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 610041, China Chengdu Institute of Biology, Chinese Academy of ciences, Chengdu 610041, China University of Chinese Academy of ciences, Beijing 100049, China *E-mail: xuxy@cioc.ac.cn *E-mail: yuanwc@cioc.ac.cn upporting Information Table of Contents 1. General experimental information...1 2. onlinear effect experiment...1 3. General experimental procedures for asymmetric synthesis of compounds 3...1 4. Copy of EI-M spectrum...7 5. 1 MR, PLC spectra for compounds 3a-3w, and 13 C MR for compounds 3f and 3q...7
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 39.51 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 (%) 1 0 0 2 16 17 3 40 48 4 62 73 5 79 85 6 100 99 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
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 = -87.9 (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 = 15.70 min, t minor = 10.41 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), 7.28-7.42 (m, 4), 7.46 (d, J = 8.1 z, 1), 7.52-7.57 (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 = -27.5 (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 = 15.26 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), 7.36-7.42 (m, 4), 7.48-7.52 (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 = 15.14 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), 7.40-7.47 (m, 4), 7.90-7.94 (m, 1), 8.08 (d, J = 2.1 z, 1), 11.99 (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 = -74.5 (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 = 27.24 min, t minor = 11.76 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), 7.28-7.36 (m, 6), 7.39-7.43 (m, 1), 7.46 (d, J = 2.4 z, 1), 11.88 (s, 1). 2
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 = 35.15 min, t minor = 13.79 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), 7.11-7.18 (m, 3), 7.33-7.47 (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. 164.5-165.4 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 = 24.23 min, t minor = 17.66 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), 7.42-7.47 (m, 1), 7.49-7.52 (m, 2), 7.61 (d, J = 7.8 z, 1), 8.15-8.19 (m, 1), 8.35 (d, J = 1.5 z, 1), 12.03 (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 26 19 5 5 2 [M+a] + : 568.07; found: 568.0721. 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 = -109.4 (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 = 17.51 min, t minor = 10.10 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), 7.39-7.45 (m, 4), 7.46-7.49 (m, 1), 7.67 (t, J = 8.1 z, 1), 11.73 (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 = -86.1 (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 = 45.37 min, t minor = 14.18 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), 7.45-7.48 (m, 1), 7.55 (t, J = 8.1 z, 1), 7.63-7.66 (m, 1), 11.68 (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
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 = 10.24 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), 7.26-7.29 (m, 1), 7.37-7.49 (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 = -101.7 (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 = 16.21 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), 7.29-7.44 (m, 5), 7.51-7.58 (m, 2), 7.92 (d, J = 6.9 z, 1), 11.66 (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 = -103.0 (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 = 15.48 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), 7.32-7.38 (m, 4), 7.47-7.56 (m, 5), 8.06-8.09 (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 = -138.7 (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 = 11.28 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), 7.36-7.42 (m, 2), 7.64-7.70 (m, 1), 8.13 (d, J = 7.8 z, 1), 11.82 (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 = -88.5 (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 = 18.79 min, t minor = 12.06 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), 7.46-7.52 (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), 11.91 (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 = -377.4 (c 0.6, CCl 3 ). 4
