N
S. Matsuoka et al.
Feature
Synthesis
tracted with Et2O (3 ×), and the combined organic extracts were
washed with H2O (2 ×) and brine, dried (Na2SO4), and concentrated in
vacuo. The residue was dissolved in EtOH (1 mL), to which PPTS (27.0
mg, 0.107 mmol) was added at rt. The reaction mixture was warmed
to 60 °C and stirred for 3 h. The reaction was stopped by adding sat.
aq NaHCO3. The crude product was extracted with EtOAc (3 ×), and
the combined organic extracts were washed with brine, dried
(Na2SO4), and concentrated in vacuo. The residue was purified flash
column chromatography (SiO2, hexane/EtOAc 10:1) to afford phenol
33 (88.9 mg, 92%) as a colorless oil; Rf = 0.34 (hexane/EtOAc 6:1).
ane/EtOAc 9:1) to afford epoxy alcohol 35 (152 mg, 85%) as a white
amorphous solid; Rf = 0.70 (hexane/EtOAc 2:1); []D +24 (c 0.990,
CHCl3).
20
IR (neat): 3497, 2954, 2931, 1619, 1513, 1405, 1259, 1222, 1117, 837
cm–1
.
1H NMR (600 MHz, CDCl3): = –0.01 (s, 3 H), 0.02 (s, 3 H), 0.85 (s, 9
H), 1.40 (s, 3 H), 1.42 (s, 3 H), 3.24 (ddd, J = 6.9, 4.9, 2.7 Hz, 1 H), 3.48
(dd, J = 12.6, 2.7 Hz, 1 H), 3.66 (d, JH,F = 1.5 Hz, 1 H, OH), 3.80 (dd, J =
12.6, 6.9 Hz, 1 H), 3.85 (s, 3 H), 3.87 (s, 3 H), 4.01 (dd, J = 4.9 Hz, JH,F
=
4.9 Hz, 1 H), 5.64 (d, J = 10.0 Hz, 1 H), 6.46 (d, J = 8.6 Hz, 1 H), 6.54 (d,
IR (neat): 3434, 2969, 2916, 1619, 1599, 1467, 1285, 1165, 1032, 782
J = 10.0 Hz, 1 H), 6.60 (d, JH,F = 12.0 Hz, 1 H) 6.78 (dd, J = 8.6 Hz, JH,F
8.6 Hz, 1 H), 7.12 (d, JH,F = 7.0 Hz, 1 H).
=
cm–1
.
1H NMR (600 MHz, CDCl3): = 1.74 (s, 3 H), 1.80 (s, 3 H), 3.39 (d, J =
7.2 Hz, 2 H), 5.25 (t, J = 7.2 Hz, 1 H), 5.37 (s, 1 H, OH), 6.59 (d, J = 8.1
Hz, 1 H), 6.63 (dd, J = 8.8 Hz, JH,F = 8.9 Hz, 1 H), 7.03 (ddd, J = 8.8, 8.1
Hz, JH,F = 7.4 Hz, 1 H).
13C NMR (150 MHz, CDCl3): = –5.3, –5.1, 18.4, 26.0, 28.0, 28.2, 56.3,
56.5, 59.6, 61.1, 61.8 (d, JC,F = 7.5 Hz, 1 C), 71.9 (d, JC,F = 3.9 Hz, 1 C),
76.8, 100.2 (d, JC,F = 28.7 Hz, 1 C), 109.8 (d, JC,F = 6.0 Hz, 1 C), 110.7 (d,
JC,F = 19.0 Hz, 1 C), 111.4 (d, JC,F = 2.9 Hz, 1 C), 115.1 (d, JC,F = 6.1 Hz, 1
C), 120.4 (d, JC,F = 15.0 Hz, 1 C), 124.8 (d, JC,F = 12.0 Hz, 1 C), 127.3 (d,
JC,F = 4.5 Hz, 1 C),131.1, 145.3 (d, JC,F = 2.2 Hz, 1 C), 149.4 (d, JC,F = 10.5
Hz, 1 C), 153.2 (d, JC,F = 232.5 Hz, 1 C), 154.0, 156.4 (d, JC,F = 250.5 Hz, 1
C).
