Reaction SMILES: I[CH2:2][CH2:3][C:4]([O:6][CH3:7])=[O:5].[F:8][C:9]([F:20])([F:19])[C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][CH:18]=1)[C:13](Cl)=[O:14]>C1C=CC=CC=1.CC(N(C)C)=O.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:7][O:6][C:4](=[O:5])[CH2:3][CH2:2][C:13](=[O:14])[C:12]1[CH:16]=[CH:17][CH:18]=[C:10]([C:9]([F:8])([F:19])[F:20])[CH:11]=1
Reactant: COC(=O)CCI
Reactant: O=C(Cl)c1cccc(C(F)(F)F)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CC(=O)N(C)C
Solvent: c1ccccc1
Solvent: CCOC(C)=O
Product: COC(=O)CCC(=O)c1cccc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 89.4 %

Procedure:
A mixture of methyl 3-bromopropionate (6a, 10.0 g, 60.0 mmol) and sodium iodide (11.2 g, 74.9 mmol) in acetone (60 mL) was stirred for 30 min at room temperature, then heated at reflux for 40 min. The mixture was cooled in an ice/water bath and the white solid was filtered off, rinsing with acetone. The filtrate was evaporated to dryness to provide methyl 3-iodopropionate (12.3 g, 96%) as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 3.73 (s, 3H), 3.33 (t, J=7.2 Hz, 2H), 2.99 (t, J=7.2 Hz, 2H). (39b) To a 250-mL three-neck round-bottomed flask equipped with a thermometer, condenser, and nitrogen inlet was added Zn—Cu couple (3.41 g, 52.1 mmol). A solution of methyl 3-iodopropionate (7.27 g, 34.0 mmol) in benzene (67.7 mL) and DMA (4.5 mL) was added over 5 min and the mixture was stirred at room temperature for 1 h, then heated at 60° C. for 5 h. A mixture of Pd(PPh3)4 (1.05 g, 0.906 mmol) in benzene (22.7 mL) was added to the reaction and stirred at 60° C. for 5 min. The mixture was then removed from heat and 3-(trifluoromethyl)benzoyl chloride (3.4 mL, 23 mmol) in benzene (11.3 mL) was added immediately. After stirring for 2 h, the mixture was diluted with EtOAc, washed with 1 M HCl (3×200 mL), NaHCO3 (2×200 mL) and brine (1×200 mL), dried over Na2SO4, filtered, and evaporated. The crude material was purified by CombiFlash chromatography (silica, 0-70% ether/hexanes) to give 4-oxo-4-(3-trifluoromethylphenyl)butyric acid methyl ester (5.35 g, 91%) as an orange oil: 1H NMR (300 MHz CDCl3) δ 8.24 (s, 1H), 8.17 (d, J=7.8 Hz, 1H), 7.84 (d, J=7.8 Hz, 1H), 7.63 (t, J=7.8 Hz, 1H), 3.72 (s, 3H), 3.35 (t, J=6.5 Hz, 2H), 2.81 (t, J=6.5 Hz, 2H); 19F NMR (282 MHz, CDCl3) δ −63.3; ESI MS m/z 261 [C12H11F3O3+H]+. (39c) A solution of 4-oxo-4-(3-trifluoromethylphenyl)butyric acid methyl ester (2.47 g, 9.50 mmol), trimethylorthoformate (4.8 mL), p-TsOH (181 mg, 0.95 mmol) and ethylene glycol (7.3 mL) was heated at 50° C. for 3 h. The mixture was diluted with EtOAc (500 mL), washed with saturated NaHCO3 (3×200 mL), water (2×200 mL), and brine (150 mL), dried over Na2SO4, filtered and evaporated to give a mixture of esters. The mixture was stirred in MeOH (25 mL) with NaOMe (400 mg) at room temperature for 6 h. The reaction was quenched with saturated NH4Cl and the methanol was removed by evaporation. The residue was dissolved in EtOAc, washed with saturated NH4Cl (2×200 mL), water (2×200 mL) and brine (200 mL), dried over Na2SO4, and evaporated to give 3-[2-(3-trifluoromethylphenyl)-[1,3]dioxolan-2-yl]propionic acid methyl ester (2.71 g, 94%) as a light yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.73 (s, 1H), 7.65 (d, J=7.7 Hz, 1H), 7.56 (d, J=7.7 Hz, 1H), 7.47 (t, J=7.7 Hz, 1H), 4.10-3.99 (m, 2H), 3.80-3.70 (m, 2H), 3.65 (s, 3H), 2.44 (t, J=7.8 Hz, 2H), 2.24 (t, J=7.8 Hz, 2H); 19F NMR (282 MHz, CDCl3) δ −62.9; ESI MS m/z 305 [C14H15F3O4+H]+. (39d) Diisopropylamine (1.74 mL, 12.5 mmol) was dissolved in THF (6.2 mL) under a nitrogen atmosphere and cooled to −78° C. A solution of n-BuLi (2.5 M in hexanes, 5.3 mL) was added dropwise, keeping the temperature below −67° C. The reaction was warmed to −15° C. for 15 min, then cooled back down to −78° C. A solution of 3-[2-(3-trifluoromethylphenyl)-[1,3]dioxolan-2-yl]propionic acid methyl ester (2.71 g, 8.90 mmol) in THF (1.5 mL) was added and the mixture was stirred for 40 min. Allyl bromide (0.92 mL, 