1614 J . Org. Chem., Vol. 61, No. 5, 1996
Burgey et al.
94%): 1H NMR (300 MHz, CDCl3) δ 1.69 (s, 3H), 2.98 (d, J )
17.6 Hz, 1H), 3.48 (d, J ) 17.6 Hz, 1H), 3.65 (bs, 1H), 4.10 (d,
J ) 6.4 Hz, 1H), 4.41 (d, J ) 3.0 Hz, 1H), 4.43 (d, J ) 12.3 Hz,
1H), 4.59 (bs, 2H), 4.61 (dd, J ) 3.0 Hz, J ) 6.4 Hz, 1H), 4.91
(d, J ) 12.3 Hz, 1H), 5.01 (s, 1H), 5.67 (d, J ) 1.4 Hz, 1H),
7.27-7.51 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 23.87, 40.86,
58.51, 72.47, 72.56, 74.07, 75.35, 78.91, 100.42, 128.01, 128.50,
128.61, 128.89, 129.13, 137.02, 137.67, 169.68, 203.38; GC/MS
deacetylation (NaOMe, MeOH) of 4 above (16 mg, 65 µmol)
was dissolved in DMF under argon. Sodium hydride (10.3 mg,
259 mmol, 60% suspension) was added, and 5 min later BnBr
was added. After 5 h the reaction was quenched by addition
of saturated aqueous NH4
Cl, and the solution was processed
and chromatographed to give 15 (9.5 mg, 28%) and 11b (11.9
mg, 35%). For 11b: 1H NMR (300 MHz, CDCl3) δ 1.65 (s, 3H),
2.48 (dd, J ) 8.6 Hz, J ) 13.2 Hz, 1H), 2.64 (ddd, J ) 8.2 Hz,
J ) 13.2 Hz, 1H), 3.55 (bs, 1H), 3.72 (dd, J ) 8.2 Hz, J ) 8.6
Hz, 1H), 4.33-4.45 (m, 4H), 4.50 (d, J ) 11.8 Hz, 1H), 4.51 (d,
J ) 12.1 Hz, 1H), 4.55 (d, J ) 11.8 Hz, 1H), 4.62 (d, J ) 12.1
Hz, 1H), 4.89 (d, J ) 12.4 Hz, 1H), 4.98 (s, 1H), 5.50 (d, J )
1.4 Hz, 1H), 7.26-7.48 (m, 15H); 13C NMR (75 MHz, CDCl3) δ
24.01, 30.44, 58.93, 70.62, 70.81, 71.78, 72.28, 72.47, 73.31,
78.31, 98.60, 127.67, 127.80, 128.35, 128.41, 128.63, 128.66,
129.00, 137.48, 138.05, 138.25, 169.68; GC/MS (NH3) m/z 516
(NH3) m/z 441 (M + NH4)+, 424 (MH)+; [R]20 ) -98.2° (c 0.5,
D
CHCl3); HRMS calcd for C24H25NO6 424.1753, found 424.1755.
N-[(1R,3R,4R,6R,7S,8R,10S)-7,10-Dia cet oxy-4-m et h yl-
en e-2,9-d ioxa tr icyclo[4.3.1.03,8]d ec-6-yl]a ceta m id e (9b).
