Takashima and Kobayashi
JOCArticle
(R)-2-(4-(tert-Butyldimethylsilyloxy)-3-methoxyphenyl)-1-
((2R,3R)-3-(trimethylsilyl)oxiran-2-yl)ethanol (24) and (E,R)-1-
(4-(tert-Butyldimethylsilyloxy)-3-methoxyphenyl)-4-(trimethylsilyl)-
but-3-en-2-ol ((S)-23). To a solution of Ti(O-i-Pr)4 (0.88 mL,
2.97 mmol) in CH2Cl2 (22 mL) was added (-)-DIPT (0.74 mL,
3.53 mmol) at -10 °C under an argon atmosphere. After 50 min
of stirring at -10 °C, a solution of allylic alcohol rac-23 (1.13 g,
2.97 mmol) in CH2Cl2 (8 mL) was added to the solution. After
50 min of stirring at -10 °C, the solution was cooled to -40 °C,
and t-BuOOH (0.56 mL, 5.86 M in CH2Cl2, 3.28 mmol) was
added. The solution was stirred at -20 °C for 7 h, and Me2S
(0.24 mL, 3.27 mmol) was added. The solution was stirred
at room temperature for 0.5 h, and 10% aqueous tartaric acid
(0.5 mL) and NaF (174 mg, 4.14 mmol) were added. The
resulting mixture was stirred for 30 min and filtered through a
pad of Celite. The filtrate was concentrated in vacuo to afford a
residual oil, which was chromatographed on silica gel with
hexane/EtOAc (from 100:1 to 4:1) to afford allylic alcohol (S)-
23 (572 mg, 51%) and epoxy alcohol 24 (525 mg, 44%) as a
colorless oil. Epoxy alcohol 24: [R]27D -3.7 (c 0.22, CHCl3); IR
(neat) 3447, 1516, 1282, 1250, 841 cm-1; 1H NMR (300 MHz,
CDCl3) δ 0.06 (s, 9 H), 0.14 (s, 6 H), 0.99 (s, 9 H), 1.95 (d, J=
2 Hz, 1 H), 2.36 (d, J=4 Hz, 1 H), 2.77-2.81 (m, 2H), 2.85 (t, J=
4 Hz, 1 H), 3.79 (s, 3 H), 3.96-4.04 (m, 1 H), 6.67 (dd, J=8, 2 Hz,
1 H), 6.74 (d, J=2 Hz, 1 H), 6.78 (d, J=8 Hz, 1 H); 13C NMR
(75 MHz, CDCl3) δ -4.6 (-), -3.6 (-), 18.5 (þ), 25.8 (-), 40.2
(þ), 48.0 (-), 55.5 (-), 57.9 (-), 70.6 (-), 113.3 (-), 120.9 (-),
121.6 (-), 130.6 (þ), 143.8 (þ), 151.0 (þ); HRMS (FAB) calcd
for C20H36O4Si2Na [(M þ Na)þ] 419.2050, found 419.2045.
Allylic alcohol (S)-23: [R]23D -9.3 (c 0.56, CHCl3).
(S)-2-(4-(tert-Butyldimethylsilyloxy)-3-methoxyphenyl)-1-
((2S,3S)-3-(trimethylsilyl)-oxiran-2-yl)ethanol (ent-24). To a solu-
tion of Ti(O-i-Pr)4 (0.45 mL, 1.52 mmol) in CH2Cl2 (10 mL) was
added (þ)-DIPT (0.38 mL, 1.82 mmol) at -10 °C under an argon
atmosphere. After 30 min of stirring at -10 °C, a solution of
allylic alcohol (S)-23 (577 mg, 1.52 mmol) in CH2Cl2 (5 mL) was
added to the solution. After 45 min of stirring at -20 °C, the
solution was cooled to -30 °C, and t-BuOOH (0.29 mL, 5.86 M
in CH2Cl2, 1.70 mmol) was added. The solution was stirred at
-20 °C for 13 h, and Me2S (0.12 mL, 1.63 mmol) was added. The
solution was stirred at room temperature for 0.5 h, and 10%
aqueoustartaricacid(0.3 mL) andNaF(0.114 g, 2.74mmol) were
added. The resulting mixture was stirred for 30 min and filtered
through a pad of Celite. The filtrate was concentrated in vacuo to
afford a residual oil, which was chromatographed on silica gel with
hexane/EtOAc (from 100:1 to 4:1) to afford epoxy alcohol ent-24
(0.505 g, 84%) as a colorless oil: [R]25D þ3.5 (c 0.63, CHCl3).
