134 J . Org. Chem., Vol. 63, No. 1, 1998
J ohnston et al.
3.80 (s, 3 H), 3.75 (br s, 1 H), 3.45 (s, 3 H), 3.40 (s, 3 H), 3.34
(s, 3 H), 3.11 (s, 1 H), 2.48-2.40 (br q, J ) 7.2 Hz, 1 H), 1.97-
1.74 (m, 3 H), 1.55-1.50 (m, 1 H), 1.48 (s, 3 H), 1.34 (s, 3 H),
1.15 (s, 3 H), 1.13-1.02 (m, 1 H), 0.98 (s, 3 H), 0.97 (d, J ) 7.1
Hz, 3 H); 13C NMR (75 MHz, CDCl3) ppm 159.0, 146.9, 134.7,
130.1, 129.7, 126.6, 119.2, 113.6, 109.3, 96.2, 85.8, 85.1, 83.0,
81.2, 80.9, 70.9 (2 C), 60.1, 55.9, 55.2, 53.5, 52.3, 49.4, 45.1,
26.7, 25.6, 25.4, 24.3, 23.4, 21.5, 10.1; MS molecular ion too
fleeting for accurate measurement; [R]20D +47.7 (c 0.83, CHCl3).
(1S,2R,3S,4S,5S,6R,7E)-5-[(4S)-4-[(1R)-1-[(p -Met h oxy-
ben zyl)oxy]a llyl]-2,2-d im eth yl-1,3-d ioxola n -4-yl]-2-(m eth -
oxym et h oxy)-4,11,11-t r im et h yl-6-(p h en ylt h io)b icyclo-
[6.2.1]u n d ec-7-en -3-on e (12a ) a n d (1S,2R,3R,4S,5S,6R,7E)-
5-[(4S )-4-[(1R )-1-[(p -Me t h oxyb e n zyl)oxy]a llyl]-2,2-d i-
m et h yl-1,3-d ioxola n -4-yl]-2-(m et h oxym et h oxy)-4,11,11-
t r im et h yl-6-(p h en ylt h io)b icyclo[6.2.1]u n d ec-7-en -3-on e
(12b). Lithium aluminum hydride (141 mg, 3.72 mmol) was
added to a cold (0 °C) solution of 8 (2.02 g, 3.10 mmol) in
anhydrous ether (30 mL). The suspension was stirred for 2
h, treated with saturated Rochelle’s salt solution, and stirred
for an additional 12 h. Following extraction with ethyl acetate,
the combined organic layers were dried and concentrated. The
residue was chromatographed on silica gel (elution with 20%
ethyl acetate in hexanes) to furnish 1.57 g (77%) of 12a and
134 mg (7%) of 12b, both as colorless oils.
ethyl acetate in hexanes furnished 13a (97 mg, 53%) as a
1
colorless oil; IR (film, cm-1) 3498, 1783, 1613; H NMR (300
MHz, C6D6) δ 7.14 (d, J ) 8.6 Hz, 2 H), 6.79 (d, J ) 8.6 Hz, 2
H), 6.15 (ddd, J ) 17.3, 10.5, 5.7 Hz, 1 H), 5.67 (dd, J ) 12.2,
12.2 Hz, 1 H), 5.37 (d, J ) 17.5 Hz, 1 H), 5.36 (d, J ) 12.2 Hz,
1 H), 5.27 (d, J ) 10.5 Hz, 1 H), 4.47 (d, J ) 11.0 Hz, 1 H),
4.31 (d, J ) 6.9 Hz, 1 H), 4.26 (d, J ) 7.0 Hz, 1 H), 4.09 (d, J
) 11.0 Hz, 1 H), 4.04 (d, J ) 9.2 Hz, 1 H), 3.98 (d, J ) 9.2 Hz,
1 H), 3.95 (d, J ) 5.6 Hz, 1 H), 3.75 (dd, J ) 3.4, 3.4 Hz, 1 H),
3.47-3.37 (m, 2 H), 3.29 (s, 3 H), 3.32-3.24 (m, 1 H), 3.06 (s,
3 H), 2.42 (br d, J ) 11.8 Hz, 1 H), 2.17-2.09 (m, 1 H), 2.08-
1.71 (series of m, 4 H), 1.50 (s, 6 H), 1.46 (s, 3 H), 1.10 (s, 3
H), 1.08 (d, J ) 7.0 Hz, 3 H); 13C NMR (75 MHz, C6D6) ppm
159.9, 135.5, 132.6, 130.4, 130.3, 129.5, 117.9, 114.1, 109.3,
97.8, 95.8, 87.5, 87.0, 84.2, 79.9, 72.3, 66.4, 55.5, 54.7, 53.4,
51.6, 39.6, 35.0, 32.7, 30.1, 27.9, 26.9, 25.6, 20.4, 15.7 (CF3CO
carbons not observed); FAB MS m/z (M+ + H) calcd 657.33,
obsd 657.32; [R]23 -6.9 (c 0.71, CHCl3).
