4632 J . Org. Chem., Vol. 67, No. 13, 2002
Notes
mixture was cooled (ice bath), and the reaction was quenched
by an addition of saturated aqueous sodium bicarbonate. The
solids were filtered through a Celite pad, and the filtrate was
extracted with dichloromethane. The organic layer was washed
with water and brine, dried over anhydrous sodium sulfate, and
concentrated in vacuo to give an aldehyde. The crude aldehyde
was taken into ethanol (10 mL), and the solution was treated
with NaBH4 (188 mg, 4.98 mmol) in portions at 0 °C for 1 h.
Most of the ethanol was removed in vacuo, and the crude was
partitioned between EtOAc and water. The organic layer was
separated out, washed with water and brine, dried over anhy-
drous sodium sulfate, and concentrated in vacuo to give an
alcohol as a colorless liquid (920 mg). A solution of the alcohol
(900 mg, 2.41 mmol) and triethylamine (1.3 mL, 9.64 mmol) in
DCM (5 mL) was treated with tosyl chloride (600 mg, 3.13 mmol)
at 0 °C, and the reaction mixture was stirred at room temper-
ature for 12 h. The mixture was diluted with ether and washed
with water and brine. The organic layer was dried over anhy-
drous sodium sulfate and concentrated in vacuo. The crude
tosylate was taken in DMF (8 mL) and treated with NaN3 (626
mg, 9.64 mmol) at 80 °C for 12 h. The reaction mixture was
taken in water and extracted with ether several times. The
combined organic layer was washed with water and brine, dried
over anhydrous sodium sulfate, and concentrated in vacuo. The
crude material was chromatographed over silica gel to give the
azide 8 as a colorless oil: yield 864 mg (80%); Rf 0.65 (10% EtOAc
in petroleum ether); [R]25D -11.5 (c 1, CHCl3); IR (thin film) 2987,
concentrated to provide a residue, which was chromatographed
over silica gel to give a diastereomerically pure homoallylic
alcohol 4: diastereomeric ratio 99:1 (HPLC, silica gel column
100 × 4.6 mm, solvent 99:1 n-hexanes/2-propanol, flow rate 1.25
mL/min, UV 254 nm, RT 3.04 min for major and 2.52 min for
minor diastereomers); yield 362 mg (82%); Rf 0.70 (30% EtOAc
in petroleum ether); [R]25 -28.7 (c 1.08, CHCl3); IR (thin film)
D
3450, 2877, 2096, 1068 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.05
(d, 1H, -OH), 2.19 (m, 2H), 3.44 (m, 3H), 3.73 (m, 2H), 4.52
(dd, J ) 13.9, 11.5 Hz, 2H), 4.64 (dd, J ) 18.3, 11.5 Hz, 2H),
5.01 (m, 2H), 5.69 (m,1H), 7.3 (m, 10H); 13C NMR (100 MHz,
CDCl3) δ 39.31, 51.56, 69.52, 73.22, 74.41, 78.99, 117.86, 128.13,
128.48, 134.47, 137.70, 137.74. Anal. Calcd for C21H25N3O3: C,
68.66; H, 6.81; N, 11.44. Found: C, 68.70; H, 6.78; N, 11.42.
(4S,5S,6R)-7-Azid o-5,6-bis-ben zyloxy-h ep t-1-en -4-m eth -
a n esu lfon a te (10). A solution of the homoallylic alcohol 4 (183
mg, 0.5 mmol) and triethylamine (210 µL, 1.5 mmol) in dry DCM
(5 mL) was treated with methanesulfonyl chloride (60 µL, 0.75
mmol) at 0 °C under a N2 atmosphere. The reaction mixture
was stirred for 6 h (from 0 °C to rt). It was diluted with diethyl
ether and washed with water and brine. After drying (anhydrous
sodium sulfate) and concentration in vacuo, the residue was
purified over silica gel to give a pure mesylated product 10: yield
205 mg (92%); Rf 0.65 (EtOAc in petroleum ether); [R]25 -14.3
D
(c 2.3, CHCl3); IR (thin film) 2931, 2100, 1346, 917 cm-1; 1H NMR
(400 MHz, CDCl3) δ 2.34 (m, 1H), 2.58 (m, 1H), 2.93 (s, 3H),
3.48 (m, 2H), 3.69 (m, 2H), 4.57 (d, J ) 11.5 Hz, 1H), 4.68 (m,
3H), 4.79 (q, J ) 5.6 Hz, 1H), 5.06 (dd, J ) 17.1, 1.0 Hz, 1H),
2882, 2098, 1374 cm-1 1H NMR (400 MHz, CDCl3) δ 1.36 (s,
;
3H), 1.45 (s, 3H), 3.41 (d, J ) 6.0 Hz, 2H), 3.70 (m, 1H), 3.76
(dd, J ) 4.0, 4.0 Hz, 1H), 3.93 (dd, J ) 8.0, 6.8 Hz, 1H), 4.02
(dd, J ) 8.0, 6.4 Hz, 1H), 4.23 (m, 1H), 4.58-4.80 (m, 4H), 7.3
(m, 10 H);13C NMR (100 MHz, CDCl3) δ 25.03, 26.44, 51.25,
66.09, 73.41, 74.61, 76.01, 78.60, 108.55, 127.83, 128.01, 128.08,
128.34, 137.55, 137.83; MS (FAB) 398 (M++1). Anal. Calcd for
C22H27N3O4: C, 66.50; H, 6.80; N, 10.58. Found: C, 66.48; H,
6.83; N, 10.51.
