Supporting Information

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1 Supporting Information Brønsted Acid-Catalyzed [6+2]-Cycloaddition of 2-Vinylindoles with In Situ Generated 2-Methide-2H-pyrroles: Direct, Catalytic, and Enantioselective Synthesis of 2,3-Dihydro-H-pyrrolizines Isa Kallweit, and Christoph Schneider*

2 Table of Contents General Information... 2 Experimental procedures... 3 Characterization of Products... 3 MR-Spectra... 2 HPLC-Chromatograms Crystallographic data General Information H and 3 C MR spectra were recorded in CDCl 3 using a Brucker Avance III HD (400 MHz), a Varian MERCURYplus 400 (400 MHz) or a Varian MERCURYplus 300 (300 MHz). The signals were referenced to residual chloroform (7.26 ppm, H, ppm, 3 C). Chemical shifts are reported in ppm, multiplicities are indicated by s (singlet), d (doublet), t (triplet), q (quartet) and m (multiplet). Melting points are uncorrected and were determined on a Büchi melting point apparatus. IR spectra were obtained with a FTIR spectrometer (JASCO FT/IR-400). Optical rotations were measured using a Polarotronic polarimeter (Schmidt & Haensch). All ESI mass spectra were recorded on a Brucker ESI-TOF microtof. HPLC analyses were carried out on a Jasco MD-200 plus or Jasco MD-405 instrument with chiral stationary phase column (Daicel Chiralpak IA column). tert-butyl methyl ether and hexane were technical grade and distilled from KOH, toluene was purified and dried by a Solvent Purification System MB SPS-800 (Braun). Flash column chromatography was performed by using Merck silica gel mesh ( mm). All reactions were monitored by thin layer chromatography using precoated silica gel plates. Spots were visualized by UV (λ = 254 nm) and were treated with a vanillin solution in methanol (technical grade). 2-Vinyl indoles 5 were known and prepared by following the literature procedure. [] X-ray data were collected with a GEMII CCD diffractometer (Rigaku Inc.), λ(mo-kα) = Å, T = 30(2) K, empirical absorption corrections with SCALE3 ABSPACK. [2] The structure was solved by dual space methods with SIR-92. [3] Structure refinement was done with SHELXL-206 [4] by using full-matrix least-square routines against F2. All hydrogen atoms were calculated on idealized positions with exception of the OH proton which was detected in the difference map and refined with a restraint. The absolute structure was established by anomalous dispersion effects. The picture was generated with the program ORTEP. [5] CCDC (9) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via (or from the Cambridge Crystallographic Data Centre, 2 Union Road, Cambridge CB2 EZ, UK; fax: (+44) ; or deposit@ccdc.cam.uk). [] W. Tan, X. Li, Y.-X. Gong, M.-D. Ge, F. Shi, Chem. Commun. 204, 50, , K. Bera, C. Schneider, Chem. Eur. J. 206, 22, [2] Empirical absorption correction, CrysAlis-Pro Software package, Oxford Diffraction Ltd [3] A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, M. C. Burla, G. Polidori, M. Camalli, J. Appl. Cryst. 994, 27, 435. [4] a) SHELX includes SHELXS-203, SHELXL-206: G. M. Sheldrick, Acta Crystallogr. Sect. C 205, 7, 3 8; b) SHELXT: G. M. Sheldrick, Acta Crystallogr. Sect. A 205, 7, 3 8. [5] L. J. Farrugia, J. Appl. Cryst. 202, 45,

3 Experimental procedures General procedure A: Enantioselective Cycloaddition To a suspension of (H-pyrrol-2-yl)(aryl)methanol 4 (0.2 mmol,.2 equiv), (E)-3-methyl-2-(styryl)-H-indole 5 (0. mmol, equiv) and pulverized 4 Å molecular sieves (30 mg, 300 mg/mmol) in toluene ( ml), catalyst 7g (6.3 mg, 0.0 mmol, 0 mol%) was added at rt. The reaction mixture was stirred at 60 C and monitored by TLC. After completion of the reaction the crude reaction mixture was purified by column chromatography using hexane-mtbe (0.5-0 %, gradient elution) as eluent to afford products 6/8. The enantiomeric excess was determined by HPLC on a chiral stationary phase. Diastereomeric ratio was determined via H-MR and was >20: in all cases. Large scale synthesis: Analogous to General Procedure A the reaction was performed using 4h (.62 g, 4.80 mmol,.2 eq.), 5a (933 mg, 4.00 mmol,.0 eq.),.0 g pulverized 4 Å molecular sieves and catalyst 7g (23 mg, mmol, 5 mol%) in toluene (40 ml) and gave product 6h in 89 % yield (.95 g) and 96:4 e.r. The enantiomeric ratio was further enhanced to >99.5:0.5 e.r. by single recrystallization. General procedure B: Photocatalytic Autooxidation 3-(3-Methyl-H-Indol-2-yl)-2,3-dihydro-H-pyrrolizine 6 (0.0 mmol,.0 eq.) was dissolved in toluene and 0.5 mg (> mol%) rose bengal was added. A continuous stream of oxygen was bubbled through the reaction mixture and it was irradiated with green LEDs for 4 h. The precipitate was collected, washed with hexanes and dried under reduced pressure to give hydroperoxide 9 as pale pink solid. Characterization of Products Methyl (S,2S,3R)-6-ethyl-7-methyl-3-(3-methyl-H-indol-2-yl)-,2-diphenyl-2,3-dihydro-H-pyrrolizine-5-carboxylate (6a) According to General Procedure A: 33 mg (0.2 mmol) 4a, 23 mg (0.0 mmol) 5a, 48 h. Yield 43 mg, 90 % as a white solid, e.r. 94:6, [α] D 25 = 30 (c = 2.0, CHCl 3). mp = 82 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 2H), (m, 4H), (m, 6H), (m, H), 7.04 (td, J = 7.3,.4 Hz, H), 5.90 (d, J = 6. Hz, H), 4.52 (d, J = 6.8 Hz, H), 3.76 (t, J = 6.4 Hz, H), 2.93 (dq, J = 3.0, 7.4 Hz, H), 2.76 (dq, J = 3., 7.4 Hz, H),.92 (s, 3H),.78 (s, 3H),.9 (t, J = 7.4 Hz, 3H) , 65.00, 52.02, 50.5, 9.22, 5.38, 8.92, C MR (75 MHz, CDCl 3) δ [ppm] = 6.09, 4.48, 40.97, 40.79, 40.52, 35.37, 34.60, 29.4, 29.08, 28.99, 27.73, 27.55, 27.30, 2.68, 9.22, 8.54, 4.48, 2.03, 0.82, 07.49, IR (KBr) ν [cm - ] = 342, 2954, 2924, 2869, 682, 495, 456, 280, 30, 759, 743, 70. HR-MS (ESI) calc. for: C 33H 3 2O 2 - ([M-H] - ): , found: HPLC IA column (90 % hexane, 0 % iso-propanol, ml/min, 278 nm) R t = 4.5 min, R t2 = 9. min. 3

