Single and Double Stereoselective Fluorination of (E)-Allylsilanes Marcin Sawicki, Angela Kwok, Matthew Tredwell, Véronique Gouverneur* University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, UK, OX1 3TA. Additional Material General Information 1 H NMR spectra were recorded in deuterated solvents by using Bruker AV400 or AV500 spectrometers, calibrated using residual protonated solvent as an internal reference. 13C NMR spectra were recorded in deutrated solvent by using Bruker AV400 or AV500 spectrometers. 19 F NMR spectra were recorded on a Bruker AV400 spectrometer. Chemical shifts () are reported in parts per million (ppm) and coupling constants (J) are measured in hertz (Hz). The following abbreviations are used to describe multiplicities s = singlet, d = doublet, t = triplet, q = quartet, br = broad, m = multiplet. NMR were processed in either MestRe-C or ACD/SpecManager. IR spectra were recorded on a Bruker Tensor 27 FTIR spectrometer. Absorption bands are measured in wavenumbers (cm-1) and only peaks on interest are reported. Mass spectra (m/z) and HRMS were recorded on a Micromass LCT in ElectronSpray Ionisation (ESI), Field Ionization (FI) mode or on a Micromass AutoSpec (CI+). All reactions requiring anhydrous conditions were conducted in dried apparatus under an inert atmosphere of argon or nitrogen. Solvents were dried and purified before use, according to standard procedures. Thin layer chromatography (TLC) was performed using Merck Kieselgel 60F254 and visualized with a UV lamp or by staining with S1 KMnO4. Column chromatography was carried out over Merck silica gel C60 (40-60 µm) and eluents as indicated. Compounds 1a, 1e and 1h were synthesized according to reported procedures.1 (E)-3-(Trimethylsilyl)hex-4-en-1-ol (1b). OH SiMe3 A solution of (E)-3-(trimethylsilyl)hex-4-enoate (897mg, 4.2mmol) in Et2O (21ml) was added dropwise to a slurry of LiAlH4 (800mg, 21mmol) in Et2O (21ml) and allowed to stir at room temperature for 4hrs. The reaction was quenched by the addition of a saturated solution of NH4Cl at 0°C. The aqueous phase was extracted with Et2O. The combined organic phases were dried over MgSO4 and the solvent removed in vacuo. Purification by silica gel chromatography (pentane: Et2O, 80:20; Rf = 0.19) afforded (E)-3-(trimethylsilyl)hex-4-en-1-ol (1b) (791mg, 84% yield). 1H NMR (400 MHz, C6D6): δ -0.46 (s, 9H), 0.77 (br, 1H), 1.31-1.41 (m, 1H), 1.44-1.52 (m, 1H), 1.52-1.58 (m, 1H), 1.56 (d, J=5.7 Hz, 3H), 3.43 (ddd, J=10.4 Hz, 7.6 Hz, 6.4 Hz, 1H), 3.53 (ddd, J=10.4 Hz, 7.1 Hz, 4.6 Hz, 1H), 5.28 (dd, J=15.1 Hz, 7.4 Hz, 1H), 5.30 (dq, J=15.1 Hz, 5.7 Hz 1H); 13C NMR (100 MHz, C6D6) δ -3.2 (3 x CH3), 18.2 (CH3), 29.7 (CH2), 32.2 (CH), 62.5 (CH2), 123.2 (CH), 132.3 (CH); IR (neat): 3333, 2956, 1248, 1034, 968, 837; MS: HRMS: calculated for C9H20NaOSi: m/z 195.1181, found: m/z 195.1186. (E)-2,2-Dimethyl-3-(trimethylsilyl)hex-4-enoate (1c). O Me3 Si O To a solution of diisopropylamine (1.57ml, 11.8mmol, 1.3 eq) in THF (9ml) at 0°C was added n-BuLi (2.5M, 4.4ml, 11.0mmol, 1.2eq) and allowed to stir for 30 min. S2 The solution was cooled to -78°C and a solution of ethyl-(E)-2-methyl-3trimethylsilylhex-4-enoate (2.052g, 9.0mmol) in THF (4.5ml) was added via a syringe. The temperature was gradually raised to -40°C over a period of 2hrs. After which time iodomethane (0.735ml, 11.8mmol, 1.3 eq) was added and the reaction mixture was allowed to warm to room temperature overnight. The reaction was quenched with saturated NH4Cl at 0°C. The aqueous phase was extracted with Et2O, the combined organic extracts were washed with saturated brine and dried over MgSO4, filtered and the solvent removed in vacuo to afford crude ethyl (E)-2-methyl3-(trimethylsilyl)hex-4-enoate (1c) as a yellow oil. Purification by silica gel chromatography (40°-60° petroleum ether: Et2O, 9:1, Rf = 0.40) afforded (1c) 1.560g, 71% yield. 1H NMR (400 MHz, CDCl3): δ -0.23 (s, 9H), 1.13 (s, 3H), 1.19 (s, 3H), 1.24 (t, J=7.1 Hz, 3H), 1.67 (d, J=4.9 Hz, 3H), 1.94 (d, J=10.2 Hz, 1H), 4.04 (dq, J=10.5 Hz, 7.1 Hz, 1H), 4.10 (dq, J=10.5 Hz, 7.1 Hz, 1H), 5.28 (dd, J=14.9 Hz, J=9.8 Hz, 1H), 5.30 (dq, J=14.9 Hz, 4.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ -0.9 (3 x CH3), 14.2 (CH3), 18.1 (CH3), 23.8 (CH3), 26.4 (CH3), 42.3 (CH), 44.2 (C), 60.2 (CH2), 126.1 (CH), 128.3 (CH), 178.3 (C); IR (neat): 2966, 1729, 1248, 1147, 971, 839; HRMS: calculated for C13H26O2Si: m/z 242.1702, found: m/z 242.1709. (E)-2,2-Dimethyl-3-(trimethylsilyl)hex-4-en-1-ol (1d). OH SiMe 3 A solution of ethyl-(E)-2,2-dimethyl-3-(trimethylsilyl)hex-4-enoate (1c) (1.150g, 4.5mmol) in Et2O (22.5ml) was added to a slurry of LiAlH4 (860mg, 22.5mmol) in Et2O (22.5ml) dropwise, the reaction was allowed to stir at room temperature for 4hrs. The reaction was quenched by the addition of a saturated solution of NH4Cl at 0°C. The aqueous phase was extracted with Et2O, the combined organic extracts were S3 washed with saturated brine and dried over MgSO4, filtered and the solvent removed in vacuo. Purification by silica gel chromatography (hexane: Et2O, 80:20; Rf = 0.35) afforded (1d) 772mg, 80% yield. 