Humphries et al.
fractions were dried (MgSO4), filtered, and concentrated. The
residue was purified by silica gel column chromatography
eluting with petroleum ether/ethyl acetate (20:3) to give 18
anhydrous THF (10 mL). The mixture was stirred for 2 h at
-78 °C and then allowed to warm to room temperature over
16 h. Water (5 mL), ethyl acetate (20 mL), and 10% aqueous
HCl (20 mL) were added, and the mixture was vigorously
stirred for 20 min. The organic layer was separated, and the
aqueous phase was back-extracted with ethyl acetate (4 × 20
mL). The combined organic fractions were dried (MgSO4),
filtered, and concentrated to give a residue that was purified
by silica gel column chromatography eluting with petroleum
ether/ethyl acetate.(7:3) to give 22 as a light yellow oil that
(573 mg, 44%): [R]20 ) +1.6 (c 1, CHCl3); νmax cm-1 1641; 1H
D
NMR (500 MHz, CDCl3) δ 2.49 (1H, m), 2.81 (1H, dd, J ) 3.4
and 13.7 Hz), 2.90 (2H, m), 3.17 (1H, dd, J ) 4.4 and 14.2
Hz), 3.93 (1H, m), 3.98 (1H, d, J ) 15.1 Hz), 5.57 (2H, m),
5.67(1H, d, J ) 15.1 Hz), 7.00-7.28 (15H, m); 13C NMR (75
MHz, CDCl3) δ 37.23, 39.04, 41.52, 46.59, 57.47, 125.06, 126.09,
126.68, 127.21, 127.40, 127.57, 128.09, 128.17, 128.55, 129.60,
129.91, 135.88, 136.81, 138.93, 170.525; m/z (ES+) MH+, 368.2
(100%). Further elution gave 19 as a colorless solid (568 mg,
44%), which was recrystallized from ethyl acetate/ petroleum
crystallized on standing (144 mg, 76%): [R]20 ) -90.4 (c 1,
D
CHCl3); mp ) 130-133 °C; νmax cm-1 3382, 1646, 1608; 1H
NMR (500 MHz, CDCl3) δ 1.80 (1H, br), 2.60 (1H, dd, J ) 8.3
and 13.7 Hz), 2.80 (1H, dd, J ) 6.3 and 13.7 Hz), 3.58 (1H, d,
J ) 14.6 Hz), 3.65 (2H, m), 3.76 (1H, d, J ) 15.6 Hz), 3.88
(1H, m), 5.27 (1H, d, J ) 14.6 Hz), 6.10 (1H, m), 6.98-7.34
(15H, m); 13C NMR (75 MHz, CDCl3) δ 36.78, 38.03, 48.92,
63.57, 63.72, 126.40, 126.93, 127.69, 128.39, 128.54, 128.75,
128.81, 129.10, 129.34, 131.52, 137.02, 137.11, 138.54, 139.05,
162.69; HRMS calcd for C26H25O2N 383.1885, found 383.1879.
ether to give colorless bricks: [R]20 ) -109.0 (c 1, CHCl3);
D
1
mp ) 155 °C; νmax cm-1 1639; H NMR (500 MHz, CDCl3) δ
2.15 (2H, m), 2.71 (1H, dd, J ) 3.4 and 13.2 Hz), 2.96 (1H, dd,
J ) 3.9 and 12.7 Hz), 3.21 (1H, m), 3.93 (1H, m), 4.00 (1H, d,
J ) 15.1 Hz), 5.46 (1H, dd, J ) 3.4 and 10.7 Hz), 5.51 (1H, dd,
J ) 3.4 and 10.7 Hz), 5.67 (1H, d, J ) 15.1 Hz), 6.97-7.34
(15H, m); 13C NMR (126 MHz, CDCl3) δ 39.57, 39.82, 43.77,
46.68, 57.72, 124.89, 126.09, 126.37, 126.74, 127.41, 128.00,
128.15, 128.31, 128.63, 129.60, 129.81, 136.32, 136.90, 138.51,
170.37; m/z (ES+) MH+, 368.2 (100%).
