William and Kobayashi
1
NaHCO3. The product was extracted with EtOAc twice. The
combined organic extracts were dried and concentrated to
afford an oily residue, which was purified by chromatography
(hexane/EtOAc) to furnish aldol 28 (40 mg, 79% yield): IR
(neat) 3515, 1683, 1609, 1581 cm-1; 1H NMR δ 0.47-0.68 (m,
6 H), 0.80-1.10 (m, 13 H), 1.02 (s, 3 H), 1.14 (s, 3 H), 1.20-
2.00 (m, 9 H), 2.25-2.64 (m, 6 H), 2.82-3.03 (m, 1 H), 3.09-
3.31 (m, 2 H), 3.35 (s, 3 H), 3.48 (s, 3 H), 3.33-3.52 (m, 1 H),
3.68 (t, J ) 9 Hz, 1 H), 4.93 (d, J ) 7 Hz, 1 H), 5.02-5.26 (m,
4 H), 6.60 (s, 2 H), 7.07-7.32 (m, 5 H). HRMS (CI) m/z calcd
for C39H62O7Si (M+) 670.4265, found 670.4266.
yield): IR (neat) 1601, 1456 cm-1; H NMR δ 0.55 (q, J ) 8
Hz, 6 H), 0.94 (t, J ) 8 Hz, 9 H), 1.05 (s, 3 H), 1.13 (s, 3 H),
1.49-1.64 (m, 1 H), 1.68 (s, 3 H), 1.73-1.85 (m, 1 H), 1.87-
2.06 (m, 3 H), 3.39-3.47 (m, 2 H), 5.21 (br s, 1 H), 7.09-7.32
(m, 5 H); 13C NMR δ 7.0, 7.4, 22.6, 23.7, 28.6, 29.5, 30.0, 43.9,
51.3, 76.3, 125.5, 125.8, 128.2, 128.3, 133.3, 148.6. Anal. Calcd
for C22H36OSi: C, 76.68; H, 10.53. Found: C, 76.66; H, 10.56.
3-[(2,6-Bis(m eth oxym eth oxy)-4-p en tyl)p h en yl]-1-m eth -
yl-4-[(1-m et h yl-1-t r iet h ylsilyloxy)et h yl]-1-cycloh exen e
(31b). To an ice-cold solution of Ni(acac)2 (8 mg, 0.03 mmol)
in THF (5 mL) was added MeMgCl (0.27 mL, 2.80 M in THF,
0.76 mmol). After 10 min at 0 °C, a solution of enol phosphate
12b (200 mg, 0.297 mmol) in THF (5 mL) was added. The
solution was stirred at ambient temperature overnight and
diluted with saturated NaHCO3 at 0 °C. The product was
extracted with EtOAc twice. The combined organic layers were
dried and concentrated to afford an oily residue, which was
purified by chromatography (hexane/EtOAc) to furnish 31b
3-[(2,6-Bis(m et h oxym et h oxy)-4-p en t yl)p h en yl]-2-h y-
d r oxym eth yl-4-[(1-m eth yl-1-tr ieth ylsilyloxy)eth yl]-1-cy-
cloh exa n on e (29). To an ice-cold solution of iodoketone 23b
(220 mg, 0.332 mmol) in THF (2 mL) was added EtMgBr (0.50
mL, 1.0 M in THF, 0.50 mmol). After 10 min of stirring,
gaseous CH2O in THF (5 mL) freshly prepared by cracking
(CH2O)n (200 mg, 6.6 mmol) was added to the resulting pale
yellow solution. The reaction was continued at 0 °C for 2 h
and quenched with saturated NaHCO3. The product was
extracted with EtOAc twice. The combined organic extracts
were dried and concentrated to afford an oily residue, which
was purified by chromatography (hexane/EtOAc) to furnish
(146 mg, 92% yield): IR (neat) 1608, 1579 cm-1; H NMR δ
1
0.44-0.55 (m, 6 H), 0.85-0.96 (m, 15 H), 1.11 (s, 3 H), 1.22-
1.64 (m, 10 H), 1.84-2.20 (m, 3 H), 2.38-2.54 (m, 3 H), 3.46
(br s, 6 H), 3.93 (d, J ) 9 Hz, 1 H), 4.96-5.15 (m, 5 H), 6.57 (s,
2 H); 13C NMR δ 7.0, 7.4, 14.3, 22.7, 23.5, 25.4, 26.4, 30.1, 30.9,
31.2, 31.9, 34.6, 36.4, 47.3, 56.1 (br s), 76.6, 94.3, 95.0, 108.4,
108.9, 122.9, 125.7, 132.3, 142.0, 154.8 (br s), 156.5 (br s). Anal.
Calcd for C31H54O5Si: C, 69.62; H, 10.18. Found: C, 69.20; H,
10.09.