4 Methyl (S,2S,3R)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)-,2-diphenyl-2,3-dihydro-H-pyrrolizine-5-carboxylate (6b) According to General Procedure A: 3 mg (0.2 mmol) 4b, 23 mg (0.0 mmol) 5a, 48 h. 25 Yield 36 mg, 75 % as a white solid, e.r. 93:7, [α] D = 46 (c = 2.0, CHCl 3). mp = 96 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 7H), (m, 6H), (m, H), 7.04 (td, J = 7.3,.4 Hz, H), 5.92 (d, J = 5.8 Hz, H), 4.52 (d, J = 6.5 Hz, H), 3.77 (t, J = 6.2 Hz, H), 3.39 (s, 3H), 2.37 (s, 3H),.94 (s, 3H),.78 (s, 3H). 3 C MR (0 MHz, CDCl 3) δ [ppm] = 6.3, 4.80, 4.04, 40.7, 35.37, 34.53, 33.93, 29.39, 29.2, 29.02, 27.62, 27.56, 27.49, 27.32, 2.70, 9.22, 8.55, 5.6, 2.85, 0.83, 07.56, 67.22, 64.96, 5.98, 50.57,.5, 9.5, IR (KBr) ν [cm - ] = 3327, 299, 698, 684, 495, 446, 335, 274, 26, 28, 755, 699. HR-MS (ESI) calc. for: C 32H 29 2O - 2 ([M-H] - ): , found: HPLC IA column (95 % hexane, 5 % iso-propanol, ml/min, 278 nm) R t = 5.3 min, R t2 = 9.8 min. Methyl (S,2S,3R)-7-methyl-3-(3-methyl-H-indol-2-yl)-,2,6-triphenyl-2,3-dihydro-H-pyrrolizine-5-carboxylate (6c) According to General Procedure A: 40 mg (0.2 mmol) 4c, 23 mg (0.0 mmol) 5a, 48 h. 25 Yield 42 mg, 78 % as a white solid, e.r. 97:3, [α] D = +6 (c =.0, CHCl 3). mp = 205 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = 7.53 (s, H), (m, H), (m, 5H), 7.0 (ddd, J = 8., 7.0,.4 Hz, H), 7.05 (td, J = 7.4,.2 Hz, H), 6.0 (d, J = 6.4 Hz, H), 4.6 (d, J = 7. Hz, H), 3.83 (t, J = 6.8 Hz, H), 3.22 (s, 3H),.94 (s, 3H),.72 (s, 3H). 3 C MR (0 MHz, CDCl 3) δ [ppm] = 60.75, 40.98, 40.67, 40.60, 37.59, 35.44, 35.6, 33.93, 30.37, 29.37, 29.2, 29.05, 27.85, 27.74, 27.68, 27.60, 27.42, 26.96, 2.84, 9.30, 8.60, 4.80, 2.64, 0.9, 07.93, 67.4, 65.22, 52.3, 50.68, 9.78, IR (KBr) ν [cm - ] = 3425, 693, 458, 288, 202, 42, 089, 744, 702. HR-MS (ESI) calc. for: C 37H 32 2O 2a + ([M+a] + ): , found: HPLC IA column (90 % hexane, 0 % iso-propanol, ml/min, 282 nm) R t = 4.9 min, R t2 = 3.4 min. Methyl (S,2S,3R)- 7-methyl-3-(3-methyl-H-indol-2-yl)-,2-diphenyl-2,3-dihydro-H-pyrrolizine-5-carboxylate (6d) According to General Procedure A: 30 mg (0.2 mmol) 4d, 23 mg (0.0 mmol) 5a, 48 h. 22 Yield 23 mg, 49 % as a white solid, e.r. 94:6, [α] D = 42 (c =.0, CHCl 3). mp = 0 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 4H), 5.92 (d, J = 5.8 Hz, H), 4.54 (d, J = 6.4 Hz, H), 3.84 (t, J = 6. Hz, H), 3.48 (s, 3H),.97 (s, 3H),.88 (s, 3H). 3 C MR (0 MHz, CDCl 3) δ [ppm] = 60.56, 4.67, 4.64, 40.84, 35.45, 33.85, 29.34, 29.6, 29.08, 27.64, 27.56, 27.47, 27.40, 23.09, 2.80, 9.24, 8.70, 7.9, 3.30, 0.8, 08.3, 67.69, 64.36, 5.8, 5.08,.5, IR (KBr) ν [cm - ] = 334, 295, 2922, 687, 472, 454, 335, 242, 098, 0, 757, 700, 457. HR-MS (ESI) calc. for: C 3H 27 2O - 2 ([M-H] - ): , found: HPLC IA column (90 % hexane, 0 % iso-propanol, ml/min, 278 nm) R t = 5.8 min, R t2 = 0.7 min. 4

5 Methyl (S,2S,3R)-3-(3-methyl-H-indol-2-yl)-,2-diphenyl-2,3,6,7,8,9-hexahydro-H-pyrrolo[2,-a]isoindole-5- carboxylate (6e) According to General Procedure A: 34 mg (0.2 mmol) 4e, 23 mg (0.0 mmol) 5a, 48 h. Yield 34 mg, 68 % as a white solid, e.r. 9:9, [α] D 25 = 42 (c =.0, CHCl 3). mp = 22 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 2H), (m, 6H), (m, 6H), 5.93 (d, J = 6. Hz, H), 4.50 (d, J = 6.8 Hz, H), 3.78 (t, J = 6.5 Hz, H), 3.40 (s, 2H), (m, 2H), (m, 2H),.93 (s, 3H), (m, 4H). 3 C MR (0 MHz, CDCl 3) δ [ppm] = 6.06, 4.53, 40.66, 39.73, 35.70, 35.45, 34.47, 29.45, 29.09, 28.98, 27.72, 27.57, 27.53, 27.30, 2.68, 9.2, 8.59, 4.57, 3.80, 0.85, 07.70, 67.26, 64.78, 5.96, 50.54, 24.38, 23.37, 23.26, 2.58, IR (KBr) ν [cm - ] = 3434, 2930, 2842, 696, 679, 496, 453, 374, 33, 268, 9, 04, 762, 743, 70. HR-MS (ESI) calc. for: C 34H 32 2O 2a + ([M+a] + ): , found: HPLC IA column (95 % hexane, 5 % iso-propanol, ml/min, 278 nm) R t = 6. min, R t2 = 3.2 min. Methyl (S,2S,3R)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)-2-phenyl--(p-tolyl)-2,3-dihydro-H-pyrrolizine-5- carboxylate (6f) According to General Procedure A: 33 mg (0.2 mmol) 4f, 23 mg (0.0 mmol) 5a, 48 h. Yield 34 mg, 70 % as a white solid, e.r. 92:8, [α] D 25 = 2 (c = 2.0, CHCl 3). mp = 3 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 2H), (m, 3H), (m, 9H), 5.9 (d, J = 5.8 Hz, H), 4.49 (d, J = 6.4 Hz, H), 3.74 (t, J = 6. Hz, H), 3.39 (s, 3H), 2.37 (s, 3H), 2.3 (s, 3H),.94 (s, 3H),.79 (s, 3H). 3 C MR (0 MHz, CDCl 3) δ [ppm] = 6.32, 4.9, 40.93, 37.97, 36.90, 35.33, 34.58, 33.9, 29.67, 29.36, 29.08, 27.6, 27.50, 27.34, 2.63, 9.6, 8.53, 5.03, 2.78, 0.8, 07.48, 67.23, 64.92, 5.60, 50.55, 2.20,.53, 9.7, IR (KBr) ν [cm - ] = 3443, 697, 683, 53, 496, 456, 443, 334, 304, 268, 27, 742, 70. HR-MS (ESI) calc. for: C 33H 32 2O 2a + ([M+a] + ): , found: HPLC IA column (90 % hexane, 0 % iso-propanol, ml/min, 278 nm) R t = 4.4 min, R t2 = 7.0 min. Methyl (S,2S,3R)--(4-methoxyphenyl)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)-2-phenyl-2,3-dihydro-H-pyrrolizine-5- carboxylate (6g) According to General Procedure A: 35 mg (0.2 mmol) 4g, 23 mg (0.0 mmol) 5a, 48 h. Yield 33 mg, 66 % as a white solid, e.r. 94:6, [α] D 24 = 6 (c = 2.0, CHCl 3). mp = 88 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = 7.43 (d, J = 8.0 Hz, 2H), (m, 2H), (m, 7H), (m, 2H), 5.90 (d, J = 6.0 Hz, H), 4.46 (d, J = 6.7 Hz, H), 3.77 (s, 3H), 3.72 (t, J = 6.3 Hz, H), 3.38 (s, 3H), 2.36 (s, 3H),.92 (s, 3H),.77 (s, 3H). 3 C MR (0 MHz, CDCl 3) δ [ppm] = 6.32, 58.83, 4.74, 4.09, 35.40, 34.63, 33.9, 33.03, 29.45, 29.09, 28.55, 27.66, 27.52, 2.68, 9.22, 8.55, 5.08, 4.38, 2.74, 0.84, 07.53, 67.39, 64.92, 55.40, 5.35, 50.53,.49, 9.09, IR (KBr) ν [cm - ] = 3444, 2923, 698, 683, 5, 496, 457, 440, 389, 334, 303, 265, 246, 75, 27, 033, 830, 743, 70. HR-MS (ESI) calc. for: C 37H 32 2O 3a + ([M+a] + ): , found: HPLC IA column (95 % hexane, 5 % iso-propanol, ml/min, 229 nm) R t = 6.5 min, R t2 = 5.2 min. 5

