Tetrahydrofuran → (1S,2S)-6,7-Difluoro-2-methoxy-1,2-dihydro-naphthalen-1-ol
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[CH:8]1[O:13][CH:5]2[CH:6]=[CH:7]1.C1C[O:17][CH2:16]C1>CO>[F:12][C:11]1[CH:10]=[C:9]2[C:4](=[CH:3][C:2]=1[F:1])[C@H:5]([OH:13])[C@@H:6]([O:17][CH3:16])[CH:7]=[CH:8]2Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To a flame dried round bottom flask, [Rh(COD)Cl]2 (2.5 mg, 0.005 mmol), (S)-(R)-PPF-PtBu2 (5.4 mg, 0.010 mmol) and 24 (72 mg, 0.40 mmol) were added followed by addition of THF (1.0 mL) and methanol (1.0 mL). The mixture was heated to reflux for 1 hour. The solvents were then removed in vacuo. The resulting solid was purified by flash chromatography (20% ethyl acetate in hexanes) to give 27 as a white crystalline solid (74.9 mg, 88%). The ee was determined to be 96.4% using HPLC analysis on a CHIRALCEL OD column, λ=486 nm. Retention times in 4% isopropanol in hexanes were 8.9 min and 10.1 min (major). Rf=0.27 on silica gel (30% ethyl acetate:hexanes); mp 129-131° (Et2O); [α]25D=+134.4° (c=9.3, CHCl3); IR (KBr, cm−1) 3269 (br), 2937 (w), 1597 (m), 1503 (s), 1306 (s), 1103 (s), 893 (s); 1H NMR (400 MHz, CDCl3) δ7.40 (1H, ddd, JH-F=10.8, 7.8 Hz, JH-H=0.6 Hz), 6.85 (1H, dd, JH-F=10.9, 7.8 Hz), 6.31 (1H, dd, J=10.0, 2.0 Hz), 6.05 (1H, dd, J=10.0, 2.0 Hz), 4.79 (1H, d, J=11.0 Hz), 4.05 (1H, ddd, J=11.0, 2.0, 2.0 Hz), 3.49 (3H, s), 2.94 (1H, d, J=2.2 Hz); 13C NMR (400 MHz, CDCl3) δ151.0 (d, JH-F=12.5 Hz), 148.5 (dd, JH-F=12.5,2.9 Hz), 133.2 (dd, JH-F=5.2, 3.6 Hz), 128.9 (dd, JH-F=6.6, 4.4 Hz), 128.0 (d, JH-F=2.2 Hz), 126.5 (dd, JH-F=2.2, 1.5 Hz), 115.1 (d, JH-F=18.3 Hz), 114.8 (d, JH-F=19.8 Hz), 82.3, 72.0, 57.0. HRMS calcd for C11H10O2F2 (M+): 212.0649. Found: 212.0658.