Reaction Steps
A solution of the product mixture containing β-hydroxy imine 31 (˜0.943 mmol) and imine 26 (˜0.178 mmol) in THF (3.50 mL) was cooled to −78° C. Ti(OEt)4 (0.469 mL, 2.24 mmol) was added, followed by NaBH4 (0.0847 g, 2.24 mmol), and the solution was stirred at −78° C. for 12 h. The solution was acidified using a 4:1 (v/v) solution of THF/AcOH (3.2 mL) followed by addition of EtOH (2 mL) and H2O (10 mL). The solution was warmed to rt and diluted with EtOAc. The mixture was washed once with brine, and the aqueous fraction was extracted once with EtOAc. The combined organic fractions were dried with Na2SO4, filtered, and concentrated. NMR analysis on the unpurified material established a 92:8 ratio of diastereomers. HPFC purification (100% EtOAc) produced 0.332 g (74%, over two steps) of the pure major diastereomer 32 as a colorless oil. [α]25D=+103.2 (c=1.0, CHCl3). IR (film): 1474, 1718, 2868, 2929, 2960, 3283 cm−1. 1H NMR (500 MHz, CDCl3): δ 0.90 (d, 3H, J=6.8 Hz), 0.93 (d, 3H, J=6.8 Hz), 1.29 (s, 9H), 1.40 (t, 3H, J=7.1 Hz), 1.70 (doublet of septets, 1H, J=2.3, 6.8 Hz), 1.91 (ddd, 1H, J=3.6, 11.5, 14.7 Hz), 2.30 (ddd, 1H, J=3.0, 11.8, 14.7 Hz), 3.30 (d, 1H, J=8.5 Hz), 3.40-3.47 (m, 1H), 4.38-4.45 (m, 2H), 5.18 (ddd, 1H, J=3.1, 6.7, 11.6 Hz), 5.48 (d, 1H, J=6.7 Hz), 8.11 (s, 1H). 13C NMR (125 MHz, CDCl3): δ 14.4, 17.3, 19.7, 23.0, 33.9, 40.6, 56.3, 58.5, 61.3, 67.8, 127.4, 147.0, 161.6, 177.6. HRMS (FAB) calcd. for C16H28N2O4NaS2 (M+Na): 399.1388. Found 399.1389.