1H NMR (400 MHz, C6D6): δ 0.06 (s, 9H), 0.86 (s, 3H), 0.96 (s, 3H), 1.20 (br, 1H), 1.56 (d, J=11.8 Hz, 1H), 1.57 (dd, J=6.2 Hz, 1.4 Hz, 3H), 3.12 (d, J=10.6 Hz, 1H), 3.26 (d, J=10.6 Hz, 1H), 5.15 (dq, J=14.9 Hz, 6.2 Hz, 1H), 5.45 (ddq, J=14.9 Hz, 11.8 Hz, 1.4 Hz, 1H; H4); 13C NMR (100 MHz, C6D6): δ 0.4 (3 x CH3), 18.1 (CH3), 23.7 (CH3), 25.7 (CH3), 38.2 (C), 41.9 (CH), 72.2 (CH2), 125.0 (CH), 130.4 (CH); IR (neat): 3385, 1248, 1038, 973, 836. HRMS: calculated for C11H24OSi: m/z 223.1489, found: m/z 223.1493. anti-(E)-Ethyl-2-methyl-3-(trimethylsilyl)hex-4-enoate (1f). O Me3 Si O To a solution of diisopropylamine (1.10ml, 7.8mmol, 1.3 eq) in THF (5.0ml) at 0°C was added n-BuLi (2.5M, 2.9ml, 7.2mmol, 1.2eq.), the reaction was allowed to stir for 30 min. The solution was cooled to -78°C and a solution of ethyl-(E)-3trimethylsilylhex-4-enoate (1.28g, 6.0mmol) in THF (5ml) was added via a syringe. The light yellow solution was stirred for 30 min, followed by the dropwise addition of a solution of benzyl bromide (0.890ml, 7.5mmol, 1.2 eq) in THF (1 mL). The reaction mixture was allowed to stir and warm to room temperature overnight. The reaction was quenched by the addition of a saturated solution of NH4Cl at 0°C. The aqueous phase was extracted with Et2O. The combined organic phases were washed with saturated brine, dried over MgSO4, filtered and the solvent removed in vacuo. Purification by silica gel chromatography (hexane: Et2O, 9:1; Rf = 0.50) afforded (1f) as a colourless oil 1.480g, 81% yield, d.r >20:1. 1H NMR (400 MHz, acetone-d6) δ - S4 0.03 (s, 9H), 1.01 (t, J=7.1 Hz, 3H), 1.72 (d, J=4.8 Hz, 3H), 1.89-1.95 (m, 1H), 2.70 (t, J=11.6 Hz, 1H), 2.76 (ddd, J=11.6 Hz, 8.8 Hz, 3.0 Hz, 1H), 2.99 (dd, J=12.4 Hz, J=2.3 Hz, 1H), 3.90 (qd, J=7.1 Hz, 1.8 Hz, 1H), 5.36-5.48 (m, 3H), 7.14-7.19 (m, 2H), 7.22-7.28 (m, 2H); 13C NMR (100 MHz, acetone-d6) δ -2.5 (3 x CH3), 13.9 (CH3), 17.8 (CH3), 37.0 (CH), 38.9 (CH2), 48.9 (CH), 59.8 (CH2), 125.4 (CH),126.4 (CH), 128.5 (2 x CH), 129.3 (2 x CH), 130.0 (CH), 140.5 (C), 174.6 (C); IR (neat): 2957, 1732, 1453, 1249, 1153, 839, 699; HRMS: calculated for C18H29O2Si: m/z 305.1931, found: m/z 305.1921. (E)-2-Methyl-3-(trimethylsilyl)hex-4-en-1-ol (1g). OH SiMe3 A solution of anti-ethyl-(E)-2-methyl-3-(trimethylsilyl)hex-4-enoate (1.030g, 4.5mmol) in Et2O (22.5ml) was added dropwise to a slurry of LiAlH4 (860mg, 22.5mmol) in Et2O (22.5ml) and allowed to stir at room temperature for 4hrs. The reaction was quenched by the addition of a saturated solution of NH4Cl at 0°C. The aqueous phase was extracted with Et2O. The combined organic phases were dried over MgSO4, filtered and the solvent removed in vacuo. Purification by silica gel chromatography (hexane: EtOAc, 80:20; Rf = 0.34) gave (1g) 757mg, 90% yield, dr >20:1. 1H NMR (400 MHz, CDCl3): δ –0.35 (s, 9H), 0.89 (d, J=7.0 Hz, 3H) 1.50 (br, 1H), 1.64 (d, J=4.8 Hz, 3H), 1.69 (dd, J=9.9 Hz, 3.4 Hz, 1H), 1.84 (qtd, J=7.0 Hz, 7.0 Hz, 3.4 Hz, 1H), 3.37 (dd, J=10.6 Hz, 7.0 Hz, 1H), 3.41 (dd, J=10.6 Hz, 7.0 Hz, 1H), 5.22-5.38 (m, 2H); 13C NMR (100 MHz, CDCl3): δ -2.1 (3 x CH3), 13.9 (CH3), 18.2 (CH3), 35.0 (CH), 35.5 (CH), 68.3 (CH2), 125.0 (CH), 127.9 (CH); IR (neat): 3334, 2958, 1248, 1033, 971, 836. HRMS: calculated for C10H22NaOSi: m/z 209.1332, found: m/z 209.1338. S5 (E)-2-Methyl-3-(trimethylsilyl)hex-4-en-1-ol (1i). OH SiMe3 A solution of syn-ethyl-(E)-2-methyl-3-(trimethylsilyl)hex-4-enoate (41 mg, 0.2 mmol) in Et2O (1.0 ml) was added dropwise to a slurry of LiAlH4 (35 mg, 1.0 mmol) in Et2O (1.0 ml) and allowed to stir at room temperature for 4hrs. The reaction was quenched by the addition of a saturated solution of NH4Cl at 0°C. The aqueous phase was extracted with Et2O. The combined organic phases were dried over MgSO4, filtered and the solvent removed in vacuo. Purification by silica gel chromatography (hexane: Et2O, 1:1; Rf = 0.4) afforded (1i) 31 mg, 84% yield, d.r = 9:1. 1H NMR (400 MHz, acetone-d6): δ 0.02 (s, 9H), 0.98 (d, J=6.6 Hz, 3H), 1.48 (dd, J=9.9 Hz, 6.6 Hz, 1H), 1.65 (d, J= 4.8 Hz, 3H), 1.77-1.87 (m, 1H), 3.26 (ddd, J=10.4 Hz, 7.8 Hz,5.6 Hz, 1H), 3.42 (t, J=5.3 Hz, 1H), 3.61 (dt, 10.4 Hz, 4.8 Hz, 1H), 5.26 (dq, J=15.2 Hz, 5.6 Hz, 1H), 5.33 (dd, J=15.2 Hz, 5.6 Hz, 1H); 13C NMR (100 MHz, acetone-d6): δ 2.1 (3 x CH3), 13.9 (CH3), 18.2 (CH3), 35.0 (CH), 35.5 (CH), 68.3 (CH2), 125.0 (CH), 127.9 (CH); IR (neat): 3333, 2957, 1453, 1248, 1030, 97, 835. HRMS: calculated for C10H22NaOSi: m/z 209.1332, found: m/z 209.1336. General Procedure A for the electrophilic fluorodesilylation of esters. To a solution of substrate in acetonitrile (0.1 M) was added Selectfluor™ (1.5 eq.) and NaHCO3 (1eq.). The reaction mixture was allowed to stir at room temperature for 12hrs. The reaction was diluted with Et2O, filtered and the organic phase was washed with water. The organic phase was dried over MgSO4, filtered and the solvent removed in vacuo. (Caution: The corresponding