4300 J . Org. Chem., Vol. 62, No. 13, 1997
Paquette et al.
mmol) was dissolved with 2,6-di-tert-butyl-4-methylpyridine
(37 mg, 0.18 mmol) in dry CH2Cl2 (0.5 mL), cooled to 0 °C,
and treated with triflic anhydride (27 mg, 0.094 mmol) in 0.75
mL of CH2Cl2. The reaction mixture was allowed to warm to
20 °C, stirred for 2 h, and quenched by the addtion of a
saturated NaHCO3 solution (1 mL). The products were
extracted into ethyl acetate, dried, and concentrated. Chro-
matography of the residue on silica gel (gradient elution from
6:1 ethyl acetate/hexanes to pure ethyl acetate) gave pure
samples of 30 and 31.
2.1, 10.3 Hz, 1 H), 5.43 (d, J ) 10.0 Hz, 1 H), 5.37 (dd, J )
2.3, 7.0 Hz, 1 H), 5.20-5.09 (m, 1 H), 5.03 (ddd, J ) 2.7, 6.3,
12.4 Hz, 1 H), 4.39 (dd, J ) 2.6, 12.5 Hz, 1 H), 4.14-3.98 (m,
1 H), 4.03 (dd, J ) 6.7, 12.4 Hz, 1 H), 3.76 (dd, J ) 2.4, 10.4
Hz, 1 H), 2.20 (ddd, J ) 2.1, 5.1, 12.3 Hz, 1 H), 2.12 (s, 3 H),
2.09 (s, 3 H), 2.08 (s, 3 H), 2.03 (s, 3 H), 2.02 (s, 3 H), 1.94-
1.83 (m, 1 H), 1.88 (s, 3 H); 13C NMR (75 MHz, CDCl3) ppm
170.9, 170.6, 170.3, 170.1, 169.8, 168.7, 73.7, 70.2 (2 C), 70.1,
67.1, 62.0, 49.3, 35.1, 23.2, 20.9, 20.8 (2 C), 20.74, 20.72; MS
m/ z (M++1) calcd 476.1767, obsd 476.1790.
F or 30: 1H NMR (300 MHz, C6D6) δ 5.54-5.36 (m, 1 H),
4.97-4.82 (m, 2 H), 4.01 (dd, J ) 7.7, 14.7 Hz, 1 H), 3.60-
2.41 (m, 1 H), 3.39-3.27 (m, 2 H), 2.16-2.04 (m, 1 H), 1.82 (s,
3 H), 1.77-1.67 (m, 1 H), 1.30 (s, 3 H); 13C NMR (75 MHz,
C6D6) ppm 156.6, 132.4, 118.3, 94.7, 73.2, 63.4, 60.9, 34.8, 28.3,
23.7; MS m/ z (M+) calcd 197.1052, obsd 197.1059.
Anal. Calcd for C20H29NO12: C, 50.52; H, 6.15. Found: C,
50.40; H, 6.10.
Gen er a l P r oced u r e for th e Allyla tion of 35-43.
A
mixture consisting of the aldehyde (3.24 mmol), indium powder
(409 mg, 3.56 mmol), and ammonium chloride (260 mg, 4.86
mmol) in water (21 mL) was stirred vigorously for 5-10 min
prior to the addition of allyl bromide (841 µL, 9.72 mmol).
Reaction was allowed to proceed until no starting material was
evident by TLC analysis. Ethyl acetate (20 mL) and saturated
NaHCO3 solution were introduced, the mixture was stirred
for 30 min, and the solids were removed by filtration through
a pad of Celite. The aqueous phase was separated and
extracted with ethyl acetate (2 × 10 mL). The combined
organic solutions were washed with brine, dried, and concen-
trated to leave a residue which was chromatographed on silica
gel (elution with 0-10% ethyl acetate in hexanes). The results
are compiled in Table 3, and the pertinent spectral data are
provided below.
F or 31: 1H NMR (300 MHz, C6D6) δ 5.54-5.36 (m, 1 H),
5.00-4.87 (m, 2 H), 3.71 (dd, J ) 6.3, 11.4 Hz, 1 H), 3.60-
3.41 (m, 2 H), 3.11 (t, J ) 6.8 Hz, 1 H), 2.16-2.04 (m, 1 H),
2.01-1.90 (m, 1 H), 1.80 (s, 3 H), 1.30 (s, 3 H); 13C NMR (75
MHz, C6D6) ppm 156.6, 131.6, 119.1, 94.7, 76.7, 68.1, 63.1, 38.8,
27.7, 23.6; MS m/ z (M+) calcd 197.1052, obsd 197.1059.
Anal. Calcd for C10H15NO3: C, 60.90; H, 7.67. Found: C,
60.80; H, 7.71.
