Fleming-Tamao Oxidation and Masked Hydroxyl Functionality
J . Org. Chem., Vol. 64, No. 16, 1999 6017
ous NaHCO3, dried, and rotary evaporated. The resulting
compound’s instability toward chromatographic supports, it
was used without further purification. The crude dione (108
mg, 0.139 mmol), split into three separate reaction vessels,
was dissolved in Me2CO (0.5 mL each), and the solutions were
cooled to 0 °C. Ni(acac)2 (4 mg, 15.6 µmol) in H2O (0.35 mL)
was added to each solution, after which freshly prepared
dimethyldioxirane (1.5 mL) was added, and the solutions were
allowed to warm to room temperature slowly. After 2.5 h, TLC
analysis indicated complete reaction, and the three solutions
were combined and rotary evaporated. The residue was
dissolved in CH2Cl2, washed with H2O, dried (MgSO4), filtered,
evaporated, and chromatographed (hexanes-Et2O, 4:1) to
furnish 38a (108 mg, 71% over both steps) as a colorless oil:
colorless solid was chromatographed (hexanes-Et2O, 1:2) to
afford 35 (34.0 mg, 94%): Rf ) 0.29; mp 141-143 °C; [R]25
)
D
-47.9° (c ) 1, CHCl3); IR (DRIFTS) 3491, 2957, 2865, 1772,
1
1723, 1690 cm-1; H NMR (400 MHz, CDCl3) δ 4.38 (1H, m),
4.05 (1H, m), 3.86 (1H, dd, J ) 10.7, 3.8 Hz), 3.82 (1H, dd, J
) 10.7, 2.3 Hz), 2.95 (1H, dd, J ) 18.0, 6.0 Hz), 2.36 (1H, d, J
) 18.0 Hz), 1.94 (1H, d, J ) 3.5 Hz), 1.53 (9H, s), 0.86 (9H, s),
0.03 (3H, s), 0.02 (3H, s); 13C NMR (100 MHz CDCl3) δ 172.8,
150.0, 83.1, 68.0, 67.5, 62.4, 42.7, 28.1, 25.8, 18.2, -5.6; MS-
(CI) m/e 363 (M + NH4)+, 346 (M + H)+; HRMS(CI) calcd for
C16H35N2O5Si (M + NH4)+ 363.2315, found (M + NH4)+
363.2322. Anal. Calcd for C16H31NO5Si: C, 55.62; H, 9.04; N,
4.05. Found: C, 55.82; H, 9.13; N, 4.12.
Rf ) 0.19; [R]25 ) -6.1° (c ) 1, CHCl3); IR (film) 3448, 3072,
D
ter t-Bu tyl (2R,3S,4R)-2-[(ter t-Bu tyld im eth ylsiloxy)-
m eth yl]-4-[(E)-(4R,5R)-ep oxytetr a d ec-(1R)-h yd r oxy-2-en -
1-yl]-3-(eth oxyd ip h en ylsilyl)-5-oxop yr r olid in e-1-ca r box-
yla te (37a ). (Et2N)Ph2SiLi (0.233 M; 3.0 mL, 0.70 mmol) was
added to Et2Zn in hexanes (1 M; 0.7 mL, 0.70 mmol) in THF
(7.5 mL) at -10 °C. After 20 min, the solution was cooled to
-78 °C when 3 (229 mg, 0.70 mmol) in THF (7 mL) was added
via cannula. An instantaneous color change occurred, from
green-brown to pale yellow, and following 5 min of stirring,
(4R,5R)-18 (157 mg, 0.70 mmol) in THF (7 mL) was added via
