Notes
J . Org. Chem., Vol. 65, No. 8, 2000 2601
MHz, and 13C NMR spectra were recorded at 75 MHz. Internal
slowly added. The reaction mixture was stirred at room tem-
perature for 60 h, diluted with EtOAc (200 mL), and poured into
aqueous NaHCO3 solution (100 mL). The resulting mixture was
extracted with EtOAc, and the combined extracts were washed
with brine, dried (MgSO4), and concentrated. This was employed
for the next step without further purification.
1
standards used in H NMR spectra were TMS (δ 0.00) for CDCl3
and HOD (δ 4.78) for D2O and in 13C NMR were CDCl3 (δ 75.0)
for CDCl3 and CH3CN (δ 1.30) for D2O. Mass spectral data were
analyzed by the Mass Spectrometry Laboratory at University
of Illinois and Mass Spectrometry Facility at J ohns Hopkins
University.
To a solution of the above mixture (4.0 g) in DMF (60 mL)
were added imidazole (3.4 g, 43.1 mmol) and tert-butylchlo-
rodiphenyl silane (5.1 mL, 18.5 mmol) at 0-5 °C, and the
mixture was stirred for 2 h at room temperature. The reaction
mixture was poured into ice-cooled aqueous NaHCO3 solution
(150 mL) and extracted with Et2O. The combined extracts were
successively washed with aqueous NaHCO3 solution and brine,
dried (MgSO4), and concentrated. The residue was chromato-
graphed on silica gel with EtOAc-hexane (1:30) to give the 8
(6.5 g, 88% in 2 steps) as a colorless oil: 1H NMR (CDCl3) δ
1.14 (s, 9H), 1.44 (m, 3Η, cyclohexylidene group), 1.51 (m, 7H,
cyclohexylidene group), 2.35 (d, 1H, J ) 8.7 Hz), 2.88 (dt, 1H, J
) 4.5, 13.8 Hz), 3.95 (m, 3H), 4.11 (m, 2H), 4.45 (dt, J ) 2.1,
6.3, 8.7 Hz), 7.43 (m, 6H), 7.77 (m, 4H); 13C NMR (CDCl3) δ 19.3,
23.6, 23.9, 25.0, 26.7, 34.2, 35.9, 39.1, 60.6, 65.7, 68.1, 75.3, 110.5,
118.6, 27.8, 129.9, 123.0, 135.6, 135.6; HRMS FAB calcd for
C28H38NO4Si (M + H)+ 480.2570, found 480.2571.
(2R,3R,4S)-1-[(ter t-Bu tyld ip h en ylsilyl)oxy)]-2-cya n o-3,4-
d ih yd r oxy-5-[(p-tolu en esu lfon yl)oxy]p en ta n e (9). A solu-
tion of 8 (2.0 g, 4.2 mmol) in 80% acetic acid (30 mL) was stirred
at room temperature for 40 h. The resulting reaction mixture
was then concentrated and coevaporated with toluene (30 mL
× 2), and the residue was employed for the next step without
further purification.
To a stirred solution of the above residue (1.7 g) in pyridine
(40 mL) was added p-toluenesulfonyl chloride (1.0 g, 5.5 mmol)
in one portion at room temperature, and the resulting mixture
was stirred for 4 h at room temperature. The reaction mixture
was poured into ice water (100 mL) and extracted with EtOAc.
The combined extracts were successively washed with aqueous
NaHCO3 solution and brine, dried (MgSO4), and concentrated.
The residue was chromatographed on silica gel with EtOAc-
hexane (1:4) to give 9 (1.6 g, 70% in 2 steps) as a colorless oil:
1H NMR (CDCl3) δ 1.01 (s, 9H), 2.44 (s, 3H), 3.00 (dt, 2H, J )
4.5, 13.5 Hz), 3.39 (br, 1H, hydroxyl group), 3.98 (m, 3H), 4.17
(bs, 3H), 7.34 (d, 2H, J ) 8.4 Hz), 7.42 (m, 6H), 7.70 (m, 4H),
7.82 (d, 2H, J ) 8.4 Hz); 13C NMR (CDCl3) δ 19.1, 21.5, 26.6,
37.5, 60.5, 67.9, 68.8, 70.3, 118.4, 127.6, 129.9, 132.2, 132.3,
135.4, 135.5, 145.2; HRMS FAB calcd for C29H36NO6SSi (M +
H)+ 554.2032, found 554.2031.
