M. Takahashi et al. / Tetrahedron 68 (2012) 7997e8002
8001
nmax 3434 (OeH), 3019 (CeH), 2926 (CeH), 2871 (CeH), 1782 (C]
O), 758 (C]C) cmꢁ1 1H NMR (300 MHz, CDCl3):
7.36e7.23 (m,
(CH3), ꢁ4.00 (CH3). Anal. Calcd for C21H36O4Si2: C, 61.72; H, 8.88.
;
d
Found: C, 62.11; H, 9.05.
10H, ArH), 4.68 (d, J¼11.4 Hz, 1H, CH2), 4.62 (dd, J¼3.6, 6.0 Hz, 1H,
CH), 4.54 (d, J¼11.4 Hz, 1H, CH2), 4.51 (s, 2H, CH2), 4.44 (q, J¼6.0 Hz,
1H, CH), 4.44 (br s, 1H, OH), 4.11 (br s, 1H, OH), 4.04 (dd, J¼3.6,
5.1 Hz, 1H, CH), 3.89 (d, J¼6.0 Hz, 1H, CH), 3.75 (dd, J¼5.1, 10.5 Hz,
1H, CH2), 3.68 (dd, J¼5.1, 10.5 Hz, 1H, CH2); 13C NMR (75 MHz,
4.2.5. Synthesis and characterization of 6. To a solution containing 4
(355 mg, 0.873 mmol) and 5 (392 mg, 0.960 mmol) in anhydrous
CH2Cl2 (8.80 mL) were successively added 1-ethyl-3-(3-
dimethylaminopropyl)carbodiimide hydrochloride (EDCI, 201 mg,
1.05 mmol) and N,N-dimethyl-4-aminopyridine (DMAP, 138 mg,
1.13 mmol) at 0 ꢀC. The reaction mixture was stirred for 4 h,
quenched by addition of water (15 mL), extracted with AcOEt
(40 mL), washed with brine (20 mL), dried over Na2SO4, filtered, and
concentrated in vacuo to provide a crude residue. Purification of the
residue by column chromatography on silica gel (eluent: hexane/
AcOEt, 20:1) gave 6 (391 mg, 0.490 mmol, 56%) as colorless oil:
CDCl3): d 175.5 (C]O), 137.6 (C), 137.4 (C), 128.83 (CH), 128.76 (CH),
128.42 (CH), 128.39 (CH), 128.2 (CH), 128.0 (CH), 79.4 (CH), 78.1
(CH), 74.7 (CH), 73.8 (CH), 73.7 (CH2), 73.6 (CH2), 69.0 (CH2). Anal.
Calcd for C20H22O6: C, 67.03; H, 6.19. Found: C, 67.11; H, 6.25.
4.2.3. Synthesis and characterization of 4. To a solution of
3
(406 mg, 1.13 mmol) in DMF (0.380 mL) were added tert-butyldi-
methylsilyl chloride (TBSCl, 1.70 g, 11.3 mmol) and imidazole
(846 mg, 12.4 mmol) at room temperature. The reaction mixture
was stirred for 17 h, quenched by addition of water (10 mL),
extracted with AcOEt (40 mL), washed with brine (40 mL), dried
over Na2SO4, filtered, and concentrated in vacuo to provide a crude
TBS ether. To a solution of the TBS ether (1.26 g) in ethanol
(2.30 mL) was added palladium hydroxide on carbon (Pd(OH)2/C,
94.5 mg), and the resulting mixture was hydrogenated at room
temperature. After 1 h, the reaction mixture was filtrated through
a pad of Celite followed by successive washings with AcOEt
(100 mL). The filtrate was concentrated in vacuo and the residue
was purified by column chromatography on silica gel (eluent:
hexane/AcOEt, 5:1) to give 4 (355 mg, 0.873 mmol, 77% for two
Rf¼0.51 (silica gel, hexane/AcOEt¼4:1); [
a
]
23 þ31.0 (c 0.875, CHCl3);
D
IR (NaCl): nmax 3465 (OeH), 3020 (CeH), 2956 (CeH), 2931 (CeH),
