Reaction SMILES: COC(=O)CCC/C=C\C[C@H]1C(=O)C[C@@H](CC)[C@@H]1/C=C/C(O)CCC1SC2C=CC=CC=2C=1Cl.[CH3:35][O:36][C:37](=[O:75])[CH2:38][CH2:39][CH2:40]/[CH:41]=[CH:42]\[CH2:43][C@H:44]1[C:48](=[O:49])[CH2:47][C@@H:46](CC)[C@@H:45]1/[CH:52]=[CH:53]/[CH:54]([O:67][Si:68]([C:71]([CH3:74])([CH3:73])[CH3:72])([CH3:70])[CH3:69])[CH2:55][CH2:56][C:57]1[S:61][C:60]2[CH:62]=[CH:63][CH:64]=[CH:65][C:59]=2[C:58]=1[Cl:66].C1C=CN=CC=1.F.C([O-])(O)=O.[Na+]>C(#N)C>[CH3:35][O:36][C:37](=[O:75])[CH2:38][CH2:39][CH2:40]/[CH:41]=[CH:42]\[CH2:43][C@H:44]1[C:48](=[O:49])[CH2:47][CH2:46][C@@H:45]1/[CH:52]=[CH:53]/[CH:54]([O:67][Si:68]([C:71]([CH3:73])([CH3:72])[CH3:74])([CH3:69])[CH3:70])[CH2:55][CH2:56][C:57]1[S:61][C:60]2[CH:62]=[CH:63][CH:64]=[CH:65][C:59]=2[C:58]=1[Cl:66]
Reactant: CC[C@@H]1CC(=O)[C@H](C/C=C\CCCC(=O)OC)[C@H]1/C=C/C(CCc1sc2ccccc2c1Cl)O[Si](C)(C)C(C)(C)C
Agent: CC[C@@H]1CC(=O)[C@H](C/C=C\CCCC(=O)OC)[C@H]1/C=C/C(O)CCc1sc2ccccc2c1Cl
Agent: F
Agent: O=C([O-])O
Solvent: c1ccncc1
Solvent: CC#N
Product: COC(=O)CCC/C=C\C[C@H]1C(=O)CC[C@@H]1/C=C/C(CCc1sc2ccccc2c1Cl)O[Si](C)(C)C(C)(C)C
Reaction time: 4 h
Yield: 70 %

Procedure:
A solution of enone 13 (145 mg, 0.25 mmol) in toluene (4 mL) was added to a −45° C. mixture of [Ph3PCuH]6 in toluene (4 mL), rinsing with 0.5 mL toluene. The mixture was allowed to stir for 1 h and then was allowed to warm to room temperature. After 19 h at room temperature, the reaction was quenched by addition of 15 mL saturated NH4Cl solution. The resulting mixture was extracted with ethyl acetate (3×15 mL) and the combined ethyl acetate solution was dried (Na2SO4), filtered and evaporated. Purification by flash chromatography on silica gel (7.5% ethyl acetate/hexanes→12.5%) gave ketone 14 (R=H, 111 mg, 0.19 mmol, 76%). (Z)-7-{(1R,2R,3R)-2-[(E)-3-(tert-Butyl-dimethyl-silanyloxy)-5-(3-chloro-benzo[1b]thiophen-2-yl)-pent-1-enyl]-3-methyl-5-oxo-cyclopentyl}-hept-5-enoic acid methyl ester 14 (R=methyl). A −78° C. mixture of CuCN (47 mg, 0.52 mmol) in 0.5 mL THF was treated with methyllithium (0.57 mL, 0.80 mmol, 1.4 M/ether). The reaction was stirred for 5 minutes at −78° C. and then for 10 min. at room temperature. The reaction was cooled back down to −78° C. and then a solution of enone 13 (80 mg, 0.14 mmol) in 0.5 mL THF was added by cannula, rinsing with 0.2 mL THF. The reaction was stirred for 2 h at −78° C. and then 10 mL saturated ammonium chloride solution was added. The resulting mixture was stirred for 20 min. at room temperature and then was extracted with dichloromethane (3×15 mL). The combined dichloromethane solution was dried (Na2SO4), filtered and evaporated to leave the title compound. (Z)-7-{(1R,2R,3R)-2-[(E)-3-(tert-Butyl-dimethyl-silanyloxy)-5-(3-chloro-benzo[b]thiophen-2-yl)-pent-1-enyl]-3-ethyl-5-oxo-cyclopentyl}-hept-5-enoic acid methyl ester 14 (R=Et). A 0° C. mixture of CuI (77 mg, 0.4 mmol) in 0.2 mL THF was treated with ethylmagnesium bromide (0.72 mL, 0.72 mmol, 1 M/THF). After 5 min., the grey mixture was cooled to −78° C. and a solution of enone 13 (67 mg, 0.11 mmol) in 0.5 mL THF was added by cannula, rinsing with 0.25 mL THF. After 45 min., saturated ammonium chloride solution was added. The