMS (ESI) for C14H16N3O3, [M+H]+ (274.1192) found: 274.1195.
Synthesis of (E)-1-methyl-3-(2-(4-nitrobenzylidene)-3-oxopentyl)imidazolidine-2,4-dione ((E)-10h):
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Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
O O O2N
N O
N
Prepared according to TP 4 from 4-nitrobenzaldehyde (1a) (151.1 mg, 1.0 mmol), ethyl vinyl ketone (2b) (142.2 μL, 1.4 equiv.), 1-methylhydantoin (3c) (119.8 mg, 1.05 equiv.), and triphenylphosphine (52.5 mg, 20 mol%) in THF (1.0 mL) [reaction condition: RT for 3.5 h]; triethylamine (0.35 mL, 2.5 equiv.), acetic anhydride (0.11 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (12.2 mg, 0.1 equiv.) and additional THF (1.0 mL) [reaction condition: reflux for 3 h], Purification by flash-chromatography (dichloromethane/methanol: 400/1 to 200/1) yielded 10h (E/Z = 86/14, 265.8 mg, 80%). yellow solid mp.: 140.6-141.4 °C. 1 H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.26 (d, 2H, J = 8.6 Hz), 7.70-7.60 (m, 3H), 4.46 (s, 2H), 3.71 (s, 2H), 2.91 (s, 3H), 2.85 (quartet, 2H, J = 14.4, 7.2 Hz), 1.15 (t, 3H, J = 7.2 Hz). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 200.8, 169.1, 156.2, 147.5, 141.3, 138.1, 137.3, 129.7, 123.6, 51.3, 36.2, 31.0, 29.4, 8.1. MS (20 eV, EI) m/z (%): 332 (10) [M+1]+, 302 (15), 217 (100), 188 (28), 115 (33). IR (CH2Cl2) ~ (cm−1): 3110 (w), 2983 (m), 2940 (m), 1769 (s), 1718 (s), 1664 (s), 1388 (m), 1345 (s). HRMS (MALDI) for C16H18N3O5, [M+H]+ (332.1246) found: 332.1253. Anal. Calcd. for C16H17N3O5: C, 58.00; H, 5.17; N, 12.68. found: C, 58.15; H, 5.18; N, 12.49. (E)- and (Z)-1-methyl-3-(2-(4-nitrobenzylidene)-3-oxopentyl)imidazolidine-2,4-dione ((E)-10h and (Z)-10h): O O O2 N
N O
S33
N
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.24 (d, 2H’, J = 8.5 Hz), 8.16 (d, 2H, J = 8.6 Hz), 7.74-7.62 (m, 3H’), 7.35 (d, 2H, J = 8.4 Hz), 6.80 (s, 1H), 4.46 (s, 2H’), 4.41 (s, 2H), 3.97 (s, 2H), 3.74 (s, 2H’), 3.03 (s, 3H), 2.92 (s, 3H’), 2.87 (quartet, 2H’, J = 14.4, 7.2 Hz), 2.39 (quartet, 2H, J = 14.4, 7.2 Hz), 1.14 (t, 3H’, J = 7.2 Hz), 0.98 (t, 3H, J = 7.2 Hz). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 207.0, 200.7, 169.1, 169.0, 156.1, 155.8, 147.4, 147.3, 141.4, 141.3, 140.7, 138.0, 137.2, 129.6, 129.0, 123.5, 123.4, 51.5, 51.2, 41.5, 36.0, 35.9, 30.9, 29.5, 29.3, 8.0, 7.5. MS (20 eV, EI) m/z (%): 332 (15) [M+1]+, 217 (100), 188 (34), 134(11), 115 (43). IR (CH2Cl2) ~ (cm−1): 3110 (w), 2983 (m), 2940 (m), 1769 (s), 1718 (s), 1664 (s), 1388 (m), 1345 (s).
Synthesis of (E)-1-methyl-3-(2-(3-nitrobenzylidene)-3-oxopentyl)imidazolidine-2,4-dione ((E)-10i): O O N NO 2
O
N
Prepared according to TP 4 from 3-nitrobenzaldehyde (1b) (151.1 mg, 1.0 mmol), ethyl vinyl ketone (2b) (142.2 μL, 1.4 equiv.), 1-methylhydantoin (3c) (119.8 mg, 1.05 equiv.), and triphenylphosphine (52.5 mg, 20 mol%) in THF (1.0 mL) [reaction condition: RT for 6 h]; triethylamine (0.35 mL, 2.5 equiv.), acetic anhydride (0.11 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (12.2 mg, 0.1 equiv.) and additional THF (1.0 mL) [reaction condition: reflux for 3 h], Purification by flash-chromatography (hexanes/ethyl acetate: 3/1) yielded 10i (E/Z = 87/13, 284.9 mg, 86%). white solid mp.: 104.2-105.0 °C. 1 H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.31 (s, 1H), 8.23-8.19 (m, 1H, ), 7.84 (d, 1H, J = 7.7 Hz), 7.67 (s, 1H), 7.60 (t, 1H, J=8Hz), 4.47 (s, 2H), 3.73 (s, 2H), 2.93(s, 3H) 2.86 (q, 2H, J=7.2Hz), 1.16 (t, 3H, J=7.24Hz). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 200.8, 169.2, 156.1, 148.1, 138.1, 137.0, 136.3, 134.6, 129.5, 123.7, 123.1, 51.3, 36.0, 30.9, 29.4, 8.1. MS (20 eV, EI) m/z (%): 332 (17) [M+1]+, 252 (17), 217 (100), 188 (25), 127 (8), 115 (38), 57 (6). S34
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
IR (CH2Cl2) ~ (cm−1): 3474 (w), 3074 (m), 2979 (m), 2940 (m), 1714 (s), 1352 (s). HRMS (MALDI) for C16H17 N3NaO5, [M+H]+ (353.1066) found: 354.1073.