6 Methyl (S,2S,3R)- -(4-bromophenyl)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)-2-phenyl-2,3-dihydro-H-pyrrolizine-5- carboxylate (6h) According to General Procedure A: 40 mg (0.24 mmol) 4h, 23 mg (0.20 mmol) 5a, 48 h. Yield 36 mg, 64 % as a white solid, e.r. 96:4, [α] D 22 = +68 (c =.0, CHCl 3). mp = 87 C (CH 2Cl 2/hexane). H MR (300 MHz, CDCl 3) δ [ppm] = (m, 4H), (m, 3H), (m, H), (m, 6H), 5.90 (d, J = 6.4 Hz, H), 4.46 (d, J = 7.2 Hz, H), 3.68 (t, J = 6.5 Hz, H), 3.35 (s, 3H), 2.35 (s, 3H),.88 (s, 3H),.74 (s, 3H). 3 C MR (75 MHz, CDCl 3) δ [ppm] = 6.23, 40.75, 40.2, 39.90, 35.37, 34.34, 33.93, 32.08, 29.48, 29.26, 29.5, 27.78, 2.80, 2.6, 9.33, 8.55, 5.3, 2.76, 0.88, 07.58, 67.44, 65.06, 5.65, 50.58,.46, 9.3, IR (KBr) ν [cm - ] = 3444, 697, 683, 49, 457, 442, 403, 390, 27, 29, 0, 743, 700. HR-MS (ESI) calc. for: C 32H 29Br 2O 2a + ([M+a] + ): , found: HPLC IA column (90 % hexane, 0 % iso-propanol, ml/min, 278 nm) R t = 4.7 min, R t2 = 9.2 min. Methyl (S,2S,3R)- -(4-(tert-butyl)phenyl)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)-2-phenyl-2,3-dihydro-H-pyrrolizine- 5-carboxylate (6i) According to General Procedure A: 38 mg (0.2 mmol) 4i, 23 mg (0.0 mmol) 5a, 48 h. Yield 47 mg, 89 % as a white solid, e.r. 94:6, [α] D 25 = 9 (c = 2.0, CHCl 3). mp = 99 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = 7.44 (d, J = 7.5 Hz, H), (m, 6H), (m, 6H), 5.9 (d, J = 4.9 Hz, H), 4.5 (d, J = 5.5 Hz, H), 3.78 (t, J = 5.3 Hz, H), 3.43 (s, 3H), 2.38 (s, 3H), 2.00 (s, 3H),.84 (s, 3H),.30 (s, 9H). 3 C MR (0 MHz, CDCl 3) δ [ppm] = 6.37, 50.23, 42.83, 40.87, 38.9, 35.39, 34.57, 33.90, 29.3, 29.6, 27.46, 27.40, 27.04, 25.94, 2.68, 9.6, 8.57, 5.9, 2.97, 0.76, 07.60, 66.75, 64.88, 5.2, 50.56, 34.6, 3.48,.57, 9.30, 8.4. IR (KBr) ν [cm - ] = 346, 2960, 70, 685, 496, 458, 442, 364, 334, 302, 269, 28, 763, 74, 700. HR-MS (ESI) calc. for: C 36H 38 2O 2a + ([M+a] + ): , found: HPLC IA column (95 % hexane, 5 % iso-propanol, ml/min, 278 nm) R t = 4.8 min, R t2 = 7.3 min. Methyl (S,2S,3R)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)-2-phenyl--(4-(trifluoromethyl)phenyl)-2,3-dihydro-Hpyrrolizine-5-carboxylate (6j) According to General Procedure A: 39 mg (0.2 mmol) 4j, 23 mg (0.0 mmol) 5a, 48 h. Yield 40 mg, 74 % as an orange solid, e.r. 95:5, [α] D 25 = 8 (c =.0, CHCl 3). mp = 0 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = 7.53 (d, J = 8.0 Hz, 2H), (m, 2H), (m, 5H), (m, 4H), 5.92 (d, J = 6.4 Hz, H), 4.57 (d, J = 7.3 Hz, H), 3.7 (t, J = 6.8 Hz, H), 3.36 (s, 3H), 2.37 (s, 3H),.88 (s, 3H),.74 (s, 3H). 3 C MR (0 MHz, CDCl 3) δ [ppm] = 6.2, 44.97, 40.60, 39.77, 35.4, 34.24, (q, J = 33.3 Hz), 29.52, 29.22, 27.9, 27.87, 27.79, (q, J = 3.8 Hz), 24.8 (q, J = Hz), 2.87, 9.39, 8.57, 5.49, 2.84, 0.88, 07.67, 67.4, 65.8, 5.94, 50.6,.45, 9.7, IR (KBr) ν [cm - ] = 3446, 698, 685, 69, 496, 326, 269, 67, 27, 0, 068, 08, 742, 70. HR-MS (ESI) calc. for: C 33H 29F 3 2O 2a + ([M+a] + ): , found: HPLC IA column (95 % hexane, 5 % iso-propanol, ml/min, 275 nm) R t = 5.5 min, R t2 = 3.0 min. 6

7 Methyl (S,2S,3R)--(3,5-dimethylphenyl)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)-2-phenyl-2,3-dihydro-H-pyrrolizine- 5-carboxylate (6k) According to General Procedure A: 35 mg (0.2 mmol) 4k, 23 mg (0.0 mmol) 5a, 48 h. Yield 4 mg, 82 % as a white solid, e.r. 94:6, [α] D 25 = 2 (c = 2.0, CHCl 3). mp = 95 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 2H), (m, 3H), (m, 4H), 6.86 (s, H), 6.75 (s, 2H), 5.92 (d, J = 5.0 Hz, H), 4.44 (d, J = 5.6 Hz, H), (m, H), 3.43 (s, 3H), 2.38 (s, 3H), 2.24 (s, 6H), 2.00 (s, 3H),.8 (s, 3H). 3 C MR (75 MHz, CDCl 3) δ [ppm] = 6.38, 42.77, 4.6, 40.98, 38.56, 35.3, 34.6, 33.89, 29.37, 29.4, 28.95, 27.46, 27.38, 25.23, 2.70, 9.9, 8.57, 5.4, 2.93, 0.77, 07.56, 66.7, 64.89, 5.66, 50.58, 2.49,.59, 9.22, IR (KBr) θ [cm - ] = 3444, 292, 698, 685, 605, 485, 457, 270, 29, 849, 742, 700. HR-MS (ESI) calc. for: C 34H 34 2O 2a + ([M+a] + ): , found: HPLC IA column (95 % hexane, 5 % iso-propanol, ml/min, 278 nm) R t = 4.5 min, R t2 = 6.7 min. Methyl (S,2S,3R)--(benzo[d][,3]dioxol-5-yl)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)-2-phenyl-2,3-dihydro-Hpyrrolizine-5-carboxylate (6l) 762, 743, 70. According to General Procedure A: 36 mg (0.2 mmol) 4l, 23 mg (0.0 mmol) 5a, 48 h. Yield 42 mg, 8 % as a white solid, e.r. 93:7, [α] D 25 = (c = 2.0, CHCl 3). mp = 5 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 2H), (m, 2H), (m, 5H), 6.7 (d, J = 7.9 Hz, H), (m, H), 6.6 (dd, J = 8.0,.8 Hz, H), (m, 2H), 5.88 (d, J = 6.0 Hz, H), 4.43 (d, J = 6.7 Hz, H), 3.70 (t, J = 6.3 Hz, H), 3.37 (s, 3H), 2.36 (s, 3H),.92 (s, 3H),.80 (s, 3H). 3 C MR (75 MHz, CDCl 3) δ [ppm] = 6.29, 48.33, 46.84, 4.56, 40.73, 35.40, 34.9, 34.53, 33.9, 29.43, 29.2, 27.66, 27.59, 2.7, 20.53, 9.24, 8.55, 5.5, 2.8, 0.87, 08.46, 07.84, 07.55, 0.24, 67.42, 64.90, 5.79, 50.54,.48, 9.3, IR (KBr) ν [cm - ] = 342, 698, 685, 503, 489, 456, 442, 365, 269, 248, 240, 038, 933, HR-MS (ESI) calc. for: C 33H 30 2O 4a + ([M+a] + ): , found: HPLC IA column (95 % hexane, 5 % iso-propanol, ml/min, 280 nm) R t = 6.8 min, R t2 = 4.2 min. Methyl (S,2S,3R)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)--(naphthalen-2-yl)-2-phenyl-2,3-dihydro-H-pyrrolizine-5- carboxylate (6m) According to General Procedure A: 37 mg (0.2 mmol) 4m, 23 mg (0.0 mmol) 5a, 48 h. Yield 37 mg, 70 % as a white solid, e.r. 96:4, [α] D 25 = +72 (c =.0, CHCl 3). mp = 28 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 3H), (m, 4H), (m, 4H), (m, 2H), (m, 3H), 5.98 (d, J = 5.9 Hz, H), 4.69 (d, J = 6.6 Hz, H), 3.88 (t, J = 6.3 Hz, H), 3.40 (s, 3H), 2.40 (s, 3H),.95 (s, 3H),.77 (s, 3H). 3 C MR (0 MHz, CDCl 3) δ [ppm] = 6.33, 4.63, 40.76, 38.44, 35.38, 34.5, 33.97, 33.58, 32.75, 29.44, 29.5, 29.04, 27.83, 27.82, 27.69, 27.62, 26.46, 26.0, 26.03, 25.73, 2.73, 9.25, 8.54, 5.29, 2.97, 0.85, 07.65, 67.07, 65.09, 52.30, 50.58,.53, 9.2, IR (KBr) ν [cm - ] = 3434, 698, 684, 495, 456, 44, 388, 27, 3, 820, 744, 700. HR-MS (ESI) calc. for: C 36H 32 2O 2a + ([M+a] + ): , found: HPLC IA column (90 % hexane, 0 % iso-propanol, ml/min, 278 nm) R t = 4.8 min, R t2 = 8.0 min. 7