cannula. The mixture was allowed to warm to room temper-
ature, when a slurry of NH4Cl in absolute EtOH (∼20 mL)
was added and stirring continued for 12 h. The suspension
was diluted with Et2O and washed with H2O and the aqueous
layer extracted with Et2O. The combined organic phases were
dried (MgSO4), filtered, and rotary evaporated. Chromatog-
raphy (hexanes-Et2O, 3:1) gave 37a (273 mg, 50%) as a
colorless oil and 55 mg (10%) of the corresponding silanol, also
as a colorless oil. Data for 37a : Rf ) 0.13; IR (film) 3474, 3071,
3050, 2928, 2857, 1780, 1722 cm-1; 1H NMR (300 MHz, CDCl3)
δ 7.62 (4H, m), 7.46 (6H, m), 5.67 (1H, dd, J ) 15.5, 6.6 Hz),
5.45 (1H, dd, J ) 15.5, 7.8 Hz), 4.47 (1H, m), 4.40 (1H, d, J )
2.9 Hz), 4.14 (1H, m), 3.94 (1H, dd, J ) 10.6, 3.8 Hz), 3.72
(2H, q, J ) 7.0 Hz), 3.47 (1H, dd, J ) 10.6, 1.9 Hz), 2.99 (1H,
dd, J ) 7.8, 2.0 Hz), 2.82 (1H, m), 2.76 (1H, app t, J ) 6.9
Hz), 2.06 (1H, dd, J ) 6.4, 4.6 Hz), 1.55 (2H, m), 1.46 (9H, s),
1.27-1.40 (14H, m), 1.19 (3H, t, J ) 7.0 Hz), 0.90 (9H, s), 0.89
(3H, t, J ) 7.0 Hz), 0.05 (6H, s); 13C NMR (75 MHz CDCl3) δ
175.4, 149.6, 135.2, 134.6, 131.6, 131.2, 130.8, 130.7, 128.3,
83.2, 73.5, 63.9, 60.3, 59.9, 58.5, 57.8, 49.3, 32.1, 31.9, 30.3,
29.6, 29.5, 29.3, 28.0, 26.0, 25.9, 22.7, 19.9, 18.5, 18.2, 14.1,
-5.3, -5.4; MS(FAB+) m/e 780 (M + H)+; HRMS(FAB+) calcd
for C44H70NO7Si2 (M + H)+ 780.4691, found (M + H)+ 780.4688.
Data for corresponding silanol (HO)Ph2SiR (see the text): Rf
) 0.40 (hexanes-Et2O, 1:1); IR (film) 3422, 3071, 3051, 2955,
2928, 2856, 1775, 1721, 1590 cm-1; 1H NMR (400 MHz, CDCl3)
δ 7.61 (4H, m), 7.43 (6H, m), 5.69 (1H, dd, J ) 15.6, 7.0 Hz),
5.50 (1H, dd, J ) 15.6, 7.3 Hz), 4.45 (1H, m), 4.15 (1H, m),
3.94 (1H, d, J ) 1.6 Hz), 3.86 (1H, dd, J ) 10.5, 3.8 Hz), 3.37
(1H, dd, J ) 10.5, 1.8 Hz), 2.98 (1H, dd, J ) 7.2, 2.0 Hz), 2.87
(1H, ddd, J ) 7.4, 5.7, 2.0 Hz), 2.79 (1H, app t, J ) 7.4 Hz),
1.98 (1H, dd, J ) 7.8, 5.7 Hz), 1.55 (2H, m), 1.26-1.49 (14H,
m′s), 1.46 (9H, s), 0.88 (9H, s), 0.86 (3H, t, J ) 6.7 Hz), 0.03
(3H, s), 0.02 (3H, s); 13C NMR (100 MHz, CDCl3) δ 175.2, 162.9,
149.7, 134.6, 134.6, 134.1, 133.6, 130.6, 130.5, 128.3, 83.4, 73.4,
63.7, 60.5, 58.7, 57.3, 49.2, 31.93, 31.86, 29.51, 29.48, 29.4, 29.3,
28.0, 26.0, 25.8, 22.7, 20.8, 18.5, 14.1, -5.38, -5.43; MS(FAB+)
m/e 752 (M + H)+. Anal. Calcd for C42H65NO7Si2: C, 67.07; H,
8.71; N, 1.86. Found: C, 66.76; H, 8.52; N, 1.78.