Methyltriphenylphosphonium iodide (91 mg, 224 µmol) was
suspended in THF (5 mL), and n-BuLi (100 µL of a 2.0 M
solution in THF, 200 µmol) was added at -10 °C. The solution
was allowed to warm to rt and stirred for 1 h, and then 9a (21
mg, 50 µmol), dissolved in THF (2 mL), was added. After 10
h the reaction was quenched by the addition of acetone. The
solution was adsorbed onto silica gel and filtered through a
pad of silica with Et2O and concentrated, and the residue was
chromatographed with 30% ethyl acetate/hexanes (17 mg, 79%,
colorless syrup): 1H NMR (300 MHz, CDCl3) δ 1.66 (s, 3H),
2.90 (d, J ) 16.1 Hz, 1H), 3.20 (ddd, J ) 2.2 Hz, J ) 2.2 Hz,
J ) 16.1 Hz, 1H), 3.56 (bs, 1H), 4.33 (d, J ) 2.6 Hz, 1H), 4.40-
4.49 (m, 3H), 4.52 (d, J ) 11.6 Hz, 1H), 4.59 (d, J ) 11.6 Hz,
1H), 4.86 (d, J ) 12.3 Hz, 1H), 4.99 (s, 1H), 5.02 (bs, 1H), 5.08
(bs, 1H), 5.47 (m, 1H), 7.25-7.45 (m, 10H); 13C NMR (75 MHz,
CDCl3) δ 24.07, 32.72, 58.19, 72.02, 72.27, 74.24, 75.41, 78.77,
79.38, 98.76, 113.99, 127.68, 127.85, 128.33 128.52, 128.60,
128.97, 137.48, 138.35, 139.97, 169.56; GC/MS (NH3) m/z 587
(M + NH4)+; 422 (MH)+; [R]20D ) -119.9° (c 0.5, CHCl3); HRMS
calcd for C25H27NO5 422.1960, found 422.1969.
(MH)+; [R]20D ) -94.6° (c 0.5, CHCl3); HRMS calcd for C31H33
-
NO6 516.2377, found 516.2375. For 15: 1H NMR (300 MHz,
CDCl3) δ 1.69 (s, 3H), 2.58-2.63 (m, 2H), 3.56 (bs, 1H), 4.04
(m, 1H), 4.25 (dd, J ) 4.4 Hz, J ) 6.0 Hz, 1H), 4.32 (d, J )
11.4 Hz, 1H), 4.42 (d, J ) 12.5 Hz, 1H), 4.43 (dd, J ) 3.2 Hz,
J ) 6.0 Hz, 1H), 4.55 (d, J ) 11.7 Hz, 1H), 4.61 (d, J ) 11.7
Hz, 1H), 4.78 (d, J ) 11.4 Hz, 1H), 4.82 (d, J ) 12.5 Hz, 1H),
4.99 (s, 1H), 5.03 (d, J ) 3.2 Hz, 1H), 5.40 (d, J ) 1.4 Hz, 1H),
7.23-7.48 (m, 15 H); 13C NMR (75 MHz, CDCl3) δ 24.21, 29.33,
57.79, 70.97, 72.13, 72.36, 72.90, 73.55, 74.41, 75.15, 78.68,
98.80, 127.63, 127.70, 128.00, 128.30, 128.42, 128.54, 128.59,
128.96, 137.50, 137.98, 138.49, 169.46; GC/MS (NH3) m/z 516
(MH)+; [R]20D ) -90.3° (c 0.5, CHCl3); HRMS calcd for C31H33
NO6 516.2377, found 516.2399.
-
N -[(1R ,3R ,5S ,6S ,7R ,9R ,10S )-6,9,10-T r ia c e t o x y -2,4-
d ioxa tr icyclo[3.3.1.13,7]d ec-7-yl]a ceta m id e (12a ). Com-
pound 11a (13 mg, 35 µmol) was subjected to the standard
acetolysis procedure at 0 °C and warmed to rt. After 24 h the
addition was repeated, no change being observed after 48 h.
After workup the residue was chromatographed on silica gel
with 80% EtOAc/hexane to give 8 mg (65%) of a brown syrup:
1H NMR (300 MHz, CDCl3) δ 1.71 (s, 3H), 2.06 (s, 3H), 2.18
(s, 3H), 2.68 (d, J ) 12.8 Hz, 1H), 3.08 (d, J ) 12.8 Hz, 1H),
3.86 (d, J ) 2.0 Hz, 1H), 4.31 (dd, J ) 1.9 Hz, J ) 1.8 Hz, 1H),
4.43-4.62 (m, 3H), 4.85 (d, J ) 12.0 Hz, 1H), 4.95 (d, J ) 1.8
Hz, 1H), 5.29 (d, J ) 1.9 Hz, 1H), 5.34 (bs, 1H), 5.40 (d, J )
2.0 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 20.92, 21.66, 23.91,
32.48, 57.02, 68.03, 70.88, 72.11, 72.27, 72.55, 75.34, 94.36,
97.70, 137.26, 137.77, 167.47, 170.02, 170.88; GC/MS (NH3)
m/z 526 (MH)+.