8 Methyl (S,2S,3R)--(3-methoxyphenyl)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)-2-phenyl-2,3-dihydro-H-pyrrolizine-5- carboxylate (6n) According to General Procedure A: 35 mg (0.2 mmol) 4n, 23 mg (0.0 mmol) 5a, 48 h. Yield 40 mg, 79 % as a white solid, e.r. 97:3, [α] D 25 = 29 (c = 2.0, CHCl 3). mp = 5 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 2H), (m, 3H), 7.2 (t, J = 7.9 Hz, H), (m, 3H), (m, 2mH), 6.76 (dd, J = 8.3, 2.3 Hz, 2H), 6.69 (d, J = 2. Hz, H), 5.92 (d, J = 5.4 Hz, H), 4.48 (d, J = 6. Hz, H), 3.77 (t, J = 5.7 Hz, H), 3.69 (s, 3H), 3.40 (s, 3H), 2.37 (s, 3H),.96 (s, 3H),.8 (s, 3H). 3 C MR (0 MHz, CDCl 3) δ [ppm] = 6.34, 60.5, 42.80, 42.7, 40.60, 35.35, 34.57, 33.95, 30.00, 29.39, 29.5, 27.56, 27.5, 2.69, 9.79, 9.2, 8.54, 5.8, 3.45, 2.95, 2.35, 0.84, 07.5, 66.94, 64.95, 55.29, 5.95, 50.59,.54, 9.23, IR (KBr) ν [cm - ] = 3445, 2923, 698, 684, 602, 490, 456, 438, 336, 267, 27, 048, 743, 70. HR-MS (ESI) calc. for: C 33H 32 2O 3a + ([M+a] + ): , found: HPLC IA column (95 % hexane, 5 % iso-propanol, ml/min, 278 nm) R t = 6. min, R t2 = 0.7 min. Methyl (S,2S,3R)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)-2-phenyl--(o-tolyl)-2,3-dihydro-H-pyrrolizine-5- carboxylate (6o) According to General Procedure A: 33 mg (0.2 mmol) 4o, 23 mg (0.0 mmol) 5a, 4 d. Yield 34 mg, 69 % as a white solid, e.r. 77:23, [α] D 25 = 38 (c =.0, CHCl 3). mp = 04 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 2H), (m, 2H), (m, 9H), 5.90 (d, J = 5. Hz, H), 4.72 (d, J = 5.6 Hz, H), 3.68 (t, J = 5.4 Hz, H), 3.42 (s, 3H), 2.38 (s, 3H),.99 (s, 6H),.75 (s, 3H). 3 C MR (0 MHz, CDCl 3) δ [ppm] = 6.7, 42.75, 4.22, 39.47, 36.48, 35.24, 34.38, 33.82, 3.03, 29.3, 29., 29.03, 27.40, 27.4, 27.2, 26.38, 2.57, 9.07, 8.43, 5.5, 2.47, 0.70, 07.53, 66.0, 65.04, 50.44, 48.44, 9.97,.46, 8.92, IR (KBr) ν [cm - ] = 3445, 697, 683, 65, 637, 494, 458, 270, 76, 743, 70. HR-MS (ESI) calc. for: C 33H 32 2O 2a + ([M+a] + ): , found: HPLC IA column (95 % hexane, 5 % iso-propanol, ml/min, 278 nm) R t = 4.6 min, R t2 = 7.3 min. Methyl (S,2S,3R)-2-(4-methoxyphenyl)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)--phenyl-2,3-dihydro-H-pyrrolizine-5- carboxylate (8a) According to General Procedure A: 3 mg (0.2 mmol) 4b, 26 mg (0.0 mmol) 5b, 48 h. Yield 35 mg, 70 % as a white solid, e.r. 92:8, [α] D 25 = 46 (c =.0, CHCl 3). mp = 02 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 2H), (m, 2H), (m, 7H), 6.85 (d, J = 8.2 Hz, 2H), 5.85 (d, J = 6.2 Hz, H), 4.47 (d, J = 7.0 Hz, H), 3.8 (s, 3H), 3.7 (t, J = 6.6 Hz, H), 3.37 (s, 3H), 2.36 (s, 3H),.94 (s, 3H),.76 (s, 3H). 3 C MR (0 MHz, CDCl 3) δ [ppm] = 6.30, 59.03, 4.03, 40.78, 35.39, 34.59, 33.82, 33.49, 29.43, 28.96, 28.76, 27.53, 27.25, 2.65, 9.20, 8.5, 5.5, 4.4, 2.78, 0.82, 07.5, 66.67, 65.09, 55.40, 52.2, 50.5,.46, 9.0, IR (KBr) ν [cm - ] = 3445, 697, 685, 62, 54, 496, 456, 442, 304, 287, 264, 25, 80, 27, 034, 743, 704. HR-MS (ESI) calc. for: C 33H 32 2O 3a + ([M+a] + ): , found: HPLC IA column (95 % hexane, 5 % iso-propanol, ml/min, 278 nm) R t = 6.8 min, R t2 = 2.5 min. 8

9 Methyl (S,2S,3R)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)--phenyl-2-(p-tolyl)-2,3-dihydro-H-pyrrolizine-5- carboxylate (8b) According to General Procedure A: 3 mg (0.2 mmol) 4b, 25 mg (0.0 mmol) 5c, 48 h. Yield 36 mg, 73 % as a white solid, e.r. 9:9, [α] D 25 = 58 (c =.0, CHCl 3). mp = 92 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 2H), (m, 2H), (m, 9H), 5.89 (d, J = 5.8 Hz, H), 4.50 (d, J = 6.6 Hz, H), 3.74 (t, J = 6.2 Hz, H), 3.39 (s, 3H), 2.37 (s, 3H), 2.36 (s, 3H),.96 (s, 3H),.78 (s, 3H). 3 C MR (0 MHz, CDCl 3) δ [ppm] = 6.3, 4.3, 40.80, 38.75, 37.5, 35.36, 34.66, 33.87, 29.75, 29.4, 28.98, 27.49, 27.25, 2.64, 9.8, 8.52, 5.4, 2.79, 0.8, 07.48, 66.88, 65.02, 52.03, 50.53, 2.27,.50, 9.4, IR (KBr) ν [cm - ] = 3443, 698, 683, 496, 455, 389, 302, 270, 27, 742, 703. HR-MS (ESI) calc. for C 33H 32 2O 2a + ([M+a] + ): , found: HPLC IA column (95 % hexane, 5 % iso-propanol, ml/min, 278 nm) R t = 5.2 min, R t2 = 6.6 min. Methyl (S,2S,3R)-2-(4-chlorophenyl)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)--phenyl-2,3-dihydro-H-pyrrolizine-5- carboxylate (8c) According to General Procedure A: 3 mg (0.2 mmol) 4b, 27 mg (0.0 mmol) 5d, 48 h. Yield 34 mg, 67 % as a white solid, e.r. 9:9, [α] D 25 = 56 (c =.0, CHCl 3). mp = 05 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 2H), (m, 4H), (m, 7H), 5.87 (d, J = 6. Hz, H), 4.46 (d, J = 6.9 Hz, H), 3.74 (t, J = 6.5 Hz, H), 3.38 (s, 3H), 2.36 (s, 3H),.94 (s, 3H),.76 (s, 3H). 3 C MR (0 MHz, CDCl 3) δ [ppm] = 6.25, 40.62, 40.38, 40.00, 35.42, 34.20, 33.98, 33.45, 29.34, 29.29, 29.08, 29.06, 2.84, 9.33, 8.60, 5.24, 2.94, 0.87, 07.66, 66.73, 64.76, 52.05, 50.59,.48, 9.09, IR (KBr) ν [cm - ] = 3444, 2924, 697, 683, 65, 494, 455, 270, 29, 743, 702. HR-MS (ESI) calc. for: C 32H 29Cl 2O 2a + ([M+a] + ): 53.80, found: HPLC IA column (95 % hexane, 5 % iso-propanol, ml/min, 278 nm) R t = 6.0 min, R t2 = 8.9 min. Methyl (S,2S,3R)-2-(4-fluorophenyl)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)--phenyl-2,3-dihydro-H-pyrrolizine-5- carboxylate (8d) 52.5, 50.58,.48, 9.0, According to General Procedure A: 3 mg (0.2 mmol) 4b, 25 mg (0.0 mmol) 5e, 48 h. Yield 33 mg, 67 % as a white solid, e.r. 92:8, [α] D 25 = 28 (c =.0, CHCl 3). mp = 98 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 2H), (m, 3H), (m, 8H), 5.86 (d, J = 6.2 Hz, H), 4.46 (d, J = 7.0 Hz, H), 3.74 (t, J = 6.6 Hz, H), 3.38 (s, 3H), 2.36 (s, 3H),.93 (s, 3H),.76 (s, 3H). 3 C MR (75 MHz, CDCl 3) δ [ppm] = (d, J = Hz), 6.26, 40.70, 40.48, 37.8 (d, J = 3. Hz), 35.4, 34.25, 33.93, 29.36, (d, J = 8.0 Hz), 29.05, 27.48, 27.42, 2.80, 9.30, 8.58, 5.98 (d, J = 2.5 Hz), 5.2, 2.9, 0.86, 07.63, 66.65, 64.94, IR (KBr) ν [cm - ] = 3445, 698, 684, 509, 496, 456, 270, 227, 28, 743, 704. HR-MS (ESI) calc. for: C 32H 29F 2O 2a + ([M+a] + ): , found: HPLC IA column (95 % hexane, 5 % iso-propanol, ml/min, 278 nm) R t = 5.8 min, R t2 = 9.4 min. 9