D
(1R,2Z,4S,5S,6S,7R,8S)-4-[(4S)-4-[(1R)-1-[(p -Met h oxy-
ben zyl)oxy]a llyl]-2,2-dim eth yl-1,3-d ioxola n -4-yl]-7-(m eth -
oxym eth oxy)-5,11,11-tr im eth ylbicyclo[6.2.1]u n d ec-2-en e-
1,6-d iol Bis(tr iflu or oa ceta te) (14a ). MCPBA (231 mg, 1.34
mmol) was added to a cold (0 °C) mixture of 12a (796 mg of
80% purity, 0.98 mmol) and NaHCO3 (51 mg, 0.61 mmol) in
CH2Cl2 (15 mL). This mixture was stirred for 1.5 h and treated
with trifluoroacetic anhydride (0.86 mL, 6.1 mmol) followed
by pyridine (0.69 mL, 8.5 mmol). After 1 h, water was
introduced and the separated aqueous layer was further
extracted with CH2Cl2. The combined organic layers were
dried and concentrated. Purification of the residue by chro-
matography on silica gel (elution with 8-20% ethyl acetate
in hexanes) provided 14a as a colorless oil (403 mg, 55%); IR
For 12a : IR (film, cm-1) 3485, 1613; 1H NMR (300 MHz,
C6D6) δ 7.33 (d, J ) 7.3 Hz, 2 H), 7.22 (d, J ) 8.6 Hz, 2 H),
7.04 (dd, J ) 7.2 Hz, 2 H), 6.93 (dd, J ) 7.3 Hz, 1 H), 6.73 (dd,
J ) 8.6 Hz, 2 H), 6.28 (ddd, J ) 17.3, 10.4, 6.8 Hz, 1 H), 5.78
(d, J ) 7.5 Hz, 1 H), 5.39 (d, J ) 10.3 Hz, 1 H), 5.34 (br d, J
) 17.3 Hz, 1 H), 4.53 (d, J ) 11.1 Hz, 1 H), 4.45 (d, J ) 6.4
Hz, 2 H), 4.37 (d, J ) 11.1 Hz, 1 H), 4.33 (d, J ) 6.5 Hz, 1 H),
4.31 (d, J ) 11.1 Hz, 1 H), 4.19 (d, J ) 6.9 Hz, 1 H), 4.16 (d,
J ) 11.2 Hz, 1 H), 3.92-3.85 (m, 2 H), 3.77 (d, J ) 5.7 Hz, 1
H), 3.36 (d, J ) 11.5 Hz, 1 H), 3.25 (s, 3 H), 3.10 (s, 3 H), 3.08-
2.97 (m, 1 H), 2.79 (br s, 1 H), 2.31 (br dd, J ) 12.3 Hz, 1 H),
1.87 (dd, J ) 6.9 Hz, 1 H), 1.64 (ddd, J ) 12.4, 12.4, 5.4 Hz,
1H), 1.45 (s, 3 H), 1.44 (s, 3 H), 1.41 (d, J ) 6.8 Hz, 3 H), 1.33
(s, 3 H), 1.16-1.07 (m, 2 H), 0.82 (s, 3 H); 13C NMR (75 MHz,
C6D6) ppm 159.8, 148.5, 148.4, 136.1, 131.4, 130.3, 130.2, 128.6,
126.1, 120.4, 118.9, 114.2, 109.7, 97.7, 90.3, 87.5, 83.9, 80.7,
72.0, 71.3, 55.7, 54.6, 52.2, 45.8, 45.2, 44.9 (2 C), 27.4, 27.3,
1
(film, cm-1) 1783, 1613, 1515; H NMR (300 MHz, CDCl3) δ
7.24 (d, J ) 8.7 Hz, 2 H), 6.91 (d, J ) 8.6 Hz, 2 H), 6.08 (ddd,
