Reaction SMILES: [CH2:1]([O:3][C:4](=[O:21])[CH:5]([CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=1)[CH2:6][CH:7]=[CH2:8])[CH3:2].[O:22]=[O+:23][O-:24].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C(Cl)Cl>[O:22]1[CH2:8][CH:7]([CH2:6][CH:5]([CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:19])([F:20])[F:18])[CH:12]=2)[C:4]([O:3][CH2:1][CH3:2])=[O:21])[O:24][O:23]1
Reactant: C=CCC(CCc1cccc(C(F)(F)F)c1)C(=O)OCC
Reactant: O=[O+][O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CCOC(=O)C(CCc1cccc(C(F)(F)F)c1)CC1COOO1
Temperature: -78 °C
Reaction time: 3 h
Yield: 25 %

Procedure:
3-(Trifluoromethyl)phenethyl alcohol (10.0 g, 52.6 mmol), triphenylphosphine (17.9 g, 68.4 mmol), and imidazole (5.00 g, 73.6 mmol) were dissolved in acetonitrile (42 mL) and ether (70 mL), then the mixture was cooled to 0° C. Iodine (18.7 g, 73.6 mmol) was added in portions, then the mixture was stirred for 4 h. The reaction mixture was diluted with ether (1 L), washed with saturated Na2S2O3 (3×300 mL), aqueous CuSO4 (2×300 mL), and brine (2×300 mL), dried over Na2SO4, filtered, and concentrated to a volume of 200 mL. The precipitate of triphenylphosphineoxide was removed by filtration and the filtrate was triturated with ether/hexanes (2:1, 300 mL). Additional triphenylphosphine-oxide was removed by filtration, and the filtrate was concentrated to dryness to provide 1-(2-iodoethyl)-3-trifluoromethylbenzene as a yellow oil (16.5 g, quantitative): 1H NMR (300 MHz, CDCl3) δ 7.54-7.35 (m, 4H), 3.37 (t, J=8.3 Hz, 2H), 3.24 (t, J=8.3 Hz, 2H); 19F NMR (282 MHz, CDCl3) δ −63.1. (35b) To a 100-mL three-neck round-bottomed flask equipped with a thermometer, addition funnel, and nitrogen inlet was added diisopropylamine (2.4 mL, 17.2 mmol) in THF (4 mL). The solution was cooled to −78° C., then a solution of n-BuLi (2.5 M in hexanes, 6.9 mL) was added slowly, followed by HMPA (3.1 mL, 18.0 mmol) and the reaction was stirred at this temperature for 30 min. A solution of ethylpent-4-enoate (2.0 g, 15.6 mmol) in THF (15.6 mL) was added dropwise, then the mixture was stirred for 45 min. To this mixture was added a solution of 1-(2-iodoethyl)-3-trifluoromethylbenzene (35a) (1.37 g, 4.58 mmol) in THF (2 mL) and the resulting mixture was allowed to warm to room temperature overnight. The mixture was diluted with ether (500 mL), washed with water (2×250 mL), and brine (2×250 mL), dried over Na2SO4, filtered, and evaporated. The residue was purified by flash chromatography to provide 2-[2-(3-trifluoromethylphenyl)ethyl]pent-4-enoic acid ethyl ester (529 mg, 39%) as a colorless oil: ESI MS m/z 301 [C16H19F3O2+H]+. (35c) 2-[2-(3-Trifluoromethylphenyl)ethyl]pent-4-enoic acid ethyl ester (529 mg, 1.76 mmol) was dissolved in CH2Cl2 and cooled to −78° C. The resulting solution was treated with ozone until a light blue color was observed. The solution was degassed with N2, then polymer-supported Ph3P (3 mmol/g, 882 mg, 2.64 mmol) was added and the mixture was stirred for 3 h at room temperature. The solid was removed by filtration and rinsed with CH2Cl2. Evaporation of the filtrate provided an oil, which was purified by flash column chromatography (hexanes/ether) to give ethyl 2-((1,2,3-trioxolan-4-yl)methyl)-4-(3-(trifluoromethyl)phenyl)butanoate as a colorless oil (151 mg, 25%) and the desired ethyl 2-(2-oxoethyl)-4-(3-(trifluoromethyl)phenyl)butanoate as a colorless oil (83 mg, 16%). A solution of ethyl 2-((1,2,3-trioxolan-4-yl)methyl)-4-(3-(trifluoromethyl)phenyl)butanoate (150 mg, 431 μmol) in CH2Cl2 (20 mL) was cooled to −78° C., then Me2S (0.3 mL, 4.1 mmol) was added and the mixture was stirred for 2 d. The reaction mixture was diluted with CH2Cl2 (300 mL), washed with water (2×100 mL), and brine (100 mL), dried over Na2SO4, filtered, and evaporated to provide additional ethyl 2-(2-oxoethyl)-4-(3-(trifluoromethyl)phenyl)butanoate (123 mg): 1H NMR (300 MHz CDCl3) δ 7.50-7.30 (m, 4H), 5.26-5.20 (m, 1H), 5.14 (d, J=1.6 Hz, 1H), 5.04 (d, J=6.3 Hz, 1H), 4.37 (q, J=7.0 Hz, 2H), 2.73-2.57 (m, 3H), 2.35-1.77 (m, 4H), 1.29 (t, J=7.1 Hz, 3H); 19F NMR (282 MHz, CDCl3) δ −63.0. (35d) Ethyl 2-(2-oxoethyl)-4-(3-(trifluoromethyl)phenyl)butanoate (83 mg, 275 μmol) and (7R,8S)-7-(benzene-4-sulfonylmethyl)-1,4-dioxa-spiro[4.5]dec-8-ylamine [3 g by substitution of phenyl disulfide into step (3d) and skipping step (3f)] (68 mg, 218 μmol) were dissolved in 1,2-dichloroethane (2.3 mL). The resulting solution was stirred at room temperature for 10 min, then sodium triacetoxyborohydride (58 mg, 275 μmol) was added and the mixture was stirred overnight. The reaction mixture was diluted with CH2Cl2 (400 mL), washed with saturated NH4Cl (3×150 mL), and brine (200 mL), dried over Na2SO4, filtered and evaporated. The residue was purified by flash column chromatography to give an inseparable mixture of diastereomers 4-(7-benzenesulfonylmethyl-1,4-dioxaspiro[4.5]dec-8-ylamino)-2-[2-(3-trifluoromethylphenyl)ethyl]butyric acid ethyl ester (64 mg, 49%): ESI MS m/z 598 [C30H38F3NO6S+H]+. (35e) The mixture of diastereomers from above (35d) (92 mg, 154 mmol) was dissolved in MeOH (10 mL) and NaOMe (85 mg) was added. The mixture was heated at 50° C. for 16 h, then diluted with EtOAc (300 mL). The mixture was washed with water (3×150 mL) and brine (200 mL), dried over Na2SO4, and evaporated in vacuo to dryness. The residue was purified by flash column chromatography to provide (1S,2R)-1-(7-benzenesulfonylmethyl-1,4-dioxaspiro[4.5]dec-8-yl)-3(R)-[2-(3-trifluoromethylphenyl)ethyl]pyrrolidin-2-one (upper TLC spot; 30 mg, 35%): 1H NMR (300 MHz, CDCl3) δ 7.88-7.80 (m, 2H), 7.62-7.35 (m, 7H), 4.03-3.70 (m, 6H), 3.52-3.39 (m, 1H), 3.37-3.25 (m, 1H), 3.06 (dd, J=14.6, 2.1 Hz, 1H), 2.88-2.67 (m, 3H), 2.33-1.55 (m, 11H); 19F NMR (282 MHz, CDCl3) δ −63.0; ESI MS m/z 552 [C28H32F3NO5S+H]+; and (1S, 2R)-1-(7-benzenesulfonylmethyl-1,4-dioxaspiro[4.5]dec-8-yl)-3(S)-[2-(3-trifluoromethylphenyl)ethyl]pyrrolidin-2-one (lower TLC spot; 34 mg, 41%) 1H NMR (300 MHz, CDCl3) δ 7.88-7.80 (m, 2H), 7.60-7.35 (m, 7H), 4.03-3.73 (m, 6H), 3.40-3.25 (m, 2H), 2.97 (dd, J=14.3, 1.9 Hz, 1H), 2.80-2.62 (m, 3H), 2.40-1.40 (m, 11H); 19F NMR (282 MHz, CDCl3) δ −63.0; ESI MS m/z 552 [C28H32F3NO5S+H]+. (35f) (1S,2R)-1-(7-benzenesulfonylmethyl-1,4-dioxaspiro[4.5]dec-8-yl)-3(R)-[2-(3-trifluoromethylphenyl)ethyl]pyrrolidin-2-one (29 mg, 53 mmol) and p-TsOH (4 mg) in acetone (5 mL) was stirred overnight at room temperature. A second portion-of p-TsOH (4 mg) was added and the reaction mixture was stirred for an additional 24 h. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography to afford (R)-3-(3-(trifluoromethyl)phenethyl)-1-((1S,2R)-4-oxo-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one (17 mg, 64%) as a white solid: ESI MS m/z 508 [C26H28F3NO4S+H]+. (35 g) To a stirred mixture of the above compound (35f) (17 mg, 34 mmol) and titanium(IV) isopropoxide (0.5 mL, 1.67 mmol) was added 2-propylamine (36 mg, 600 mmol). The mixture was stirred at room temperature for 3 h, then MeOH (5 mL) was added, followed by NaBH4 (3.5 mg, 94 mmol). After 2 h, the reaction mixture was quenched with 0.5 M NaOH (30 mL) and the resulting mixture was stirred for 2 h. The mixture was diluted with EtOAc (400 mL), washed with 0.5 M NaOH (3×150 mL) and brine (200 mL), dried over Na2SO4, filtered, and evaporated. Purification of the residue by semi-preparative HPLC gave the title compound (10 mg) as a mixture of diastereomers: 1H NMR (300 MHz, CDCl3) δ 8.00-7.75 (m, 2H), 7.73-7.30 (m, 7H), 4.60-1.50 (m, 20H), 1.49-1.20 (m, 6H).