10 Methyl (S,2S,3R)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)--phenyl-2-(3-(trifluoromethyl)phenyl)-2,3-dihydro-Hpyrrolizine-5-carboxylate (8e) According to General Procedure A: 3 mg (0.2 mmol) 4b, 30 mg (0.0 mmol) 5f, 48 h at 80 C. Yield 26 mg, 47 % as a white solid, e.r. 92:8, [α] D 25 = 38 (c =.0, CHCl 3). mp = 96 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = 7.58 (d, J = 7.8 Hz, H), (m, 4H), (m, 5H), (m, 5H), 5.9 (d, J = 6. Hz, H), 4.5 (d, J = 6.9 Hz, H), 3.84 (t, J = 6.6 Hz, H), 3.39 (s, 3H), 2.36 (s, 3H),.92 (s, 3H),.76 (s, 3H). 3 C MR (75 MHz, CDCl 3) δ [ppm] = 6.24, 42.37, 40.4, 40.26, 35.47, 34.0, 34.02, 3.47 (q, J = 3.5 Hz), 3.29, 29.7, 29.50, 29.35, 29.4, 27.59, 27.48, 25.89, (q, J = 3.6 Hz), (q, J = 3.7 Hz), (q, J = Hz), 22.28, 2.94, 9.39, 8.64, 5.28, 3.0, 0.89, 07.72, 67.06, 64.68, 5.95, 50.6,.49, 9.07, IR (KBr) ν [cm - ] = 3357, 2923, 698, 684, 495, 455, 329, 268, 67, 26, 074, 742, 702, 505. HR-MS (ESI) calc. for: C 33H 29F 3 2O 2a + ([M+a] + ): , found: HPLC IA column (95 % hexane, 5 % iso-propanol, ml/min, 278 nm) R t = 5.0 min, R t2 = 2.3 min. Methyl (S,2S,3R)-2-(3-bromophenyl)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)--phenyl-2,3-dihydro-H-pyrrolizine-5- carboxylate (8f) According to General Procedure A: 3 mg (0.2 mmol) 4b, 3 mg (0.0 mmol) 5g, 48 h at 80 C. Yield 26 mg, 46 % as a white solid, e.r. 92:8, [α] D 25 = 50 (c =.0, CHCl 3). mp = 98 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 6H), (m, 7H), 5.89 (d, J = 5.8 Hz, H), 4.48 (d, J = 6.6 Hz, H), 3.73 (t, J = 6.3 Hz, H), 3.40 (s, 3H), 2.36 (s, 3H),.96 (s, 3H),.76 (s, 3H). 3 C MR (75 MHz, CDCl 3) δ [ppm] = 6.25, 44.07, 40.66, 40.34, 35.43, 34.23, 34.08, 30.82, 30.73, 30.54, 29.38, 29.2, 27.5, 27.46, 26.49, 23.6, 2.87, 9.35, 8.64, 5.24, 2.97, 0.88, 07.68, 66.85, 64.77, 5.96, 50.6,.50, 9.0, IR (KBr) ν [cm - ] = 3435, 685, 648, 637, 596, 496, 456, 30, 27, 28, 742, 700, 505. HR-MS (ESI) calc. for: C 32H 29Br 2O 2a + ([M+a] + ): , found: HPLC IA column (95 % hexane, 5 % iso-propanol, ml/min, 225 nm) R t = 5.5 min, R t2 = 5.9 min. Methyl (S,2S,3R)-2-(2-fluorophenyl)-6,7-dimethyl-3-(3-methyl-H-indol-2-yl)--phenyl-2,3-dihydro-H-pyrrolizine-5- carboxylate (8g) According to General Procedure A: 3 mg (0.2 mmol) 4b, 25 mg (0.0 mmol) 5h, 48 h at 80 C. Yield 3 mg, 63 % as a white solid, e.r. 90:0, [α] D 25 = 44 (c =.0, CHCl 3). mp = 98 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 2H), (m, 3H), (m, 7H), 6.94 (t, J = 7.5 Hz, H), 6.03 (d, J = 5.9 Hz, H), 4.56 (d, J = 6.6 Hz, H), 3.94 (t, J = 6.2 Hz, H), 3.39 (s, 3H), 2.36 (s, 3H),.94 (s, 3H),.77 (s, 3H). 3 C MR (75 MHz, CDCl 3) δ [ppm] = 6.33, (d, J = Hz), 40.88, 40.65, 35.40, 34.39, 33.83, (d, J = 4.3 Hz), (d, J = 8.2 Hz), 29.38, 29.06, (d, J = 3. Hz), 27.54, 27.40, (d, J = 3.3 Hz), 2.73, 9.22, 8.57, 6.0 (d, J = 2.9 Hz), 5.26, 2.98, 0.85, 07.64, 63.07, 6.65, 50.59, (d, J = 5. Hz),.53, 9.6, 8.7. IR (KBr) ν [cm - ] = 3444, 698, 684, 650, 635, 622, 494, 456, 272, 29, 759, 745, 703. HR-MS (ESI) calc. for: C 32H 29F 2O 2a + ([M+a] + ):, found:. HPLC IA column (95 % hexane, 5 % iso-propanol, ml/min, 278 nm) R t = 5.3 min, R t2 = 8.6 min. 0

11 Methyl (S,2R,3R)-2,6,7-trimethyl-3-(3-methyl-H-indol-2-yl)--phenyl-2,3-dihydro-H-pyrrolizine-5-carboxylate (8h) According to General Procedure A: 3 mg (0.2 mmol) 4b, 7 mg (0.0 mmol) 5i, 48 h at room temperature. 25 Yield 4 mg, 33 % as a white solid, e.r. 77:23, [α] D = +26 (c =.0, CHCl 3). mp = 92 C (CH 2Cl 2/hexane). H MR (400 MHz, CDCl 3) δ [ppm] = (m, 2H), (m, 2H), (m, 3H), (m, H), (m, 2H), 5.45 (d, J = 6.7 Hz, H), 3.94 (d, J = 7.4 Hz, H), 3.36 (s, 3H), (m, H), 2.35 (s, 3H), 2.30 (s, 3H),.67 (s, 3H),.35 (d, J = 6.9 Hz, 3H). 3 C MR (0 MHz, CDCl 3) δ [ppm] = 6.3, 4.38, 4., 35.4, 34.62, 33.4, 29.36, 28.99, 27.8, 27.26, 2.74, 9.26, 8.46, 5.07, 2.56, 0.80, 07.54, 63.83, 56.76, 5.42, 50.44, 8.00, H.33, 8.89, IR (KBr) ν [cm - ] = 3433, 679, 495, 453, 27, 9, 742, 703. HR-MS (ESI) calc. for: C 27H 28 2O 2a + ([M+a] + ): , found: HPLC IA column (90 % hexane, 0 % iso-propanol, ml/min, 278 nm) R t = 4.7 min, R t2 = 7.6 min. Methyl (S,2S,3R)--(4-bromophenyl)-3-((R)-3-hydroperoxy-3-methyl-3H-indol-2-yl)-6,7-dimethyl-2-phenyl-2,3-dihydro- H-pyrrolizine-5-carboxylate (9) According to General Procedure B: 55 mg (0.0 mmol) 4b. Yield 5 mg, 26 % as a pale pink solid, d.r. >20:, [α] D 24 = +56 (c =.0, THF). mp = 29 C (toluene). H MR (400 MHz, CDCl 3) δ [ppm] = 7.64 (s, H), 7.46 (d, J = 7.6 Hz, H), (m, 9H), (m, 3H), 5.70 (d, J = 2.8 Hz, H), (m, 2H), 3.66 (s, 3H), 2.36 (s, 3H),.79 (s, 3H),.57 (s, 3H). 3 C MR (0 MHz, CDCl 3) δ [ppm] = 8.80, 62.28, 53.50, 45.56, 4.60, 4.5, 37.5, 32.87, 3.35, 30.22, 30.02, 29.3, 27.22, 26.55, 26.28, 2.53, 20.4, 5.26, 2.3, 94.2, 66.30, 59.6, 52.4, 50.60, 9.44, 2.04, 9.0. IR (KBr) ν [cm - ] = 3425, 2925, 697, 488, 458, 269, 252, 27, 0, 74, 700. HR-MS (ESI) calc. for: C 32H 30Br 2O 4 + ([M+H] + ): , found:

12 MR-Spectra H MR (400 MHz, CDCl3) 3 C MR (75 MHz, CDCl3) 2

13 H 6b H MR (400 MHz, CDCl3) H 6b 3 C MR (0 MHz, CDCl3) 3

14 H 6c H MR (400 MHz, CDCl3) H 6c 3 C MR (0 MHz, CDCl3) 4

15 H 6d H MR (400 MHz, CDCl3) H 6d 3 C MR (0 MHz, CDCl3) 5

16 H 6e H MR (400 MHz, CDCl3) H 6e 3 C MR (0 MHz, CDCl3) 6

17 H 6f H MR (400 MHz, CDCl3) H 6f 3 C MR (0 MHz, CDCl3) 7

18 OMe H 6g H MR (400 MHz, CDCl3) OMe H 6g 3 C MR (0 MHz, CDCl3) 8

19 Br H 6h H MR (300 MHz, CDCl3) Br H 6h 3 C MR (75 MHz, CDCl3) 9

20 H 6i H MR (400 MHz, CDCl3) H 6i 3 C MR (0 MHz, CDCl3) 20

21 CF 3 H 6j H MR (400 MHz, CDCl3) CF 3 H 6j 3 C MR (0 MHz, CDCl3) 2

22 H 6k H MR (400 MHz, CDCl3) H 6k 3 C MR (75 MHz, CDCl3) 22

23 O O H 6l H MR (400 MHz, CDCl3) O O H 6l 3 C MR (75 MHz, CDCl3) 23

24 H 6m H MR (400 MHz, CDCl3) H 6m 3 C MR (0 MHz, CDCl3) 24

25 H MR (400 MHz, CDCl3) 3 C MR (0 MHz, CDCl3) 25

26 H 6o H MR (400 MHz, CDCl3) H 6o 3 C MR (0 MHz, CDCl3) 26

27 H OMe 8a H MR (400 MHz, CDCl3) H OMe 8a 3 C MR (0 MHz, CDCl3) 27

28 H 8b H MR (400 MHz, CDCl3) H 8b 3 C MR (0 MHz, CDCl3) 28

29 H MR (400 MHz, CDCl3) 3 C MR (0 MHz, CDCl3) 29

30 H F 8d H MR (400 MHz, CDCl3) H F 8d 3 C MR (75 MHz, CDCl3) 30

31 CF 3 H 8e H MR (400 MHz, CDCl3) CF 3 H 8e 3 C MR (75 MHz, CDCl3) 3

32 Br H 8f H MR (400 MHz, CDCl3) Br H 8f 3 C MR (75 MHz, CDCl3) 32

33 F H 8g H MR (400 MHz, CDCl3) F H 8g 3 C MR (75 MHz, CDCl3) 33

34 H 8h H MR (400 MHz, CDCl3) H 8h 3 C MR (0 MHz, CDCl3) 34

35 Br OOH 9 H MR (400 MHz, CDCl3) before (bottom) and after (top) treatment with D2O Br OOH 9 3 C MR (0 MHz, CDCl3) 35

36 HPLC-Chromatograms H rac-6a H 6a 36

37 H rac-6b H 6b 37

38 H rac-6c H 6c 38

39 H rac-6d H 6d 39

40 H rac-6e H 6e 40

41 H rac-6f H 6f 4

42 OMe H rac-6g OMe H 6g 42

43 Br H rac-6h Br H 6h 43

44 H rac-6i H 6i 44

45 CF 3 H rac-6j CF 3 H 6j 45

46 H rac-6k H 6k 46

47 O O H rac-6l O O H 6l 47

48 H rac-6m H 6m 48

49 OMe H rac-6n OMe H 6n 49

50 H rac-6o H 6o 50

51 5

52 H rac-8b H 8b 52

53 53

54 H F rac-8d H F 8d 54

55 CF 3 H rac-8e CF 3 H 8e 55

56 Br H rac-8f Br H 8f 56

57 F H rac-8g F H 8g 57

58 H rac-8h H 8h 58

59 Crystallographic data 59

60 Table. Crystal data and structure refinement for 9. Identification code shelx Empirical formula C32 H29 Br 2 O4 Formula weight Temperature 30(2) K Wavelength Å Crystal system Orthorhombic Space group P Unit cell dimensions a = 0.247(2) Å a= 90. b = 3.475(2) Å b= 90. c = (4) Å g = 90. Volume (9) Å 3 Z 4 Density (calculated).435 Mg/m 3 Absorption coefficient.558 mm - F(000) 208 Crystal size x x mm 3 Theta range for data collection 2.23 to Index ranges -4<=h<=7, -9<=k<=2, -33<=l<=27 Reflections collected Independent reflections 308 [R(int) = ] Completeness to theta = % Absorption correction Semi-empirical from equivalents Max. and min. transmission and Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 308 / / 359 Goodness-of-fit on F Final R indices [I>2sigma(I)] R = , wr2 = R indices (all data) R = 0.076, wr2 = Absolute structure parameter -0.04(4) Extinction coefficient n/a Largest diff. peak and hole and e.å -3 60

61 Table 2. Atomic coordinates ( x 0 4 ) and equivalent isotropic displacement parameters (Å 2 x 0 3 ) for 9. U(eq) is defined as one third of the trace of the orthogonalized U ij tensor. x y z U(eq) C() -448(3) 240(2) 823(2) 24() C(2) -2565(3) 74(2) 8450(2) 3() C(3) -3384(3) 244(3) 7973(2) 37() C(4) -3086(4) 2077(2) 7306(2) 38() C(5) -974(3) 567(2) 7088(2) 32() C(6) -59(3) 5(2) 7556(2) 25() C(7) 8(3) 536(2) 7503() 22() C(8) -40(3) -509(2) 797(2) 29() C(9) 424(3) 450(2) 8244() 9() C(0) 660(3) -42(2) 8484() 9() C() 2885(3) 674(2) 8473() 20() C(2) 4056(3) 78(2) 8226() 22() C(3) 4397(4) 30(3) 7564(2) 34() C(4) 545(4) -449(3) 73(2) 4() C(5) 623(3) -069(3) 7722(2) 36() C(6) 5802(3) -26(3) 8384(2) 36() C(7) 4773(3) -557(3) 8638(2) 3() C(8) 3052(3) 074(2) 9204() 20() C(9) 2734(3) 282(2) 9325() 2() C(20) 3734(3) 2859(2) 9482(2) 27() C(2) 3476(3) 3867(2) 9636(2) 30() C(22) 222(3) 420(2) 967() 25() C(23) 96(3) 3557(2) 9463(2) 27() C(24) 466(3) 2545(2) 9322(2) 27() C(25) 2205(3) 364(2) 9592() 9() C(26) 867(3) 59(2) 0239() 9() C(27) 989(2) -670(2) 0225() 20() C(28) 805(3) -934(2) 9560() 9() C(29) 235(3) 703(2) 0847() 26() C(30) 404(3) -63(2) 0824() 27() C(3) 24(3) -7(2) 9244(2) 22() C(32) -362(4) -304(2) 9449(2) 38() () -454(2) 795(2) 8636() 22() (2) 574(2) -294(2) 989() 8() O() 089(2) 967(2) 702() 26() 6