allylic fluoride products are volatile, unstable on silica, alumina (basic and neutral) and decompose upon heating). S6 Ethyl 5-fluorohex-3-enoate (2a). O F O General procedure A. 515mg, 81 % yield, E/Z = 1.3:1. The trans isomer: 1H NMR (400 MHz, C6D6): δ 0.92 (t, J=7.1Hz, 3H), 1.11 (ddd, J=23.1 Hz, 6.4 Hz, 2.2 Hz, 3H), 2.76 (m,1H), 3.88 (q, J=7.1 Hz, 2H), 4.74 (dqd, J=48.2 Hz, J=6.4 Hz, J=6.4 Hz, 1H), 5.32-5.42 (m, 1H), 5.75 (dtd, J=15.6 Hz, 7.2 Hz, 4.1Hz, 1H); 13C NMR (100 MHz, C6D6): δ 14.1 (CH3), 21.1 (d, J=24.4 Hz; CH3), 30.1 (CH2), 60.5 (CH2), 89.2 (d, J=163.8 Hz; CH), 125.2 (d , J=11.7 Hz; CH), 133.6 (d , J=19.6Hz; CH), 170.4 (C); 19F NMR (376.5 MHz, C6D6) δ -166.6 (dqdd, J=48.2 Hz, 23.1Hz, 11.8Hz, 4.1Hz), HRMS: calculated for C8H13FNaO2 m/z 183,0792 found: m/z 183.0793. The cis isomer: 1H NMR (400 MHz, C6D6): δ 0.93 (t, J=7.1 Hz, 3H), 1.13 (ddd, J=23.2 Hz, 6.4 Hz, 2.5 Hz 3H), 2.84 (m,1H), 3.89 (q, J=7.1 Hz, 2H), 5.05 (dm, J=48.7 Hz, 1H), 5.42-5.52 (m, 1H), 5.60-5.70 (m, 1H); 13C NMR (100 MHz, C6D6): δ 14.1 (CH3), 21.4 (d, J=24.9 Hz; CH3), 33.1 (CH2), 60.5 (CH2), 85.4 (d, J=161.4 Hz; CH), 125.0 (d, J=9.9 Hz, CH), 132.6 (d, J=20.3 Hz; CH), 170.5 (C); 19F NMR (376.5 MHz, C6D6) δ -166.9 (dqdd, J=48.7 Hz, 23.2 Hz, 11.8 Hz, 2.5 Hz). Ethyl-(E)-5-fluoro-2,2-dimethylhex-3-enoate (2c). O F O General procedure A. 95% yield, E/Z > 20:1. The trans isomer (major): 1H NMR (400 MHz, C6D6): δ 0.89 (t, J=7.1 Hz, 3H), 1.13 (dd, J=23.0 Hz, 6.3 Hz, 3H), 1.23 (s, 6H), 3.89 (q, J=7.1 Hz, 2H), 4.79 (dqd, J=48.3 Hz, 6.3 Hz, 6.3 Hz, 1H), 5.54 (ddd, J=15.9 Hz, 11.8 Hz, 6.3 Hz, 1H); 5.97 (dd., J=15.9 Hz, 3.8 Hz, 1H); 13C NMR (100 MHz, C6D6): δ 14.0 (CH3), 21.6 (CH3), 21.9 (CH3), 25.2 (d, J=21.7 Hz; CH3), 44.2 S7 (C), 60.9 (CH2), 89.8 (d, J=164.1 Hz; CH), 128.9 (d, J=19.7 Hz; CH), 137.6 (d , J=11.1 Hz; CH), 175.5 (C). 19F NMR (376.5 MHz, C6D6): δ -166.4 (dqdd J=48.3 Hz, 23.0Hz, 11.8 Hz, 3.8 Hz); IR (neat): 2983, 1732,1471, 1386, 1250, 1145, 1050, 972, 860HRMS: calculated for C10H17FNaO2 m/z 211.1105, found: m/z 211.1105 syn-Ethyl 5-fluoro-2-methyl-hex-3-enoate (2e). O F O General procedure A. 310mg, 95% yield, syn/anti = 19:1, E/Z (syn) 15:1, E/Z (anti) >20:1. The trans-syn: 1H NMR (400 MHz, C6D6): δ 0.90 (t, J=7.1 Hz, 3H), 1.09 (dd, J=23.3 Hz, 6.3 Hz, 3H), 1.12 (d, J=6.8 Hz, 3H), 2.93 (dq, J=7.2 Hz, 6.8 Hz, 1H), 3.89 (q, J=7.1 Hz, 2H), 4.73 (dqd, J=47.8 Hz, 6.3 Hz, 6.3Hz, 1H), 5.46 (ddd., J=15.6 Hz, 11.7 Hz, 6.3 Hz, 1H); 5.80 (ddd, J=15.6 Hz, 7.2 Hz, 3.9 Hz 1H); 13C NMR (100 MHz, C6D6): δ 14.1 (CH3), 17,1 (CH3), 21.4 (d, J=24.4 Hz; CH3), 42.6 (CH), 60.5 (CH2), 89.3 (d, J=164.8 Hz; CH), 131.6 (d , J=19.7 Hz; CH), 132.0 (d , J=11.3 Hz; CH), 173.5 (C). 19F NMR (376.5 MHz, C6D6): δ -166.6 (dqddd, J=47.8 Hz, 23.3Hz, 11.7 Hz, 3.9 Hz, 2.4 Hz); IR (neat): 2983, 1737,1457, 1376, 1325, 1260, 1046, 971, 805HRMS: calculated for C9H15FNaO2 m/z 197.0948, found: m/z 197.0946. syn-(E)-Ethyl-2-benzyl-5-fluorohex-3-enoate (2f). O F O General procedure A. 112.0mg, 90% yield, syn/anti >20:1, E/Z (syn) 11:1, E/Z (anti) >20:1. The trans-syn isomer: 1H NMR (400 MHz, C6D6): δ 0.93 (t, J=7.1 Hz, 3H), 1.15 (dd, J=23.2 Hz, 6.6 Hz, 3H), 2.83 (dd, J=13.4 Hz, 6.6 Hz, 1H), 3.16 (dd, J=13.4 Hz, 6.6 Hz, 1H), 3.37 (dd, J=8.1 Hz, 6.6 Hz, 1H), 3.96 (q, J=7.1 Hz, 2H), 4.80 (dqd, S8 J=48.3 Hz, 6.3 Hz, 6.3 Hz, 1H), 5.53 (ddd., J=15.7 Hz, 12.6 Hz, 6.8 Hz, 1H); 5.80 (ddd, J=15.7 Hz, 8.6 Hz, 3.5 Hz 1H); 13C NMR (100 MHz, C6D6): δ 14.0 (CH3), 21.2 (d, J=24.0 Hz; CH3), 39.0 (CH2), 50.9 (CH), 60.5 (CH2), 88.5 (d, J=166.2 Hz; CH), 126.7 (CH), 128.5 (2 x CH), 129.4 (2 x CH), 129.8 (d , J=11.2 Hz; CH), 132.0 (d , J=19.2 Hz; CH), 172.6 (C). 19F NMR (376.5 MHz, C6D6): δ -166.6 (dqdd, J=48.3 Hz, 23.2 Hz, 12.6 Hz, 3.5 Hz); IR (neat): 2982, 1733, 1454, 1260, 1158, 1033, 799, 700HRMS: calculated for C15H19FNaO2 m/z 273.1261, found: m/z 273.1262. anti-(E)-Ethyl 5-fluoro-2-methyl-hex-3-enoate (2h). O F O General procedure A. 33mg, 96% yield, syn/anti 1:6, E/Z (syn) >20:1, E/Z (anti) 11:1. The trans-anti isomer: 1H NMR (400 MHz, C6D6): δ 1.02 (t, J=7.3 Hz, 3H), 1.20 (dd, J=23.2 Hz, 6.3 Hz, 3H), 1.23 (d, J=7.1 Hz, 3H), 3.06 (qd, J=7.1 Hz, 2.8 Hz, 1H), 4.01 (q, J=7.1 Hz, 2H), 4.85 (dqd, J=48.3 Hz, 6.3 Hz, 6.3Hz, 1H), 5.58 (dddd, J=15.6 Hz, 11.2 Hz, 6.1, 1.0 Hz, 1H); 5.93 (dddd, J=15.7 Hz, 7.6 Hz, 3.8 Hz, 1.0 Hz, 1H); 13C NMR (100 MHz, C6D6): δ 14.1 (CH3), 17,0 (CH3), 21.3 (d, J=24.8 Hz; CH3), 42.5 (CH), 60.5 (CH2), 89.2 (d, J=164.6 Hz; CH), 131.5 (d , J=20.0 Hz; CH), 131.8 (d , J=11.2 Hz; CH), 173.5 (C). 