Total Synthesis of (()- and (+)-Valienamine
J. Am. Chem. Soc., Vol. 120, No. 8, 1998 1739
NMR (75 MHz, CDCl3): δ 166.4, 135.2, 129.7, 62.7, 60.5, 54.2, 49.2,
25.7, 25.6, 17.9, 14.0, -4.9, -5.0. HRMS Calcd for C14H26O4Si: C,
60.37; H, 8.78. Found: C, 60.19; H, 8.53.
1-3% ethyl acetate:petroleum ether, (-)-9b (0.061 g, 0.15 mmol, 88%),
[R]D20 -140.26° (c ) 3.05, CH2Cl2). IR (neat): 1721, 1473 cm-1. 1H
NMR (300 MHz, CDCl3): δ 7.28 (d, J ) 4.2 Hz, 1 H), 4.56 (dd, J )
2.1 Hz, 1 H), 4.25 (dd, J ) 2.1 Hz, 1 H), 3.76 (s, 3 H), 3.53 (m, 1 H),
3.42 (dd, J ) 4.0 Hz, 1 H), 0.86 (br s, 18 H), 0.16 (s, 3 H), 0.15 (s, 3
H), 0.12 (s, 3 H), 0.11 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ 166.6,
137.6, 134.0, 69.3, 68.1, 58.0, 51.8, 45.1, 25.6, 17.9, 17.8, -4.5, -4.8,
-4.9, -5.1. HRMS Calcd for C20H38O5Si2 (M+): 414.2258. Found:
414.2248.
(+)-5b. To a mixture of phenylselenide 28b (0.173 g, 0.406 mmol)
and CaCO3 (0.17 g, 1.7 mmol) in dichloromethane (12.5 mL) at -78
°C was added m-CPBA (0.081 g, 0.469 mmol) in dichloromethane (2.5
mL). After 15 min, 2-methoxypropene (0.377 g, 5.22 mmol) was
added. After an additional 15 min at -78 °C, the reaction was removed
from the cooling bath and stirred 45 min. The solvent was removed
in vacuo. The residue was chromatographed immediately with 5:95
ethyl acetate:petroleum ether to give semipure diene 6b (0.10 g). This
compound was immediately epoxidized as above using sodium
bicarbonate (0.206 g, 2.24 mmol) and m-CPBA (0.14 g, 0.81 mmol)
in 1.5 mL of dichloromethane. After 20 h at room temperature, water,
sodium bisulfite, and ethyl acetate were added. After the organic layer
(MgSO4) was dried, the solvent was removed in vacuo and the residue
was chromatographed with 5:95 ethyl acetate:petroleum ether to give
Preparation of 10a and 10b. rac-10a. A solution of the active
catalyst was generated by sequential addition to 1 mL of THF of
palladium acetate (11.2 mg, 0.05 mmol), phosphite 14 (50.8 mg, 0.30
mmol), and n-butyllithium (66.7 µL, 0.10 mmol, 1.5 M in hexanes).
After 30 min at room temperature, epoxide 9a (0.428 g, 1.0 mmol) in
1 mL of THF, p-toluenesulfonylisocyanate (0.59 g, 3.0 mmol), and
trimethyltin acetate (22.3 mg, 0.10 mmol) were added. Heating at reflux
for 42 h, concentration in vacuo, and direct flash chromatography (10:1
hexane:ethyl acetate) gave 10a (337.2 mg, 0.54 mmol, 54% yield) and
11a (56.1 mg, 0.09 mmol, 9% yield). 10a: IR (film): 1791, 1722,
25
scalemic epoxide 5b (0.053 g, 0.2 mmol, 48.3% for two steps), [R]D
+1.60° (c ) 2.57, CH2Cl2).
1598, 1472, 1464, 1367 cm-1 1H NMR (300 MHz, CDCl3): δ 7.78
.
Preparation of rac-8a and (-)-8b. rac-8a. DBU (0.760 g, 5.50
mmol) in 1 mL of dichloromethane was added to a solution of epoxide
5a (1.18 g, 3.95 mmol), TBDMS-Cl (0.72 g, 4.78 mmol), and DMAP
(0.048, 0.41 mmol) in 7 mL of dichloromethane. After stirring 24 h
at room temperature, the reaction was diluted with ether, washed with
saturated aqueous sodium bicarbonate and brine, dried (MgSO4), and
evaporated in vacuo. The residue was flash chromatographed (19:1
hexane:ethyl acetate) to give rac-8a (1.24 g, 3.00 mmol, 76% yield).
