676
C. R. Reddy, G. Dharmapuri
PAPER
matography (10→20% EtOAc in hexanes) to afford 14 (4.54 g,
98%) as a colorless oil.
Ethyl (E,S)-5-(tert-Butyldimethylsilyloxy)-5-[(4S,6R)-2,2,6-tri-
methyl-1,3-dioxepan-4-yl]pent-2-enoate (17)
To a soln of alcohol 16 (1.5 g, 4.51 mmol) in CH2Cl2–DMSO (3:1
v/v, 30 mL) at 0 °C were added Et3N (3.16 mL, 22.5 mmol) and
py·SO3 (3.59 g, 22.5 mmol). After being stirred at 0 °C for 2 h, the
reaction mixture was diluted with Et2O (30 mL), washed with H2O
(20 mL) and brine (20 mL), dried (Na2SO4), filtered and concentrat-
ed under reduced pressure. The residual crude aldehyde was used in
the next step without further purification.
[α]D25 +1.2 (c 2.0, CHCl3).
IR (KBr): 3299, 2954, 2931, 2858, 1466, 1249, 1086, 835, 775
cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.69–7.57 (m, 4 H), 7.46–7.32 (m,
6 H), 3.81–3.65 (m, 3 H), 3.65–3.57 (m, 1 H), 3.55–3.38 (m, 2 H),
2.66 (br s, 1 H), 2.46 (br s, 1 H), 1.98–1.76 (m, 2 H), 1.71–1.60 (m,
1 H), 1.57–1.36 (m, 2 H), 1.06 (s, 9 H), 0.94 (d, J = 6.5 Hz, 3 H),
0.88 (s, 9 H), 0.09 (s, 3 H), 0.05 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 135.4, 133.4, 129.6, 127.6, 72.7,
70.2, 67.4, 60.3, 37.4, 36.3, 32.4, 26.7, 25.8, 19.0, 18.0, 17.0, –4.3,
–4.6.
To a soln of the crude aldehyde in benzene (10 mL) at 0 °C was add-
ed Ph3P=CHCO2Et (3.10 g, 9.03 mmol) and the reaction mixture
was allowed to warm to r.t. After being stirred at r.t. for 12 h, the
reaction mixture was concentrated under reduced pressure. Purifi-
cation by flash chromatography (2→3% EtOAc in hexanes) afford-
ed α,β-unsaturated ester 17 (1.59 g, 88%) as a colorless oil.
[α]D25 –60.2 (c 0.5, CHCl3).
IR (KBr): 2928, 2857, 1718, 1654, 1167, 1042, 774 cm–1.
HRMS (ESI): m/z [M + H]+ calcd for C30H51O4Si2: 531.3320;
found: 531.3342.
(S)-2,2,3,3,10,10-Hexamethyl-9,9-diphenyl-5-[(4S,6R)-2,2,6-tri-
methyl-1,3-dioxepan-4-yl]-4,8-dioxa-3,9-disilaundecane (15)
To a soln of diol 14 (2.2 g, 4.15 mmol) in CH2Cl2 (20 mL) at 0 °C
were added 2,2-dimethoxypropane (1.01 mL, 8.29 mmol) and CSA
(48 mg, 0.20 mmol), and the mixture was stirred at r.t. for 30 min.
Then, the reaction was quenched by adding sat. aq NH4Cl soln and
the resulting mixture was extracted with CH2Cl2 (2 × 20 mL). The
combined organic layers were washed with brine (20 mL), dried
(Na2SO4), filtered and concentrated, and the residue was purified by
column chromatography (2→5% EtOAc in hexanes) to afford ace-
tonide 15 (2.28 g, 96%) as a colorless oil.
1H NMR (300 MHz, CDCl3): δ = 7.01–6.86 (m, 1 H), 5.80 (d, J =
15.4 Hz, 1 H), 4.16 (q, J = 7.1 Hz, 2 H), 3.88–3.73 (m, 2 H), 3.71–
3.59 (m, 1 H), 3.40–3.27 (m, 1 H), 2.54–2.34 (m, 1 H), 2.28–2.10
(m, 1 H), 1.92–1.76 (m, 1 H), 1.63–1.20 (m, 11 H), 1.01 (d, J = 6.0
Hz, 3 H), 0.88 (s, 9 H), 0.06 (s, 3 H), 0.02 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 165.6, 146.8, 123.3, 100.5, 73.5,
69.7, 65.9, 59.7, 34.6, 34.0, 30.9, 26.0, 25.2, 25.0, 18.1, 17.0, 14.5,
–4.1, –4.4.
HRMS (ESI): m/z [M + Na]+ calcd for C21H40O5SiNa: 423.2537;
found: 423.2543.
[α]D25 –25.2 (c 2.0, CHCl3).
(E,S)-5-(tert-Butyldimethylsilyloxy)-5-[(4S,6R)-2,2,6-trimethyl-
1,3-dioxepan-4-yl]pent-2-en-1-ol (18)
IR (KBr): 2931, 2858, 1465, 1251, 1103, 999, 833, 703 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.68–7.60 (m, 4 H), 7.42–7.29 (m,
6 H), 3.91–3.63 (m, 5 H), 3.36–3.27 (m, 1 H), 1.93–1.72 (m, 2 H),
1.57–1.33 (m, 3 H), 1.32–1.22 (m, 6 H), 1.05 (s, 9 H), 1.03 (d, J =
6.0 Hz, 3 H), 0.85 (s, 9 H), 0.07 (s, 3 H), 0.00 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 135.5, 133.9, 129.4, 127.5, 100.3,
70.2, 69.6, 66.1, 60.9, 34.2, 33.6, 30.7, 26.8, 25.8, 25.0, 24.9, 19.2,
17.8, 16.8, –4.2, –4.8.
