1592
S. YAMAUCHI and Y. OMI
47.1 mmol) and MS 4A (0.3 g) in CH2Cl2 (300 ml) was
stirred at room temperature for 15 h before filtration. The
resulting filtrate was concentrated, and the residue was
applied to silica gel column chromatography (EtOAc=
(2H, m), 2.27 (1H, ddd, J ¼ 17:8, 10.9, 5.9 Hz, 3-HH),
2.39 (1H, m, 3-HH), 3.60 (1H, m, 6-H), 3.72–3.80 (2H,
m, CH2OTBDPS), 6.31 (1H, br. s, NH), 7.38–7.46 (6H,
m, ArH), 7.65–7.66 (4H, m, ArH). 13C-NMR (CDCl3) ꢁ
19.1, 19.9, 26.8, 29.0, 31.2, 39.0, 52.0, 61.8, 127.78,
127.80, 129.8, 129.9, 133.1, 133.2, 135.5, 171.8. IRꢂmax
(CHCl3): 3376, 2934, 1649, 1472, 1113, 1092, 909.
Anal. Calcd. for C23H31O2NSi: C, 72.39; H, 8.19; N,
hexane ¼ 1=9) to give (S)-aldehyde 11 (13.0 g, 31.7
20
mmol, 74%) as a colorless oil, ½ꢀꢂ
¼ þ3:1 (c 1.3,
D
CHCl3). 1H-NMR (CDCl3) ꢁ 1.06 (9H, s, tert-Bu), 1.46–
1.62 (2H, m), 1.62–1.85 (4H, m), 2.47 (2H, td, J ¼ 7:1,
1.5 Hz, 2-H2), 3.59 (1H, m, 5-H), 3.74 (1H, ddd, J ¼
10:7, 10.7, 5.4 Hz, 7-HH), 3.80 (1H, ddd, J ¼ 10:7, 7.8,
4.9 Hz, 7-HH), 7.37–7.45 (6H, m, ArH), 7.64–7.67 (4H,
m, ArH), 9.77 (1H, d, J ¼ 1:5 Hz, CHO). 13C-NMR
(CDCl3) ꢁ 18.7, 19.2, 26.8, 33.9, 36.9, 43.4, 59.4, 60.3,
127.7, 129.7, 133.5, 133.6, 135.50, 135.54, 201.8.
IRꢂmax (CHCl3): 3073, 2932, 2103, 1725, 1113, 909,
824. Anal. Calcd. for C23H31O2N3Si: C, 67.44; H, 7.63;
3.67. Found: C, 72.35; H, 8.14; N, 3.73. (R)-13,
20
½ꢀꢂ
¼ ꢀ3:8 (c 1.3, CHCl3).
D
(S)-2-[2-(tert-Butyldiphenylsilyloxy)ethyl]piperidine
(14). To a solution of (S)-amide 13 (3.26 g, 8.54 mmol)
in CH2Cl2 (50 ml) was added DIBAL-H (18.8 ml, 1 M in
toluene, 18.8 mmol) at 0 ꢁC. After the reaction solution
was stirred at 0 ꢁC for 1 h, a sat. aq. NH4Cl solution was
added. The organic solution was separated, washed with
brine, and dried (Na2SO4). Concentration followed by
silica gel column chromatography (CHCl3=MeOH=
Et3N ¼ 19=1=1) gave (S)-piperidine 14 (1.50 g, 4.08
mmol, 48% yield, 51% of amide was recovered) as a
N, 10.26. Found: C, 67.47; H, 7.67; N, 10.09. (R)-11,
20
½ꢀꢂ
¼ ꢀ3:1 (c 1.6, CHCl3).
D
(S)-5-Azido-7-(tert-butyldiphenylsilyloxy)heptanoic
acid (12). To an ice-cooled solution of (S)-aldehyde 11
(11.6 g, 28.3 mmol), 2-methyl-2-butene (13.2 ml, 125
20
1
colorless oil, ½ꢀꢂ
¼ ꢀ3:2 (c 2.2, CHCl3). H-NMR
D
.
mmol) and NaH2PO4 2H2O (4.42 g, 28.3 mmol) in tert-
(CDCl3) ꢁ 1.04–1.15 (1H, m), 1.05 (9H, s, tert-Bu),
1.25–1.46 (2H, m), 1.54–1.68 (4H, m), 1.75 (1H, m),
2.02 (1H, br. s, NH), 2.60 (1H, ddd, J ¼ 11:7, 11.7,
2.5 Hz, 6-HH), 2.66 (1H, m, 6-HH), 3.00 (1H, m, 2-H),
3.74 (2H, t, J ¼ 6:3 Hz, CH2OTBDPS), 7.26–7.44 (6H,
m, ArH), 7.65–7.67 (4H, m, ArH). 13C-NMR (CDCl3) ꢁ
19.2, 24.9, 26.3, 26.8, 33.0, 39.6, 47.1, 54.8, 61.8, 127.6,
129.6, 133.7, 133.8, 135.5. IRꢂmax (CHCl3): 2934, 2859,
1732, 1429, 1111. Anal. Calcd. for C23H33ONSi: C,
BuOH (70 ml) and H2O (20 ml) was added NaClO2
(8.70 g, 96.2 mmol), and then the resulting reaction
solution was stirred in an ice-cooled bath for 1 h. After
addition of CHCl3, the mixture was acidified with a 1 M
aq. HCl solution. The organic solution was separated,
washed with H2O and brine, and dried (Na2SO4).