Synthesis of (E)-4-(2-((3-methyl-2,5-dioxoimidazolidin-1-yl)methyl)-3-oxopent-1-enyl) benzonitrile ((E)-10j): O O NC
N O
N
Prepared according to TP 4 from 4-cyanobenzaldehyde (1d) (133.8 mg, 1.0 mmol), ethyl vinyl ketone (2b) (142.2 μL, 1.4 equiv.), 1-methylhydantoin (3c) (119.8 mg, 1.05 equiv.), and triphenylphosphine (52.5 mg, 20 mol%) in THF (1.0 mL) [reaction condition: RT for 3.5 h]; triethylamine (0.35 mL, 2.5 equiv.), acetic anhydride (0.11 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (12.2 mg, 0.1 equiv.) and additional THF (1.0 mL) [reaction condition: reflux for 4 h], Purification by flash-chromatography (hexanes/ethyl acetate: 1/1) yielded 10j (E/Z = 85/15, 258.2 mg, 83%). white solid mp.: 137.8-138.5 °C. 1 H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 7.66 (d, 2H, J = 8.1 Hz), 7.61 (s, 1H), 7.55 (d, 2H, J = 8.0 Hz), 4.42 (s, 2H), 3.67 (s, 2H), 2.88 (s, 3H), 2.81 (quartet, 2H, J = 14.3, 7.2 Hz), 1.10 (t, 3H, J = 7.2 Hz). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 200.8, 169.2, 156.2, 139.4, 138.6, 136.8, 132.1, 129.4, 118.2, 112.1, 51.3, 36.2, 30.9, 29.4, 8.1. MS (20 eV, EI) m/z (%): 312 (8) [M+1]+, 197 (100), 168 (65), 134 (97), 115 (75), 98 (89), 74 (40). IR (CH Cl ) ~ (cm−1): 3059 (m), 2922 (s), 2852 (s), 2229 (s), 1774 (s), 1711 (s), 1605 (m), 2
2
1243 (s). HRMS (ESI) for C17H17N3O3Na, [M+Na]+ (334.1168) found: 334.1174. Anal. Calcd. for C17H17N3O3: C, 65.58; H, 5.50; N, 13.50. found: C, 65.80; H,5.51; N,13.29.
Synthesis ((E)-11a):
of
(E)-2-(2-(4-nitrobenzylidene)-3-oxobutyl)-1-phenylpyrazolidin-3-one
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Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
O O O 2N Ph
N N
Prepared according to TP 4 from 4-nitrobenzaldehyde (1a) (158.7 mg, 1.05 equiv.), methyl vinyl ketone (2a) (113.6 μL, 1.4 equiv.), 1-phenyl-3-pyrazolidinone (3d) (167.2 mg, 1.0 mmol), and triphenylphosphine (52.5 mg, 20 mol%) in THF (1.0 mL) [reaction condition: RT for 1 h]; triethylamine (0.35 mL, 2.5 equiv.), acetic anhydride (0.11 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (12.2 mg, 0.1 equiv.) and additional THF (1.0 mL) [reaction condition: 50℃ for 2 h], Purification by flash-chromatography (hexanes/ethyl acetate: 1/1) then recrystallized with CH2Cl2, yielded 11a (E/Z = 97/3, 301.6 mg, 83%). yellow solid mp.: 129.3-130.2 °C. 1 H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.06-7.99 (m, 2H), 7.52 (s, 1H), 7.30-7.19 (m, 4H), 7.12-7.06 (m, 1H), 6.87-6.80 (m, 2H), 4.46 (s, 2H), 3.66 (t, 2H, J = 7.5 Hz), 2.49 (t, 2H, J = 7.5 Hz), 2.43 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 197.9, 172.7, 149.5, 147.1, 140.7, 139.2, 138.3, 129.3, 129.1, 123.9, 123.2, 118.6, 55.6, 39.3, 29.0, 26.0. MS (20 eV, EI) m/z (%): 365 (36) [M]+, 328 (20), 268 (28), 161 (100), 134 (38) , 98 (31), 74 (13). IR (CH Cl ) ~ (cm−1): 3056 (s), 2987 (m), 2958 (s), 2918 (s), 2851(m), 1732 (s), 1599(w), 2
2
1375 (s), 1265 (s). HRMS (ESI) for C20H19N3O4Na, [M+Na]+ (388.1273) found: 388.1280.
