C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=1[F:14].[N:15]1[O:16][CH2:17][C@@H:18]2[CH2:23][CH2:22][O:21][CH2:20][C:19]=12.B(F)(F)F.CCOCC>C1(C)C=CC=CC=1.O1CCCC1>[F:14][C:8]1[CH:9]=[C:10]([F:13])[CH:11]=[CH:12][C:7]=1[C@:19]12[CH2:20][O:21][CH2:22][CH2:23][C@H:18]1[CH2:17][O:16][NH:15]2n-Butyllithium (2.5 M solution in hexanes, 3.95 mL, 9.88 mmol) was added to a solution of 1-bromo-2,4-difluorobenzene (0.558 mL, 4.94 mmol) in a 1:3 mixture of tetrahydrofuran and toluene (25 mL) at −78° C., and the reaction mixture was stirred at this temperature for 1 hour. In a separate flask, a solution of (3aR)-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c][1,2]oxazole (C9) (628 mg, 4.94 mmol) in toluene (15 mL) was cooled to −78° C. and treated with boron trifluoride diethyl etherate (1.22 mL, 9.88 mmol); this mixture was also allowed to stir at −78° C. for 1 hour, and then added via cannula to the aryllithium solution. The reaction mixture was stirred for 1 hour and was then quenched with saturated aqueous ammonium chloride solution. After dilution with ethyl acetate, the layers were separated, and the organic layer was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. Chromatography on silica gel (Gradient: 0% to 40% ethyl acetate in heptane) provided the product. Yield: 610 mg, 2.53 mmol, 51%. The cis ring fusion was assigned on the basis of analogy with compound C17, whose stereochemistry was confirmed via single crystal X-ray analysis (vide infra). LCMS m/z 242.0 (M+1). 1H NMR (400 MHz, CD3OD) δ 1.75-1.93 (m, 2H), 3.03-3.10 (m, 1H), 3.53-3.76 (m, 4H), 3.95-4.02 (br m, 1H), 4.03 (dd, J=12.5, 1.8 Hz, 1H), 6.93-7.00 (m, 2H), 7.84-7.92 (m, 1H).
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