Reaction Steps
A solution of freshly distilled hydrocinnamaldehyde (132 μL, 1.0 mmol) in 500 μL dimethylformamide was added slowly over the course of 24 h to a stirring suspension of isobutyraldehyde (272 μL, 3.0 mmol), L-proline (11.5 mg, 0.10 mmol) and 500 μL dimethylformamide at room temperature. After 26 h, the resulting solution was diluted with ethyl acetate and washed successively with water and brine. The combined aqueous layers were back-extracted with 3 portions dichloromethane. The organic layers were combined, dried over anhydrous Na2SO4, and concentrated in vacuo. Flash chromatography (3:1 hexanes:ethyl acetate) afforded the title compound as a clear, colorless oil in 75% yield (155 mg, 0.75 mmol), 91% ee and 95:5 anti:syn. IR (film) 3466, 3086, 3063, 3028, 2962, 2932, 2834, 2733, 1950, 1875, 1806, 1722, 1604, 1496, 1454, 1390, 1368, 1244, 1180, 1136, 1049, 1031, 993.0, 964.3, 849.7, 800.6, 739.8, 700.2 cm−1; 1H NMR (300 MHz, CDCl3) δ9.83 (d, 1H, J=2.1 Hz, CHO); 7.27 (m, 5H, Ar—H); 3.43 (ddd, 1 H, J=6.6, 6.6, 4.5 Hz, CHOH); 3.06 (dd, 1H, J=13.2, 7.8 Hz, PhCH2); 2.92 (dd, 1H, J=13.2, 6.9 Hz, PhCH2); 2.81 (m, 1H, CHCH2); 2.15 (d, 1H, J=6.0 Hz, OH); 1.90 (m, 1H, CH(CH3)2); 0.96 (d, 3H, J=6.6 Hz, CH(CH3)2); 0.92 (d, 3H, J=7.2 Hz, CH(CH3)2); 13C NMR (75 MHz, CDCl3) δ205.6, 129.2, 128.9, 128.6, 126.8, 76.9, 55.8, 33.4, 32.0, 19.7, 18.2; HRMS (CI) exact mass calcd for [M+H]+ (C13H19O2) requires m/z 207.1385, found m/z 207.1386; [α]D=−7.9 (c=1.0, CHCl3). The product ratios were determined by HPLC analysis of the corresponding alcohol (obtained by NaBH4 reduction) using a Chiracel OJ and OJ guard column (1.0% ethanol/hexanes, 1 mL/min); (2S, 3S) anti isomer tr=7.5 min, (2R, 3R) anti isomer tr=9.4 min, (2R, 3S) and (2S, 3R) syn isomers tr=6.3, 6.9 min.