Synthesis of ((E)-11b):
(E)-2-(3-oxo-2-(pyridin-4-ylmethylene)butyl)-1-phenylpyrazolidin-3-one
O O
N Ph
S36
N N
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
Prepared according to TP 4 from nicotinaldehyde (1j) (96.0 μL, 1.0 mmol), methyl vinyl ketone (2a) (113.6 μL, 1.4 equiv.), 1-phenyl-3-pyrazolidinone (3d) (175.6 mg, 1.05 equiv.), and triphenylphosphine (52.5 mg, 20 mol%) in THF (1.0 mL) [reaction condition: RT for 7 h]; triethylamine (0.35 mL, 2.5 equiv.), acetic anhydride (0.11 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (12.2 mg, 0.1 equiv.) and additional THF (1.0 mL) [reaction condition: 50℃ for 2 h], Purification by flash-chromatography (ethyl acetate) yielded 11b (yellow oil) (E/Z = 92/8, 314.7 mg, 98%). 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.43 (d, 2H, J = 5.8 Hz), 7.39 (s, 1H), 7.30-7.22 (m, 2H), 7.08 (t, 1H, J = 7.4 Hz), 6.92 (d, 2H, J = 5.8 Hz), 6.84 (d, 2H, J = 7.6 Hz), 4.44 (s, 2H), 3.64 (t, 2H, J = 7.5 Hz), 2.48 (t, 2H, J = 7.5 Hz), 2.41 (s, 3H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 197.9, 172.8, 149.6, 149.5, 141.9, 138.6, 138.5, 129.2, 124.0, 122.7, 118.6, 55.6, 39.5, 29.0, 26.0. MS (20 eV, EI) m/z (%): 321 (24) [M]+, 162 (8), 161 (100). IR (CH2Cl2) ~ (cm−1): 3047 (w), 2919 (m), 2850 (w), 1696 (s), 1387 (m). HRMS (ESI) for C19H20N3O2, [M+H]+ (322.1556) found: 322.1564.
Synthesis of (E)- and (Z)-3-((5-oxo-2-phenylpyrazolidin-1-yl)methyl)-1-phenylpent-2-ene -1,4-dione ((E)-11c and (Z)-11c): O Ph O
O Ph
N N
Prepared according to TP 4 from phenylglyoxal monohydrate (1n) (155.8 mg, 1.0 mmol), methyl vinyl ketone (2a) (113.6 μL, 1.4 equiv.), 1-phenyl-3-pyrazolidinone (3d) (175.6 mg, 1.05 equiv.), and triphenylphosphine (52.5 mg, 20 mol%) in THF (1.0 mL) [reaction condition: RT for 4 h]; triethylamine (0.35 mL, 2.5 equiv.), acetic anhydride (0.11 mL, 1.2 equiv), 4-(Dimethylamino)pyridine (12.2 mg, 0.1 equiv.) and additional THF (1.0 mL) [reaction condition: 50℃ for 2 h], Purification by flash-chromatography (hexanes/ethyl acetate: 2/1) yielded 11c (E/Z = 44/56, 348.1 mg, 92%). 1
H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.20 (s, 1H), 7.92-7.86 (m, 2H’), 7.86-7.79 (m, 2H), 7.62-6.90 (m, 6H+8H’), 6.59 (s, 1H’), 6.50-6.42 (m, 2H), 3.96-3.80 (m, 2H+4H’), 3.56 (t, 2H, J = 7.0 Hz), 2.61 (t, 2H’, J = 7.4 Hz), 2.53-2.46 (m, 5H), 2.44 (s, 3H’). S37
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 201.9, 197.1, 196.7, 193.8, 172.7, 171.4, 148.8, 148.5, 136.7, 135.9, 133.3, 132.6, 131.1, 129.4, 129.3, 128.5, 128.3, 128.0, 127.9, 124.4, 124.3, 123.2, 122.2, 118.3, 117.0, 116.4, 54.5, 54.1, 43.3, 33.5, 30.1, 29.1, 28.2, 25.2. MS (20 eV, EI) m/z (%):348 (100) [M]+, 243 (31), 201 (51), 162 (17) , 105 (15). IR (CH2Cl2) ~ (cm−1): 3065 (w), 2982 (s), 2959 (s), 2918 (s), 2851 (m), 1736 (s), 1688 (s), 1632 (s), 1244 (s). Synthesis of (E)-3-((5-oxo-2-phenylpyrazolidin-1-yl)methyl)-1-phenylpent-2-ene-1,4 -dione ((E)-11c): O Ph O
O Ph
N N
yellow solid mp.: 155.8-156.8 °C. 1 H-NMR (400 MHz, CDCl3, 25 °C) δ/ppm: 8.19 (s, 1H), 7.84-7.76 (m, 2H), 7.55 (t, 1H, J = 7.4 Hz), 7.42 (t, 2H, J = 7.7 Hz), 7.19 (t, 2H, J = 7.9 Hz), 7.04 (t, 1H, J = 7.3 Hz), 6.44 (d, 2H, J = 7.8 Hz), 3.84 (s, 2H), 3.54 (t, 2H, J = 7.0 Hz), 2.50-2.40 (m, 5H). 13
C-NMR (100 MHz, CDCl3, 25 °C) δ/ppm: 197.1, 193.7, 172.7, 148.5, 136.8, 132.6, 131.1, 129.4, 128.3, 127.9, 124.4, 117.0, 116.4, 54.1, 33.5, 28.3, 25.2. MS (20 eV, EI) m/z (%):348 (100) [M]+, 305 (8), 243 (32), 201 (41) , 105 (17). IR (CH2Cl2) ~ (cm−1): 3065 (w), 2982 (s), 2959 (s), 2918 (s), 2851 (m), 1736 (s), 1688 (s), 1632 (s), 1244 (s). HRMS (ESI) for C21H20N2O3Na, [M+Na]+ (371.1372) found: 371.1374.