13C NMR (150 MHz, CDCl3): = 17.8 22.0 (d, JC,F = 4.5 Hz, 1 C), 25.8,
107.6 (d, JC,F = 23.2 Hz, 1 C), 111.4 (d, JC,F = 3.0 Hz, 1 C), 114.8 (d, JC,F
18.8 Hz, 1 C), 120.9, 127.3 (d, JC,F = 10.5 Hz, 1 C), 135.2, 155.7 (d, JC,F
7.4 Hz, 1 C), 161.3 (d, JC,F = 243.7 Hz, 1 C).
=
=
19F NMR (565 MHz, CDCl3): = –120.4.
19F NMR (565 MHz, CDCl3): = –125.7, –121.2.
HRMS (ESI): m/z calcd for C11H12FO [M – H]–: 179.08777; found:
HRMS (ESI): m/z calcd for C29H39F2O6Si [M + H]+: 549.24785; found:
179.08734.
549.24903.
ether 34
Diol 37
To a solution of phenol 33 (302mg, 1.68 mmol) in EtOH (16.6 mL) was
added CuCl2 (113 mg, 0.850 mmol) and PdCl2 (45.0 mg, 0.254 mmol)
at rt. After stirring for 6 h at 60 °C, the reaction mixture was filtered
through a Celite pad (washed with Et2O) and the filtrate was concen-
trated to half its volume in vacuo. The crude products were added to
aq 1 M NaOH. After extraction with hexane (3 ×), the combined or-
ganic extracts were washed with brine, dried (Na2SO4), and concen-
trated in vacuo. The residue was purified by bulb-to-bulb distillation
(140 °C (oven temp)/20 mmHg) to afford ether 34 (220 mg, 74%) as a
colorless oil; Rf = 0.80 (hexane/EtOAc 6:1).
To a solution of epoxy alcohol 35 (2.09 g, 3.81 mmol) in CH2Cl2 (70
mL) was added BF3·OEt2 (126 mg, 0.888 mmol) in CH2Cl2 (6.2 mL) at
–15 °C. After stirring for 40 min, the reaction was stopped by adding
sat. aq NaHCO3. The crude product was extracted with CH2Cl2 (3 ×),
and the combined organic extracts were washed with brine, dried
(Na2SO4), and concentrated in vacuo. The residue was dissolved in
THF (76 mL), to which i-Bu2AlH (1.0 M in hexane, 11.4 mL, 11.4
mmol) was added at –78 °C. After stirring for 20 min at –78 °C, the
reaction was stopped by adding sat. aq Rochelle’s salt. After stirring
for 40 min at rt, the crude products were extracted with EtOAc (3 ×).
The combined organic extracts were washed with brine, dried
(Na2SO4), and concentrated in vacuo. The residue was purified by
flash chromatography (SiO2, hexane/EtOAc 1:2) to afford diol 37 (1.85
g, 88%) as a white amorphous solid; Rf = 0.42 (hexane/EtOAc 2:1);
[]D20 +111 (c 1.60, CHCl3).
IR (neat): 2977, 2928, 1619, 1463, 1284, 1238, 1210, 1117, 1041, 754
cm–1
.
1H NMR (600 MHz, CDCl3): = 1.44 (s, 6 H), 5.64 (d, J = 9.8 Hz, 1 H),
6.52–6.59 (m, 3 H), 7.02 (ddd, J = 11.5, 7.2 Hz, JH,F = 7.2 Hz, 1 H).
13C NMR (150 MHz, CDCl3): = 27.9, 76.4, 107.3 (d, JC,F = 21.0 Hz, 1 C),
IR (neat): 3476, 2930, 2857, 1624, 1577, 1513, 1465, 1448, 1257, 1116
110.0 (d, JC,F = 18.2 Hz, 1 C), 112.1 (d, JC,F = 3.1 Hz, 1 C), 115.1 (d, JC,F
=
cm–1
.