Meth yl (4S)-4,5-(Cycloh exyliden edioxy)-(2E)-pen ten oate
(4). To a mixture of NaH (6.5 g, 163.8 mmol) in benzene (80
mL) was added a solution of trimethylphosphonoacetate (26 mL,
180 mmol) in THF (100 mL) at 0 °C, and the mixture was stirred
at the same temperature for 1 h. Then, a solution of (R)-2,3-O-
cyclohexylidene glyceraldehyde 34 (14.0 g, 81.9 mmol) in THF
(80 mL) was added, and the resulting mixture was allowed to
warm to room temperature and stirred for 2 h. The reaction
mixture was poured into ice water (250 mL) and extracted with
EtOAc. The combined extracts were washed with brine, dried
(MgSO4), and concentrated. The residue was chromatographed
on silica gel with EtOAc-hexane (1:6) to give the E-isomer 4
(14.1 g, 76%) and Z-isomer (1.4 g, 7%) as a colorless oil: 1H NMR
(CDCl3) δ 1.35 (m, 3Η, cyclohexylidene group), 1.56 (m, 7H,
cyclohexylidene group), 3.61 (dd, 1H, J ) 7.5 Hz), 3.69 (s, 3H),
4.12 (dd, 1H, J ) 6.9, 7.8 Hz), 4.61 (dd, 1H, J ) 5.7, 3 Hz), 6.06
(d, 1H, J ) 15.3 Hz), 6.83 (dd, 1H, J ) 5.4, 15.3 Hz); 13C NMR
(CDCl3) δ 23.5, 23.6, 24.8, 35.0, 35.8, 51.3, 68.1, 74.3, 110.4,
121.4, 145.2, 166.0; HRMS FAB calcd for C12H18O4 (M+) 226.1205,
found. 226.1208.
(4S)-4,5-(Cycloh exylid en ed ioxy)-(2E)-p en ten -1-ol (5). To
a solution of 4 (5.0 g, 22 mmol) in CH2Cl2 (150 mL) under argon
was added a 1.0 M solution of DIBAL in toluene (44.0 mL, 44
mmol) at 0 °C, and the mixture was stirred for 2 h at room
temperature. Acetone (20 mL) was slowly added to the reaction
mixture. An aqueous sodium potassium tartrate solution (100
mL) and EtOAc (200 mL) were subsequently added, and the
resulting mixture was stirred until the layers were clearly
separated. The aqueous layer was extracted with EtOAc, and
the combined extracts were washed with brine, dried (MgSO4),
and concentrated. The residue was chromatographed on silica
gel with EtOAc-hexane (1:3) to give 5 (4.0 g, 92%) as a colorless
oil: 1H NMR (CDCl3) δ 1.24 (m, 3Η, cyclohexylidene group), 1.46
(m, 7H, cyclohexylidene group), 3.42 (m, 2H, 1H of hydroxyl
group), 3.93 (m, 3H), 4.37 (dd, 1H, J ) 7.2, 13.8 Hz), 5.53 (dd,
1H, J ) 7.5, 15.6 Hz), 5.76 (dt, 1H, J ) 5.1, 9.9, 15.6 Hz); 13C
NMR (CDCl3) δ 23.5, 23.5, 24.7, 35.0, 35.9, 61.7, 68.6, 75.8, 109.6,
127.9, 133.1; HRMS FAB calcd for C11H18O3 (M+) 198.1256,
found 198.1259.