J ) 17.2, 10.6, 5.6 Hz, 1 H), 5.62 (dd, J ) 12.1, 12.1 Hz, 1 H),
5.49 (m, 2 H), 5.45 (d, J ) 10.2 Hz, 1 H), 5.29 (dd, J ) 3.4, 3.4
Hz, 1 H), 4.61 (d, J ) 11.2 Hz, 1 H), 4.58 (d, J ) 7.4 Hz, 1 H),
4.51 (d, J ) 7.4 Hz, 1 H), 4.33 (d, J ) 11.2 Hz, 1 H), 3.97 (d,
J ) 9.2 Hz, 1 H), 3.93 (d, J ) 9.2 Hz, 1 H), 3.92 (d, J ) 5.7 Hz,
1 H), 3.82 (s, 3 H), 3.57 (dd, J ) 3.6, 3.6 Hz, 1 H), 3.41 (s, 3
H), 3.55-3.37 (m, 1 H), 3.20 (ddd, J ) 13.7, 11.4, 4.5 Hz, 1 H),
2.47 (br d, J ) 12.9 Hz, 1 H), 2.43-2.29 (m, 1 H), 2.29-2.20
(m, 1 H), 2.07-1.82 (series of m, 2 H),1.45 (s, 3 H), 1.31 (s, 3
H), 1.20 (s, 3 H), 1.16 (s, 3 H), 0.77 (d, J ) 7.0 Hz, 3 H); 13C
NMR (75 MHz, CDCl3) ppm 159.5, 134.4, 133.8, 130.1, 129.5,
127.2, 118.6, 113.9, 109.3, 96.6, 95.2, 86.7, 83.0, 82.9, 82.4, 71.8,
66.0, 56.3, 55.2, 52.8, 51.4, 38.9, 34.7, 32.2, 29.8, 27.5, 26.5,
25.5, 18.8, 13.7 (CF3CO carbons not observed); FAB MS m/z
26.9, 26.0, 23.1, 22.5, 13.2; [R]21 -284 (c 1.10, CHCl3).
D
For 12b: 1H NMR (300 MHz, CDCl3) δ 7.36 (d, J ) 6.9 Hz,
2 H), 7.26-7.15 (m, 5H), 6.85 (d, J ) 8.7 Hz, 2 H), 5.97 (ddd,
J ) 17.6, 10.2, 7.1 Hz, 1 H), 5.42 (d, J ) 6.6 Hz, 1 H), 5.32 (d,
J ) 17.6 Hz, 1 H), 5.26 (d, J ) 10.2 Hz, 1 H), 4.72 (d, J ) 6.7
Hz, 1 H), 4.66 (d, J ) 6.7 Hz, 1 H), 4.55 (d, J ) 11.6 Hz, 1 H),
4.54 (d, J ) 6.6 Hz, 1 H), 4.41 (d, J ) 9.2 Hz, 1 H), 4.32 (d, J
) 11.6 Hz, 1 H), 4.14 (d, J ) 9.5 Hz, 1 H), 4.07 (d, J ) 9.2 Hz,
1 H), 4.07 (d, J ) 7.1 Hz, 1 H), 3.78 (s, 3 H), 3.77-3.71 (m, 2
H), 3.41 (s, 1 H), 3.39 (s, 3 H), 3.31 (d, J ) 9.5 Hz, 1 H), 2.59
(br s, 1 H), 2.25 (q, J ) 7.6 Hz, 1 H), 2.21-2.16 (m, 3 H), 1.41
(s, 3 H), 1.40 (s, 3 H), 1.31 (s, 3 H), 1.36-1.28 (m, 1 H), 1.09
(d, J ) 7.6 Hz, 3 H), 1.03 (s, 3 H); 13C NMR (75 MHz, CDCl3)
ppm 159.0, 152.0, 136.8, 134.6, 130.7, 130.1, 129.3, 128.4,
126.2, 119.5, 116.8, 113.6, 108.4, 97.6, 88.3, 88.1, 82.5, 70.7,
69.8, 68.0, 55.8, 55.2, 51.8, 50.2, 47.1, 46.3, 33.0, 27.7, 27.5,
26.7, 26.1, 25.2, 21.7, 16.2; MS m/z (M+) calcd 652.3434, obsd
(M+ + H) calcd 753.31, obsd 753.43; [R]21 +28.4 (c 1.33,
D
CHCl3). Anal. Calcd for C36H46F6O10
Found: C, 57.55; H, 6.23.
