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purified by flash chromatography (99.5:0.5:1 CH2Cl2−acetone−Et3N)
to provide imidate 14 (249 mg, 0.521 mmol, 90%) as a pale yellow oil:
1H NMR (500 MHz, DMSO) δ 9.57 (br s, 1H), 9.25 (br s, 1H), 7.57
(d, J = 8.2, 2H), 7.35 (d, J = 8.2, 2H), 7.10 (td, J = 8.1, 1.3, 1H), 6.92
(d, J = 7.8, 1H), 6.79 (d, J = 8.1, 1H), 6.70 (t, J = 7.7, 1H), 5.78−5.68
(m, 2H), 4.62 (d, J = 4.5, 2H), 4.19 (d, J = 4.0, 2H), 2.38 (s, 3H); 13C
NMR (125 MHz, DMSO) δ 159.7 (C), 154.9 (C), 142.8 (C), 137.2
(C), 132.0 (CH), 129.6 (CH), 129.4 (CH), 129.3 (CH), 127.3 (CH),
126.6 (CH), 124.8 (C), 118.7 (CH), 116.5 (CH), 90.7 (C), 67.6
(CH2), 50.6 (CH2), 21.0 (CH3); IR (thin film) 3436, 3336, 2924,
49 (319 mg, 1.14 mmol, 80%) as a pale yellow oil: H NMR (500
MHz, CDCl3) δ 7.42 (dd, J = 7.7, 1.6, 1H), 7.28−7.23 (m, 1H), 6.98
(dd, J = 8.1, 1.1, 1H), 6.88−6.84 (m, 1H), 6.68 (s, 1H), 5.73 (dt, J =
15.2, 7.5, 1H), 5.41 (dt, J = 15.2, 5.5, 1H), 4.56 (t, J = 2.9, 1H), 4.11
(dd, J = 12.9, 4.8, 1H), 3.89 (dd, J = 13.0, 6.3, 1H), 3.83 (td, J = 11.0,
3.0, 1H), 3.52−3.46 (m, 1H), 3.32 (d, J = 7.5, 2H), 1.85−1.79 (m,
1H), 1.73−1.68 (m, 1H), 1.62−1.51 (m, 4H); 13C NMR (125 MHz,
CDCl3) δ 157.3 (C), 136.7 (CH), 136.4 (C), 131.5 (CH), 130.7
(CH), 127.6 (CH), 120.8 (CH), 114.9 (CH), 97.8 (CH), 66.7 (CH2),
62.2 (CH2), 38.8 (CH2), 30.7 (CH2), 25.6 (CH2), 19.5 (CH2); IR
(thin film) 3404, 2940, 1470, 1119, 966 cm−1; HRMS (ESI) m/z calcd
for C15H20O3SNa, (M + Na)+ 303.1031, found 303.1029.
1664, 1344, 1090 cm−1
; HRMS (ESI) m/z calcd for
C19H19Cl3N2O4SNa, (M + Na)+ 499.0029, found 499.0024.
(E)-2-(4-Hydroxybut-2-enylthio)phenol (51). In a 25-mL
round-bottomed flask, protected alcohol 49 (319 mg, 1.14 mmol)
and p-TsOH·H2O (43 mg, 0.23 mmol) were dissolved in MeOH (9.5
mL), and the solution was refluxed for 6 h and then allowed to cool to
room temperature. After 18 h, the solvent was removed in vacuo, and
the residue was purified by flash chromatography to yield alcohol 51
(E)-tert-Butyldimethyl(3-methyl-4-(2-triisopropylsilyloxy)-
phenoxy)but-2-enyloxy)silane (54). In a 200-mL round-bottomed
flask, PPh3 (1.34 g, 5.11 mmol) was added to a mixture of 2-
((triisopropylsilyl)oxy)phenol (52) (1.30 g, 4.87 mmol), (E)-4-((tert-
butyldimethylsilyl)oxy)-2-methylbut-2-en-1-ol (53)39 (1.12 mg, 5.17
mmol), and diethyl azodicarboxylate (40% in toluene, 2.3 mL, 5.2
mmol) in THF (54 mL) at 0 °C. The reaction mixture was allowed to
warm to room temperature. After 3 h, the reaction mixture was
concentrated in vacuo to give a residue that was purified by flash
chromatography (99.5:0.5 to 98.5:1.5 pentane−Et2O) to provide ether
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(142 mg, 0.723 mmol, 64%) as a clear colorless oil. H NMR data
were consistent with those previously reported.40
(E)-4-(2-Hydroxyphenylthio)but-2-enyl 2′,2′,2′-trichloroace-
timidate (16). Following the procedure described for the preparation
of (E)-11a, alcohol 51 (132 mg, 0.673 mmol) was treated with DBU
and Cl3CCN. After 5 min, the reaction mixture was concentrated in
vacuo, and the residue was purified by flash chromatography
(98.5:0.5:1 CH2Cl2−acetone−Et3N) to provide imidate 16 (191 mg,
0.563 mmol, 84%) as a pale yellow oil: 1H NMR (500 MHz, CDCl3) δ
8.30 (br s, 1H), 7.42 (dd, J = 7.7, 1.4, 1H), 7.29−7.25 (m, 1H), 6.99
(d, J = 8.2, 1H), 6.86 (t, J = 7.6, 1H), 6.66 (s, 1H), 5.87 (dt, J = 15.3,
7.5, 1H), 5.48 (dt, J = 15.3, 5.8, 1H), 4.69 (d, J = 5.8, 2H), 3.33 (d, J =
7.5, 2H); 13C NMR (125 MHz, CDCl3) δ 162.4 (C), 157.3 (C), 136.7
(CH), 131.5 (CH), 129.8 (CH), 127.0 (CH), 120.7 (CH), 117.7 (C),
114.9 (CH), 91.4 (C), 68.6 (CH2), 38.4 (CH2); IR (thin film) 3408,
3337, 2916, 1662, 1470, 984 cm−1; HRMS (GC−MS) m/z calcd for
C12H16Cl3N2O2S, (M + NH4)+ 356.9998, found 357.0004.