CCDC number: 775300
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Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
VIII. Spectra of X-ray crystallography: a) X-ray crystal structure (10837.cif) of threo-4a: CCDC No. 778973 OH O
O 2N
N
O
O
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Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
b) X-ray crystal structure (10539.cif) of erythro-4h: CCDC No. 778974 Cl
OH
O
O N O
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Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
c) X-ray crystal structure (10628.cif) of (E)-8c: CCDC No. 769605
O O F3 C
N O
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Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
d) X-ray crystal structure (10628.cif) of (E)-10f: CCDC No. 770519 O O Br
N O
N
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Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
e) X-ray crystal structure (10628.cif) of (E)-11c: CCDC No. 775300 O Ph O
O Ph
N N
S43
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
3
3.06 6.54
2
1
IX. Spectra of 1H NMR and 13C NMR:
4
1.00 2.06
9 10
4.15 2.09 6.30 6.75 4.49 2.35
8
7
6
2.18 2.32 2.35
5
2.52 1.53
S44
S45 210
208.94 208.25
200 190 180 170
168.61 168.15
160 150
148.50 148.38 147.46 147.10
140 130
134.40 131.55 131.49 127.11 127.09 123.74 123.51 123.46
120 110 100 90 80 70
77.31 77.00 76.68 72.49 70.19
60
57.90 56.48
50 40 30
36.70 34.79 32.04 30.87
20 10 ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
3
2.93
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
1.00
7
6
0.99 1.07
5
2.08
8
1.92 2.16 2.04
10
9
1.91
S46
20
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
32.11
40
36.72
60
56.48
120
100
80
77.33 77.01 76.69 72.48
140
134.44 131.56 127.11 123.77 123.55
160
148.37 147.48
200
180
168.19
220
208.99
S47
3
1.71 3.00
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
9 10
1.55 0.99 0.56 3.10 4.24 0.58 1.06 0.56
8
7
6
1.59
5
0.59 1.09 2.14
4
2.06 0.59
S48
S49 210
209.09 208.24
200 190 180 170
168.69 168.13
160 150 140
148.29 143.51 143.42 134.42 134.38 132.67 132.37 131.55 131.50 129.62 129.22 123.57 123.52 122.86 122.48 121.33 121.22
130 120 110 100 90 80
77.32 77.21 77.00 76.68 72.39 70.10
70 60
58.23 56.64
50 40 30
36.66 35.00 32.01 30.96
20 ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
1.41
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
3
3.10
5
1.57 1.62
4
1.14 0.58 0.43
8 9 10
0.45 0.99 2.05 0.73 3.00 3.01 1.22 0.55 1.11
7
6
1.00
S50
S51 210
209.84 209.20
200 190 180 170
168.46 168.16
160 150
147.37 147.10 137.25 136.15 134.26 134.14 133.85 133.30 131.77 131.60 128.79 128.70 128.39 125.00 123.56 123.36
140 130 120 110 100 90 80
77.32 77.21 77.00 76.69
70
68.14 67.53
60
55.46 54.87
50 40 30
36.61 34.67 31.80 30.39
20 10 ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
3
2.98 2.26
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
1.00 0.77
7
6
2.10 1.70
5
0.87 1.09
10
9
8
7.12 1.59 3.59 2.05
S52
S53 220 210 200 190 180 170 160 150 140 130 120 110 100
209.02 208.25
168.58 168.11
146.53 146.44 134.40 132.31 132.05 131.54 131.50 126.97 126.91 123.46 118.41 118.30 111.76 111.23
90 80 70
77.31 77.00 76.68 72.70 70.40
60
57.78 56.40
50 40 30
36.69 34.82 31.98 30.84
20 10 ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
7
6
0.64 1.00
5
0.69 0.69 2.00 1.08 0.77
4
3
4.93
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
10
9
8
3.17 3.29 4.10 2.63
S54
S55 210
209.36 208.42
200 190 180 170 160
168.58 168.08 145.23 134.24 134.01 131.49 130.57 130.24 130.04 129.92 129.72 129.60 129.39 129.07 127.94 127.89 126.77 126.43 125.49 125.46 125.42 125.38 125.23 125.18 125.15 125.11 123.60 123.34 123.31 122.53 122.48 119.77
150 140 130 120 110 100 90 80
80.48 77.40 77.29 77.08 76.77 73.17 70.76
70 60
57.59 56.42
50 40
36.73 35.39 34.94 32.99 32.48 32.28 31.84 31.53 30.70 21.37 20.61 18.10
30 20 10 ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
3
4.65
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
1.06 0.53 0.99
8 9 10
2.97 3.22 1.98 1.02 2.03 1.10
7
6
0.51 1.00
5
1.04
4
2.57
S56
S57 210
209.50 208.42
200 190 180 170