(br d, J ) 8.5 Hz, 2 H), 7.28 (br d, J ) 8.5 Hz, 2 H), 5.14 (dd, J )
8.6, 4.5 Hz, 1 H), 4.52 (br s, 1 H), 4.58-4.55 (m, 1 H), 4.35 (dq, J )
10.9, 7.2 Hz, 1 H), 4.23 (dq, J ) 10.9, 7.2 Hz, 1 H), 4.12 (dd, J ) 3.2,
2.4 Hz, 1 H), 2.40 (s, 3 H), 1.36 (t, J ) 7.2 Hz, 3 H), 0.81 (s, 9 H),
0.63 (s, 9 H), 0.08 (s, 3 H), 0.07 (s, 3 H), 0.03 (s, 3 H), -0.13 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ 165.7, 150.4, 145.5, 135.5, 135.1, 132.5,
129.7 (2 C), 128.8 (2 C), 73.6, 68.8, 64.9, 61.3, 52.0, 25.3, 25.1, 21.4,
17.6, 17.4, 14.0, -5.2, -5.3, -5.5. HRMS Calcd for C28H44NO8SSi2
(M+ - CH3): 610.2326. Found: 610.2315. 11a: IR (film): 1718,
IR (film): 1712, 1587, 1472, 1463, 1405 cm-1 1H NMR (300 MHz,
.
CDCl3): δ 7.10 (dd, J ) 5.1, 1.5 Hz, 1 H), 6.20 (dd, J ) 9.4, 4.9 Hz,
1 H), 6.15 (ddd, J ) 9.4, 5.2, 1.0 Hz, 1 H), 4.57 (br s, J ) 1.3 Hz, 1
H), 4.28 (dq, J ) 10.9, 7.1 Hz, 1 H), 4.18 (dq, J ) 10.9, 7.1 Hz, 1 H),
4.10 (dd, J ) 4.8, 1.6 Hz, 1 H), 1.31 (t, J ) 7.1 Hz, 3 H), 0.86 (s, 9
H), 0.82 (s, 9 H), 0.16 (s, 3 H), 0.10 (s, 3 H), 0.07 (s, 3 H), 0.04 (s, 3
H). 13C NMR (75 MHz, CDCl3): δ 167.2, 133.0, 132.7, 129.8, 123.8,
69.8, 67.8, 60.3, 25.6, 25.5, 17.9, 17.8, 14.1, -4.5, -4.7, -4.8, -5.2.
HRMS Calcd for C15H24O3Si (M+ - TBDSOH): 280.1495. Found:
280.1485.
1638, 1472, 1464, 1363 cm-1 1H NMR (300 MHz, CDCl3): δ 7.81
.
(d, J ) 6.5 Hz, 2 H), 7.24 (d, J ) 7.9 Hz, 2 H), 6.88 (d, J ) 4.7 Hz,
1 H), 5.50 (dd, J ) 8.1, 4.8 Hz, 1 H), 4.77 (ddd, J ) 8.1, 2.5, 1.5 Hz,
1 H), 4.64 (dd, J ) 3.1, 1.5 Hz, 1 H), 4.32 (dq, J ) 10.8, 7.1 Hz, 1 H),
4.27 (t, J ) 2.9 Hz, 1 H), 4.22 (dq, J ) 10.7, 7.1 Hz, 1 H), 2.30 (s, 3
H), 1.33 (t, J ) 7.1 Hz, 3 H), 0.81 (s, 9 H), 0.80 (s, 9 H), 0.13 (s, 3 H),
0.10 (s, 3 H), 0.09 (s, 3 H), 0.02 (s, 3 H). 13C NMR (75 MHz,
CDCl3): δ 165.2, 158.6, 143.3, 138.9, 137.5, 129.3 (2 C), 128.4 (2 C),
127.2, 77.2, 77.1, 68.7, 65.0, 61.5, 25.4, 25.3, 21.3, 17.7, 17.6, 13.9,
-5.0, -5.3 (2 C). HRMS Calcd for C25H38NO8SSi2 (M+ - t-C4H9):
568.1857. Found: 568.1873.
(-)-8b Epoxide. Epoxide (+)-5b (0.056 g, 0.19 mmol) was added
to a 0 °C solution of TBDMS-Cl (0.037 g, 0.25 mmol), DBU (0.038
g, 0.25 mmol), and DMAP (0.0025 g, 0.020 mmol) in 0.5 mL of
dichloromethane. The cooling bath was removed, the reaction per-
formed, and the product purified (99.6:0.4 petroleum ether:ethyl acetate)
10b. The catalyst was prepared as above from recrystallized
palladium acetate (11 mg, 0.05 mmol), phosphite 14 (51 mg, 0.14
mmol), and n-butyllithium (0.075 mL, 1.35 M in hexane, 0.101 mmol)
in 2 mL of THF. Tosyl isocyanate (0.29 g, 1.48 mmol) and an aliquot
of the palladium solution (0.5 mL, 0.0125 mmol) were added
sequentially to epoxide 9b (0.061 g, 0.15 mmol) and trimethyltin acetate
(0.018 g, 0.08 mmol) under Ar. After heating and workup as above,
28
as above to give (-)-8b (0.066 g, 0.17 mmol, 90%), [R]D -305.1°
(c ) 3.29, CH2Cl2). IR (neat): 1715, 1651, 1589, 1463, 1437 cm-1
.