(E)-5-(2-Hydroxyphenyl)pent-2-enyl acetate ((E)-19a). In a
25-mL round-bottomed flask, alcohol (E)-36 (700 mg, 3.93 mmol) in
THF (5.9 mL) was cooled to 0 °C, and then acetic anhydride (1.1 mL,
12 mmol) was added via syringe. BF3·OEt2 (0.12 mL, 0.98 mmol) was
added via syringe, and the solution was maintained at 0 °C. After 1.5 h,
cold aqueous NaHCO3 (5% solution, 10 mL) was added, the mixture
was stirred for 2 min, extracted with CH2Cl2 (3 × 10 mL), dried over
Na2SO4, filtered, and concentrated in vacuo to yield a residue that was
purified by flash chromatography (80:20 hexanes−Et2O) to give
acetate (E)-19a (691 mg, 3.14 mmol, 80%) as a clear colorless oil: 1H
NMR (500 MHz, CDCl3) δ 7.12−7.08 (m, 2H), 6.87 (t, J = 7.4, 1H),
6.76 (d, J = 7.9, 1H), 5.86 (dt, J = 15.4, 7.7, 1H), 5.61 (dt, J = 15.4, 6.6,
1H), 5.16 (br s, 1H), 4.53 (d, J = 6.5, 2H), 2.72 (t, J = 7.4, 2H), 2.41−
2.37 (m, 2H), 2.08 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 171.4
(C), 153.7 (C), 135.9 (CH), 130.4 (CH), 127.8 (C), 127.4 (CH),
124.4 (CH), 120.9 (CH), 115.5 (CH), 65.4 (CH2), 32.5 (CH2), 30.0
(CH2), 21.2 (CH3); IR (thin film) 3411, 2925, 1739, 1672, 1235, 965
cm−1; HRMS (ESI) m/z calcd for C13H16O3Na, (M + Na)+ 243.0997,
found 243.0992.
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54 (1.61 g, 3.17 mmol, 65%) as a clear colorless oil: H NMR (500
MHz, CDCl3) δ 6.90−6.86 (m, 3H), 6.83−6.81 (m, 1H), 5.72 (m,
1H), 4.41 (s, 2H), 4.28 (d, J = 6.2, 2H), 1.77 (s, 3H), 1.32−1.26 (m,
3H), 1.13 (d, J = 6.1, 18H), 0.93 (s, 9H), 0.09 (s, 6H); 13C NMR (125
MHz, CDCl3) δ 150.3 (C), 145.9 (C), 132.6 (C), 128.3 (CH), 121.4
(CH), 121.1 (CH), 120.5 (CH), 114.2 (CH), 74.3 (CH2), 60.1
(CH2), 26.1 (CH3), 18.1 (C, CH3), 14.3 (CH3), 13.0 (CH), −5.0
(CH3); IR (thin film) 3064, 2947, 1267, 1116, 1073, 921 cm−1; HRMS
(ESI) m/z calcd for C26H48O3Si2Na, (M + Na)+ 487.3040, found
487.3038.