168.67 168.09
160 150 140
140.23 140.09 134.28 134.25 131.72 131.60 131.46 127.96 127.89 123.46 123.38 122.00 121.52
130 120 110 100 90 80
77.32 77.21 77.00 76.68 73.10 70.83
70 60
57.89 56.41
50 40 30
36.78 35.14 32.00 31.02
20 10 ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
3
5.05
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
1.11 0.66 2.16 3.03 1.14
7
6
0.60 1.00
5
1.15
4
2.09
10
9
8
3.18 3.25
S58
S59 220 210 200 190 180 170 160 150 140 130 120 110 100
209.39 208.37
168.49 167.94
139.72 139.64 134.11 134.08 133.68 133.22 131.50 131.46 128.59 128.36 127.65 127.49 123.28 123.20
90 80 70
77.32 77.00 76.69 73.02 70.92
60
57.80 56.50
50 40 30
36.66 35.23 31.64 30.83
20 10 ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
3
2.97
5
1.05 1.06 1.02
4
1.00
8 9 10
1.95 2.00 1.01 0.98 1.00 0.99
7
6
1.00
S60
30
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30.40
50
40
34.61
60
53.65 53.63
70
68.91
120
110
100
90
80
77.32 77.21 77.00 76.69
170
160
150
140
130
137.77 134.00 131.75 131.63 129.69 128.82 127.92 126.95 123.26
210
200
190
180
168.17 209.50
S61
8 9 10
S62
3.23 3.55 2.12 2.99 3.54
7
6
0.61 1.00
5
1.28 1.11 1.08 1.04 0.61
4
3
3.16 1.82
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
S63 210
209.72 208.53
200 190 180 170
168.53 167.98
160 150 140
141.13 141.04 133.99 131.66 131.59 128.52 128.31 127.94 127.56 126.16 126.08 123.29 123.22
130 120 110 100 90 80
77.32 77.00 76.68 73.76 71.94
70 60
57.94 56.70
50 40 30
36.87 35.51 31.62 30.88
20 10 ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
3
4.83 1.41
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
0.47 0.59 0.86
4
2.25 2.14 2.16
7
6
5
1.00
10
9
8
4.05
S64
S65 210
209.72 208.50
200 190 180 170
168.37 167.81
160 150 140
138.03 137.97 137.61 137.09 133.84 133.79 131.53 131.45 129.03 128.85 126.13 125.84 123.10 123.00
130 120 110 100 90 80
77.32 77.00 76.68 73.76 71.73
70 60
57.60 56.44
50 40 30
36.69 35.44 31.36 30.67
20
20.80 20.77
10 ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
3
1.92 3.04
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
7
6
0.61 1.00
5
1.26 2.03
4
1.08 0.68 1.96 1.29
8
3.23 3.34
10
9
2.04 1.22
S66
S67 210
208.95 208.11
200 190 180 170
168.59 168.15
160 150
150.61 150.47 149.80 149.52
140 130
134.33 131.57 131.48
120
123.49 121.17 121.11
110 100 90 80 70
77.32 77.00 76.68 71.80 69.85
60
57.58 56.26
50 40 30
36.81 34.89 31.96 30.84
20 10 ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
3
3.05
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
0.56 0.59
4
1.09
7
6
1.00
5
1.28 1.94 2.51 0.62
8
0.55
10
9
1.08 1.04
S68
S69 210
209.19 208.11
200 190 180 170
168.70 168.03
160 150
148.89 148.38 147.70
140
137.35 134.73 134.46 134.33 134.23 131.60 123.66 123.58 123.45 123.40
130 120 110 100 90 80 70
77.32 77.00 76.68 71.30 69.30
60
58.45 56.76
50 40 30
36.73 35.40 31.74 31.01 30.85
20 10 ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
1.89
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
3
3.09
4
1.00 0.53
8
1.11 5.90 1.06 0.67 1.03 0.60 1.02
7
6
3.11
5
1.54
10
9
0.56 0.99
S70
S71 210
209.56 208.52
200 190 180 170
168.29 168.20
160
159.74 158.99
150
148.49 148.12
140
136.90 136.57 134.10 133.94 131.80 131.70 123.37 123.17 122.68 122.28 121.36 121.23
130 120 110 100 90 80 70
77.32 77.00 76.68 73.03 71.52
60
55.89 55.69
50 40 30
36.77 34.63 31.18 30.03
20 10 ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
3
4.75
7
0.56 0.57 0.96 0.95
5
1.00 0.57
6
2.16
4
1.23 0.65 1.06 0.64 0.91
10
9
8
3.14 3.25
S72
S73 210
209.29 207.60
200 190 180 170
168.65 168.00
160 150
153.63 153.57
140
142.24 142.02
130
134.13 134.07 131.63
120
123.37 123.29
110
110.36 110.24 107.75 107.14
100 90 80
77.32 77.00 76.68
70
67.43 65.77
60 55.26 54.40
50 40 30
36.39 35.14 31.06 30.15
20 10 ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
3
2.97
7
6
5
2.00
8
2.92 1.94 1.92
10
9
1.88
S74
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
26.05
70
60
50
40
35.06
120
110
100
90
80
77.32 77.00 76.68
130
123.69 123.16
140
141.23 139.40 138.19 134.02 131.70 129.42
160
150
147.46
200
190
180
170
167.68
210
198.05
S75
2.97
