Tuning of Coupling Reaction Regioselectivity
J . Org. Chem., Vol. 67, No. 7, 2002 2293
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) 11.53 Hz, 1H, dCH), 5.75 (d, 3J (H,H) ) 11.53 Hz, 1H, d
ArH), 7.88 (d, J (H,H) ) 7.45 Hz, 1H, ArH), 7.77 (d, J (H,H)
3
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CH), 4.54-4.40 (m, 1H, CH), 4.16 (q, J (H,H) ) 7.10 Hz, 2H,
) 8.28 Hz, 1H, ArH), 7.66 (d, J (H,H) ) 7.06 Hz, 1H, ArH),
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OCH2), 1.55-1.40 (m, 4H, CH2), 1.27 (t, J (H,H) ) 7.10 Hz,
7.60-7.40 (m, 3H, ArH), 4.06 (s, 2H, CH2), 0.20 (s, 9H, Me3-
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3H, CH3), 0.92 (t, J (H,H) ) 6.94 Hz, 3H, CH3), 0.11 (s, 9H,
Si); MS (EI) m/z (%) 238 (89.56) [M]+; HRMS calcd for C16H18
-
Me3Si); 13C NMR (75.4 MHz, CDCl3) δ 165.688, 148.578,
119.092, 107.269, 85.580, 59.944, 37.226, 31.037, 19.989,
14.091, 13.629, 0.001; MS (EI) m/z (%) 253 (6.93) [M + 1]+.
Anal. Calcd for C14H24O2Si: C, 66.61; H, 9.58. Found: C, 66.65;
H, 9.37.
Si 238.1173, found 238.1162.
1-(ter t-Bu tyld im eth ylsilyl)-3-n a p h th ylp r op -1-yn e (2g).
1-(tert-Butyldimethylsilyl)prop-1-yne (231 mg, 1.5 mmol), Zn-
Br2 (398 mg, 1.77 mmol), and naphthyl iodide (128 mg, 0.5
mmol) afforded 73 mg (52%) of 2g: IR (film) 2175, 1597, 1502,
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Eth yl 6-(Tr im eth ylsilyl)-4-p r op ylh ex-5-yn -(2E)-en oa te
((E)-2c). 1-(Trimethylsilyl)hex-1-yne (134 mg, 0.87 mmol), ZnI2
(388 mg, 1.22 mmol), and ethyl 3-iodo-(2E)-propenoate (112
mg, 0.5 mmol) afforded 73 mg (58%) of (E)-2c: IR (film) 2169,
1720, 1651, 1178 cm-1; 1H NMR (300 MHz, CDCl3) δ 6.82 (dd,
1459 cm-1; H NMR (300 MHz, CDCl3) δ 8.05-7.25 (m, 7H,
ArH), 4.08 (s, 2H, CH2), 0.97 (s, 9H, TBS), 0.14 (s, 6H, TBS);
MS (EI) m/z (%) 280 (11.09) [M]+; HRMS calcd for C19H24Si
280.1641, found 280.1652.
Syn th esis of Or ga n ic Zin c Rea gen t.9 To a dry, 25 mL
three-necked flask were added activated zinc powder (1.625
g, 25 mmol), THF (3 mL), and 1,2-dibromoethane (94 mg, 0.5
mmol, 0.04 mL) under N2 and, the mixture was heated to 65
°C for 1 min. It was then cooled to rt and treated with
trimethylchloromethane (40 mg, 0.4 mmol, 0.05 mL). After 15
min at rt, a solution of organic halides (10 mmol) in THF (4
mL) was slowly added and heated to 45 °C. After the reaction
was complete, as monitored by TLC, it was reserved for further
use under an atmosphere of N2. The concentrations of the
organozinc reagents prepared were calculated on the basis of
the assumption that the yields for these oxidative addition
steps were 100%.
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3J (H,H) ) 15.56 Hz, J (H,H) ) 5.81 Hz, 1H, dCH), 6.05 (d,
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3J (H,H) ) 15.56, Hz, 1H, dCH), 4.18 (q, J (H,H) ) 6.98 Hz,
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2H, OCH2), 3.21 (q, J (H,H) ) 5.88 Hz, 1H, CH), 1.60-1.40