2897 (CeH), 2886 (CeH), 2859 (CeH), 1789 (C]O), 1705 (C]O)
cmꢁ1; 1H NMR (300 MHz, CDCl3):
d
7.63 (d, J¼15.9 Hz, 1H, CH]CH),
7.03 (dd, J¼2.1, 8.7 Hz, 1H, ArH), 7.03 (d, J¼2.1 Hz, 1H, ArH), 6.83 (d,
J¼8.7 Hz, 1H, ArH), 6.29 (d, J¼15.9 Hz, 1H, CH]CH), 4.62 (dd, J¼2.4,
12.0 Hz, 1H, CH2), 4.54 (dd, J¼3.9, 8.4 Hz, 1H, CH), 4.37 (dd, J¼5.7,
12.0 Hz, 1H, CH2), 4.32 (dd, J¼2.4, 3.9 Hz, 1H, CH), 4.21 (dddd, J¼2.4,
5.1, 5.7, 8.4 Hz, 1H, CHOH), 4.10 (d, J¼2.4 Hz, 1H, CH), 2.97 (d,
J¼5.1 Hz,1H, OH),1.00 (s, 9H, CH3), 0.99 (s, 9H, CH3), 0.91 (s, 9H, CH3),
0.91 (s, 9H, CH3), 0.23 (s, 6H, CH3), 0.22 (s, 6H, CH3), 0.17 (s, 6H, CH3),
0.16 (s, 3H, CH3), 0.15 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3):
d 174.1
(C]O), 168.6 (C]O), 150.1 (C), 147.6 (C), 146.4 (C), 128.0 (CH), 122.8
(CH), 121.4 (CH), 120.8 (CH), 114.9 (CH), 80.5 (CH), 75.1 (CH), 74.9
(CH), 67.8 (CH), 66.6 (CH2), 26.02 (CH3), 25.99 (CH3), 25.77 (CH3),
25.72 (CH3), 18.61 (C), 18.56 (C), 18.21 (C), 18.09 (C), ꢁ3.97 (CH3),
ꢁ4.01 (CH3), ꢁ4.65 (CH3), ꢁ4.94 (CH3), ꢁ4.96 (CH3). Anal. Calcd for
C39H72O9Si4: C, 58.75; H, 9.10. Found: C, 58.48; H, 9.41.
steps) as a white solid: Rf¼0.17 (silica gel, hexane/AcOEt¼4:1); mp
20
71e72 ꢀC; [
a]
þ34.6 (c 1.31, CHCl3); IR (KBr): nmax 3494 (OeH),
D
3397 (OeH), 2953 (CeH), 2930 (CeH), 2887 (CeH), 2858 (CeH),
1786 (C]O) cmꢁ1 1H NMR (300 MHz, CDCl3):
;
d
4.52 (dd, J¼4.2,
8.4 Hz, 1H, CH), 4.31 (dd, J¼3.0, 4.2 Hz, 1H, CH), 4.10 (d, J¼3.0 Hz,
1H, CH), 4.01 (dddd, J¼3.6, 4.5, 5.4, 8.4 Hz, 1H, CHOH), 3.90 (dt,
J¼3.6, 11.1 Hz, 1H, CH2), 3.79 (dt, J¼4.5, 11.1 Hz, 1H, CH2), 2.78 (d,
J¼5.4 Hz, 1H, OH), 2.18 (dd, J¼3.6, 4.5 Hz, 1H, OH), 0.91 (s, 18H,
CH3), 0.17 (s, 6H, CH3), 0.16 (s, 3H, CH3), 0.15 (s, 3H, CH3); 13C NMR
4.2.6. Synthesis and characterization of (5R)-7. To a solution of 6
(383 mg, 0.480 mmol) in anhydrous CH3CN (2.40 mL) was added
boron trifluoride ethyl ether complex (BF3$OEt2, 300 mg,
2.11 mmol) at 0 ꢀC. After stirring for 20 min at this temperature, the
reaction mixture was quenched by addition of water (0.5 mL) and
powders of NaHCO3 (1 g), dried over Na2SO4, filtered through cot-
ton followed by successive washings with AcOEt (100 mL), and
concentrated in vacuo to provide a crude residue. Purification of the
residue by column chromatography on silica gel (eluent: hexane/
AcOEt, 1:3) gave (5R)-7 (81.0 mg, 0.238 mmol, 50%) as pale yellow
(75 MHz, CDCl3):
d 174.4 (C]O), 80.5 (CH), 75.0 (CH), 74.9 (CH),
68.6 (CH), 63.9 (CH2), 25.71 (CH3), 25.67 (CH3), 18.1 (C), 18.0 (C),
ꢁ4.69 (CH3), ꢁ4.71 (CH3), ꢁ5.0 (CH3). Anal. Calcd for C18H38O6Si2:
C, 53.16; H, 9.42. Found: C, 52.93; H, 9.29.
