Total Synthesis of the Neoclerodane Diterpene Salvinorin A via an Intramolecular Diels Alder Strategy

Transcription

1 Total Synthesis of the Neoclerodane Diterpene Salvinorin A via an Intramolecular Diels Alder Strategy Yuzhou Wang and Peter Metz* Fakultät Chemie und Lebensmittelchemie, Organische Chemie I, Technische Universität Dresden, Bergstrasse 66, Dresden, Germany Supporting Information S1

2 Table of contents 1. General information S3 2. Improved preparation of diene 10 S3 3. Improved preparation of BC building block 5 S4 4. Preparation of keto aldehyde 4 S4 5. Preparation of vinyl iodide 14 S5 6. HWE reaction of 14 to give enoates 16 and 17 S6 7. Epimerization of enoate 16 with DBU to give enoate 17 S8 8. Preparation of triene 19 S8 9. IMDA of triene 19 S9 10. Preparation of triene 3 S IMDA of triene 3 S Preparation of diol 23 S Preparation of ketone 25 S Preparation of 2-epi-salvinorin B (26) S Preparation of salvinorin A (1) and 2-epi-1 S References S NMR spectra S20 S2

3 1. General information THF, toluene, and CH 2 Cl 2 were dried and purified by passage through a MB-SPS-800 device using molecular sieves. Et 3 N was freshly distilled over CaH 2, DME over LiAlH 4, and NMP and chlorobenzene were dried over molecular sieves 4Å. All other commercially available reagents were used as received. Reactions were performed under argon atmosphere. Thin layer chromatography (TLC) was performed on Merck silica gel 60 F mm precoated plates. Product spots were visualized by UV light at 254 nm and subsequently developed using anisaldehyde solution as appropriate. Flash column chromatography was carried out using silica gel (Merck, particle size microns). Semi-preparative HPLC separations were performed with a Waters 600 pump, a Waters 600 controller, a Waters 2996 photodiode array detector, and a Macherey-Nagel SP 250/21 Nucleosil column. Melting points were measured on a Wagner & Munz PolyTherm A and are uncorrected. Infrared spectra were recorded on a THERMONICOLET Avatar 360 instrument using ATR. NMR spectra were recorded on a Bruker AC 300 P (300 MHz 1 H, 75 MHz 13 C), on a Bruker DRX 500 P (500 MHz 1 H, 125 MHz 13 C) or on a Bruker AC 600-P (600 MHz 1 H, 151 MHz 13 C) spectrometer. Chemical shifts ( ) are quoted in parts per million (ppm) downfield of tetramethylsilane, using residual proton-containing solvent as internal standard (CDCl 3 at 7.26 ppm). Abbreviations used in the description of resonances are: s (singlet), d (doublet), t (triplet), q (quartet), br (broad). Coupling constants (J) are quoted to the nearest 0.1 Hz. Mass spectra were recorded with an Agilent 5973N detector coupled with an Agilent 6890N GC (GC-MS, 70 ev) or else with a Bruker Esquire-LC (direct injection as a methanolic NH 4 OAc solution, ESI). HRMS spectra were recorded on a Bruker Daltonic "Impact II" (ESI-TOF). Elemental analysis was performed on a Hekatech EA Improved preparation of diene 10 To a solution of vinyl iodide 7 (1.39 g, 5.00 mmol) and stannane 8 (3.50 g, 10.0 mmol) in NMP (10 ml) cooled to 0 C was added carboxylate 9 (2.34 g, 12.5 mmol). After stirring the brown mixture for 24 h at 0 C, it had turned green and was filtered through silica gel (elution with Et 2 O). The colorless filtrate was washed with saturated aqueous NaHCO 3 (3 30 ml), water (3 30 ml), and brine (3 30 ml), dried over MgSO 4, and concentrated under S3

4 vacuum. Flash chromatography over silica gel (pentane/et 2 O, 8:2) afforded 1,3-diene 10 1 (909 mg, 95%) as a colorless oil. 3. Improved preparation of BC building block 5 Acryloyl chloride (1.23 g, 13.6 mmol) was added dropwise to a stirred solution of alcohol 10 (1.31 g, 6.81 mmol), triethylamine (5.7 ml, 40.9 mmol), and DMAP (83.2 mg, 0.68 mmol) in CH 2 Cl 2 (34 ml) cooled to 78 C. The mixture was allowed to warm to room temperature overnight with stirring. After addition of Et 2 O (100 ml), the mixture was filtered through a short pad of silica gel (elution with Et 2 O) and then concentrated under vacuum to give acrylate 11 (1.57 g) as a yellowish oil that was immediately used for the next step without further purification. A solution of crude acrylate 11 (1.57 g) and 2,6-di-tert-butyl-4- methylphenol (140 mg, mmol) in chlorobenzene (80 ml) was heated in a sealed tube to 183 C for 73 h. After cooling to room temperature and concentration under vacuum, flash chromatography over silica gel (pentane/et 2 O, 8:2) afforded lactone 5 1 (1.16 g, 69% over 2 steps, 86% ds according to GC analysis) as a colorless oil. 4. Preparation of keto aldehyde 4 To a solution of cycloadduct 5 (0.493 g, 2.00 mmol, 97% ds) in a mixture of acetone (20 ml) and water (0.3 ml) cooled to 0 C was added a solution of osmium tetroxide (0.5 ml, 0.2 M in toluene, 5 mol %) and NMO monohydrate (0.541 g, 4.00 mmol). The mixture was allowed to warm to room temperature, and stirring was continued for 24 h. Then additional NMO monohydrate (0.541 g, 4.00 mmol) was added, and the mixture was stirred for another 24 h. After addition of Na 2 S 2 O 5 (3.8 g) in buffer ph 7 (10 ml), the mixture was diluted with ethyl acetate (20 ml). The layers were separated, the aqueous layer was extracted with ethyl acetate (3 15 ml), and the combined organic layers were dried over MgSO 4 and concentrated under vacuum. Flash chromatography over silica gel (CH 2 Cl 2 /Et 2 O, 1:1) gave S4

