1,4-Addition of Organoindiums onto R,â-Enones
A R T I C L E S
concentrated under reduced pressure. The residue was purified by silica
gel, which was treated with 5% Et3N in hexane, column chromatography
using n-hexane to give 1-(tert-butyldimethylsiloxy)-3-(prop-2-ynyl)-
cyclohexene (215 mg, 86%). 1H NMR (400 MHz, CDCl3): δ 4.83 (br
s, 1H), 2.40-2.30 (m, 1H), 2.12 (dd, J ) 7.2, 2.7 Hz, 2H), 2.01-1.90
(m, 2H), 1.93 (t, J ) 2.7 Hz, 1H), 1.80-1.60 (m, 2H), 1.68-1.43 (m,
1H), 1.29-1.16 (m, 1H), 0.90 (s, 9H), 0.11 (s, 6H). 13C NMR (100
MHz, CDCl3): δ 151.8, 107.8, 83.4, 68.9, 34.3, 29.8, 28.3, 25.8, 25.7,
21.4, 18.0, -4.3, -4.5. IR (film): 3313, 2929, 2858, 2118, 1666, 1200
cm-1. HRMS (EI): calcd for C15H26OSi M+ 250.1753, found 250.1759.
generally accessible to R,â-enones by conjugate addition of
copper reagent to R,â-enones followed by enolate trapping, few
reports for the Michael addition reaction of allyl, propargyl,
and allenyl reagents to R,â-enones have been published.5,6 Thus,
the present method would find an abundant use as a synthetic
method, for example, for cyclopentene annulation. Also, because
sulfonium salts have been utilized mainly in the generation of
sulfur ylides21 and have seldom been used as leaving groups,22
the present method enhances the synthetic utility of 3-tert-
butyldimethylsilyloxylalk-2-enylsulfonium salts.
Typical Experimental Procedure of â-Allenylation onto r,â-
Enones. Dimethyl sulfide (75.0 mg, 1.2 mmol) and TBSOTf (278 mg,
1.05 mmol) were added successively to a stirred solution of 2-cyclo-
hexen-1-one (96.0 mg, 1.0 mmol) in THF (1.5 mL) at -78 °C under
a nitrogen atmosphere. After 10 min, allenylindium reagent, which is
generated from 1-bromo-2-butyne (199.0 mg, 1.5 mmol), indium (115
mg, 1.0 mmol), and lithium iodide (134 mg, 1.0 mmol) in THF (1.5
mL), was added, and the mixture was stirred at -78 °C for 30 min.
The reaction mixture was quenched with NaHCO3 (saturated aqueous).
The aqueous layer was extracted with ether (3 × 20 mL), and combined
organics were washed with water and brine (20 mL), dried with MgSO4,
filtered, and concentrated under reduced pressure. The residue was
purified by silica gel, which was treated with 5% Et3N in hexane,
column chromatography using n-hexane to give 1-(tert-butyldimeth-
ylsiloxy)-3-(1-methyl-1,2-propadienyl)cyclohexene (169 mg, 64%). 1H
NMR (400 MHz, CDCl3): δ 4.97 (bs, 1H), 4.76-4.70 (m, 2H), 2.87-
2.84 (m, 1H), 2.12-1.85 (m, 4H), 1.81 (t, J ) 3.11 Hz, 3H), 1.71-
1.67 (m, 2H), 1.04 (s, 9H), 0.14 (s, 6H). 13C NMR (100 MHz, CDCl3):
δ 206.32, 151.35, 107.09, 102.62, 74.69, 38.79, 29.84, 27.37, 25.87,
21.59, 18.02, 16.86, -4.21, -4.57. IR (film): 2929, 2242, 1446, 1383,
1350 cm-1. HRMS (EI): calcd for C16H28OSi M+ 262.4784, found
262.4781.
