2188
Y. Liu et al.
LETTER
PdCl2 (dppf)·CH2Cl2 (40.0 mg, 4.9×10–2 mmol), AsPh3 (44.0
mg, 0.14 mmol), and Cs2CO3 (1.04 g, 3.2 mmol). The loaded
flask was evacuated and backfilled with nitrogen for five
times. A solution of the vinyl iodide 5 (360.0 mg, 0.79
mmol) in degassed DMF (12.0 mL) was added through a
syringe followed by adding degassed H2O (0.36 mL, 20
mmol). Some blocky solid in the resultant yellow suspension
was crushed with ultrasonication. After stirring at ambient
temperature for 5 min, the above solution of the B-alkyl
boronate was added via a syringe followed by stirring for
another 4 h at ambient temperature. The reaction was
quenched with sat. aq NH4Cl solution. The resultant mixture
was extracted with EtOAc (3 × 30 mL). The combined
organic layer was washed with brine, dried over anhyd
Na2SO4, filtered, and concentrated under reduced pressure.
The residue was purified by flash chromatography (silica
gel, first with PE and then with 2% EtOAc in PE) to afford
the coupling product 19 (485.0 mg, 85%).
(m, 2 H), 4.96 (s, 1 H), 4.83 (s, 1 H), 4.48 and 4.33 (ABq,
J = 11.2 Hz, 2 H), 3.82–3.75 (m, 1 H), 3.80 (s, 3 H), 3.71–
3.64 (m, 1 H), 3.43 and 3.38 (ABq, J = 18.0 Hz, 2 H), 3.36–
3.31 (m, 1 H), 2.30–1.49 (m, 10 H), 1.44 (s, 3 H), 1.18 (br
dd, J = 12.4, 11.6 Hz, 1 H), 1.07 (d, J = 6.0 Hz, 3 H), 0.97 (t,
J = 8.4 Hz, 9 H), 0.87–0.84 (m, 21 H), 0.78 (d, J = 6.4 Hz, 3
H), 0.68–0.60 (m, 6 H), 0.05–0.01 (m, 12 H). 13C NMR (100
MHz, CDCl3): d = 210.2, 159.0, 140.8, 135.1, 133.9, 131.2,
130.3, 129.2 (2×), 117.0, 116.5, 113.7 (2×), 82.4, 79.9, 72.6,
71.0, 70.8, 55.3, 43.7, 43.5, 41.8, 36.1 (2×), 35.4, 33.7, 25.9
(6×), 24.4, 20.8, 18.1, 18.1, 14.2, 13.4, 7.1 (3×), 6.6 (3×),
–4.3, –4.5 (2×), –4.8. HRMS (+ESI): m/z [M + Na+] calcd for
C48H88O6Si3Na: 867.5781; found: 867.5781.
(16) Procedure for the Synthesis of Hemiacetal 23
To a solution of the ketone 22a (7.8 mg, 9.2×10–3 mmol) in
dry THF (1.0 mL) was added pyridine-buffered HF (0.15
mL, prepared from 0.5 mL of HF·pyridine, 0.7 mL of
pyridine, and 1.6 mL of THF) at r.t. After stirring at the same
temperature for 1 h, no reaction had taken place according to
TLC analysis. Additional HF·pyridine (0.25 mL) was added
followed by stirring at r.t. for 23 h. The reaction was
quenched by adding sat. aq NaHCO3. The mixture was
extracted with EtOAc (3 × 5 mL). The combined organic
layer was washed with brine, dried over anhyd Na2SO4,
filtered, and concentrated under reduced pressure. The
residue was purified by flash column chromatography (silica
gel, 33% EtOAc in hexane) to give the hemiacetal 23 (2.3
mg, 50%) along with the hydroxy ketone 22b (0.6 mg, 9%).