5 diols 12 and 13 (0.385 g, 69%, 12:13 = 2:1 according to 1 H NMR integration) as a white solid with R f = 0.26 (CH 2 Cl 2 /Et 2 O, 1:1), which was used for the following step without further separation. A solution of the 2:1 mixture of diols 12 and 13 (0.362 g, 1.29 mmol) in CH 2 Cl 2 (13 ml) was treated with PIDA (0.499 g, 1.55 mmol) at room temperature, and stirring was continued for 1.5 h. After addition of saturated aqueous Na 2 S 2 O 3 (2.5 ml) and saturated aqueous NaHCO 3 (3 ml), the layers were separated, and the aqueous layer was extracted with CH 2 Cl 2 (3 10 ml). The combined organic layers were dried over MgSO 4 and concentrated under vacuum. Flash chromatography over silica gel (CH 2 Cl 2 /Et 2 O, 7:3) gave keto aldehyde 4 (317.2 mg, 88%) as a white solid. 4: R f = 0.43 (CH 2 Cl 2 /Et 2 O, 7:3). M.p. = C. 1 H NMR (500 MHz, CDCl 3 ): = 1.48 (s, 3 H), (m, 2 H), 1.88 (dd, J = 14.7, 3.0 Hz, 1 H), 2.13 (s, 3 H), 2.33 (dd, J = 14.8, 12.0 Hz, 1 H), 2.62 (dd, J = 10.4, 2.8 Hz, 1 H), 2.68 (ddd, J = 18.9, 8.8, 5.8 Hz, 1 H), 2.77 (ddd, J = 18.9, 5.4, 5.4 Hz, 1 H), 5.37 (dd, J = 11.7, 2.8 Hz, 1 H), 6.45 (dd, J = 1.7, 0.8 Hz, 1 H), 7.43 (t, J = 1.7 Hz, 1 H), (m, 1 H), 9.48 (s, 1 H) ppm. 13 C NMR (126 MHz, CDCl 3 ): = (t), (q), (q), (t), (t), (d), (s), (d), (d), (s), (d), (d), (s), (d), (s) ppm. IR (ATR): = 3134 (w), 3107 (w), 2965 (w), 2938 (w), 2876 (w), 2813 (w), 2717 (w), 1739 (s),1702 (s), 1651 (w), 1603 (w), 1503 (w), 1404 (w), 1377 (m), 1357 (m), 1324 (w), 1269 (w), 1214 (m), 1159 (s), 1069 (m), 1022 (s), 994 (m), 971 (w), 898 (w), 873 (s), 803 (s), 738 (m), 695 (w) cm 1. HRMS: m/z calcd for [2M Na] : ; found Preparation of vinyl iodide 14 Chromium dichloride (0.430 g, 3.50 mmol) was suspended in THF (5 ml), and the mixture was stirred for 1 h at room temperature. The suspension was cooled to 8 10 C, a solution of 4 (139.2 mg, mmol) and iodoform (207 mg, mmol) was added, and stirring was continued for 5 h. After addition of saturated aqueous Na 2 S 2 O 3 (3 ml), the layers were separated, and the aqueous layer was extracted with Et 2 O (4 10 ml). The combined organic S5

6 layers were dried over MgSO 4 and concentrated under vacuum. Flash chromatography over silica gel (CH 2 Cl 2 /Et 2 O, 20:1) gave vinyl iodide 14 (117 mg, 58%) as a colorless oil. 14: R f = 0.37 (CH 2 Cl 2 /Et 2 O, 20:1). 1 H NMR (300 MHz, CDCl 3 ): = 1.39 (s, 3 H), (m, 1 H), 1.96 (dd, J = 14.7, 3.2 Hz, 1 H), 2.07 (dd, J = 14.7, 11.9 Hz, 1 H), 2.12 (s, 3 H), 2.41 (dd, J = 9.6, 3.6 Hz, 1 H), (m, 1 H), 2.75 (dt, J = 18.7, 5.7 Hz, 1 H), 5.34 (dd, J = 11.5, 3.2 Hz, 1 H), 6.16 (d, J = 14.6 Hz, 1 H), 6.37 (d, J = 14.5 Hz, 1 H), 6.42 (dd, J = 1.7, 0.8 Hz, 1 H), 7.41 (t, J = 1.7 Hz, 1 H), 7.46 (br s, 1 H) ppm. 13 C NMR (75 MHz, CDCl 3 ): = (t), (q), (q), (s), (t), (t), (d), (d), (d), (d), (s), (d), (d), (d), (s), (s) ppm. IR (ATR): = 3139 (w), 3028 (w), 2964 (w), 2931 (w), 1734 (s), 1709 (s), 1652 (w), 1600 (w), 1503 (w), 1404 (w), 1373 (m), 1247 (m), 1185 (m), 1158 (s), 1063 (m), 1022 (s), 960 (s), 874 (s), 788 (s), 717 (m) cm 1. HRMS: m/z calcd for [M Na] : ; found HWE reaction of 14 to give enoates 16 and 17 Sodium hydride (36.7 mg, 1.53 mmol) was suspended in DME (5 ml), and the mixture was cooled to 0 C. Methyl diethylphosphonoacetate (366 mg, 1.74 mmol) was added dropwise, and stirring was continued for 1 h at room temperature. A solution of 14 (280 mg, mmol) in DME (2 ml) was added dropwise, and stirring was continued for 48 h at room temperature. After addition of saturated aqueous NH 4 Cl (3 ml), the layers were separated, and the aqueous layer was extracted with CH 2 Cl 2 (4 5 ml). The combined organic layers were dried over MgSO 4 and concentrated under vacuum. Flash chromatography over silica gel (pentane/et 2 O, 6:4) and subsequent semi-preparative HPLC (isohexane/etoac, 86:14) to provide homogeneous fractions 2 and 3 gave four isomeric enoates SI-1, SI-2, 17, and 16. S6

