Substituted Oxindoles Azomethine Ylide Route Synthesis of ... · 1 Direct N-H/α, α, β,...

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Direct N-H/α, α, β, β-C(sp3)-H functionalization of Piperidine via an

Azomethine Ylide Route：Synthesis of Spirooxindoles Bearing 3-

Substituted OxindolesYanlong Du, Aimin Yu, * Jiru Jia, Youquan Zhang and Xiangtai Meng*

Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion, School of Chemistry & Chemical Engineering, Tianjin University of Technology, Tianjin 300384, P. R. China. E-mail: [email protected], [email protected]

Contents

1. General information and materials……………………………………………………….... 2

2. Synthesis of N-protected isatins 1…………………………………………………………..3

3. Synthesis of 3 …………………………………………………………................................4

4. Optimization of the domino reaction…………………………………….………………… 6

5. Crystal structures of 4b, 5f and 7……………………………………………………………7

6. General procedure for the synthesis of 4…………………………………………………….8

7. NMR spectra data (1H NMR, 13C NMR)…………………………………………………….8

Electronic Supplementary Material (ESI) for ChemComm.This journal is © The Royal Society of Chemistry 2017

mailto:[email protected]

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1. General information and materials

All reactions were performed under Ar atmospheres in oven-dried glassware with magnetic stirring. Unless otherwise stated, all reagents including isatins, 1w, 3d, 3-bromoprop-1-ene, sodium benzenesulfinate, sodium 4-methylbenzenesulfinate, sodium 4-chlorobenzenesulfinate, 1H-indene-1,2,3-trione, phenanthrene-9,10-dione and 9H-fluoren-9-one were purchased from commercial suppliers (Aldrich, TCI or Alfa Aesar) and used without further purification. All solvents were purified and dried according to standard methods prior to use. TLC monitored all reactions with silica gel-coated plates. Flash column chromatography was performed using 200-300 mesh silica gel. 1H- and 13C-NMR spectrum was recorded at ambient temperature on Bruker 400 instruments. All spectra were referenced to CDCl3 (1H δ 7.26 ppm and 13C NMR δ 77.00 ppm). HRMS were obtained on Waters Xevo Q-TOF MS with ESI resource. Melting points were measured on a RY-I apparatus and are reported uncorrected. Compound 1x was synthesized according to literature.1 Compounds 3e 2, 3f 3 were synthesized according to literatures.

1. J. H. Yao, C. Chi, J. Wu and K.-P. Loh Chem. Eur. J., 2009, 15, 9299-9302.2. F. Caturla and C. Nájera, Tetrahedron, 1996, 52, 15243-15256.3. T. Llamas, R. Gómez, Arrayás and J. C. Carretero, Org. Lett., 2006, 8, 1795-1798.

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2. Synthesis of N-protected isatins 1

NH

O

OR1

CH3I

ClCH2OCH2CH3

PhCH2Br

+ NaHDMF

N

O

OR1

R2

R2 = CH3, CH2OCH2CH3,PhCH2

1

Under Ar atmosphere, to a solution of isatin (10 mmol, 1.0 eq) in DMF 45 ml was added NaH (12 mmol, 1.2 eq.) in portions at 0 oC. After stirring for 5 min, MeI (12 mmol, 1.2 eq.), ClCH2OCH2CH3 (12 mmol, 1.2 eq.) or BnBr (12 mmol, 1.2 eq.) was added to the above mixture slowly. After warming to room temperature, the reaction mixture was stirred for 12-20 h. The reaction was then quenched by water and extracted with EtOAc. The organic layer was separated and washed with water, then the ethyl acetate layer was dried over MgSO4, filtered and concentrated in vacuum. The crude product was purified by chromatography (SiO2, ethyl acetate : petroleum ether = 1:2). The spectral data consist with the data reported in the literatures.

Entry R1 R2 Time (h) Yield (%)

1 5-CH3 (1a) 4 CH3 16 822 H (1b) 4 CH3 16 893 5-CH3O (1c) 4 CH3 12 984 5-tBu (1d) 5 CH3 16 905 5-F (1e) 4 CH3 20 696 5-Cl (1f) CH3 16 787 5-Br (1g)6 CH3 16 758 5-OCF3 (1h)7 CH3 16 589 5-NO2 (1i)6 CH3 16 4610 5,6-F2 (1j) CH3 12 6411 6-Br (1k)8 CH3 16 7712 7-CH3 (1l) 4 CH3 12 8613 7-Cl (1m)9 CH3 16 7614 7-Br (1n)10 CH3 16 7015 4-Br (1o)8 CH3 16 6616 H (1p) CH2OEt 12 8017 5-CH3 (1q) CH2OEt 12 8318 5-Br (1r) CH2OEt 12 6719 H (1s) 4 CH2Ph 12 8820 5-CH3 (1t)11 CH2Ph 12 8621 5-Cl (1u)11 CH2Ph 12 9022 5-Br (1v)12 CH2Ph 12 71

The spectral data of known N-methyl isatins as below:4. B.-X. Tang, R.-J. Song, C.-Y. Wu, Y. Liu, M.-B. Zhou, W.-T. Wei, G.-B. Deng, D.-L. Yin, and J.-H. Li, J. Am. Chem. Soc., 2010, 132, 8900-8902.

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5. W. Li, Z. Duan, X. Zhang, H. Zhang, M. Wang, R. Jiang, H. Zeng, C. Liu and A. Lei, Angew. Chem. Int. Ed., 2015, 54, 1893-1896. 6. A. Beauchard, Y. Ferandin, S. Frère, O. Lozach, M. Blairvacq, L. Meijer, V. Thiéry and T. Besson, Bioorg. Med. Chem., 2006, 14, 6434-6443.7. A. D. Mamuye, S. Monticelli, L. Castoldi, W. Holzer and V. Pace, Green Chem., 2015, 17, 4194-41978. Y. Wang, W. Li, X. Cheng, Z. Zhan, X. Ma, L. Guo, H. Jin and Y. Wu, Tetrahedron, 2016, 72, 3193-3197.9. Q. Gui, F. Dai, J. Liu, P. Chen, Z. Yang, X. Chen and Z. Tan, Org. Biomol. Chem., 2014, 12, 3349-335310. K. Engen, J. Sävmarker, U. Rosenström, J. Wannberg, T. Lundbäck, A. Jenmalm-Jensen and M. Larhed, Org. Process Res. Dev., 2014, 18, 1582-1588.11. G. Satish, A. Polu, T. Ramar and A. Ilangovan, J. Org. Chem., 2015, 80, 5167-5175.12. K. Aikawa, S. Mimura, Y. Numata and K. Mikami, Eur. J. Org. Chem., 2011, 62-65

3. Synthesis of 3

BrRSO2Na

EtOH, RefluxRO2S

Br2CCl4

RO2S BrBr

Et3N

THFRO2S Br

RSO2Na

MeOH, RefluxRO2S SO2R

A B

C 3

R = Ph, 3aR = p-ClPh, 3bR = p-CH3Ph, 3c

Entry R A B C 31 Ph 89% 85% 65% 3a, 87%2 p-ClC6H4 75% 80% 62% 3b, 94%3 p-CH3C6H4 88% 89% 90% 3c, 84%

3a as an exampleUnder Ar atmosphere, to a well stirred ethanol (60 mL) solution of sodium benzenesulfinate (10.00 g,

82.60 mmol) was added 3-bromoprop-1-ene (13.57 g, 82.66 mmol). The reaction mixture was refluxed for 4 h. After cooling to room temperature, the reaction mixture was filtrated and removed the white solid. The filtrate was concentrated under vacuum and the crude product A (13.4 g, 89%) was taken for the next reaction.

To a well stirred CCl4 (26 mL) solution of A (13 g, 71.34 mmol) was added a CCl4 (10 mL) solution of Br2 (11.96 g, 74.90 mmol) dropwise. After completion of the reaction (monitored by TLC), the reaction was quenched by addition of saturated aqueous NaHSO3 solution and extracted by CH2Cl2 (50

5

mL × 3). The organic layer was separated and dried over anhydrous Na2SO4. The organic layer was concentrated under vacuum, and the crude product B (20.82 g, 85%) was taken for the next reaction.

To a THF (55 mL) solution of B (20 g, 58.47 mmol) was added Et3N (6.21 g, 61.39 mmol) dropwise at 0 oC, and the reaction mixture was stirred under the same temperature for 1 h. After completion of the reaction (monitored by TLC), the reaction was acidified by addition of HCl (1M) and extracted by CH2Cl2 (50 mL × 3). The combined organic extract was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was recrystallized (ethanol) to afford the pure product C (10.34 g, 65%).

To a CH3OH (25 mL) solution of C (5.00 g, 19.15 mmol) was added sodium benzenesulfinate (6.29 g, 38.30 mmol), and the reaction mixture was refluxed for 3 h. After completion of the reaction (monitored by TLC), the reaction was quenched by addition of 30 mL saturated aqueous ammonium chloride solution. The organic layer was extracted with CH2Cl2 (30 mL×3), and then washed with a saturated aqueous sodium bicarbonate solution. The combined organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product (3a, 5.4 g, 87%) was used in the next step without further purification. The spectral data (3a, 3b) consist with the data reported in the literatures.13

13. (a) P. R. Joshi, S. Undeela, D. D. Reddy, K. K. Singarapu and R. S. Menon, Org. Lett., 2015, 17, 1449-1452. (b) C. Nájera, A. Pérez-Pinar and J. M. Sansano, Tetrahedron, 1991, 47, 6337-6352.

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4. Optimization of the domino reaction

N

O

O

SO2Ph

NH

NO

N

NO

PhO2S

1a 3a2

+ +Additive

Solvent, T

4a

SO2Ph

PhO2SH

Entry Ratio Additive Solvent T (oC) Yield (%)

1 1.2:1.2:1 4-TFBA (0.1) toluene 110 422 1.2:1.2:1 4-TFBA (0.3) toluene 110 513 1.2:1.2:1 4-TFBA (0.5) toluene 110 544 1.2:1.2:1 4-TFBA (0.7) toluene 110 505 1.2:1.2:1 4-TFBA (1.2) toluene 110 686 1.2:1.2:1 4-TFBA toluene 90 407 1.2:1.2:1 4-TFBA toluene 70 trace8 1.2:1.2:1 4-TFBA toluene 50 trace9 1.4:1.2:1 4-TFBA toluene 110 7010 1.6:1.2:1 4-TFBA toluene 110 6411 1.8:1.2:1 4-TFBA toluene 110 6212 2.4:1.2:1 4-TFBA toluene 110 66

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5. Crystal structures of 4b, 5f and 7

NO

N

NO

PhO2S

4b

PhO2SH

Crystal structure of 4b

N

O

TsO

Ts

H

Crystal structure of 5f

8

NO

N

NO

SO2N

H

Crystal structure of 7

6. General procedure for the synthesis of 4 4a as an example

To a stirred solution of 3a (100 mg, 0.31 mmol) in toluene (2 mL), 4-(trifluoromethyl)benzoic acid

(59 mg, 0.31 mmol), piperidine (32 mg, 0.37 mmol), and 1a (65 mg, 0.37 mmol) were added under

argon atmosphere, and the reaction mixture was stirred for 1 h at 110 oC. After the reaction complete

(monitored by TLC), the reaction was quenched by the addition of water (5 mL), extracted by CH2Cl2

(10 mL×3 ). Combined the organic phase and washed with saturated NaHCO3 solution (10 mL×3 ), and

dried with Na2SO4. The solvent was evaporated and the reside was purified by silica-gel column

chromatography (ethyl acetate : petroleum ether = 1:1) to give 4a (93 mg, 70%) as colorless solid.

7. NMR spectra data

5,6-difluoro-1-methylindoline-2,3-dione (1j): 64%, red solid; Rf (ethyl acetate : petroleum ether = 1:2) = 0.60; m.p. 138-139 oC; IR(KBr): 3063, 1738, 1627, 1615, 1498, 1474, 1434, 1388 1247, 1104 cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 7.47 (t, J = 7.8 Hz, 1H), 6.75 (dd, J = 9.2, 5.6 Hz, 1H), 3.24

(s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ = 180.88, 157.75, 156.93 (dd, J = 260.7, 14.2 Hz), 149.08 (dd, J = 10.0, 1.6 Hz), 147.30 (dd, J = 246.2, 13.6 Hz), 114.72 (dd, J = 19.3, 2.9 Hz), 112.65 (t, J = 4.5 Hz), 100.59 (d, J = 23.3 Hz), 26.41 ppm; ESI-HRMS: calcd. For C9H5F2NO2+H 198.0367, found 198.0371.

N

O

OF

F

9

1-(ethoxymethyl)indoline-2,3-dione (1p): 80%, yellow solid; Rf (ethyl acetate : petroleum ether = 1:2) = 0.50; m.p. 81-82 oC; IR(KBr): 2975, 1741, 1727, 1605, 1470, 1343, 1287, 1222, 1191, 1095, 1077 cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 7.52 – 7.77 (m, 2H), 7.02 – 7.21 (m, 2H), 5.18 (s, 2H), 3.56 (q, J = 7.0 Hz, 2H), 1.18 (t, J = 7.0 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ =

182.91, 158.22, 150.22, 138.53, 125.30, 124.16, 117.46, 111.59, 70.08, 64.63, 14.76 ppm; ESI-HRMS: calcd. For C11H11NO3+H 206.0817, found 206.0815.

1-(ethoxymethyl)-5-methylindoline-2,3-dione (1q): 83%, orange solid;

Rf (ethyl acetate : petroleum ether = 1:2) = 0.55; m.p. 94-95 oC; IR(KBr):

2970, 1745, 1735, 1619, 1598, 1491, 1456, 1355, 1331, 1298, 1220, 1096 cm-

1; 1H NMR (400 MHz, Chloroform-d) δ = 7.34 – 7.51 (m, 2H), 7.02 (d, J =

8.0 Hz, 1H), 5.15 (s, 2H), 3.55 (q, J = 6.8 Hz, 2H), 2.33 (s, 3H), 1.17 (t, J = 7.0 Hz, 3H) ppm; 13C

NMR (100 MHz, CDCl3) δ = 183.14, 158.39, 148.08, 139.03, 134.03, 125.52, 117.49, 111.39, 70.06,

64.54, 20.63, 14.76 ppm; ESI-HRMS: calcd. For C12H13NO3+H 220.0974, found 220.0977.

5-bromo-1-(ethoxymethyl)indoline-2,3-dione (1r): 67%, orange solid; Rf (ethyl acetate : petroleum ether = 1:2) = 0.48; m.p. 103-104 oC; IR(KBr): 2968, 1746, 1607, 1473, 1441, 1348, 1320, 1284, 1223, 1093, 1077 cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 7.87 – 7.63 (m, 2H), 7.07 (dd, J = 8.2, 0.6 Hz, 1H), 5.18 (s, 2H), 3.56 (q, J = 7.0 Hz, 2H), 1.19 (t,

J = 7.0 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ = 181.81, 157.44, 148.89, 140.80, 128.05, 118.63, 117.16, 113.43, 70.18, 64.75, 14.75 ppm; ESI-HRMS: calcd. For C11H10BrNO3+H 283.9922, found 283.9915.

(E)-4,4'-(prop-1-ene-1,3-diyldisulfonyl)bis(chlorobenzene) (3b):

white solid; Rf (ethyl acetate : petroleum ether = 1:2) = 0.47; m.p.

135-136 oC; IR(KBr): 2361, 2342, 1577, 1559, 1473, 1396, 1320,

1279, 1150, 1086, 1012 cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 7.65 – 7.85 (m, 4H), 7.49 – 7.65

(m, 2H), 7.40 – 7.49 (m, 2H), 6.81 (dt, J = 15.4, 7.8 Hz, 1H), 6.37 (d, J = 15.2 Hz, 1H), 3.95 (d, J = 7.6

Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ = 141.37, 140.93, 138.51, 137.60, 135.96, 131.49,

129.86, 129.78, 129.71, 129.33, 57.73 ppm; ESI-HRMS: calcd. For C15H12Cl2S2O4+H 390.9632, found

390.9626.

Following the general procedure, treatment of 1a (65 mg, 0.37 mmol) with 2 (32 mg, 0.37 mmol),

3a(100 mg, 0.31 mmol) and 4-TFBA (59 mg, 0.31 mmol) in toluene (2 mL) at 110 oC for 1 h followed

by column chromatography afforded the product 4a:

8'-(1,5-dimethyl-2-oxoindolin-3-yl)-1,5-dimethyl-1'-(phenylsulfonyl)-

2'-((phenylsulfonyl)methyl)-1',5',6',7'-tetrahydro-2'H-spiro[indoline-

3,3'-indolizin]-2-one (4a); 93 mg; white solid; Rf (ethyl acetate :

NO

N

NO

PhO2SPhO2S

H

N

O

O

CH2OEt

N

O

O

CH2OEt

N

O

O

CH2OEt

Br

SO2

SO2

Cl Cl

10

petroleum ether = 1:1) = 0.45; m.p. 215-216 oC; IR(KBr): 3059, 2926, 2841, 2356, 2343, 1700, 1621,

1499, 1447, 1363, 1353, 1324, 1312, 1282, 1204, 1169, 1144, 1084 cm-1; 1H NMR (400 MHz,

Chloroform-d) δ = 8.10 (d, J = 7.6 Hz, 2H), 7.69-7.77 (m, 2H), 7.56 (t, J = 8.0 Hz, 4H), 7.45 – 7.51 (m,

2H), 7.23 (s, 1H), 7.14 (d, J = 7.6 Hz, 1H), 7.07 (d, J = 7.6 Hz, 1H), 6.71 (dd, J = 8.0, 2.0 Hz, 2H),

5.74 (s, 1H), 5.35 (s, 1H), 4.36 (d, J = 7.6 Hz, 1H), 4.03 (dd, J = 14.8, 2.4 Hz, 1H), 3.80 (dd, J = 14.8,

11.6 Hz, 1H), 3.23 (s, 3H), 3.20 (s, 3H), 2.88 (ddd, J = 11.6, 7.4, 2.2 Hz, 1H), 2.40 (s, 3H), 2.28 (s, 3H),

2.12 (dd, J = 7.2, 3.6 Hz, 2H), 1.60 – 1.72 (m, 2H), 1.30 – 1.48 (m, 2H) ppm; 13C NMR (100 MHz,

CDCl3) δ = 177.20, 174.18, 143.38, 141.80, 137.94, 134.62, 134.26, 133.70, 133.55, 132.30, 131.87,

131.28, 130.50, 130.33, 128.89, 128.70, 128.58, 128.56, 128.26, 128.12, 125.68, 125.51, 125.47,

124.95, 124.59, 108.46, 108.28, 107.36, 71.87, 69.86, 56.75, 49.83, 42.14, 41.33, 26.31, 26.21, 22.64,

21.27, 21.03, 20.76 ppm; ESI-HRMS: calcd. For C40H39N3O6S2+H 722.2359, found 722.2358.

Following the general procedure, treatment of 1b (60 mg, 0.37 mmol) with 2

(32 mg, 0.37 mmol), 3a (100 mg, 0.31 mmol) and 4-TFBA (59 mg, 0.31

mmol) in toluene (2 mL) at 110 oC for 1 h followed by column

chromatography afforded the product 4b:

1-methyl-8'-(1-methyl-2-oxoindolin-3-yl)-1'-(phenylsulfonyl)-2'-((phenylsulfonyl)methyl)-

1',5',6',7'-tetrahydro-2'H-spiro[indoline-3,3'-indolizin]-2-one (4b); 94 mg; white solid; Rf (ethyl

acetate : petroleum ether = 1:1) = 0.42; m.p. 205-206 oC; IR (KBr): 3055, 2925, 2841, 1709, 1613,

1493, 1470, 1447, 1422, 1374, 1346, 1310, 1279, 1209, 1184, 1145, 1134, 1084 cm-1; 1H NMR (400

MHz, Chloroform-d) δ = 8.20 (d, J = 7.6 Hz, 2H), 7.67 – 7.76 (m, 2H), 7.60 (t, J = 7.8 Hz, 2H), 7.55 (d,

J = 4.4 Hz, 4H), 7.45 (d, J = 7.2 Hz, 1H), 7.36 (td, J = 8.3, 1.2 Hz, 1H), 7.26 – 7.31 (m, 1H), 7.12 (t, J

= 7.4 Hz, 1H), 6.99 (t, J = 7.4 Hz, 1H), 6.82 (dd, J = 8.0, 4.0 Hz, 2H), 6.16 (d, J = 7.2 Hz, 1H), 5.41 (s,

1H), 4.40 (d, J = 7.6 Hz, 1H), 4.02 (dd, J = 14.6, 2.2 Hz, 1H), 3.71 (dd, J = 14.8, 11.6 Hz, 1H), 3.26 (s,

3H), 3.23 (s, 3H), 3.07 (ddd, J = 11.6, 7.6, 2.4 Hz, 1H), 2.04 – 2.17 (m, 2H), 1.54 – 1.74 (m, 2H), 1.26

– 1.47 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ = 177.18, 174.34, 145.68, 144.13, 138.23, 134.76,

134.42, 133.66, 133.50, 131.27, 130.52, 130.31, 129.04, 128.59, 128.49, 127.88, 125.40, 124.09,

123.84, 122.89, 122.69, 108.81, 108.57, 107.64, 71.98, 69.58, 56.78, 49.71, 42.26, 41.15, 26.28, 26.17,

22.61, 20.72 ppm; ESI-HRMS: calcd. For C38H35N3O6S2+Na 716.1865, found 716.1875.

Following the general procedure, treatment of 1c (71 mg, 0.37 mmol) with 2 (32 mg, 0.37 mmol),

3a(100 mg, 0.31 mmol) and 4-TFBA (59 mg, 0.31 mmol) in toluene (2 mL) at 110 oC for 1 h followed

by column chromatography afforded the product 4c:

5-methoxy-8'-(5-methoxy-1-methyl-2-oxoindolin-3-yl)-1-

methyl-1'-(phenylsulfonyl)-2'-((phenylsulfonyl)methyl)-

1',5',6',7'-tetrahydro-2'H-spiro[indoline-3,3'-indolizin]-2-one

NO

N

NO

PhO2SPhO2S

H

NO

N

NO

PhO2SPhO2S

H3CO

OCH3H

11

(4c); 110 mg; white solid; Rf (ethyl acetate : petroleum ether = 1:1) = 0.30; m.p. 218-219 oC; IR(KBr):

3003, 2926, 2841, 2357, 2343, 1699, 1671, 1542, 1521, 1507, 1498, 1473, 1447, 1363, 1313, 1288,

1142, 1084 cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 8.15 (d, J = 7.2 Hz, 2H), 7.67 – 7.75 (m, 2H),

7.51 – 7.64 (m, 6H), 7.20 – 7.22 (m, 1H), 6.86 (dd, J = 8.4, 2.4 Hz, 1H), 6.77 – 6.82 (m, 1H), 6.71 (dd,

J = 8.4, 4.8 Hz, 2H), 5.77 (d, J = 2.4 Hz, 1H), 5.38 (s, 1H), 4.39 (d, J = 7.6 Hz, 1H), 4.04 (dd, J = 14.6,

2.2 Hz, 1H), 3.87 (s, 3H), 3.75 (s, 3H), 3.68 – 3.75 (m, 1H), 3.23 (s, 3H), 3.18 (s, 3H), 2.98 (ddd, J =

11.6, 7.6, 2.2 Hz, 1H), 2.00 – 2.15 (m, 2H), 1.67 – 1.78 (m, 1H), 1.21 – 1.56 (m, 3H) ppm; 13C NMR

(100 MHz, CDCl3) δ = 176.68, 173.69, 156.35, 156.01, 139.17, 138.16, 137.61, 134.79, 134.34, 133.63,

133.53, 131.28, 130.05, 129.01, 128.53, 128.50, 126.45, 114.42, 112.67, 111.07, 111.05, 109.18,

108.91, 107.95, 72.22, 69.55, 56.73, 55.87, 55.71, 50.04, 42.27, 41.26, 26.33, 26.16, 22.50, 20.75 ppm;

ESI-HRMS: calcd. For C40H39N3O8S2+H 754.2257, found 754.2244.

Following the general procedure, treatment of 1d (81 mg, 0.37 mmol) with 2 (32 mg, 0.37 mmol), 3a

(100 mg, 0.31 mmol) and 4-TFBA (59 mg, 0.31 mmol) in toluene (2 mL) at 110 oC for 1 h followed by

column chromatography afforded the product 4d:

5-(tert-butyl)-8'-(5-(tert-butyl)-1-methyl-2-oxoindolin-3-yl)-1-

methyl-1'-(phenylsulfonyl)-2'-((phenylsulfonyl)methyl)-1',5',6',7'-

tetrahydro-2'H-spiro[indoline-3,3'-indolizin]-2-one (4d); 127 mg;

white solid; Rf (ethyl acetate : petroleum ether = 1:1) = 0.65; m.p. 213-

214 oC; IR(KBr): 3059, 2954, 2908, 2358, 2342, 1710, 1622, 1500,

1472, 1459, 1447, 1369, 1348, 1311, 1279, 1209, 1143, 1082 cm-1; 1H

NMR (400 MHz, Chloroform-d) δ = 8.15 (d, J = 7.2 Hz, 2H), 7.68 – 7.75 (m, 2H), 7.53 – 7.67 (m, 7H),

7.34 (dd, J = 8.4, 2.0 Hz, 1H), 7.27 – 7.31 (m, 1H), 6.73 (d, J = 8.0 Hz, 2H), 6.36 (d, J = 2.0 Hz, 1H),

5.39 (s, 1H), 4.44 (d, J = 8.0 Hz, 1H), 4.03 (dd, J = 14.8, 2.0 Hz, 1H), 3.73 (dd, J = 14.8, 11.6 Hz, 1H),

3.24 (s, 3H), 3.18 (s, 3H), 3.09 (ddd, J = 11.6, 7.6, 2.0 Hz, 1H), 1.96 – 2.14 (m, 2H), 1.49 – 1.77 (m,

3H), 1.38 (s, 9H), 1.33 – 1.36 (m, 1H), 1.31 (s, 9H) ppm; 13C NMR (100 MHz, CDCl3) δ = 177.27,

173.92, 146.22, 145.60, 143.31, 141.71, 138.63, 134.75, 134.11, 133.71, 133.59, 131.24, 129.02,

128.52, 128.51 128.49, 126.70, 124.90, 124.08, 121.80, 120.84, 109.25, 107.74, 106.83, 72.33, 69.50,

56.77, 49.91, 42.36, 41.00, 34.72, 34.61, 31.65, 31.61, 26.23, 25.93, 22.63, 20.77 ppm; ESI-HRMS:

calcd. For C46H51N3O6S2+H 806.3298, found 806.3295.

Following the general procedure, treatment of 1e (67 mg, 0.37 mmol) with 2 (32 mg, 0.37 mmol), 3a


column chromatography afforded the product 4e:

5-fluoro-8'-(5-fluoro-1-methyl-2-oxoindolin-3-yl)-1-methyl-1'-

(phenylsulfonyl)-2'-((phenylsulfonyl)methyl)-1',5',6',7'-tetrahydro-N

O

N

NO

PhO2SPhO2S

F

FH

NO

N

NO

PhO2SPhO2S

tBu

tBuH

12

2'H-spiro[indoline-3,3'-indolizin]-2-one (4e); 71 mg; white solid; Rf (ethyl acetate : petroleum ether =

1:1) = 0.51; m.p. 210-211oC; IR(KBr): 3048, 2950, 2902, 2351, 2340, 1710, 1612, 1510, 1479, 1459,

1437, 1368, 1348, 1301, 1249, 1209, 1113, 1081 cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 8.16 (d,

J = 7.6 Hz, 2H), 7.71 – 7.78 (m, 2H), 7.57 – 7.64 (m, 6H), 7.22 – 7.25 (m, 1H), 7.05 (td, J = 8.8, 2.8

Hz, 1H), 6.98 (td, J = 8.6, 2.4 Hz, 1H), 6.74 (td, J = 8.8, 4.0 Hz, 2H), 5.86 (dd, J = 7.8, 2.6 Hz, 1H),

5.39 (s, 1H), 4.35 (d, J = 7.6 Hz, 1H), 4.01 (dd, J = 14.6, 2.2 Hz, 1H), 3.70 (dd, J = 14.6, 11.6 Hz, 1H),

3.25 (s, 3H), 3.22 (s, 3H), 3.00 (ddd, J = 11.8, 7.6, 2.2 Hz, 1H), 2.02 – 2.20 (m, 2H), 1.59 – 1.77 (m,

2H), 1.23 – 1.50 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ = 176.63, 173.89, 160.60 (d, J = 31.0

Hz), 158.20 (d, J = 33.0 Hz), 141.68 (d, J = 1.8 Hz), 140.11 (d, J = 1.6 Hz), 138.12, 135.01, 134.67,

133.83, 133.31, 131.22, 130.20 (d, J = 8.1 Hz), 129.14, 128.71, 128.39, 126.99 (d, J = 7.7 Hz), 116.46

(d, J = 23.3 Hz), 114.16 (d, J = 23.4 Hz), 112.40, 112.14 (d, J = 2.0 Hz), 111.88, 109.21 (d, J = 7.8 Hz),

108.60, 108.05 (d, J = 8.0 Hz), 72.05, 69.44, 56.61, 49.99, 42.29, 41.16, 26.43, 26.31, 22.53, 20.66

ppm; ESI-HRMS: calcd. For C38H33N3O6S2F2+H 730.1857, found 730.1836.

Following the general procedure, treatment of 1f (73 mg, 0.37 mmol) with 2 (32 mg, 0.37 mmol), 3a


column chromatography afforded the product 4f:

5-chloro-8'-(5-chloro-1-methyl-2-oxoindolin-3-yl)-1-methyl-1'-

(phenylsulfonyl)-2'-((phenylsulfonyl)methyl)-1',5',6',7'-tetrahydro-

2'H-spiro[indoline-3,3'-indolizin]-2-one (4f); 107 mg; white solid; Rf

(ethyl acetate : petroleum ether = 1:1) = 0.55; m.p. 190-191 oC; IR(KBr):

3056; 2953, 2913, 2358, 2343, 1716, 1685, 1558, 1542, 1490, 1436,

1339, 1320, 1309, 1281, 1216, 1145, 1082 cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 8.21 (d, J =

7.6 Hz, 2H), 7.67 – 7.78 (m, 2H), 7.52 – 7.65 (m, 6H), 7.31 – 7.36 (m, 1H), 7.24 – 7.28 (m, 1H), 7.17 –

7.22 (m, 1H), 6.99 – 7.05 (m, 1H), 6.86 – 6.93 (m, 1H), 6.05 (d, J = 7.2 Hz, 1H), 5.39 (s, 1H), 4.35 (d,

J = 7.6 Hz, 1H), 3.99 (dd, J = 14.4, 2.0 Hz, 1H), 3.61 – 3.66 (m, 4H), 3.57 (s, 3H), 3.07 (ddd, J = 11.6,

7.8, 2.2 Hz, 1H), 2.02 – 2.20 (m, 2H), 1.65 – 1.77 (m, 1H), 1.28 – 1.59 (m, 3H) ppm; 13C NMR (100

MHz, CDCl3) δ = 177.11, 174.67, 141.51, 139.88, 138.38, 134.96, 134.56, 133.78, 132.55, 133.40,

131.27, 131.19, 130.25, 129.10, 128.67, 128.34, 128.23, 123.63, 123.49, 122.62, 122.34, 116.15,

115.06, 108.96, 71.59, 69.32, 56.58, 49.56, 42.33, 41.38, 29.62, 29.59, 22.53, 20.67 ppm;

C38H33N3O6S2Cl2+H 762.1266, found 762.1245.

Following the general procedure, treatment of 1g (89 mg, 0.37 mmol) with 2 (32 mg, 0.37 mmol), 3a


column chromatography afforded the product 4g:

NO

N

NO

PhO2SPhO2S

Cl

ClH

13

5-bromo-8'-(5-bromo-1-methyl-2-oxoindolin-3-yl)-1-methyl-1'-

(phenylsulfonyl)-2'-((phenylsulfonyl)methyl)-1',5',6',7'-tetrahydro-2'H-

spiro[indoline-3,3'-indolizin]-2-one (4g); 102 mg; white solid; Rf (ethyl

acetate : petroleum ether = 1:1) = 0.55; m.p. 198-199 oC; IR(KBr): 3057,

2913, 1840, 2358, 2342, 1715, 1609, 1488, 1474, 1447, 1434, 1362, 1340,

1319, 1278, 1214, 1182, 1140, 1084 cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 7.94 (d, J = 7.6 Hz,

2H), 7.72 – 7.85 (m, 2H), 7.68 (t, J = 7.8 Hz, 2H), 7.56 (t, J = 7.8 Hz, 2H), 7.45 – 7.53 (m, 4H), 7.42

(dd, J = 8.0, 2.0 Hz, 1H), 6.71 (dd, J = 8.4, 6.4 Hz, 2H), 5.96 (d, J = 2.0 Hz, 1H), 5.36 (s, 1H), 4.31 (d,

J = 7.2 Hz, 1H), 4.03 (dd, J = 14.8, 2.2 Hz, 1H), 3.79 (dd, J = 14.8, 11.8 Hz, 1H), 3.24 (s, 3H), 3.21 (s,

3H), 2.74 (ddd, J = 11.8, 7.6, 2.0 Hz, 1H), 2.08 – 2.18 (m, 2H), 1.59 – 1.73 (m, 2H), 1.34 – 1.51 (m,

2H) ppm; 13C NMR (100 MHz, CDCl3) δ = 176.39, 173.46, 144.92, 143.23, 137.32, 134.95, 134.72,

133.80, 133.17, 132.93, 131.05, 130.93, 130.47, 129.23, 128.79, 128.73, 127.84, 127.21, 126.98,

115.54, 115.16, 110.10, 109.15, 107.99, 71.64, 69.61, 56.50, 49.71, 42.12, 41.37, 26.39, 26.34, 22.52,

20.65 ppm; ESI-HRMS: calcd. For C38H33N3O6S2Br2+H 850.0256, found 850.0240.

Following the general procedure, treatment of 1h (91 mg, 0.37 mmol) with 2 (32 mg, 0.37 mmol), 3a

(100 mg, 0.31 mmol) and 4-TFBA (59 mg, 0.31 mmol) in toluene (2 mL) at 110 oC for 1.5 h followed

by column chromatography afforded the product 4h:

1-methyl-8'-(1-methyl-2-oxo-5-(trifluoromethoxy)indolin-3-yl)-1'-

(phenylsulfonyl)-2'-((phenylsulfonyl)methyl)-5-(trifluoromethoxy)-

1',5',6',7'-tetrahydro-2'H-spiro[indoline-3,3'-indolizin]-2-one (4h);

84 mg; white solid; Rf (ethyl acetate : petroleum ether = 1:1) = 0.55;

m.p. 169-170 oC; IR(KBr): 3064, 2936, 2844, 2358, 2342, 1747, 1649,

1623, 1541, 1507, 1497, 1473, 1313, 1261, 1217, 1168, 1146, 1086 cm-1; 1H NMR (400 MHz,

Chloroform-d) δ = 8.10 (d, J = 7.6 Hz, 2H), 7.70 – 7.79 (m, 2H), 7.52 – 7.67 (m, 6H), 7.35 (d, J = 2.4

Hz, 1H), 7.13 – 7.24 (m, 2H), 6.80 (dd, J = 8.4, 6.0 Hz, 2H), 6.03 (s, 1H), 5.39 (s, 1H), 4.36 (d, J = 7.6

Hz, 1H), 4.00 (dd, J = 14.8, 2.0 Hz, 1H), 3.71 (dd, J = 14.4, 11.6 Hz, 1H), 3.26 (s, 3H), 3.23 (s, 3H),

3.00 (ddd, J = 11.6, 7.6, 2.9 Hz, 1H), 2.02 – 2.16 (m, 2H), 1.60 – 1.76 (m, 1H), 1.23 – 1.55 (m, 3H)

ppm; 13C NMR (100 MHz, CDCl3) δ = 176.71, 173.86, 145.07, 144.79, 144.33, 142.79, 137.99, 135.10,

134.66, 133.91, 133.13, 131.09, 129.97, 129.20, 128.74, 128.38, 127.01, 123.33, 120.99, 118.08,

117.26, 109.15, 108.34, 108.02, 72.00, 69.30, 56.50, 49.87, 42.30, 41.07, 26.46, 26.29, 22.55, 20.62

ppm; ESI-HRMS: calcd. For C40H33N3O8S2F6+H 863.1692, found 863.1666.

Following the general procedure, treatment of 1j (73 mg, 0.37 mmol) with 2 (32 mg, 0.37 mmol), 3a


column chromatography afforded the product 4j:

NO

N

NO

PhO2SPhO2S

Br

BrH

NO

N

NO

PhO2SPhO2S

F3CO

OCF3H

14

8'-(5,6-difluoro-1-methyl-2-oxoindolin-3-yl)-5,6-difluoro-1-methyl-

1'-(phenylsulfonyl)-2'-((phenylsulfonyl)methyl)-1',5',6',7'-

tetrahydro-2'H-spiro[indoline-3,3'-indolizin]-2-one (4j); 58 mg; white

solid; Rf (ethyl acetate : petroleum ether = 1:1) = 0.48; m.p. 198-199 oC;

IR(KBr): 3063, 2930, 2842, 2358, 2342, 1717, 1626, 1508, 1471, 1448,

1427, 1395, 1310, 1253, 1206, 1144, 1132, 1083 cm-1; 1H NMR (400

MHz, Chloroform-d) δ = 8.21 (d, J = 7.6 Hz, 2H), 7.70-7.82 (m, 2H), 7.46 – 7.70 (m, 6H), 7.30 (t, J =

8.4 Hz, 1H), 6.66 (ddd, J = 8.6, 6.2, 2.0 Hz, 2H), 6.02 (t, J = 8.2 Hz, 1H), 5.34 (s, 1H), 4.32 (d, J = 7.6

Hz, 1H), 3.99 (dd, J = 14.8, 2.4 Hz, 1H), 3.62 (dd, J = 14.4, 11.6 Hz, 1H), 3.22 (s, 3H), 3.19 (s, 3H),

3.02 – 3.13 (m, 1H), 1.99 – 2.18 (m, 2H), 1.64 – 1.78 (m, 1H), 1.15 – 1.56 (m, 3H), ppm; 13C NMR

(100 MHz, CDCl3) δ = 176.63, 174.00, 138.35, 138.32, 135.03, 134.80, 134.66, 134.34 (d, J = 1.4 Hz),

134.03 (d, J = 1.7 Hz), 133.97, 133.92, 133.28, 131.24, 129.59, 129.49, 129.37, 129.35, 129.25, 128.77,

128.26, 128.20, 128.10, 128.06, 113.82 (d, J = 18.6 Hz), 113.62 (d, J = 16.9 Hz), 108.68, 99.15 (d, J =

22.7 Hz), 98.41 (d, J = 60.0 Hz), 71.83, 69.17, 56.49, 49.41, 42.27, 40.98, 26.54, 26.41, 22.43, 20.61

ppm; C38H31N3O6S2F4+H 766.1669, found 766.1675.

Following the general procedure, treatment of 1k (89 mg, 0.37 mmol) with 2 (32 mg, 0.37 mmol), 3a

(100 mg, 0.31 mmol) and 4-TFBA (59 mg, 0.31 mmol) in toluene (2

mL) at 110 oC for 1.5 h followed by column chromatography

afforded the product 4k:


(phenylsulfonyl)-2'-((phenylsulfonyl)methyl)-1',5',6',7'-

tetrahydro-2'H-spiro[indoline-3,3'-indolizin]-2-one (4k); 80 mg;

white solid; Rf (ethyl acetate : petroleum ether = 1:1) = 0.52; m.p. 195-196 oC; IR(KBr): 3068, 2929,

2839, 2358, 2342, 1714, 1649, 1607, 1491, 1447, 1368, 1313, 1278, 1245, 1207, 1182, 1145, 1085 cm-

1; 1H NMR (400 MHz, Chloroform-d) δ = 8.23 (d, J = 7.2 Hz, 2H), 7.71 – 7.79 (m, 2H), 7.52 – 7.69 (m,

6H), 7.29 – 7.32 (m, 1H), 7.26 (dd, J = 8.0, 1.6 Hz, 1H), 7.16 (dd, J = 8.0, 1.9 Hz, 1H), 6.99 (s, 2H),

6.07 (d, J = 8.0 Hz, 1H), 5.35 (s, 1H), 4.38 (d, J = 7.6 Hz, 1H), 4.01 (dd, J = 14.6, 2.2 Hz, 1H), 3.66

(dd, J = 14.4, 11.6 Hz, 1H), 3.26 (s, 3H), 3.22 (s, 3H), 3.13 (ddd, J = 11.8, 7.6, 2.4 Hz, 1H), 2.02 – 2.19

(m, 2H), 1.59 – 1.82 (m, 2H), 1.25 – 1.51 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ = 176.78,

174.11, 146.81, 145.45, 138.26, 134.82, 134.57, 133.83, 133.34, 131.21, 129.16, 128.64, 128.26,

127.32, 125.67, 125.60, 125.38, 124.99, 124.17, 124.04, 121.39, 112.24, 111.19, 108.62, 71.67, 69.28,

56.51, 49.30, 42.22, 40.77, 26.39, 26.25, 22.48, 20.60 ppm; ESI-HRMS: calcd. For

C38H33N3O6S2Br2+H 850.0256, found 850.0223.

NO

N

NO

PhO2SPhO2S

F

F

F

F

H

NO

N

NO

PhO2SPhO2S

Br

Br

H

15

Following the general procedure, treatment of 1l (65 mg, 0.37 mmol) with 2 (32 mg, 0.37 mmol), 3a


column chromatography afforded the product 4l:

8'-(1,7-dimethyl-2-oxoindolin-3-yl)-1,7-dimethyl-1'-(phenylsulfonyl)-2'-

((phenylsulfonyl)methyl)-1',5',6',7'-tetrahydro-2'H-spiro[indoline-3,3'-

indolizin]-2-one (4l); 100 mg; white solid; Rf (ethyl acetate : petroleum

ether = 1:1) = 0.39; m.p. 213-214 oC; IR(KBr): 3058, 2939, 2842, 2358,

2342, 1705, 1604, 1458, 1447, 1363, 1339, 1312, 1278, 1185, 1150, 1134,

1113, 1084 cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 8.15 (d, J = 7.6

Hz, 2H), 7.66 – 7.76 (m, 2H), 7.49 – 7.64 (m, 6H), 7.28 – 7.33 (m, 1H), 7.06 (d, J = 7.6 Hz, 1H), 6.95

– 7.03 (m, 2H), 6.85 (t, J = 7.6 Hz, 1H), 5.91 (d, J = 7.2 Hz, 1H), 5.34 (s, 1H), 4.35 (d, J = 7.6 Hz, 1H),

4.01 (dd, J = 14.8, 2.0 Hz, 1H), 3.69 (dd, J = 14.8, 11.6 Hz, 1H), 3.54 (s, 3H), 3.49 (s, 3H), 2.94 (ddd, J

= 11.6, 7.6, 2.2 Hz, 1H), 2.58 (s, 3H), 2.55 (s, 3H), 2.02 – 2.15 (m, 2H), 1.57 – 1.74 (m, 2H), 1.27 –

1.46 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ = 177.80, 175.02, 143.43, 141.80, 138.15, 134.74,

134.34, 133.91, 133.56, 133.49, 131.57, 131.23, 129.12, 128.96, 128.59, 128.53, 126.01, 122.73,

122.51, 122.04, 121.72, 120.23, 119.12, 108.91, 71.39, 69.61, 56.86, 49.39, 42.25, 41.64, 29.57, 22.61,

20.75, 18.97, 18.94, 14.17 ppm; ESI-HRMS: calcd. For C40H39N3O6S2+Na 744.2178, found 744.2169.

Following the general procedure, treatment of 1m (73 mg, 0.37 mmol) with

2 (32 mg, 0.37 mmol), 3a (100 mg, 0.31 mmol) and 4-TFBA (59 mg, 0.31


chromatography afforded the product 4m:

7-chloro-8'-(7-chloro-1-methyl-2-oxoindolin-3-yl)-1-methyl-1'-


spiro[indoline-3,3'-indolizin]-2-one (4m); 86 mg; white solid; Rf (ethyl acetate : petroleum ether = 1:1)

= 0.63; m.p. 187-188 oC; IR(KBr): 3065, 2940, 2842, 2360, 2342, 1715, 1684, 1558, 1541, 1521, 1507,


J = 7.6 Hz, 2H), 7.67 – 7.77 (m, 2H), 7.50 – 7.66 (m, 6H), 7.31 – 7.36 (m, 1H), 7.24 – 7.30 (m, 1H),

7.19 (d, J = 8.2 Hz, 1H), 7.02 (t, J = 7.8 Hz, 1H), 6.90 (t, J = 7.8 Hz, 1H), 6.05 (d, J = 7.2 Hz, 1H),

5.39 (s, 1H), 4.35 (d, J = 7.6 Hz, 1H), 3.99 (dd, J = 14.6, 2.2 Hz, 1H), 3.63 (s, 4H), 3.58 (s, 3H), 3.07

(ddd, J = 11.6, 7.6, 2.2 Hz, 1H), 2.02 – 2.18 (m, 2H), 1.59 – 1.80 (m, 2H), 1.32 – 1.55 (m, 2H) ppm;

13C NMR (100 MHz, CDCl3) δ = 177.10, 174.63, 141.47, 139.84, 138.29, 134.93, 134.57, 133.79,

133.32, 132.54, 131.23, 131.15, 130.23, 129.09, 128.66, 128.33, 128.18, 123.62, 123.48, 122.59,

122.31, 116.12, 115.04, 108.93, 71.56, 69.25, 56.53, 49.55, 42.31, 41.35, 29.61, 29.59, 22.51, 20.66

ppm; ESI-HRMS: calcd. For C38H33N3O6S2Cl2+H 762.1266, found 762.1233.

NO

N

NO

PhO2SPhO2S

H

NO

N

NO

PhO2SPhO2S

Cl

Cl

H

16

Following the general procedure, treatment of 1n (89 mg, 0.37 mmol) with 2 (32 mg, 0.37 mmol), 3a


column chromatography afforded the product 4n:



spiro[indoline-3,3'-indolizin]-2-one (4n); 91 mg; white solid; Rf (ethyl


2944, 2841, 2344, 2307, 1710, 1607, 1578, 1460, 1447, 1364, 1339, 1313,

1198, 1177, 1152, 1132, 1104, 1055 cm-1; 1H NMR (400 MHz, Chloroform-d)

δ = 8.21 (d, J = 7.2 Hz, 2H), 7.67 – 7.78 (m, 2H), 7.49 – 7.67 (m, 6H), 7.44 (dd, J = 8.4, 1.2 Hz, 1H),

7.37 (dd, J = 7.6, 1.2 Hz, 2H), 6.96 (t, J = 7.8 Hz, 1H), 6.83 (t, J = 7.8 Hz, 1H), 6.08 (d, J = 7.2 Hz,

1H), 5.40 (s, 1H), 4.34 (d, J = 7.6 Hz, 1H), 3.99 (dd, J = 14.8, 2.2 Hz, 1H), 3.64 (s, 3H), 3.56 – 3.62 (m,

4H), 3.06 (ddd, J = 11.8, 7.6, 2.4 Hz, 1H), 1.98 – 2.20 (m, 2H), 1.63 – 1.78 (m, 1H), 1.41 – 1.57 (m,

2H), 1.17 – 1.40 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ = 177.26, 174.80, 142.95, 141.26,

138.26, 135.85, 134.95, 134.57, 133.79, 133.55, 133.30, 131.49, 131.22, 129.08, 128.66, 128.51,

128.33, 124.05, 123.85, 123.12, 122.85, 108.92, 103.01, 102.01, 71.48, 69.25, 56.53, 49.55, 42.30,

41.38, 29.83, 29.79, 22.51, 20.64 ppm; ESI-HRMS: calcd. For C38H33N3O6S2Br2+Na 872.0075, found

872.0051.

Following the general procedure, treatment of 1p (76 mg, 0.37 mmol) with 2

(32 mg, 0.37 mmol), 3a (100 mg, 0.31 mmol) and 4-TFBA (59 mg, 0.31


chromatography afforded the product 4p:

1-(ethoxymethyl)-8'-(1-(ethoxymethyl)-2-oxoindolin-3-yl)-1'-


spiro[indoline-3,3'-indolizin]-2-one (4p) ; 130 mg; white solid; Rf (ethyl acetate : petroleum ether =

1:1) = 0.58; m.p. 187-188 oC; IR(KBr): 3055, 2977, 2927, 2354, 2338, 1715, 1614, 1505, 1470, 1455,


J = 7.6 Hz, 2H), 7.69 – 7.78 (m, 2H), 7.61 (t, J = 7.8 Hz, 2H), 7.54 – 7.58 (m, 4H), 7.45 (d, J = 7.2 Hz,

1H), 7.36 (td, J = 7.8, 1.2 Hz, 1H), 7.28 (t, J = 6.6 Hz, 1H), 7.15 (t, J = 7.2 Hz, 1H), 7.06 (t, J = 7.6 Hz,

2H), 7.02 (t, J = 7.6 Hz, 1H), 6.17 (d, J = 6.8 Hz, 1H), 5.51 (s, 1H), 5.17 – 5.28 (m, 3H), 5.10 (d, J =

11.2 Hz, 1H), 4.39 (d, J = 7.6 Hz, 1H), 4.03 (dd, J = 14.8, 2.2 Hz, 1H), 3.52 – 3.70 (m, 5H), 3.04 –

3.12 (m, 1H), 2.06 – 2.21 (m, 2H), 1.59 – 1.79 (m, 2H), 1.26 – 1.49 (m, 2H), 1.20 (q, J = 7.0 Hz, 6H)


133.39, 131.15, 130.48, 129.06, 128.64, 128.50, 128.05, 128.00, 124.84, 124.15, 123.84, 123.24,

NO

N

NO

PhO2SPhO2S

Br

Br

H

NO

N

NO

CH2OEt

EtOH2C

PhO2SPhO2S

H

17

123.05, 110.06, 109.23, 108.80, 72.21, 70.57, 70.06, 69.45, 64.48, 64.24, 56.66, 49.87, 42.26, 41.01,

22.62, 20.58, 14.96, 14.90 ppm; ESI-HRMS: calcd. For C42H43N3O8S2+H 782.2570, found 782.2560.

Following the general procedure, treatment of 1q (82 mg, 0.37 mmol) with 2 (32 mg, 0.37 mmol), 3a


column chromatography afforded the product 4q:

1-(ethoxymethyl)-8'-(1-(ethoxymethyl)-5-methyl-2-oxoindolin-3-yl)-5-

methyl-1'-(phenylsulfonyl)-2'-((phenylsulfonyl)methyl)-1',5',6',7'-

tetrahydro-2'H-spiro[indoline-3,3'-indolizin]-2-one (4q); 99 mg; white


IR(KBr): 3056, 2976, 2355, 2339, 1715, 1603, 1496, 1447, 1394, 1367,

1330, 1311, 1281, 1214, 1145, 1133, 1086 cm-1; 1H NMR (400 MHz,

Chloroform-d) δ = 8.04 (d, J = 7.6 Hz, 2H), 7.71 – 7.78 (m, 2H), 7.54 – 7.60 (m, 4H), 7.49 – 7.53 (m,

2H), 7.15 (d, J = 7.6 Hz, 1H), 7.08 (d, J = 7.6 Hz, 1H), 6.95 (dd, J = 8.0, 5.2 Hz, 2H), 5.78 (s, 1H),

5.45 (s, 1H), 5.15 – 5.27 (m, 3H), 5.06 (d, J = 11.2 Hz, 1H), 4.36 (d, J = 7.6 Hz, 1H), 4.04 (dd, J = 14.8,

2.0 Hz, 1H), 3.74 (dd, J = 14.8, 11.6 Hz, 1H), 3.48 – 3.64 (m, 5H), 2.91 (ddd, J = 11.8, 7.6, 2.2 Hz,

1H), 2.40 (s, 3H), 2.29 (s, 3H), 2.08 – 2.20 (m, 2H), 1.59 – 1.78 (m, 2H), 1.26 – 1.52 (m, 2H), 1.14 –


134.33, 133.64, 133.49, 132.68, 132.24, 131.12, 130.60, 128.91, 128.69, 128.61, 128.30, 128.03,

125.01, 124.92, 124.50, 109.74, 108.92, 108.57, 72.07, 70.55, 70.07, 69.62, 64.33, 64.14, 56.60, 49.93,

42.14, 41.14, 22.60, 21.23, 21.03, 20.59, 14.95, 14.84 ppm; ESI-HRMS: calcd. For C44H47N3O8S2+H

810.2883, found 810.2867.

Following the general procedure, treatment of 1r (106 mg, 0.37 mmol) with 2 (32 mg, 0.37 mmol), 3a


column chromatography afforded the product 4r:

5-bromo-8'-(5-bromo-1-(ethoxymethyl)-2-oxoindolin-3-yl)-1-

(ethoxymethyl)-1'-(phenylsulfonyl)-2'-((phenylsulfonyl)methyl)-

1',5',6',7'-tetrahydro-2'H-spiro[indoline-3,3'-indolizin]-2-one (4r);

106 mg; white solid; Rf (ethyl acetate : petroleum ether = 1:1) = 0.58;

m.p. 162-163 oC; IR(KBr): 3058, 2977, 2930, 2356, 2329, 1722, 1608,

1584, 1480, 1446, 1428, 1357, 1323, 1312, 1262, 1207, 1148, 1084 cm-1;

1H NMR (400 MHz, Chloroform-d) δ = 7.88 (d, J = 7.6 Hz, 2H), 7.74 – 7.83 (m, 2H), 7.69 (t, J = 7.8

Hz, 2H), 7.44 – 7.63 (m, 6H), 7.39 – 7.44 (m, 1H), 6.96 (dd, J = 13.2, 8.2 Hz, 2H), 5.99 (d, J = 2.0 Hz,

1H), 5.45 (s, 1H), 5.13 – 5.28 (m, 3H), 5.06 (d, J = 11.2 Hz, 1H), 4.31 (d, J = 7.2 Hz, 1H), 4.05 (dd, J =

14.8, 2.0 Hz, 1H), 3.74 (dd, J = 14.8, 11.6 Hz, 1H), 3.47 – 3.66 (m, 4H), 2.76 (ddd, J = 12.0, 7.6, 2.2

NO

N

NO

CH2OEt

EtOH2C

PhO2SPhO2S

H

NO

N

NO

CH2OEt

EtOH2C

PhO2SPhO2S

Br

BrH

18

Hz, 1H), 2.08 – 2.23 (m, 2H), 1.62 – 1.78 (m, 2H), 1.29 – 1.54 (m, 2H), 1.14 – 1.25 (m, 6H) ppm; 13C

NMR (100 MHz, CDCl3) δ = 176.59, 173.75, 143.54, 141.54, 137.15, 134.94, 134.79, 133.89, 133.17,

133.01, 131.09, 130.93, 130.03, 129.26, 128.83, 128.78, 127.32, 127.28, 126.96, 116.07, 115.70,

111.79, 110.89, 108.06, 71.91, 70.73, 70.13, 69.41, 64.62, 64.33, 56.39, 49.87, 42.15, 41.28, 22.52,

20.55, 14.92, 14.82 ppm; ESI-HRMS: calcd. For C42H41N3O8S2Br2+H 938.0780, found 938.0742.

Following the general procedure, treatment of 1s (88 mg, 0.37 mmol) with 2 (32 mg, 0.37 mmol), 3a


column chromatography afforded the product 4s:

1-benzyl-8'-(1-benzyl-2-oxoindolin-3-yl)-1'-(phenylsulfonyl)-2'-

((phenylsulfonyl)methyl)-1',5',6',7'-tetrahydro-2'H-spiro[indoline-3,3'-

indolizin]-2-one (4s); 122 mg; white solid; Rf (ethyl acetate : petroleum

ether = 1:1) = 0.61; m.p. 144-145 oC; IR(KBr): 3014, 2946, 2838, 2353,

2321, 1713, 1613, 1486, 1454, 1447, 1359, 1311, 1210, 1181, 1145, 1132,

1083 cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 8.24 (d, J = 7.6 Hz, 2H),

7.68 – 7.79 (m, 2H), 7.50 – 7.68 (m, 6H), 7.48 (d, J = 7.2 Hz, 1H), 7.27 – 7.35 (m, 9H), 7.20 – 7.25 (m,

2H), 7.15 (t, J = 7.6 Hz, 1H), 7.08 (t, J = 7.4 Hz, 1H), 6.97 (t, J = 7.6 Hz, 1H), 6.69 (t, J = 8.0 Hz, 2H),

6.23 (d, J = 7.2 Hz, 1H), 5.56 (s, 1H), 5.24 (d, J = 15.6 Hz, 1H), 5.07 (d, J = 16.0 Hz, 1H), 4.91 (d, J =

15.6 Hz, 1H), 4.66 (d, J = 15.6 Hz, 1H), 4.47 (d, J = 7.6 Hz, 1H), 4.05 (dd, J = 14.4, 2.0 Hz, 1H), 3.72

(dd, J = 14.6, 11.4 Hz, 1H), 3.17 (ddd, J = 11.6, 7.6, 2.0 Hz, 1H), 2.12 – 2.30 (m, 2H), 1.62 – 1.90 (m,


143.29, 138.40, 136.10, 136.07, 135.70, 135.68, 134.81, 134.44, 133.69, 133.55, 133.53, 131.29,

130.23, 129.06, 128.76, 128.70, 128.63, 128.48, 127.79, 127.59, 127.43, 127.20, 125.36, 124.24,

123.92, 122.87, 122.75, 109.65, 109.14, 108.73, 71.95, 69.59, 56.77, 49.64, 44.25, 43.87, 42.37, 41.10,

22.70, 20.66 ppm; ESI-HRMS: calcd. For C50H43N3O6S2+H 846.2672, found 846.2654.

Following the general procedure, treatment of 1t (94 mg, 0.37 mmol) with 2 (32 mg, 0.37 mmol), 3a


column chromatography afforded the product 4t:

1-benzyl-8'-(1-benzyl-5-methyl-2-oxoindolin-3-yl)-5-methyl-1'-


2'H-spiro[indoline-3,3'-indolizin]-2-one (4t); 113 mg; white solid; Rf

(ethyl acetate : petroleum ether = 1:1) = 0.60; m.p.165-166 oC; IR(KBr):

3028, 2918, 2840, 2356, 2339, 1709, 1602, 1584, 1514, 1446, 1346, 1324,

1311, 1281, 1203, 1185, 1144, 1084 cm-1; 1H NMR (400 MHz,

Chloroform-d) δ = 8.12 (d, J = 7.8 Hz, 2H), 7.74 (t, J = 7.2 Hz, 2H), 7.42 – 7.66 (m, 6H), 7.25 – 7.37

NO

N

NO

Bn

Bn

PhO2SPhO2S

H

NO

N

NO

Bn

Bn

PhO2SPhO2S

H

19

(m, 10H), 7.21 – 7.24 (m, 1H), 7.02 (d, J = 8.0 Hz, 1H), 6.94 (d, J = 7.6 Hz, 1H), 6.56 (dd, J = 8.0, 4.0

Hz, 2H), 5.82 (s, 1H), 5.50 (s, 1H), 5.25 (d, J = 16.0 Hz, 1H), 5.05 (d, J = 16.0 Hz, 1H), 4.89 (d, J =

15.6 Hz, 1H), 4.61 (d, J = 16.0 Hz, 1H), 4.43 (d, J = 7.6 Hz, 1H), 4.06 (d, J = 16.0 Hz, 1H), 3.81 (dd, J

= 14.8, 11.6 Hz, 1H), 2.93 – 3.04 (m, 1H), 2.34 (s, 3H), 2.25 (s, 3H), 2.20 (t, J = 5.6 Hz, 2H), 1.62 –

1.88 (m, 2H), 1.31 – 1.54 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ = 177.03, 174.18, 142.71,

140.89, 138.05, 136.19, 135.95, 134.66, 134.29, 133.66, 133.60, 132.31, 131.91, 131.27, 130.30,

128.93, 128.71, 128.69, 128.66, 128.61, 128.04, 127.51, 127.36, 127.24, 127.16, 125.59, 125.08,

124.65, 109.37, 108.89, 108.46, 71.81, 69.79, 56.73, 49.72, 44.27, 43.87, 42.25, 41.23, 22.71, 21.20,

21.01, 20.68. ppm; ESI-HRMS: calcd. For C52H47N3O6S2+H 874.2985, found 874.2976.

Following the general procedure, treatment of 1u (101 mg, 0.37 mmol)

with 2 (32 mg, 0.37 mmol), 3a (100 mg, 0.31 mmol) and 4-TFBA (59 mg,

0.31 mmol) in toluene (2 mL) at 110 oC for 1 h followed by column

chromatography afforded the product 4u:

1-benzyl-8'-(1-benzyl-5-chloro-2-oxoindolin-3-yl)-5-chloro-1'-


2'H-spiro[indoline-3,3'-indolizin]-2-one (4u); 133 mg; white solid; Rf (ethyl acetate : petroleum ether

= 1:1) = 0.61; m.p. 195-196 oC; IR(KBr): 3029, 2918, 2840, 2356, 2329, 1710, 1602, 1584, 1496, 1446,


J = 7.6 Hz, 2H), 7.73 – 7.81 (m, 2H), 7.63 – 7.68 (m, 2H), 7.59 (t, J = 7.8 Hz, 2H), 7.52 – 7.56 (m, 2H),

7.43 – 7.46 (m, 1H), 7.26 – 7.37 (m, 10H), 7.20 (dd, J = 8.4, 2.0 Hz, 1H), 7.10 – 7.14 (m, 1H), 6.59 (t,

J = 8.4 Hz, 2H), 5.94 (d, J = 2.0 Hz, 1H), 5.51 (s, 1H), 5.26 (d, J = 16.0 Hz, 1H), 5.06 (d, J = 15.6 Hz,

1H), 4.87 (d, J = 15.6 Hz, 1H), 4.61 (d, J = 16.0 Hz, 1H), 4.39 (d, J = 7.2 Hz, 1H), 4.07 (dd, J = 14.8,

2.0 Hz, 1H), 3.79 (dd, J = 14.8, 11.6 Hz, 1H), 2.85 – 2.94 (m, 2H), 2.15 – 2.25 (m, 2H), 1.64 – 1.86 (m,


137.51, 135.56, 135.22, 135.02, 134.75, 133.87, 133.14, 131.09, 130.16, 130.01, 129.20, 128.86,

128.81, 128.69, 128.27, 128.06, 127.93, 127.78, 127.64, 127.36, 127.30, 127.30, 127.14, 127.14,

124.65, 124.36, 110.79, 109.76, 108.46, 71.69, 69.48, 56.50, 49.69, 44.46, 43.98, 42.24, 41.28, 22.60,

20.61 ppm; ESI-HRMS: calcd. For C50H41N3O6S2Cl2+H 914.1892, found 914.1880.

Following the general procedure, treatment of 1v (118 mg, 0.37 mmol) with 2 (32 mg, 0.37 mmol), 3a


column chromatography afforded the product 4v:

1-benzyl-8'-(1-benzyl-5-bromo-2-oxoindolin-3-yl)-5-bromo-1'-


2'H-spiro[indoline-3,3'-indolizin]-2-one (4v); 126 mg; white solid; Rf

NO

N

NO

Bn

Bn

PhO2SPhO2S

Cl

ClH

NO

N

NO

Bn

Bn

PhO2SPhO2S

Br

BrH

20

(ethyl acetate : petroleum ether = 1:1) = 0.61; m.p. 206-207 oC; IR(KBr): 3059, 3030, 2917, 2359,

2341, 1717, 1608, 1583, 1483, 1447, 1429, 1379, 1343, 1315, 1278, 1211, 1143, 1082 cm-1; 1H NMR

(400 MHz, Chloroform-d) δ = 7.96 (d, J = 7.6 Hz, 2H), 7.73 – 7.83 (m, 2H), 7.68 (t, J = 7.8 Hz, 2H),

7.47 – 7.63 (m, 5H), 7.26 – 7.38 (m, 12H), 6.55 (t, J = 8.8 Hz, 2H), 6.03 (d, J = 2.0 Hz, 1H), 5.51 (s,

1H), 5.27 (d, J = 15.6 Hz, 1H), 5.06 (d, J = 16.0 Hz, 1H), 4.87 (d, J = 16.0 Hz, 1H), 4.59 (d, J = 16.0

Hz, 1H), 4.38 (d, J = 7.6 Hz, 1H), 4.07 (dd, J = 14.8, 2.0 Hz, 1H), 3.82 (dd, J = 14.8, 11.6 Hz, 1H),

2.83 (ddd, J = 11.8, 7.6, 2.0 Hz, 1H), 2.12 – 2.28 (m, 2H), 1.64 – 1.88 (m, 2H), 1.31 – 1.56 (m, 2H)


135.21, 135.01, 134.76, 133.86, 133.11, 132.87, 131.05, 130.85, 130.53, 129.26, 128.87, 128.82,

128.79, 127.82, 127.79, 127.65, 127.37, 127.33, 127.13, 127.04, 115.66, 115.30, 115.21, 111.27,

110.29, 108.37, 71.62, 69.53, 56.50, 49.64, 44.46, 43.97, 42.23, 41.34, 22.60, 20.63 ppm；ESI-HRMS:

calcd. For C50H41N3O6S2Br2+H 1002.0882, found 1002.0860.

Following the general procedure, treatment of 1b (49 mg, 0.31 mmol) with 2 (26 mg, 0.31 mmol), 3b


column chromatography afforded the product 4w:

1'-((4-chlorophenyl)sulfonyl)-2'-(((4-chlorophenyl)sulfonyl)methyl)-

1-methyl-8'-(1-methyl-2-oxoindolin-3-yl)-1',5',6',7'-tetrahydro-2'H-

spiro[indoline-3,3'-indolizin]-2-one (4w); 91 mg; white solid; Rf (ethyl


2930, 2839, 2355, 2329, 1705, 1613, 1524, 1494, 1471, 1373, 1346,

1318, 1278, 1210, 1183, 1146, 1089 cm-1; 1H NMR (400 MHz,

Chloroform-d) δ = 8.24 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.46 – 7.57 (m, 4H), 7.43 (d, J =

7.2 Hz, 1H), 7.38 (d, J = 7.6, Hz, 1H), 7.24 – 7.33 (m, 1H), 7.12 (t, J = 7.4 Hz, 1H), 7.06 (t, J = 7.6 Hz,

1H), 6.83 (t, J = 7.4 Hz, 2H), 6.27 (d, J = 7.6 Hz, 1H), 5.35 (s, 1H), 4.42 (d, J = 7.6 Hz, 1H), 3.96 (dd,

J = 14.6, 2.2 Hz, 1H), 3.67 (dd, J = 14.8, 11.6 Hz, 1H), 3.26 (s, 3H), 3.23 (s, 3H), 3.04 (ddd, J = 11.2,

7.6, 2.2 Hz, 1H), 2.15 – 2.24 (m, 1H), 2.10 (td, J = 10.8, 2.8 Hz, 1H), 1.60 – 1.77 (m, 2H), 1.41 – 1.53

(m, 1H), 1.23 – 1.36 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ = 177.06, 174.15, 145.65, 144.14,

141.50, 140.57, 136.76, 134.56, 132.74, 132.16, 130.54, 129.96, 129.35, 128.94, 128.39, 127.97,

125.02, 124.09, 123.75, 122.91, 122.87, 109.40, 108.73, 107.72, 71.95, 69.58, 56.82, 49.67, 42.36,

41.30, 26.29, 26.17, 22.58, 20.79 ppm; ESI-HRMS: calcd. For C38H33N3O6S2Cl2+H 762.1266, found

762.1252.

Following the general procedure, treatment of 1a (60 mg, 0.31 mmol) with 2 (26 mg, 0.31 mmol), 3b


column chromatography afforded the product 4x:

NO

N

NO

p-ClPhO2Sp-ClPhO2S

H

21


8'-(1,5-dimethyl-2-oxoindolin-3-yl)-1,5-dimethyl-1',5',6',7'-

tetrahydro-2'H-spiro[indoline-3,3'-indolizin]-2-one (4x); 95 mg;

white solid; Rf (ethyl acetate : petroleum ether = 1:1) = 0.47; m.p.

199-200 oC; IR(KBr): 3051, 2937, 2839, 2355, 2329, 1700, 1611,

1524, 1484, 1461, 1373, 1336, 1318, 1294, 1210, 1183, 1146, 1085

cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 8.13 (d, J = 8.0 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H), 7.52 (d,

J = 8.8 Hz, 2H), 7.40 (d, J = 8.8 Hz, 2H), 7.20 (s, 1H), 7.16 (dd, J = 8.0, 1.4 Hz, 1H), 7.08 (d, J = 7.6

Hz, 1H), 6.72 (dd, J = 7.8, 4.2 Hz, 2H), 5.73 (d, J = 1.6 Hz, 1H), 5.29 (s, 1H), 4.37 (d, J = 7.6 Hz, 1H),

3.96 (dd, J = 14.8, 2.4 Hz, 1H), 3.79 (dd, J = 14.8, 11.6 Hz, 1H), 3.23 (s, 3H), 3.20 (s, 3H), 2.80 (ddd, J

= 11.6, 7.6, 2.4 Hz, 1H), 2.39 (s, 3H), 2.32 (s, 3H), 2.10 – 2.22 (m, 2H), 1.64 (d, J = 9.2 Hz, 2H), 1.35

– 1.53 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ = 177.10, 173.94, 143.29, 141.77, 141.42, 140.45,

136.24, 134.35, 132.65, 132.31, 132.11, 130.54, 130.18, 130.07, 129.41, 129.31, 129.18, 128.97,

128.29, 128.21, 127.63, 108.80, 108.45, 107.46, 71.74, 69.78, 56.75, 49.81, 42.17, 41.43, 26.32, 26.22,

22.61, 21.26, 21.10, 20.79 ppm; ESI-HRMS: calcd. For C40H37N3O6S2Cl2+H 790.1579, found

790.1570.

Following the general procedure, treatment of 1g (74 mg, 0.31 mmol) with 2 (26 mg, 0.31 mmol), 3b


column chromatography afforded the product 4y:

5-bromo-8'-(5-bromo-1-methyl-2-oxoindolin-3-yl)-1'-((4-

chlorophenyl)sulfonyl)-2'-(((4-chlorophenyl)sulfonyl)methyl)-1-

methyl-1',5',6',7'-tetrahydro-2'H-spiro[indoline-3,3'-indolizin]-2-

one (4y); 87 mg; white solid; Rf (ethyl acetate : petroleum ether = 1:1)

= 0.48; m.p. 184-85 oC; IR(KBr): 3084, 2925, 2839, 2355, 2320, 1712, 1609, 1574, 1487, 1475, 1360,


7.8 Hz, 2H), 7.75 – 7.84 (m, 2H), 7.70 (t, J = 7.8 Hz, 2H), 7.59 (t, J = 7.8 Hz, 2H), 7.49 – 7.52 (m, 3H),

7.42 – 7.46 (m, 1H), 6.73 (dd, J = 8.0, 6.4 Hz, 2H), 5.99 (d, J = 2.0 Hz, 1H), 5.38 (s, 1H), 4.34 (d, J =

7.4 Hz, 1H), 4.05 (dd, J = 14.8, 2.2 Hz, 1H), 3.81 (dd, J = 14.8, 11.6 Hz, 1H), 3.26 (s, 3H), 3.24 (s, 3H),

2.77 (ddd, J = 11.8, 7.4, 2.2 Hz, 1H), 2.08 – 2.21 (m, 2H), 1.63 – 1.76 (m, 1H), 1.30 – 1.56 (m, 3H)


133.39, 131.26, 129.21, 128.69, 128.31, 127.37, 125.72, 125.65, 125.43, 125.04, 124.23, 124.09,

121.44, 112.29, 111.24, 108.67, 71.72, 69.33, 56.56, 49.35, 42.27, 40.82, 26.44, 26.30, 22.53, 20.65

ppm; ESI-HRMS: calcd. For C38H31N3O6S2Cl2Br2+H 917.9476, found 917.9488.

NO

N

NO

p-ClPhO2Sp-ClPhO2S

H

NO

N

NO

p-ClPhO2Sp-ClPhO2S

Br

BrH

22

Following the general procedure, treatment of 1a (60 mg, 0.34 mmol) with 2 (29 mg, 0.34 mmol), 3c


column chromatography afforded the product 4z:

8'-(1,5-dimethyl-2-oxoindolin-3-yl)-1,5-dimethyl-1'-tosyl-2'-(tosylmethyl)-

1',5',6',7'-tetrahydro-2'H-spiro[indoline-3,3'-indolizin]-2-one (4z); 65

mg; white solid; Rf (ethyl acetate : petroleum ether = 1:1) = 0.62; m.p.218-

219 oC; IR(KBr): 3045, 2926, 2840, 2354, 2321, 1712, 1621, 1598, 1499,

1446, 1363, 1352, 1322, 1309, 1280, 1203, 1142, 1086 cm-1; 1H NMR (400

MHz, Chloroform-d) δ = 7.87 – 7.99 (m, 2H), 7.28 – 7.40 (m, 6H), 7.22 (s, 1H), 7.13 (d, J = 8.0 Hz,

1H), 7.06 (d, J = 8.0 Hz, 1H), 6.69 (d, J = 7.8 Hz, 2H), 5.70 (s, 1H), 5.35 (s, 1H), 4.32 (d, J = 7.2 Hz,

1H), 3.92 – 4.01 (m, 1H), 3.78 (t, J = 13.2 Hz, 1H), 3.22 (s, 3H), 3.20 (s, 3H), 2.79 – 2.88 (m, 1H),

2.53 (s, 3H), 2.51 (s, 3H), 2.39 (s, 3H), 2.28 (s, 3H), 2.09 – 2.19 (m, 2H), 1.60 – 1.74 (m, 2H), 1.34 –


134.90, 134.70, 132.21, 131.63, 131.27, 130.90, 130.21, 129.42, 129.20, 128.81, 128.59, 128.07,

125.97, 124.90, 124.63, 108.17, 108.03, 107.30, 71.85, 69.84, 56.86, 49.83, 42.10, 41.34, 26.27, 26.19,

22.65, 21.87, 21.70, 21.28, 21.02, 20.81 ppm; ESI-HRMS: calcd. For C42H43N3O6S2+H 750.2672,

found 750.2666.

Following the general procedure, treatment of 1g (60 mg, 0.34 mmol) with 2 (29 mg, 0.34 mmol), 3c


column chromatography afforded the product 4aa:


tosyl-2'-(tosylmethyl)-1',5',6',7'-tetrahydro-2'H-spiro[indoline-3,3'-

indolizin]-2-one (4aa); 72 mg; white solid; Rf (ethyl acetate :

petroleum ether = 1:1) = 0.69; m.p. 190-191 oC; IR(KBr): 3048, 2981,

2838, 2355, 2328, 1713, 1682, 1593, 1495, 1434, 1359, 1318, 1284,

1221, 1187, 1154, 1144, 1084 cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 7.76 (d, J = 7.6 Hz, 2H),

7.43 – 7.50 (m, 4H), 7.38 – 7.44 (m, 1H), 7.28 – 7.36 (m, 4H), 6.70 (dd, J = 8.0, 5.2 Hz, 2H), 5.84 (d, J

= 2.0 Hz, 1H), 5.35 (s, 1H), 4.27 (d, J = 7.2 Hz, 1H), 3.98 (dd, J = 14.8, 2.4 Hz, 1H), 3.79 (dd, J = 14.8,

11.6 Hz, 1H), 3.23 (s, 3H), 3.21 (s, 3H), 2.67 (ddd, J = 11.8, 7.2, 2.2 Hz, 1H), 2.58 (s, 3H), 2.53 (s, 3H),

2.10 – 2.19 (m, 2H), 1.60 – 1.69 (m, 2H), 1.45 – 1.52 (m, 1H), 1.36 – 1.44 (m, 1H) ppm; 13C NMR

(100 MHz, CDCl3) δ = 176.43, 173.57, 145.88, 144.96, 144.89, 143.28, 135.07, 134.33, 132.78, 131.08,

130.92, 130.56, 130.40, 130.05, 130.01, 129.78, 129.48, 128.83, 128.35, 128.25, 128.03, 127.20,

127.07, 115.11, 110.04, 109.11, 107.55, 76.68, 71.66, 69.70, 56.65, 49.76, 42.11, 41.44, 26.38, 26.34,

22.58, 21.96, 21.75, 20.72 ppm; ESI-HRMS: calcd. For C40H37N3O6S2Br2+H 878.0569, found

878.0580.

NO

N

NO

TsTs

H

NO

N

NO

TsTs

Br

BrH

23

Following the general procedure, treatment of 1b (115 mg, 0.71 mmol) with 2 (61 mg, 0.71 mmol), 3d

(100 mg, 0.59 mmol) and 4-TFBA (113 mg, 0.59 mmol) in toluene (4 mL) at 110 oC for 1 h followed

by column chromatography afforded the product 4ab:

1-methyl-8'-(1-methyl-2-oxoindolin-3-yl)-1'-(phenylsulfonyl)-1',5',6',7'-

tetrahydro-2'H-spiro[indoline-3,3'-indolizin]-2-one (4ab); 118 mg; white


IR(KBr): 3043, 2931, 2838, 2353, 2321, 1713, 1613, 1494, 1470, 1446, 1372,

1346, 1308, 1258, 1204, 1132, 1085 cm-1; 1H NMR (400 MHz, Chloroform-d) δ

= 8.56 (d, J = 7.2 Hz, 2H), 7.76 (t, J = 7.4 Hz, 1H), 7.69 (t, J = 7.4 Hz, 2H),

7.52 (d, J = 7.2 Hz, 1H), 7.29 (t, J = 8.0 Hz, 2H), 7.13 (t, J = 7.4 Hz, 1H), 6.98 (t, J = 7.4 Hz, 1H), 6.83

(d, J = 7.6 Hz, 1H), 6.77 (d, J = 7.6 Hz, 1H), 6.46 (d, J = 7.2 Hz, 1H), 5.53 (s, 1H), 4.95 (dd, J = 9.8,

6.6 Hz, 1H), 3.28 (s, 3H), 3.15 (s, 3H), 2.73 (dd, J = 14.8, 10.0 Hz, 1H), 2.51 (dd, J = 14.8, 6.8 Hz, 1H),

2.17 – 2.28 (m, 1H), 2.11 (td, J = 10.4, 3.2 Hz, 1H), 1.70 – 1.82 (m, 1H), 1.59 – 1.68 (m, 1H), 1.31 –


134.10, 131.33, 129.88, 128.95, 128.49, 127.75, 126.69, 125.97, 124.19, 123.67, 123.20, 122.85,

108.31, 108.23, 107.52, 69.33, 64.96, 49.80, 42.49, 35.38, 26.27, 25.95, 22.46, 20.92 ppm; ESI-HRMS:

calcd. For C31H29N3O4S+H 540.1957, found 540.1965.

Following the general procedure, treatment of 1a (125 mg, 0.71 mmol) with 2 (61 mg, 0.71 mmol), 3d


by column chromatography afforded the product 4ac:

8'-(1,5-dimethyl-2-oxoindolin-3-yl)-1,5-dimethyl-1'-(phenylsulfonyl)-

1',5',6',7'-tetrahydro-2'H-spiro[indoline-3,3'-indolizin]-2-one (4ac);

119 mg; white solid; Rf (ethyl acetate : petroleum ether = 1:1) = 0.53; m.p.

170-171; IR(KBr): 3032, 2921, 2836, 2351, 2311, 1714, 1612, 1493, 1471,

1445, 1373, 1345, 1309, 1254, 1200, 1132, 1088 cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 8.55 –

8.61 (m, 2H), 7.74 – 7.80 (m, 1H), 7.65 – 7.74 (m, 2H), 7.32 (s, 1H), 6.98 – 7.10 (m, 2H), 6.71 (d, J =

8.0 Hz, 1H), 6.65 (d, J = 8.0 Hz, 1H), 6.15 (s, 1H), 5.49 (s, 1H), 4.92 (dd, J = 10.4, 6.8 Hz, 1H), 3.26 (s,

3H), 3.12 (s, 3H), 2.73 (dd, J = 14.6, 10.2 Hz, 1H), 2.48 (dd, J = 14.8, 6.4 Hz, 1H), 2.40 (s, 3H), 2.26 (s,

3H), 2.09 – 2.24 (m, 2H), 1.70 – 1.82 (m, 1H), 1.60 – 1.70 (m, 1H), 1.35 – 1.55 (m, 2H) ppm; 13C

NMR (100 MHz, CDCl3) δ = 177.36, 177.34, 141.87, 141.71, 137.10, 133.98, 132.72, 132.18, 131.41,

129.98, 128.96, 128.50, 127.96, 126.93, 125.08, 124.48, 108.02, 107.21, 69.39, 65.12, 49.89, 42.41,

35.42, 26.27, 25.94, 22.49, 21.25, 20.95, 20.94 ppm; ESI-HRMS: calcd. For C33H33N3O4S+H 568.2270,

found 568.2272.

NO

N

NO

PhO2S H

NO

N

NO

PhO2S H

24

Following the general procedure, treatment of 1w (68 mg, 0.37 mmol) with 2 (32 mg, 0.27 mmol), 3a


by column chromatography afforded the product 5a:

8'-(2-oxo-1,2-dihydroacenaphthylen-1-yl)-1'-(phenylsulfonyl)-2'-

((phenylsulfonyl)methyl)-1',5',6',7'-tetrahydro-2H,2'H-

spiro[acenaphthylene-1,3'-indolizin]-2-one (5a); 79 mg; yellow solid;

Rf (e ethyl acetate : petroleum ether = 1:1) = 0.44; m.p. 214-215 oC;

IR(KBr): 3054, 2929, 2839, 2353, 2321, 1716, 1605, 1583, 1494, 1464,


7.6 Hz, 2H), 8.14 (dd, J = 11.2, 8.0 Hz, 2H), 7.90 – 8.02 (m, 3H), 7.86 (d, J = 7.6 Hz, 2H), 7.79 – 7.84

(m, 1H), 7.67 – 7.79 (m, 5H), 7.59 – 7.67 (m, 2H), 7.44 – 7.55 (m, 4H), 6.68 (d, J = 6.8 Hz, 1H), 5.78

(s, 1H), 4.63 (d, J = 7.6 Hz, 1H), 4.05 (dd, J = 14.2, 1.8 Hz, 1H), 3.58 (dd, J = 14.2, 11.4 Hz, 1H), 3.44

– 3.52 (m, 1H), 2.07 (t, J = 5.4 Hz, 2H), 1.56 – 1.80 (m, 2H), 1.14 – 1.35 (m, 2H) ppm; 13C NMR (100

MHz, CDCl3) δ = 205.76, 205.16, 143.58, 141.47, 138.36, 137.80, 135.29, 134.48, 133.88, 133.18,

133.06, 131.46, 130.83, 130.81, 130.17, 129.69, 128.43, 128.36, 128.04, 127.69, 127.61, 127.40,

125.49, 123.33, 120.60, 120.46, 120.14, 120.08, 109.82, 74.75, 69.12, 55.77, 55.13, 41.88, 40.37, 22.40,

20.19 ppm; C44H33NO6S2+H 736.1828, found 736.1816.

Following the general procedure, treatment of 1w (56 mg, 0.31 mmol) with 2 (26 mg, 0.31 mmol), 3b


by column chromatography afforded the product 5b:

1'-((4-chlorophenyl)sulfonyl)-2'-(((4-

chlorophenyl)sulfonyl)methyl)-8'-(2-oxo-1,2-

dihydroacenaphthylen-1-yl)-1',5',6',7'-tetrahydro-2H,2'H-

spiro[acenaphthylene-1,3'-indolizin]-2-one (5b); 97 mg; yellow

solid; Rf (ethyl acetate : petroleum ether = 1:1) = 0.44; m.p. 200-201oC; IR(KBr): 3086, 2948, 2837,

2353, 2321, 1713, 1604, 1581, 1494, 1477, 1464, 1433, 1396, 1365, 1316, 1178, 1144, 1089 cm-1; 1H

NMR (400 MHz, Chloroform-d) δ = 8.46 (d, J = 8.4 Hz, 2H), 8.15 (dd, J = 14.4, 8.0 Hz, 2H), 7.89 –

8.01 (m, 3H), 7.83 – 7.89 (m, 2H), 7.64 – 7.81 (m, 6H), 7.42 (s, 4H), 6.80 (d, J = 6.8 Hz, 1H), 5.74 (s,

1H), 4.67 (d, J = 7.2 Hz, 1H), 4.00 (d, J = 12.4 Hz, 1H), 3.40 – 3.63 (m, 2H), 1.95 – 2.24 (m, 2H), 1.55

– 1.74 (m, 2H), 1.08 – 1.43 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ = 206.13, 205.69, 144.12,

142.13, 141.53, 140.44, 138.78, 137.08, 135.43, 134.94, 134.43, 132.95, 132.67, 132.51, 131.85,

131.50, 130.82, 130.42, 129.53, 129.26, 129.02, 128.40, 128.05, 126.30, 124.03, 121.30, 121.15,

120.77, 111.04, 75.36, 69.75, 56.44, 55.72, 42.60, 41.17, 22.99, 20.88 ppm; ESI-HRMS: calcd. For

C44H31NO6S2Cl2+H 804.1048, found 804.1034.

NO

SO2PhO

SO2Ph

H

N

O

p-ClPhO2SOp-ClPhO2SH

25

Following the general procedure, treatment of 1w (62 mg, 0.34 mmol) with 2 (29 mg, 0.34 mmol), 3c


column chromatography afforded the product 5c:

8'-(2-oxo-1,2-dihydroacenaphthylen-1-yl)-1'-tosyl-2'-(tosylmethyl)-

1',5',6',7'-tetrahydro-2H,2'H-spiro[acenaphthylene-1,3'-indolizin]-

2-one (5c); 96 mg; yellow solid; Rf (ethyl acetate : petroleum ether =

1:1) = 0.45; m.p. 190-191 oC; IR(KBr): 3043, 2946, 2838, 2353, 2320,

1722, 1682, 1594, 1574, 1487, 1434, 1416, 1318, 1305, 1218, 1196,

1135, 1085 cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 8.23 (d, J = 8.0 Hz, 2H), 8.13 (dd, J = 11.6,

8.0 Hz, 2H), 7.93 – 8.02 (m, 2H), 7.92 (s, 1H), 7.86 (dd, J = 7.6, 2.8 Hz, 2H), 7.68 – 7.79 (m, 3H), 7.64

(dd, J = 8.4, 6.8 Hz, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.34 – 7.41 (m, 2H), 7.28 (d, J = 8.0 Hz, 2H), 6.72

(d, J = 6.8 Hz, 1H), 5.79 (s, 1H), 4.60 (d, J = 7.6 Hz, 1H), 4.01 (dd, J = 14.0, 1.2 Hz, 1H), 3.42 – 3.60

(m, 2H), 2.57 (s, 3H), 2.46 (s, 3H), 2.03 – 2.12 (m, 2H), 1.69-1.81 (m, 1H), 1.59-1.68 (m, 1H), 1.27-


139.07, 138.72, 136.07, 135.52, 135.20, 134.54, 132.43, 132.11, 131.47, 131.35, 131.10, 130.88,

130.77, 130.04, 129.99, 129.50, 129.25, 129.03, 128.32, 128.24, 128.17, 128.01, 127.97, 126.02,

123.88, 121.15, 121.01, 120.73, 110.22, 75.41, 69.74, 57.85, 56.51, 55.74, 42.49, 41.03, 23.00, 21.97,

21.64, 20.86 ppm; ESI-HRMS: calcd. For C46H37NO6S2+H 764.2141, found 764.2178.

Following the general procedure, treatment of 1x (86 mg, 0.37 mmol)

with 2 (32 mg, 0.27 mmol), 3a (100 mg, 0.31 mmol) and 4-TFBA

(59 mg, 0.31 mmol) in toluene (2 mL) at 110 oC for 1.5 h followed

by column chromatography afforded the product 5d:

8'-(1-oxo-1,2-dihydroaceanthrylen-2-yl)-1'-(phenylsulfonyl)-2'-

((phenylsulfonyl)methyl)-1',5',6',7'-tetrahydro-1H,2'H-spiro[aceanthrylene-2,3'-indolizin]-1-one

(5d)； 113 mg; yellow solid; Rf (ethyl acetate : petroleum ether = 1:1) = 0.53; m.p. 227-228 oC; IR(KBr): 3048, 2924, 2839, 2403, 2307, 1691, 1626, 1595, 1579, 1532, 1458, 1403, 1318, 1305, 1221,

1154, 1143, 1085 cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 9.27 (d, J = 8.4 Hz, 1H), 9.19 (d, J =

8.8 Hz, 1H), 8.73 (d, J = 9.6 Hz, 2H), 8.39 – 8.49 (m, 2H), 8.17 (dd, J = 8.4, 5.2 Hz, 2H), 8.04 (d, J =

8.4 Hz, 1H), 7.99 (dd, J = 7.6, 6.0 Hz, 2H), 7.71 – 7.88 (m, 6H), 7.56 – 7.68 (m, 4H), 7.44 – 7.53 (m,

4H), 6.67 (d, J = 6.4 Hz, 1H), 5.94 (s, 1H), 4.77 (d, J = 8.0 Hz, 1H), 4.10 (dd, J = 14.4, 1.2 Hz, 1H),

3.69 (dd, J = 14.4, 11.2 Hz, 1H), 3.49 – 3.59 (m, 1H), 2.08 – 2.21 (m, 2H), 1.74 – 1.86 (m, 1H), 1.54 –

1.68 (m, 1H), 1.20 – 1.35 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ = 205.76, 205.73, 146.41,

144.20, 139.27, 138.48, 136.36, 135.36, 134.41, 133.89, 133.73, 133.51, 133.48, 133.40, 132.28,

131.49, 130.44, 129.51, 129.19, 128.86, 128.64, 128.46, 128.27, 128.09, 128.01, 127.66, 127.55,

NO

TsO

Ts

H

N

O

SO2PhO

SO2Ph

H

26

127.23, 126.56, 126.26, 125.42, 125.38, 125.09, 124.77, 124.65, 124.12, 120.23, 120.17, 110.32, 75.54,

69.86, 56.49, 55.99, 42.47, 40.89, 22.87, 20.85 ppm; ESI-HRMS: calcd. For C52H37NO6S2+H 836.2141,

found 836.2114.

Following the general procedure, treatment of 1x (71 mg, 0.31 mmol) with 2 (26 mg, 0.31 mmol), 3b


by column chromatography afforded the product 5e:


8'-(1-oxo-1,2-dihydroaceanthrylen-2-yl)-1',5',6',7'-tetrahydro-

1H,2'H-spiro[aceanthrylene-2,3'-indolizin]-1-one (5e)；99 mg;

yellow solid; Rf (ethyl acetate : petroleum ether = 1:1) = 0.52; m.p.

217-218 oC; IR(KBr): 3045, 2911, 2839, 2397, 2307, 1710, 1624,

1592, 1570, 1530, 1448, 1413, 1315, 1305, 1211, 1162, 1144, 1080

cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 9.25 (d, J = 8.4 Hz, 1H),

9.16 (d, J = 8.4 Hz, 1H), 8.74 (d, J = 12.0 Hz, 2H), 8.55 (d, J = 8.4 Hz, 2H), 8.18 (d, J = 8.4 Hz, 2H),

8.06 (d, J = 8.8 Hz, 1H), 7.98 (dd, J = 10.8, 7.6 Hz, 2H), 7.73 – 7.88 (m, 5H), 7.58 – 7.82 (m, 3H), 7.35

– 7.42 (m, 2H), 7.31 – 7.34 (m, 2H), 6.80 (d, J = 6.6 Hz, 1H), 5.90 (s, 1H), 4.81 (d, J = 7.6 Hz, 1H),

4.05 (d, J = 14.0 Hz, 1H), 3.52 – 3.72 (m, 2H), 2.12 – 2.22 (m, 2H), 1.72 – 1.83 (m, 1H), 1.58 – 1.70

(m, 1H), 1.25 – 1.32 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ = 205.75, 205.55, 146.33, 144.30,

141.46, 140.26, 139.11, 137.09, 135.84, 135.20, 133.98, 133.50, 133.45, 133.03, 132.55, 132.43,

129.71, 129.64, 129.43, 129.24, 129.11, 129.03, 128.99, 128.48, 128.26, 128.17, 128.03, 127.54,

127.38, 126.70, 126.48, 126.35, 124.87, 124.76, 124.57, 124.23, 120.36, 120.27, 110.95, 75.52, 69.79,

56.47, 55.96, 42.58, 41.08, 22.87, 20.95 ppm; ESI-HRMS: calcd. For C52H35NO6S2Cl2+H 904.1361,

found 904.1328.

Following the general procedure, treatment of 1x (80 mg, 0.34 mmol) with 2 (29 mg, 0.34 mmol), 3c


column chromatography afforded the product 5f:

8'-(1-oxo-1,2-dihydroaceanthrylen-2-yl)-1'-tosyl-2'-(tosylmethyl)-

1',5',6',7'-tetrahydro-1H,2'H-spiro[aceanthrylene-2,3'-indolizin]-

1-one (5f): 123 mg; yellow solid; Rf (ethyl acetate : petroleum ether =

1:1) = 0.50; m.p. 245-246 oC; IR(KBr): 3044, 2901, 2811, 2388, 2317,

1716, 1614, 1591, 1561, 1524, 1449, 1411, 1324, 1311, 1231, 1154,

1114, 1076 cm-1; 1H NMR (400 MHz, Chloroform-d) δ = 9.26 (d, J = 8.8 Hz, 1H), 9.18 (d, J = 8.8 Hz,

1H), 8.72 (d, J = 11.6 Hz, 2H), 8.29 (d, J = 7.6 Hz, 2H), 8.12 – 8.20 (m, 2H), 8.04 (d, J = 8.8 Hz, 1H),

7.95 – 8.01 (m, 2H), 7.77 – 7.84 (m, 2H), 7.74 (t, J = 7.8 Hz, 1H), 7.57 – 7.68 (m, 3H), 7.52 (d, J = 8.0

N

O


N

O

TsO

Ts

H

27

Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 6.70 (d, J = 6.8 Hz, 1H), 5.94 (s, 1H), 4.75

(d, J = 8.0 Hz, 1H), 4.00 – 4.13 (m, 1H), 3.70 (dd, J = 14.8, 11.6 Hz, 1H), 3.41 – 3.58 (m, 2H), 3.09 (s,

1H), 2.60 (s, 3H), 2.41 (s, 3H), 2.11 – 2.19 (m, 2H)., 1.74 – 1.84 (m, 1H), 1.52 – 1.69 (m, 1H) ppm; 13C

NMR (100 MHz, CDCl3) δ = 205.80, 205.75, 146.38, 144.45, 144.18, 139.39, 136.53, 135.57, 133.62,

133.46, 133.41, 132.22, 131.54, 131.19, 129.49, 129.46, 129.39, 129.26, 129.18, 128.81, 128.47,

128.29, 128.27, 128.09, 128.02, 127.71, 127.54, 127.23, 126.54, 126.24, 126.20, 125.11, 124.80,

124.66, 124.08, 120.21, 110.14, 75.58, 69.85, 56.61, 55.99, 42.48, 40.95, 22.89, 21.98, 21.57, 20.92.

ppm; ESI-HRMS: calcd. For C54H41NO6S2+H 864.2454, found 864.2438.

Following the general procedure, treatment of 1b (114 mg, 0.71 mmol) with 2 (61 mg, 0.71 mmol), 3f


by column chromatography afforded the product 6 and 7:

1-methyl-8'-(1-methyl-2-oxoindolin-3-yl)-1'-(pyridin-2-ylsulfonyl)-

1',5',6',7'-tetrahydro-2'H-spiro[indoline-3,3'-indolizin]-2-one (6): 46 mg;

white solid; Rf (ethyl acetate : petroleum ether = 1:1) = 0.38; m.p. 170-171

oC; IR(KBr): 3035, 2928, 2833, 2348, 2311, 1714, 1611, 1492, 1469, 1444,

1377, 1349, 1306, 1251, 1210, 1122, 1087 cm-1; 1H NMR (400 MHz,

Chloroform-d) δ = 9.15 (d, J = 8.0 Hz, 1H), 8.89 (d, J = 4.8 Hz, 1H), 8.07 (td, J = 7.6, 2.0 Hz, 1H),

7.59 – 7.64 (m, 1H), 7.54 (d, J = 7.2 Hz, 1H), 7.27 – 7.34 (m, 2H), 7.24 (d, J = 7.6 Hz, 1H), 7.07 – 7.15

(m, 2H), 6.80 (t, J = 8.4 Hz, 2H), 5.38 (s, 1H), 5.02 (dd, J = 10.0, 6.4 Hz, 1H), 3.32 (dd, J = 14.4, 6.4

Hz, 1H), 3.26 (s, 3H), 3.16 (s, 3H), 2.74 (dd, J = 14.8, 10.0 Hz, 1H), 2.16 – 2.24 (m, 1H), 2.06 – 2.14

(m, 1H), 1.60 – 1.68 (m, 1H), 1.49 – 1.58 (m, 1H), 1.35 – 1.45 (m, 1H), 0.99 – 1.15 (m, 1H) ppm; 13C

NMR (100 MHz, CDCl3) δ = 177.27, 177.10, 154.83, 149.22, 144.18, 144.04, 137.53, 136.90, 129.91,

128.90, 128.15, 127.78, 127.61, 126.56, 124.78, 124.23, 123.26, 122.97, 108.38, 108.18, 107.51, 69.68,

64.68, 49.68, 42.33, 34.72, 26.25, 25.93, 22.29, 20.96. ppm; ESI-HRMS: calcd. For C30H28N4O4S+H

541.1910, found 541.1932.

(Z)-1-methyl-8'-(1-methyl-2-oxoindolin-3-ylidene)-1'-(pyridin-2-

ylsulfonyl)-1',5',6',7',8',8a'-hexahydro-2'H-spiro[indoline-3,3'-indolizin]-

2-one (7); 92 mg; yellow solid; Rf (ethyl acetate : petroleum ether = 1:1) =

0.32; m.p. 165-166 oC; IR(KBr): 2924, 2854, 2361, 2343, 1734, 1717, 1686,

1654, 1611, 1472, 1459, 1375, 1319, 1261, 1164, 1090 cm-1; 1H NMR (400

MHz, Chloroform-d) δ = 7.92 (d, J = 7.8 Hz, 1H), 7.81 (d, J = 4.8 Hz, 1H),

7.77 (d, J = 7.2 Hz, 1H), 7.67 (td, J = 7.8, 1.6 Hz, 1H), 7.36 (td, J = 7.8, 1.2 Hz, 1H), 7.31 (d, J = 7.6

Hz, 1H), 7.17 – 7.25 (m, 2H), 7.06 (td, J = 7.6, 1.2 Hz, 1H), 7.00 (ddd, J = 7.6, 4.6, 1.2 Hz, 1H), 6.83

(d, J = 7.8 Hz, 1H), 6.59 (dd, J = 7.8, 1.2 Hz, 1H), 5.40 – 5.45 (m, 1H), 5.24 – 5.32 (m, 1H), 4.38 (ddd,

NO

N

NO

SO2N

H

NO

N

NO

SO2N

H

28

J = 12.8, 5.6, 1.6 Hz, 1H), 3.24 (dd, J = 15.4, 3.6 Hz, 1H), 3.18 (s, 3H), 3.05 (s, 3H), 2.96 – 3.04 (m,

1H), 2.92 (dd, J = 15.4, 9.8 Hz, 1H), 2.49 (td, J = 11.2, 3.6 Hz, 1H), 2.22 – 2.33 (m, 1H), 2.02 – 2.15

(m, 1H), 1.33 – 1.49 (m, 1H), ppm; 13C NMR (100 MHz, CDCl3) δ = 178.48, 166.65, 157.15, 149.22,

143.99, 141.54, 136.87, 129.61, 128.49, 128.30, 125.95, 125.34, 124.06, 123.81, 123.37, 122.98,

122.37, 122.20, 121.21, 107.92, 107.09, 66.53, 62.84, 56.31, 40.06, 33.94, 25.78, 25.45, 23.29, 22.67

ppm; ESI-HRMS: calcd. For C30H28N4O4S+H 541.1910, found 541.1917.

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.07

1.00

1.02

3.26

5

6.75

96.

773

6.78

26.

796

7.47

57.

494

7.51

4

N

O

O

1j,1H NMR, CDCl3,400 MHz

F

F

29

N

O

O

CH2OEt

1p,1H NMR, CDCl3,400 MHz

0102030405060708090100110120130140150160170180190f1 (ppm)

26.4

15

100.

478

100.

712

112.

605

112.

649

112.

695

114.

611

114.

641

114.

806

114.

835

145.

994

146.

131

148.

466

148.

602

149.

027

149.

041

149.

125

149.

143

155.

549

155.

691

157.

745

158.

165

158.

307

180.

881

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

3.00

1.97

2.00

1.93

1.98

1.16

41.

181

1.19

9

3.53

43.

552

3.56

93.

587

5.17

6

7.12

37.

139

7.14

37.

158

7.17

67.

178

7.58

97.

592

7.61

27.

631

N

O

O

1j,13C NMR, CDCl3,100 MHz

F

F

30

0102030405060708090100110120130140150160170180190200f1 (ppm)

14.7

58

64.6

3570

.075

111.

588

117.

460

124.

164

125.

295

138.

528

150.

221

158.

221

182.

914

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

2.93

3.04

2.00

1.96

0.98

1.97

1.15

61.

174

1.19

1

2.33

3

3.52

03.

537

3.55

53.

572

5.15

0

7.01

17.

031

7.39

87.

403

7.42

3

N

O

O

CH2OEt

1p,13C NMR, CDCl3,100 MHz

N

O

O

CH2OEt

1q,1H NMR, CDCl3,400 MHz

31

-100102030405060708090100110120130140150160170180190200f1 (ppm)

14.7

6420

.635

64.5

4470

.059

111.

389

117.

487

125.

520

134.

026

139.

028

148.

082

158.

394

183.

144

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.09

2.00

1.97

1.01

1.92

1.17

61.

194

1.21

1

3.53

13.

548

3.56

63.

584

5.18

5

7.05

87.

059

7.07

87.

080

7.72

27.

727

7.74

27.

748

7.75

37.

755

7.75

87.

760

N

O

O

CH2OEt

1q,13C NMR, CDCl3,100 MHz

N

O

O

CH2OEt

Br

1r,1H NMR, CDCl3,400 MHz

32

-100102030405060708090100110120130140150160170180190f1 (ppm)

14.7

46

64.7

5370

.178

113.

428

117.

165

118.

627

128.

049

140.

804

148.

886

157.

443

181.

807

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

1.99

1.00

0.99

2.02

2.08

3.92

3.94

23.

961

6.35

56.

393

6.77

56.

794

6.81

36.

832

6.85

17.

438

7.44

27.

454

7.45

97.

537

7.54

17.

553

7.55

87.

689

7.69

37.

705

7.71

07.

731

7.73

57.

747

7.75

2

N

O

O

CH2OEt

Br

1r,13C NMR, CDCl3,100 MHz

SO2

SO2

Cl Cl

3b 1H NMR, CDCl3, 400 MHz

33

0102030405060708090100110120130140150f1 (ppm)

57.7

33

129.

335

129.

714

129.

784

129.

855

131.

485

135.

958

137.

601

138.

514

140.

934

141.

369

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

1.99

2.01

2.00

3.01

2.94

1.00

3.01

2.94

1.02

1.02

1.03

1.00

1.00

2.02

1.03

1.05

1.04

2.05

4.00

2.03

1.90

1.60

71.

610

1.65

42.

105

2.11

42.

123

2.13

22.

281

2.39

93.

203

3.23

43.

804

3.83

34.

008

4.01

34.

045

4.35

24.

371

5.34

85.

740

5.74

46.

694

6.69

86.

713

6.71

87.

060

7.07

97.

129

7.14

87.

233

7.47

17.

475

7.49

27.

495

7.54

17.

560

7.57

87.

582

7.70

67.

709

7.71

37.

725

7.73

18.

094

8.11

3

4a 1H NMR, CDCl3, 400 MHz

NO

N

NO

PhO2SPhO2S

H

SO2

SO2

Cl Cl

3b 13C NMR, CDCl3, 100 MHz

34

0102030405060708090100110120130140150160170180190f1 (ppm)

20.7

6121

.030

21.2

7322

.639

26.2

0926

.306

41.3

3142

.138

49.8

2856

.752

69.8

5771

.867

107.

363

108.

277

108.

456

124.

594

124.

947

125.

474

125.

509

125.

678

128.

118

128.

255

128.

560

128.

584

128.

697

128.

893

130.

332

130.

502

131.

277

131.

866

132.

299

133.

550

133.

700

134.

264

134.

624

137.

937

141.

799

143.

385

174.

178

177.

196

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.09

2.19

2.01

1.01

3.04

2.91

1.01

1.00

1.00

1.00

0.99

1.99

1.00

1.00

1.09

1.03

0.99

3.79

2.01

2.07

2.08

2.10

72.

118

3.22

93.

261

3.67

63.

713

3.74

23.

996

4.00

24.

033

4.03

84.

388

4.40

75.

410

6.15

66.

174

6.80

76.

817

6.82

76.

837

6.99

37.

012

7.11

77.

136

7.27

27.

275

7.27

87.

337

7.35

47.

357

7.43

77.

455

7.54

77.

558

7.57

97.

599

7.61

87.

695

7.70

67.

717

7.73

37.

737

7.75

68.

190

8.20

9

4a 13C NMR, CDCl3, 100 MHz

NO

N

NO

PhO2SPhO2S

H


NO

N

NO

PhO2SPhO2S

H

35

-100102030405060708090100110120130140150160170180190f1 (ppm)

20.7

2222

.606

26.1

6726

.284

41.1

4742

.262

49.7

1456

.776

69.5

8171

.981

107.

643

108.

565

108.

812

122.

688

122.

887

123.

838

124.

093

125.

405

127.

879

128.

487

128.

586

129.

040

130.

312

130.

519

131.

273

133.

501

133.

661

134.

423

134.

764

138.

229

144.

130

145.

683

174.

339

177.

177

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

3.06

1.05

2.03

1.03

2.96

3.09

1.00

3.04

3.01

1.02

1.03

1.00

1.02

2.00

1.03

1.02

0.99

6.01

2.02

2.00

2.10

73.

177

3.23

03.

695

3.72

43.

731

3.75

43.

760

3.87

14.

023

4.02

94.

060

4.06

54.

384

4.40

35.

381

5.76

75.

773

6.69

66.

708

6.71

76.

729

6.78

06.

782

6.78

66.

788

6.84

76.

853

6.86

86.

874

7.20

57.

208

7.21

17.

214

7.55

17.

568

7.57

87.

590

7.69

17.

709

7.72

07.

728

7.73

28.

141

8.15

9

4c 1H NMR, CDCl3, 400 MHz

NO

N

NO

PhO2SPhO2S

H3CO

OCH3H


NO

N

NO

PhO2SPhO2S

H

36

-100102030405060708090100110120130140150160170180f1 (ppm)

20.7

4922

.495

26.1

6026

.332

41.2

6042

.272

50.0

3955

.713

55.8

6956

.733

69.5

5372

.215

107.

952

108.

906

109.

184

111.

047

111.

067

112.

667

114.

421

126.

455

128.

500

128.

534

129.

008

130.

053

131.

276

133.

534

133.

635

134.

345

134.

789

137.

614

138.

158

139.

171

156.

013

156.

354

173.

690

176.

683

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

8.99

1.00

9.09

3.07

2.05

1.04

3.00

3.03

1.03

1.02

1.01

1.00

0.99

2.01

1.00

1.05

7.09

2.02

1.99

1.31

21.

348

1.35

81.

380

1.38

71.

600

1.60

62.

074

3.17

93.

240

3.69

63.

732

3.76

14.

005

4.01

04.

042

4.04

74.

427

4.44

75.

389

6.35

56.

360

6.72

36.

743

7.27

07.

273

7.29

07.

293

7.33

27.

337

7.35

37.

358

7.54

97.

569

7.58

77.

604

7.62

37.

638

7.64

17.

659

7.68

67.

704

7.72

28.

146

8.16

4

4c 13C NMR, CDCl3, 100 MHz

NO

N

NO

PhO2SPhO2S

H3CO

OCH3H

4d 1H NMR, CDCl3, 400 MHz

NO

N

NO

PhO2SPhO2S

tBu

tBuH

37

0102030405060708090100110120130140150160170180f1 (ppm)

20.7

6722

.635

25.9

2626

.233

31.6

0631

.654

34.6

0934

.720

41.0

0242

.362

49.9

0656

.769

69.4

9872

.326

106.

829

107.

743

109.

248

120.

842

121.

798

124.

081

124.

902

126.

702

128.

487

128.

506

128.

520

129.

024

131.

243

133.

591

133.

708

134.

115

134.

751

138.

633

141.

713

143.

313

145.

603

146.

222

173.

922

177.

275

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.07

2.09

2.06

1.04

2.97

2.90

0.99

1.02

1.02

1.00

0.99

2.01

1.03

1.04

1.00

6.07

2.05

2.01

1.58

42.

118

2.12

93.

218

3.24

63.

668

3.69

73.

704

3.73

33.

993

3.99

94.

030

4.03

54.

345

4.36

45.

386

5.84

85.

854

5.86

75.

874

6.71

46.

724

6.73

66.

746

6.75

86.

768

6.97

26.

979

7.05

07.

057

7.22

57.

228

7.24

47.

248

7.58

87.

596

7.60

07.

611

7.63

07.

737

7.74

17.

744

7.75

98.

155

8.17

4

4e 1H NMR, CDCl3, 400 MHz

NO

N

NO

PhO2SPhO2S

F

FH

4d 13C NMR, CDCl3, 100 MHz

NO

N

NO

PhO2SPhO2S

tBu

tBuH

38

0102030405060708090100110120130140150160170180f1 (ppm)

20.6

6322

.532

26.3

1226

.425

41.1

6442

.293

49.9

9356

.606

69.4

3672

.047

108.

014

108.

094

108.

595

109.

172

109.

251

111.

882

112.

132

112.

153

112.

400

114.

041

114.

275

116.

344

116.

577

126.

955

127.

032

128.

388

128.

705

129.

140

130.

161

130.

242

131.

224

133.

312

133.

828

134.

675

135.

010

138.

117

140.

104

140.

120

141.

676

141.

694

158.

044

158.

363

160.

757

173.

894

176.

625

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.98

1.00

2.00

1.00

3.02

3.80

0.98

1.00

1.00

0.99

0.98

1.03

1.00

1.40

1.04

6.01

2.02

2.00

1.58

03.

574

3.60

83.

615

3.62

93.

644

3.97

23.

977

4.33

74.

356

5.39

46.

044

6.06

26.

879

6.89

96.

917

6.99

97.

019

7.03

77.

182

7.18

57.

203

7.25

17.

253

7.26

07.

271

7.27

47.

326

7.33

07.

345

7.55

47.

573

7.59

07.

595

7.60

07.

609

7.61

77.

620

7.62

97.

705

7.72

37.

727

7.74

68.

200

8.21

9

4e 13C NMR, CDCl3, 100 MHz

NO

N

NO

PhO2SPhO2S

F

FH

4f 1H NMR, CDCl3, 400 MHz

NO

N

NO

PhO2SPhO2S

Cl

ClH

39

0102030405060708090100110120130140150160170180f1 (ppm)

20.6

6622

.532

29.5

9029

.616

41.3

8242

.331

49.5

6056

.577

69.3

2571

.589

108.

963

115.

064

116.

146

122.

341

122.

617

123.

488

123.

626

128.

228

128.

342

128.

671

129.

099

130.

247

131.

186

131.

267

132.

551

133.

399

133.

780

134.

559

134.

958

138.

383

139.

880

141.

508

174.

665

177.

112

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.09

2.03

2.02

1.05

3.02

2.82

1.03

1.01

1.01

1.00

1.01

2.01

1.01

4.02

2.07

2.03

2.20

2.01

1.65

12.

113

2.12

72.

137

3.21

43.

236

3.75

73.

787

3.79

43.

824

4.01

14.

017

4.04

94.

306

4.32

45.

358

5.96

25.

967

6.68

96.

705

6.71

06.

726

7.40

47.

409

7.42

47.

429

7.47

17.

475

7.49

17.

496

7.51

67.

520

7.52

47.

543

7.56

27.

582

7.65

77.

677

7.69

67.

732

7.75

17.

772

7.79

37.

933

7.95

2

4f 13C NMR, CDCl3, 100 MHz

NO

N

NO

PhO2SPhO2S

Cl

ClH

4g 1H NMR, CDCl3, 400 MHz

NO

N

NO

PhO2SPhO2S

Br

BrH

40

0102030405060708090100110120130140150160170180f1 (ppm)

20.6

5522

.521

26.3

3626

.386

41.3

6742

.120

49.7

0956

.504

69.6

0571

.644

107.

990

109.

147

110.

101

115.

162

115.

539

126.

980

127.

214

127.

838

128.

729

128.

789

129.

232

130.

473

130.

928

131.

047

132.

927

133.

169

133.

798

134.

718

134.

953

137.

317

143.

234

144.

925

173.

461

176.

392

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

3.02

1.13

2.02

1.03

3.02

2.93

1.01

0.99

1.00

1.00

1.00

2.00

2.03

0.99

5.90

2.03

2.02

2.09

72.

103

2.11

02.

113

3.22

93.

263

3.68

03.

716

3.74

53.

983

3.98

84.

020

4.02

54.

346

4.36

55.

395

6.03

06.

787

6.80

26.

808

6.82

37.

149

7.15

37.

157

7.17

47.

197

7.20

37.

219

7.22

47.

346

7.35

27.

574

7.59

27.

596

7.59

97.

608

7.61

37.

728

7.73

17.

739

7.74

37.

747

7.75

28.

095

8.11

4

4g 13C NMR, CDCl3, 100 MHz

NO

N

NO

PhO2SPhO2S

Br

BrH

4h 1H NMR, CDCl3, 400 MHz

NO

N

NO

PhO2SPhO2S

F3CO

OCF3H

41

0102030405060708090100110120130140150160170180f1 (ppm)

20.6

2122

.550

26.2

9026

.463

41.0

7042

.296

49.8

7156

.497

69.2

9971

.997

108.

021

108.

344

109.

147

117.

256

118.

082

120.

990

123.

332

127.

010

128.

381

128.

739

129.

198

129.

971

131.

088

133.

130

133.

910

134.

655

135.

102

137.

989

142.

787

144.

325

144.

788

145.

072

173.

857

176.

710

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

3.06

1.10

2.00

1.02

3.02

2.89

1.03

1.04

1.01

1.00

1.02

2.00

0.97

6.08

2.16

1.91

2.05

72.

064

2.13

93.

075

3.07

73.

194

3.22

33.

592

3.62

13.

628

3.65

73.

965

3.97

14.

002

4.00

84.

314

4.33

35.

342

5.99

76.

016

6.03

86.

634

6.63

96.

649

6.65

56.

663

6.67

46.

679

7.28

37.

304

7.58

37.

603

7.62

17.

638

7.64

57.

649

7.65

77.

667

7.71

87.

736

7.75

97.

779

7.79

98.

199

8.21

8

4h 13C NMR, CDCl3, 100 MHz

NO

N

NO

PhO2SPhO2S

F3CO

OCF3H

4j 1H NMR, CDCl3, 400 MHz

NO

N

NO

PhO2SPhO2S

F

F

F

FH

42

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.05

1.95

2.02

1.03

2.92

2.93

1.02

1.00

1.03

1.00

1.00

1.99

1.00

1.00

1.05

5.93

2.02

2.03

3.21

73.

257

3.62

93.

665

3.69

43.

991

3.99

74.

028

4.03

34.

369

4.38

85.

350

6.05

86.

078

6.98

77.

150

7.15

47.

169

7.17

47.

243

7.26

37.

267

7.28

77.

292

7.30

97.

312

7.57

77.

594

7.59

77.

606

7.60

97.

615

7.62

57.

629

7.63

37.

646

7.65

07.

654

7.72

17.

738

7.74

57.

760

7.76

58.

225

8.24

3

4j 13C NMR, CDCl3, 100 MHz

NO

N

NO

PhO2SPhO2S

F

F

F

FH

4k 1H NMR, CDCl3, 400 MHz

NO

N

NO

PhO2SPhO2S

Br

Br

H

43

0102030405060708090100110120130140150160170180190f1 (ppm)

20.6

0322

.477

26.2

5326

.388

40.7

6842

.221

49.2

9756

.506

69.2

8171

.674

108.

623

111.

191

112.

242

121.

391

124.

042

124.

174

124.

986

125.

377

125.

603

125.

669

127.

316

128.

260

128.

643

129.

162

131.

205

133.

340

133.

826

134.

566

134.

823

138.

256

145.

447

146.

808

174.

113

176.

776

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.10

2.02

2.01

2.95

2.91

1.01

2.99

3.02

1.04

1.03

1.01

1.00

1.01

1.01

1.97

1.02

1.03

6.04

1.99

2.03

2.07

12.

090

2.10

12.

546

2.58

13.

487

3.54

13.

653

3.68

23.

690

3.71

93.

987

3.99

24.

024

4.02

94.

339

4.35

85.

343

5.89

95.

917

6.82

86.

847

6.86

66.

989

6.99

77.

002

7.05

47.

073

7.28

87.

300

7.51

57.

531

7.53

57.

548

7.55

47.

574

7.59

47.

688

7.70

07.

704

7.71

07.

715

7.72

08.

142

8.16

1

4k 13C NMR, CDCl3, 100 MHz

NO

N

NO

PhO2SPhO2S

Br

Br

H

4l 1H NMR, CDCl3, 400 MHz

NO

N

NO

PhO2SPhO2S

H

44

0102030405060708090100110120130140150160170180f1 (ppm)

14.1

7018

.939

18.9

7220

.755

22.6

1029

.569

41.6

4042

.253

49.3

9056

.863

69.6

1271

.390

108.

906

119.

124

120.

228

121.

724

122.

037

122.

506

122.

735

126.

013

128.

533

128.

586

128.

958

129.

117

131.

225

131.

566

133.

489

133.

561

133.

906

134.

341

134.

738

138.

146

141.

801

143.

425

175.

020

177.

796

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.08

1.63

1.98

1.03

3.11

3.83

1.00

1.01

1.00

1.00

0.98

1.00

1.03

1.32

1.05

5.99

2.13

2.03

3.57

53.

606

3.61

43.

630

3.64

33.

971

3.97

64.

007

4.33

64.

355

5.39

36.

044

6.06

36.

880

6.90

06.

919

6.99

97.

019

7.03

87.

183

7.20

47.

252

7.25

47.

260

7.27

27.

275

7.32

57.

328

7.34

37.

536

7.55

57.

574

7.59

17.

597

7.60

17.

611

7.61

87.

622

7.63

17.

706

7.72

57.

729

7.74

88.

201

8.22

0

4l 13C NMR, CDCl3, 100 MHz

NO

N

NO

PhO2SPhO2S

H

4m 1H NMR, CDCl3, 400 MHz

NO

N

NO

PhO2SPhO2S

Cl

Cl

H

45

0102030405060708090100110120130140150160170180f1 (ppm)

20.6

5522

.513

29.5

8629

.606

41.3

4942

.306

49.5

4656

.535

69.2

5471

.558

108.

928

115.

042

116.

118

122.

313

122.

590

123.

477

123.

618

128.

182

128.

332

128.

660

129.

088

130.

233

131.

147

131.

232

132.

539

133.

316

133.

787

134.

569

134.

929

138.

289

139.

839

141.

473

174.

633

177.

102

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

1.11

2.07

1.03

2.02

1.02

3.87

3.04

1.03

1.01

1.00

0.99

0.99

1.03

2.01

1.01

5.83

2.07

2.02

1.56

21.

577

3.57

33.

589

3.60

23.

609

3.64

23.

970

3.97

54.

006

4.33

04.

349

5.39

66.

069

6.08

76.

813

6.83

36.

852

6.93

86.

957

6.97

77.

363

7.36

67.

382

7.38

57.

433

7.43

67.

454

7.45

77.

552

7.55

67.

574

7.59

07.

594

7.59

87.

609

7.61

57.

619

7.62

97.

707

7.72

57.

728

7.74

78.

196

8.21

4

4m 13C NMR, CDCl3, 100 MHz

NO

N

NO

PhO2SPhO2S

Cl

Cl

H

4n 1H NMR, CDCl3, 400 MHz

NO

N

NO

PhO2SPhO2S

Br

Br

H

46

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

6.05

2.04

2.04

2.04

1.02

5.06

1.01

1.00

0.99

3.00

1.00

1.00

1.01

2.00

1.00

0.98

1.02

0.99

4.02

2.01

2.03

2.01

1.17

01.

188

1.20

61.

223

3.54

43.

553

3.56

23.

571

3.58

73.

601

3.60

43.

619

3.62

13.

624

5.08

35.

111

5.21

55.

225

5.23

85.

253

5.50

86.

158

6.17

57.

019

7.04

47.

063

7.08

27.

146

7.28

07.

355

7.35

87.

441

7.56

07.

561

7.56

37.

572

7.57

37.

575

7.58

57.

604

7.62

47.

729

7.74

78.

133

8.15

2

4n 13C NMR, CDCl3, 100 MHz

NO

N

NO

PhO2SPhO2S

Br

Br

H

4p 1H NMR, CDCl3, 400 MHz

NO

N

NO

CH2OEt

EtOH2C

PhO2SPhO2S

H

47

0102030405060708090100110120130140150160170180f1 (ppm)

14.8

9914

.955

20.5

7522

.619

41.0

1242

.257

49.8

6556

.658

64.2

3964

.476

69.4

4870

.063

70.5

6672

.209

108.

799

109.

228

110.

058

123.

053

123.

239

123.

839

124.

153

124.

835

128.

002

128.

048

128.

503

128.

636

129.

063

130.

479

131.

151

133.

385

133.

734

134.

473

134.

710

138.

102

142.

504

144.

366

174.

622

177.

386

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

6.02

2.01

1.99

2.03

3.01

2.99

1.00

4.53

1.02

1.02

1.03

1.00

3.03

1.00

1.00

2.01

1.00

0.99

2.01

4.01

2.03

2.01

1.15

91.

177

1.18

21.

194

1.19

91.

217

2.28

82.

398

3.52

93.

535

3.55

23.

568

3.58

23.

586

3.60

04.

352

4.37

15.

041

5.06

95.

190

5.21

55.

220

5.24

85.

445

5.78

16.

930

6.94

36.

950

6.96

37.

069

7.13

77.

506

7.51

07.

527

7.53

17.

550

7.55

47.

572

7.59

07.

593

7.71

87.

736

7.74

18.

034

8.05

3

4p 13C NMR, CDCl3, 100 MHz

NO

N

NO

CH2OEt

EtOH2C

PhO2SPhO2S

H

4q 1H NMR, CDCl3, 400 MHz

NO

N

NO

CH2OEt

EtOH2C

PhO2SPhO2S

H

48

0102030405060708090100110120130140150160170180190f1 (ppm)

14.8

3614

.950

20.5

9121

.033

21.2

2822

.600

41.1

4342

.136

49.9

2956

.596

64.1

3664

.334

69.6

2270

.066

70.5

4772

.074

108.

570

108.

924

109.

737

124.

501

124.

920

125.

009

128.

034

128.

295

128.

606

128.

695

128.

914

130.

598

131.

118

132.

242

132.

682

133.

494

133.

643

134.

325

134.

560

137.

748

140.

093

142.

029

174.

460

177.

420

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

6.00

2.03

1.99

2.03

0.99

4.06

1.02

1.01

0.99

0.99

3.02

1.00

1.00

2.04

1.02

5.99

2.03

2.03

2.01

1.16

21.

179

1.18

71.

197

1.20

51.

222

3.52

23.

539

3.55

73.

598

5.04

45.

072

5.17

55.

213

5.23

55.

241

5.26

35.

449

5.98

35.

988

6.93

26.

952

6.96

46.

985

7.47

17.

476

7.49

27.

497

7.50

07.

514

7.51

77.

520

7.53

37.

537

7.54

17.

548

7.56

67.

569

7.58

77.

668

7.68

77.

707

7.80

27.

874

7.89

3

4q 13C NMR, CDCl3, 100 MHz

NO

N

NO

CH2OEt

EtOH2C

PhO2SPhO2S

H

4r 1H NMR, CDCl3, 400 MHz

NO

N

NO

CH2OEt

EtOH2C

PhO2SPhO2S

Br

BrH

49

0102030405060708090100110120130140150160170180190f1 (ppm)

14.8

1814

.922

20.5

4622

.524

41.2

7742

.151

49.8

6656

.391

64.3

3264

.619

69.4

1570

.132

70.7

3071

.911

108.

057

110.

894

111.

793

115.

696

116.

068

126.

956

127.

280

127.

318

128.

784

128.

834

129.

263

130.

027

130.

932

131.

090

133.

010

133.

168

133.

885

134.

788

134.

941

137.

148

141.

544

143.

539

173.

748

176.

593

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.03

2.01

1.99

1.01

1.04

1.04

1.00

1.00

1.01

0.99

0.99

1.00

1.01

2.02

0.99

1.00

1.01

2.03

8.98

0.99

5.71

1.99

1.99

2.20

84.

456

4.47

54.

640

4.67

94.

888

4.92

75.

053

5.09

35.

219

5.25

85.

564

6.21

86.

236

6.66

66.

686

6.70

66.

974

7.07

67.

145

7.23

37.

236

7.26

07.

268

7.27

87.

302

7.30

77.

310

7.31

37.

319

7.47

17.

489

7.56

77.

584

7.58

87.

593

7.60

67.

610

7.62

57.

644

7.71

57.

732

7.75

28.

226

8.24

5

4r 13C NMR, CDCl3, 100 MHz

NO

N

NO

CH2OEt

EtOH2C

PhO2SPhO2S

Br

BrH

4s 1H NMR, CDCl3, 400 MHz

NO

N

NO

Bn

Bn

PhO2SPhO2S

H

50

0102030405060708090100110120130140150160170180f1 (ppm)

20.6

6222

.705

41.0

9642

.375

43.8

6844

.246

49.6

3756

.766

69.5

9071

.953

108.

735

109.

138

109.

652

122.

748

122.

872

123.

918

124.

244

125.

361

127.

204

127.

431

127.

595

127.

786

128.

484

128.

629

128.

700

128.

760

129.

065

130.

230

131.

290

133.

532

133.

547

133.

691

134.

439

134.

813

135.

678

135.

698

136.

071

136.

098

138.

396

143.

286

145.

043

145.

056

174.

417

177.

033

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

1.98

2.06

1.95

2.75

2.94

1.03

1.00

1.02

0.99

1.02

1.01

1.00

1.00

1.00

1.00

2.04

0.96

1.02

0.99

9.99

5.90

2.01

1.98

2.19

12.

205

2.21

92.

254

2.34

54.

043

4.42

34.

442

4.58

64.

626

4.86

64.

905

5.02

85.

227

5.26

75.

497

5.81

66.

541

6.55

16.

561

6.57

16.

927

6.94

67.

006

7.02

67.

236

7.26

07.

280

7.28

17.

294

7.30

57.

308

7.31

07.

525

7.54

57.

558

7.56

67.

575

7.58

67.

596

7.60

57.

721

7.73

98.

115

8.13

4

4s 13C NMR, CDCl3, 100 MHz

NO

N

NO

Bn

Bn

PhO2SPhO2S

H

4t 1H NMR, CDCl3, 400 MHz

NO

N

NO

Bn

Bn

PhO2SPhO2S

H

51

-100102030405060708090100110120130140150160170180f1 (ppm)

20.6

7921

.007

21.2

0022

.705

41.2

3142

.247

43.8

6844

.275

49.7

2356

.726

69.7

8871

.815

108.

464

108.

886

109.

372

124.

648

125.

083

125.

586

127.

156

127.

240

127.

356

127.

507

128.

042

128.

607

128.

658

128.

691

128.

710

128.

927

130.

296

131.

267

131.

910

132.

314

133.

604

133.

660

134.

291

134.

665

135.

945

136.

189

138.

055

140.

890

142.

706

174.

178

177.

031

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.13

2.25

2.00

1.03

1.03

1.02

1.01

1.00

1.02

1.02

1.00

1.00

1.00

2.03

1.03

1.03

10.0

71.

001.

992.

032.

002.

052.

01

2.20

94.

588

4.62

84.

894

5.03

85.

244

5.51

45.

939

5.94

46.

573

6.59

46.

615

7.19

07.

266

7.27

27.

278

7.28

17.

288

7.29

47.

301

7.30

47.

310

7.31

47.

317

7.32

17.

324

7.44

17.

445

7.44

97.

531

7.53

57.

549

7.55

37.

555

7.57

37.

592

7.61

27.

636

7.65

67.

675

7.76

17.

764

7.78

28.

013

8.03

2

4u 1H NMR, CDCl3, 400 MHz

NO

N

NO

Bn

Bn

PhO2SPhO2S

Cl

ClH

4t 13C NMR, CDCl3, 100 MHz

NO

N

NO

Bn

Bn

PhO2SPhO2S

H

52

0102030405060708090100110120130140150160170180f1 (ppm)

20.6

1422

.596

41.2

8442

.243

43.9

8544

.459

49.6

9456

.504

69.4

8271

.694

108.

455

109.

761

110.

791

124.

359

124.

648

127.

139

127.

143

127.

298

127.

302

127.

355

127.

641

127.

779

127.

928

128.

061

128.

273

128.

694

128.

812

128.

861

129.

203

130.

012

130.

163

131.

088

133.

139

133.

873

134.

754

135.

018

135.

217

135.

556

137.

509

141.

797

143.

672

173.

727

176.

448

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

2.00

2.00

1.95

1.04

1.01

0.99

1.01

0.99

1.01

1.01

1.01

1.00

1.02

2.01

12.0

14.

911.

942.

011.

99

2.20

44.

372

4.57

44.

614

4.88

75.

037

5.25

15.

290

5.51

06.

025

6.03

06.

531

6.55

36.

574

7.26

67.

272

7.27

97.

285

7.29

57.

301

7.31

57.

319

7.32

27.

335

7.34

07.

517

7.52

17.

535

7.53

97.

541

7.56

27.

566

7.57

07.

574

7.58

17.

584

7.60

27.

665

7.68

47.

704

7.76

07.

778

7.79

77.

955

7.97

4

4u 13C NMR, CDCl3, 100 MHz

NO

N

NO

Bn

Bn

PhO2SPhO2S

Cl

ClH

4v 1H NMR, CDCl3, 400 MHz

NO

N

NO

Bn

Bn

PhO2SPhO2S

Br

BrH

53

-100102030405060708090100110120130140150160170180f1 (ppm)

20.6

2622

.597

41.3

4142

.227

43.9

6844

.459

49.6

4356

.496

69.5

3471

.619

108.

371

110.

289

111.

272

115.

208

115.

298

115.

657

127.

040

127.

133

127.

333

127.

373

127.

653

127.

791

127.

819

128.

787

128.

821

128.

865

129.

258

130.

535

130.

855

131.

049

132.

874

133.

111

133.

857

134.

760

135.

014

135.

206

135.

517

137.

380

142.

298

144.

195

152.

520

155.

011

173.

567

176.

327

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

1.12

1.10

1.99

1.02

0.98

1.01

2.98

2.98

0.99

1.01

0.99

1.00

1.00

2.00

0.98

1.03

0.96

1.02

1.04

3.95

1.98

2.00

2.09

82.

105

2.18

23.

227

3.25

83.

640

3.66

93.

677

3.70

63.

938

3.94

33.

974

3.98

04.

408

4.42

75.

351

6.26

06.

279

6.81

46.

833

6.85

17.

045

7.06

47.

083

7.09

97.

117

7.13

67.

265

7.28

27.

362

7.36

57.

381

7.38

47.

425

7.44

37.

475

7.47

97.

490

7.49

67.

515

7.53

77.

599

7.62

08.

228

8.24

9

4w 1H NMR, CDCl3, 400 MHz

NO

N

NO

p-ClPhO2Sp-ClPhO2S

H

4v 13C NMR, CDCl3, 100 MHz

NO

N

NO

Bn

Bn

PhO2SPhO2S

Br

BrH

54

-100102030405060708090100110120130140150160170180190f1 (ppm)

20.7

8622

.577

26.1

6626

.289

41.3

0042

.364

49.6

7256

.824

69.5

7971

.951

107.

719

108.

726

109.

397

122.

869

122.

915

123.

747

124.

089

125.

021

127.

972

128.

386

128.

945

129.

355

129.

957

130.

540

132.

162

132.

736

134.

562

136.

761

140.

570

141.

500

144.

144

145.

654

174.

155

177.

064

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

1.99

2.02

2.03

3.06

3.02

1.01

3.03

2.98

1.05

1.01

1.04

1.03

1.00

2.01

1.03

0.99

1.02

2.01

2.02

1.99

2.01

1.62

81.

639

1.65

12.

135

2.14

32.

160

2.17

02.

322

2.39

22.

795

3.20

03.

232

3.75

83.

786

3.79

43.

823

3.93

53.

941

3.97

23.

978

4.35

84.

377

5.28

65.

732

5.73

66.

701

6.71

16.

720

6.73

17.

066

7.08

57.

152

7.15

57.

171

7.17

57.