resulting mixture was stirred for 15 min. and then was extracted with ethyl acetate (3×15 mL). The combined ethyl acetate solution was dried (Na2SO4), filtered and evaporated. Purification by flash chromatography on silica gel (5% ethyl acetate/hexanes→7.5%) gave the title compound (31 mg, 0.05 mmol, 46%). A similar procedure was used to prepare 14 (R=iPr, vinyl). (Z)-7-{(1R,2R,3R)-2-[(E)-5-(3-Chloro-benzo[b]thiophen-2-yl)-3-hydroxy-pent-1-enyl]-3-ethyl-5-oxo-cyclopentyl}-hept-5-enoic acid methyl ester 15 (R=Et). A solution of 14 (R=Et, 31 mg, 0.05 mmol) in acetonitrile (1 mL) was treated with HF-pyridine (0.19 mL). After 4 h, the reaction was poured into 20 mL of saturated NaHCO3 solution. The resulting mixture was extracted with dichloromethane (3×15 mL) and the combined dichloromethane solution was dried (Na2SO4), filtered and evaporated. Purification by flash chromatography (25% ethyl acetate/hexanes) gave the title compound (18 mg, 0.035 mmol, 71%). Compounds 15 (R=H, Me, iPr, vinyl) were prepared in a similar way. In the case of 15 (R=H), the C15 diastereomers were separated by preparative TLC on silica gel (30% ethyl acetate/hexanes). (Z)-7-{(1R,2R,3R)-2-[(E)-5-(3-Chloro-benzo[b]thiophen-2-yl)-3-hydroxy-pent-1-enyl]-3-ethyl-5-oxo-cyclopentyl}-hept-5-enoic acid 16a (R=Et). A solution of ester 15 (R=Et, 10 mg, 0.020 mmol), 0.5 M LiOH (0.10 mL, 0.05 mmol) and THF (0.7 mL) was stirred at room temperature for 17 h. HCl (10 mL, 1 M) was added and the resulting mixture was extracted with dichloromethane (3×15 mL). The combined dichloromethane solution was then dried (Na2SO4), filtered and evaporated. Purification by flash chromatography on silica gel (2% methanol/dichloromethane→5%) gave the title acid (9 mg, 0.018 mmol, 92%). 300 MHz 1H NMR (CDCl3, ppm) δ 7.73 (2 H, d, J=8.0 Hz) 7.4–7.3 (2H, m) 5.7–5.3 (4H, m) 4.3–4.2 (1H, m) 3.1–3.0 (2 H, m) 2.6–1.1 (17H, overlapping m) 0.94–0.85 (3H, m). The other acids 16a (R=H, Me, iPr, vinyl) were prepared in a similar way. (Z)-7-{(1R,2R)-2-[(E)-5-(3-Chloro-benzo[b]thiophen-2-yl)-3-hydroxy-pent-1-enyl]-5-oxo-cyclopentyl}-hept-5-enoic acid isopropyl ester; general procedure for isopropyl ester formation (16b, R=H, high Rf diastereomer). An acetone (0.2 mL) solution of 16a (R=H, high Rf diastereomer, 6 mg, 0.013 mmol), DBU (4 μL, 0.027 mmol) and 2-iodopropane (20 μL, 0.20 mmol) was stirred at room temperature for 4 days. HCl (10 mL, 1 M) was added and the resulting mixture was extracted with dichloromethane (3×15 mL). The combined dichloromethane solution was dried (Na2SO4), filtered and evaporated. The residue was purified by flash chromatography on silica gel (30% ethyl acetate/hexanes) to give the title compound (6 mg, 0.012 mmol, 92%). tert-Butyl-hex-5-ynyloxy-dimethyl-silane (18, scheme 3). A solution of 5-hexyn-1-ol (17, 5.20 g, 0.053 mmol), imidazole (7.2 g, 0.106 mmol) and TBSCl (11.8 g, 0.079 mmol) in DMF (53 mL) was stirred for 12 h. The reaction was diluted with ether and washed with 1 M HCl, saturated aqueous sodium bicarbonate, and brine. The solution was then dried (MgSO4), filtered and concentrated in vacuo. Purification by flash chromatography on silica gel (19:1 hexane/ethyl acetate) gave 8.65 g (77%) of 18. 