7 Fraction 1: SI-1 (22.0 mg, 7%). Colorless oil. R f = 0.31 (pentane/et 2 O, 6:4). Fraction 2: SI-2 (54.2 mg, 17%). Colorless oil. SI-2: R f = 0.26 (pentane/et 2 O, 6:4). 1 H NMR (600 MHz, CDCl 3 ): = 1.34 (s, 3 H), (m, 1 H), (m, 1 H), 1.94 (d, J = 1.5 Hz, 3 H), 1.97 (dd, J = 14.7, 3.0 Hz, 1 H), 2.06 (dd, J = 14.7, 11.7 Hz, 1 H), 2.38 (ddd, J = 11.7, 10.0, 5.5 Hz, 1 H), 2.44 (dd, J = 10.0, 1.7 Hz, 1 H), 2.96 (ddd, J = 11.7, 9.6, 6.2 Hz, 1 H), 3.67 (s, 3 H), 5.35 (dd, J = 11.9, 2.8 Hz, 1 H), 5.70 (s, 1 H), 6.13 (d, J = 14.7 Hz, 1 H), 6.37 (d, J = 14.7 Hz, 1 H), 6.43 (d, J = 1.1 Hz, 1 H), 7.42 (t, J = 1.7 Hz, 1 H), 7.49 (s, 1 H) ppm. 13 C NMR (151 MHz, CDCl 3 ): = (t), (q), (q), (t), (t), (s), (d), (q), (d), (d), (d), (d), (s), (d), (d), (d), (s), (s), (s) ppm. IR (ATR): = 3067 (w), 2947 (w), 1737 (m), 1709 (s), 1651 (w), 1600 (w), 1503 (w), 1456 (w), 1437 (w), 1377 (w), 1241 (m), 1195 (s), 1161 (s), 1139 (s), 1068 (m), 1023 (m), 961 (m), 920 (w), 874 (m), 855 (m), 788 (m), 732 (s) cm 1. HRMS: m/z calcd for [M Na] : ; found Fraction 3: 17 (68.3 mg, 21%). White solid. 17: R f = 0.26 (pentane/et 2 O, 6:4). M.p. = C. 1 H NMR (600 MHz, CDCl 3 ): = 1.20 (s, 3 H), 1.51 (dddd, J = 13.8, 8.2, 8.2, 1.9 Hz, 1 H), (m, 1 H), 1.95 (dd, J = 14.12, 4.33 Hz, 1 H), 2.08 (dd, J = 13.93, Hz, 1 H), 2.15 (d, J = 1.1 Hz, 3 H), 2.20 (dd, J = 9.41, 1.51 Hz, 1 H), 2.28 (dt, J = 14.3, 8.3 Hz, 1 H), (m, 1 H), 3.70 (s, 3 H), 5.43 (dd, J = 11.7, 4.1 Hz, 1 H), 5.68 (d, J = 0.8 Hz, 1 H), 6.26 (d, J = 14.7 Hz, 1 H), 6.41 (d, J = 14.7 Hz, 1 H), 6.41 (d, J = 1.0 Hz, 1 H), 7.42 (t, J = 1.7 Hz, 1 H), 7.45 (d, J = 0.8 Hz, 1 H) ppm. 13 C NMR (151 MHz, CDCl 3 ): = (q), (q), (t), (t), (t), (s), (d), (q), (d), (d), (d), (d), (s), (d), (d), (d), (s), (s), (s) ppm. IR (ATR): = 3108 (w), 3081 (w), 2949 (w), 2924 (w), 2854 (w), 1710 (s), 1685 (w), 1651 (m), 1640 (m), 1457 (m), 1432 (m), 1389 (w), 1354 (w), 1223 (m), 1203 (m), 1142 (s), 1080 (m), 1063 (m), 1020 (m), 945 (m), 926 (m), 867 (m), 826 (m), 809 (m), 771 (w), 718 (w) cm 1. HRMS: m/z calcd for [2M Na] : ; found Fraction 4: 16 (126.4 mg, 40%). Colorless oil. S7

8 16: R f = 0.21 (pentane/et 2 O, 6:4). 1 H NMR (500 MHz, CDCl 3 ): = 1.32 (s, 3 H), (m, 1 H), (m, 1 H), 1.97 (dd, J = 14.8, 2.8 Hz, 1 H), 2.07 (dd, J = 14.8, 11.7 Hz, 1 H), (m, 1 H), 2.17 (d, J = 1.0 Hz, 3 H), 2.25 (dd, J = 10.6, 1.7 Hz, 1 H), 2.44 (ddd, J = 14.0, 9.1, 4.7 Hz, 1 H), 3.69 (s, 3 H), 5.36 (dd, J = 11.7, 2.8 Hz, 1 H), 5.68 (s, 1 H), 6.16 (d, J = 14.8 Hz, 1 H), 6.36 (d, J = 14.8 Hz, 1 H), 6.42 (d, J = 1.0 Hz, 1 H), 7.42 (t, J = 1.6 Hz, 1 H), 7.48 (s, 1 H) ppm. 13 C NMR (126 MHz, CDCl 3 ): = (q), (t), (q), (t), (s), (t), (d), (q), (d), (d), (d), (d), (s), (d), (d), (d), (s), (s), (s) ppm. IR (ATR): = 3141 (w), 3068 (w), 2947 (w), 2869 (w), 1736 (m), 1710 (s), 1650 (m), 1600 (w), 1435 (w), 1379 (w), 1222 (s), 1144 (s), 1067 (m), 1023 (m), 959 (m), 873 (m), 787 (m), 718 (m) cm 1. HRMS: m/z calcd for [M Na] : ; found Epimerization of enoate 16 with DBU to give enoate 17 A solution of vinyl iodide 16 (146.5 mg, mmol) and DBU (96.2 mg, 0.32 mmol) in CH 2 Cl 2 (3 ml) was stirred for 3 h at room temperature. After filtration through a short pad of silica gel and concentration, the residue was subjected to flash chromatography (pentane/et 2 O, 8:2) to give epimer 17 (49.5 mg, 34%) and reisolated 16 (97.0 mg, 66%). 8. Preparation of triene 19 A solution of vinyl iodide 16 (112.6 mg, mmol) and stannane 18 (155.4 mg, 0.49 mmol) in NMP (2 ml) was cooled to 0 C, and Pd(MeCN) 2 Cl 2 (6.4 mg, mmol, 10 mol %) was added. After stirring the mixture for 17 h at 0 C, it was diluted with water (10 ml) and extracted with EtOAc (3 10 ml). The combined organic layers were dried over MgSO 4 and concentrated under vacuum. Flash chromatography over silica gel (pentane/et 2 O, 6:4) afforded the 1,3-diene 19 (78.6 mg, 90%) as a colorless oil. S8