Experimental Section
General. Reactions were carried out in oven-dried glassware under
a nitrogen atmosphere. All commercial reagents were used without
purification, and all solvents were reaction grade. THF was freshly
distilled from sodium/benzophenone under nitrogen. All reaction
mixtures were stirred magnetically and were monitored by thin-layer
chromatography using Merck silica gel 60 F254 precoated glass plates,
which were visualized with UV light and then developed by using Fluka
silica gel 60 (0.040-0.063 mm, 230-400 mesh). H NMR and 13C
1
NMR spectra were recorded on a Brucker DPX FT(400 MHz)
spectrometer. Deuterated chloroform was used as the slovent, and
chemical shift values (δ) are reported in parts per million relative to
the residual signals of this solvent (δ 7.24 for H and δ 77.0 for 13C).
1
High-resolution mass spectra were recorded on a VG Autospec Ulpima.
Infrared spectra were recorded on a JASCO FT/IR-460 plus FT-IR
spectrometer as either a thin film pressed between two sodium chloride
plates or a solid suspended in a potassium bromide disk.
Typical Experimental Procedure of â-Allylation onto r,â-Enones.
Dimethyl sulfide (75.0 mg, 1.2 mmol) and TBSOTf (278 mg, 1.05
mmol) were added successively to a stirred solution of 2-cyclohexen-
1-one (96.0 mg, 1.0 mmol) in THF (1.5 mL) at -78 °C under a nitrogen
atmosphere. After 10 min, allylindium reagent, which is generated from
allyl bromide (218 mg, 1.5 mmol) and indium (115 mg, 1.0 mmol) in
THF (1.5 mL), was added, and the mixture was stirred at -78 °C for
30 min. The reaction mixture was quenched with NaHCO3 (saturated
aqueous). The aqueous layer was extracted with ether (3 × 20 mL),
and combined organics were washed with water and brine (20 mL),
dried with MgSO4, filtered, and concentrated under reduced pressure.
The residue was purified by silica gel column chromatography using
n-hexane to give 1-(tert-butyldimethylsiloxy)-3-(prop-2-enyl)cyclohex-
(Z)-1-(tert-Butyldimethylsilyloxy)-4-methyl-1,3-diphenylhex-1-en-
1
5-yne (35). H NMR (400 MHz, CDCl3) major isomer: δ 7.64-7.44
(m, 10H), 5.63 (d, J ) 10.10 Hz, 1H), 4.06 (dd, J ) 10.10, 7.13 Hz,
1H), 3.03-2.99 (m, 1H), 2.21 (d, J ) 6.49, 1H), 1.39 (d, J ) 7.02 Hz,
3H), 1.19 (s, 9H), 0.07 (s, 6H). Minor isomer: δ 7.64-7.44 (m, 10H),
5.72 (d, J ) 10.10 Hz, 1H), 4.14 (dd, J ) 10.10, 7.13 Hz, 1H), 3.08-
3.06 (m, 1H), 2.28 (d, J ) 6.49, 1H), 1.42 (d, J ) 7.02 Hz, 3H), 1.16
(s, 9H), 0.08 (s, 6H). 13C NMR (100 MHz, CDCl3) major isomer: δ
150.26, 142.31, 139.64, 128.64, 128.12, 127.81, 127.69, 126.58, 126.36,
112.66, 87.33, 70.16, 46.45, 32.61, 25.91, 19.21, 18.29, -4.02, -3.75.
Minor isomer: δ 151.07, 143.37, 139.81, 128.36, 128.08, 127.96,
127.69, 126.25, 110.87, 86.93, 65.86, 45.95, 33.28, 25.91, 19.71, 15.28,
-4.02, -3.75. IR (film): 3303, 3055, 2986, 1645, 1265 cm-1. HRMS
(EI): calcd for C25H32OSi M+ 376.2222, found 376.2228.