62 O(2) 34(2) 2006(2) 733() 3() O(3) -9(2) -82(2) 8653() 28() O(4) -509(2) -2327(2) 9697() 28() Br() 836() 5583() 982() 37() 62

63 Table 3. Bond lengths [Å] and angles [ ] for 9. C()-C(2).376(4) C()-C(6).394(4) C()-().430(4) C(2)-C(3).395(5) C(2)-H(2) C(3)-C(4).379(5) C(3)-H(3) C(4)-C(5).392(5) C(4)-H(4) C(5)-C(6).372(4) C(5)-H(5) C(6)-C(7).509(4) C(7)-O().428(3) C(7)-C(8).523(4) C(7)-C(9).536(4) C(8)-H(8A) C(8)-H(8B) C(8)-H(8C) C(9)-().279(4) C(9)-C(0).50(4) C(0)-(2).458(3) C(0)-C().568(4) C(0)-H(0).0000 C()-C(2).56(4) C()-C(8).572(4) C()-H().0000 C(2)-C(3).380(4) C(2)-C(7).387(4) C(3)-C(4).387(5) C(3)-H(3) C(4)-C(5).370(5) C(4)-H(4) C(5)-C(6).373(5) C(5)-H(5) C(6)-C(7).390(5) C(6)-H(6) C(7)-H(7) C(8)-C(25).495(4) 63

64 C(8)-C(9).53(4) C(8)-H(8).0000 C(9)-C(24).383(4) C(9)-C(20).394(4) C(20)-C(2).387(4) C(20)-H(20) C(2)-C(22).367(4) C(2)-H(2) C(22)-C(23).376(4) C(22)-Br().903(3) C(23)-C(24).388(4) C(23)-H(23) C(24)-H(24) C(25)-(2).350(3) C(25)-C(26).374(4) C(26)-C(27).43(4) C(26)-C(29).500(4) C(27)-C(28).393(4) C(27)-C(30).495(4) C(28)-(2).374(3) C(28)-C(3).445(4) C(29)-H(29A) C(29)-H(29B) C(29)-H(29C) C(30)-H(30A) C(30)-H(30B) C(30)-H(30C) C(3)-O(3).205(4) C(3)-O(4).336(3) C(32)-O(4).434(4) C(32)-H(32A) C(32)-H(32B) C(32)-H(32C) O()-O(2).46(3) O(2)-H(7) 0.85(2) C(2)-C()-C(6) 2.8(3) C(2)-C()-() 26.5(3) C(6)-C()-().7(3) C()-C(2)-C(3) 7.5(3) 64

65 C()-C(2)-H(2) 2.2 C(3)-C(2)-H(2) 2.2 C(4)-C(3)-C(2) 20.8(3) C(4)-C(3)-H(3) 9.6 C(2)-C(3)-H(3) 9.6 C(3)-C(4)-C(5) 2.2(3) C(3)-C(4)-H(4) 9.4 C(5)-C(4)-H(4) 9.4 C(6)-C(5)-C(4) 8.3(3) C(6)-C(5)-H(5) 20.9 C(4)-C(5)-H(5) 20.9 C(5)-C(6)-C() 20.4(3) C(5)-C(6)-C(7) 32.6(3) C()-C(6)-C(7) 07.0(2) O()-C(7)-C(6) 5.9(2) O()-C(7)-C(8) 03.7(2) C(6)-C(7)-C(8) 2.7(2) O()-C(7)-C(9) 4.4(2) C(6)-C(7)-C(9) 99.4(2) C(8)-C(7)-C(9).(2) C(7)-C(8)-H(8A) 09.5 C(7)-C(8)-H(8B) 09.5 H(8A)-C(8)-H(8B) 09.5 C(7)-C(8)-H(8C) 09.5 H(8A)-C(8)-H(8C) 09.5 H(8B)-C(8)-H(8C) 09.5 ()-C(9)-C(0) 23.2(2) ()-C(9)-C(7) 4.3(2) C(0)-C(9)-C(7) 22.5(2) (2)-C(0)-C(9).(2) (2)-C(0)-C() 0.5(2) C(9)-C(0)-C() 4.3(2) (2)-C(0)-H(0) 09.9 C(9)-C(0)-H(0) 09.9 C()-C(0)-H(0) 09.9 C(2)-C()-C(0) 09.(2) C(2)-C()-C(8) 3.(2) C(0)-C()-C(8) 05.9(2) C(2)-C()-H() 09.5 C(0)-C()-H()

66 C(8)-C()-H() 09.5 C(3)-C(2)-C(7) 8.3(3) C(3)-C(2)-C() 9.4(3) C(7)-C(2)-C() 22.3(3) C(2)-C(3)-C(4) 2.(3) C(2)-C(3)-H(3) 9.4 C(4)-C(3)-H(3) 9.4 C(5)-C(4)-C(3) 20.2(3) C(5)-C(4)-H(4) 9.9 C(3)-C(4)-H(4) 9.9 C(4)-C(5)-C(6) 9.4(3) C(4)-C(5)-H(5) 20.3 C(6)-C(5)-H(5) 20.3 C(5)-C(6)-C(7) 20.7(3) C(5)-C(6)-H(6) 9.7 C(7)-C(6)-H(6) 9.7 C(2)-C(7)-C(6) 20.3(3) C(2)-C(7)-H(7) 9.8 C(6)-C(7)-H(7) 9.8 C(25)-C(8)-C(9) 3.(2) C(25)-C(8)-C() 02.5(2) C(9)-C(8)-C() 6.7(2) C(25)-C(8)-H(8) 08.0 C(9)-C(8)-H(8) 08.0 C()-C(8)-H(8) 08.0 C(24)-C(9)-C(20) 8.(3) C(24)-C(9)-C(8) 22.3(2) C(20)-C(9)-C(8) 9.5(3) C(2)-C(20)-C(9) 2.4(3) C(2)-C(20)-H(20) 9.3 C(9)-C(20)-H(20) 9.3 C(22)-C(2)-C(20) 8.7(3) C(22)-C(2)-H(2) 20.6 C(20)-C(2)-H(2) 20.6 C(2)-C(22)-C(23) 2.7(3) C(2)-C(22)-Br() 9.5(2) C(23)-C(22)-Br() 8.8(2) C(22)-C(23)-C(24) 9.0(3) C(22)-C(23)-H(23) 20.5 C(24)-C(23)-H(23)

67 C(9)-C(24)-C(23) 2.(3) C(9)-C(24)-H(24) 9.4 C(23)-C(24)-H(24) 9.4 (2)-C(25)-C(26) 08.9(2) (2)-C(25)-C(8).3(2) C(26)-C(25)-C(8) 39.8(2) C(25)-C(26)-C(27) 06.9(2) C(25)-C(26)-C(29) 26.6(2) C(27)-C(26)-C(29) 26.5(2) C(28)-C(27)-C(26) 07.4(2) C(28)-C(27)-C(30) 27.7(2) C(26)-C(27)-C(30) 24.9(2) (2)-C(28)-C(27) 07.0(2) (2)-C(28)-C(3) 20.7(2) C(27)-C(28)-C(3) 32.3(2) C(26)-C(29)-H(29A) 09.5 C(26)-C(29)-H(29B) 09.5 H(29A)-C(29)-H(29B) 09.5 C(26)-C(29)-H(29C) 09.5 H(29A)-C(29)-H(29C) 09.5 H(29B)-C(29)-H(29C) 09.5 C(27)-C(30)-H(30A) 09.5 C(27)-C(30)-H(30B) 09.5 H(30A)-C(30)-H(30B) 09.5 C(27)-C(30)-H(30C) 09.5 H(30A)-C(30)-H(30C) 09.5 H(30B)-C(30)-H(30C) 09.5 O(3)-C(3)-O(4) 23.8(3) O(3)-C(3)-C(28) 25.4(3) O(4)-C(3)-C(28) 0.7(2) O(4)-C(32)-H(32A) 09.5 O(4)-C(32)-H(32B) 09.5 H(32A)-C(32)-H(32B) 09.5 O(4)-C(32)-H(32C) 09.5 H(32A)-C(32)-H(32C) 09.5 H(32B)-C(32)-H(32C) 09.5 C(9)-()-C() 07.(2) C(25)-(2)-C(28) 09.8(2) C(25)-(2)-C(0) 4.2(2) C(28)-(2)-C(0) 34.6(2) 67

68 C(7)-O()-O(2) 07.8(2) O()-O(2)-H(7) 98(3) C(3)-O(4)-C(32) 6.3(2) Symmetry transformations used to generate equivalent atoms: 68