Rou te B. Epoxide 21 (150 mg, 0.41 mmol) in anhydrous
THF (10 mL) was similarly treated with a 2 M solution of
lithium diisopropylamide in THF/benzene (0.203 mL, 0.41
mmol) to give 22 as a light yellow oil (81 mg, 54%). Spectro-
scopic data as above.
(1S,2S,5S,6R)-(2,3,5)-Tr iben zyl-7-oxa-3-aza-bicyclo[4.1.0]-
h ep ta n -4-on e (20). To a solution of 18 (333 mg, 0.94 mmol)
in acetone (12 mL) and water (10 mL) was added sodium
hydrogen carbonate (2.694 g, 32.07 mmol). The mixture was
cooled in an ice bath, and Oxone (5.801 g, 9.43 mmol) was
added portion-wise over 5 min. The resulting mixture was
vigorously stirred at this temperature for 2 h and then at room
temperature for 16 h. The majority of acetone was removed
under reduced pressure before ethyl acetate (50 mL) and water
were added (50 mL). The organic layer was separated, and
the aqueous layer was back-extracted with ethyl acetate (4 ×
30 mL). The combined organic fractions were dried (MgSO4),
filtered, and concentrated, and the resulting residue was
purified by silica gel column chromatography eluting with
petroleum ether/ethyl acetate (10:2) to give 20 as a white solid
(3S ,5R ,6S )-(1,3,6)-Tr ib e n zyl-5-h yd r oxy-p ip e r id in -2-
on e (23) a n d (3R,5R,6S)-(1,3,6)-Tr iben zyl-5-h yd r oxy-p i-
p er id in -2-on e (24). A solution of 22 (67 mg, 0.17 mmol) in
ethyl acetate (10 mL) was vigorously stirred with 10% pal-
ladium on carbon (10 mg) under a atmosphere of hydrogen
for 72 h at room temperature. The mixture was filtered
through a pad of Celite and concentrated to give a residue that
was purified by silica gel column chromatography eluting with
petroleum ether/ethyl acetate (7:3) to give two products.
Compound 23 was obtained as a colorless oil (25 mg, 37%):
[R]20 ) -62.5 (c 2, CHCl3); νmax cm-1 3351, 1611; 1H NMR
D
(500 MHz, CDCl3) δ 1.71 (1H, s), 1.78 (2H, m), 2.14 (1H, dd,
J ) 9.3 and 14.2 Hz), 2.71 (1H, dd, J ) 5.4 and 14.2 Hz), 3.00
(2H, m), 3.21 (1H, dd, J ) 3.4 and 12.2 Hz), 3.39 (1H, m), 3.73
(2H, m), 5.45 (1H, d, J ) 15.1 Hz), 6.93-7.33 (15H, m); 13C
NMR (75 MHz, CDCl3) δ 28.17, 37.65, 37.72, 39.24, 48.51,
63.80, 64.76, 126.38, 126.82, 127.37, 128.03, 128.34, 128.59,
128.73, 128.81, 129.67, 137.24, 137.31, 138.28, 171.42; HRMS
calcd for C25H27NO2 385.2042, found 385.2031. Compound 24
(189 mg, 54%). [R]20 ) +68.5 (c 3.3, CHCl3); νmax cm-1 1645;
D
1H NMR (500 MHz, CDCl3) δ 1.79 (1H, dd, J ) 3.9 and 11.2
Hz), 2.73 (1H, dd, J ) 11.2 and 14.2 Hz), 2.86 (1H, dd, J ) 3.9
and 14.2 Hz), 2.91 (1H, m), 3.01 (1H, dd, J ) 6.3 and 14.2
Hz), 3.25 (1H, m), 3.54 (1H, dd, J ) 3.9 and 13.7 Hz), 3.86
(1H, d, J ) 15.1 Hz), 3.98 (1H, m), 5.46 (1H, d, J ) 15.1 Hz),
7.05-7.35 (15H, m); 13C NMR (126 MHz, CDCl3) δ 34.52, 37.09,
42.54, 48.08, 52.54, 53.09, 55.66, 126.20, 127.21, 127.29,
127.51, 128.39, 128.64, 128.67, 129.20, 129.76, 135.56, 136.41,
139.22, 168.69; HRMS calcd for C26H25NO2 383.1885, found
383.1881. Compound 22 (12%) was also isolated (data as
reported below).