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 = 30.72 min, t minor = 19.80 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), 7.06-7.18 (m, 1), 7.32-7.41 (m, 3), 7.67 (s, 1), 8. (s, 1), 11.65 (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 = -93.2 (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 = 18.29 min, t minor = 11.47 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), 6.00-6.06 (m, 2), 6.84-6.95 (m, 2), 7.19-7.21 (m, 2), 7.34-7.40 (m, 5), 7.66-7.76 (m, 2), 8.15 (d, J = 5.7 z, 1), 11.64 (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 = -252.5 (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 = 10.87 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), 3.66-3.69 (m, 1), 3.83-3.86 (m, 1), 5.95-5.98 (m, 2), 6.85 (t, J = 7.5 z, 1), 7.15 (d, J = 7.8 z, 1), 7.30-7.42 (m, 2), 7.62-7.67 (m, 2), 8.12 (d, J = 7.8 z, 1), 11.72 (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 = -271.7 (c 1.0, CCl 3 ); m.p. 222.1 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 = 16.82 min, t minor = 7.91 min); 1 MR (300 Mz, DM-d 6 ), δ (ppm): 3.28 (s, 3), 3.30 (s, 3), 5.92-5.95 (m, 2), 6.84 (t, J = 7.5 z, 1), 7.15 (d, J = 7.8 z, 1), 7.31-7.42 (m, 2), 7.62-7.68 (m, 2), 8.12 (d, J = 7.8 z, 1), 11.74 (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 16 4 5 [M+a] + : 447.0739; found: 447.0736. 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 = -284.4 (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 = 10.60 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), 6.87-6.91 (m, 1), 7.18 (d, J = 5.7 z, 1), 7.31-7.42 (m, 1), 7.44-7.62 (m, 1), 7.62-7.66 (m, 1), 7.75-7.77 (m, 1), 8.12 (d, 5
J = 5.7 z, 1), 11.63 (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 = -79.6 (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 = 16.67 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), 3.67-3.74 ( m, 1), 3.97-4.06 (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), 7.28-7.33 (m, 2), 7.34-7.42 (m, 2), 7.46-7.49 (m, 1), 7.52-7.57 (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 = -83.9 (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 = 13.34 min, t minor = 11.50 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), 5.98-6.01 (m, 2), 6.73-6.77 (m, 2), 7.13 (d, J = 8.1 z, 2), 7.18-7.21 (m, 1), 7.26-7.35 (m, 4), 7.37-7.46 (m, 4), 7.53-7.56 (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 = +47.4 (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 = 12.49 min); 1 MR (300 Mz, CDCl 3 ), δ (ppm): 2.32 (s, 3), 6.01 (s, 1), 6.04-6.06 (m, 1), 6.78-6.83 (m, 2), 7.13 (d, J = 8.1 z, 2), 7.24-7.34 (m, 2), 7.43-7.46 (m, 2), 7.47-7.59 (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 = -113.2 (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 = 29.65 min, t minor = 14.23 min); 1 MR (300 Mz, CDCl 3 ), δ (ppm): 2.32 (s, 3), 3.32 (s, 3), 5.68-5.71 (m, 1), 5.87 (s, 1), 6.84-6.88 (m, 1), 7.03-7.10 (m, 1), 7.13 (d, J = 8.1 z, 2), 7.29-7.35 (m, 1), 7.39 (d, J = 8.4 z, 2), 7.49 (d, J = 7.8 z, 1), 7.55-7.60 (m, 1), 8.04-8.07 (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 = -101.7 (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 = 23.78 min, t minor = 11.45 min); 1 MR (300 Mz, CDCl 3 ), δ (ppm): 1.99 (s, 3), 2.32 (s, 3), 6
3.30 (s, 3), 5.66 (s, 1), 5.86 (s, 1), 6.79 (d, J = 7.8 z, 1), 7.11-7.14 (m, 3), 7.29-7.34 (m, 1), 7.39 (d, J = 8.4 z, 2), 7.44 (d, J = 8.1 z, 1), 7.52-7.58 (m, 1), 8.07-8.10 (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, 2238. 4. Copy of EI-M spectrum. [L1+Zn(Tf) 2 +a] + 5. 1 MR, PLC spectra for compounds 3a-3w, and 13 C MR for compounds 3f and 3q 1 MR of 3a 7
PLC of 3a derivative 8
1 MR of 3b Cl PLC of 3b derivative Cl 9
Cl 1 and 13 C MR of 3c Br 10
PLC of 3c derivative Br Br 11
1 MR of 3d PLC of 3d derivative 12
1 MR of 3e Bn 13
PLC of 3e derivative Bn 14
1 and 13 C MR of 3f C C 15
PLC of 3f derivative C C 16
1 MR of 3g PLC of 3g derivative 17
1 MR of 3h 18
PLC of 3h derivative 19
1 MR of 3i PLC of 3i derivative
Cl 1 MR of 3j 21
PLC of 3j derivative 22
1 MR of 3k PLC of 3k derivative 23
1 MR of 3l 24
PLC of 3l derivative 25
1 MR of 3m PLC of 3m derivative 26
1 MR of 3n 27
PLC of 3m derivative 28
1 MR of 3o PLC of 3o derivative 29
1 MR of 3p CEt 30
PLC of 3p derivative 31
1 and 13 C MR of 3q C C 32
PLC of 3q derivative C C 33
1 MR of 3r PLC of 3r derivative 34
1 MR of 3s Et 35
PLC of 3s derivative 36
1 MR of 3t Bn PLC of 3t derivative 37
1 MR of 3u Ph 38
PLC of 3u derivative 39
1 MR of 3v PLC of 3v derivative 40
1 MR of 3w 41
PLC of 3w derivative 42