7-(tert-Butyl-dimethyl-silanyloxy)-hept-2-yn-1-ol (19). n-butyllithium (15.3 mL, 0.025 mmol, 1.6 M/hexane) was added to a solution of 18 (5.0 g, 0.024 mmol) in THF (48 mL) at −10° C. After 0.5 h at 0° C., the reaction was recooled to −10° C. and paraformaldehyde (1.06 g, 0.035 mmol) was added. The reaction was allowed to warm to 23° C., stirred for 16 h and then was quenched by addition of saturated aqueous ammonium chloride. The reaction ws extracted with ethyl acetate and the organic portion was washed with brine. The solution was then dried (MgSO4), filtered and concentrated in vacuo. Purification by flash chromatography on silica gel (4:1 hexane/ethyl acetate) gave 3.0 g (52%) of 19. Acetic acid 7-(tert-butyl-dimethyl-silanyloxy)-hept-2-ynyl ester (20). A solution of 7-(tert-Butyl-dimethyl-silanyloxy)-hept-2-yn-1-ol 19 (4.507 g, 21 mmol) in pyridine (20 mL) was treated with acetic anhydride (3.0 mL, 31.8 mmol). After 18 h, the solvent was evaporated and the residue co-evaporated with toluene. The residue was used directly in the next step. 7-Acetoxy-hept-5-ynoic acid (21). A solution of crude 20 in acetone (100 mL) was treated with Jones Reagent (18.0 mL, 41.4 mmol, 2.3 M). The mixture became warm and so was cooled with an ice bath. After 1 h at room temperature, 10 mL isopropyl alcohol was added and the mixture stirred further for 15 min. The mixture still had a brown color so another 10 mL isopropyl alcohol was added. After another 15 min., the color had not changed so the mixture was filtered through celite and the filtrate evaporated in vacuo. The residue was partitioned between 100 mL ether and 100 mL saturated ammonium chloride solution. The aqueous layer was extracted with 100 mL ether and the combined ether solution washed with brine and then was dried (MgSO4), filtered and evaporated to leave a yellow oil (21, 6.333 g) that was used directly in the next step. 7-Hydroxy-hept-5-ynoic acid methyl ester (22). The crude acid 21 (6.333 g) was treated with a 1% solution of acetyl chloride in methanol (60 mL). After 16 h, sodium bicarbonate (1.966 g, 23.4 mmol) was added. The mixture was dried (MgSO4), filtered through celite and evaporated in vacuo. Purification by flash chromatography on silica gel (30–40% ethyl acetate/hexanes) gave 7-Hydroxy-hept-5-ynoic acid methyl ester 22 (3.022 g, 19.3 mmol, 92% from 7-(tert-Butyl-dimethyl-silanyloxy)-hept-2-yn-1-ol 20). 7-Iodo-hept-5-ynoic acid methyl ester (23). A solution of 22 (1.347 g, 8.6 mmol) in 5 mL dichloromethane was added to a mixture of triphenylphosphine (2.725 g, 10.4 mmol), imidazole (726 mg, 10.7 mmol), and iodine (2.602 g, 10.3 mmol) in 34 mL dichloromethane, rinsing with 5 mL dichloromethane. After 40 min., the dichloromethane was evaporated in vacuo to a few mL's and the resulting mixture filtered through basic alumina, washing with 10% ethyl acetate/hexanes. Purification by flash chromatography on silica gel (10% ethyl acetate/hexanes) gave 23 (1.878 g, 7.1 mmol, 83%) of the propargyl iodide. 