was obtained as a white gum (25 mg, 37%). [R]20 ) +10.9 (c
D
2, CHCl3); νmax cm-1 3393, 1602; 1H NMR (500 MHz, CDCl3) δ
1.25 (1H, br), 1.62 (1H, m), 2.01 (1H, ddd J ) 4.4, 7.8 and
14.65 Hz), 2.57 (1H, m), 2.71 (1H, dd, J ) 8.3 and 13.7 Hz,),
2.85 (1H, dd, J ) 10.2 and 13.7 Hz), 2.97 (1H, dd, J ) 4.9 and
13.7 Hz), 3.45 (1H, dd, J ) 4.4 and 7.8 Hz), 3.48 (1H, dd, J )
4.4 and 13.7 Hz), 3.80 (1H, m), 3.81 (1H, d, J ) 14.6 Hz), 5.46
(1H, d, J ) 14.6 Hz), 7.05-7.34 (15H, m); 13C NMR (126 MHz,
CDCl3) δ 29.95, 38.41, 38.57, 39.37, 48.31, 64.09, 66.75, 126.19,
126.95, 127.51, 128.19, 128.39, 128.69, 128.82, 129.06, 129.49,
137.04, 137.15, 140.06, 172.28; HRMS calcd for C26H27NO2
385.2042, found 385.2045.
(1S,2S,5R,6R)-(2,3,5)-Tr iben zyl-7-oxa-3-aza-bicyclo[4.1.0]-
h ep ta n -4-on e (21). Alkene 18 (228 mg, 0.65 mmol) in acetone
(8 mL) and water (7 mL) was treated with sodium hydrogen
carbonate (1.845 g, 21.96 mmol) and Oxone (3.972 g, 6.46
mmol) as described for the preparation of 20. The crude
product was purified by silica gel column chromatography
eluting with petroleum ether/ethyl acetate (20:3) to give 21
as a white solid (150 mg, 60%): [R]20 ) -49.3 (c 1, CHCl3);
D
Ack n ow led gm en t. The work was supported by a
Royal Society of New Zealand Marsden grant. The
authors would also like to thank Dr. J . Wikaira and
Professor W. Robinson (University of Canterbury) for
help with the X-ray crystallography.
mp ) 123-125 °C; νmax cm-1 1643; 1H NMR (500 MHz, CDCl3)
δ 2.30 (2H, m), 2.82 (1H, dd, J ) 3.9 and 14.2 Hz), 3.08 (1H,
dd, J ) 3.9 and 13.7 Hz), 3.16 (2H, br), 3.29 (1H, m), 3.86 (1H,
d, J ) 15.6 Hz), 3.90 (1H, br), 5.51 (1H, d, J ) 15.6 Hz), 7.03-
7.35 (15H, m); 13C NMR (75 MHz, CDCl3) δ 36.19, 37.59, 44.19,
47.72, 52.37, 53.71, 56.14, 126.87, 127.18, 127.39, 127.66,
128.67, 128.75, 128.92, 129.18, 129.38, 136.21, 136.29, 138.24,
168.73; HRMS calcd for C26H25NO2 383.1885, found 383.1889.
(5R,6S)-(1,3,6)-Tr ib en zyl-5-h yd r oxy-5,6-d ih yd r o-1H -
p yr id in -2-on e (22). Rou te A. A solution of LDA (0.248 mL,
2 M solution in THF/benzene, 0.50 mmol) was added dropwise
to a -78 °C stirred solution of 20 (190 mg, 0.50 mmol) in
Su p p or tin g In for m a tion Ava ila ble: Details of the crys-
tal structure analyses of 9, 10, and 19. NMR spectra of
compounds 7-12, 16, and 18-24. This material is available
J O0267091
2436 J . Org. Chem., Vol. 68, No. 6, 2003