Concentration followed by silica gel column chroma-
tography (EtOAc=hexane ¼ 1=6) gave (S)-acid 12
20
(11.7 g, 27.5 mmol, 97%) as a colorless oil, ½ꢀꢂ
¼
75.15; H, 9.05; N, 3.81. Found: C, 74.85; H, 8.90; N,
20
D
1
þ2:8 (c 5.3, CHCl3). H-NMR (CDCl3) ꢁ 1.05 (9H, s,
tert-Bu), 1.50–1.60 (2H, m), 1.60–1.85 (4H, m), 2.39
(2H, t, J ¼ 7:3 Hz, 2-H2), 3.60 (1H, m, 5-H), 3.74 (1H,
ddd, J ¼ 10:7, 10.7, 5.4 Hz, 7-HH), 3.80 (1H, ddd,
J ¼ 10:7, 7.8, 4.9 Hz, 7-HH), 7.37–7.45 (6H, m, ArH),
7.65–7.67 (4H, m, ArH). 13C-NMR (CDCl3) ꢁ 19.2,
21.2, 26.8, 33.6, 33.8, 36.9, 59.4, 60.3, 127.7, 129.7,
133.4, 133.6, 135.49, 135.53, 179.1. IRꢂmax (CHCl3):
2932, 2105, 1713, 1113, 1092, 909. Anal. Calcd. for
3.77. (R)-14, ½ꢀꢂ
¼ þ3:2 (c 2.2, CHCl3).
D
Determination of the enantiomeric excess of (S)-14
and (R)-14. To an ice-cooled solution of (S)-piperidine
14 (20 mg, 54.4 mmol) in pyridine (0.5 ml) was added
(ꢀ)-menthyl chloroformate (17.5 ml, 81.6 mmol). The
reaction mixture was stirred at room temperature for 2 h,
and then CHCl3 and H2O were added. The organic
solution was separated, successively washed with a 1 M
aq. HCl solution, sat. aq. NaHCO3 solution, and brine,
and then dried (Na2SO4). After concentration, the
residue was applied to HPLC (Cica-Merk Lichrospher
Si60, 2% EtOAc in hexane, 2.0 ml/min, detected at
270 nm, tR ¼ 20 min) to determine >99% de. Product
from (R)-14, tR ¼ 16 min, >99% de.
C23H31O3N3Si: C, 64.91; H, 7.34; N, 9.87. Found: C,
20
65.11; H, 7.39; N, 9.76. (R)-12, ½ꢀꢂ
¼ ꢀ2:8 (c 1.8,
D
CHCl3).
(S)-6-[2-(tert-Butyldiphenylsilyloxy)ethyl]-2-piperidin-
one (13). A reaction mixture of (S)-azide 12 (5.30 g,
12.5 mmol) and 20% Pd(OH)2/C (0.20 g) in EtOH
(40 ml) was stirred under H2 gas at ambient temperature
for 4 h before filtration. The filtrate was concentrated,
and the resulting residue was dissolved in toluene
(80 ml), this reaction solution then beeing heated under
reflux for 1 h. After concentration, the residue was
applied to silica gel column chromatography (EtOAc=
tert-Butyl (S)-2-[2-(tert-butyldiphenylsilyloxy)]ethyl]-
piperidine-1-carboxylate (15). A reaction mixture of
(S)-piperidine 14 (1.10 g, 2.99 mmol) and (Boc)2O
(0.72 g, 3.30 mmol) in THF (10 ml) and a 2 M aq.
K2CO3 solution (10 ml) was stirred at 0 ꢁC for 2 h before
additions of EtOAc and H2O. The organic solution was
separated, washed with brine, and dried (Na2SO4).
Concentration followed by silica gel column chroma-
tography (EtOAc=hexane ¼ 1=9) gave (S)-Boc-piperi-
dine 15 (1.36 g, 2.91 mmol, 97%) as a colorless oil,
hexane ¼ 1=1) to give (S)-amide 13 (4.29 g, 11.2 mmol,
20
90%) as colorless crystals, mp 94–95 ꢁC, ½ꢀꢂ
¼ þ3:8
D
1
(c 4.8, CHCl3). H-NMR (CDCl3) ꢁ 1.07 (9H, s, tert-
Bu), 1.32–1.41 (1H, m), 1.60–1.75 (3H, m), 1.80–1.91