1268
M. NAMUTEBI ET AL.
Reduction of Imines 2a:2b to Amino Sulfides 1a:1b:1c:1d Using NaBH4
NaBH4 (0.83 g, 22 mmol) was added carefully in small proportions to a solution of
imine 2a:2b (51:49) (1.09 g, 4.37 mmol) in dry MeOH (15 mL), while stirring the reaction
mixture, over a period of 30 minutes. The reaction was further stirred for 30 minutes at rt,
and then water (20 mL) was added to quench the reaction. The mixture was extracted with
EtOAc (3 × 15 mL), and the combined organic layers were the extracted with 1N HCl (20
mL); the resulting aqueous layer was treated with sat. NaHCO3 until basic (pH 8), then
extracted with CH2Cl2 (3 × 15 mL) and dried over MgSO4, and the solvent was removed
under reduced pressure to yield 1a:1b:1c:1d as mixture of four diastereoisomers. We were
unable to determine the ratio of diastereoisomers from the crude NMR, as the spectrum was
difficult and complex. The crude material was however purified via flash chromatography
(silica gel; petrol:EtOAc, 99:1, 1% NH3(aq)) to afford 1a (0.06 g, 6%), 1b (0.20 g, 18%), 1c
(0.19 g, 17%), and 1d (0.04 g, 4%). The assigned stereochemistries of the diastereoisomers
are based on COSY, HMQC, HMBC, NOE spectra and X-ray structures of derivatives of
1a and 1b (see below).
Diastereoisomer 1a (0.06 g, 6%); Rf 0.58 (petrol:EtOAc, 9:1, 2.5% NEt3); υmax
(neat)/cm−1 3340 (N H), 2890 (C H), 2850 (C H), 1053 (C N); δH (400 MHz; CDCl3);
3.02 (1H, dd, J 9.0, 6.1, C10H), 2.87 (1H, d, J 14.4, SCHH), 2.67 (1H, ddd, J 11.8, 9.6,
7.1, C8H), 2.51 (1H, d, J 14.4, SCHH), 2.47 (1H, ddd, J 11.8, 9.5, 7.1, C4H), 1.96–1.65
(7H, m, C5HH, C6HH, C7HH, C6HH, C12H, C11HH, C13HH), 1.60–1.53 (1H, m, C14HH),
1.47–1.32 (4H, m, C5HH, C7HH, C11HH, C14HH), 1.18–1.07 (2H, m, C13HH, NH), 1.06
(3H, s, CH3), 0.81 (3H, s, CH3); δC (101 MHz, CDCl3) 74.3 (C8), 68.5 (C10), 57.5 (C4),
55.8 (C15), 47.4 (C1), 45.7 (C12), 39.5 (C11), 34.7 (C2), 34.4 (C14), 31.0 (C7), 29.0
(C5), 26.8 (C13), 20.8 (CH3), 20.7 (C6), 19.8 (CH3); m/z (%) (EI+) 251.2 (32, M+), 141.1
(18), 128.1 (100), 100.1 (17), 67.1 (26); HRMS (EI+) C15H25NS requires: 251.1708; found
251.1707; [α]2D0 +16.0 (c 1.00, CHCl3); Anal. Calc’d for C15H25NS: C, 71.7; H, 10.0; N,
5.6; found: C, 71.9; H, 10.1; N, 5.4.
Diastereoisomer 1b (0.20 g, 18%); Rf 0.21 (petrol:EtOAc, 9:1, 2.5% NEt3); υmax
(neat)/cm−1 3340 (N H), 2890 (C H), 2850 (C H), 1055 (C N); δH (400 MHz; CDCl3);
3.39 (1H, ddd, J 10.6, 4.0, 2.2, C10H), 3.21 (1H, dt, J 10.4, 7.3, C8H), 2.76 (1H, dt, J 10.4,
8.6, C4H), 2.60 (1H, d, J 13.9, SC2HH), 2.33 (1H, d, J 13.9, SC2HH), 2.35–2.26 (1H, m,
C11HH), 2.20–1.86 (4H, m, C5HH, C7HH, C14HH, NH), 1.78–1.59 (3H, m, C6HH, C13HH,
C6HH), 1.56 (1H, t, J 4.6, C12H), 1.49–1.27 (3H, m, C5HH, C7HH, C14HH), 1.18 (1H,
ddd, J 12.9, 8.6, 4.6, C13HH), 0.87 (3H, s, CH3), 0.85 (3H, s, CH3), 0.72 (1H, 13.2, 4.0,
C11HH); δC (101 MHz, CDCl3) 68.1 (C8) 57.9 (C10), 55.8 (C15 or C1), 50.7 (C1 or C15),
48.2 (C4), 44.6 (C12), 39.7 (C11), 34.8 (C2), 34.7 (C14), 30.7 (C7), 27.9 (C13), 25.7 (C5),
21.3 (C6), 20.6 (CH3), 18.6 (CH3); m/z (%) (EI+) 251.2 (50, M+), 141.1 (33), 128.1 (100),
100.1 (25), 67.1 (37); HRMS (EI+) C15H25NS requires: 251.1708; found: 251.1706; [α]2D4
+39.3 (c 0.53, CHCl3); Anal. Calc’d for C15H25NS: C, 71.7; H, 10.0; N, 5.6; found: C,
71.6; H, 9.9; N, 5.4.
Diastereoisomer 1c (0.19 g, 17%); Rf 0.47 (petrol: EtOAc, 9:1, 2.5% NEt3); υmax
(neat)/cm−1 3341 (N H), 2889 (C H), 2853 (C H), 1055 (C N); δH (400 MHz; CDCl3);
3.54 (1H, dt, J 9.7, 7.3, C8H), 3.33 (1H, dt, J 9.7, 7.8, C4H), 3.31 (1H, d, J 13.9, SCHH), 3.21
(1H, dd, J 8.6, 5.4, C10H), 2.18 (1H, d, J 13.9, SCHH), 2.11–1.99 (2H, m, C5HH, C7HH),
1.77–1.64 (5H, m, C6HH, C6HH, C12H, C11HH, C13HH), 1.58–1.17 (6H, m, C11HH, C5HH,
C7HH, C14HH, C14HH, NH), 1.14–1.02 (1H, m, C13HH), 1.04 (3H, s, CH3), 0.81 (3H, s,
CH3); δC (101 MHz, CDCl3) 62.2 (C8), 61.9 (C10), 55.1 (C15), 47.4 (C1), 45.4 (C12),