4.2.4. Synthesis and characterization of 5. To a solution of caffeic
acid (585 mg, 3.25 mmol) in DMF (1.10 mL) were added tert-
butyldimethylsilyl chloride (TBSCl, 1.62 g, 10.7 mmol) and imidaz-
ole (1.46 g, 21.5 mmol) at room temperature. The reaction mixture
was stirred for 6 h, quenched by addition of water (10 mL),
extracted with AcOEt (40 mL), washed with brine (40 mL), dried
over Na2SO4, filtered, and concentrated in vacuo to provide a crude
mixture. To a solution of this mixture in 50% v/v aqueous methanol
(11.0 mL) was added potassium carbonate (K2CO3, 449 mg,
3.25 mmol) at room temperature. The reaction mixture was stirred
for 1 h, quenched by addition of 3% w/w HClaq (35 mL), extracted
with AcOEt (40 mL), washed with brine (40 mL), dried over Na2SO4,
filtered, and concentrated in vacuo to provide a crude residue.
Purification of the residue by column chromatography on silica gel
(eluent: hexane/AcOEt, 4:1) gave 5 (948 mg, 2.32 mmol, 71% for
two steps) as a white solid: Rf¼0.43 (silica gel, hexane/AcOEt¼2:1);
mp 158e159 ꢀC; IR (KBr): nmax 3422 (OeH), 2962 (CeH), 2930
(CeH), 2859 (CeH), 1685 (C]O), 1629 (C]C), 1508 (C]C) cmꢁ1; 1H
oil: Rf¼0.42 (silica gel, AcOEt); [
a
]
25 þ49.8 (c 1.80, MeOH); IR (KBr):
D
nmax 3359 (OeH), 2964 (CeH), 1698 (C]O), 1632 (C]C), 1601 (C]
C), 1523 (C]C) cmꢁ1 1H NMR (300 MHz, acetone-d6):
; d 7.59 (d,
J¼15.9 Hz, 1H, CH]CH), 7.17 (d, J¼2.1 Hz, 1H, ArH), 7.05 (dd, J¼2.1,
8.4 Hz, 1H, ArH), 6.87 (d, J¼8.4 Hz, 1H, ArH), 6.31 (d, J¼15.9 Hz, 1H,
CH]CH), 4.64 (dd, J¼5.4, 6.6 Hz, 1H, CH), 4.52 (dd, J¼4.5, 5.4 Hz,1H,
CH), 4.48 (dd, J¼2.7, 10.8 Hz, 1H, CH2), 4.38 (d, J¼4.5 Hz, 1H, CH),
4.35 (dd, J¼2.7,10.8 Hz,1H, CH2), 4.31 (dd, J¼2.7, 6.6 Hz,1H, CH); 13
C
NMR (75 MHz, acetone-d6):
d 175.3 (C]O), 167.4 (C]O), 148.8 (C),
146.3 (CH), 146.0 (CH), 127.6 (C), 122.5 (CH), 116.3 (C), 115.3 (CH),
115.2 (CH), 80.1 (CH), 74.5 (CH), 74.4 (CH), 68.9 (CH), 66.3 (CH2).
Anal. Calcd for C15H16O9: C, 52.94; H, 4.74. Found: C, 53.18; H, 5.07.
4.2.7. Synthesis and characterization of 1a0 and all the related
compounds. To a solution of 1a (1.77 g, 8.19 mmol) in anhydrous
CH2Cl2 (8.20 mL) were added pyridine (842 mg, 10.6 mmol) and
triflic anhydride (Tf2O, 2.77 g, 9.83 mmol) at 0 ꢀC. After stirring at
this temperature for 10 min, the reaction mixture was quenched by
addition of saturated aqueous NaHCO3 (10 mL), extracted with
CH2Cl2 (100 mL), washed with brine (40 mL), dried over Na2SO4,
filtered, and concentrated in vacuo to provide a crude triflate
(7.46 g). To a solution of the crude triflate (7.46 g) in DMF (8.20 mL)
were added 18-crown-6 (216 mg, 0.819 mmol) and potassium
NMR (300 MHz, CDCl3):
d
7.67 (d, J¼15.9 Hz, 1H, CH]CH), 7.05 (dd,
J¼2.1, 8.4 Hz, 1H, ArH), 7.05 (d, J¼2.1 Hz, 1H, ArH), 6.84 (d, J¼8.4 Hz,
1H, ArH), 6.25 (d, J¼15.9 Hz, 1H, CH]CH), 1.00 (s, 9H, CH3), 0.99 (s,
9H, CH3), 0.23 (s, 3H, CH3), 0.23 (s, 3H, CH3), 0.22 (s, 3H, CH3), 0.22
(s, 3H, CH3); 13C NMR (75 MHz, CDCl3):
d 172.2 (C]O), 150.3 (C),
147.6 (C), 147.3 (C), 128.0 (CH), 123.0 (CH), 121.5 (CH), 120.9 (CH),
114.9 (CH), 26.05 (CH3), 26.02 (CH3), 18.64 (C), 18.59 (C), ꢁ3.95