1
aldol 29 (120 mg, 64% yield): IR (neat) 3567, 1700 cm-1; H
NMR (diagnostic signals) δ 0.51-0.65 (m, 6 H), 1.05 (s, CH3),
1.11 (s, CH3), 3.43 and 3.50 (2s, minor isomer, 2 CH3), 3.47
and 3.50 (2s, major isomer, 2 CH3). HRMS (CI) m/z calcd for
C
31H54O7Si (M+) 566.3639, found 566.3638.
3-[(2,6-B is (m e t h o x y m e t h o x y )-4-p e n t y l)p h e n y l]-1-
[(d im eth yl(p r op yloxy)silyl)m eth yl]-4-[(1-m eth yl-1-tr ieth -
ylsilyloxy)eth yl]-1-cycloh exen e (33b). To an ice-cold solu-
tion of Ni(acac)2 (0.10 mg, 0.039 mmol) in THF (5 mL) was
added ClMgCH2Si(Me)2(OPr-i) (1.01 mL, 0.95 M in THF, 0.96
mmol). After 10 min of stirring at 0 °C, a solution of enol
phosphate 12b (260 mg, 0.386 mmol) in THF (5 mL) was added
and stirring was continued overnight at ambient temperature.
The reaction was cooled to 0 °C and quenched with saturated
NaHCO3. The product was extracted with EtOAc twice. The
combined organic layers were dried and concentrated to afford
an oily residue, which was purified by chromatography (hex-
ane/EtOAc) to furnish 33b (220 mg, 88% yield): IR (neat) 1608,
1579 cm-1; 1H NMR δ 0.09 and 0.10 2s, 6 H), 0.45-0.56 (m, 6
H), 0.85-0.97 (m, 15 H), 1.07-1.18 (m, 9 H), 1.25-1.64 (m, 9
H), 1.88-2.18 (m, 3 H), 2.37-2.56 (m, 3 H), 3.46 (s, 3 H), 3.48
(s, 3 H), 3.89-4.04 (m, 2 H), 4.86 (s, 1 H), 5.02-5.26 (m, 4 H),
6.57 (s, 2 H); 13C NMR δ -1.1, -1.0, 7.0, 7.4, 14.3, 22.7, 25.6,
25.9, 26.6, 27.3, 30.1, 31.2, 31.6, 31.9, 34.6, 36.3, 47.1, 56.0,
56.2, 64.9, 76.5, 94.4, 95.1, 108.5, 108.9, 123.0, 124.3, 132.4,
141.8, 154.8, 156.6. Anal. Calcd for C36H66O6Si2: C, 66.41; H,
10.22. Found: C, 66.13; H, 10.11.
3-[(2,6-Bis(m eth oxym eth oxy)-4-p en tyl)p h en yl]-2-m eth -
ylen e-4-[(1-m et h yl-1-t r iet h ylsilyloxy)et h yl]-1-cycloh ex-
a n on e (30). To an ice-cold solution of aldol 29 (50 mg, 0.088
mmol) and Et3N (0.12 mL, 0.88 mmol) in CH2Cl2 (2 mL) was
added MsCl (0.054 mL, 0.698 mmol). After 1 h of stirring at 0
°C, the reaction was quenched with NaHCO3 and the product
was extracted with EtOAc twice. The combined organic
extracts were dried and concentrated to afford an oily residue,
which was purified by chromatography (hexane/EtOAc) to
furnish the corresponding mesylate (44 mg, 79% yield): IR
(neat) 1715, 1357 cm-1; 1H NMR δ 0.51-0.63 (m, 6 H), 0.84-
1.00 (m, 12 H), 1.05 (s, 3 H), 1.13 (s, 3 H), 1.23-1.42 (m, 4 H),
1.50-1.66 (m, 2 H), 1.83-1.98 (m, 1 H), 2.30-2.75 (m, 6 H),
2.97 (s, 3 H), 3.39-3.52 (m, 1 H), 3.47 (s, 3 H), 3.50 (s, 3 H),
3.73 (dd, J ) 12, 8 Hz, 1 H), 4.02 (dd, J ) 10, 3 Hz, 1 H), 4.14
(dd, J ) 10, 6 Hz, 1 H), 5.16 (s, 2 H), 5.23 (s, 2 H), 6.60 (br s,
1 H), 6.67 (d, J ) 1 Hz, 1 H); 13C NMR δ 6.8, 7.3, 14.3, 22.7,
24.1, 27.3, 30.2, 31.1, 31.9, 34.7, 36.5, 36.8, 38.9, 49.3, 50.0,
56.3, 56.6, 67.8, 76.8, 94.3, 95.2, 107.85, 107.92, 117.3, 144.0,
155.4, 156.3, 211.0. HRMS (CI) m/z calcd for C32H56O9SSi (M+)
644.3414, found 644.3408.
