3294
A. L. Braga et al. / Tetrahedron 57 72001) 3291±3295
5.74 /s, 1H), 4.14±4.08 /m, 1H), 3.45±3.25 /m, 1H), 3.15±
2.80 /m, 1H). Isomer B: d 7.63 /s, 1H), 6.5±6.2 /m, 2H),
5.59 /s, 1H), 3.86 /dd, 1H, J7.0 Hz, J8.8 Hz), 3.45±3.25
/m, 1H), 3.15±2.80 /m, 1H). 13C NMR /100 MHz, DMSO-
d6) Isomer A: d 37.81, 63.92, 64.77, 106.34, 110.35, 142.43,
154.44, 172.54 Isomer B: d 38.11, 64.21, 65.35, 107.52,
110.65, 142.91, 151.38, 172.20. Anal. Calcd for
C8H9NO3S: C, 48.23; H, 4.55; N, 7.03. Found: C, 48.01;
H, 4.43; N, 6.97.
3 mmol) and p-toluenesulfonic acid /10 mg). The mixture
was heated at re¯ux for 5 h and cooled to room temperature.
The benzene was removed under vacuum and the residue
dissolved in CH2Cl2 /30 mL), washed with 0.5N NaOH
aquous solution, dried with MgSO4, ®ltered, and the solvent
removed under vacuum to afford 3.
20
1
3a. Yield: 87%; [a]D 114.8 /c 1.96, CHCl3); H NMR
/200 MHz, CDCl3) d 7.34±7.19 /m, 10H), 4.29 /s, 4H), 4.04
/dd, 2H, J7.0 Hz, J8.4 Hz), 3.76±3.70 /m, 4H), 3.48 /dd,
2H, J5.0 Hz, J8.4 Hz), 3.36±3.21 /m, 2H), 2.76 /dd, 2H,
J5.8 Hz, J13.2 Hz), 2.47 /dd, 2H, J8.4 Hz, J
13.2 Hz); 13C NMR /50 MHz, CDCl3) d 41.08; 58.92;
62.06; 69.06; 85.98; 127.19; 127.97, 128.24, 128.40,
128.60. Anal. Calcd for C22H28N2O2S2: C, 63.43; H, 6.77;
N, 6.72. Found: C, 63.20; H, 7.26; N, 7.10.
4.1.2. Amino alcohol disul®de ꢀ2). In a 100 mL two necked
round-bottomed ¯ask equipped with a re¯ux condenser and
an addition funnel, dry THF /85 mL), NaBH4 /3.24 g;
85.5 mmol) and 1 /34.2 mmol) were introduced under
argon atmosphere. Under stirring, iodine /8.68 g;
34.2 mmol) dissolved in THF /30 mL) was added slowly.
After complete addition, the reaction mixture was heated at
re¯ux for 20 h and then cooled to room temperature. Metha-
nol was added to the mixture until a clear solution was
obtained. The solvent was removed under vacuum and the
residue dissolved in 70 mL of a 20% aqueous K2CO3 solu-
tion, stirring for 4 h at room temperature. After the mixture
was extracted with CH2Cl2 /3£30 mL) and the organic layer
dried with MgSO4 and ®ltered, the solvent was removed in
vacuo.
20
1
3b. Yield: 92%; [a]D 230.32 /c 0.8, CH2Cl2); H NMR
/400 MHz, CD3OD) d 7.23 /d, 4H, J7.8 Hz), 7.11 /d, 4H,
J7.8 Hz), 4.32 /s, 4H), 4.05 /m, 2H,), 3.72 /m, 4H), 3.50
/dd, 2H, J5.0 Hz, J8.2 Hz), 3.33 /dd, 2H, J6.30 Hz,
J13.2 Hz), 2.78 /dd, 2H, J6.3 Hz, J13.20 Hz), 2.50
/dd, 2H, J8.2 Hz, J13.2 Hz), 2.33 /s, 6H); 13C NMR
/100 MHz, CDCl3) d 21.02; 41.83; 58.63; 62.31; 69.09;
85.95; 128.68; 128.95; 135.53; 136.79. Anal. Calcd for
C24H32N2O2S2: C, 64.83; H, 7.25; N, 6.30. Found: C,
64.56; H, 7.24; N, 6.79.
20
2a. Yield: 75%; mp 105.7±106.18C; [a]D 229.0 /c 1.0,
CH3OH); 1H NMR /400 MHz, DMSO-d6) d 7.30±7.17 /m,
10H), 3.74 /s, 4H), 3.44±3.37 /m, 4H), 2.90±2.74 /m, 6H);
13C NMR /50 MHz, DMSO-d6) d 40.90; 50.31; 57.90;
61.82; 126.53; 127.90, 128.07. Anal. Calcd for
C20H28N2O2S2: C, 61.19; H, 7.19; N, 7.14. Found: C,
60.84; H, 6.84; N, 7.13.
