Organocatalytic Tandem Three-Component Reaction of Aldehyde

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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.

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)

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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:

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VII. Spectra data of compounds 4a-n, 8a-j, 9a-b, 10a-j and 11a-c

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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

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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

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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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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

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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

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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.

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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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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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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

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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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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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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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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

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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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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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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

S41

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

S42

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

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