5.13 (dd, J ) 10.2, 1.0 Hz, 1H), 5.71 (m, 1H), 7.34 (m, 10H); 13
C
NMR (100 MHz, CDCl3) δ 35.75, 38.73, 50.60, 73.08, 75.07, 77.43,
77.95, 80.92, 119.35, 128.12, 128.21, 128.22, 128.30, 128.52,
128.56, 132.18, 137.27, 137.39. Anal. Calcd for C22H27N3O5S: C,
59.32; H, 6.07; N, 9.44; S, 7.19. Found: C, 59.37; H, 6.10; N,
9.48; S, 7.21.
(2R,3R,4R)-2-Allyl-3,4-bis-ben zyloxy-p yr r olid in e (11). A
solution of the azido mesylate 10 (190 mg, 0.43 mmol) in dry
THF (3 mL) was treated with lithium aluminum hydride solution
(850 µL, 1.0 M) at 0 °C. The reaction mixture was refluxed for
12 h, and the reaction was quenched by the addition of EtOAc
and water (3-4 drops). The solids were filtered through a Celite
pad, and the filtrate was concentrated in vacuo. The crude
material was chromatographed over silica gel to give the pure
cyclized product 11: yield 94 mg (68%); Rf 0.70 (10% MeOH in
(2R,3R,4R)-5-Azido-3,4-bis-ben zyloxy-pen tan e-1,2-diol (9).
A solution of 8 (800 mg, 2.01 mmol) in THF/H2O (4:1; 10 mL)
was treated with trifluoroacetic acid (310 µL, 4.03 mmol) at room
temperature and further refluxed for 8 h. The solvent was
removed in vacuo, and the residue was taken in water and
extracted with EtOAc. The organic layer was washed with
aqueous sodium bicarbonate, water, and brine, dried over
anhydrous sodium sulfate, concentrated in vacuo, and chro-
matographed over silica gel to give a diol 9 as a low-melting
solid: yield 700 mg (97%), Rf 0.45 (40% EtOAc in petroleum
CH2Cl2); [R]25 +10.2 (c 2.1, CHCl3); IR (thin film) 2922, 1368,
D
1075, 738 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.29 (m, 2H), 2.65
(bs, -NH), 3.03 (m, 3H), 3.60 (d, J ) 4.4 Hz, 1H), 3.91 (m, 1H),
4.45 (m, 4H), 5.01 (m, 2H), 5.73 (m, 1H), 7.30 (m, 10H); 13C NMR
(100 MHz, CDCl3) δ 37.60, 50.76, 63.87, 71.04, 71.86, 83.93,
87.88, 117.35, 127.67, 127.75, 128.39, 128.43, 134.94, 137.93; MS
(FAB) 324 (M+ + 1). Anal. Calcd for C21H25NO2: C, 78.02; H,
7.74; N, 4.33. Found: C, 78.16; H, 7.70; N, 4.28.