3050, 2956, 2928, 2857, 1962, 1897, 1786, 1726, 1687, 1624
1
cm-1; H NMR (300 MHz, CDCl3) δ 7.73 (2H, dd, J ) 7.6, 1.7
Hz), 7.57 (2H, dd, J ) 7.6, 1.7 Hz), 7.41 (6H, m), 6.93 (1H, d,
J ) 15.5 Hz), 6.33 (1H, dd, J ) 15.5, 7.6 Hz), 4.69 (1H, s),
4.49 (1H, d, J ) 6.6 Hz), 4.24 (1H, dd, J ) 11.0, 2.1 Hz), 3.66
(2H, m), 3.42 (1H, dd, J ) 11.0, 0.8 Hz), 3.12 (1H, dd, J ) 7.6,
1.7 Hz), 2.81 (1H, ddd, J ) 7.3, 5.9, 1.7 Hz), 2.54 (1H, d, J )
6.6 Hz), 1.58 (2H, m), 1.47 (9H, s), 1.28-1.46 (14H, m), 1.13
(3H, t, J ) 6.9 Hz), 0.91 (12H, m), 0.05 (6H, s); 13C NMR (75
MHz, CDCl3) δ 196.8, 171.4, 149.7, 145.3, 135.6, 135.0, 133.4,
132.9, 130.2, 130.1, 127.9, 127.8, 125.6, 85.3, 83.6, 62.0, 61.4,
59.6, 58.4, 57.0, 33.1, 32.0, 31.9, 30.3, 29.5, 29.4, 29.3, 28.0,
25.9, 22.7, 18.4, 18.1, 14.1, -5.5; MS(FAB+) m/e 793 (M•+);
HRMS(FAB+) calcd for C44H67NO8Si2 (M•+) 793.4405, found
(M•+) 793.4408. Anal. Calcd for C44H67NO8Si2: C, 66.54; H, 8.50;
N, 1.76. Found: C, 66.34; H, 8.37; N, 1.64.
(-)-ter t-Bu tyl (2R,3R,4R)-2-[(ter t-Bu tyldim eth ylsiloxy)-
m eth yl]-3,4-dih ydr oxy-4-[(E)-(4R,5R)-epoxy-1-oxotetr adec-
2-en -1-yl]-5-oxop yr r olid in e-1-ca r boxyla te (39a ). KHF2 (13
mg, 166.5 µmol) and 3-chloroperbenzoic acid (assumed 70%
activity; 50 mg, 203 µmol) were sequentially added to 38a (52
mg, 65.5 µmol) in DMF (4 mL) at 0 °C. The mixture was
allowed to warm to room temperature, and after 1.5 h, the
solution was diluted with EtOAc, washed with saturated
aqueous NaHCO3 and H2O, dried (MgSO4), filtered, and
evaporated to dryness. The residue was chromatographed
(hexanes-Et2O, 3:2) to afford 39a (21 mg, 55%) as a colorless
oil: Rf ) 0.25; [R]25D ) -1.3° (c ) 0.61, CHCl3); IR (film) 3454,
2955, 2928, 2856, 1784, 1732, 1694, 1627 cm-1; 1H NMR (300
MHz, CDCl3) δ 7.12 (1H, d, J ) 15.5 Hz), 6.78 (1H, dd, J )
15.5, 7.3 Hz), 5.12 (1H, br s), 4.32 (1H, d, J ) 3.0 Hz), 4.15
(1H, dd, J ) 10.6, 4.0 Hz), 4.05 (1H, m), 3.98 (1H, dd, J )
10.6, 2.0 Hz), 3.91 (1H, br s), 3.28 (1H, dd, J ) 7.3, 1.7 Hz),
2.93 (1H, ddd, J ) 7.0, 5.6, 1.7 Hz), 1.63 (2H, m), 1.56 (9H, s),
1.45 (2H, m), 1.29 (12H, m), 0.91 (9H, s), 0.90 (3H, t, J ) 6.9
Hz), 0.12 (6H, s); 13C NMR (75 MHz, CDCl3) δ 196.5, 169.7,
149.6, 146.8, 126.2, 84.3, 82.4, 75.9, 64.2, 61.9, 61.3, 56.8, 32.0,
31.9, 30.3, 29.5, 29.34, 29.31, 28.0, 25.8, 22.7, 18.3, 14.1, -5.6.