(E)-2-(4-Hydroxy-2-methylbut-2-enyloxy)phenol (55). A 50-
mL round-bottomed flask was charged with bis-silyl ether 54 (1.61 g,
3.17 mmol) and THF (16 mL), and then TBAF (1.0 M in THF, 7.0
mL, 7.0 mmol) was added. The reaction mixture was stirred at room
temperature for 3 h, and then the reaction mixture was concentrated in
vacuo and the residue was purified by flash chromatography (94:6
CH2Cl2−acetone) to provide diol 55 (616 mg, 3.17 mmol, 100%) as a
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clear colorless oil: H NMR (500 MHz, CDCl3) δ 6.95 (d, J = 7.7,
1H), 6.94−6.80 (m, 3H), 6.23 (br s, 1H), 5.77 (t, J = 6.6, 1H), 4.44 (s,
2H), 4.23 (d, J = 6.9, 2H), 2.60 (br s, 1H), 1.76 (s, 3H); 13C NMR
(125 MHz, CDCl3) δ 145.9 (C), 145.8 (C), 133.8 (C), 127.2 (CH),
121.8 (CH), 120.1 (CH), 115.1 (CH), 112.5 (CH), 73.8 (CH2), 58.8
(CH2), 14.0 (CH3); IR (thin film) 3418, 2924, 1679, 1596, 845 cm−1;
HRMS (ESI) m/z calcd for C11H14O3Na, (M + Na)+ 217.0841, found
217.0841.
(E)-4-(2-Hydroxyphenoxy)-3-methylbut-2-enyl 2′,2′,2′-tri-
chloroacetimidate (15). Following the procedure described for the
preparation of (E)-11a, alcohol 55 (26 mg, 0.13 mmol) was treated
with DBU and Cl3CCN. After 5 min, the reaction mixture was
concentrated in vacuo, and the residue was purified by flash
chromatography (97.5:1.5:1 CH2Cl2−acetone−Et3N) to provide
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imidate 15 (41 mg, 0.12 mmol, 91%) as a pale yellow oil: H NMR
(500 MHz, CDCl3) δ 8.33 (br s, 1H), 6.95 (dd, J = 7.8, 1.5, 1H),
6.91−6.80 (m, 3H), 5.88−5.85 (m, 1H), 5.64 (s, 1H), 4.91 (d, J = 6.7,
2H), 4.54 (s, 2H), 1.88 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 162.6
(C), 145.9 (C), 145.6 (C), 137.3 (C), 121.9 (CH), 121.4 (CH),
120.11 (CH), 115.0 (CH), 112.4 (CH), 91.4 (C), 73.6 (CH2), 65.4
(CH2), 14.3 (CH3); IR (thin film) 3414, 3337, 2923, 1662, 1501, 988
cm−1; HRMS (ESI) m/z calcd for C13H14Cl3NO3Na, (M + Na)+
359.9937, found 359.9928.
(E)-2-(4-(Tetrahydro-2H-pyran-2-yloxy)but-2-enylthio)-
phenol (49). Following the procedure described for the preparation
of 48, 2-mercaptophenol (46) (902 mg, 7.15 mmol) was alkylated
using (E)-2-((4-bromobut-2-en-1-yl)oxy)tetrahydro-2H-pyran (47).38
After 24 h, water (20 mL) and brine (10 mL) were added, and the
mixture was extracted with CH2Cl2 (3 × 20 mL), dried over Na2SO4,
filtered, and concentrated in vacuo to yield a residue that was purified
by flash chromatography (70:30 hexanes−Et2O) to provide thioether
(Z)-5-(2-Hydroxyphenyl)pent-2-enyl acetate ((Z)-19a). Fol-
lowing the procedure described for the preparation of (E)-19a, alcohol
(Z)-36 (100 mg, 0.561 mmol) was acetylated using acetic anhydride
(0.16 mL, 1.7 mmol) to give a residue that was purified by flash
chromatography (80:20 hexanes−Et2O) to provide acetate (Z)-19a
(93 mg, 0.42 mmol, 75%) as a clear colorless oil: 1H NMR (500 MHz,
CDCl3) δ 7.11−7.08 (m, 2H), 6.88 (t, J = 7.4, 1H), 6.80 (d, J = 7.7,
1H), 5.78−5.68 (br m, 2H), 5.58−5.53 (m, 1H), 4.59 (d, J = 7.2, 2H),
2.69 (t, J = 7.4, 2H), 2.45 (app q, J = 8.0, 2H), 2.07 (s, 3H); 13C NMR
(125 MHz, CDCl3) δ 171.6 (C), 154.0 (C), 134.8 (CH), 130.5 (CH),
127.6 (CH), 127.4 (C), 123.9 (CH), 120.7 (CH), 115.7 (CH), 60.5
(CH2), 30.4 (CH2), 28.1 (CH2), 21.2 (CH3); IR (thin film) 3306,
3026, 2929, 1731, 1609, 754 cm−1; HRMS (ESI) m/z calcd for
C13H16O3Na, (M + Na)+ 243.0997, found 243.0997.
(E)-5-(5-Bromo-2-hydroxyphenyl)pent-2-enyl acetate ((E)-
19b). Following the procedure described for the preparation of (E)-
1969
dx.doi.org/10.1021/jo202553a | J. Org. Chem. 2012, 77, 1961−1973