Paquette et al.
MHz, CDCl3) δ 5.93 (s, 1H), 5.79 (dd, J ) 7.5, 2.5 Hz, 1H), 5.68
(s, 1H), 5.59 (dd, J ) 7.5, 2.0 Hz, 1H), 5.48 (dd, J ) 7.5, 4.0 Hz,
1H), 4.30 (t, J ) 7.5 Hz, 1H), 4.22 (dd, J ) 7.5, 5.5 Hz, 1H), 4.16
(dd, J ) 10, 7.5 Hz, 1H), 3.97 (d, J ) 10 Hz, 1H), 2.92 (s, 1H),
2.51 (s, 15H), 1.66 (dt, J ) 7.5, 3.5 Hz, 1H), 0.88 (s, 18H), 0.03
(s, 3H), 0.02 (s, 3H), 0.01 (s, 6H); 13C NMR (125 MHz, CDCl3) δ
162.4, 159.9, 159.7, 158.9, 78.7, 78.6, 75.9, 72.4, 71.1, 70.2, 66.2,
63.1, 47.4, 26.0, 25.9, 25.8, 21.6, 21.5, 21.4, 18.2, 18.1, -4.1, -4.2,
-4.3, -4.4; HRMS exact mass calcd for C31H56O13Si2Na+ 715.3152,
found 715.3148.
IR (thin film, cm-1) 3455, 1727, 1218; 1H NMR (500 MHz, CDCl3)
δ 5.91 (s, 1H), 5.76 (dd, J ) 7.5, 4 Hz, 1H), 5.68 (dd, J ) 7.5, 2.5
Hz, 1H), 5.55 (dd, J ) 5.5, 2 Hz, 1H), 5.39 (dd, J ) 7.5, 4 Hz,
1H), 4.32 (dd, J ) 7.5, 2 Hz, 1H), 4.21 (t, J ) 7.5 Hz, 1H),
3.95-3.89 (m, 2H), 2.70 (s, 1H), 2.51(s, 15H), 1.61 (t, J ) 7.5
Hz, 1H), 0.88 (s, 18H), 0.03 (s, 3H), 0.02 (s, 3H), 0.01 (s, 6H); 13
C
NMR (125 MHz, CDCl3) δ 162.9, 160.0, 159.9, 159.2, 78.3, 78.2,
75.9, 74.6, 69.3, 68.9, 61.3, 61.1, 46.8, 26.3, 26.2, 26.1, 21.4, 21.3,
21.2, 18.3, 18.2, -4.1, -4.3, -4.4; HRMS exact mass calcd for
C31H56O13Si2Na+ 715.3152, found 715.3156.
(1R,2R,3S,4S,5S,6R,7R,8R)-6,7-Bis(tert-butyldimethylsilyloxy)-
8-(hydroxymethyl)cyclooctane-1,2,3,4,5-pentaacetate (21). The
hydroboration of olefin 15 also provided the more polar alcohol
(1R,2S,3R,4R,5S,6S,7S,8R)-8-(Hydroxymethyl)cyclooctane-
1,2,3,4,5,6,7-heptaol (26). A 10 mL round-bottomed flask was
charged with alcohol 18 (19 mg, 0.027 mmol) and THF (2 mL).