9 19: R f = 0.31 (pentane/et 2 O, 6:4). 1 H NMR (600 MHz, CDCl 3 ): = 1.35 (s, 3 H), (m, 1 H), (m, 1 H), 1.98 (dd, J = 14.7, 3.0 Hz, 1 H), 2.07 (dd, J = 14.7, 12.0 Hz, 1 H), (m, 1 H), 2.16 (d, J = 1.1 Hz, 3 H), 2.29 (dd, J = 10.5, 1.9 Hz, 1 H), 2.43 (ddd, J = 13.8, 9.3, 4.7 Hz, 1 H), 3.68 (s, 3 H), 5.09 (d, J = 10.2 Hz, 1 H), 5.20 (d, J = 17.3 Hz, 1 H), 5.38 (dd, J = 11.9, 2.8 Hz, 1 H), 5.50 (d, J = 15.4 Hz, 1 H), 5.68 (d, J = 1.1 Hz, 1 H), 6.02 (dd, J = 15.4, 10.2 Hz, 1 H), 6.29 (dt, J = 16.8, 10.4 Hz, 1 H), 6.43 (dd, J = 1.9, 0.8 Hz, 1 H), 7.42 (t, J = 1.7 Hz, 1 H), (m, 1 H) ppm. 13 C NMR (151 MHz, CDCl 3 ): = (q), (t), (q), (s), (t), (t), (d), (q), (d), (d), (d), (t), (d), (d), (d), (d), (d), (d), (s), (s), (s) ppm. IR (ATR): = 3139 (w), 3087 (w), 2950 (w), 2869 (w), 1734 (m), 1711 (s), 1650 (m), 1603 (w), 1435 (w), 1379 (w), 1221 (s), 1145 (s), 1103 (m), 1067 (m), 1022 (m), 1006 (m), 962 (w), 906 (m), 873 (m), 784 (m), 733 (m) cm 1. ESI-MS: m/z = [M NH 4 ]. HRMS: m/z calcd for [M Na] : ; found IMDA of triene 19 A solution of 1,3-diene 19 (78.6 mg, mmol) and 2,6-di-tert-butyl-4-methylphenol (4.8 mg, mmol, 10 mol %) in toluene (6 ml) was heated in a sealed tube to 200 C for 5 d. After cooling to room temperature and removal of the solvent under vacuum, flash chromatography over silica gel (pentane/et 2 O, 6:4) afforded a mixture of diastereomeric cycloadducts 20 and 2 (20.6 mg, 26%, 20:2 = 84:16 according to GC analysis) as a solid and cycloadduct 21 (12.8 mg, 16%) as a colorless oil. 20: R f = 0.34 (pentane/et 2 O, 4:6). 1 H NMR (600 MHz, CDCl 3 ): = 1.06 (s, 3 H, H-19), 1.23 (s, 3 H, H-20), 1.38 (dt, J = 13.4, 3.3 Hz, 1 H, H-6 ), 1.73 (td, J = 13.9, 3.8 Hz, 1 H, H-6 ), 1.78 (dd, J = 14.1, 12.6 Hz, 1 H, H-11 ), (m, 1 H, H-7 ), 1.97 (br s, 1 H, H-10), 2.05 (dd, J = 14.3, 1.9 Hz, 1 H, H-11 ), (m, 1 H, H-3 ), (m, 1 H, H-7 ), (m, 2 H, H-3, H-4), 2.51 (d, J = 4.1 Hz, 1 H, H-8), 3.63 (s, 3 H, OCH 3 ), 5.27 (d, J S9

10 = 11.3 Hz, 1 H, H-12), (m, 1 H, H-2), (m, 1 H, H-14), 7.41 (t, J = 1.0 Hz, 1 H, H-15), 7.47 (d, J = 0.8 Hz, 1 H, H-16) ppm. 13 C NMR (151 MHz, CDCl 3 ): = (q, C-19), (t, C-7), (q, C-20), (t, C-3), (t, C-6), (s, C-9), (s, C-5), (d, C-8), (t, C-11), (q, OCH 3 ), (d, 4-C), (d, C-10), (d, C-12), (d, C-14), (s, C-13), (d, C-1), (d, C-2), (d, C-16), (d, C-15), (s, C-17, C-18) ppm. ESI-MS: m/z = [M NH 4 ], [M H]. 21: R f = 0.28 (pentane/et 2 O, 4:6). 1 H NMR (600 MHz, CDCl 3 ): = 1.08 (s, 3 H, H-19), 1.23 (s, 3 H, H-20), 1.45 (td, J = 13.4, 3.8 Hz, 1 H, H-6 ), (m, 1 H, H-6 ), 1.73 (ddd, J = 14.1, 3.6, 1.5 Hz, 1 H, H-11 ), 1.86 (qd, J = 13.5, 3.6 Hz, 1 H, H-7 ), (m, 1 H, H-10), (m, 1 H, H-7 ), (m, 1 H, H-3 ), 2.21 (dd, J =14.3, 12.2 Hz, 1 H, H-11 ), 2.34 (ddd, J=12.9, 4.6, 1.3 Hz, 1 H, H-8), (m, 2 H, H-4, H-3 ), 3.66 (s, 3 H, OCH 3 ), 5.37 (dd, J = 12.0, 3.8 Hz, 1 H, H-12), 5.63 (dd, J = 10.2, 1.5 Hz, 1 H, H-1), (m, 1 H, H-2), 6.40 (d, J = 0.8 Hz, 1 H, H-14), 7.41 (t, J = 1.5 Hz, 1 H, H-15), 7.44 (s, 1 H, H-16) ppm. 13 C NMR (151 MHz, CDCl 3 ): = (q, C-19), (t, C-7), (t, C- 3), (q, C-20), (t, C-11), (s, C-9), (s, C-5), (t, C-6), (d, C- 8), (q, OCH 3 ), (d, C-4), (d, C-10), (d, C-12), (d, C-14), (d, C-1), (s, C-13), (d, C-2), (d, C-16), (d, C-15), (s, C-18, C-17) ppm. ESI-MS: m/z = [M NH 4 ], [M H]. 10. Preparation of triene 3 A solution of vinyl iodide 17 (49.0 mg, mmol) and stannane 18 (67.8 mg, mmol) in NMP (1 ml) was cooled to 0 C, and Pd(MeCN) 2 Cl 2 (2.8 mg, mmol, 10 mol %) was added. After stirring the mixture for 24 h at 0 C, it was diluted with water (10 ml) and extracted with CH 2 Cl 2 (4 10 ml). The combined organic layers were washed with water (10 ml), dried over MgSO 4, and concentrated under vacuum. Flash chromatography over silica gel (pentane/et 2 O, 6:4) afforded the 1,3-diene 3 (35.6 mg, 93%) as a colorless oil. S10

