Ait-Youcef et al.
JOCNote
Experimental Section
colorless oil; [R]25D = -5.9 (c 0.5, CHCl3); IR (ATR, cm-1) 2944,
2922, 2855, 2161, 2013, 1974, 1704, 1471, 1255, 1218, 1082, 834; 1H
NMR (300 MHz, CDCl3) δ -0.07-0.10 (m, 12H), 0.84-0.90 (m,
21H), 1.09-1.31 (m, 28H), 3.46-4.01 (m, 3H), 4.12-4.40 (m, 1H),
5.04-5.29 (m, 4H), 6.19-6.52 (s, 1H), 7.20-7.46 (m, 10H);
13C NMR (300 MHz, CDCl3) δ 157.7, 156.9, 156.6, 156.1, 135.9,
135.7, 135.5, 128.6, 128.5, 128.4, 128.4, 128.2, 128.2, 128.0, 127.6,
127.6, 71.0, 70.7, 68.4, 67.9, 67.6, 67.4, 61.2, 61.2, 33.6, 33.4, 31.9,
30.0, 29.6, 29.6, 29.5, 29.3, 22.6, 17.9, 14.1, 14.0, -4.0, -4.1, -4.9,
-5.0, -5.5, -5.6. Anal. Calcd for C46H80N2O6Si2: C, 67.93; H,
9.91; N, 3.44. Found: C, 68.21; H, 10.14; N, 3.61.
General Procedure for Hydrogenation Reaction at Atmo-
spheric Pressure. A solution of the β-keto ester 3 (500 mg,
2.18 mmol) or 4 (500 mg, 1.60 mmol) was diluted in degassed
methanol (4 mL). This solution was canulated into a Schlenk
tube and degassed by three cycles of vacuum/argon. The mixture
was added to the in situ generated catalyst (2 mol % [(R)-
10
BinapRu]Br2 in a glass vessel and placed under argon. The
argon atmosphere was replaced with 6 atm of hydrogen, and the
mixture was heated to 50 °C. The solvent was evaporated under
vacuum, and the β-hydroxy esters were purified on a short pad
of silica using a pentane/Et2O = 8/2 mixture.
General Procedure for the Organocatalytic r-Amination. To a
solution of 7 or 8 (1.72 mmol) in CH2Cl2 (10 mL) was added
DIBAL-H (1.80 mmol, 1 M in hexane) at -78 °C. The mixture
was stirred for 30 min, and then MeOH (1 mL) and HCl (1 N)
(3 mL) were added, and the solution was stirred during 30 min
at rt. The layers were separated, and the aqueous layer was ex-
tracted with CH2Cl2. The combined organic layers were washed
with water and then brine, dried over MgSO4, and concentrated
in vacuo. The crude aldehyde was immediately dissolved in
MeCN (10 mL). To this solution were added dibenzyl azodi-
carboxylate (1.14 mmol) and L-proline (0.22 mmol) at rt. The
reaction mixture was stirred during 2 h at this temperature. The
mixture was thentreated withEtOH (10mL) andNaBH4 (40mg)
and was stirred for 5 min at 0 °C. The reaction was worked up
with aq NH4Cl solution and EtOAc. The organic layers were
dried (MgSO4), filtered, and concentrated. The resulting crude
product 9 or 10 was purified by flash chromatography on silica
(pentane/Et2O = 8/2).
Methyl (R)-3-hydroxydodecanoate (5): yield 445 mg (89%);
white solid; mp 28-29 °C (lit.9 mp 26-28 °C); [R]25D=-21.4
(c 0.9, CHCl3) [lit.9 [R]25D =-21.1 (c 1.5, CHCl3)]; H NMR
1
(CDCl3) δ 0.86 (t, J = 6.9 Hz, 3H), 1.25 (s, 14H), 1.46 (m, 2H),
2.43 (m, 2H), 3.69 (s, 3H), 3.98 (m, 1H); 13C NMR (300 MHz,
CDCl3) δ 173.4, 67.9, 51.6, 41.0, 36.4, 31.8, 29.5, 29.4, 29.4, 29.2,
25.4, 22.6, 14.0.