The mixture was charged with 2.5 N HCl in THF (1 mL). The
reaction mixture was stirred at rt for 6 h and quenched with solid
sodium bicarbonate. The residue was triturated with MeOH (2 mL)
and reacted with K2CO3 (76 mg). The resulting mixture was stirred
at rt for 2 h, and the solvent was removed under vacuum. The crude
mixture was purified by flash chromatography using a reverse phase
column (elution with MeOH/CHCl3 1:3) to yield 26 (6 mg, 90%)
21 (13 mg, 27%) as a colorless oil: [R]20 -21.1 (c 1.0, CHCl3);
D
IR (thin film, cm-1) 3471, 1722, 1247; 1H NMR (500 MHz, CDCl3)
δ 5.96 (s, 1H), 5.82 (dd, J ) 7.5, 4 Hz, 1H), 5.71 (dd, J ) 7.5, 2.5
Hz, 1H), 5.65 (dd, J ) 7.5, 2 Hz, 1H), 4.19 (t, J ) 7.5 Hz, 1H),
4.06 (dd, J ) 7.5, 2 Hz, 1H), 3.95-3.90 (m, 2H), 3.41 (s, 1H),
2.51(s, 15H), 1.57 (t, J ) 7.5 Hz, 1H), 0.88 (s, 18H), 0.03 (s, 3H),
0.02 (s, 3H), 0.01 (s, 6H); 13C NMR (125 MHz, CDCl3) δ 160.4,
160.3, 160.2, 81.3, 78.9, 75.8, 73.6, 73.5, 71.9, 63.9, 46.9, 26.0,
25.9, 21.9, 21.8, 21.7, 18.2, 18.1, -4.1, -4.3, -4.4; HRMS exact
mass calcd for C31H56O13Si2Na+ 715.3152, found 715.3151.
(1R,2R,3R,4R,5R,6R,7R,8S)-6,7-Bis(tert-butyldimethylsilyloxy)-
8-(hydroxymethyl)cyclooctane-1,2,3,4,5-pentaacetate (22). The
hydroboration of olefin 16 (82 mg, 0.12 mmol) provided the less
as a white powder: mp 291-293 °C; [R]20 -1.3 (c 1.0, MeOH);
D
IR (thin film, cm-1) 3487, 3259, 1121; 1H NMR (500 MHz, D2O)
δ 4.32 (dd, J ) 7.5, 2.5 Hz, 1H), 4.28 (s, 1H), 4.12 (dd, J ) 7.5,
4.5 Hz, 2H), 3.98 (dd, J ) 10, 7.5 Hz, 1H), 3.91 (d, J ) 10 Hz,
1H), 3.82 (t, J ) 7.5 Hz, 1H), 3.72 (s, 1H), 3.70 (s, 1H), 1.70-1.66
(m, 1H); 13C NMR (125 MHz, D2O) δ 78.2, 74.8, 73.5, 70.9, 69.9,
65.1, 64.9, 63.5, 47.8; HRMS exact mass calcd for C9H18O8Na+
277.0894, found 277.0897.
polar alcohol 22 (20 mg, 24%) as a colorless oil: [R]20 +9.1 (c
D
1.0, CHCl3); IR (thin film, cm-1) 3460, 1723, 1229; 1H NMR (500
MHz, CDCl3) δ 5.90 (s, 1H), 5.73 (s, 1H), 5.62 (s, 1H), 5.45 (s,
2H), 4.32 (dd, J ) 7.5, 2 Hz, 1H), 4.26 (dd, J ) 7.5, 5.5 Hz, 1H),
3.92 (dd, J ) 10, 7.5 Hz, 1H), 3.81 (d, J ) 10 Hz, 1H), 2.91 (d,
J ) 10 Hz, 1H), 2.51 (s, 15H), 1.59 (dt, J ) 7.5, 4 Hz, 1H), 0.88
(s, 18H), 0.03 (s, 3H), 0.02 (s, 3H), 0.01 (s, 6H); 13C NMR (125
MHz, CDCl3) δ 162.1, 160.9, 160.8, 159.8, 80.1, 74.9, 74.4, 73.3,
68.8, 65.1, 64.3, 62.1, 47.1, 25.9, 25.8, 25.7, 22.6, 22.5, 22.4, 18.3,
18.2, -4.4, -4.8. -4.9; HRMS exact mass calcd for
C31H56O13Si2Na+ 715.3152, found 715.3154.