To a stirred soln of conjugated ester 17 (1.2 g, 3.0 mmol) in CH2Cl2
(15 mL) cooled to –78 °C was added a 20% soln of DIBAL-H in tol-
uene (4.26 mL, 6.0 mmol) dropwise. The solution was stirred at
–78 °C for 1 h, and the reaction was quenched by the addition of sat.
aq potassium sodium tartrate soln (20 mL). Then, the mixture was
warmed to r.t. and filtered through a pad of Celite®, and the residue
was washed with sat. aq NaCl. The resulting mixture was extracted
with CH2Cl2 (25 mL). The organic extract was concentrated to ob-
tain the crude product, which was purified by column chromatogra-
phy (5→10% EtOAc in hexanes) to give 18 (1.0 g, 94%) as a
colorless oil.
HRMS (ESI): m/z [M + Na]+ calcd for C33H54O4Si2Na: 593.3453;
found: 593.3480.
(S)-3-(tert-Butyldimethylsilyloxy)-3-[(4S,6R)-2,2,6-trimethyl-
1,3-dioxepan-4-yl]propan-1-ol (16)
[α]D25 –34.0 (c 1.0, CHCl3).
To a cooled (0 °C) stirred soln of 15 (2.45 g, 4.29 mmol) in MeOH
(15 mL) was added NH4F (1.5 g, 42.1 mmol), and the mixture was
stirred for 36 h. The reaction was quenched with sat. aq NaHCO3,
and the mixture was extracted with CH2Cl2 (2 × 15 mL). The com-
bined organic layers were dried (Na2SO4) and concentrated under
reduced pressure. The residue was purified by column chromatog-
raphy (5→10% EtOAc in hexanes) to provide 16 (1.32 g, 95%) as
a colorless oil; 15 (50 mg) was recovered.
IR (KBr): 3464, 2930, 2854, 1218, 1075, 970, 834, 772 cm–1.
1H NMR (300 MHz, CDCl3): δ = 5.78–5.58 (m, 2 H), 4.05 (q, J =
4.5 Hz, 2 H), 3.89–3.69 (m, 2 H), 3.63–3.52 (m, 1 H), 3.37–3.27 (m,
1 H), 2.36–2.24 (m, 1 H), 2.13–1.98 (m, 1 H), 1.90–1.75 (m, 1 H),
1.60–1.35 (m, 2 H), 1.29 (s, 6 H), 1.01 (d, J = 6.7 Hz, 3 H), 0.89 (s,
9 H), 0.06 (s, 3 H), 0.02 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 131.0, 130.4, 100.4, 74.0, 69.9,
66.0, 63.7, 34.8, 34.2, 30.7, 25.8, 25.0, 24.9, 17.9, 16.8, –4.2, –4.5.
[α]D25 –25.0 (c 1.0, CHCl3).
HRMS (ESI): m/z [M + Na]+ calcd for C19H38O4SiNa: 381.2432;
found: 381.2439.
IR (KBr): 3415, 2935, 1466, 1381, 1219, 1165, 1071, 835, 775
cm–1.
1H NMR (300 MHz, CDCl3): δ = 3.90–3.54 (m, 5 H), 3.42–3.30 (m,
1 H), 2.43 (br s, 1 H), 1.95–1.77 (m, 2 H), 1.68–1.37 (m, 3 H), 1.31
(s, 6 H), 1.03 (d, J = 6.0 Hz, 3 H), 0.90 (s, 9 H), 0.09 (s, 3 H), 0.08
(s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 100.6, 72.9, 69.8, 66.2, 60.3, 34.6,
33.7, 30.6, 25.7, 25.0, 24.6, 17.8, 16.7, –4.4, –4.9.
[(2S,3S)-3-{(S)-2-(tert-Butyldimethylsilyloxy)-2-[(4S,6R)-2,2,6-
trimethyl-1,3-dioxepan-4-yl]ethyl}oxiran-2-yl]methanol (5)
To a stirred mixture of powdered molecular sieves (4 Å, 4.0 g) and
Ti(Oi-Pr)4 (0.083 mL, 0.27 mmol) in CH2Cl2 (10 mL) cooled at
–20 °C was added (+)-DIPT (0.22 mL, 0.94 mmol). The mixture
was stirred at –20 °C for 10 min and a soln of allylic alcohol 18 (1.4
g, 3.9 mmol) in CH2Cl2 (12 mL) and 4 M t-BuOOH in toluene (3.8
mL, 15.6 mmol) were added successively. The resulting mixture
was stirred at –20 °C for 12 h, then the reaction was quenched with
H2O (0.02 mL) and 20% aq NaOH (0.015 mL). The mixture was
stirred at r.t. for 45 min, then the organic layer was separated and
the reaction mixture was filtered. The aqueous layer was extracted
with CH2Cl2 (2 × 25 mL). The organic layer and the extracts were
HRMS (ESI): m/z [M + Na]+ calcd for C17H36O4SiNa: 355.2275;
found: 355.2290.
Synthesis 2013, 45, 673–677
© Georg Thieme Verlag Stuttgart · New York