11 3: R f = 0.27 (pentane/et 2 O, 6:4). M.p. = C. 1 H NMR (500 MHz, CDCl 3 ): = 1.20 (s, 3 H), (m, 1 H), (m, 1 H), 1.93 (dd, J = 14.0, 4.3 Hz, 1 H), 2.06 (dd, J = 13.9, 12.0 Hz, 1 H), 2.12 (d, J = 0.9 Hz, 3 H), (m, 1 H), 2.27 (dt, J = 14.5, 7.6 Hz, 1 H), 2.58 (ddd, J = 14.0, 8.6, 4.9 Hz, 1 H), (m, 3 H), 5.12 (d, J = 10.1 Hz, 1 H), 5.23 (d, J = 16.7 Hz, 1 H), 5.44 (dd, J = 11.8, 3.9 Hz, 1 H), 5.53 (d, J = 15.4 Hz, 1 H), 5.67 (d, J = 0.9 Hz, 1 H), 6.09 (dd, J = 15.6, 10.2 Hz, 1 H), 6.32 (dt, J = 16.9, 10.1 Hz, 1 H), 6.42 (d, J = 0.9 Hz, 1 H), 7.41 (t, J = 1.7 Hz, 1 H), 7.45 (s, 1 H) ppm. 13 C NMR (126 MHz, CDCl 3 ): = (q), (q), (t), (s), (t), (t), (d), (q), (d), (d), (d), (t), (s), (d), (d), (d), (d), (d), (s), (s), (s) ppm. IR (ATR): = 3111 (w), 2969 (w), 2955 (w), 2860 (w), 1713 (s), 1650 (m), 1222 (m), 1204 (m), 1144 (s), 1083 (m), 1063 (m), 1020 (m), 1006 (m), 952 (w), 916 (m), 865 (m), 826 (w), 806 (m), 741 (m), 695 (w), 653 (w) cm 1. ESI-MS: m/z = [M NH 4 ]. HRMS: m/z calcd for [M Na] : ; found IMDA of triene 3 A solution of 1,3-diene 3 (50 mg, mmol) and 2,6-di-tert-butyl-4-methylphenol (36.9 mg, mmol, 1.2 equiv) in chlorobenzene (25 ml) was degassed through two freezepump-thaw cycles and then heated in a sealed tube to 200 C for 87.5 h. After cooling to room temperature and removal of the solvent under vacuum, flash chromatography over silica gel (pentane/et 2 O, 6:4) afforded a mixture of cycloadduct 2 (33.0 mg, 66%, 88% brsm, 94% ds according to GC analysis) as a colorless oil and starting material 3 (12.5 mg, 25%). A sample of the isomeric cycloadduct 22 (colorless oil) was collected from several runs. 2: R f = 0.24 (pentane/et 2 O, 6:4). 1 H NMR (600 MHz, CDCl 3 ): = 1.06 (s, 3 H, H-20), 1.08 (s, 3 H, H-19), 1.37 (td, J = 13.4, 3.8 Hz, 1 H, H-6 ), (m, 2 H, H-11, H-6 ), (m, 1 H, H-7 ), 1.96 (br s, 1 H, H-10), 2.09 (dq, J = 14.5, 3.5 Hz, 1 H, H-7 ), (m, 2 H, H-8, H-3 ), 2.39 (dd, J = 13.6, 6.0 Hz, 1 H, H-11 ), (m, 2 H, H-4, H-3 ), S11

12 3.66 (s, 3 H, H-OMe), 5.54 (dd, J = 11.1, 5.8 Hz, 1 H, H-12), 5.57 (d, J=10.2 Hz, 1 H, H-1), (m, 1 H, H-2), 6.42 (d, J=0.8 Hz, 1 H, H-14), (m, 1 H, H-15), 7.44 (s, 1 H, H-16) ppm. 13 C NMR (151 MHz, CDCl 3 ): = (q, C-19), (q, C-20), (t, C-7), (t, C-3), (s, C-5), (t, C-6), (s, C-9), (t, C-11), (d, C- 8), (q, OCH 3 ), (d, C-4), (d, C-10), (d, C-12), (d, C-14), (d, C-1), (s, C-13), (d, C-2), (d, C-16), (d, C-15), (s, C-17), (s, C-18) ppm. IR (ATR): = 3149 (w), 3132 (w), 2952 (w), 2930 (w), 2850 (w), 1721 (s), 1685 (w), 1652 (w), 1436 (w), 1367 (m), 1339 (w), 1309 (m), 1255 (w), 1202 (m), 1157 (s), 1141 (s), 1087 (m), 1072 (m), 1023 (m), 990 (m), 957 (w), 903 (w), 875 (m), 814 (m), 788 (m), 773 (m), 700 (w), 660 (w) cm 1. ESI-MS: m/z = [M NH 4 ], [2M NH 4 ]. HRMS: m/z calcd for [M Na] : ; found : 1 H NMR (600 MHz, CDCl 3 ): = 1.21 (s, 3 H, H-19), (m, 1 H, H-6 ) 1.36 (s, 3 H, H-20), (m, 1 H, H-6 ), (m, 1 H, H-7 ), (m, 1 H, H-11 ), (m, 3 H, H-7, H-3, H-11 ), (m, 4 H, H-8, H-3, H-4, H-10), 3.66 (s, 3 H, OCH 3 ), 5.52 (dd, J = 12.0, 4.1 Hz, 1 H, H-12), 5.77 (s, 2 H, H-1, H-2), (m, 1 H, H- 14), (m, 1 H, H-15), (m, 1 H, H-16) ppm. 13 C NMR (151 MHz, CDCl 3 ): = (t, C-7), (q, C-20), (t, C-3), (q, C-19), (t, C-6), (s, C- 5), (s, C-9), (t, C-11), (d, C-8), (d, C-10), (d, C-4), (q, OCH 3 ), (d, C-12), (d, C-14), (d, C-2), (s, C-13), (d, C-1), (d, C-16), (d, C-15), (s, C-17), (s, C-18) ppm. 12. Preparation of diol 23 To a solution of cycloadduct 2 (23.0 mg, 64.2 mol) and 3,5-lutidine (13.8 mg, mol) in THF (1.5 ml) cooled to 0 C was added a solution of osmium tetroxide (321 L, 0.2 M in toluene, 64.2 mol). The mixture was allowed to warm to room temperature, and stirring was continued for 24 h. After addition of Na 2 S 2 O 5 (98.0 mg) in buffer ph 7 (2 ml), the mixture was extracted with ethyl acetate (4 4 ml), and the combined organic layers were dried over S12