Methyl (R)-3-hydroxyoctadecanoate (6): yield 450 mg (90%);
white solid; mp 57-58 °C (lit.10 mp 55-56 °C); [R]25D=-15.9
(c 0.9, CHCl3) [lit.10 [R]25D=-15.5 (c 1.0, CHCl3)]; H NMR
1
(CDCl3) δ 0.86 (t, J=6.9 Hz, 3H), 1.25 (s, 28H), 1.47 (m, 2H),
2.46 (m, 2H), 3.71 (s, 3H), 3.99 (m, 1H); 13C NMR (300 MHz,
CDCl3) δ 173.4, 67.9, 51.6, 41.0, 36.5, 31.9, 29.6, 29.6, 29.6, 29.5,
29.5, 29.4, 29.3, 25.4, 22.6, 14.0.
General Procedure for Formation of Silyl Ethers. To a stirred
solution of alcohol (2 mmol) in dry CH2Cl2 (10 mL) cooled to
-78 °C were added 2,6-lutidine (4 mmol) and tert-butyldi-
methylsilyl triflate (3 mmol). After 2 h of stirring at -78 °C,
MeOH (3 mL) was added, and the solution was warmed to room
temperature. The organic layers were evaporated under va-
cuum, and the residue was purified by flash chromatography
on silica (pentane/ether =9/1).
(2S,3R)-2-(N,N0-Bis(benzyloxycarbonyl)hydrazino)-3-(tert-
butyldimethylsilyloxy)dodecanol (9): yield 803 mg (76%); color-
less oil; [R]25D = -12.2 (c 0.4, CHCl3); IR (ATR, cm-1) 3482,
1
3282, 2915, 2848, 1726, 1679, 1526, 1429, 1259, 1055, 836; H
NMR (300 MHz, CDCl3) δ 0.004-0.04 (m, 6H), 0.87 (s, 12H),
1.12-1.44 (m, 16H), 3.50-4.12 (m, 4H), 4.31-4.47 (m, 1H),
5.15-5.31 (m, 4H), 6.54 (s, 1H), 7.24-7.38 (m, 10H); 13C NMR
(300 MHz, CDCl3) δ 158.8, 158.1, 156.8, 155.6, 135.7, 135.4,
134.9, 128.6, 128.5, 128.4, 128.2, 128.1, 127.7, 71.1, 70.5, 68.7,
68.1, 67.8, 63.2, 59.8, 34.4, 34.1, 31.8, 30.3, 29.6, 29.5, 29.3, 25.7,
23.1, 22.6, 17.9, 14.1, -4.1, -4.8. Anal. Calcd for C34H54N2O6-
Si: C, 66.41; H, 8.85; N, 4.56. Found: C, 66.31; H, 8.81; N, 4.47.
(2S,3R)-2-(N,N0-Bis(benzyloxycarbonyl)hydrazino)-3-(tert-
butyldimethylsilyloxy)octadecanol (10): yield 925 mg (77%);
Methyl (R)-3-(tert-butyldimethylsilyloxy)dodecanoate (7): yield
406 mg (89%); colorless oil; [R]25D =-13.2 (c 1.0, CHCl3); IR
(ATR, cm-1) 2953, 2926, 2850, 1734, 1469, 1250, 1069, 834; H
1
NMR (300 MHz, CDCl3) δ0.03 (s, 3H), 0.05 (s, 3H), 0.86 (s, 12H),
1.26 (s, 14H), 1.43-1.52 (m, 2H), 2.42 (d br., J = 6.9 Hz, 2H), 3.66
(s, 3H), 4.12 (m, 1H); 13C NMR (300 MHz, CDCl3) δ 172.3, 69.4,
51.3, 42.5, 37.6, 31.8, 29.6, 29.5, 29.5, 29.2, 25.7, 25.6, 24.9, 22.6,
17.9, 14.0, -2.9, -4.5, -4.8. Anal. Calcd for C19H40O3Si: C, 66.22;
H, 11.70. Found: C, 65.92; H, 11.88.