19F NMR (376.5 MHz, C6D6): δ -166.6 (dqddd, J=48.1 Hz, 23.1 Hz, 12.0 Hz, 3.8 Hz, 2.7 Hz); IR (neat): 2982, 2360, 1736, 1456, 1376, 1259, 1181, 1046, 970, 853, 738HRMS: calculated for C9H15FNaO2 m/z 197.0948, found: m/z 197.0954. General Procedure B for electrophilic fluorodesilylation of alcohols. To a solution of substrate in acetonitrile (0.1 M) was added Selectfluor™ (1.5 eq.) and NaHCO3 (1eq.). The reaction was allowed to stir for 4hrs at room temperature. The reaction was diluted with Et2O, filtered and the organic phase was washed with S9 water. The organic phase was dried over MgSO4, filtered and the solvent removed in vacuo. The crude products were purified by rapid silica gel chromatography. (Caution: The corresponding allylic fluoride products are volatile, unstable on silica, alumina (basic and neutral) on prolonged exposure and decompose upon heating). (E)-5-Fluorohex-3-en-1-ol (2b). OH F General procedure B. 86mg, 64% yield, E/Z = 3:1. The trans isomer: 1H NMR (400 MHz, C6D6): δ 1.27 (dd, J=23.0 Hz, 6.3 Hz, 3H), 2.03 (br, 1H), 2.14 (td, J=6.5 Hz, 6.0Hz, 2H), 3.46 (t, J=6.5 Hz, 2H), 4.90 (dqd, J=48.6 Hz, 6.3 Hz, 6.3 Hz, 1H), 5.525.70 (m, 2H); 13C NMR (100 MHz, C6D6): δ 21.4 (d, J=24.7 Hz, CH3), 35.8 (CH2), 61.3 (CH2), 89.7 (d, J=163.2 Hz; CH), 130.0 (d , J=11.2 Hz; CH), 132.6 (d , J=19.2 Hz; CH); 19F NMR (376.5 MHz, C6D6): δ -164.6 (m). HRMS: calculated for C6H11FNaO m/z 141.0686, found: m/z 141.0684. The cis isomer: 1H NMR (400 MHz, C6D6): δ 1.29 (dd, J=23.0 Hz, 6.2 Hz, 3H), 2.03 (br, 1H), 2.14 (td, J=6.5 Hz, 6.0 Hz, 2H), 3.41 (t, J=6.5 Hz, 2H), 5.32 (dqd, J=48.8 Hz, 6.5 Hz, 6.5 Hz, 1H), 5.425.52 (m, 1H); 5.52-5.70 (m, 1H); 13C NMR (100 MHz, C6D6): δ 21.7 (d, J=25.2 Hz; CH3), 31.4 (CH2), 65.9 (CH2), 85.4 (d, J=159.9 Hz; CH), 130.1 (d , J=10.4 Hz; CH), 132.1 (d , J=20.4 Hz; CH): 19F NMR (376.5 MHz, C6D6): δ -166.5 (m). (E)-5-Fluoro-2,2-dimethylhex-3-enoate (2d). OH F General procedure B. Purification by silica gel chromatography (20-50% Et2O/hexane) 46mg, 70% yield, E/Z > 20:1. The trans- isomer: 1H NMR (400 MHz, C6D6): δ 0.87 (s, 3H), 0.88 (s, 3H), 1.18 (dd, J=23.0 Hz, 6.3 Hz, 3H), 1.94 (br, 1H), S10 3.13 (s, 2H), 4.83 (dqdd, J=48.4 Hz, 6.3 Hz, 6.3 Hz, 0.7 Hz, 1H), 5.47 (ddd, J=15.9 Hz, 10.6 Hz, 6.3 Hz, 1H), 5.61 (ddd, J=15.9 Hz, 3.9 Hz, 0.7 Hz, 1H); 13C NMR (100 MHz, C6D6): δ 21.3 (d, J=24.8 Hz; CH3), 23.3 (CH3), 23.4 (CH3), 37.8 (C), 71.0 (d, J=2.3 Hz, CH2), 90.3 (d, J=163.6 Hz; CH), 128.2 (d , J=19.4 Hz, CH), 140.0 (d , J=10.7 Hz, CH); 19F NMR (376.5 MHz, C6D6): δ -164.7 (dqdd, J=48.4 Hz, 23.0 Hz, 10.6 Hz, 3.9 Hz); IR (neat): 3386, 2963, 1379, 1048, 975, 856; HRMS: calculated for C8H15FNaO m/z 169.0999, found: m/z 169.1001. syn-(E)-5-Fluoro-2-methylhex-3-en-1-ol (2g). OH F General procedure B. Purification by silica gel chromatography (20-50% Et2O/hexane) 87mg, 66% yield, syn/anti >20:1, E/Z (syn) 15:1, E/Z (anti) >20:1. The trans-syn isomer: 1H NMR (400 MHz, C6D6): δ 0.86 (d, J=6.8 Hz, 3H), 1.18 (dd, J=23.0 Hz, 6.3 Hz, 3H), 1.96 (br, 1H), 2.08-2.18 (m, 1H), 3.23 (t, J=6.5 Hz, 2H), 4.81 (dqd, J=47.6 Hz, 6.3 Hz, 5.9 Hz, 1H), 5.43-5.56 (m, 2H); 13C NMR (100 MHz, C6D6): δ 16.6 (CH3), 22.0 (d, J=24.7 Hz, CH3), 39.6 (CH), 67.5 (CH2), 90.2 (d, J=163.5 Hz, CH), 131.0 (d , J=19.3 Hz, CH), 136.2 (d , J=10.8 Hz; CH); 19F NMR (376.5 MHz, C6D6): δ -164.7 (dqdd, J=47.6 Hz, 23.0 Hz, 8.2 Hz, 4.3 Hz); IR (neat): 3374, 2930, 1377, 1041, 972, 844HRMS: calculated for C7H13FNaO m/z 155.0843, found: m/z 155.0842. anti-(E)-5-Fluoro-2-methylhex-3-en-1-ol (2i). OH F General procedure B. 11.5mg, 86% yield, syn/anti 1:8, E/Z (syn) 14:1, E/Z (anti) 10:1. The trans-anti isomer: 1H NMR (400 MHz, C6D6): δ 0.92 (d, J=6.8 Hz, 3H), 1.27 S11 (dd, J=23.0 Hz, 6.3 Hz, 3H), 2.16-2.22 (m, 1H), 3.29 (d, J=6.6 Hz, 2H), 4.89 (dm, J=48.3 Hz, 1H), 5.43-5.56 (m, 2H); 13C NMR (100 MHz, C6D6): δ 16.2 (CH3), 21.5 (d, J=24.8 Hz, CH3), 39.2 (CH), 67.0 (CH2), 89.7 (d, J=163.8 Hz, CH), 130.7 (d , J=19.2 Hz, CH), 135.8 (d , J=10.4 Hz; CH); 19F NMR (376.5 MHz, C6D6): δ -164.7 (dqdd, J=51.7 Hz, 23.0 Hz, 7.1 Hz, 2.8 Hz); IR (neat): 3385, 2962, 2927, 2281, 1455, 1377, 1037, 802HRMS: calculated for C7H13FNaO m/z 155.0843, found: m/z 155.0844. (E)-Ethyl 6-(benzyloxy)-3-(trimethylsilyl)hex-4-enoate (4). Me3Si BnO O O A mixture of (E)-1-(benzyloxy)-4-(trimethylsilyl)but-3-en-2-ol (735mg, 2.95mmol, 1eq.), triethylacetate (1.08ml, 5.9mmol, 2eq.) and catalytic propionic acid in toluene was allowed to reflux for 3 days. After that time the mixture was cooled to room temperature. The crude reaction mixture was diluted with hexane (15ml) and purified directly by silica gel chromatography (100% hexane to hexane:Et2O 2:1) to afford (4) 700 mg, 74% yield. 1H NMR (400 MHz, acetone-d6): δ 0.05 (s, 9H), 1.20 (t, J=7.1 Hz, 3H), 2.10 (td, J=9.4 Hz, 4.8 Hz, 3H), 2.38 (dd, J=15.2 Hz, 10.4 Hz, 1H), 2.46 (dd, J=15.2 Hz, 4.8 Hz, 1H), 3.97 (d, J=6.1 Hz, 2H), 4.07 (q, J=7.1 Hz, 2H), 4.46 (s, 2H), 5.45 (dt, J=15.4 Hz, 6.3 Hz, 1H), 5.69 (dd, J=15.4 Hz, 8.8 Hz, 1H), 7.24-7.30 (m, 1H), 7.33-7.35 (m, 4H); 13C NMR (100 MHz, acetone-d6): δ -3.6 (3 x CH3), 14.2 (CH3), 29.7 (CH), 34.1 (CH2), 60.1 (CH2), 70.9 (CH2), 71.1 (CH2), 125.0 (CH), 127.6 (CH), 127.8 (2 x CH), 128.5 (2 x CH), 134.7 (CH), 139.6 (C), 172.9 (C); IR (neat): 2955, 1736, 1249, 1097, 841, 737; HRMS: calculated for C18H28NaO3Si m/z 343.1700, found: m/z 343.1701. S12 (E)-ethyl 6-(benzyloxy)-2-fluoro-3-(trimethylsilyl)hex-4-enoate (6). Me3Si O BnO O F To a solution of diisopropylamine (430uL, 2.6mmol, 1.3eq.) in THF (2 ml) at 0°C was added n-BuLi (2.5M, 1.2ml, 2.4mmol, 