13 MgSO 4 and concentrated under vacuum. Flash chromatography over silica gel (CH 2 Cl 2 /Et 2 O, 9:1 and 1:1) gave diol 23 (23.9 mg, 95%) as a white solid. 23: R f = 0.26 (CH 2 Cl 2 /Et 2 O, 1:1). M.p. = C. 1 H NMR (600 MHz, CDCl 3 ): = 1.10 (s, 3 H, H-19), 1.24 (s, 3 H, H-20), 1.38 (td, J = 13.5, 3.2 Hz, 1 H, H-6 ), 1.54 (dt, J = 13.4, 3.3 Hz, 1 H, H-6 ), (m, 1 H, H-7 ), 1.60 (d, J = 11.3 Hz, 1 H, H-10), 1.75 (dd, J = 13.7, 11.5 Hz, 1 H, H-11 ), 1.85 (dt, J = 14.8, 3.0 Hz, 1 H, H-3 ), 2.04 (dq, J = 14.5, 3.2 Hz, 1 H, H-7 ), (m, 1 H, H-3 ), (m, 2 H, H-8, OH), 2.34 (br s, 1 H, OH), 2.60 (dd, J = 13.6, 3.4 Hz, 1 H, H-4), 3.33 (dd, J = 13.9, 6.0 Hz, 1 H, H-11 ), 3.64 (s, 3 H, OCH 3 ), (m, 2 H, H-1, H-2), 5.44 (dd, J = 11.3, 5.6 Hz, 1 H, H-12), 6.40 (d, J = 0.8 Hz, 1 H, H-14), 7.40 (t, J = 1.7 Hz, 1 H, H-15), 7.42 (s, 1 H, H-16) ppm. 13 C NMR (151 MHz, CDCl 3 ): = (q, C-20), (q, C-19), (t, C-7), (t, C-3), (s, C- 9), (s, C-5), (t, C-6), (t, C-11), (d, C-4), (q, OCH 3 ), (d, C-10), (d, C-8), (d, C-1), (d, C-2), (d, C-12), (d, C-14), (s, C-13), (d, C-16), (d, C-15), (s, C-17), (s, C-18) ppm. IR (ATR): = 3475 (m), 3141 (w), 3097 (w), 2992 (w), 2932 (m), 2879 (w), 2851 (w), 1712 (s), 1685 (w), 1652 (w), 1635 (w), 1449 (w), 1406 (w), 1357 (w), 1267 (m), 1226 (m), 1192 (m), 1157 (s), 1090 (s), 1022 (s), 996 (m), 974 (m), 908 (w), 871 (m), 819 (m), 788 (m), 763 (m), 678 (m) cm 1. ESI-MS: m/z = [M H], [M NH 4 ], [2M NH 4 ]. HRMS: m/z calcd for [M Na] : ; found Preparation of ketone 25 A solution of diol 23 (36.0 mg, 91.7 mol) and imidazole (50.0 mg, 734 mol) in CH 2 Cl 2 (4.5 ml) was heated to 40 C. Triethylchlorosilane (92.4 L, 550 mol) was added dropwise, and stirring was continued for 2 h at C. Then the mixture was cooled to 0 C, saturated aqueous NaHCO 3 (2 ml) was added, and the layers were separated. The aqueous layer was extracted with CH 2 Cl 2 (4 3 ml), and the combined organic layers were dried over MgSO 4 and concentrated under vacuum. Flash chromatography over silica gel (pentane/et 2 O, 4:6) S13

14 afforded a mixture of 24 and the regioisomeric C1 OTES ether (43.0 mg, 24:regioisomer = 85:15 according to 1 H NMR integration) as a white foam with R f = 0.35 (pentane/et 2 O, 4:6). The mixture of regioisomeric silyl ethers (43.0 mg) described above was dissolved in CH 2 Cl 2 (3 ml) and treated with molecular sieves 4 Å (110 mg). In a second flask, MgSO 4 (57.7 mg) was added to a solution of NMO monohydrate (91.7 mg, 679 mol) in CH 2 Cl 2 (6.8 ml), and the mixture was stirred for 30 min at room temperature. Subsequently, this NMO solution was transferred to the first flask by syringe through a cotton plug. The resultant mixture was stirred for 10 min, treated with TPAP (3.0 mg, 8.5 mol), and stirring was continued for 5.5 h at room temperature. Then the mixture was filtered through silica gel (elution with CH 2 Cl 2 /Et 2 O, 4:1), and concentrated under vacuum. Flash chromatography over silica gel (pentane/et 2 O, 6:4) afforded ketone 25 (33.4 mg, 72%) and the regioisomeric ketone SI-3 (6.8 mg, 15%) as white solids. 25: R f = 0.28 (pentane/et 2 O, 6:4). M.p. = C. 1 H NMR (600 MHz, CDCl 3 ): = (m, 6 H, SiCH 2 CH 3 ), 0.92 (t, J = 7.90 Hz, 9 H, SiCH 2 CH 3 ), 1.06 (s, 3 H, H-19), 1.43 (s, 3 H, H-20), 1.54 (dd, J = 13.2, 11.7 Hz, 1 H, H-11 ), (m, 2 H, H-6, H- 7 ), (m, 1 H, H-6 ), 1.92 (dt, J = 14.7, 3.0 Hz, 1 H, H-3 ), (m, 2 H, H- 7, H-8), (m, 1 H, H-3 ), 2.50 (dd, J = 13.2, 5.3 Hz, 1 H, H-11 ), 2.83 (s, 1 H, H- 10), 3.02 (dd, J = 13.2, 3.0 Hz, 1 H, H-4), 3.69 (s, 3 H, OCH 3 ), 3.93 (t, J = 2.5 Hz, 1 H, H-2), 5.53 (dd, J = 11.7, 5.3 Hz, 1 H, H-12), 6.35 (d, J = 1.1 Hz, 1 H, H-14), 7.37 (s, 1 H, H-16), 7.39 (t, J = 1.5 Hz, 1 H, H-15) ppm. 13 C NMR (151 MHz, CDCl 3 ): = 4.61 (t, SiCH 2 CH 3 ), 6.67 (q, SiCH 2 CH 3 ), (q, C-20), (q, C-19), (t, C-7), (t, C-3), (s, C-9), (t, C-6), (s, C-5), (t, C-11), (d, C-4), (d, OCH 3 ), (d, C-8), (d, C-10), (d, C-12), (d, C-2), (d, C-14), (s, C-13), (d, C-16), (d, C-15), (s, C-17), (s, C-18), (s, C-1) ppm. IR (ATR): = 3125 (w), 2953 (w), 2926 (m), 2884 (w), 1728 (s), 1712 (m), 1685 (w), 1652 (w), 1397 (w), 1374 (w), 1347 (w), 1282 (w), 1220 (w), 1192 (w), 1165 (m), 1149 (s), 1074 (s), 1057 (m), 1007 (s), 973 (w), 937 (m), 912 (w), 873 (w), 829 (m), 810 (m), 762 (m), 736 (s), 672 (m) cm 1. ESI-MS: m/z = [M H], [M NH 4 ]. HRMS: m/z calcd for [M H] : ; found SI-3: R f = 0.14 (pentane/et 2 O, 6:4). M.p. = C C. 1 H NMR (600 MHz, CDCl 3 ): = (m, 6 H, SiCH 2 CH 3 ), 0.94 (t, J = 7.9 Hz, 9 H, SiCH 2 CH 3 ), 1.28 (s, 3 H, H-20), S14