Characterization Data for Hemiacetal 23
Characterization Data for Alkene 19
Colorless oil. [a]D20 –18.1 (c 2.50, CHCl3). Rf = 0.21 (100%
PE). 1H NMR (400 MHz, CDCl3): d = 7.25 (d, J = 7.6 Hz, 2
H), 6.86 (d, J = 7.6 Hz, 2 H), 5.60 (dt, J = 16.0, 6.4 Hz, 1 H),
5.51 (d, J = 16.0 Hz, 1 H), 4.50 and 4.32 (ABq, J = 11.2 Hz,
2 H), 3.80 (s, 3 H), 3.73–3.64 (m, 1 H), 3.41–3.34 (m, 1 H),
3.37 (s, 2 H), 2.10–1.80 (m, 3 H), 1.71–1.60 (m, 1 H), 1.51
(br dd, J = 12.8, 10.8 Hz, 1 H), 1.28 (s, 3 H), 1.20 (br dd,
J = 12.8, 12.0 Hz, 1 H), 1.07 (d, J = 6.0 Hz, 3 H), 1.00–0.90
(m, 18 H), 0.88 (br s, 12 H), 0.78 (d, J = 6.4 Hz, 3 H), 0.58
(q, J = 8.0 Hz, 12 H), 0.02 (br s, 6 H). 13C NMR (100 MHz,
CDCl3): d = 159.0, 136.7, 131.3, 129.2 (2×), 127.5, 113.6
(2×), 79.7, 75.6, 72.7, 71.4, 70.7, 55.3, 36.3, 36.0, 35.3, 33.6,
25.9 (3×), 24.5, 20.9, 18.1, 14.1, 13.1, 7.1 (3×), 6.8 (3×), 6.7
(3×), 4.4 (3×), –4.3, –4.8. HRMS (+ESI): m/z [M + Na+]
calcd for C40H78O5Si3Na: 745.5049; found: 745.5013.
Pale yellow oil. [a]D20 –17.6 (c 0.23, CHCl3). IR (film):
3459, 2924, 1613, 1514, 1264, 1035 cm–1. 1H NMR (400
MHz, CDCl3): d = 7.25 (d, J = 8.8 Hz, 2 H), 6.87 (d, J = 8.8
Hz, 2 H), 5.88–5.70 (m, 3 H), 5.11–5.03 (m, 2 H), 4.87 (d,
J = 2.0 Hz, 1 H), 4.83 (d, J = 2.0 Hz, 1 H), 4.53 and 4.32
(ABq, J = 11.0 Hz, 2 H), 3.95–3.84 (m, 1 H), 3.80 (s, 3 H),
3.79–3.70 (m, 1 H), 3.42–3.33 (m, 1 H), 3.03 (d, J = 1.6 Hz,
1 H), 2.40 (s, 1 H), 2.36–2.20 (m, 4 H), 2.17–1.84 (m, 5 H),
1.71–1.50 (m, 2 H), 1.35–1.17 (m, 2 H), 1.31 (s, 3 H), 1.12
(d, J = 6.6 Hz, 3 H), 0.89 (d, J = 6.5 Hz, 3 H), 0.83 (d, J = 7.0
Hz, 3 H). 13C NMR (100 MHz, CDCl3): d = 159.2, 141.5,
134.4, 133.9, 129.5 (2×), 129.3, 117.2, 113.8 (3×), 111.3,
99.2, 80.3, 77.1, 70.8, 70.7, 70.5, 55.3, 40.2, 39.3, 37.8, 36.7,
36.5, 34.9, 32.5, 21.0, 19.6, 14.5, 13.7. MS (+TOF LD):
m/z (%) = 525 (100) [M + Na+], 467 (55) [M+ – H2O – OH].