N-[(1S,3S,4S,5S,7R,8S,9S)-7,8-Dia cet oxy-4,9-b is(b en -
zyloxy)-2-oxa tr icyclo[3.3.1.13,7]d ec-5-yl]a ceta m id e (10b).
Compound 9b (19 mg, 45 µmol) was subjected to the standard
acetolysis conditions, and after 1 h at 0 °C, TLC indicated
completion. Workup and chromatography with 30-40% ethyl
acetate/hexanes afforded 10b (12 mg, 56%) as a colorless
syrup: 1H NMR (300 MHz, CDCl3) δ 1.71 (s, 3H), 1.96 (s, 3H),
2.14 (s, 3H), 2.30 (ddd, J ) 2.2 Hz, J ) 2.2 Hz, J ) 12.5 Hz,
1H), 2.61 (bd, J ) 12.5 Hz, 1H), 2.71 (d, J ) 12.5 Hz, 1H),
2.80 (dd, J ) 2.0 Hz, J ) 12.5 Hz, 1H), 3.97 (d, J ) 3.9 Hz,
1H), 4.14 (m, 1H), 4.30 (ddd, 1H), 4.42 (d, J ) 11.9 Hz, 1H),
4.49 (d, J ) 11.6 Hz, 1H), 4.59 (d, J ) 11.6 Hz, 1H), 4.73 (d,
J ) 11.9 Hz, 1H), 4.81 (d, J ) 1.7 Hz, 1H), 5.19 (m, 1H), 5.41
(s, 1H), 7.20-7.44 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 21.11,
22.11, 24.08, 28.37, 33.34, 58.40, 69.74, 71.11, 72.02, 72.54,
72.64, 72.71, 76.12, 76.18, 127.61, 128.31, 128.46, 128.95,
137.63, 138.19, 169.70, 169.97, 170.11; GC/MS (NH3) m/z 524
N -[(1R ,3R ,5S ,6S ,7R ,9R ,10S )-9-Ace t oxy-6,10-b is(b e n -
zyloxy)-2,4-d ioxa t r icyclo[3.3.1.13,7]d ec-7-yl]a cet a m id e
(12b). Compound 11b (19 mg, 45 µmol) was subjected to the
standard acetolysis procedure at 0 °C for 1 h. Workup and
chromatography on silica gel with 30-40% EtOAc/hexane gave
12b (11.4 mg, 48%) as a colorless syrup: 1H NMR (300 MHz,
CDCl3) δ 1.73 (s, 3H), 2.19 (s, 3H), 2.45 (d, J ) 3.0 Hz, 1H),
3.91 (d, J ) 2.2 Hz, H1), 4.17 (m, 1H), 4.20 (m, 1H), 4.44 (d, J
) 12.0 Hz, H1), 4.51 (d, J ) 11.7 Hz, H1), 4.59 (bs, 1H), 4.61
(d, J ) 11.7 Hz, 1H), 4.82 (d, J ) 12.0 Hz, 1H), 4.84 (bs, 1H),
(MH)+; [R]20D ) -32.90° (c 0.3, CHCl3); HRMS calcd for C29H33
NO8 524.2275, found 524.2203.