1.2eq.) dropwise. The mixture was allowed to stir at this temperature for 30 min. The reaction was then cooled to –78°C and (E)-ethyl-6-(benzyloxy)-3-(trimethylsilyl)hex-4-enoate (4) (640mg, 2.0mmol, 1eq.) in THF (2 mL) was added dropwise. The reaction was allowed to stir at –78°C for 1hr. After this time N-fluorobenzenesulfonimide (NFSI) (950mg, 3.0mmol, 1.5eq.) in THF (2 mL) was added dropwise and the mixture allowed to warm room temperature overnight. The reaction was then cooled to 0°C and quenched by the addition of a saturated solution of NH4Cl. The organic phase was separated and aqueous phase extracted with Et2O. The combined organic extracts were dried over MgSO4, filtered and the solvent removed in vacuo. Purification by silica gel chromatography gave (6) 380mg 56% yield, d.r >20:1. 1H NMR (400 MHz, acetoned6): δ 0.14 (s, 9H), 1.23 (t, J=7.1 Hz, 3H), 2.28 (ddd, J=45.0 Hz, 10.4 Hz, 3.0 Hz, 1H), 3.97 (dd, J=12.4 Hz, 6.1 Hz, 1H), 4.01 (dd, J=11.9 Hz, 5.3 Hz, 1H), 4.15 (dq, J=10.9 Hz, 7.1 Hz, 1H), 4.21 (dq, J=10.9 Hz, 7.1 Hz, 1H), 4.48 (s, 2H), 5.21 (dd, J=47.0 Hz, 3.0 Hz, 1H), 5.29 (dd, J=15.4 Hz, 6.0 Hz, 1H), 7.24-7.31 (m, 1H), 7.337.37 (m, 4H); 13C NMR (100 MHz, acetone-d6): δ -2.8 (3 x CH3), 14.3 (CH3), 37.8 (d, J=25.6 Hz, CH), 61.1 (CH2), 70.6 (CH2), 71.3 (CH2), 90.2 (d, J=182.2 Hz, CH), 127.7 (CH), 127.8 (2 x CH), 128.4 (CH), 128.6 (2 x CH), 128.8 (CH), 139.4 (C), 169.4 (d, J=27.2 Hz, C); 19F NMR (376.5 MHz, acetone-d6): δ –196.1 (dtd, J=47.3 Hz, 26.9 Hz, 9.9 Hz, 1F), -191.3 (pt, J=46.1 Hz, 1F), IR (neat): 2957, 1760, 1250, 1205, 1097, S13 843, 738; HRMS: calculated for C18H27F1NaO3Si1 m/z 361.1606, found: m/z 361.1605. (E)-Ethyl 6-(benzyloxy)-2,5-difluorohex-3-enoate (3). F O BnO O F To a solution of (E)-ethyl-6-(benzyloxy)-2-fluoro-3-(trimethylsilyl)hex-4-enoate (6) (340mg, 1.0mmol, 1eq) in acetonitrile (10ml) was added Selectfluor™ (700mg, 2.5mmol, 2.5 eq.) and NaHCO3 (84mg, 1.0mmol, 1eq.) at 50°C. The reaction was allowed to stir at this temperature for 12hrs. The reaction mixture was cooled to room temperature, diluted with Et2O, filtered and the organic phase washed with water. The organic phase was dried over MgSO4, filtered and the solvent removed in vacuo to give (3) as colourless oil, 280mg 98% yield, syn/anti = 5:1, E/Z (syn) 6:1, E/Z (anti) 1:1. 1H NMR (400 MHz, acetone-d6): δ 1.26 (t, J=7.1 Hz, 3H), 3.66 (ddd, J=22.5 Hz, 11.4 Hz, 6.1 Hz, 1H), 3.71 (ddd, J=26.0 Hz, 11.4 Hz, 3.3Hz, 1H), 4.23 (q, J=7.1 Hz, 2H), 4.60 (s, 2H), 5.26 (dm, J=49.0 Hz, 1H), 5.53 (dm, J=47.8, 1H), 6.02-6.22, (m, 2H), 7.27-7.32 (m, 1H), 7.34-7.39 (m, 4H); 13C NMR (100 MHz, acetone-d6): δ 13.9 (CH3), 61.8 (CH2), 72.0 (dd, J=22.4 Hz, 1.6 Hz, CH2), 73.3 (CH2), 87.8 (d, J=182.1 Hz, CH), 91.3 (d, J=172.6 Hz, CH), 128.0 (CH), 128.1 (2 x CH), 128.7 (2 x CH), 131.0 (dd, J=19.2 Hz, 11.2Hz, CH), 138.8 (C), 167.9 (dd, J=24.8 Hz, 1.6 Hz, C); 19F NMR (376.5 MHz, acetone-d6): δ –188.4 (ddm, J=47.4 Hz, 14.7 Hz, 1F), -186.3 (m, 1F), IR (neat): 2937, 1761, 1453, 1371, 1274, 1207, 1115, 1027, 970, 740. 700; HRMS: calculated for C15H18FNaO3 m/z 307.1116, found: m/z 307.1110. S14 Ethyl 6-(benzyloxy)-2,5-(syn)-difluoro-3,4-(anti)-dihydroxyhexanoate (8). F OH BnO O O OH F To a solution of N-methylmorpholine (246mg, 2.1mmol, 3eq), osmium tetraoxide (9mg, 0.05eq) in water (38uL) and DCM (3.5 mL) was added (E)-ethyl-6(benzyloxy)-2,5-difluorohex-3-enoate (3) (200mg, 0.7mmol, 1eq) in DCM (3.5 mL). The mixture was allowed to stir at room temperature for 3hrs. A saturated solution of NaHSO3 was then added and stirred for a further 15 min. DCM was added and the phases separated. The aqueous phase was extracted with EtOAc and the combined organic phases were dried over Na2SO4, filtered and the solvent removed in vacuo Purification by silica gel chromatography (EtOAc:hexane 2:1, Rf = 0.5) to yield (8) 126mg, 56% yield. NMR data of the major diastereoisomer: 1H NMR (400 MHz, acetone-d6): δ 1.47 (t, J=7.1 Hz, 3H), 4.03 (ddd, J=30.1 Hz, 11.9 Hz, 5.1 Hz, 1H), 4.13 (ddd, J=25.0 Hz, 11.9 Hz, 2.0 Hz, 1H), 4.18-4.24 (m, 1H), 4.26-4.33 (m, 1H), 4.44 (q, J=7.1 Hz, 2H), 4.65 (d, J=7.8, 1H), 4.72, (d, J=8.1 Hz, 1H), 4.79 9s, 2H), 4.92 (dm, J=47.5 Hz, 1H), 5.14 (dd, J=48.5 Hz, 8.1 Hz, 1H), 7.46-7.50 (m, 1H), 7.537.58 (m, 4H); 13C NMR (100 MHz, acetone-d6): δ 14.1 (CH3), 61.7 (CH2), 67.5 (d, J=24.8 Hz, CH2), 69.4 (dd, J=24.8 Hz, 3.2 Hz, CH), 70.1 (d, J=19.2 Hz, CH), 73.5 (CH2), 88.7 (d, J=182.2 Hz, CH), 91.5 (d, J=175.0 Hz, CH), 128.0 (CH), 128.1 (2 x CH), 128.8 (2 x CH), 139.2 (C), 168.9 (d, J=22.4 Hz, C); 19F NMR (376.5 MHz, acetone-d6): δ –194.1 (ddddd, J=47.6 Hz, 29.6 Hz, 27.1 Hz, 5.1 Hz, 2.5 Hz, 1F), 196.1 (ddd, J=48.5 Hz, 9.7 Hz, 2.3 Hz 1F), HRMS: calculated for C15H20F2NaO5 m/z 341.1171, found: m/z 341.1170. S15 Ethyl-6-(benzyloxy)-2,5-(syn)-difluoro-3-O-,4-O-(anti)-isopropylidene-hexanoate (9). BnO F F O O O To a O solution of ethyl-6-(benzyloxy)-2,5-(syn)-difluoro-3,4-(anti)- dihydroxyhexanoate (8) (95mg, 0.3mmol, 1eq.) in acetone (1.5ml) was added dimethoxypropane (1.5ml) and p-TSA (6mg). The