1H NMR (300 MHz, CDCl3): δ 7.07 (dd, J ) 1.3, 9.4 Hz, 1 H), 6.15
(m, 2 H), 4.54 (s, 1 H), 4.08 (d, J ) 4.4 Hz, 1 H), 3.75 (s, 3 H), 0.84
(s, 9 H), 0.80 (s, 9 H), 0.14 (s, 3 H), 0.09 (s, 3 H), 0.06 (s, 3 H), 0.02
(s, 3 H). 13C NMR (75 MHz, CDCl3): δ 167.4, 133.1, 132.9, 129.4,
123.6, 69.9, 68.0.0, 51.5, 25.7, 25.6, 18.0, 17.9, -4.3, -4.7, -5.0.
HRMS Calcd for C20H38O4Si2 (M+): 398.2309. Found: 398.2306.
Preparation of rac-9a and (-)-9b. rac-9a. m-CPBA was added
portionwise to a mixture of diene 8a (2.82 g, 6.83 mmol) and sodium
bicarbonate (1.72 g, 20.5 mmol) in 17 mL of methylene chloride. After
stirring 3 h at room temperature, the reaction was filtered and diluted
with ether. The resultant organic layer was washed with saturated
aqueous sodium bisulfite, sodium bicarbonate, and brine. After drying
(MgSO4) and evaporation in vacuo, the residue was flash chromato-
graphed (12:1 hexane:ethyl acetate) or distilled (bp 175-200 °C at
0.025 Torr, bath temperature) to give rac-9a (1.71 g, 3.99 mmol, 86%
20
10b [0.064 g, 0.11 mmol, 70% yield, [R]D -32.6° (c ) 1.0, CH2-
Cl2)] was obtained. IR (CDCl3): 1788, 1721, 1472, 1438, 1363 cm-1
.
1H NMR (300 MHz, CDCl3): δ 7.92 (d, J ) 8.4 Hz, 2 H), 7.27 (m, 3
H), 5.12 (dd, J ) 4.7, 8.5 Hz, 1 H), 4.55 (m, 2 H), 4.11 (m, 1 H), 3.83
(s, 3 H), 2.41 (s, 3 H), 0.81 (s, 9 H), 0.65 (s, 9 H), 0.08 (s, 3 H), 0.07
(s, 3 H), 0.03 (s, 3 H), -0.12 (s, 3 H). 13C NMR (75 MHz, CDCl3):
δ 165.9, 150.1, 145.4, 134.9, 132.4, 129.6, 128.7, 73.6, 68.8, 65.1, 52.2,
25.5, 25.3, 17.8, 17.6, -4.9, -5.0, -5.1, -5.2. HRMS Calcd for
C24H36NO8SSi2 (M+ - t-C4H9): 554.1700. Found: 554.1714.
Preparation of (3S,4S,5R,6R)-5,6-Bis(tert-Butyldimethylsiloxyl)-
1-(hydroxymethyl)-3-[N-(p-toluenesulfonyl)amino]cyclohex-1-en-4-
ol (17b). DIBAL-H (2.75 mL, 1.0 M in hexane, 2.75 mmol) was added
over 30 min to a -78 °C solution of oxazolidinone 10a (0.313 g, 0.50
mmol) in 1.5 mL of dichloromethane. After 2 h at -78 °C, methanol
was added and the reaction allowed to warm to room temperature, at
which point 30% aqueous sodium potassium tartrate and triethanolamine
were added until a clear solution resulted. After extraction with ethyl
acetate, the resulting organic layer was washed with brine, dried
(MgSO4), filtered, and concentrated in vacuo. The residue was
dissolved in 5 mL of methanol containing a catalytic amount of sodium
methoxide and the resultant solution stirred overnight at room tem-
perature. After concentration in vacuo and flash chromatography (3:1
hexane:ethyl acetate), rac-17b (212 mg, 0.38 mmol, 76% yield) was
obtained. In the same way, oxazolidinone 10b (0.064 g, 0.10 mmol)
yield). IR (film): 1720, 1475, 1473, 1395 cm-1 1H NMR (300 MHz,
.
CDCl3): δ 7.27 (d, J ) 4.2 Hz, 1 H), 4.57 (dd, J ) 2.1 Hz, 1 H), 4.27
(dq, J ) 10.9, 7.1 Hz, 1 H), 4.25 (m, 1 H), 4.15 (dq, J ) 10.9, 7.1 Hz,
1 H), 3.51 (dt, J ) 3.8, 2.4 Hz, 1 H), 3.40 (t, J ) 4.0 Hz, 1 H), 1.28
(t, J ) 7.1 Hz, 3 H), 0.84 (s, 18 H), 0.14 (s, 3 H), 0.11 (s, 3 H), 0.10
(s, 3 H), -0.01 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ 166.3, 137.4,
134.4, 69.3, 67.9, 60.7, 57.9, 45.1, 25.5, 25.4, 17.8, 17.7, 14.0, -4.6,
-4.9, -5.0, -5.3. HRMS Calcd for C20H37O5Si2: C, 58.83; H, 9.40.
Found: C, 58.71; H, 9.20
(-)-9b. Diene 8b (0.067 g, 0.17 mmol), sodium bicarbonate (0.84
g, 1 mmol), and m-CPBA (0.061 g, 0.36 mmol) in 0.5 mL of
dichloromethane as above gave, after flash chromatography eluting with