(+)-(2R,3R,4R)-2-[(ter t-Bu t yld im et h ylsiloxy)m et h yl]-
3,4-d ih yd r oxy-4-[(E)-(4R,5R)-ep oxytetr a d ec-2-en -1-oxy]-
5-oxop yr r olid in e (40a ). Carbamate 39a (13.0 mg, 22.9 µmol)
in EtOAc (∼3 mL) was added to silica gel (40-63 mesh; 300
mg) and the slurry dried in vacuo. The silica gel was placed
under high vacuum (0.1 mmHg) at 40 °C for 12 h, cooled, and
extracted with EtOAc, and the filtrate was rotary evaporated.
Chromatography (hexanes-diethyl ether, 1:2) afforded 40a (9
mg, 84%) as a colorless solid: Rf ) 0.19; mp 123-125 °C; [R]25
D
) +70.0° (c ) 0.27, CHCl3); IR (film) 3338, 2954, 2925, 2855,
1722, 1685, 1626 cm-1 1H NMR (400 MHz, CD3OD) δ 7.05
;
(-)-ter t-Bu tyl (2R,3R,4R)-2-[(ter t-Bu tyldim eth ylsiloxy)-
m eth yl]-4-[(E)-(4R,5R)-ep oxy-1-oxotetr a d ec-2-en -1-yl]-3-
(eth oxyd ip h en ylsilyl)-4-h yd r oxy-5-oxop yr r olid in e-1-ca r -
boxyla te (38a ). Dess-Martin periodinane (106 mg, 0.250
mmol) was added to 37a (150 mg, 0.192 mmol) in CH2Cl2 (60
mL) at 0 °C. After the mixture was warmed to room temper-
ature over 1 h, saturated aqueous NaHCO3 (15 mL) and
saturated aqueous Na2S2O3 (15 mL) were added. The two-
phase mixture was rapidly stirred until complete dissolution
of the white precipitate in the CH2Cl2 layer. The organic phase
was separated, washed with H2O, dried (MgSO4), filtered, and
rotary evaporated to yield a pale yellow oil. Due to the
(1H, dd, J ) 15.7, 0.8 Hz), 6.62 (1H, dd, J ) 15.7, 7.1 Hz),
4.23 (1H, d, J ) 7.2 Hz), 3.86 (1H, dd, J ) 11.1, 2.7 Hz), 3.68
(1H, dd, J ) 11.1, 4.4 Hz), 3.46 (1H, ddd, J ) 7.2, 4.4, 2.7 Hz),
3.32 (1H, m), 2.92 (1H, ddd, J ) 7.1, 5.1, 1.9 Hz), 1.62 (1H,
m), 1.55 (1H, m), 1.45 (2H, m), 1.29 (12H, br s), 0.92 (9H, s),
0.89 (3H, t, J ) 7.0 Hz), 0.10 (3H, s), 0.09 (3H, s); 13C NMR
(100 MHz, CD3OD) δ 198.0, 174.8, 145.2, 127.9, 88.2, 78.4,
62.9, 62.5, 60.2, 57.8, 33.1, 30.7, 30.5, 30.5, 27.0, 26.4, 23.8,
19.2, 14.5, -5.3, -5.4; MS(FAB+) m/e 484 (M + H)+; HRMS-
(FAB+) calcd for C25H46NO6Si (M + H)+ 484.3094, found (M +
H)+ 484.3090.