(2S,3R,4R)-2,3-Ep oxy-4,5-(cycloh exylid en ed ioxy)p en ta n -
1-ol (6). To a slurry of flame-dried powdered MS4A (15 g) in
dry CH2Cl2 (400 mL) under argon were sequentially added
titanium tetraisopropoxide (23.4 mL, 78.6 mmol) and diethyl
L-(+)-tartrate (13.5 mL, 78.6 mmol) at -20 °C, and the mixture
was stirred for 30 min. A solution of 5 (10.4 g, 52.4 mmol) in
dry CH2Cl2 (120 mL) was added, and the resulting mixture was
stirred at -20 °C for 30 min. A solution of tert-butylhydroper-
oxide in decane (5.0-6.0M, 21 mL, 104.8 mmol) was subse-
quently added dropwise to the mixture, and the resulting
mixture was kept for 16 h at -15 °C. Aqueous tartaric acid (10%,
200 mL) was added at -20 °C, and the whole was allowed to
warm to room temperature. After being stirred for 1 h, the
reaction mixture was filtered, and the filtrate was extracted with
CH2Cl2. The combined extracts were washed with brine, dried
(MgSO4), and concentrated. The residue was chromatographed
on silica gel with EtOAc-hexane (1:6) to give 6 (10.1 g, 90%) as
a colorless oil: 1H NMR (CDCl3) δ 1.30 (br s, 3Η, cyclohexylidene
group), 1.51 (m, 7H, cyclohexylidene group), 2.01 (br s, 1H,
hydroxyl group), 2.97 (dd, 1H, J ) 2.4, 4.8 Hz), 3.03 (dd, 2H, J
) 2.4, 4.8 Hz, 1H of hydroxyl group), 3.54 (dd, 1H, J ) 3.9, 12.6
Hz), 3.74 (m, 1H), 3.81 (dd, 1H, J ) 1.8, 12.9 Hz), 4.00 (m, 2H);
13C NMR (CDCl3) δ 23.5, 23.7, 24.8, 34.8, 35.7, 55.1, 55.4, 60.8,
65.4, 74.6, 110.3; HRMS FAB calcd for C11H18O4 (M+) 214.1205,
found 214.1207.
D-Glu cose Type 1-N-Im in osu gar : (3R,4R,5R)-5-(Hydr oxy-
m eth yl)-p ip er id in e-3,4-d iol Hyd r och lor id e Sa lt (1). A solu-
tion of 9 (2.0 g, 3.6 mmol) and Raney Ni (5 mL) in EtOH (20
mL) was stirred vigorously under H2 atmosphere at room
temperature for 50 h. After removal of the catalyst by filtration,
the filtrate was concentrated to give a crude product 10, which
was employed for the next step without further purification.
A solution of the residue 10 in 2 N HCl (15 mL) was stirred
overnight at room temperature, and the reaction mixture was
concentrated. The residue was diluted with water (10 mL) and
applied onto a column of Dowex 50W-X8 [H+] resin. The column
was washed with water, and the product was eluted out with
3% NH4OH. The fractions containing 1 were pooled and con-
centrated. The residue was chromatographed on silica gel with
2-propanol-H2O-NH4OH (7:2:1) to give chromatographically
pure 1. Water (10 mL) and 1 N HCl (20 mL) were added to the
residue, and the solution was concentrated to form a hydrochlo-
ride salt of the iminosugar. The residue was applied onto a
column of Sephadex G-25 (2 cm × 65 cm) and eluted with water.
The fractions containing 1 were pooled and lyophilized from
water to afford 1 (300 mg, 58% in 2 steps) as a colorless
amorphous powder (HCl salt): 1H and 13C NMR spectra were
in good agreement with those reported;1b,2a 1H NMR (D2O) δ
1.91-2.02 (m, 1H, H-5), 2.88 (t, 1H, J ) 11.9 Hz), 2.97 (t, 1H, J
) 12.7 Hz), 3.48-3.56 (m, 3H), 3.71-3.85 (m, 3H); 13C NMR
(D2O) δ 43.6, 45.6, 49.4, 61.8, 71.1, 73.9; HRMS FAB calcd for
C6H13NO3 (M + H)+ 148.0974, found 148.0976.
(2R,3R,4R)-1-[(ter t-Bu tyld ip h en ylsilyl)oxy)]-2-cya n o-4,5-
(cycloh exylid en ed ioxy)-3-h yd r oxyp en ta n e (8). To a stirred
solution of 6 (3.3 g, 15.4 mmol) in DMSO (60 mL) under argon
were added potassium cyanide (2.5 g, 38.5 mmol) and tetrabu-
tylammonium iodide (10.2 g, 27.7 mmol) at room temperature,
and then titanium tetraisopropoxide (11.4 mL, 38.5 mmol) was
ter t-Bu tyl (3R,4R,5S)-5-[(ter t-Bu tyld ip h en ylsilyl)oxy)]-
3,4-d ih yd r oxyp ip er id in e-1-ca r boxyla te (11). A mixture of 9
(1.6 g, 2.9 mmol) and Raney Ni (3 mL) in EtOH (20 mL) was
stirred vigorously under H2 atmosphere at room temperature