HRMS (+TOF CI): m/z [M+ – H2O – OH] calcd for
(15) Procedure for the Synthesis of Ketone 22a
A mixture of the allyl bromide 4 (63.0 mg, 0.20 mmol), the
aldehyde 20 (100.0 mg, 0.16 mmol), and indium powder
(24.0 mg, 0.20 mmol) in THF–H2O (1:1, 0.4 mL) was stirred
at 70 °C for 16 h in a sealed pressurized vial. After cooling
to r.t., the reaction mixture was diluted with 10% aq
NaHCO3 (2 mL) and extracted with EtOAc (3 × 5 mL). The
combined organic layer was washed with brine, dried over
anhyd Na2SO4, filtered, and concentrated under reduced
pressure. The residue was purified by flash column
chromatography (silica gel, 9% EtOAc in hexane) to provide
the alcohol 21a (79.0 mg, 57%) along with the diol 21b (24.2
mg, 20%).
+
C30H43O4 : 467.3161; found: 467.3158.
(17) Characterization Data for Hemiacetal 27
To a suspension of the alcohol 21a (69.0 mg, 8.1×10–2
mmol) and solid NaHCO3 (68.0 mg, 0.81 mmol) in CH2Cl2
(1 mL) cooled at 0 °C was added Dess–Martin periodinane
(0.3 M in CH2Cl2, 0.83 mL, 0.25 mmol) followed by stirring
at 25 °C for 2 h. The reaction was quenched by adding sat.
aq Na2S2O3 and sat. aq. NaHCO3. The resultant mixture was
extracted with EtOAc (3 × 5 mL), and the combined organic
layer was washed with brine, dried over anhyd Na2SO4,
filtered, and concentrated under reduced pressure. The
residue was purified by flash column chromatography (silica
gel, 9% EtOAc in hexane) to provide the ketone 22a (42.0
mg, 61%).
Pale yellow oil. [a]D20 –2.3 (c 0.28, CHCl3). IR (film): 3445,
2967, 2919, 1613, 1513, 1248, 1036 cm–1. 1H NMR (500
MHz, CDCl3): d = 7.25 (d, J = 8.8 Hz, 2 H), 6.87 (d, J = 8.8
Hz, 2 H), 5.85–5.70 (m, 3 H), 5.12–5.03 (m, 2 H), 4.87 (s, 1
H), 4.83 (s, 1 H), 4.47 and 4.38 (ABq, J = 11.5 Hz, 2 H),
3.95–3.85 (m, 1 H), 3.80 (s, 3 H), 3.74–3.66 (m, 1 H), 3.42–
3.35 (m, 1 H), 3.09 (s, 1 H), 2.45 (br s, 1 H), 2.35–2.14 (m,
5 H), 2.07–1.93 (m, 3 H), 1.90 (dd, J = 12.5, 12.5 Hz, 1 H),
1.75–1.60 (m, 2 H), 1.45–1.32 (m, 2 H), 1.29 (s, 3 H), 1.09
(d, J = 7.0 Hz, 3 H), 0.90 (d, J = 6.5 Hz, 3 H), 0.88 (d, J = 7.0
Hz, 3 H). 13C NMR (125 MHz, CDCl3): d = 159.3, 141.6,
134.4, 133.8, 129.5 (2×), 129.3, 117.1, 113.9, 113.9 (2×),
111.2, 99.2, 80.0, 77.1, 70.7, 70.6, 70.0, 55.3, 40.2, 39.4,
37.9, 36.0, 36.0, 35.0, 32.7, 21.1, 20.1, 14.8, 14.6. HRMS
Characterization Data for Ketone 22a
Colorless oil. [a]D20 +16.4 (c 1.13, CHCl3). IR (film): 2956,
1722, 1514, 1465, 1251, 1083 cm–1. 1H NMR (400 MHz,
CDCl3): d = 7.24 (d, J = 8.8 Hz, 2 H), 6.86 (d, J = 8.8 Hz, 2
H), 5.87–5.68 (m, 2 H), 5.44 (d, J = 15.2 Hz, 1 H), 5.07–4.99
+
(+TOF EI): m/z [M+] calcd for C30H46O6 : 502.3294; found:
502.3316.
Synlett 2010, No. 14, 2184–2188 © Thieme Stuttgart · New York