ether); [R]25 -38.7 (c 2.9, CHCl3); IR (thin film) 3450, 2101,
D
1266, 1072 cm-1
;
1H NMR (400 MHz, CDCl3) δ 2.56 (bs, OH),
3.42 (dd, J ) 13.0, 4.4 Hz, 1H), 3.48 (dd, J ) 13.0, 7.3 Hz, 1H),
3.57 (m, 1H), 3.59 (dd, J ) 9.7, 4.1 Hz, 1H), 3.66 (dd, J ) 11.7,
3.4, Hz, 1H), 3.74 (m, 2H), 4.49 (d, J ) 11.5 Hz, 1H), 4.53 (d, J
) 11.5, 1H), 4.54 (d, J ) 11.2 Hz, 1H), 4.63 (d, J ) 11.2 Hz,
1H), 7.28 (m, 10H); 13C NMR (100 MHz, CDCl3) δ 51.09, 63.18,
71.34, 73.39, 73.70,76.06, 78.38, 128.14, 128.27, 128.50, 128.56,
136.91, 137.34; MS (FAB): 358 (M+ + 1). Anal. Calcd for
(2R,3R,4R)-1-(2-Allyl-3,4-bis-ben zyloxy-p yr r olid in -1-yl)-
p r op en on e (3). A solution of the cyclized amine 11 (106 mg,
0.33 mmol) and triethylamine (180 µL, 1.31 mmol) in dry DCM
(1 mL) was treated with acryloyl chloride (40 µL, 0.49 mmol) at
0 °C under a N2 atmosphere. The reaction mixture was stirred
for 12 h (from 0 °C to rt) and then diluted with diethyl ether
and washed with water and brine. The mixture was dried over
anhydrous sodium sulfate, concentrated in vacuo and chromato-
graphed over silica gel to give the pure amide 3: yield 105 mg
(85%); Rf 0.65 (50% EtOAc in petroleum ether); 1H NMR (400
MHz, CDCl3) δ 2.32 (m, 1H), 2.53 (m, 0.5H, rotamer), 2.75 (m,
0.5H, rotamer), 3.64 (m, 1H), 3.84 (dd, J ) 11.2, 5.6 Hz, 0.5H,
rotamer), 3.95 (m, 3H), 4.25 (dd, J ) 10.7, 3.9 Hz, 0.5H, rotamer),
4.45 (m, 4H), 5.02 (m, 2H), 5.62 (m, 1H), 5.75 (m, 1H), 6.34 (m,
2H), 7.28 (m, 10H); 13C NMR (100 MHz, CDCl3) δ 34.84, 37.60,
50.48, 51.65, 61.82, 62.49, 71.09, 71.34, 71.50, 71.60, 79.72, 81.11,
81.74, 83.89, 117.75, 118.56, 127.52, 127.56, 127.63, 127.75,
127.80, 127.86, 127.94, 128.04, 128.41, 128.48, 128.53, 133.58,
134.85, 137.35, 137.51, 164.72 (most of the carbons are showing
two peaks because of the presence of rotamers). Anal. Calcd for
C24H27NO3: C, 76.39; H, 7.16; N, 3.71. Found: C, 76.34; H, 7.20;
N, 3.68.
C
19H23N3O4: C, 63.86; H, 6.44; N, 11.76. Found: C, 63.90; H,
6.48; N, 11.81.
(4S,5R,6R)-7-Azid o-5,6-bis-ben zyloxy-h ep t-1-en -4-ol (4).
A solution of the azido diol 9 (430 mg, 1.20 mmol) in dry DCM
(6 mL) was treated with lead tetraacetate at 0 °C and further
stirred for 3 h (0 °C - rt). The reaction mixture was cooled (ice
bath), and the reaction was quenched with aqueous NaHCO3.
The solids were filtered through a Celite pad, and the filtrate
was extracted with dichloromethane. The organic layer was
washed with water and brine and dried over anhydrous sodium
sulfate before being concentrated in vacuo to provide an alde-
hyde. A solution of this crude aldehyde in dry DCM (5 mL) was
cooled to -78 °C under a N2 atmosphere, and to this was added
SnCl4 (155 µL, 1.32 mmol, in 1.2 mL of DCM). Then, a solution
of allyltributyl stannane (405 µL, 1.32 mmol) in DCM (1.2 mL)
was added dropwise at the same temperature. The reaction
mixture was stirred for 1 h, and then the reaction was quenched
by an addition of 1 N NaOH in wet MeOH. The cooling bath
was removed, and the flask was brought to room temperature.
The solvent was removed in vacuo, and the residue was taken
in water and extracted with DCM. The organic layer was washed
with water and brine, dried (anhydrous sodium sulfate), and
(1R,2R,8a R)-1,2-Bis-b en zyloxy-2,3,8,8a -t et r a h yd r o-1H -
in d olizid in -5-on e (2). Grubbs catalyst (13 mg, 0.0154 mmol)
was added to a solution of 3 (58 mg, 0.15 mmol) in toluene (20
mL) and refluxed for 24 h. The solvent was evaporated, and the