69 Table 4. Anisotropic displacement parameters (Å 2 x 0 3 )for x292. The anisotropic displacement factor exponent takes the form: -2p 2 [ h 2 a* 2 U h k a* b* U 2 ] U U 22 U 33 U 23 U 3 U 2 C() 2() 23() 27() -2() -4() -2() C(2) 28(2) 32(2) 35(2) -6() -3() 4() C(3) 26(2) 34(2) 5(2) -7() -8(2) 6() C(4) 29(2) 38(2) 47(2) 6() -5(2) 6(2) C(5) 27(2) 38(2) 3(2) 5() -9() -2() C(6) 20() 26() 28(2) 2() -5() -2() C(7) 2() 26() 9() 3() -() -() C(8) 33(2) 32(2) 24() -3() -3() -2() C(9) 20() 9() 8() () -2() -4() C(0) 2() 2() 3() 2() -() -2() C() 2() 9() 20() 3() -2() -() C(2) 2() 23() 22() () -2() -4() C(3) 35(2) 43(2) 24(2) 4() 2() 6() C(4) 37(2) 52(2) 32(2) -2(2) 0() 4(2) C(5) 22(2) 39(2) 46(2) -(2) 5(2) 0() C(6) 30(2) 36(2) 42(2) () -3(2) 9() C(7) 28(2) 36(2) 27() 4() 0() 2() C(8) 7() 20() 22() () -2() -() C(9) 23() 2() 8() 3() -2() -4() C(20) 2() 25() 34(2) () -4() -4() C(2) 28(2) 25() 36(2) 0() -2() -8() C(22) 33(2) 20() 23() -() 3() -() C(23) 24() 28(2) 29(2) -2() -3() 0() C(24) 24() 24() 3(2) -3() -3() -4() C(25) 9() 6() 2() 0() -4() 0() C(26) 20() 8() 9() -() -() 2() C(27) 20() 2() 8() 0() -() 3() C(28) 7() 8() 2() 2() 0() () C(29) 32(2) 26() 9() -4() -3() () C(30) 3(2) 3(2) 20() 3() 2() -() C(3) 20() 8() 27() () 0() 0() C(32) 35(2) 32(2) 49(2) 2(2) -(2) -8() () 2() 24() 20() -2() -3() 0() (2) 20() 9() 6() 2() -() -2() O() 28() 26() 23() 3() () -2() 69

70 O(2) 35() 27() 32() 7() -() -6() O(3) 33() 25() 24() -2() -5() -8() O(4) 32() 25() 28() -() 3() -() Br() 46() 23() 42() -6() 0() -2() 70

71 Table 5. Torsion angles [ ] for 9. C(6)-C()-C(2)-C(3) -2.5(5) ()-C()-C(2)-C(3) 76.9(3) C()-C(2)-C(3)-C(4).0(5) C(2)-C(3)-C(4)-C(5).0(5) C(3)-C(4)-C(5)-C(6) -.6(5) C(4)-C(5)-C(6)-C() 0.(5) C(4)-C(5)-C(6)-C(7) 78.(3) C(2)-C()-C(6)-C(5) 2.0(4) ()-C()-C(6)-C(5) -77.5(3) C(2)-C()-C(6)-C(7) -76.5(3) ()-C()-C(6)-C(7) 4.0(3) C(5)-C(6)-C(7)-O() 52.6(4) C()-C(6)-C(7)-O() -29.2(3) C(5)-C(6)-C(7)-C(8) -66.6(4) C()-C(6)-C(7)-C(8).6(3) C(5)-C(6)-C(7)-C(9) 75.7(3) C()-C(6)-C(7)-C(9) -6.(3) O()-C(7)-C(9)-() 3.2(2) C(6)-C(7)-C(9)-() 7.(3) C(8)-C(7)-C(9)-() -.9(3) O()-C(7)-C(9)-C(0) -5.4(4) C(6)-C(7)-C(9)-C(0) -75.5(2) C(8)-C(7)-C(9)-C(0) 65.5(3) ()-C(9)-C(0)-(2) 4.0(4) C(7)-C(9)-C(0)-(2) -63.2(2) ()-C(9)-C(0)-C() -00.(3) C(7)-C(9)-C(0)-C() 82.7(3) (2)-C(0)-C()-C(2) 0.4(2) C(9)-C(0)-C()-C(2) -39.0(2) (2)-C(0)-C()-C(8) -20.7(2) C(9)-C(0)-C()-C(8) 99.0(2) C(0)-C()-C(2)-C(3) 96.0(3) C(8)-C()-C(2)-C(3) -46.4(3) C(0)-C()-C(2)-C(7) -8.2(3) C(8)-C()-C(2)-C(7) 36.3(4) C(7)-C(2)-C(3)-C(4).(5) C()-C(2)-C(3)-C(4) -76.3(3) C(2)-C(3)-C(4)-C(5) -.5(6) 7

72 C(3)-C(4)-C(5)-C(6).(6) C(4)-C(5)-C(6)-C(7) -0.3(5) C(3)-C(2)-C(7)-C(6) -0.3(5) C()-C(2)-C(7)-C(6) 77.0(3) C(5)-C(6)-C(7)-C(2) -0.(5) C(2)-C()-C(8)-C(25) -04.3(2) C(0)-C()-C(8)-C(25) 5.2(3) C(2)-C()-C(8)-C(9) 3.5(3) C(0)-C()-C(8)-C(9) -09.0(3) C(25)-C(8)-C(9)-C(24) -46.4(4) C()-C(8)-C(9)-C(24) 72.2(3) C(25)-C(8)-C(9)-C(20) 30.0(3) C()-C(8)-C(9)-C(20) -.4(3) C(24)-C(9)-C(20)-C(2) 0.5(4) C(8)-C(9)-C(20)-C(2) -76.0(3) C(9)-C(20)-C(2)-C(22) -.6(5) C(20)-C(2)-C(22)-C(23).4(5) C(20)-C(2)-C(22)-Br() -79.6(2) C(2)-C(22)-C(23)-C(24) -0.2(5) Br()-C(22)-C(23)-C(24) -79.(2) C(20)-C(9)-C(24)-C(23) 0.8(4) C(8)-C(9)-C(24)-C(23) 77.2(3) C(22)-C(23)-C(24)-C(9) -.0(5) C(9)-C(8)-C(25)-(2) 23.(2) C()-C(8)-C(25)-(2) -3.5(3) C(9)-C(8)-C(25)-C(26) -57.6(4) C()-C(8)-C(25)-C(26) 75.8(3) (2)-C(25)-C(26)-C(27) 0.3(3) C(8)-C(25)-C(26)-C(27) -79.0(3) (2)-C(25)-C(26)-C(29) 79.5(3) C(8)-C(25)-C(26)-C(29) 0.2(5) C(25)-C(26)-C(27)-C(28) -.0(3) C(29)-C(26)-C(27)-C(28) 79.8(3) C(25)-C(26)-C(27)-C(30) 78.(3) C(29)-C(26)-C(27)-C(30) -.(4) C(26)-C(27)-C(28)-(2).3(3) C(30)-C(27)-C(28)-(2) -77.8(3) C(26)-C(27)-C(28)-C(3) -80.0(3) C(30)-C(27)-C(28)-C(3).0(5) (2)-C(28)-C(3)-O(3) -7.0(4) 72

73 C(27)-C(28)-C(3)-O(3) 74.4(3) (2)-C(28)-C(3)-O(4) 7.9(2) C(27)-C(28)-C(3)-O(4) -6.7(4) C(0)-C(9)-()-C() 77.6(2) C(7)-C(9)-()-C() -5.0(3) C(2)-C()-()-C(9) -79.0(3) C(6)-C()-()-C(9) 0.5(3) C(26)-C(25)-(2)-C(28) 0.5(3) C(8)-C(25)-(2)-C(28) -80.0(2) C(26)-C(25)-(2)-C(0) 69.3(2) C(8)-C(25)-(2)-C(0) -.(3) C(27)-C(28)-(2)-C(25) -.(3) C(3)-C(28)-(2)-C(25) 79.9(2) C(27)-C(28)-(2)-C(0) -66.7(3) C(3)-C(28)-(2)-C(0) 4.3(4) C(9)-C(0)-(2)-C(25) -0.8(3) C()-C(0)-(2)-C(25) 20.(3) C(9)-C(0)-(2)-C(28) 63.4(4) C()-C(0)-(2)-C(28) -74.7(3) C(6)-C(7)-O()-O(2) 52.3(3) C(8)-C(7)-O()-O(2) 76.4(2) C(9)-C(7)-O()-O(2) -62.5(3) O(3)-C(3)-O(4)-C(32) -4.0(4) C(28)-C(3)-O(4)-C(32) 77.(3) Symmetry transformations used to generate equivalent atoms: 73