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
3
0.14
6
5
2.04
7
1.00 1.97 2.10
8
2.04
10
9
2.07
S76
30
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
40
30.53
70
60
50
40.55
120
110
100
90
80
77.32 77.21 77.00 76.68
140
130
134.36 131.86 130.85 129.39 123.83 123.66 141.61 140.95
160
150
147.64
200
190
180
170
167.70
210
203.53
S77
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
3
2.95
9 10
0.91 0.92 1.00 2.87 1.95 1.01
8
7
6
5
2.00
S78
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
25.99
70
60
50
40
34.82
120
110
100
90
80
77.32 77.00 76.69
150
140
130
139.41 137.89 136.21 134.42 133.93 131.62 129.62 123.49 123.17 123.07
160
148.07
200
190
180
170
167.58
210
198.08
S79
4
3
2.87
2
1
0
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
6
5
2.00
9 10 11 12 13
0.93 0.93 1.88 1.96 1.96
8
7
0.95
S80
30
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
40
30.41
70
60
50
40.45
120
110
100
90
80
77.32 77.20 77.00 76.68
150
140
130
140.29 136.72 134.32 131.86 130.93 129.61 123.63 123.40 123.28
160
148.29
200
190
180
170
167.69
210
203.27
S81
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
3
3.01
7
6
5
2.00
10
9
8
3.05 2.02 4.05
S82
S83 210 200
198.30
190 180 170
167.67
160 150
140.45 138.21 137.27 133.84 131.65 130.81 130.49 130.16 129.83 128.69 127.73 125.38 125.35 125.31 125.28 125.02 122.98 122.31 119.61
140 130 120 110 100 90 80
77.32 77.00 76.68
70 60 50 40 35.04
30 25.95
20 10 ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
3
2.90
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
6
5
2.00
9 10
1.87 1.99 2.01 1.95
8
7
0.94
S84
30
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
40
30.52
70
60
50
40.53
110
100
90
80
77.32 77.00 76.68
160
150
140
130
120
139.60 138.76 134.25 132.09 131.93 130.74 130.42 128.85 125.53 125.50 125.19 123.58 122.49
200
190
180
170
167.72
210
203.83
S85
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
3
3.04
7
6
5
2.00
10
9
8
2.00 3.04 2.02 1.99
S86
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
25.93
70
60
50
40
35.09
120
110
100
90
80
77.32 77.00 76.68
160
150
140
130
141.23 136.19 134.81 133.83 132.95 131.82 130.10 128.78 123.05
200
190
180
170
167.81
210
198.46
S87
1.00
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
3
2.98
6
5
2.00 0.68
8 9 10
0.69 2.63 2.95 1.97 2.76 0.68
7
0.33
S88
S89 210 204.16
200
198.45
190 180 170
167.80 167.69
160 150
141.23 138.15 136.17 134.80 134.67 134.14 133.82 133.55 132.94 132.69 131.88 131.81 130.10 129.86 128.77 128.74 123.46 123.04
140 130 120 110 100 90 80
77.32 77.00 76.68
70 60 50 40
40.49 35.09
30
30.42 25.93
20 10 ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
3
3.04
7
6
5
2.00
10
9
8
3.02 2.03 1.02 0.96 2.27
S90
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
26.02
70
60
50
40
34.98
120
110
100
90
80
77.32 77.00 76.68
160
150
140
130
139.74 137.09 133.74 133.44 133.22 131.89 130.01 129.92 129.46 126.81 123.03
200
190
180
170
167.64
210
198.42
S91
4
3
3.08
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
8 9
1.99 2.26
10
0.99 0.69 2.26 1.00
7
6
5
1.99
S92
30
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
40
30.29
70
60
50
40.17
120
110
100
90
80
77.32 77.00 76.68
160
150
140
130
138.62 134.14 133.11 132.28 132.01 130.69 130.04 129.58 126.85 123.52
200
190
180
170
167.74
210
202.97
S93
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
3
3.08
7
6
5
2.00
8
2.12 2.08 1.04 1.97
10
9
2.04
S94
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
25.99
70
60
50
40
34.95
120
110
100
90
80
77.32 77.00 76.68
130
123.14 122.86
150
140
142.65 138.89 138.28 133.97 131.64
160
149.79
200
190
180
170
167.69
210
198.10
S95
4
3
3.03
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
6
5
2.04 1.97 2.08
8
1.95
7
1.00
10
9
1.81
S96
30
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
40
30.51
70
60
50
40.48
120
110
100
90
80
77.32 77.21 77.00 76.68
130
123.63
140
134.32 131.88 130.29
150
142.77 141.08
160
150.23
200
190
180
170
167.67
210
203.55
S97
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
3
3.00
7
6
5
2.00 1.05 2.00 3.02
8
1.00
10
9
0.96 0.98
S98
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