(R)-2-(4-(tert-Butyldimethylsilyloxy)-3-methoxyphenyl)-1-
((2S,3S)-3-(trimethylsilyl)-oxiran-2-yl)ethanol (25). To an ice-cold
solution of epoxy alcohol ent-24 (99 mg, 0.25 mmol), PPh3 (104 mg,
0.397 mmol), and ClCH2COOH (31 mg, 0.31 mmol) in THF
(1.5 mL) was added DIAD (0.15 mL, 0.305 mmol) dropwise. After
3 h of stirring at 0 °C, the mixture was allowed to warm to room
temperature over 13 h. The reaction mixture was concentrated in
vacuo to afford a residual oil, which was chromatographed on silica
gel with hexane/EtOAc (from 1:0 to 20:1) to afford the correspond-
ing chloroacetate (106 mg, 90%) as a colorless oil: 1H NMR
(300 MHz, CDCl3) δ 0.00 (s, 9 H), 0.14 (s, 6 H), 0.99 (s, 9 H),
1.95 (d, J=3 Hz, 1 H), 2.89 (dd, J=14, 8 Hz, 1 H), 2.94 (dd, J=
6, 3 Hz, 1 H), 3.01 (dd, J=14, 6 Hz, 1 H), 3.79 (s, 3 H), 4.05 (d, J=
15 Hz, 1 H), 4.10 (d, J=15 Hz, 1 H), 4.84 (dt, J=6, 8 Hz, 1 H), 6.63
(dd, J=8, 2 Hz, 1 H), 6.72 (d, J=2 Hz, 1 H), 6.77 (d, J=8 Hz, 1 H);
13C NMR (75 MHz, CDCl3) δ -4.6 (-), -3.7 (-), 18.5 (þ), 25.8
(-), 37.7 (þ), 41.0 (þ), 49.8 (-), 55.5 (-), 56.2 (-), 79.4 (-), 113.0
(-), 121.0 (-), 121.7 (-), 129.2 (þ), 144.1 (þ), 151.0 (þ), 166.7 (þ).
To an ice-cold solution of the above chloroacetate (327 mg,
0.691 mmol) in MeOH (3 mL) was added n-PrNH2 (0.06 mL,
0.73 mmol). After 1.5 h of stirring at 0 °C, the mixture was
poured into saturated NH4Cl. The product was extracted with
EtOAc twice. The combined organic layers were washed with
brine, dried over MgSO4, and concentrated in vacuo to afford a
residual oil, which was chromatographed on silica gel with
hexane/EtOAc (from 10:1 to 4:1) to afford epoxy alcohol 25
(269 mg, 98%) as a colorless oil: [R]24D -29 (c 0.18, CHCl3); IR
(neat) 3394, 1513, 1281, 1250, 841 cm-1; 1H NMR (300 MHz,
CDCl3) δ 0.02 (s, 9 H), 0.14 (s, 6 H), 0.99 (s, 9 H), 2.00 (d, J=
5 Hz, 1 H), 2.13 (d, J=4 Hz, 1 H), 2.79 (dd, J=13, 7 Hz, 1 H),
2.84-2.96 (m, 2 H), 3.59-3.69 (m, 1 H), 3.79 (s, 3 H), 6.66 (dd,
J=8, 2 Hz, 1 H), 6.72 (d, J=2 Hz, 1 H), 6.78 (d, J=8 Hz, 1 H);
13C NMR (75 MHz, CDCl3) δ -4.6 (-), -3.6 (-), 18.5 (þ), 25.8
(-), 40.7 (þ), 49.7 (-), 55.6 (-), 58.7 (-), 74.3 (-), 113.3 (-),
120.9 (-), 121.6 (-), 130.7 (þ), 143.8 (þ), 151.0 (þ); HRMS
(FAB) calcd for C20H36O4Si2Na [(M þ Na)þ] 419.2050, found
419.2061.