To an ice-cold solution of the above mesylate (40 mg, 0.062
mmol) in CH2Cl2 (2 mL) was added Al2O3 (63 mg, 0.62 mmol).46
After stirring overnight at ambient temperature, the reaction
mixture was filtered through a pad of Celite and the solvent
was evaporated under reduced pressure to afford an oily
residue, which was purified by chromatography (hexane/
EtOAc) to furnish 30 (30 mg, 88% yield): IR (neat) 1721, 1697,
3-[(2,6-Dim eth oxy-4-p en tyl)p h en yl]-1-[(d im eth yl(p r o-
pyloxy)silyl)m eth yl]-4-[(1-m eth yl-1-tr ieth ylsilyloxy)eth yl]-
1-cycloh exen e (33c). According to the procedure for synthesis
of 33b, the silylmethylation of enol phosphate 12c (350 mg,
0.571 mmol) in THF (5 mL) was carried out with ClMgCH2-
Si(Me)2(OPr-i) (1.32 mL, 1.08 M in THF, 1.43 mmol) and
Ni(acac)2 (15 mg, 0.058 mmol) in THF (5 mL) to afford 33c
(286 mg, 85% yield): IR (neat) 1607, 1579, 1456 cm-1; 1H NMR
δ 0.06 (s, 3 H), 0.12 (s, 3 H), 0.45-0.54 (m, 6 H), 0.85-0.95
(m, 15 H), 1.05 (br s, 3 H), 1.11 (d, J ) 6 Hz, 3 H), 1.12 (d, J
) 6 Hz, 3 H), 1.27-1.67 (m, 9 H), 1.81-1.94 (m, 1 H), 2.03-
2.23 (m, 2 H), 2.32-2.45 (m, 1 H), 2.53 (t, J ) 8 Hz, 2 H), 3.70
(br s, 3 H), 3.77 (br s, 3 H), 3.88-3.97 (m, 2 H), 4.83 (br s, 1
H), 6.47 (br s, 2 H); 13C NMR δ -1.4, -0.9, 7.0, 7.4, 14.3, 22.8,
25.7, 26.0, 26.4, 27.8, 30.1, 31.3, 31.8, 31.9, 34.2, 36.6, 46.8,
55.3, 55.9, 64.9, 76.6, 104.1, 104.7, 121.1, 124.4, 132.3, 141.5,
157.0, 158.8. Anal. Calcd for C34H62O4Si2: C, 69.09; H, 10.57.
Found: C, 69.04; H, 10.22.
1
1608 cm-1; H NMR δ 0.55 (q, J ) 8 Hz, 6 H), 0.85-0.97 (m,
12 H), 1.14 (s, 3 H), 1.23 (s, 3 H), 1.2-1.4 (m, 4 H), 1.49-1.82
(m, 3 H), 2.04-2.27 (m, 2 H), 2.39-2.69 (m, 4 H), 3.39 (br s, 3
H), 3.50 (br s, 3 H), 4.61 (d, J ) 7 Hz, 1 H), 5.00 (br s, 2 H),
5.08 (t, J ) 1.5 Hz, 1 H), 5.21 (br s, 2 H), 5.79 (t, J ) 1.5 Hz,
1 H), 6.58 (br s, 2 H); 13C NMR δ 6.9, 7.4, 14.3, 22.7, 22.8,
27.4, 30.0, 31.2, 31.8, 36.4, 36.9, 37.9, 49.7, 56.3, 76.3, 94.0,
94.7, 107.7, 108.0, 121.3, 122.5, 142.9, 149.0, 154 (br s), 155
(br s), 202.6. HRMS (CI) m/z calcd for
C
31H52O6Si (M+)
548.3533, found 548.3530.
1-Meth yl-4-[(1-m eth yl-1-tr ieth ylsilyloxy)eth yl]-3-p h en -
yl-1-cycloh exen e (31a ). According to the procedure for
synthesis of 31b (below), methylation of enol phosphate 12a
(90 mg, 0.186 mmol) in THF (2 mL) was carried out with
MeMgCl (0.17 mL, 2.80 M in THF, 0.48 mmol) and Ni(acac)2
(5 mg, 0.019 mmol) in THF (2 mL) to afford 31a (60 mg, 94%
3-[(2,6-Bis(m et h oxym et h oxy)-4-p en t yl)p h en yl]-1-h y-
d r oxym eth yl-4-[(1-m eth yl-1-tr ieth ylsilyloxy)eth yl]-1-cy-
cloh exen e (34b). To a solution of 33b (200 mg, 0.307 mmol),
NaHCO3 (103 mg, 1.23 mmol), and KF (124 mg, 2.13 mmol)
in THF/MeOH (1:1) (5 mL) was added 35% H2O2 (0.24 mL,
8780 J . Org. Chem., Vol. 67, No. 25, 2002