1-(tert-Butyldimethylsiloxy)-3-(prop-2-ynyl)cyclopentene (36). 1H
NMR (400 MHz, CDCl3): δ 4.66 (s, 1H), 2.85-2.81 (m, 1H), 2.30-
2.08 (m, 5H), 1.92 (t, J ) 2.68 Hz, 1H), 1.58-1.55 (m, 1H), 0.92 (s,
9H), 0.16 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 156.58, 106.28,
84.16, 68.76, 41.68, 33.59, 27.85, 26.32, 26.07, 18.55, -4.20, -4.27.
IR (film): 3303, 3053, 2931, 1686, 1264 cm-1. HRMS (EI): calcd for
C14H24OSi M+ 236.1596, found 236.1578.
1
ene (163 mg, 65%). H NMR (400 MHz, CDCl3): δ 5.78 (ddt, J )
17.38, 10.13, 7.09 Hz, 1H), 4.95 (d, J ) 17.38 Hz, 1H), 4.92 (d, J )
10.13 Hz, 1H), 4.80 (s, 1H), 2.21-2.19 (m, 1H), 2.05-1.97 (m, 4H),
1.77-1.66 (m, 2H), 1.56-1.53 (m, 1H), 1.16-1.07 (m, 1H), 0.92 (s,
9H), 0.12 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 150.90, 137.35,
115.70, 108.84, 41.38, 34.54, 29.96, 28.67, 25.73, 21.71, 18.06, -4.32,
-4.49. IR (film): 3053, 2930, 1664, 1472, 1366, 1265, 1180 cm-1
.
HRMS (EI): calcd for C15H28OSi M+ 252.1909, found 252.1905.
Typical Experimental Procedure of â-Propargylation onto r,â-
Enones. Dimethyl sulfide (75.0 mg, 1.2 mmol) and TBSOTf (278 mg,
1.05 mmol) were added successively to a stirred solution of 2-cyclo-
hexen-1-one (96.0 mg, 1.0 mmol) in THF (1.5 mL) at -78 °C under
a nitrogen atmosphere. After 10 min, propargylindium reagent, which
is generated from propargyl bromide (80% in toluene, 223.0 mg, 1.5
mmol) and indium (115 mg, 1.0 mmol) in THF (1.5 mL), was added,
and the mixture was stirred at -78 °C for 30 min. The reaction mixture
was quenched with NaHCO3 (saturated aqueous). The aqueous layer
was extracted with ether (3 × 20 mL), and combined organics were
washed with water and brine (20 mL), dried with MgSO4, filtered, and
1-(tert-Butyldimethylsiloxy)-3-(1-methylprop-2-ynyl)cyclopen-
tene (37). 1H NMR (400 MHz, CDCl3) major isomer: δ 4.71 (bs, 1H),
2.70-2.67 (m, 1H), 2.36-2.27 (m, 4H), 2.05-2.00 (m, 2H), 1.14 (d,
J ) 7.00 Hz, 3H), 0.93 (s, 9H), 0.173 (s, 3H), 0.168 (s, 3H). Minor
isomer: δ 4.63 (bs, 1H), 2.70-2.67 (m, 1H), 2.36-2.27 (m, 4H), 2.05-
2.00 (m, 2H), 1.15 (d, J ) 7.00 Hz, 3H), 0.93 (s, 9H), 0.173 (s, 3H),
0.168 (s, 3H). 13C NMR (100 MHz, CDCl3) major isomer: δ 156.33,
104.59, 88.42, 68.36, 47.47, 33.49, 31.73, 25.69, 25.44, 18.19, 15.29,
-4.55, -4.66. Minor isomer: δ 153.90, 101.59, 87.76, 69.06, 41.09,
33.23, 30.97, 26.18, 25.44, 18.50, 14.13, -4.55, -4.66. IR (film): 3303,
3053, 2932, 1687, 1265 cm-1. HRMS (EI): calcd for C15H26OSi M+
250.1753, found 250.1799.
(21) (a) Johnson, A. W. Ylide Chemistry; Academic Press: New York, 1966.
(b) Trost, B. M.; Melvin, L. S., