Zn-Catalyzed Diastereo- and Enantioselective Cascade. Reaction of 3-Isothiocyanato Oxindoles and 3-Nitroindoles:

Transcription

1 Zn-Catalyzed Diastereo- and Enantioselective Cascade Reaction of 3-Isothiocyanato xindoles and 3-itroindoles: tereocontrolled yntheses of Polycyclic pirooxindoles Jian-Qiang Zhao,, Zhi-Jun Wu, Ming-Qiang Zhou, Xiao-Ying Xu,*, Xiao-i Zhang and Wei-Cheng Yuan*, ational Engineering Research Center of Chiral Drugs, Chengdu Institute of rganic Chemistry, Chinese Academy of ciences, Chengdu , China Chengdu Institute of Biology, Chinese Academy of ciences, Chengdu , China University of Chinese Academy of ciences, Beijing , China * * upporting Information Table of Contents 1. General experimental information onlinear effect experiment General experimental procedures for asymmetric synthesis of compounds Copy of EI-M spectrum MR, PLC spectra for compounds 3a-3w, and 13 C MR for compounds 3f and 3q...7

2 1. General experimental information Reagents were purchased from commercial sources and were used as received unless mentioned otherwise. Reactions were monitored by TLC. 1 MR and 13 C MR spectra were recorded in CDCl 3 and DM-d 6. 1 MR chemical shifts are reported in ppm relative to tetramethylsilane (TM) with the solvent resonance employed as the internal standard (CDCl 3 at 7.26 ppm, DM-d 6 at 2.50 ppm). Data are reported as follows: chemical shift, multiplicity (s = singlet, br s = broad singlet, d = doublet, t = triplet, q = quartet, m = multiplet), coupling constants (z) and integration. 13 C MR chemical shifts are reported in ppm from tetramethylsilane (TM) with the solvent resonance as the internal standard (CDCl 3 at 77. ppm, DM-d 6 at ppm). lting points were recorded on a melting point apparatus. 2. onlinear effect experiment To a flame dried reaction tube were added activated 4 Å M (100 mg), Zn(Tf) 2 (3.6 mg, 10 mol %) and ligand L1 in different enantiomeric purities (6.7 mg, 11 mol %), followed by addition toluene (1.0 ml). The reaction solution was stirred at room temperature for 2 h under a nitrogen atmosphere and then the 3-nitroindole 2a (0.11 mmol) was added. The mixture was further stirred at room temperature for 15- min before the addition of 3-isothiocyanato oxindole 1a (0.10 mmol). After stirring for 8 time at 50 o C, the reaction mixture was directly purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 3:1) to give the desired product 3a. entry ee of ligand L1 (%) ee of product 3a (%) Figure 1 Investigation of nonlinear effect. 3. General experimental procedures for asymmetric synthesis of compounds 3 (Table 2) To a flame dried reaction tube were added activated 4 Å molecular sieve (100 mg), Zn(Tf) 2 (3.6 mg, 10 mol %) and chiral ligand L1 (6.7 mg, 11 mol %), followed by addition toluene (1.0 ml). The reaction solution was stirred at room temperature for 2 h under a nitrogen atmosphere and then the 3-nitroindole 2 (0.11 mmol) was added. The mixture was further stirred at room temperature for 15- min before the addition of 3-isothiocyanato oxindole 1 (0.10 mmol). After stirring for specific time at 50 o C, the reaction mixture was directly purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 3:1~3:2) to give the desired 1

3 product 3. We provide the 13 C MR spectra for compounds 3f and 3q. Regarding to the 13 C MR spectra of other compounds in this work, please see Ref 1. (3,3a'R,8b')-1-methyl-8b'-nitro-1'-thioxo-4'-tosyl-2',3a',4',8b'-tetrahyd ro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3a). light yellow foam; 51.5 mg, yield 99%; dr >99:1, 99% ee, [α] D = (c 1.35, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/et; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = min); 1 MR (300 Mz, CDCl 3 ), δ (ppm): 2.32 (s, 3), 3.32 (s, 3), 5.89 (s, 1), 5.98 (d, J = 7.5 z, 1), 6.79 (t, J = 7.5 z, 1), 6.92 (d, J = 7.8 z, 1), 7.13 (d, J = 8.1 z, 2), (m, 4), 7.46 (d, J = 8.1 z, 1), (m, 1), 8.08 (d, J = 7.8 z, 1), 8.52 (s, 1). Cl (3,3a'R,8b')-7'-chloro-1-methyl-8b'-nitro-1'-thioxo-4'-tosyl-2',3a',4',8 b'-tetrahydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3b). light yellow foam; 53.8 mg, yield 97%; dr >99:1, 98% ee, [α] D = (c 1.3, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/i-pr; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = 8.34 min); 1 MR (300 Mz, CDCl 3 ), δ (ppm): 2.34 (s, 3), 3.32 (s, 3), 5.86 (s, 1), 6.08 (d, J = 7.5 z, 1), 6.84 (t, J = 7.5 z, 1), 6.93 (d, J = 7.8 z, 1), 7.15 (d, J = 8.1 z, 2), (m, 4), (m, 1), 8.04 (d, J = 2.1 z, 1), 8.54 (s, 1). Br (3,3a'R,8b')-7'-bromo-1-methyl-8b'-nitro-1'-thioxo-4'-tosyl-2',3a',4',8b' -tetrahydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3c). light yellow oil; 58.7 mg, yield 98%; dr >99:1, 95% ee, [α] D = +1.6 (c 1.14 CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/i-pr; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = 8.80 min); 1 MR (300 Mz, DM-d 6 ), δ (ppm): 2.33 (s, 3), 3.27 (s, 3), 5.74 (s, 1), 5.98 (d, J = 7.5 z, 1), 6.90 (t, J = 7.5 z, 1), 7. (d, J = 7.8 z, 1), 7.33 (d, J = 8.1 z, 2), (m, 4), (m, 1), 8.08 (d, J = 2.1 z, 1), (s, 1). (3,3a'R,8b')-7'-methoxy-1-methyl-8b'-nitro-1'-thioxo-4'-tosyl-2',3a',4 ',8b'-tetrahydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3d). light yellow foam; 52.9 mg, yield 96%; dr >99:1, 98% ee, [α] D = (c 0.62, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/i-pr; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = min); 1 MR (300 Mz, DM-d 6 ), δ (ppm): 2.32 (s, 3), 3.26 (s, 3), 3.83 (s, 3), 5.70 (s, 1), 5.82 (d, J = 7.5 z, 1), 6.85 (t, J = 7.5 z, 1), 7.19 (d, J = 7.8 z, 1), (m, 6), (m, 1), 7.46 (d, J = 2.4 z, 1), (s, 1). 2

4 Bn (3,3a'R,8b')-7'-(benzyloxy)-1-methyl-8b'-nitro-1'-thioxo-4'-tosyl- 2',3a',4',8b'-tetrahydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3e). light yellow oil; 62.1 mg, yield 99%; dr >99:1, 98% ee, [α] D = +1.1 (c 0.75, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/i-pr; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = min); 1 MR (300 Mz, CDCl 3 ), δ (ppm): 2.34 (s, 3), 3.32 (s, 3), 5.06 (d, J = 11.4 z, 1), 5.12 (d, J = 11.4 z, 1 ), 5.83 (s, 1), 5.97 (d, J = 7.5 z, 1), 6.79 (t, J = 7.5 z, 1), 6.91 (d, J = 7.8 z, 1), (m, 3), (m, 9), 7.66 (d, J = 2.7 z, 1), 8.51 (s, 1). C (3,3a'R,8b')-1-methyl-8b'-nitro-2-oxo-1'-thioxo-4'-tosyl-2',3a',4',8b'-t etrahydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indole]-7'-carbonitrile (3f). light yellow foam; 54.1 mg, yield 99%; dr >99:1, 99% ee, [α] D = +8.5 (c 1.3, CCl 3 ); m.p C. The ee was determined by PLC analysis through derivatization using a Chiralpak D- column (90/10 hexane/i-pr; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = min); 1 MR (300 Mz, DM-d 6 ), δ (ppm): 2.33 (s, 3), 3.27 (s, 3), 5.84 (s, 1), 6.05 (d, J = 7.5 z, 1), 6.89 (t, J = 7.5 z, 1), 7.19 (d, J = 7.8 z, 1), 7.34 (d, J = 8.1 z, 2), (m, 1), (m, 2), 7.61 (d, J = 7.8 z, 1), (m, 1), 8.35 (d, J = 1.5 z, 1), (s, 1); 13 C MR (75 Mz, DM-d 6 ), δ (ppm): 21.0, 26.9, 73.2, 73.6, 101.5, 108.2, 110.0, 116.3, 117.7, 122.7, 123.0, 123.3, 124.4, 126.6, 130.6, 131.6, 132.2, 132.5, 138.3, 143.8, 145.4, 146.2, 171.8, 190.6; RM (EI) Calcd. for C [M+a] + : ; found: Cl (3,3a'R,8b')-8'-chloro-1-methyl-8b'-nitro-1'-thioxo-4'-tosyl-2',3a',4',8b'- tetrahydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3g). light yellow foam; 54.9 mg, yield 99%; dr 95:5, 95% ee, [α] D = (c 0.61 CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/et; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = min); 1 MR (300 Mz, DM-d 6 ), δ (ppm): 2.33 (s, 3), 3.25 (s, 3), 5.66 (s, 1), 6.00 (d, J = 7.5 z, 1), 6.85 (t, J = 7.5 z, 1), 7.18 (d, J = 7.8 z, 1), 7.32 (d, J = 8.4 z, 2), (m, 4), (m, 1), 7.67 (t, J = 8.1 z, 1), (s, 1). Br (3,3a'R,8b')-8'-bromo-1-methyl-8b'-nitro-1'-thioxo-4'-tosyl-2',3a',4',8b' -tetrahydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3h). light yellow oil; 56.9 mg, yield 95%; dr 93:7, 91% ee, [α] D = (c 0.71, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/i-pr; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = min); 1 MR (300 Mz, DM-d 6 ), δ (ppm): 2.33 (s, 3), 3.25 (s, 3), 5.64 (s, 1), 6.04 (d, J = 7.5 z, 1), 6.86 (t, J = 7.5 z, 1), 7.17 (d, J = 7.8 z, 1), 7.32 (d, J = 8.4 z, 2), 7.41 (d, J = 8.4 z, 3), (m, 1), 7.55 (t, J = 8.1 z, 1), (m, 1), (s, 1). Cl (3,3a'R,8b')-6'-chloro-1-methyl-8b'-nitro-1'-thioxo-4'-tosyl-2',3a',4',8b'-tetrahydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3i). light yellow foam; 54.8 mg, yield 99%; dr >99:1, 99% ee, [α] D = -4.4 (c 3

5 1.1, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/et; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = 9.43 min); 1 MR (300 Mz, CDCl 3 ), δ (ppm): 2.34 (s, 3), 3.32 (s, 3), 5.86 (s, 1), 6.11 (d, J = 7.5 z, 1), 6.90 (t, J = 7.5 z, 1), 6.94 (d, J = 7.8 z, 1), 7.17 (d, J = 8.1 z, 2), (m, 1), (m, 4), 8.01 (d, J = 8.4 z, 1), 8.56 (s, 1). (3,3a'R,8b')-1,5'-dimethyl-8b'-nitro-1'-thioxo-4'-tosyl-2',3a',4',8b'-tet rahydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3j). light yellow foam; 51.9 mg, yield 97%; dr >99:1, 98% ee, [α] D = (c 1.1, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/et; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = 7.27 min); 1 MR (300 Mz, DM-d 6 ), δ (ppm): 2.06 (s, 3), 2.42 (s, 3), 3.02 (s, 3), 5.27 (d, J = 7.5 z, 1), 5.70 (s, 1), 6.76 (t, J = 7.2 z, 1), 7.12 (d, J = 7.5 z, 1), (m, 5), (m, 2), 7.92 (d, J = 6.9 z, 1), (s, 1). (3,3a'R,8b')-1-methyl-8b'-nitro-4'-(phenylsulfonyl)-1'-thioxo-2',3a',4',8 b'-tetrahydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3k). light yellow foam; 49.6 mg, yield 98%; dr >99:1, 99% ee, [α] D = (c 1.23, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/et; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = 9.54 min); 1 MR (300 Mz, CDCl 3 ), δ (ppm): 3.33 (s, 3), 5.87 (s, 1), 5.98 (d, J = 7.5 z, 1), 6.79 (t, J = 7.5 z, 1), 6.92 (d, J = 7.8 z, 1), (m, 4), (m, 5), (m, 1), 8.52 (s, 1). (3,3a'R,8b')-1-methyl-4'-(methylsulfonyl)-8b'-nitro-1'-thioxo-2',3a',4',8 b'-tetrahydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3l). light yellow foam; 43.1 mg, yield 97%; dr >99:1, 98% ee, [α] D = (c 1.0, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak D- column (80/ hexane/i-pr; flow rate: 1.0 ml/min; λ = 254 nm; t major = 9.56 min, t minor = min); 1 MR (300 Mz, DM-d 6 ), δ (ppm): 3.02 (s, 3), 3. (s, 3), 5.94 (d, J = 6.9 z, 1), 5.98 (s, 1), 6.83 (t, J = 7.5 z, 1), 7.12 (d, J = 7.8 z, 1), 7.24 (d, J = 8.1 z, 1), (m, 2), (m, 1), 8.13 (d, J = 7.8 z, 1), (s, 1). s (3,3a'R,8b')-1-methyl-8b'-nitro-4'-((4-nitrophenyl)sulfonyl)-1'-thioxo-2', 3a',4',8b'-tetrahydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3m). light yellow foam; 54.5 mg, yield 99%; dr >99:1, 99% ee, [α] D = (c 1.1, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak D- column (80/ hexane/i-pr; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = min); 1 MR (300 Mz, DM-d 6 ), δ (ppm): 3.28 (s, 3), 5.80 (d, J = 7.5 z, 1), 5.83 (s, 1), 6.85 (t, J = 7.5 z, 1), 7.19 (d, J = 7.8 z, 1), 7.42 (d, J = 7.8 z, 1), (m, 2), 7.76 (t, J = 7.8 z, 1), 7.87 (d, J = 8.7 z, 2), 8.06 (d, J = 8.1 z, 1), 8.31 (d, J = 8.7 z, 2), (s, 1). Bs Ms Ac (3,3a'R,8b')-4'-acetyl-1-methyl-8b'-nitro-1'-thioxo-2',3a',4',8b'-tetrahy dro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3n). light yellow foam; 40.4 mg, yield 99%; dr > 99:1, >99% ee, [α] D = (c 0.6, CCl 3 ). 4

6 The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/et; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = min); 1 MR (300 Mz, 50 o C, DM-d 6 ), δ (ppm): 2.03 (s, 3), 3.24 (s, 3), 5.89 (d, J = 5.7 z, 1), 6.01 (s, 1), 6.82 (s, 1), (m, 1), (m, 3), 7.67 (s, 1), 8. (s, 1), (s, 1). Cbz (3,3a'R,8b')-benzyl 1-methyl-8b'-nitro-2-oxo-1'-thioxo-3a',8b'-dihydro -1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indole]-4'(2')-carboxylate (3o). light yellow foam; 48.1 mg, yield 96%; dr >99:1, >99% ee, [α] D = (c 0.5, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/i-pr; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = min); 1 MR (300 Mz, 50 o C, DM-d 6 ), δ (major, ppm): 2.69 (s, 3), 4.58 (d, J = 9.6 z, 1), 4.94 (d, J = 9.6 z, 1), (m, 2), (m, 2), (m, 2), (m, 5), (m, 2), 8.15 (d, J = 5.7 z, 1), (s, 1). CEt (3,3a'R,8b')-ethyl 1-methyl-8b'-nitro-2-oxo-1'-thioxo-3a',8b'- dihydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indole]-4'(2')-carboxylat e (3p). light yellow foam; 42.9 mg, yield 98%; dr >99:1, >99% ee, [α] D = (c 1.1, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/et; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = 7.38 min); 1 MR (300 Mz, DM-d 6 ), δ (major, ppm): 0.97 (t, J = 6.9 z, 3), 3.26 (s, 3), (m, 1), (m, 1), (m, 2), 6.85 (t, J = 7.5 z, 1), 7.15 (d, J = 7.8 z, 1), (m, 2), (m, 2), 8.12 (d, J = 7.8 z, 1), (s, 1). C (3,3a'R,8b')-methyl 1-methyl-8b'-nitro-2-oxo-1'-thioxo-3a',8b'- dihydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indole]-4'(2')-carboxyl ate (3q). light yellow foam; 41.2 mg, yield 97%; dr >99:1, >99% ee, [α] D = (c 1.0, CCl 3 ); m.p C(decomposition). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/i-pr; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = 7.91 min); 1 MR (300 Mz, DM-d 6 ), δ (ppm): 3.28 (s, 3), 3.30 (s, 3), (m, 2), 6.84 (t, J = 7.5 z, 1), 7.15 (d, J = 7.8 z, 1), (m, 2), (m, 2), 8.12 (d, J = 7.8 z, 1), (s, 1); 13 C MR (75 Mz, DM-d 6 ), δ (ppm): 26.6, 52.6, 71.0, 73.3, 103.0, 109.4, 114.1, 121.1, 122.7, 122.9, 123.5, 124.0, 128.2, 131.4, 133.4, 143.4, 143.8, 150.3, 172.5, 193.2; RM (EI) Calcd. for C [M+a] + : ; found: Boc (3,3a'R,8b')-tert-butyl 1-methyl-8b'-nitro-2-oxo-1'-thioxo-3a',8b'- dihydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indole]-4'(2')-carboxylate (3r). light yellow foam; 45.3 mg, yield 97%; dr >99:1, >99% ee, [α] D = (c 1.07, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (90/10 hexane/i-pr; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = 6.85 min); 1 MR (300 Mz, 50 o C, DM-d 6 ), δ (ppm): 1.16 (s, 9), 3.25 (s, 3), 5.93 (s, 1), 6.04 (d, J = 5.4 z, 1), (m, 1), 7.18 (d, J = 5.7 z, 1), (m, 1), (m, 1), (m, 1), (m, 1), 8.12 (d, 5

7 J = 5.7 z, 1), (s, 1). (3,3a'R,8b')-1-ethyl-8b'-nitro-1'-thioxo-4'-tosyl-2',3a',4',8b'-tetrahydro- 1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3s). light yellow foam; 53.0 mg, yield 99%; dr >99:1, 98% ee, [α] D = (c 1.1, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/et; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = 9.46 min); 1 MR (300 Mz, CDCl 3 ), δ (ppm): 1.39 (t, J = 7.2 z, 3), 2.32 (s, 3), ( m, 1), (m, 1), 5.91 (s, 1), 5.99 (d, J = 7.5 z, 1), 6.77 (t, J = 7.5 z, 1), 6.94 (d, J = 7.8 z, 1), 7.13 (d, J = 8.4 z, 2), (m, 2), (m, 2), (m, 1), (m, 1), 8.07 (d, J = 7.8 z, 1), 8.44 (s, 1). (3,3a'R,8b')-1-benzyl-8b'-nitro-1'-thioxo-4'-tosyl-2',3a',4',8b'-tetrahydr o-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3t). light yellow foam; 57.3 mg, yield 96%; dr >99:1, 94% ee, [α] D = (c 1.32, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak D- column (90/10 hexane/i-pr; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = min); 1 MR (300 Mz, CDCl 3 ), δ (ppm): 2.33 (s, 3), 4.96 (d, J = 15.9 z, 1), 5.07 (d, J = 15.9 z, 1), (m, 2), (m, 2), 7.13 (d, J = 8.1 z, 2), (m, 1), (m, 4), (m, 4), (m, 2), 8.07 (d, J = 7.8 z, 1), 8.59 (s, 1). Et Bn Ph (3,3a'R,8b')-8b'-nitro-1-phenyl-1'-thioxo-4'-tosyl-2',3a',4',8b'-tetrahydr o-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3u). light yellow foam; 56.0 mg, yield 96%; dr 85:15, 92% ee, [α] D = (c 1.42, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak D- column (90/10 hexane/i-pr; flow rate: 1.0 ml/min; λ = 254 nm; t major = 9.50 min, t minor = min); 1 MR (300 Mz, CDCl 3 ), δ (ppm): 2.32 (s, 3), 6.01 (s, 1), (m, 1), (m, 2), 7.13 (d, J = 8.1 z, 2), (m, 2), (m, 2), (m, 7), 8.11 (d, J = 7.8 z, 1), 8.53 (s, 1). F (3,3a'R,8b')-5-fluoro-1-methyl-8b'-nitro-1'-thioxo-4'-tosyl-2',3a',4',8 b'-tetrahydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3v). light yellow foam; 52.2 mg, yield 97%; dr >99:1, 99% ee, [α] D = (c 1.02, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/i-pr; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = min); 1 MR (300 Mz, CDCl 3 ), δ (ppm): 2.32 (s, 3), 3.32 (s, 3), (m, 1), 5.87 (s, 1), (m, 1), (m, 1), 7.13 (d, J = 8.1 z, 2), (m, 1), 7.39 (d, J = 8.4 z, 2), 7.49 (d, J = 7.8 z, 1), (m, 1), (m, 1), 8.67 (s, 1). (3,3a'R,8b')-1,5-dimethyl-8b'-nitro-1'-thioxo-4'-tosyl-2',3a',4',8b'-te trahydro-1'-spiro[indoline-3,3'-pyrrolo[3,4-b]indol]-2-one (3w). light yellow oil; 52.4 mg, yield 98%; dr >99:1, 97% ee, [α] D = (c 1.3, CCl 3 ). The ee was determined by PLC analysis through derivatization using a Chiralpak AD- column (80/ hexane/i-pr; flow rate: 1.0 ml/min; λ = 254 nm; t major = min, t minor = min); 1 MR (300 Mz, CDCl 3 ), δ (ppm): 1.99 (s, 3), 2.32 (s, 3), 6

8 3.30 (s, 3), 5.66 (s, 1), 5.86 (s, 1), 6.79 (d, J = 7.8 z, 1), (m, 3), (m, 1), 7.39 (d, J = 8.4 z, 2), 7.44 (d, J = 8.1 z, 1), (m, 1), (d, J = 7.8 z, 1), 8.59 (s, 1). 1. Zhao, J.-Q.; Zhou, M.-Q.; Wu, Z.-J.; Wang, Z.-.; Yue, D.-F.; Xu, X.-Y.; Zhang, X.-M.; Yuan, W.-C. rg. Lett. 15, 17, Copy of EI-M spectrum. [L1+Zn(Tf) 2 +a] MR, PLC spectra for compounds 3a-3w, and 13 C MR for compounds 3f and 3q 1 MR of 3a 7

9 PLC of 3a derivative 8

10 1 MR of 3b Cl PLC of 3b derivative Cl 9

11 Cl 1 and 13 C MR of 3c Br 10

12 PLC of 3c derivative Br Br 11

13 1 MR of 3d PLC of 3d derivative 12

14 1 MR of 3e Bn 13

15 PLC of 3e derivative Bn 14

16 1 and 13 C MR of 3f C C 15

17 PLC of 3f derivative C C 16

18 1 MR of 3g PLC of 3g derivative 17

19 1 MR of 3h 18

20 PLC of 3h derivative 19

21 1 MR of 3i PLC of 3i derivative

22 Cl 1 MR of 3j 21

23 PLC of 3j derivative 22

24 1 MR of 3k PLC of 3k derivative 23

25 1 MR of 3l 24

26 PLC of 3l derivative 25

27 1 MR of 3m PLC of 3m derivative 26

28 1 MR of 3n 27

29 PLC of 3m derivative 28

30 1 MR of 3o PLC of 3o derivative 29

31 1 MR of 3p CEt 30

32 PLC of 3p derivative 31

33 1 and 13 C MR of 3q C C 32

34 PLC of 3q derivative C C 33

35 1 MR of 3r PLC of 3r derivative 34

36 1 MR of 3s Et 35

37 PLC of 3s derivative 36

38 1 MR of 3t Bn PLC of 3t derivative 37

39 1 MR of 3u Ph 38

40 PLC of 3u derivative 39

41 1 MR of 3v PLC of 3v derivative 40

42 1 MR of 3w 41

43 PLC of 3w derivative 42