(m, 4H, CH2), 1.28 (t, 3J (H,H) ) 6.98 Hz, 3H, CH3), 0.91 (t, 3J
(H,H) ) 7.01 Hz, 3H, CH3), 0.15 (s, 9H, Me3Si); MS (EI) m/z
(%) 252 (1.51) [M]+. Anal. Calcd for C14H24O2Si: C, 66.61; H,
9.58. Found: C, 66.80; H, 9.59.
P d (P P h 3)4-Ca ta lyzed Cou p lin g Rea ction of Ar yl Iod id e
w ith Allen ylic/P r op a r gylic Zin c Rea gen ts F or m ed by th e
Rea ction of 1-Su bstitu ted P r op -1-yn e w ith n -Bu Li a n d
Zn Br 2: Typ ica l P r oced u r e for th e Syn th esis of 1-P h en yl-
1-(o-m eth ylp h en yl)p r op a -1,2-d ien e (6a ). To a solution of
1-phenylprop-1-yne (97 mg, 0.85 mmol) in THF (2 mL) in a
dry Schlenk tube was added n-BuLi (0.47 mL, 2.0 M in hexane,
0.94 mmol) at -78 °C under N2. After 100 min at -78 °C, dry
ZnBr2 (378 mg, 1.68 mmol) in THF (3 mL) was added. After 5
min at this temperature, the reaction mixture was warmed to
rt and stirred at rt for 20 min, and Pd(PPh3)4 (29 mg, 0.025
mmol) and o-methylphenyl iodide (109 mg, 0.5 mmol) in THF
(1 mL) were added at rt. After the reaction was complete, as
monitored by TLC (eluent: hexane), it was quenched with
water, and the mixture was extracted with diethyl ether and
washed with water. Drying over MgSO4, rotary evaporation,
and chromatography on silica gel (eluent: hexane) afforded
88 mg (85%) of 6a : IR (film) 1930, 1697, 1595, 1575, 1489,
Gen er a l P r oced u r e for Iod in olysis of 12a , 12c, a n d
12d . To a solution of organozinc reagent (1 mL, ca. 1 mmol)
in THF (1 mL) at -78 °C was added iodine (381 mg, 1.5 mmol)
in THF (4 mL). The mixture was then warmed to rt, extracted
with diethyl ether, and washed subsequently with saturated
aqueous sodium thiosulfate and saturated aqueous sodium
chloride. Drying over MgSO4, rotary evaporation, and chro-
matography on silica gel afforded the iodolysis product(s).
Hyd r olysis of 12b. To a dilute aqueous solution of hydro-
chloric acid (5 mL) was added organozinc reagent 12b (1 mL).
The mixture was extracted with diethyl ether and washed with
water. Drying over MgSO4, rotary evaporation, and chroma-
tography on silica gel afforded the hydroysis products.
Syn th esis of P r op a r gylic Ca r bon a tes: Typ ica l P r oce-
d u r e for th e Syn th esis of Meth yl 3-P h en ylp r op -2-yn yl
Ca r bon a te (11b). To a solution of 3-phenylprop-2-ynol (4.27
g, 32 mmol) and pyridine (70 mmol, 5.71 mL) in Et2O (40 mL)
at 0 °C was slowly added methyl chloroformate (64 mmol, 2.55
mL) for 5 min, and the reaction mixture was then warmed to
rt. After the reaction was complete, as monitored by TLC, it
was quenched with a dilute aqueous solution of hydrochloric
acid, extracted with diethyl ether, and washed with saturated
aqueous sodium chloride. Drying over MgSO4, rotary evapora-
tion, and recrystallization from ether afforded 5.126 g (84%)
of 11b: mp 50-51 °C (diethyl ether); IR (film) 2219, 1752,
1626, 1099 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.50-7.40 (m,
2H, PhH), 7.40-7.25 (m, 3H, PhH), 4.96 (s, 2H, CH2), 3.83 (s,
3H, OCH3); MS (EI) m/z (%) 190 (13.59) [M]+. Anal. Calcd for
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1449 cm-1; H NMR (300 MHz, CDCl3) δ 7.35-7.15 (m, 9H,
PhH), 5.20 (s, 2H, dCH2), 2.25 (s, 3H); MS (EI) m/z (%) 206
(100) [M]+; HRMS (-CH3) calcd for C15H11 191.0858, found
191.0852. Compounds 2d , 6b , 2e, 6c, 2f, and 2g were
synthesized similarly.
1-(Tr im eth ylsilyl)-3-(o-m eth ylp h en yl)p r op -1-yn e (2d ).
1-(Trimethylsilyl)prop-1-yne (190 mg, 1.7 mmol), ZnBr2 (635
mg, 2.82 mmol), and o-methylphenyl iodide (221 mg, 1 mmol)
afforded 104 mg (52%) of 2d : IR (film) 2174, 1603, 1490, 1460,
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1420 cm-1; H NMR (300 MHz, CDCl3) δ 7.55-7.40 (m, 1H),
7.25-7.10 (m, 3H), 3.58 (s, 2H), 2.30 (s, 3H), 0.20 (s, 9H); MS
(EI) m/z (%) 202 (7.21) [M]+; HRMS (-CH3) calcd for C12H15Si
187.0939, found 187.0963.