(1R,2S,3R,4R,5S,6S,7S,8S)-8-(Hydroxymethyl)cyclooctane-
1,2,3,4,5,6,7-heptaol (27). The global deprotection of alcohol 19
(20 mg, 0.029 mmol) provided 27 (6 mg, 82%) as white solid: mp
294-295 °C; [R]20D -1.9 (c 1.0, MeOH); IR (thin film, cm-1) 3491,
3256, 1119; 1H NMR (500 MHz, D2O) δ 4.09 (dd, J ) 7.5, 2 Hz,
2H), 3.98 (s, 2H), 3.92 (s, 1H), 3.89 (s, 1H), 3.85-3.79 (m, 2H),
3.71 (t, J ) 7.5 Hz, 2H), 1.59 (dd, J ) 6, 4 Hz, 1H); 13C NMR
(125 MHz, D2O) δ 76.0, 72.0, 71.2, 70.9, 70.5, 67.9, 61.0, 60.7,
46.2; HRMS exact mass calcd for C9H18O8Na+ 277.0894, found
277.0896.
(1R,2R,3R,4R,5R,6R,7R,8R)-6,7-Bis(tert-butyldimethylsilyloxy)-
8-(hydroxymethyl)cyclooctane-1,2,3,4,5-pentaacetate (23). The
hydroboration of olefin 16 also provided the more polar alcohol
23 (20 mg, 24%) as a pale yellow oil: [R]20D +5.3 (c 1.0, CHCl3);
IR (thin film, cm-1) 3453, 1728, 1239; 1H NMR (500 MHz, CDCl3)
δ 6.03 (s, 1H), 5.92 (s, 1H), 5.79 (s, 2H), 5.66 (dd, J ) 5.5, 2.5
Hz, 1H), 4.30 (dd, J ) 7.5, 5.5 Hz, 1H), 4.21 (dd, J ) 7.5, 2 Hz,
1H), 3.92-3.88 (m, 2H), 2.78 (d, J ) 10 Hz, 1H), 2.51 (s, 15H),
1.58 (t, J ) 7.5 Hz, 1H), 0.88 (s, 18H), 0.03 (s, 3H), 0.02 (s, 3H),
0.01 (s, 6H); 13C NMR (125 MHz, CDCl3) δ 161.1, 161.0, 160.9,
80.8, 79.0, 75.9, 74.9, 74.7, 74.3, 63.2, 46.9, 26.0, 25.9, 21.7, 21.6,
21.5, 18.3, 18.2, -3.6, -3.8. -4.0, -4.1; HRMS exact mass calcd
for C31H56O13Si2Na+ 715.3152, found 715.3153.
(1R,2R,3S,4S,5R,6S,7R,8R)-8-(Hydroxymethyl)cyclooctane-
1,2,3,4,5,6,7-heptaol (28). The global deprotection of alcohol 20
(12 mg, 0.017 mmol) provided 28 (4 mg, 88%) as white a solid:
mp 294-296 °C; [R]20D +16.1 (c 1.0, MeOH); IR (thin film, cm-1
)
3468, 3245, 1110; 1H NMR (500 MHz, D2O) δ 4.42 (dd, J ) 7.5,
5.5 Hz, 1H), 4.39 (s, 1H), 4.28 (s, 1H), 4.21 (dd, J ) 7.5, 2 Hz,
1H), 4.18 (dd, J ) 10, 2.5 Hz, 1H), 4.09 (dd, J ) 7.5, 4 Hz, 1H),
3.89 (d, J ) 10 Hz, 1H), 3.82 (dd, J ) 10, 7.5 Hz, 1H), 3.70 (t, J
) 7.5 Hz, 1H), 1.57 (dt, J ) 7.5, 4 Hz, 1H); 13C NMR (125 MHz,
D2O) δ 76.5, 75.1, 72.8, 72.4, 71.5, 69.9, 67.1, 63.5, 47.5; HRMS
exact mass calcd for C9H18O8Na+ 277.0894, found 277.0891.
(1R,2R,3S,4S,5R,6S,7R,8S)-8-(Hydroxymethyl)cyclooctane-
1,2,3,4,5,6,7-heptaol (29). The global deprotection of alcohol 21
(13 mg, 0.017 mmol) provided 29 (4 mg, 88%) as white a solid:
(1R,2R,3R,4S,5S,6R,7R,8S)-6,7-Bis(tert-butyldimethylsilyloxy)-
8-(hydroxymethyl)cyclooctane-1,2,3,4,5-pentaacetate (24). The
hydroboration of olefin 17 (40 mg, 0.06 mmol) provided the less
mp 289-290 °C; [R]20D +4.2 (c 1.0, MeOH); IR (thin film, cm-1
)
polar alcohol 24 (11 mg, 26%) as a colorless oil: [R]20 +34.9 (c
3493, 3245, 1120; 1H NMR (500 MHz, D2O) δ 4.19 (dd, J ) 7.5,
2 Hz, 1H), 4.10 (s, 1H), 3.85 (dd, J ) 7.5, 4 Hz, 2H), 3.73 (dd, J
) 7.5, 2.5 Hz, 1H), 3.62-3.55 (m, 2H), 3.32 (t, J ) 7.5 Hz, 1H),
1.59 (t, J ) 7.5 Hz, 1H); 13C NMR (125 MHz, D2O) δ 77.4, 76.1,
73.9, 71.8, 71.1, 69.8, 68.6, 66.4, 45.5; HRMS exact mass calcd
for C9H18O8Na+ 277.0894, found 277.0898.
D
1.0, CHCl3); IR (thin film, cm-1) 3449, 1722, 1221; 1H NMR (500
MHz, CDCl3) δ 6.06 (s, 1H), 5.91 (dd, J ) 7.5, 2 Hz, 1H), 5.79 (s,
1H), 5.66 (dd, J ) 7.5, 2.0 Hz, 1H), 5.57 (dd, J ) 7.5, 4.0 Hz,
1H), 4.31 (t, J ) 7.5 Hz, 1H), 4.19 (dd, J ) 7.5, 5.5 Hz, 1H), 3.98
(dd, J ) 10, 7.5 Hz, 1H), 3.89 (d, J ) 10 Hz, 1H), 2.59 (s, 1H),
2.51 (s, 15H), 1.65 (dt, J ) 7.5, 4 Hz, 1H), 0.88 (s, 18H), 0.03 (s,
3H), 0.02 (s, 3H), 0.01 (s, 6H); 13C NMR (125 MHz, CDCl3) δ
162.5, 161.9, 158.3, 158.2, 79.9, 78.8, 74.7, 74.6, 73.7, 71.3, 62.9,
62.5, 47.2, 26.2, 26.1, 26.0, 21.5, 21.4, 21.3, 18.2, 18.1, -4.1, -4.2,
-4.3, -4.4; HRMS exact mass calcd for C31H56O13Si2Na+ 715.3152,
found 715.3155.
(1R,2R,3R,4S,5S,6S,7R,8R)-8-(Hydroxymethyl)cyclooctane-
1,2,3,4,5,6,7-heptaol (30). The global deprotection of alcohol 22
(20 mg, 0.029 mmol) provided 30 (6 mg, 90%) as white a solid:
mp 292-295 °C; [R]20D -33.2 (c 1.0, MeOH); IR (thin film, cm-1
)
3488, 3258, 1121; 1H NMR (500 MHz, D2O) δ 4.26 (s, 3H), 4.21
(s, 1H), 4.04(dd, J ) 7.5, 2.5 Hz, 1H), 3.98 (s, 1H), 3.90 (d, J )
10 Hz, 1H), 3.82 (dd, J ) 10, 8 Hz, 1H), 3.72 (dd, J ) 7.5, 5.5
Hz, 1H), 1.60 (dt, J ) 7.5, 4 Hz, 1H); 13C NMR (125 MHz, D2O)
δ 75.1, 73.9, 72.5, 71.9, 68.8, 66.9, 64.3, 64.2, 47.1; HRMS exact
mass calcd for C9H18O8Na+ 277.0894, found 277.0897.
(1R,2R,3R,4S,5S,6R,7R,8R)-6,7-Bis(tert-butyldimethylsilyloxy)-
8-(hydroxymethyl)cyclooctane-1,2,3,4,5-pentaacetate (25). The
hydroboration of olefin 17 also provided the more polar alcohol
25 (11 mg, 27%) as a colorless oil: [R]20 +10.6 (c 1.0, CHCl3);
D
2106 J. Org. Chem. Vol. 74, No. 5, 2009