Reaction Steps
Prepared according to the general procedure from 4-benzyloxy-but-2-enal (143 mg, 0.750 mmol), 6-chloro-1H-indole (75.8, 0.500 mmol), 2,4-dinitrobenzoic acid (21.2 mg, 0.100 mmol) and (2S,5S)-5-benzyl-2-tert-butyl-3-methyl-imidazolidin-4-one (24.6 mg, 0.100 mmol) in CH2Cl2 (0.90 mL) and isopropanol (0.10 mL) at −60° C. for 12.75 h to provide, after silica gel chromatography (CH2Cl2), the title compound as a colorless oil (124 mg, 73% yield, 97% ee) after silica gel chromatography in CH2Cl2. IR (film) 3383, 2953, 2930, 2834, 2734, 1718, 1623, 1603, 1548, 1453, 1403, 1378, 1273, 1184, 1104, 1069, 1019, 909, 804, 774, 714 cm−1; 1HNMR (300 MHz, CDCl3) δ 9.77 (dd, J=1.8, 1.8 Hz, 1H, CHO), 8.15 (s, 1H, NH), 8.02-7.99 (m, 2H, ArH), 7.65 (dd, J=0.6, 8.7 Hz, 1H, ArH), 7.58 (tt, J=1.5, 6.6 Hz, 1H, ArH), 7.48-7.42 (m, 2H, ArH), 7.37 (d, J=1.8 Hz, 1H NCH), 7.12 (dt, J=2.1, 8.7 Hz, 2H, ArH), 4.70 (dd, J=5.1, 10.8 Hz, 1H, CH2O), 4.42 (dd, J=8.4, 11.1 Hz, 1H, CH2O), 4.08 (m, 1H, ArCH), 3.06 (ddd, J=1.8, 6.3. 16.8 Hz, 1H, CH2CO); 2.95 (ddd, J=2.1, 7.8, 16.5 Hz, 1H, CH2CO); 13C NMR (75 MHz, CDCl3) δ 200.9, 166.5, 136.7, 135.4, 133.2, 129.9, 129.6, 128.5. 125.1, 122.3, 120.7, 119.8, 115.0, 111.4, 67.8, 46.5, 31.0; HRMS (CI) exact mass calcd for (C19H16ClNO3) requires m/z 341.0819, found m/z 341.0814.[α]D=−3.3 (c=1.0 CHCl3). The enantiomeric ratio was determined by HPLC analysis of the alcohol, obtained by NaBH4 reduction of the aldehyde, using a Chiracel AD and AD guard column (10:90 ethanol/hexanes, 1 mL/min); S isomer tr=38.8 min and R isomer tr=43.3 min.