26.03
70
60
50
40
35.07
120
110
100
90
80
77.32 77.20 77.00 76.68
150
140
130
138.71 137.75 135.99 133.95 131.83 130.61 123.32 123.21
160
149.68
200
190
180
170
167.81
210
198.20
S99
3.21
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
3
0.91
6
5
0.56 2.07 2.33 2.69 0.90 1.03 1.76
8
7
1.00
10
9
0.34 1.36 1.00
S100
S101 210 200
203.37 198.14
190 180 170
167.71 167.64
160 150
149.57 149.49 149.36 139.75 138.64 137.65 135.92 135.52 134.19 133.88 131.81 131.73 130.93 130.56 130.01 123.49 123.21 123.11
140 130 120 110 100 90 80
77.32 77.00 76.68
70 60 50 40
40.51 34.98
30
30.34 25.95
20 10 ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
5
4
3
3.06
7
6
2.00
8
2.94 1.98 1.02 0.99 0.98
10
9
0.95
S102
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
26.20
70
60
50
40
34.69
120
110
100
90
80
77.31 77.00 76.68
130
126.22 123.21 122.98
150
140
139.21 138.29 136.45 133.65 132.14 149.69
170
160
153.83
200
190
180
168.02
210
199.20
S103
2
3.09
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
3
2.06
7
6
5
2.00
10
9
8
2.17 3.07 2.09 2.04
S104
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
20
10
8.17 30.97
70
60
50
40
35.18
110
100
90
80
77.32 77.00 76.68
120
111.98 118.18
160
150
140
130
139.43 138.52 137.35 133.96 132.12 131.65 129.17 123.08
200
190
180
170
167.64
210
200.82
S105
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
3
2.95
9 10
1.96 1.87 1.95 0.96 0.98 1.93
8
7
6
5
2.00
S106
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
26.02
70
60
50
40
37.92
120
110
100
90
80
77.32 77.00 76.68
160
150
140
130
136.69 134.90 132.90 132.04 131.55 129.64 128.43 128.07 124.07
190
180
170
165.62
210
200
197.28 195.85
S107
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
3
3.98 2.90
7
6
5
2.00
8
1.02 1.84
10
9
1.88
S108
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
27.93 25.96
60
50
40
35.80
120
110
100
90
80
70
77.35 77.32 77.03 77.00 76.72 76.68
130
123.68 129.70
140
141.15 139.55 137.49
170
160
150
147.58
190
180
176.57 176.53
210
200
197.98
S109
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
3
4.01 2.96
7
6
5
2.00
10
9
8
1.90 1.00 1.92
S110
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
27.67 25.70
70
60
50
40
35.43
110
100
90
80
77.31 76.99 76.67 111.90
130
120
117.99
170
160
150
140
139.64 139.02 136.80 131.93 129.17
190
180
176.34
210
200
197.85
S111
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
2.97
3
2.93
4
1.96
7
6
5
2.00
8
2.05 0.84
10
9
1.94
S112
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
29.50 26.10
50
40
35.97
70
60
51.42
120
110
100
90
80
77.50 77.18 76.86
130
123.66 129.83 129.38
140
141.28 139.65 137.63
150
147.57
170
160
156.24
200
190
180
169.26
210
198.19
S113
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
2.98
3
2.98
4
1.99
7
6
5
2.00
9 10
0.92 0.95
8
1.01 0.99 1.00
S114
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
29.37 25.95
50
40
35.71
70
60
51.29
120
110
100
90
80
77.32 77.00 76.68
130
123.66 123.23
150
140
139.41 137.34 136.16 134.59 129.56 148.11
170
160
156.08
200
190
180
169.11
210
198.06
S115
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
2.98
3
2.97
4
1.99
7
6
5
2.00
9 10
0.96 0.97
8
1.06 1.94
S116
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
29.22 25.86
50
40
35.30
70
60
51.15
120
110
100
90
80
77.32 77.00 76.68
140
130
139.75 135.23 133.68 130.62 130.55 129.35 124.66
150
146.69
170
160
155.77
200
190
180
168.87
210
197.96
S117
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
2.98
3
2.97
4
2.05
7
6
5
2.00
10
9
8
1.93 0.99 1.93
S118
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
29.27 25.86
50
40
35.74
70
60
51.18
110
100
90
80
77.32 77.20 77.00 76.68
120
111.98
130
118.10 131.98 129.31
150
140
139.77 139.11 137.03
170
160
156.01
200
190
180
169.03
210
198.01
S119
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
2.93
3
2.94
4
2.01
7
6
5
2.00
10
9
8
1.10 1.83 1.93
S120
S121 210 200
198.25
190 180 170
169.08
160
156.07
150 140
140.26 138.19 136.62 130.79 130.47 130.14 129.83 129.13 128.87 127.78 125.22 125.18 125.08 124.90 122.38 119.67
130 120 110 100 90 80
77.32 77.00 76.68
70 60 50