205

7.38

87.

404

7.41

07.

509

7.53

17.

565

7.58

68.

120

8.14

0

4w 13C NMR, CDCl3, 100 MHz

NO

N

NO

p-ClPhO2Sp-ClPhO2S

H

4x 1H NMR, CDCl3, 400 MHz

NO

N

NO

p-ClPhO2Sp-ClPhO2S

H

55

-100102030405060708090100110120130140150160170180f1 (ppm)

20.7

9021

.096

21.2

6422

.612

26.2

1926

.316

41.4

3042

.166

49.8

0756

.750

69.7

7971

.744

107.

461

108.

454

108.

803

127.

629

128.

209

128.

287

128.

972

129.

180

129.

313

129.

410

130.

072

130.

179

130.

539

132.

109

132.

313

132.

649

134.

346

136.

240

140.

454

141.

422

141.

772

143.

289

173.

938

177.

097

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

3.02

1.09

1.94

1.04

2.97

2.87

1.15

1.01

0.98

1.00

0.97

1.99

1.08

2.92

1.96

1.98

2.20

2.00

1.67

12.

135

2.14

92.

159

3.23

63.

258

3.77

93.

808

3.81

63.

846

4.03

34.

039

4.33

34.

351

5.38

25.

988

5.99

36.

711

6.72

86.

732

6.74

87.

426

7.43

17.

446

7.45

07.

453

7.49

27.

496

7.51

37.

517

7.56

67.

586

7.59

67.

605

7.67

87.

697

7.71

47.

717

7.75

47.

773

7.79

27.

795

7.81

47.

959

7.97

8

4x 13C NMR, CDCl3, 100 MHz

NO

N

NO

p-ClPhO2Sp-ClPhO2S

H

4y 1H NMR, CDCl3, 400 MHz

NO

N

NO

p-ClPhO2Sp-ClPhO2S

Br

BrH

56

0102030405060708090100110120130140150160170180f1 (ppm)

20.6

5422

.528

26.3

0426

.439

40.8

1942

.272

49.3

4856

.557

69.3

3271

.725

108.

674

111.

242

112.

293

121.

442

124.

093

124.

225

125.

037

125.

428

125.

654

125.

720

127.

367

128.

311

128.

694

129.

213

131.

256

133.

391

133.

877

134.

617

134.

874

138.

307

145.

498

146.

859

174.

164

176.

827

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

2.06

2.04

2.10

3.09

3.01

3.11

2.80

1.05

3.11

2.94

1.05

0.99

1.04

1.00

0.99

1.98

1.07

1.07

0.99

6.02

2.04

1.39

01.

404

1.41

41.

428

1.43

21.

433

1.60

61.

629

1.64

01.

655

2.12

12.

127

2.14

22.

155

2.28

32.

393

2.50

62.

528

2.83

42.

838

2.84

63.

193

3.19

83.

221

3.22

63.

785

3.95

03.

987

4.30

84.

326

5.34

75.

697

6.68

56.

704

7.05

17.

071

7.12

07.

140

7.21

87.

314

7.33

77.

343

7.92

17.

938

7.94

3

4y 13C NMR, CDCl3, 100 MHz

NO

N

NO

p-ClPhO2Sp-ClPhO2S

Br

BrH

4z 1H NMR, CDCl3, 400 MHz

NO

N

NO

TsTs

H

57

0102030405060708090100110120130140150160170180190f1 (ppm)

20.8

1421

.020

21.2

7621

.704

21.8

7322

.654

26.1

8826

.268

41.3

4242

.102

49.8

2556

.859

69.8

4171

.853

107.

299

108.

029

108.

173

124.

635

124.

898

125.

966

128.

065

128.

589

128.

811

129.

204

129.

418

130.

206

130.

897

131.

272

131.

627

132.

208

134.

701

134.

895

141.

807

143.

395

144.

554

145.

213

174.

182

177.

148

4z 13C NMR, CDCl3, 100 MHz

NO

N

NO

TsTs

H

58

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

1.08

1.05

1.93

1.98

2.97

2.93

1.04

3.06

2.91

1.08

1.04

0.99

1.00

1.03

2.01

4.01

1.06

4.04

2.05

1.64

11.

654

2.13

82.

151

2.16

12.

528

2.57

53.

206

3.22

73.

786

3.79

43.

823

3.95

53.

961

3.99

24.

260

4.27

85.

354

5.84

25.

847

6.68

26.

695

6.70

26.

715

7.30

07.

305

7.32

17.

326

7.39

77.

399

7.40

27.

404

7.41

87.

423

7.42

57.

453

7.45

97.

464

7.47

37.

480

7.48

57.

490

7.49

57.

746

7.76

5

0102030405060708090100110120130140150160170180190f1 (ppm)

20.7

2421

.749

21.9

5822

.576

26.3

4026

.379

41.4

3842

.105

49.7

6456

.648

69.6

9771

.662

76.6

8310

7.54

910

9.11

011

0.03

911

5.11

011

5.51

112

7.07

312

7.19

612

8.24

712

8.35

212

8.83

112

9.48

012

9.77

913

0.00

713

0.04

613

0.39

713

0.55

613

0.91

813

1.07

613

2.78

413

4.32

713

5.07

414

3.28

114

4.88

814

4.96

014

5.87

717

3.56

717

6.42

8

4aa 1H NMR, CDCl3, 400 MHz

NO

N

NO

TsTs

Br

BrH

4aa 13C NMR, CDCl3, 100 MHz

NO

N

NO

TsTs

Br

BrH

59

1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

2.09

0.89

1.00

1.02

1.01

1.02

1.03

2.95

2.98

1.03

1.00

1.01

0.99

0.98

1.01

0.99

1.97

1.02

1.94

1.00

2.04

1.44

91.

460

1.61

51.

739

2.10

72.

115

2.19

72.

485

2.50

22.

522

2.53

92.

700

2.72

52.

737

2.76

23.

146

3.28

14.

929

4.94

54.

953

4.97

05.

534

6.45

36.

471

6.76

26.

781

6.81

66.

835

6.96

66.

985

7.00

37.

107

7.12

57.

144

7.28

17.

301

7.50

97.

527

7.67

47.

692

7.71

17.

742

7.76

08.

553

8.57

1

0102030405060708090100110120130140150160170180f1 (ppm)

20.9

1722

.463

25.9

4726

.267

35.3

7842

.488

49.7

98

64.9

5869

.329

107.

521

108.

235

108.

308

122.

852

123.

198

123.

666

124.

187

125.

969

126.

693

127.

745

128.

489

128.

950

129.

876

131.

335

134.

096

134.

799

137.

179

144.

128

144.

181

177.

322

177.

350

4ab 1H NMR, CDCl3, 400 MHz

NO

N

NO

PhO2S H

4ab 13C NMR, CDCl3, 100 MHz

NO

N

NO

PhO2S H

60

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

2.14

0.91

1.01

1.98

2.93

3.00

1.10

1.11

3.05

2.99

1.09

1.00

1.04

1.02

1.01

2.06

0.99

1.97

1.08

2.03

1.46

52.

140

2.14

82.

205

2.26

32.

398

2.45

42.

470

2.49

12.

507

2.69

82.

723

2.73

52.

761

3.12

13.

258

4.91

84.

927

5.48

66.

152

6.15

76.

635

6.65

56.

702

6.72

27.

047

7.05

17.

060

7.06

67.

072

7.08

17.

318

7.67

57.

693

7.69

37.

697

7.71

37.

752

7.75

57.

771

8.56

08.

565

8.57

88.

582

8.58

5

0102030405060708090100110120130140150160170180f1 (ppm)

20.9

3720

.953

21.2

5322

.485

25.9

4226

.274

35.4

1842

.406

49.8

88

65.1

2469

.389

107.

210

108.

016

124.

477

125.

076

126.

927

127.

965

128.

502

128.

960

129.

976

131.

405

132.

182

132.

716

133.

984

137.

103

141.

713

141.

871

177.

337

177.

363

4ac 1H NMR, CDCl3, 400 MHz

NO

N

NO

PhO2S H

4ac 13C NMR, CDCl3, 100 MHz

NO

N

NO

PhO2S H

61

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.12

1.92

1.99

1.02

1.05

1.03

1.00

1.00

0.99

3.87

2.00

5.03

1.10

1.93

2.99

2.02

2.01

1.25

62.

053

2.06

72.

080

3.54

63.

581

4.03

34.

618

4.63

75.

784

6.67

46.

691

7.50

47.

508

7.51

77.

621

7.62

57.

643

7.68

87.

707

7.72

07.

726

7.73

77.

739

7.74

27.

755

7.75

77.

764

7.77

57.

780

7.81

77.

854

7.87

37.

925

7.93

17.

947

7.97

07.

987

7.98

88.

114

8.13

48.

142

8.16

28.

383

8.40

2

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

20.1

9222

.395

40.3

7041

.876

55.1

3455

.775

69.1

2374

.745

109.

820

120.

080

120.

144

120.

461

120.

601

123.

328

125.

492

127.

395

127.

607

127.

686

128.

037

128.

357

128.

428

129.

693

130.

173

130.

808

130.

834

131.

459

133.

058

133.

179

133.

884

134.

476

135.

291

137.

802

138.

360

141.

472

143.

581

205.

165

205.

760

5a 1H NMR, CDCl3, 400 MHz

NO

SO2PhO

SO2Ph

H

5a 13C NMR, CDCl3, 100 MHz

NO

SO2PhO

SO2Ph

H

62

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

2.07

2.03

2.03

2.02

1.02

1.00

1.00

1.02

3.97

6.02

2.01

3.03

2.03

2.02

1.27

91.

561

1.56

72.

105

3.51

13.

520

3.52

63.

553

3.98

64.

017

4.65

64.

674

5.74

26.

795

6.81

27.

417

7.66

57.

682

7.68

67.

703

7.71

07.

727

7.73

27.

741

7.74

77.

758

7.76

57.

778

7.78

67.

849

7.85

87.

866

7.87

97.

921

7.93

87.

948

7.96

97.

973

7.99

08.

121

8.14

18.

157

8.17

78.

454

8.47

5


N

O


63

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

20.8

7622

.994

41.1

6742

.603

55.7

2156

.441

69.7

4575

.360

111.

038

120.

769

121.

151

121.

302

124.

029

126.

303

128.

050

128.

398

129.

018

129.

257

129.

528

130.

417

130.

823

131.

505

131.

852

132.

509

132.

672

132.

947

134.

426

134.

937

135.

429

137.

077

138.

784

140.

442

141.

527

142.

129

144.

125

205.

685

206.

134


N

O


64

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.17

1.01

1.16

1.98

2.78

3.01

2.08

1.01

1.04

1.00

0.98

1.84

2.09

1.98

0.93

2.98

1.98

0.95

1.86

1.97

1.90

1.26

32.

081

2.09

42.

458

2.57

43.

522

3.55

73.

993

4.58

94.

608

5.78

86.

708

6.72

57.

273

7.29

37.

369

7.38

57.

389

7.46

57.

485

7.61

77.

634

7.63

87.

712

7.73

17.

749

7.75

57.

760

7.76

97.

776

7.84

67.

856

7.86

87.

873

7.92

27.

939

7.94

37.

961

7.97

88.

106

8.12

68.

135

8.15

58.

224

8.24

4

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

20.8

5921

.642

21.9

7223

.002

41.0

2742

.492

55.7

4356

.515

57.8

4669

.743

75.4

0611

0.21

612

0.73

312

1.00

612

1.15

312

3.87

812

6.01

512

7.96

612

8.01

312

8.17

212

8.23

912

8.32

412

9.03

012

9.24

612

9.49

812

9.99

213

0.03

613

0.76

813

0.87

813

1.09

713

1.35

113

1.46

913

2.10

613

2.42

613

4.54

013

5.20

313

5.51

613

6.07

313

8.71

813

9.06

914

2.04

514

4.18

014

4.60

914

5.44

020

5.72

0

5c 1H NMR, CDCl3, 400 MHz

N

O

Ts OTs

H

5c 13C NMR, CDCl3, 100 MHz

N

O

Ts OTs

H

65

1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

2.24

0.73

1.01

2.01

1.07

1.04

1.03

1.03

1.00

0.99

4.00

4.05

6.03

2.02

1.03

2.02

1.98

2.00

1.00

1.02

1.26

11.

277

1.27

81.

296

2.14

65.

944

6.65

96.

675

7.47

47.

492

7.50

57.

509

7.52

67.

593

7.60

97.

613

7.62

77.

631

7.64

87.

653

7.73

37.

751

7.75

57.

772

7.80

17.

818

7.82

57.

844

7.97

57.

985

7.99

18.

007

8.03

28.

054

8.15

78.

169

8.17

88.

190

8.43

08.

434

8.45

28.

717

8.74

29.

260

9.28

2

0102030405060708090100110120130140150160170180190200210f1 (ppm)

20.8

4722

.872

40.8

9142

.471

55.9

8856

.488

69.8

6075

.537

110.

324

120.

175

120.

226

124.

123

124.

647

124.

772

125.

090

125.

384

125.

422

126.

261

126.

560

127.

227

127.

554

127.

665

128.

009

128.

094

128.

272

128.

459

128.

639

128.

863

129.

192

129.

509

130.

441

131.

491

132.

278

133.

402

133.

477

133.

511

133.

732

133.

886

134.

406

135.

357

136.

362

138.

476

139.

272

144.

204

146.

408

205.

733

205.

765

5d 1H NMR, CDCl3, 400 MHz

N

O

SO2PhO

SO2Ph

H

5d 13C NMR, CDCl3, 100 MHz

N

O

SO2PhO

SO2Ph

H

66

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

2.19

1.05

1.08

1.99

2.04

1.06

1.00

1.00

1.03

2.07

2.10

3.14

5.05

2.05

1.00

2.02

2.00

2.06

1.01

1.07

4.03

44.

800

4.82

05.

900

6.79

26.

809

7.31

07.

326

7.33

17.

378

7.38

37.

400

7.62

47.

632

7.64

07.

646

7.65

47.

663

7.66

97.

673

7.74

67.

759

7.76

67.

772

7.78

37.

788

7.79

47.

810

7.83

77.

963

7.97

97.

985

8.00

68.

046

8.06

88.

172

8.19

48.

538

8.55

98.

719

8.75

39.

155

9.17

79.

240

9.26

2

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

20.9

5322

.868

41.0

8242

.585

55.9

6556

.468

69.7

9075

.524

110.

948

120.

271

120.

362

124.

228

124.

565

124.

764

124.

866

126.

347

126.

483

126.

701

127.

378

127.

544

128.

031

128.

165

128.

259

128.

475

128.

985

129.

033

129.

109

129.

241

129.

434

129.

638

129.

715

132.

426

132.

553

133.

035

133.

450

133.

501

133.

980

135.

205

135.

838

137.

090

139.

109

140.

262

141.

457

144.

298

146.

328

205.

554

205.

747

5e 1H NMR, CDCl3, 400 MHz

N

O


5e 13C NMR, CDCl3, 100 MHz

N

O


67

1.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

1.08

1.03

1.96

3.20

3.07

0.80

2.13

1.09

1.00

0.98

1.00

1.00

2.01

2.03

2.04

3.05

0.99

2.03

2.00

1.02

2.06

1.99

2.08

1.01

1.03

2.13

12.

145

2.15

92.

405

2.59

74.

050

4.05

44.

737

4.75

75.

940

6.69

36.

710

7.21

07.

230

7.34

17.

361

7.51

57.

535

7.59

77.

602

7.60

87.

616

7.62

47.

639

7.74

27.

793

7.81

27.

972

7.98

67.

996

8.02

98.

051

8.14

88.

151

8.15

68.

170

8.17

78.

279

8.29

88.

702

8.73

19.

165

9.18

79.

249

9.27

1

0102030405060708090100110120130140150160170180190200210f1 (ppm)

20.9

2221

.571

21.9

7522

.886

40.9

5542

.485

55.9

9056

.605

69.8

5075

.577

110.

139

120.

208

124.

078

124.

664

124.

803

125.

109

126.

195

126.

235

126.

538

127.

230

127.

538

127.

706

128.

020

128.

088

128.

271

128.

294

128.

471

128.

806

129.

182

129.

256

129.

389

129.

465

129.

494

131.

192

131.

535

132.

218

133.

406

133.

455

133.

624

135.

565

136.

529

139.

390

144.

183

144.

450

146.

379

205.

753

205.

797

5f 1H NMR, CDCl3, 400 MHz

N

O

TsO

Ts

H

5f 13C NMR, CDCl3, 100 MHz

N

O

TsO

Ts

H

68

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

1.18

1.13

1.10

0.93

1.12

1.05

1.03

2.98

3.00

1.04

1.03

1.00

2.01

2.05

1.09

1.99

1.07

1.08

1.04

1.00

0.99

2.71

32.

738

2.75

02.

775

3.15

53.

260

3.29

83.

315

3.33

53.

351

5.37

96.

778

6.79

96.

820

7.09

67.

098

7.11

17.

114

7.11

77.

130

7.14

87.

150

7.23

47.

253

7.26

87.

271

7.27

47.

296

7.31

57.

318

7.52

87.

546

7.59

77.

600

7.60

97.

611

7.61

67.

619

7.62

88.

072

8.07

68.

888

8.90

09.

142

9.16

2

0102030405060708090100110120130140150160170180190f1 (ppm)

20.9

5722

.292

25.9

3226

.245

34.7

1742

.326

49.6

81

64.6

7669

.678

107.

507

108.

182

108.

377

122.

968

123.

260

124.

235

124.

785

126.

558

127.

613

127.

783

128.

152

128.

898

129.

907

136.

899

137.

529

144.

040

144.

177

149.

223

154.

825

177.

097

177.

267

6 1H NMR, CDCl3, 400 MHz

NO

N

NO

SO2N

H

6 13C NMR, CDCl3, 100 MHz

NO

N

NO

SO2N

H

69

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

1.08

1.05

1.03

1.01

1.00

0.93

3.14

2.97

1.02

1.00

1.13

1.00

1.00

1.04

0.99

0.99

1.99

0.98

1.00

0.98

0.97

0.99

0.98

2.92

72.

951

3.05

13.

054

3.18

33.

218

3.22

75.

277

5.29

45.

297

5.41

75.

421

6.57

46.

577

6.59

46.

597

6.82

56.

844

6.99

16.

999

7.01

17.

056

7.05

87.

075

7.19

87.

200

7.20

47.

207

7.21

67.

219

7.22

37.

226

7.29

67.

315

7.34

27.

361

7.36

57.

669

7.67

37.

765

7.78

37.

806

7.81

77.

909

7.92

9

0102030405060708090100110120130140150160170180f1 (ppm)

22.6

7323

.286

25.4

4625

.781

33.9

3840

.057

56.3

1362

.843

66.5

27

107.

086

107.

915

121.

212

122.

204

122.

367

122.

976

123.

365

123.

814

124.

056

125.

344

125.

948

128.

302

128.

492

129.

613

136.

873

141.

543

143.

986

149.

217

157.

155

166.

647

178.

482

7 1H NMR, CDCl3, 400 MHz

NO

N

NO

SO2N

H

7 13C NMR, CDCl3, 100 MHz

NO

N

NO

SO2N

H

Substituted Oxindoles Azomethine Ylide Route Synthesis of ... · 1 Direct N-H/α, α, β,...

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