Stu d ies In volvin g 25. A mixture of 25 (53 mg, 0.22 mmol),
allyl bromide (48 mg, 0.40 mmol), and indium powder (28 mg,
0.24 mmol) in the solvent of choice (3.9 mL) was stirred
vigorously at rt until reaction was complete and freed of
solvent. The product mixture was dissolved in pyridine (3 mL),
treated with acetic anhydride (3 mL) together with DMAP (10
mg), stirred at rt for 24 h, and evaporated in vacuo. Chro-
matography of the residue on silica gel (elution with 2:1
hexanes/ethyl acetate) and the diastereomeric ratios were
En tr y 27. Syn diastereomer: IR (neat, cm-1) 3404, 1494,
1453; 1H NMR (300 MHz, CDCl3) δ 7.37-7.22 (m, 10 H), 5.84
(m, 1 H), 5.03 (m, 2 H), 3.84 (d, J ) 13.3 Hz, 2 H), 3.57 (m, 1
H), 3.33 (d, J ) 13.3 Hz, 2 H), 2.62 (m, 1 H), 2.30 (m, 1 H),
1.98 (m, 1 H), 1.80 (br s, 1 H), 1.04 (d, J ) 6.7 Hz, 3 H); 13C
NMR (75 MHz, CDCl3) ppm 138.8-127.2 (12 C), 135.1, 116.4,
70.4, 57.9, 53.2 (2 C), 38.0, 8.0; MS m/ z (M+) calcd 295.1935,
obsd 295.1930.
1
determined by H NMR prior to this process.
F or 32: colorless solid, mp 146 °C; IR (CHCl3, cm-1) 1750,
1
1690, 1510, 1375, 1220, 1030; H NMR (300 MHz, CDCl3) δ
Anti diastereomer: 1H NMR (300 MHz, CDCl3) δ 7.43-7.26
(m, 10 H), 5.68 (m, 1 H), 5.10 (d, J ) 12.6 Hz, 2 H), 3.80 (d, J
) 13.7 Hz, 2 H), 3.68 (m, 1 H), 3.48 (d, J ) 13.7 Hz, 2 H), 2.70
(m, 2 H), 2.09 (m, 1 H), 1.84 (br m, 1 H), 1.18 (d, J ) 6.7 Hz,
3 H); 13C NMR (75 MHz, CDCl3) ppm 140.0-126.9 (12 C),
135.4, 118.1, 72.3, 57.0, 55.5 (2 C), 39.3, 8.5; MS m/ z (M+)
calcd 295.1935, obsd 295.1926.
5.88-5.64 (m, 1 H), 5.53 (d, J ) 10.6 Hz, 1 H), 5.34 (dd, J )
2.2, 8.2 Hz, 1 H), 5.23 (dd, J ) 2.2, 5.2 Hz, 1 H), 5.06-4.99
(dm, J ) 2.9 Hz, 1 H), 4.85-4.80 (m, 2 H), 4.83 (dt, J ) 1.6,
6.8 Hz, 1 H), 4.47 (dt, J ) 1.6, 10.5 Hz, 1 H), 4.25 (dd, J ) 3.1,
12.5 Hz, 1 H), 2.23 (t, J ) 6.0 Hz, 2 H), 2.09 (d, J ) 14.4 Hz,
6 H), 2.06-1.85 (br s, 12 H), 1.78 (br s, 1 H); 13C NMR (75
MHz, CDCl3) ppm 170.6, 170.04, 170.00, 169.91, 169.88,
169.83, 132.5, 118.7, 70.4, 68.8, 68.3, 68.0, 62.1, 58.8, 35.9, 23.2,
21.0, 20.9, 20.8, 20.7, 20.6; MS m/ z (M+) calcd 473.1897, obsd
473.1871.
En tr y 28. Syn diastereomer: IR (neat, cm-1) 3506, 1494,
1454, 1265; 1H NMR (300 MHz, CDCl3) δ 7.40-7.25 (m, 15
H), 5.74 (m, 1 H), 5.16 (m, 2 H), 3.92 (m, 1 H), 3.83 (d, J )
13.9 Hz, 2 H), 3.75 (d, J ) 13.9 Hz, 2 H), 3.12 (m, 2 H), 2.97
(dd, J ) 5.2, 12.8 Hz, 1 H), 2.51 (m, 1 H), 2.19 (m, 1 H), 1.97
(m, 1 H); 13C NMR (75 MHz, CDCl3) ppm 140.9-125.8 (18 C),
135.2, 117.9, 70.7, 62.9, 54.8 (2 C), 39.8, 32.0; MS m/ z (M+)
calcd 371.2248, obsd 371.2244.
Anal. Calcd for C21H31NO11: C, 53.27; H, 6.60. Found: C,
53.40; H, 6.65.