mixture was allowed to stir at room temperature overnight. The solvent was removed in vacuo and the crude product purified by silica gel chromatography (1:1 Et2O:hexane, Rf = 0.6) to yield (9) 96mg, 90% yield as a pale yellow oil. NMR data of the major diastereoisomer: 1H NMR (400 MHz, acetone-d6): δ 1.28 (t, J=7.3 Hz, 3H), 1.37 (s, 3H), 1.38 (s, 3H), 3.75 (ddd, J=28.3 Hz, 11.9 Hz, 5.1 Hz, 1H), 3.85 (ddd, J=26.3 Hz, 11.9 Hz, 2.5 Hz, 1H), 4.23 (q, J=7.1 Hz, 2H), 4.24 (q, J=7.1 Hz, 2H), 4.46 (dt, J=9.9 Hz, 6.8 Hz, 1H), 4.53-4.63 (m, 1H), 4.76 (dddd, J=47.5 Hz, 6.8 Hz, 5.3 Hz, 2.5 Hz, 1H), 5.24 (dd, J=48.0 Hz, 2.3 Hz, 1H), 7.28-7.32 (m, 1H), 7.35-7.40 (m, 4H); 13C NMR (100 MHz, acetone-d6): δ 13.9 (CH3), 26.6 (CH3), 26.9 (CH3), 61.7 (CH2), 69.7 (d, J=20.0 Hz, CH2), 73.4 (CH2), 74.4 (dd, J=27.2 Hz, 7.2 Hz, CH), 79.5 (dd, J=22.4 Hz, 3.2 Hz, CH), 88.6 (d, J=189.3 Hz, CH), 93.1 (d, J=175.0 Hz, CH), 111.3 (C), 127.9 (CH), 128.0 (2 x CH), 128.7 (2 x CH), 138.7 (C), 166.8 (d, J=24.0 Hz, C); 19F NMR (376.5 MHz, acetone-d6): δ – 196.1 (dtd, J=47.3 Hz, 26.9 Hz, 9.9 Hz, 1F), -198.4 (dd, J=48.0 Hz, 22.1 Hz, 1F), HRMS: calculated for C18H24F2NaO5 m/z 381.1484, found: m/z 381.1484. S16 Ethyl 6-(benzyloxy)-2,5-(syn)-difluoro-3-O-,4-O-anti-isopropylidene-1-hexanol (10). BnO F F OH O O To suspension of LiAlH4 (38mg, 1mmol) in Et2O (2.5 mL) at 0°C was added ethyl-6(benzyloxy)-2,5-(syn)-difluoro-3-O-,4-O-(anti)-isopropylidene-hexonate (9) (90mg, 0.25mmol, 1eq) in Et2O (2.5 mL) dropwise. The reaction was then allowed to stir at 0°C for 3hrs. The reaction was quenched by the addition of a saturated solution of NH4Cl, and the aqueous phase extracted with Et2O. The combined organic extracts dried over Na2SO4, filtered and the solvent removed in vacuo. Purification by silica gel chromatography (1:1 Et2O:hexane Rf = 0.3), to give (10) 67mg 85 % yield as a mixture of stereoisomers. NMR data of the major diastereoisomer: 1H NMR (400 MHz, acetone-d6): δ 1.38 (s, 3H), 1.39 (s, 3H), 3.72-3.92 (m, 4H), 4.12 (t, J=6.0 Hz, 1H), 4.34 (dt, J=11.7 Hz, 6.0 Hz, 1H), 4.38 (dt, J=12.3 Hz, 6.0 Hz, 1H), 4.59 (dtd, J=48.2 Hz, 5.7 Hz, 2.8 Hz, 1H), 4.61 (s, 2H), 4.80 (dtd, J=48.2 Hz, 5.7 Hz, 2.8 Hz), 7.29-7.32 (m, 1H), 7.35-7.40 (m, 4H); 13C NMR (100 MHz, acetone-d6): δ 27.5 (2 x CH3), 60.9 (d, J=22.9 Hz, CH2), 69.9 (d, J=21.0 Hz, CH2), 73.8 (CH2), 77.1 (dd, J=25.8 Hz, 4.8 Hz, CH), 77.6 (dd, J=24.8 Hz, 3.8 Hz, CH), 93.3 (d, J=176.4 Hz, CH), 95.0 (d, J=174.5 Hz, CH), 111.3 (C), 128.4 (CH), 128.5 (2 x CH), 129.2 (2 x CH), 139.3 (C); 19F NMR (376.5 MHz, acetone-d6): δ –194.7 (m, 1F), -197.4 (m, 1F); IR (neat): 3442, 2938, 1455, 1373, 1217, 1069, 867; HRMS: calculated for C16H22F2NaO4 m/z 339.1378, found: m/z 339.1384. S17 4,5-Bis(2-(benzyloxy)-1-fluoroethyl)-2,2-dimethyl-1,3-dioxolane (11). BnO F F OBn O O To a suspension of NaH (23mg, 0.6mmol, 3eq) in DMF (1 ml) at 0°C was added ethyl-6-(benzyloxy)-2,5-(syn)-difluoro-3-O-,4-O-(anti)-isopropylidene-1-hexanol (10) (63mg, 0.2mmol, 1eq) DMF (1 mL). The mixture was allowed to stir at 0°C for 1hr after which time benzyl bromide (75uL, 0.6mmol, 3eq) was added dropwise. The reaction mixture was then heated at 40°C for 6hr. After cooling to 0°C the reaction was quenched by the addition of water. The aqueous phase was extracted with DCM, the combined organic extracts were dried over Na2SO4, filtered and the solvent removed in vacuo. Purification by silica gel chromatography (1:1 DCM:hexane) to yield (11) 63mg 78% yield as a mixture of stereoisomers. NMR data of the major diastereoisomer: 1H NMR (400 MHz, acetone-d6): δ 1.38 (s, 6H), 3.75 (ddd, J=24.6 Hz, 11.7 Hz, 6.0 Hz, 2H), 3.83 (ddd, J=27.1 Hz, 11.7 Hz, 2.5 Hz, 2H), 4.12-4.40 (m, 2H), 4.61 (s, 4H), 4.80 (dm, J=48.2 Hz, 2H), 7.29-7.32 (m, 2H), 7.35-7.40 (m, 8H); 13C NMR (100 MHz, acetone-d6): δ 27.5 (2 x CH3), 69.9 (d, J=22.9 Hz, 2 x CH2), 73.9 (2 x CH2), 77.4 (dd, J=25.8 Hz, 2.9 Hz, 2 x CH), 93.3 (d, J=175.5 Hz, 2 x CH), 111.5 (2 x C), 128.4 (2 x CH), 128.5 (4 x CH), 129.2 (4 x CH), 139.3 (2 x C); 19F NMR (376.5 MHz, acetone-d6): δ –194.5 (dtd, J=47.7 Hz, 26.8 Hz, 2.6 Hz, 1F), IR (neat): 2938, 1453, 1371, 1068, 736; HRMS: calculated for [M+NH4] C23H32F2N1O4 m/z 424.2292, found: m/z 424.2294. S18 1,6-bis(benzyloxy)-2,5-difluorohexane-3,4-diol (7). F OH BnO OBn OH F A solution of 4,5-bis(2-(benzyloxy)-1-fluoroethyl)-2,2-dimethyl-1,3-dioxolane (11) (41mg, 0.1mmol) in AcOH:H2O 7:3 (1 mL) and was heated at 100°C for 24hrs. The reaction was allowed to cool and toluene was added. The solvents were removed in vacuo. Purification by silica gel chromatography (1:1 EtOAc:hexane) to give (7) 30 mg, 82% yield as a mixture of stereoisomers. NMR data of the major diastereoisomer: 1H NMR (400 MHz, CDCl3): δ 2.77 (d, J=7.3, 2H), 3.81 (ddd, J=27.4 Hz, 11.4 Hz, 4.4 Hz, 2H), 3.88 (ddd, J=27.1 Hz, 11.4 Hz, 3.5 Hz, 2H), 4.08 (dd, J=7.9 Hz, 7.3 Hz, 2H), 4.59 (d, J=11.9 Hz, 2H), 4.64 (d, J=11.9 Hz, 2H),4.67 (dm, J=46.5 Hz, 2H), 7.30-7.38 (m, 10H); 13C NMR (100 MHz, CDCl3): δ 68.6 (dd, J=24.8 Hz, 3.8 Hz, 2 x CH), 69.5 (d, J=21.9 Hz, 2 x CH2), 74.1 (2 x CH2), 90.7 (d, J=174.5 Hz, 2 x CH), 128.1 (4 x CH), 128.3 (2 x CH), 128.8 (4 x CH), 137.7 (2 x C); 19F NMR (376.5 MHz, CDCl3): δ –194.8 (dddd, J=47.7 Hz, 28.3 Hz, 21.4 Hz, 7.9, 2F), The major stereoisomer was identical in all aspects with sample prepared by previously published method.2 References: 1. a) G. Procter, A. T. Russel, P. J. Murphy, T. S. Tan, A. N. Mather, Tetrahedron, 1988, 44, 3953; b) M. A. Sparks, J. S. Panek, J. Org. Chem. 1991, 56, 3431; c) J. S. Panek, R. Beresis, F. Xu, M. Yang, J. Org. Chem. 1991, 56, 7341; d) J. S. Panek, M. Yang, J. S. Solomon, J. Org. Chem. 1993, 58, 1003; e) C. E. Masse, B. S. Knight, P. Stavropoulos, J. S. Panek, J. Am. Chem. Soc. 1997, 119, 6040. 