4.7 Hz, 1 C), 128.9 (d, JC,F = 10.3 Hz, 1 C), 130.7 (d, JC,F = 2.5 Hz, 1 C),
154.0 (d, JC,F = 7.0 Hz, 1 C), 158.6 (d, JC,F = 248.1 Hz, 1 C).
19F NMR (565 MHz, CDCl3): = –126.5.
HRMS (APCI): m/z calcd for C11H10FO [M – H]–: 179.07212; found:
179.07276.
1H NMR (600 MHz, CDCl3): = –0.03 (s, 3 H), –0.01 (s, 3 H), 0.84 (s, 9
H), 1.39 (s, 3 H), 1.42 (s, 3 H), 2.72 (br s, 1 H, OH), 3.05 (br s, 1 H, OH),
3.28 (dd, J = 10.8, 8.2 Hz, 1 H), 3.42 (dd, J = 5.7, 3.5 Hz, 1 H), 3.51 (dd,
J = 10.8, 4.1 Hz, 1 H), 3.81 (s, 3 H), 3.88 (s, 3 H), 4.02–4.17 (m, 1 H),
5.49 (dd, J = 5.7 Hz, JH,F = 2.5 Hz, 1 H), 5.64 (d, J = 10.0 Hz, 1 H), 6.44 (d,
J = 8.4 Hz, 1 H), 6.47 (d, JH,F = 11.1 Hz, 1 H), 6.57 (d, J = 10.0 Hz, 1 H),
6.89 (dd, J = 8.4 Hz, JH,F =8.4 Hz, 1 H), 7.33 (d, JH,F = 6.7 Hz, 1 H).
Epoxy Alcohol 35
To a solution of ether 34 (83.1 mg, 0.466 mmol) in Et2O (4.0 mL) and
N,N,N′,N′-tetramethylethylenediamine (0.4 mL) was added s-BuLi
(1.07 M in cyclohexane and hexane, 0.38 mL, 0.41 mmol) at –78 °C.
After stirring for 1 h at –78 °C, a solution of azeotropically dried (tolu-
ene, 1 mL 3 ×) epoxy ketone 19 (103 mg, 0.278 mmol) in Et2O (1.5 mL)
was added. The reaction mixture was warmed to –50 °C over 1 h, and
the reaction was stopped by adding sat. aq NH4Cl. The crude products
were extracted with EtOAc (3 ×), and the combined organic extracts
were washed with brine, dried (Na2SO4), and concentrated in vacuo.
The residue was purified by flash column chromatography (SiO2, hex-
13C NMR (150 MHz, CDCl3): = –5.4, –5.3, 18.3, 25.9, 27.7, 28.0, 43.9
(br s, 1 C), 56.0, 56.5, 65.7, 70.5, 74.2, 76.5, 99.3 (d, JC,F = 30.0 Hz, 1 C),
109.6 (d, JC,F = 18.8 Hz, 1 C), 112.0 (d, JC,F = 2.8 Hz, 1 C), 113.7 (d, JC,F
4.9 Hz, 1 C), 114.3 (d, JC,F = 15.0 Hz, 1 C), 115.4 (d, JC,F = 5.7 Hz, 1 C),
121.0 (d, JC,F = 13.5 Hz, 1 C), 127.6 (d, JC,F = 6.1 Hz, 1 C), 130.8 (d, JC,F
2.1 Hz, 1 C), 144.9 (d, JC,F = 2.5 Hz, 1 C), 148.6 (d, JC,F = 10.0 Hz, 1 C),
=
=
153.2 (d, JC,F = 6.9 Hz, 1 C), 155.5 (d, JC,F = 248.4 Hz, 1 C), 156.1 (d, JC,F
=
237.5 Hz, 1 C).
19F NMR (565 MHz, CDCl3): = –132.1, –131.4.
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–R