-
N -[(1R ,3R ,4R ,6R ,7S ,8S ,10S )-4,7,10-T r ia c e t o x y -2,9-
d ioxa tr icyclo[4.3.1.03,8]d ec-6-yl]a ceta m id e (11a ) a n d Its
4-Ep im er (13). Compound 4 (48 mg, 148 µmol) was dissolved
in EtOAc (10 mL), PtO2 (9.6 mg) was added, and the mixture
was hydrogenated in a Paar apparatus (50 psi). After 9 h the
reaction was complete. The reaction was filtered and concen-
trated, and the residue was chromatographed on silica gel with
EtOAc to give (40 mg, 85%) a colorless syrup. The separation
of the two alcohol products was only possible in part. Samples
of 4R and 4S isomers were acetylated in the usual way to give
11a and 13. For 11a : 1H NMR (300 MHz, CDCl3) δ 1.95 (s,
3H), 2.17 (s, 6H), 2.30 (s, 3H), 2.45 (dd, J ) 8.8 Hz, J ) 13.4
Hz, 1H), 2.91 (dd, J ) 8.7 Hz, J ) 13.4 Hz, 1H), 4.52 (d, J )
6.2 Hz, 1H), 4.91 (dd, J ) 3 Hz, J ) 6.2 Hz, 1H), 5.08 (bs, 1H),
5.25 (dd, J ) 8.7 Hz, J ) 8.8 Hz, 1H), 5.38 (bs, 1H), 5.70 (d, J
) 3.0 Hz, 1H), 6.27 (s, 1H). For 13: 1H NMR (300 MHz,
CDCl3) δ 1.88 (s, 3H), 2.13 (s, 3H), 2.14 (s, 3H), 2.22 (s, 3H),
2.59 (d, J ) 15.6 Hz, 1H), 2.71 (dd, J ) 6.6 Hz, J ) 15.6 Hz,
1H), 4.37 (m, 1H), 4.93 (dd, J ) 3.2 Hz, J ) 6.0 Hz, 1H), 5.01-
5.04 (m, 1H), 5.28 (d, 1.9 Hz, 1H), 5.31-5.36 (m, 1H), 6.00 (d,
J ) 3.2 Hz, 1H), 6.15 (s, 1H).
5.20 (d, J ) 2.2 Hz, 1H), 5.31 (s, 1H), 7.22-7.48 (m, 10H); 13
C
NMR (75 MHz, CDCl3) δ 21.21 24.05, 29.38, 55.19, 68.86,
71.32, 72.09, 72.23, 72.56, 75.86, 77.24, 91.87, 127.63, 127.76,
128.38, 128.46, 128.59, 128.99, 137.49, 137.94, 170.18, 170.93;
GC/MS (NH3) m/z 468 (MH)+; [R]20 ) -99.6° (c 0.4, CHCl3);
D
HRMS calcd for C26H29NO7 468.2014, found 468.2040.
N-[(1S,5R,7S,8R,9S)-4,7,8,9-Tetr a a cetoxy-2-oxa bicyclo-
[3.3.1]n on -3-en -5-yl]a ceta m id e (14). Compound 13 (8 mg,
22 µmol) was subjected to the standard acetolysis conditions
and after 1 h at 0 °C the mixture was warmed to rt. After 6
and 24 h, additional TESOTf (13 µL, 57 µmol; 20 µL, 48 µmol)
was added. The reaction was then processed and the residue
chromatographed with 10, 15, and 50% acetone/CH2Cl2, yield-
1
ing a 9:1 mixture of 14 and starting material as judged by H
NMR (4 mg, 45%): 1H NMR (300 MHz, CDCl3) δ 1.95 (s, 3H),
2.00 (m, 3H), 2.09 (s, 3H), 2.11 (s, 3H), 2.23 (s, 3H), 2.56 (dd,
J ) 6.3 Hz, J ) 13.2 Hz, 1H), 2.72 (dd, J ) 11.0 Hz, J ) 13.2
Hz, 1H), 4.65 (dd, J ) 2.1 Hz, J ) 3.3 Hz, 1H), 5.15 (dd, J )
3.3 Hz, J ) 10.1 Hz, 1H), 5.52 (ddd, J ) 6.3 Hz, J ) 10.1 Hz,
J ) 11.0 Hz, 1H), 5.80 (s, 1H), 5.82 (d, J ) 2.1 Hz, 1H), 6.63
N-[(1R,3R,4R,6R,7S,8S,10S)-4,7,10-Tr is(ben zyloxy)-2,9-
d ioxa tr icyclo[4.3.1.03,8]d ec-6-yl]a ceta m id e (11b) a n d Its
4-Ep im er (15). The mixture of alcohols from reduction and