2. L. Hunter, D. O’Hagan, A. M. Z. Slawin, J. Am. Chem. Soc. 2006, 128, 16422. S19 OH SiMe3 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 9.00 1.13 1.16 3.74 2.01 1.80 1b 0.5 0 S20 200 180 160 140 120 100 80 60 40 18.18 32.20 29.66 62.47 123.16 132.33 -3.21 OH SiMe3 1b 20 0 S21 128.26 128.02 127.78 O Me 3Si O 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 9.46 6.12 3.06 1.00 2.00 2.00 1c 1.0 0.5 0 S22 178.31 180 160 140 120 100 80 60 42.34 40 18.13 14.19 Me 3Si 26.46 23.82 44.21 60.20 128.28 126.11 O O 1c 20 0 S23 -0.85 77.34 77.03 76.71 OH 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 9.23 6.45 1.07 4.06 1.04 1.00 0.96 0.93 SiMe3 1d 0.5 0 S24 200 180 160 140 120 100 80 60 40 25.70 23.73 18.09 41.94 38.16 72.20 125.04 130.40 0.40 OH SiMe3 1d 20 0 S25 128.26 128.02 127.78 Bn O Me 3Si O 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 9.71 3.03 3.05 1.01 2.22 1.09 1.97 2.00 4.83 1f-anti/ syn >20:1 0.5 0 S26 200 180 140.50 174.63 160 140 120 48.85 100 80 60 40 17.79 13.87 28.81 128.50 129.26 Me 3Si 38.88 36.97 29.96 59.83 130.00 126.41 125.43 Bn O O 1f-anti/ syn >20:1 20 0 S27 -2.48 29.77 29.57 29.38 29.19 29.00 205.63 OH SiMe3 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 9.28 3.19 4.09 1.30 0.99 2.00 1.89 1g-anti/ syn >20:1 0.5 0 S28 200 180 160 140 120 100 80 60 40 18.16 13.92 77.31 77.00 76.68 1g-anti/ syn >20:1 35.48 35.01 68.34 127.85 124.98 OH SiMe3 20 0 S29 -2.05 OH SiMe3 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 9.00 3.21 1.07 2.97 0.87 1.02 0.90 1.83 1i - anti/ sy n = 1:9 0.5 0 S30 200 180 160 140 120 100 80 60 40 17.93 17.75 37.93 37.27 66.35 123.98 130.97 29.77 29.00 SiMe3 1i - anti/ sy n = 1:9 -1.61 29.20 OH 20 0 S31 29.58 205.68 29.39 O F O 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 3.00 3.10 2.02 1.91 0.53 0.43 0.94 0.91 2a - E/ Z = 1.3:1 1.0 0.5 0 S32 200 180 160 140 133.75 120 100 80 60 40 21.57 21.30 21.05 37.45 14.11 60.52 60.43 F 33.17 89.95 88.32 86.17 84.56 125.22 125.10 125.02 124.92 133.56 170.40 O O 2a - E/ Z = 1.3:1 20 0 S33 128.24 128.00 127.76 -166.71 O F O -166.97 2a - E/ Z = 1.3:1 -166.0 -166.5 -167.0 -167.5 S34 OH F 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 3.31 2.16 1.07 2.00 0.73 0.26 1.97 2b - E/ Z = 3:1 1.5 1.0 0.5 0 S35 200 180 160 140 120 100 80 60 40 21.64 31.38 35.72 61.64 21.55 21.31 90.53 88.91 86.18 84.59 132.65 132.46 OH F 2b - E/ Z = 3:1 20 0 S36 128.24 128.00 127.76 -164.61 OH F -164.53 2b - E/ Z = 3:1 -163.5 -164.0 -164.5 -165.0 -165.5 -166.0 -166.5 S37 O F O 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 2.91 9.30 1.91 0.94 0.89 0.85 2c 1.0 0.5 0 S38 200 180 160 140 120 100 80 60 25.04 24.84 21.57 21.33 14.04 60.60 F 43.96 90.38 88.74 128.72 137.40 175.25 O O 2c 40 20 0 S39 128.23 127.99 127.75 -166.41 O F O 2c -165.0 -165.5 -166.0 -166.5 -167.0 -167.5 S40 OH F 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 6.00 2.97 1.00 1.82 0.85 1.69 2d 1.0 0.5 0 S41 200 180 160 140 120 100 80 60 40 70.97 23.38 23.29 21.46 21.21 37.82 90.66 89.03 128.28 128.08 140.06 139.95 OH F 2d 20 0 S42 127.91 127.67 127.43 -166.40 OH F 2d -164.5 -165.0 -165.5 -166.0 -166.5 -167.0 -167.5 -168.0 S43 O 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 3.00 6.29 0.87 1.95 0.90 0.98 0.84 F O 2e - sy n/ anti = 19:1, E/ Z (syn) = 15:1, E/ Z (anti) >20:1 1.0 0.5 0 S44 128.24 128.00 127.75 O 173.48 200 180 160 140 120 100 80 60 40 21.41 21.17 17.10 42.57 90.08 88.44 131.98 131.87 60.45 14.10 F O 2e - sy n/ anti = 19:1, E/ Z (syn) = 15:1, E/ Z (anti) >20:1 20 0 S45 -166.63 O -165.31 -166.86 F O 2e - sy n/ anti = 19:1, E/ Z (syn) = 15:1, E/ Z (anti) >20:1 -165.5 -166.0 -166.5 -167.0 S46 Bn O 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 2.91 3.07 1.03 1.14 0.87 0.09 1.91 0.85 0.14 0.97 0.83 5.62 F O 2f - syn/ ant i >20:1, E/ Z (sy n) = 11:1, E/ Z (sy n) >20:1 1.0 0.5 0 S47 200 180 160 140 120 100 80 60 40 21.35 21.11 60.49 126.70 14.04 50.90 39.03 89.81 88.16 138.87 133.12 132.93 129.82 172.56 129.44 128.54 Bn O F O 2f - syn/ anti >20:1, E/ Z (sy n) = 11:1, E/ Z (syn) >20:1 20 0 S48 128.25 128.01 127.76 -167.81 Bn O -165.5 -166.0 -167.39 -165.66 -166.35 F O 2f - syn/ anti >20:1, E/ Z (sy n) = 11:1, E/ Z (syn) >20:1 -166.5 -167.0 -167.5 -168.0 S49 OH 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 3.20 3.18 1.04 0.96 2.08 