11 mmol) and HMPA (0.46 mL, 2.7 mmol) were added simultan-eously and the reaction was stirred at room temperature overnight. The mixture was diluted with EtOAc (400 mL), washed with saturated NH4Cl (3×150 mL), water (2×150 mL), and brine (200 mL), dried over Na2SO4, filtered, and evaporated. The residue was purified by CombiFlash chromatography (silica, 0-40% ether/heptane) to give 2-[2-(3-trifluoromethylphenyl)-[1,3]dioxolan-2-ylmethyl]pent-4-enoic acid methyl ester (1.82 g, 59%) as a light yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.73 (s, 1H), 7.64 (d, J=7.7 Hz, 1H), 7.56 (d, J=7.7 Hz, 1H), 7.46 (t, J=7.7 Hz, 1H), 5.80-5.61 (m, 1H), 5.10-4.97 (m, 2H), 4.10-3.90 (m, 2H), 3.80-3.60 (m, 5H), 2.83-2.68 (m, 1H), 2.50-2.13 (m, 3H), 1.97 (dd, J=14.7, 2.7 Hz, 1H); 19F NMR (282 MHz, CDCl3) δ −62.9; ESI MS m/z 345 [C17H19F3O4+H]+. (39e) A solution of 2-[2-(3-trifluoromethylphenyl)-[1,3]dioxolan-2-ylmethyl]pent-4-enoic acid methyl ester (1.82 g, 5.29 mmol) in CH2Cl2 (250 mL) was cooled to −78° C. and ozone was bubbled into the solution until a light blue solution was obtained. The solution was degassed with nitrogen, then dimethylsulfide (4 mL) was added dropwise. The mixture was stirred overnight at room temperature, then heated at reflux for 24 h. The reaction was diluted with CH2Cl2 (500 mL), washed with 1 M HCl (3×150 mL) and brine (200 mL), dried over Na2SO4, filtered, and evaporated. The residue was purified by CombiFlash chromatography (silica, 0-50% ether/hexanes) to give aldehyde 4-oxo-2-[2-(3-trifluoromethylphenyl)-[1,3]dioxolan-2-ylmethyl]butyric acid methyl ester (1.41 g, 77%) as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 9.74 (s, 1H), 7.72 (s, 1H), 7.63 (d, J=7.7 Hz, 1H), 7.57 (d, J=7.7 Hz, 1H), 7.47 (t, J=7.7 Hz, 1H), 4.12-3.95 (m, 2H), 3.83-3.64 (m, 5H), 3.27-3.13 (m, 1H), 2.98-2.70 (m, 2H), 2.40 (dd, J=14.8, 7.2 Hz, 1H), 2.04 (dd, J=14.8, 5.5 Hz, lH); 19F NMR (282 MHz, CDCl3) δ −62.9. (39f) A mixture of (1S*,2R*,4R*)-4-azido-2-benzenesulfonylmethyl-cyclohexylamine (see 37c) (676 mg, 2.30 mmol) and 4-oxo-2-[2-(3-trifluoromethylphenyl)-[1,3]dioxolan-2-ylmethyl]butyric acid methyl ester (794 mg, 2.30 mmol) in 1,2-dichloroethane (46 mL) was stirred at room temperature overnight. The solvent was removed under vacuum, then the residue was dissolved in MeOH (35 mL) and cooled to 0° C. Sodium borohydride (872 mg, 23.0 mmol) was added in one portion and the mixture was stirred for 4 h. The reaction was diluted with EtOAc (500 mL), washed with saturated NaHCO3 (3×150 mL) and brine (200 mL), dried over Na2SO4, filtered, and evaporated. The residue was purified by CombiFlash chromatography (silica, 0-100% ether/hexanes) to give a mixture of diastereomers methyl 4-((1S*,2R*,4R*)-4-azido-2-(phenylsulfonylmethyl)cyclohexylamino)-2-((2-(3-(trifluoromethyl)phenyl)-1,3-dioxolan-2-yl)methyl)butanoate (1.04 g, 70%) as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 8.00-7.88 (m, 2H), 7.75-7.52 (m, 6H), 7.51-7.41 (m, 1H), 4.17-3.88 (m, 2H), 3.80-3.60 (m, 5H), 3.59-3.48 (m, 1H), 3.45-3.30 (m, 1H), 3.10-2.98 (m, 1H), 2.85-2.55 (m, 3H), 2.50-2.20 (m, 3H), 2.00-1.30 (m, 9H); 19F NMR (282 MHz, CDCl3) δ −62.9, −β 8; ESI MS m/z 625 [C29H35F3N4O6S+H]+. (39 g) A stirred mixture of diastereomers 39f (1.04 g, 1.66 mmol) and NaOMe (90 mg, 1.66 mg) in MeOH (20 mL) was heated at reflux for 4 d. The solvent was removed under vacuum and the residue was dissolved in EtOAc (350 mL). The organic mixture was washed with saturated NH4Cl (3×100 mL), water (200 mL), and brine (200 mL), dried over Na2SO4, filtered, and evaporated. The crude material was purified by CombiFlash chromatography followed by preparative TLC to give (S*)-1-((1S*,2R*,4R*)-4-azido-2-(phenylsulfonylmethyl)cyclohexyl)-3-((2-(3-(trifluoromethyl)phenyl)-1,3-dioxolan-2-yl)methyl)pyrrolidin-2-one (39 g-a, 359 mg, 36%) and (R*)-1-((1S*,2R*,4R*)-4-azido-2-(phenylsulfonylmethyl)cyclohexyl)-3-((2-(3-(trifluoromethyl)phenyl)-1,3-dioxolan-2-yl)methyl)pyrrolidin-2-one (39 g-b, 322 mg, 33%) as white solids.