1-(Tr im eth ylsilyl)-1-p h en ylp r op a -1,2-d ien e (6b) a n d
1-(Tr im eth ylsilyl)-3-p h en ylp r op -1-yn e (2e). 1-(Trimethyl-
silyl)prop-1-yne (190 mg, 1.7 mmol), ZnBr2 (546 mg, 2.43
mmol), and phenyl iodide (203 mg, 1 mmol) afforded 44 mg
(23%) of 6b and 46 mg (24%) of 2e. 6b: IR (film) 1912, 1630,
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11H10O3: C, 69.46; H, 5.30. Found: C, 69.53; H, 5.24.
Meth yl 1-(Tr im eth ylsilyl)h ex-1-yn -3-yl Car bon ate (11d).
1-(Trimethylsilyl)hex-1-yn-3-ol (5.207 g, 30.6 mmol) afforded
3.538 g (51%) of 11d , and 1.950 g (37%) of 1-(trimethylsilyl)-
hex-1-yn-3-ol was recovered. 11d : IR (film) 2177, 1747, 1180,
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1595, 1490, 1443 cm-1; H NMR (300 MHz, CDCl3) δ 7.35-
7.15 (m, 5H, PhH), 4.69 (s, 2H, dCH2), 0.26 (s, 9H, Me3Si);
MS (EI) m/z (%) 188 (35.49) [M]+. 2e: IR (film) 2176, 1697,
1119 cm-1; H NMR (300 MHz, CDCl3) δ 5.23 (t, J (H, H) )
6.65 Hz, 1H, CH), 3.83 (s, 3H, OCH3), 1.90-1.70 (m, 2H, CH2),
1.60-1.40 (m, 2H, CH2), 0.95 (t, 3J (H,H) ) 7.40 Hz, 3H, CH3),
0.16 (s, 9H, Me3Si); MS (EI) m/z (%) 228 (0.43) [M]+. Anal.
Calcd for C11H20O3Si: C, 57.86; H, 8.83. Found: C, 58.17; H,
8.66.
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1601, 1492, 1451 cm-1; H NMR (300 MHz, CDCl3) δ 7.37-
7.20 (m, 5H, PhH), 3.66 (s, 2H, CH2), 0.20 (s, 9H, Me3Si); MS
(EI) m/z (%) 188 (16.06) [M]+.
1-(Tr im eth ylsilyl)-1-n a p h th ylp r op a -1,2-d ien e (6c) a n d
1-(Tr im eth ylsilyl)-3-n a p h th ylp r op -1-yn e (2f). 1-(Trimeth-
ylsilyl)prop-1-yne (93 mg, 0.85 mmol), ZnBr2 (390 mg, 1.73
mmol), and naphthyl iodide (122 mg, 0.48 mmol) afforded 19
mg (17%) of 6c and 47 mg (41%) of 2f. 6c: IR (film) 1919, 1625,
Meth yl 1-P h en ylh ex-1-yn -3-yl Ca r bon a te (11f). 1-Phen-
ylhex-1-yn-3-ol (6.179 g, 35.5 mmol) afforded 6.08 g (74%) of
11f, and 1.503 g (24%) of 1-phenylhex-1-yn-3-ol was recovered.
1459 cm-1 ; H NMR (300 MHz, CDCl3) δ 8.10-8.00 (m, 1H,
11f: IR (film) 2236, 1747, 1597, 1489, 1441, 1181, 1115 cm-1
;
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ArH), 7.90-7.80 (m, 1H, ArH), 7.70 (d, 3J (H,H) ) 8.13 Hz,
1H, ArH), 7.55-7.40 (m, 3H, ArH), 7.21 (d, 3J (H,H) ) 7.02
Hz, 1H, ArH), 4.53 (s, 2H, dCH2), 0.15 (s, 9H, Me3Si); MS (EI)
m/z (%) 238 (19.05) [M]+; HRMS calcd for C16H18Si 238.1173,
found 238.1158. 2f: IR (film) 2176, 1597, 1509, 1414 cm-1; 1H
NMR (300 MHz, CDCl3) δ 8.14 (d, 3J (H,H) ) 9.00 Hz, 1H,
1H NMR (300 MHz, CDCl3) δ 7.50-7.40 (m, 2H, PhH), 7.37-
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7.21 (m, 3H, PhH), 5.45 (t, J (H, H) ) 6.68 Hz, 1H, CH), 3.82
(s, 3H, OCH3), 1.95-1.80 (m, 2H, CH2), 1.65-1.50 (m, 2H,
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CH2), 0.98 (t, J (H, H) ) 7.24 Hz, 3H, CH3); MS (EI) m/z (%)
232 (6.52) [M]+; HRMS calcd for C14H16O3 232.1095, found
232.1147.