(R,E)-1-(4-(tert-Butyldimethylsilyloxy)-3-methoxyphenyl-
4-(tributylstannyl)but-3-en-2-ol (26). From 25:. To an ice-cold
solution of i-Pr2NH (0.32 mL, 2.28 mmol) in THF (4 mL) was
added n-BuLi (1.14 mL, 1.55 M in THF, 1.77 mmol) under an
argon atmosphere. After 0.5 h of stirring at 0 °C, Bu3SnH
(0.20 mL, 0.744 mmol) and, after 0.5 h at 0 °C, a solution of
epoxy alcohol 25 (260 mg, 0.655 mmol) in THF (2.5 mL) were
added to the solution. Stirring was continued at 0 °C for 1 h
and at room temperature for 4 h. The solution was poured
into saturated NH4Cl. The product was extracted with EtOAc
twice. The combined organic layers were washed with brine,
dried over MgSO4, and concentrated in vacuo to afford a
residual oil, which was chromatographed on silica gel with
hexane/EtOAc (from 1:0 to 20:1) to afford γ-stannyl alcohol
26 (330 mg, 84%) as an yellow oil: [R]23D1-8.7 (c 0.62, CHCl3);
IR (neat) 3360, 1515, 1282, 840 cm-1; H NMR (300 MHz,
CDCl3) δ 0.15 (s, 6 H), 0.84-0.94 (m, 15 H), 0.99 (s, 9 H),
1.23-1.37 (m, 6 H), 1.43-1.53 (m, 6 H), 1.67 (d, J=4 Hz, 1 H),
2.70 (dd, J=14, 8 Hz, 1 H), 2.82 (dd, J=14, 5 Hz, 1 H), 3.79
(s, 3 H), 4.23-4.32 (m, 1 H), 6.05 (dd, J = 19, 5 Hz, 1 H;
J
Sn-H(cis)=65 Hz), 6.17 (dd, J=19, 0.6 Hz, 1 H; JSn-H(gem)=
71 Hz), 6.65 (dd, J=8, 2.5 Hz, 1 H), 6.70-6.73 (m, 1 H), 6.75-
6.81 (m, 1 H); 13C NMR (75 MHz, CDCl3) δ -4.6 (-), 9.5 (þ),
13.8 (-), 18.5 (þ), 25.8 (-), 27.4 (þ), 29.1 (þ), 43.7 (þ), 55.5
(-), 75.9 (-), 113.5 (-), 120.9 (-), 121.8 (-), 128.1 (-), 131.3
(þ), 143.7 (þ), 149.8 (-), 150.9 (þ). From 24: To an ice-cold
solution of i-Pr2NH (0.70 mL, 4.99 mmol) in THF (5 mL) was
added n-BuLi (2.51 mL, 1.55 M in THF, 3.89 mmol) under an
argon atmosphere. After 0.5 h of stirring at 0 °C, Bu3SnH
(0.43 mL, 1.60 mmol) and, after 0.5 h at 0 °C, a solution of
epoxy alcohol 24 (572 mg, 1.44 mmol) in THF (3 mL) were
added to the solution. Stirring was continued at 0 °C for 1 h
and at room temperature for 4 h. The solution was poured
into saturated NH4Cl. The product was extracted with EtOAc
twice and purified as above to afford alcohol 26 (646 mg,
75%) as an yellow oil.
1-(tert-Butyldimethylsilyloxy)-4-iodo-2-methoxybenzene (27).
To a solution of phenol 2-methoxyphenol (103 mg, 0.83 mmol)
and NaOH (61 mg, 1.53 mmol) in MeOH (2 mL) was added I2
(215 mg, 0.847 mmol) at -4 °C. The mixture was stirred at -4 °C
for 1 h and poured into H2O. The product was extracted with
EtOAc twice. The combined organic layers were washed with
aqueous Na2S2O and brine, dried over MgSO4, and concen-
trated in vacuo to afford a residual oil, which was chromato-
graphed on silica gel with hexane/EtOAc (from 1:0 to 10:1) to
afford 4-iodo-2-methoxyphenol (120 mg, 70%) as a colorless oil:
1H NMR (300 MHz, CDCl3) δ 3.88 (s, 3 H), 5.57 (s, 1 H), 6.68 (d,
J=8 Hz, 1 H), 7.13 (d, J=2 Hz, 1 H), 7.18 (dd, J=8, 2 Hz, 1 H).
The 1H NMR spectrum was identified with that reported.32
(32) Fryatt, T.; Botting, N. P. J. Labelled Compd. Radiopharm. 2005, 48,
951–969.
J. Org. Chem. Vol. 74, No. 16, 2009 5925