15 1.32 (s, 3 H, H-19), 1.39 (td, J = 13.6, 3.2 Hz, 1 H, H-6 ), 1.51 (d, J = 12.0 Hz, 1 H, H-10), (m, 3 H, H-6, H-7, H-11 ), 2.10 (dddd, J = 14.3, 3.5, 3.5, 3.5 Hz, 1 H, H-7 ), 2.20 (dd, J = 12.2, 3.3 Hz, 1 H, H-8), 2.48 (dd, J = 13.9, 4.5 Hz, 1 H, H-4), 2.53 (dd, J = 14.9, 4.5 Hz, 1 H, H-3 ), 2.88 (dd, J = 15.1, 13.9 Hz, 1 H, H-3 ), 3.32 (dd, J = 14.3, 5.6 Hz, 1 H, H-11 ), 3.69 (s, 3 H, OCH 3 ), 4.61 (d, J = 12.0 Hz, 1 H, H-1), 5.41 (dd, J = 11.3, 5.6 Hz, 1 H, H-12), 6.37 (d, J = 1.1 Hz, 1 H, H-14), 7.38 (br s, 1 H, H-16), 7.40 (t, J = 1.7 Hz, 1 H, H-15) ppm. 13 C NMR (151 MHz, CDCl 3 ): = 5.40 (t, SiCH 2 CH 3 ), 7.08 (q, SiCH 2 CH 3 ), (q, C- 20), (q, C-19), (t, C-7), (s, C-9), (s, C-5), (d, C-6), (t, C- 3), (t, C-11), (q, OCH 3 ), (d, C-8), (d, C-4), (d, C-10), (d, C-12), (d, C-1), (d, C-14), (s, C-13), (d, C-16), (d, C-15), (s, C-18), (s, C-17), (s, C-2) ppm. IR (ATR): = 3145 (w), 2951 (m), 2923 (w), 2875 (w), 1722 (s), 1684 (w), 1651 (w), 1459 (w), 1432 (w), 1400 (w), 1370 (w), 1271 (m), 1216 (m), 1147 (s), 1104 (m), 1072 (w), 1017 (m), 991 (m), 907 (w), 872 (m), 800 (m), 727 (s) cm 1. ESI-MS: m/z = [M H], [M NH 4 ]. Anal. calcd for C 27 H 40 O 7 Si: C, 64.26; H, 7.99; found: C, 64.25; H, Preparation of 2-epi-salvinorin B (26) To a solution of ketone 25 (33.4 mg, 66.2 mol) in THF (3.3 ml) cooled to 0 C was added a mixture of TBAF and HOAc (133 L, 106 mol) prepared from TBAF (250 L, 1 M in THF) and HOAc (60 L), and stirring was continued for 1 h at room temperature. After addition of saturated aqueous NH 4 Cl (1 ml), the mixture was extracted with CH 2 Cl 2 (5 2 ml), and the combined organic layers were dried over MgSO 4 and concentrated under vacuum. Flash chromatography over silica gel (CH 2 Cl 2 /Et 2 O, 8:2 and 1:1) gave -hydroxy ketone 26 (25.6 mg, 99%) as a white solid. 26: R f = 0.58 (CH 2 Cl 2 /Et 2 O, 1:1). M.p. = C. 1 H NMR (600 MHz, CDCl 3 ): = (m, 3 H, H-19), 1.43 (s, 3 H, H-20), (m, 3 H, H-6, H-7, H-11 ), (m, 1 H, H-6 ), 2.06 (dt, J = 14.8, 3.0 Hz, 1 H, H-3 ), (m, 2 H, H-7, H-8), S15

16 (m, 2 H, H-3, OH), 2.51 (dd, J = 13.6, 5.3 Hz, 1 H, H-11 ), 2.84 (s, 1 H, H-10), 3.05 (dd, J = 13.4, 3.6 Hz, 1 H, H-4), 3.70 (s, 3 H, H-OCH 3 ), 4.03 (q, J = 3.0 Hz, 1 H, H-2), 5.54 (dd, J = 11.7, 5.3 Hz, 1 H, H-12), (m, 1 H, H-14), 7.40 (t, J = 1.7 Hz, 1 H, H- 15), 7.41 (s, 1 H, H-16) ppm. 13 C NMR (151 MHz, CDCl 3 ): = (q, C-20), (q, C- 19), (t, C-7), (t, C-3), (s, C-9), (t, C-6), (s, C-5), (t, C- 11), (d, C-4), (q, OCH 3 ), (d, C-8), (d, C-10), (d, C-12), (d, C-2), (d, C-14), (s, C-13), (d, C-16), (d, C-15), (s, C- 17), (s, C-18), (s, C-1) ppm. IR (ATR): = 3504 (m), 3135 (w), 3101 (w), 2922 (m), 2853 (w), 1732 (m), 1708 (s), 1653 (w), 1635 (w), 1456 (m), 1445 (m), 1419 (w), 1396 (w), 1375 (m), 1346 (w), 1284 (m), 1224 (m), 1169 (m), 1148 (s), 1105 (m), 1066 (m), 1050 (m), 1020 (s), 1003 (s), 973 (m), 926 (m), 908 (m), 871 (m), 820 (m),790 (m), 758 (s), 734 (m), 675 (m), 636 (m) cm 1. ESI-MS: m/z = [M H], [M NH 4 ]. Table S1. Comparison of 13 C NMR Data [ppm] for 26 with Literature 2 Data. This Work a Ref 2 b This Work a Ref 2 b This Work a Ref 2 b a 151 MHz, CDCl 3. b 125 MHz, CDCl Preparation of salvinorin A (1) and 2-epi-1 A solution of -hydroxy ketone 26 (10.0 mg, 25.6 mol), triphenylphosphine (20.1 mg, 76.8 mol), and HOAc (9.2 mg, 154 mol) in THF (1.5 ml) was treated with di-tert-butyl azodicarboxylate (17.7 mg, 76.8 mol). After stirring the mixture at 60 C for 24 h, it was S16