7-[(1R,2S,3R)-2-[(E)-3-(tert-Butyl-dimethyl-silanyloxy)-5-(3-chloro-benzo[b]thiophen-2-yl)-pent-1-enyl]-3-(tert-butyl-dimethyl-silanyloxymethyl)-5-oxo-cyclopentyl]-hept-5-ynoic acid methyl ester (25). A −78° C. solution of iodide 10 (2.194 g, 4.45 mmol) in THF (5.0 mL) was treated with tert-butyllithium (5.2 mL, 8.84 mmol), 1.7 M/pentane). The dark brown mixture was stirred for 30 min. and then dimethylzinc (2.2 mL, 4.4 mmol, 2 M/toluene) was added. The solution was stirred at 0° C. for 15 min. and then recooled to −78° C. At this time, a solution of enone 24 (508 mg, 2.24 mmol) in THF (3.0 mL) was added over 1 h by syringe pump, rinsing with 0.5 mL THF. After 30 min., HMPA (3.8 mL, 21.8 mmol) was added followed by a solution of propargyl iodide 23 (2.379 g, 8.9 mmol) in THF (3.0 mL). The solution was stirred in a −40° C. bath for 19 h and then the reaction was quenched by addition of 50 mL saturated ammonium chloride solution. The mixture was extracted with ethyl acetate (3×75 mL) and the combined organic extracts were dried (Na2SO4), filtered and evaporated. Purification by flash chromatography on silica gel (2→8% ethyl acetate/hexanes) gave 136 mg (0.18 mmol, 8%) of 25. 7-{(1R,2S,3R)-2-[(E)-5-(3-Chloro-benzo[b]thiophen-2-yl)-3-hydroxy-pent-1-enyl]-3-hydroxymethyl-5-oxo-cyclopentyl}-hept-5-ynoic acid methyl ester (26, 27). A solution of 25 (136 mg, 0.18 mmol) in CH3CN (3 mL) was treated with HF-pyridine (1 mL). The solution was stirred for 3 h and saturated sodium bicarbonate solution (100 mL) was added. The mixture was extracted with dichloromethane (3×60 mL) and the combined dichloromethane solution was dried (Na2SO4), filtered and evaporated. Purification by flash chromatography (50% ethyl acetate/hexane→55%→60%→75%) gave 15 mg (0.03 mmol, 16%) of the less polar diastereomer (26) and 16 mg (0.03 mmol, 16%) of the more polar diastereomer (27). (Z)-7-{(1R,2S,3R)-2-[(E)-5-(3-Chloro-benzo[b]thiophen-2-yl)-3-hydroxy-pent-1-enyl]-3-hydroxymethyl-5-oxo-cyclopentyl}-hept-5-enoic acid methyl ester (28, 29). A mixture of NaBH4 (6 mg, 0.17 mmol) and NiCl2 (57 mg, 0.43 mmol) was treated with 95% ethanol (1 mL). The resulting mixture was stirred for 5 min. and then ethylenediamine (50 μL, 0.75 mmol) was added. After 15 min., a solution of 26 (15 mg) in 95% ethanol (1 mL) was added by cannula. The mixture was stirred under 1 atm H2 (balloon) overnight. The mixture was then filtered through Celite and evaporated. Purification of the residue by flash chromatography on silica gel (4% methanol/dichloromethane) followed by preparative TLC (6% methanol/dichloromethane) gave 28 (7 mg, 0.014 mmol, 46%). The more polar diastereomer 27 was converted to 29 using a similar procedure. (Z)-7-{(1R,2S,3R)-2-[(E)-5-(3-Chloro-benzo[b]thiophen-2-yl)-3-hydroxy-pent-1-enyl]-3-hydroxymethyl-5-oxo-cyclopentyl}-hept-5-enoic acid (30, 31). A solution of 28 (6 mg, 0.011 mmol) and rabbit liver esterase (1 mg) in pH 7.2 phosphate buffer (1 mL)/CH3CN (0.08 mL) was stirred for 17 h. The mixture was then coevaporated with CH3CN to remove water. The residue was purified by flash chromatography on silica gel (5% MeOH/CH2Cl2) followed by preparative TLC (5% MeOH/CH2Cl2) to give 5 mg (0.010 mmol, 93%) of the acid (30). The other diastereomer 31 was prepared by a similar procedure. 