0.96 1.90 F 2g - syn/ anti > 20:1, E/ Z (syn) = 15:1, E/ Z (anti) >20:1 1.0 0.5 S50 128.25 128.00 127.76 OH 200 180 160 140 120 100 80 60 40 21.68 21.44 16.14 39.20 90.60 88.98 67.06 135.75 130.79 F 2g - syn/ anti > 20:1, E/ Z (syn) = 15:1, E/ Z (anti) >20:1 20 0 S51 -164.77 OH -163.95 -164.36 F 2g - syn/ anti > 20:1, E/ Z (syn) = 15:1, E/ Z (anti) >20:1 -163.5 -164.0 -164.5 -165.0 S52 O 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 3.34 8.02 0.86 1.22 2.00 0.88 0.09 1.10 0.84 F O 2h - sy n/ anti = 1:6, E/ Z (syn) >20:1, E/ Z (anti) = 11:1 1.0 0.5 0 S53 128.25 128.00 127.76 O 180 160 140 120 100 80 60 40 16.97 21.38 42.46 65.87 90.00 88.36 131.86 173.47 200 60.49 14.10 F O 2h - sy n/ anti = 1:6, E/ Z (syn) >20:1, E/ Z (anti) = 11:1 20 0 S54 -166.86 O -165.29 -167.08 -166.62 F O 2h - sy n/ anti = 1:6, E/ Z (syn) >20:1, E/ Z (anti) = 11:1 -165.5 -166.0 -166.5 -167.0 S55 OH 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 3.52 6.31 1.06 4.00 0.92 0.18 1.86 F 2i - syn/ ant i = 1:8, E/ Z (syn) = 14:1, E/ Z (anti) = 10:1 2.0 1.5 1.0 0.5 0 S56 128.25 128.01 127.76 OH 200 180 160 140 120 100 80 60 40 21.67 21.42 16.18 39.24 67.04 90.54 88.91 130.64 135.80 F 2i - syn/ anti = 1:8, E/ Z (sy n) = 14:1, E/ Z (ant i) = 10:1 20 0 S57 -164.68 OH -163.02 -164.94 F 2i - syn/ anti = 1:8, E/ Z (sy n) = 14:1, E/ Z (ant i) = 10:1 -162.5 -163.0 -163.5 -164.0 -164.5 -165.0 -165.5 S58 O BnO Me 3Si O 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 10.00 3.00 0.92 2.20 3.95 1.85 0.99 0.93 4.89 4 2.0 1.5 1.0 0.5 0 S59 200 180 160 140 120 100 80 60 40 14.72 -3.09 30.22 29.61 206.11 29.91 29.76 30.07 O 29.46 34.65 129.05 128.36 Me3 Si 60.61 71.58 71.43 128.10 125.55 140.08 135.22 173.35 BnO O 4 20 0 S60 F O BnO 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 9.21 3.00 0.90 2.05 1.97 1.97 1.01 0.94 0.96 4.47 Me 3Si O 6 - major anti/ sy n >20:1 1.0 0.5 0 S61 200 180 160 140 120 100 37.89 37.63 91.13 89.32 139.44 30.03 28.88 169.52 169.25 127.84 80 60 29.65 O 40 14.25 Me3 Si O 6 - major anti/ sy n >20:1 29.27 BnO 29.84 29.07 61.06 71.26 70.58 128.82 127.66 128.59 205.61 -2.76 29.46 F 20 0 S62 -191.25 F O BnO -182.59 Me3 Si O 6 - major anti/ sy n >20:1 -181 -182 -183 -184 -185 -186 -187 -188 -189 -190 -191 -192 -193 S63 F O BnO 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.61 2.00 2.14 2.01 0.84 0.96 0.27 1.80 4.05 F O 3 - syn/ anti = 5:1, E/ Z (syn) = 6:1, E/ Z (ant i) = 1:1 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 S64 200 180 160 140 120 61.98 138.79 100 80 30.05 28.90 72.09 71.88 92.19 90.48 88.74 86.93 126.63 126.44 126.32 131.18 131.07 168.00 167.74 61.82 F O 3 - sy n/ anti = 5:1, E/ Z (syn) = 6:1, E/ Z (anti) = 1:1 60 29.67 BnO 205.86 127.95 29.28 O 40 13.94 29.86 29.09 73.27 128.68 29.47 F 20 0 S65 -188.39 -186.27 F O BnO -181 -182 -183 -184 -185 -186 -191.23 -189.22 -186.40 -183.36 -183.38 -180.12 -180.14 -180 -188.62 F O 3 - sy n/ anti = 5:1, E/ Z (syn) = 6:1, E/ Z (anti) = 1:1 -187 -188 -189 -190 -191 S66 OH F O BnO F OH O 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.00 1.88 2.07 1.75 3.40 1.06 1.02 0.28 4.11 8 - Major stereoisomer 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 S67 200 180 160 140 120 100 80 60 14.09 O 206.03 29.98 29.79 29.60 29.22 29.41 F 40 29.02 30.18 BnO 61.70 73.54 128.01 128.82 128.05 F 70.21 70.02 92.31 90.57 89.64 87.83 139.22 169.02 168.80 OH OH O 8 - Major stereoisomer 20 0 S68 OH F O BnO F OH O 8 - Major stereoisomer -180 -182 -184 -186 -188 -190 -192 -194 -196 -198 -200 -202 -204 -206 -208 -210 -212 -214 -216 -218 -220 S69 F F BnO O O O O 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.00 2.10 1.85 0.95 2.95 0.89 0.22 0.93 4.15 9 - major stereoisomer 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 S70 200 180 160 140 120 100 80 60 29.77 29.00 O 40 20 13.91 F F 26.88 28.80 26.63 29.96 73.39 128.67 127.96 O 69.66 69.46 61.71 94.00 92.27 89.52 87.64 79.56 79.37 111.31 127.86 138.69 166.91 166.67 BnO O O 9 - major stereoisomer 0 S71 29.57 29.38 29.19 205.67 BnO O F F O O O 9 - major stereoisomer -160 -170 -180 -190 -200 -210 -220 -230 S72 F F BnO OH O O 7.0 6.5 6.0 5.5 5.0 4.5 4.0 6.19 3.97 0.82 1.94 1.07 2.94 4.89 10 - major stereoisomer 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 S73 200 180 160 140 120 100 80 70.01 69.84 62.02 61.84 27.49 73.83 129.16 128.44 10 - major stereoisomer 30.35 O 77.21 77.00 95.66 94.28 94.03 92.62 111.31 139.33 O 29.42 206.19 BnO 30.19 30.04 29.88 29.72 29.57 F F OH 60 40 20 0 S74 F F BnO OH O O 10 - major stereoisomer -180 -182 -184 -186 -188 -190 -192 -194 -196 -198 -200 -202 -204 -206 -208 -210 S75 BnO F F OBn O O 7.0 6.5 6.0 5.5 5.0 4.5 4.0 5.79 4.00 3.80 1.89 2.04 9.27 11 - major stereoisomer 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 S76 200 180 160 140 120 100 80 27.48 29.43 69.82 30.35 73.85 129.17 128.45 O 77.56 77.33 94.02 92.62 111.45 139.30 BnO F F OBn O 11 - major stereoisomer 60 40 20 0 S77 30.20 30.05 29.89 29.74 29.59 206.17 BnO F F OBn O O 11 - major stereoisomer -160 -170 -180 -190 -200 -210 -220 S78