17 cooled to room temperature and filtered through silica gel (elution with CH 2 Cl 2 /Et 2 O, 9:1). Concentration under vacuum and flash chromatography over silica gel (pentane/et 2 O, 3:7) yielded 2-epi-salvinorin A (2-epi-1) (2.0 mg, 18%) and salvinorin A (1) (9.0 mg, 81%) as white solids. 2-epi-1: R f = 0.23 (pentane/et 2 O, 3:7). M.p. = C. 1 H NMR (600 MHz, CDCl 3 ): = 1.09 (s, 3 H, H-19), 1.44 (dd, J =13.6, 11.8 Hz, 1 H, H-11 ), 1.46 (s, 3 H, H-20), (m, 2 H, H-6, H-7 ), (m, 1 H, H-6 ), 2.10 (dd, J = 11.3, 3.0 Hz, 1 H, H-8), 2.13 (s, 3 H, CH 3 C=O), (m, 2 H, H-3, H-7 ), 2.33 (ddd, J = 15.6, 13.4, 3.2 Hz, 1 H, H-3 ), 2.45 (dd, J = 13.6, 5.2 Hz, 1 H, H-11 ), 2.53 (s, 1 H, H-10), 2.89 (dd, J = 13.3, 3.5 Hz, 1 H, H-4), 3.71 (s, 3 H, OCH 3 ), 4.85 (t, J = 2.9 Hz, 1 H, H-2), 5.54 (dd, J = 11.8, 5.2 Hz, 1 H, H-12), 6.37 (t, J = 1.2 Hz, 1 H, H-14), 7.40 (m, 2 H, H-15, H-16) ppm. 13 C NMR (151 MHz, CDCl 3 ): = (q, C-20), (q, C-19), (t, C-7), (q, CH 3 CO), (d, C-3), (s, C-9), (t, C-6), (s, C-5), (t, C-11), (d, C-4), (d, C-8), (q, OCH 3 ), (d, C-10), (d, C-12), (d, C-2), (d, C-14), (s, C-13), (d), (d), (s, COCH 3 ), (s, C-17), (s, C- 18), (s, C-1) ppm. IR (ATR): = 3131 (w), 2995 (w), 2949 (w), 2922 (w), 2854 (w), 1724 (s), 1652 (w), 1510 (w), 1459 (w), 1434 (w), 1375 (m), 1280 (m), 1220 (s), 1165 (m), 1146 (s), 1105 (w), 1069 (m), 1022 (s), 976 (w), 933 (m), 872 (m), 825 (m), 781 (m), 736 (m), 679 (w) cm 1. ESI-MS: m/z = [M NH 4 ], [2M NH 4 ]. Table S2. Comparison of 13 C NMR Data [ppm] for 2-epi-1 with Literature 3 Data. This Work a Ref 3 b This Work a Ref 3 b This Work a Ref 3 b a 151 MHz, CDCl 3. b 75 MHz or 151 MHz, CDCl 3. S17

18 1: R f = 0.14 (pentane/et 2 O, 3:7). M.p. = C (from C: conversion of powder to needles). 1 H NMR (500 MHz, CDCl 3 ): = 1.11 (s, 3 H), 1.45 (s, 3 H), (m, 3 H), (m, 1 H), 2.07 (dd, J = 11.7, 2.8 Hz, 1 H), (m, 2 H), 2.16 (s, 3 H), (m, 2 H), 2.50 (dd, J = 13.4, 5.2 Hz, 1 H), (m, 1 H), 3.72 (s, 3 H), (m, 1 H), 5.52 (dd, J = 11.8, 5.2 Hz, 1 H), (m, 1 H), 7.39 (t, J = 1.0 Hz, 1 H), 7.40 (s, 1 H) ppm. 13 C NMR (126 MHz, CDCl 3 ): = (q), (q), (t), (q), (t), (s), (t), (s), (t), (d), (q), (d), (d), (d), (d), (d), (s), (d), (d), (s), (s), (s), (s) ppm. IR (ATR): = 3126 (w), 2992 (w), 2957 (w), 2927 (w), 2852 (w), 1723 (s), 1685 (w), 1651 (w), 1447 (w), 1397 (w), 1374 (m), 1275 (w), 1234 (m), 1199 (m), 1159 (s), 1108 (w), 1073 (w), 1045 (m), 1020 (m), 997 (m), 949 (w), 891 (w), 872 (m), 826 (w), 780 (m), 742 (m) cm 1. ESI-MS: m/z = [M H], [M NH 4 ]. Table S3. Comparison of 13 C NMR Data [ppm] for 1 with Literature 4,5 Data. This Work a Ref 4 b Ref 5 c This Work a Ref 4 b Ref 5 c a 126 MHz, CDCl 3. b 51 MHz, CDCl 3. c 91 MHz, CDCl References (1) Wang, Y.; Rogachev, V.; Wolter, M.; Gruner, M.; Jäger, A.; Metz, P. Eur. J. Org. Chem. 2014, (2) Nozawa, M.; Suka, Y.; Hoshi, T.; Suzuki, T.; Hagiwara, H. Org. Lett. 2008, 10, S18

19 (3) Harding, W. W.; Schmidt, M.; Tidgewell, K.; Kannan, P.; Holden, K. G.; Gilmour, B.; Navarro, H.; Rothman, R. B.; Prisinzano, T. E. J. Nat. Prod. 2006, 69, (4) Ortega, A.; Blount, J. F.; Manchand, P. S. J. Chem. Soc. Perkin Trans 1, 1982, (5) Valdes III, L. J.; Butler, W. M.; Hatfield, G. M.; Paul, A. G.; Koreeda, M. J. Org. Chem. 1984, 49, S19

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