2-Benzo[b]thiophen-2-yl-ethanol (33, scheme 5). n-BuLi (100 mL, 160 mmol, 1.6M/hexanes) was added to a −78° C. mixture of thianaphthene (17.31 g, 129 mmol) in THF (70 mL)/ether (30 mL). The mixture was stirred at −78° C. for 2 h and then a solution of ethylene oxide (42.86 g, 1.071 mmol) in THF (70 mL)/ether (30 mL) was added by cannula over 15 min. The resulting mixture was stirred for 2 h at −78° C. and then at room temperature for 15 h. At this time, the mixture was evaporated, 200 mL H2O was added, and the resulting mixture was extracted with ethyl acetate (3×150 mL). The combined organic solution was washed with brine and then was dried (Na2SO4), filtered, and evaporated. Purification by flash chromatography on silica gel (20% ethyl acetate/hexanes) gave 33 (13.61 g, 78 mmol, 60%). Benzo[b]thiophen-2-yl-acetaldehyde (34). A 0° C. mixture of 33 (8.019 g, 44.9 mmol) in 100 mL dichloromethane was treated with Dess-Martin reagent (20 g, 47.2 mmol). The mixture was stirred at 0° C. for 10 min. and at room temperature for 40 min. Saturated NaHCO3 solution (200 mL) and 0.1 M NaHSO3 solution were added and the resulting mixture was extracted with ethyl acetate (3×300 mL). The combined organic solution was dried (Na2SO4), filtered and evaporated to give 34 (8.77 g). The aldehyde was taken on crude for the next reaction. 1-Benzo[b]thiophen-2-yl-but-3-yn-2-ol (35). A solution of crude 34 (8.77 g) in THF (100 mL) was added to a solution of ethynylmagnesium bromide (450 mL, 225 mmol, 0.5 M/THF) at 0° C. by cannula. The mixture was stirred for 1 h at 0° C. and for 1 h at room temperature. The reaction was then queched by addition of 200 mL saturated NH4Cl solution. The layers were separated and the aqueous layer was extracted with ethyl acetate (3×200 mL). The combined organic solution was washed with brine and then was dried (Na2SO4), filtered and evaporated. Purification by flash chromatography on silica gel (10%→20% ethyl acetate/hexanes) gave 35 (7.67 g, 37.9 mmol, 84% from 33). (1-Benzo[b]thiophen-2-ylmethyl-prop-2-ynyloxy)-tert-butyl-dimethyl-silane (36). DMAP (2.306 g, 18.9 mmol), TBSCl (11.502 g, 76.3 mmol) and triethylamine (5.25 mL, 37.7 mmol) were added to a solution of 35 (7.67 g, 37.9 mmol) in dichloromethane (120 mL). After 17 h, 150 mL of saturated NH4Cl solution was added and the layers were separated. The aqueous layer was extracted with dichloromethane (3×100 mL) and the combined organic solution was dried (Na2SO4), filtered and evaporated. Purification by flash chromatography on silica gel (4% ethyl acetate/hexanes) gave 36 (8.38 g, 26.5 mmol, 70%). ((E)-1-Benzo[b]thiophen-2-ylmethyl-3-iodo-allyloxy)-tert-butyl-dimethyl-silane (37). Cp2ZrHCl (1.719 g, 6.67 mmol) was added to a solution of 36 (1.372 g, 4.34 mmol) in dichloromethane (30 mL). The reaction was stirred for 30 min. at room temperature and N-iodosuccinimide (1.997 g, 8.88 mmol) was added. After 1 h, the reaction was poured into 100 mL of saturated NaHCO3 solution. The resulting mixture was extracted with dichloromethane (3×75 mL) and the combined organic extracts were dried (Na2SO4), filtered and evaporated. Purification by flash chromatography on silica gel (2% ethyl acetate/hexanes) gave 37 (1.7484 g, 91%).