F or 33: colorless solid, mp 117 °C (from ether-hexanes);
1H NMR (300 MHz, CDCl3) δ 5.99 (d, J ) 10.4 Hz, 1 H), 5.76-
5.63 (m, 1 H), 5.35 (dd, J ) 2.8, 7.9 Hz, 1 H), 5.17 (dd, J ) 2.8,
8.8 Hz, 1 H), 5.09 (dd, J ) 1.4, 11.2 Hz, 1 H), 5.06-4.97 (m, 2
H), 4.76 (m, 1 H), 4.56 (dt, J ) 3.8, 9.6 Hz, 1 H), 4.30 (dd, J )
3.0, 12.5 Hz, 1 H), 4.00 (dd, J ) 5.7, 12.5, Hz, 1 H), 2.46-2.12
(m, 2 H), 2.08-1.90 (six s, 18 H); 13C NMR (75 MHz, CDCl3)
ppm 170.9, 170.6, 170.23, 170.17, 170.0, 169.8, 133.1, 118.2,
73.1, 69.3, 68.7, 68.4, 61.8, 49.8, 34.8, 23.3, 20.9 (2 C), 20.8,
20.7, 20.6; MS m/ z (M+) calcd 473.1897, obsd 473.1872.
Anal. Calcd for C21H31NO11: C, 53.27; H, 6.60. Found: C,
53.27; H, 6.53.
Ozon olysis of 32. To a solution of 32 (77 mg, 0.16 mmol)
in dry methanol (11 mL) was added sodium metal (260 mg,
11.3 mmol) under N2 at 0 °C. The reaction mixture was stirred
at rt for 3 h, quenched by the addition of dry ice until near-
neutral, filtered, and freed of solvent. The residue (36 mg,
79%) was taken up in methanol (15 mL) and CH2Cl2 (4 mL),
cooled to -78 °C, ozonolyzed for 10 min, flushed with oxygen,
and quenched with 50 mg of Na2SO3. This mixture was stirred
at rt for 21 h, filtered, and evaporated to leave a gum that
was dissolved in pyridine (5 mL) and treated with acetic
anhydride (3 mL) and DMAP (10 mg). This solution was
refluxed for 1 h and stirred at rt before the excess reagents
were removed in vacuo. The residue was purified by chroma-
tography on silica gel (elution with 5:1 hexanes/ethyl acetate)
to give 19 mg (41%) of 34, a colorless solid of mp 162 °C (from
ether/hexanes): 1H NMR (300 MHz, CDCl3) δ 5.64 (dd, J )
Anti diastereomer: 1H NMR (300 MHz, CDCl3) δ 7.49-7.11
(m, 15 H), 5.74 (m, 1 H), 5.09 (m, 2 H), 3.89 (m, 1 H), 3.78 (d,
J ) 13.8 Hz, 2 H), 3.70 (d, J ) 13.8 Hz, 2 H), 3.12 (dd, J )
7.0, 12.9 Hz, 1 H), 3.04 (m, 1 H), 2.93 (dd, J ) 5.4, 12.9 Hz, 1
H), 2.47 (m, 1 H), 2.15 (m, 1 H), 1.80 (br s, 1 H); 13C NMR (75
MHz, CDCl3) 141.0-125.9 (18 C), 135.5, 116.5, 70.8, 63.0, 54.9
(2 C), 39.9, 32.2; MS m/ z (M+) calcd 371.2248, obsd 371.2214.
En tr y 29. Syn diastereomer: IR (neat, cm-1) 3490, 1494,
1453; 1H NMR (300 MHz, CDCl3) δ 7.45-7.18 (m, 10 H), 5.87
(m, 1 H), 5.05 (m, 2 H), 3.96 (d, J ) 13.0 Hz, 2 H), 3.50 (d, J
) 13.0 Hz, 2 H), 2.33 (m, 3 H), 1.97 (m, 2 H), 1.06 (d, J ) 3.3
Hz, 3 H), 1.04 (d, J ) 3.3 Hz, 3 H); 13C NMR (75 MHz, CDCl3)
ppm 138.9-127.1 (12 C), 135.5, 116.5, 66.4, 65.3, 54.0 (2 C),
39.7, 25.1, 23.8, 19.5.
Anti diastereomer: 1H NMR (300 MHz, CDCl3) δ 7.45-7.18
(m, 10 H), 5.87 (m, 1 H), 5.10 (m, 2 H), 3.83 (d, J ) 13.5 Hz,
2 H), 3.75 (d, J ) 13.5 Hz, 2 H), 3.77 (m, 1 H), 2.40 (m, 2 H),
2.19 (m, 2 H), 1.22 (d, J ) 6.7 Hz, 3 H), 1.01 (d, J ) 6.6 Hz, 3
H); 13C NMR (75 MHz, CDCl3) 139.8-127.1 (12 C), 136.2,
117.1, 69.5, 66.4, 55.9 (2 C), 38.8, 27.5, 23.3, 20.6; MS m/ z
(M+) calcd 323.2248, obsd 323.2222.
En tr y 30. Syn diastereomer: IR (neat, cm-1) 3429, 1494,
1454; 1H NMR (300 MHz, CDCl3) δ 7.45-7.18 (m, 10 H), 5.87
(m, 1 H), 5.05 (m, 2 H), 3.98 (d, J ) 13.2 Hz, 2 H), 3.45 (d, J
) 13.2 Hz, 2 H), 3.51 (m, 1 H), 2.56 (m, 2 H), 2.19 (m, 1 H),