: C, 57.44; H, 6.16.
(1R,2Z,4S,5S,6S,7R,8S)-4-[(4S)-4-[(1R)-1-Hyd r oxya llyl]-
2,2-d im et h yl-1,3-d ioxola n -4-yl]-7-(m et h oxym et h oxy)-5,-
11,11-tr im eth ylbicyclo[6.2.1]u n d ec-2-en e-1,6-d iol 1,6-Bis-
(tr iflu or oa ceta te) (14b). A solution of 14a (12.5 mg, 0.017
mmol) and DDQ (10 mg, 0.046 mmol) in CH2Cl2 (1 mL)
containing water (2 drops) was stirred vigorously at rt for 3
h, treated with saturated NaHCO3 solution, and extracted with
ether. The combined organic layers were dried and concen-
trated to leave a residue that was chromatographed on silica
gel. Elution with 30% ethyl acetate in hexanes yielded 8.3
mg (79%) of 14b as colorless crystals: mp 155-156 °C; IR
(film, cm-1) 3414, 1784, 1217, 1167; 1H NMR (300 MHz, C6D6)
δ 6.09 (ddd, J ) 17.3, 10.7, 4.0 Hz, 1 H), 5.84-5.40 (m, 2 H),
5.37 (dd, J ) 3.7, 3.7 Hz, 1 H), 5.22 (ddd, J ) 17.3, 1.8, 1.8
Hz, 1 H), 5.11 (ddd, J ) 10.7, 1.8, 1.8 Hz, 1 H), 4.36 (d, J )
7.3 Hz, 1 H), 4.28 (d, J ) 7.3 Hz, 1 H), 3.78 (br s, 1 H), 3.64 (s,
2 H), 3.52 (dd, J ) 3.8, 3.8 Hz, 1 H), 3.42 (m, 1 H), 3.30-3.19
(m, 2 H), 3.15 (s, 3 H), 2.37 (br d, J ) 12.8 Hz, 1 H), 2.08-
1.98 (m, 2 H), 1.85-1.74 (m, 2 H), 1.41 (s, 3 H), 1.39 (s, 3 H),
1.36 (s, 3 H), 1.04 (s, 3 H), 0.52 (d, J ) 7.0 Hz, 3 H); 13C NMR
(75 MHz, C6D6) ppm 137.8, 134.3, 127.3, 115.7, 109.5, 97.0,
95.4, 87.0, 83.2, 82.8, 74.8, 65.6, 56.1, 53.2, 51.6, 38.9, 35.4,
32.6, 29.9, 27.4, 26.8, 25.5, 19.2, 13.4 (CF3CO carbons not
observed); FAB MS m/z (M+ + H) calcd 633.25, obsd 633.33;
652.3451; [R]21 -103 (c 0.64, CHCl3).
D
(1R,2Z,4S,5S,6S,7R,8S)-4-[(4S)-4-[(1R)-1-[(p -Met h oxy-
ben zyl)oxy]a llyl]-2,2-d im eth yl-1,3-d ioxola n -4-yl]-7-(m eth -
oxym eth oxy)-5,11,11-tr im eth ylbicyclo[6.2.1]u n d ec-2-en e-
1,6-d iol 1-(Tr iflu or oa ceta te) (13a ). A mixture of 12a (231
mg of 80% purity, 0.28 mmol) and sodium bicarbonate (29 mg,
0.35 mmol) in dry CH2Cl2 (5 mL) at -78 °C was treated with
MCPBA (79 mg, 0.46 mmol), stirred for 1.5 h, diluted with
water, and extracted with ether. The combined organic layers
were dried and concentrated to give a foam that was im-
mediately dissolved in cold (-78 °C) CH2Cl2 (5 mL) and treated
with trifluoroacetic anhydride (100 µL, 0.71 mmol). After an
additional 30 min of stirring, the reaction mixture was diluted
with water and extracted with ether. The combined organic
layers were dried and concentrated to leave a residue that was
subjected to chromatography on silica gel. Elution with 20%