Reaction Steps
Prepared according to general procedure from crotonaldehyde (100 μL, 1.25 mmol), indole (146 mg, 1.25 mmol), 2,4-dinitrobenzoic acid (53 mg, 0.25 mmol) and (2S,5S)-5-benzyl-2-tert-butyl-3-methyl-imidazolidin-4-one (62 mg, 0.25 mmol) in CH2Cl2 (2.25 mL) and isopropanol (0.25 mL) at −60° C. for 19 h at which time an additional 30 μL (0.36 mmol) of crotonaldehyde was added. The reaction was allowed to continue stirring for an additional 3 h to provide, after silica gel chromatography (20:80 EtOAc/hexanes), the title compound as a colorless oil (168 mg, 72% yield, 91% ee). IR (film) 3408, 2962, 2875, 2833, 2729, 1716, 1617, 1451, 1420, 1337, 1223, 1099, 1010, 772, 741 cm−1; 1H NMR (300 MHz, CDCl3) δ 9.77 (dd, J=2.1, 2.1 Hz, 1H, CHO), 8.15 (s, 1H, NH), 7.68 (dt, J=0.6, 7.8 Hz, 1H, ArH), 7.35 (dt, J=1.5, 7.8 Hz, 1H, ArH), 7.27-7.15 (m, 2H, ArH), 6.94 (d, J=2.4 Hz, 1H, NCH), 3.68 (dt, J=7.2, 21 Hz, 1H, ArCH), 2.91 (ddd, J=2.4, 6.9, 16.2 Hz, 1H, CH2CO); 2.73 (ddd, J=2.1, 7.2, 16.2 Hz, 1H, CH2CO); 1.47 (d, J=6.9 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3) δ 203.0, 136.5, 126.1, 122.1, 120.7, 120.1, 119.3, 118.9, 111.4, 50.9, 26.0, 21.6; HRMS (CI) exact mass calcd for (C12H13NO) requires m/z 187.0997, found m/z 153.0993. [α]D=−2.2 (c=CHCl3). The enantiomeric ratio was determined by HPLC analysis of the alcohol, obtained by NaBH4 reduction of the aldehyde, using a Chiracel OD-H and OD guard column (10:90 ethanol/hexanes, 1 mL/min); S isomer tr=20.2 min and R isomer tr=17.6 min.