20
1
3c. Yield: 93%; [a]D 22 /c 0.64, CH2Cl2); H NMR
/200 MHz, CDCl3) d 7.26 /d, 4H, J8.7 Hz), 6.84 /d, 4H,
J8.7 Hz), 4.30 /s, 4H), 4.05 /dd, 2H, J7.0 Hz, J
8.5 Hz), 3.78 /s, 6H), 3.70 /dd, 4H, J6.0 Hz, J8.5 Hz),
3.50 /dd, 2H, J5.0 Hz, J8.5 Hz), 2.79 /dd, 2H, J
6.0 Hz, J13.2 Hz), 2.51 /dd, 2H, J8.5 Hz, J13.2 Hz);
13C NMR /100 MHz, CDCl3) d 41.95, 55.16, 58.31, 62.26,
69.12, 85.88, 113.61, 129.95, 130.70, 158.83. Anal. Calcd
for C24H32N2O4S2: C, 60.48; H, 6.77; N, 5.88. Found: C,
60.73; H, 6.41; N, 5.49.
20
2b. Yield: 94%; mp 110±110.68C; [a]D 285 /c 0.62,
1
CH2Cl2); H NMR /400 MHz, DMSO-d6) d 7.21 /d, 4H,
J8.0 Hz), 7.08 /d, 4H, J8.0 Hz), 3.71 /s, 4H,), 3.55±
3.40 /m, 4H), 2.91±2.85 /m, 4H), 2.82±2.77 /m, 2H), 2.26
/s, 6H); 13C NMR /100 MHz, DMSO-d6) d 20.75; 40.94;
50.19; 57.91; 61.91; 127.94; 128.73; 135.57; 137.82. Anal.
Calcd for C22H32N2O2S2: C, 62.82; H, 7.67; N, 6.66. Found:
C, 62.68; H, 7.50; N, 6.62.
1
20
3d. Yield: 75%; [a]D 248 /c 0.52, CH2Cl2); H NMR
/200 MHz, CDCl3) d 7.39 /s, 2H); 6.33±6.23 /m, 4H);
4.45 /d, 2H, J6.0 Hz); 4.35 /d, 2H, J6.0 Hz); 4.12±
4.01 /m, 2H); 3.78 /s, 4H); 3.55±3.33 /m, 4H); 2.83 /dd,
2H, J6.0 Hz, J13.4 Hz); 2.55 /dd, 2H, J7.9 Hz, J
13.4 Hz); 13C NMR /50 MHz, CDCl3) d 41.73; 51.14;
62.00; 69.20; 85.70; 108.53; 110.13; 142.34; 151.88.
Anal. Calcd for C18H24N2O4S2: C, 54.52; H, 6.10; N, 7.06.
Found: C, 54.76; H, 5.93; N, 6.79.
20
2c. Yield: 86%; mp 88.4±898C; [a]D 298 /c 0.52,
1
CH2Cl2); H NMR /400 MHz, DMSO-d6) d 7.24 /d, 4H,
J8.1 Hz), 6.84 /d, 4H, J8.1 Hz), 3.71 /s, 6H,), 3.67 /s,
4H), 3.50±3.41 /m, 4H), 2.91±2.80 /m, 4H), 2.78±2.72 /m,
2H). 13C NMR /100 MHz, DMSO-d6) d 40.94; 49.75;
54.95; 57.78; 61.84; 113.48; 129.08; 132.80; 158.03.
Anal. Calcd for C22H32N2O4S2: C, 58.38; H, 7.13; N, 6.19.
Found: C, 58.30; H, 6.97.
4.2. General procedure for asymmetric addition of
diethylzinc to aldehydes
20
1
2d. Yield: 76%; [a]D 255 /c 0.80, CH2Cl2); H NMR
/400 MHz, CDCl3) d 7.34 /s, 2H), 6.28 /s, 2H), 6.18 /s, 2H),
3.76 /s, 4H), 3.66±3.44 /m, 4H), 2.90±2.67 /m, 4H), 2.62±
2.42 /m, 2H); 13C NMR /100 MHz, CDCl3) d 23.73; 41.91;
58.85; 61.28; 106.54; 109.60; 141.58; 152.34. Anal. Calcd
for C16H24N2O4S2: C, 51.59; H, 6.49; N, 7.52. Found: C,
51.57; H, 6.45; N, 7.48.
In a 25 mL ¯ask with toluene /7 mL), aldehyde /3 mmol)
and catalyst /60 mmol; 2 mol%), a 1 M hexane solution of
diethylzinc /5 mL; 5 mmol) was slowly injected under
constant stirring. Stirring was continued for the time and
at the temperature indicated in Table 1. Finally the tempera-
ture was adjusted to 08C /ice bath) and 1N HCl /5 mL) was
slowly added /10 min) with continuous stirring. The organic
layer was separated and washed with 2£8 mL of 1N HCl.
After drying over sodium sulfate and ®ltration the toluene
was removed under reduced pressure. The crude alcohol
4.1.3. Oxazolidine disul®de ꢀ3). In a 50 mL round-
bottomed ¯ask with Dean±Stark apparatus was added
benzene /30 mL), 2 /1 mmol), p-formaldehyde /90 mg;