colorless oil; [R]25 = -5.6 (c 0.3, CHCl3); IR (ATR, cm-1
)
D
Methyl (R)-3-(tert-butyldimethylsilyloxy)octadecanoate (8):
3509, 3278, 2919, 2857, 1723, 1684, 1530, 1418, 1321, 1259, 1066,
835; 1H NMR (300 MHz, CDCl3) δ 0.006-0.05 (m, 6H), 0.87 (s,
12H), 1.02-1.53 (m, 28H), 3.47-4.21 (m, 4H), 4.22-4.56 (m,
yield 556 mg (89%); colorless oil; [R]25D=-16.9 (c 1.0, CHCl3);
IR (ATR, cm-1) 2923, 2846, 1742, 1452, 1252, 1078, 843; H
1
1H), 5.08-5.34 (m, 4H), 6.57 (s, 1H), 7.23-7.46 (m, 10H); 13
C
NMR (300 MHz, CDCl3) δ 0.03 (s, 3H), 0.06 (s, 3H), 0.86 (s,
12H), 1.25 (s, 26H), 1.43-1.50 (m, 2H), 2.44 (d br, J = 6.9 Hz,
2H), 3.66 (s, 3H), 4.12 (m, 1H); 13C NMR (300 MHz, CDCl3) δ
172.3, 69.5, 51.3, 42.5, 37.6, 31.9, 29.7, 29.6, 29.5, 29.3, 25.7, 25.7,
25.6, 24.9, 22.6, 18.0, 17.9, 14.1, -2.9, -4.5, -4.8. Anal. Calcd for
C25H52O3Si: C, 70.03; H, 12.22. Found: C, 70.03; H, 12.41.
(2S,3R)-2-(N,N0-Bis(benzyloxycarbonyl)hydrazino)-1,3-bis-
(tert-butyldimethylsilyloxy)dodecane (11): yield 1179 mg (96%);
NMR (300 MHz, CDCl3) δ 158.7, 158.3, 156.8, 155.5, 135.7,
135.6, 134.9, 134.9, 128.6, 128.5, 128.4, 128.3, 128.1, 127.7,
127.6, 71.2, 70.5, 68.6, 68.5, 68.4, 68.1, 67.8, 63.2, 60.1, 34.3,
34.0, 31.9, 31.8, 29.8, 29.6, 29.6, 29.3, 25.7, 25.6, 23.2, 22.6, 17.8,
14.0, -4.1, -4.8. Anal. Calcd for C40H66N2O6Si: C, 68.73; H,
9.52; N, 4.01. Found: C, 68.71; H, 9.62; N, 3.96.
General Procedure for the Conversion of Hydrazino Diols into
the Corresponding Amino Diols. To a stirred solution of hydra-
zino diols 11 or 12 (0.30 mmol) in anhydrous MeOH (5.0 mL)
were added AcOH (5 drops) and Raney-Ni (ca. 200 mg,
prewashed with anhydrous MeOH). The reaction mixture was
degassed under vacuum and saturated with hydrogen (by an H2-
filled balloon) three times. The suspension was stirred at room
temperature for 20 h under a slightly positive pressure of
hydrogen and then filtered off through a pad of Celite. The
solvent were evaporated under vacuum, and the residue was
purified by flash chromatography on silica (pentane/ether =8/2)
to give 13 or 14 as an oil.
colorless oil; [R]25 = -4.9 (c 0.9, CHCl3); IR (ATR, cm-1
)
2947, 2924, 2858, 2165, 2017, 1978, 1710, 1476, 1254, 1216, 1083,
D
1
830; H NMR (300 MHz, CDCl3) δ -0.01 (s, 12H), 0.84 (s,
21H), 1.02-1.63 (m, 16H), 3.37-4.00 (m, 3H), 4.11-4.39 (m,
1H), 5.16-5.54 (m, 4H), 6.16-6.59 (s, 1H), 7.21-7.48 (m, 10H);
13C NMR (300 MHz, CDCl3) δ 157.6, 156.9, 156.6, 156.1, 135.9,
135.7, 135.5, 128.6, 128.5, 128.3, 128.2, 128.1, 127.9, 127.6, 71.1,
70.7, 68.4, 67.6, 67.6, 67.4, 67.3, 62.0, 61.2, 33.6, 33.4, 31.8, 29.9,
29.5, 29.1, 22.6, 17.8, 14.1, -4.1, -5.1, -5.6, -5.7. Anal. Calcd
for C40H68N2O6Si2: C, 65.89; H, 9.40; N, 3.84. Found: C, 66.09;
H, 9.64; N, 3.99.
(2S,3R)-2-(N,N0-Bis(benzyloxycarbonyl)hydrazino)-1,3-bis-
(tert-butyldimethylsilyloxy)octadecane (12): yield 1341 mg (96%);
(2S,3R)-2-Amino-1,3-(di-tert-butyldimethylsilyloxy)dodecane
(13): yield 102 mg (77%); colorless oil; [R]25 = -0.6 (c 1.0,
D
5314 J. Org. Chem. Vol. 75, No. 15, 2010