51.19
40 35.96
30
29.21 25.86
20 10 ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
2.98
3
2.98
4
2.07
7
6
5
2.00
10
9
8
0.99 1.93 1.95
S122
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
29.47 25.96
50
40
36.12
70
60
51.38
120
110
100
90
80
77.31 77.20 77.00 76.68
130
123.05
140
135.70 133.41 131.68 130.41
150
141.06
170
160
156.30
200
190
180
169.23
210
198.49
S123
0.31
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
0.27 2.95
3
2.92 0.19
4
1.99
6
5
2.00 0.18 0.16
7
0.07
8
0.98 1.92
10
9
1.98 0.19
S124
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
29.31 25.90
50
40
35.89
70
60
51.20
120
110
100
90
80
77.32 77.00 76.68
130
122.79
150
140
142.40 138.64 137.55 149.77
170
160
156.01
200
190
180
169.08
210
198.05
S125
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
2.97 2.88 2.01
3
2
1.27
4
2.02
7
6
5
2.00
8
2.87
10
9
1.84
S126
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
20
10
8.11
50
40
30
36.16 30.98 29.43
70
60
51.34
120
110
100
90
80
77.32 77.00 76.68
130
123.55 129.70
140
141.33 138.10 137.27
150
147.48
170
160
156.16
200
190
180
169.13
210
200.78
S127
2
3.02 0.49
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
0.53 2.90 2.03
3
0.35 2.02
4
0.34
6
5
2.00 0.35
7
0.14 0.35
9 10
1.98 0.38
8
2.03 0.93
S128
S129 210
206.96
200
200.70
190 180 170
169.12 169.06
160 150
156.05 155.84 147.34 147.25 141.43 141.28 140.71 137.95 137.18 129.62 129.01 123.50 123.40
140 130 120 110 100 90 80
77.32 77.00 76.68
70 60 50
51.49 51.22
40
41.51 36.02 35.87 30.87 29.48 29.30
30 20 10
8.01 7.52
ppm Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
0.07 2.01
4
2.94 1.99
3
2
2.94
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
6
5
1.98 0.08
7
0.03
9 10
0.93 0.94
8
0.98 1.00 0.99 0.09
S130
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
20
10
8.09
30
30.91 29.40
50
40
35.96
70
60
51.56 51.29
120
110
100
90
80
77.32 77.00 76.68
130
123.67 123.14
150
140
138.14 136.98 136.29 134.63 129.54 148.09
170
160
156.11
200
190
180
169.16
210
200.81
S131
2.94 2.01
3
2
2.99
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
4
2.01
7
6
5
2.00
10
9
8
1.93 1.00 1.97
S132
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
20
10
8.11
50
40
30
36.15 30.92 29.43
70
60
51.32
110
100
90
80
77.32 77.00 76.68
120
112.06
130
118.23
150
140
139.38 138.55 136.82 132.10 129.42
170
160
156.16
200
190
180
169.15
210
200.84
S133
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
3
2.05 2.91
4
2.05
8 9
1.88
10
1.00 0.51 2.38 1.00 1.93
7
6
5
2.00
S134
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
40
30
28.96 26.01
50
39.30
70
60
55.58
120
110
100
90
80
77.32 77.00 76.68
130
129.26 129.07 123.89 123.16 118.56
140
140.70 139.24 138.32
170
160
150
149.49 147.10
190
180
172.72
210
200
197.85
S135
0.14
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
3
0.19 2.06
4
0.14 2.07
8
0.92 1.85 0.59 1.09 1.99 1.99 0.05
7
6
5
2.00 0.08
10
9
0.11 2.00
S136
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
40
30
29.04 26.03
50
39.54
70
60
55.58
120
110
100
90
80
77.32 77.00 76.68
130
123.98 122.65 118.62 129.15
150
140
141.93 138.56 138.52
170
160
149.58 149.54
190
180
172.77
210
200
197.86
S137
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
3
0.79 0.44 0.97
8 9 10
1.00 0.65 2.08 1.49 3.10 1.10 2.25 1.66 0.95 0.35 2.08
7
6
5
1.06 2.68
4
2.36
S138
S139 210 200
201.86 197.13 196.70 193.75
190 180 170
172.73 171.35
160 150
148.77 148.52 136.74 135.89 133.27 132.56 131.12 129.39 129.28 128.53 128.26 128.02 127.87 124.41 124.36 123.17 122.23 118.32 117.02 116.35
140 130 120 110 100 90 80
77.32 77.00 76.69
70 60 50
54.45 54.11 43.31
40 30
33.48 30.06 29.13 28.24 25.16
20 10 ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
2
1
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
3
5.10 2.05
6
5
4
2.00
8
1.97 1.00 2.02 2.01 1.02
7
1.98
10
9
0.96
S140
20
10
ppm
Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010
30
28.26 25.18
50
40
33.48
70
60
54.12
110
100
90
80
77.32 77.00 76.68
120
117.03 116.37
150
140
130
136.77 132.55 131.11 129.40 128.26 127.88 124.42
170
160
148.53
190
180
172.71
210
200
197.08 193.71
S141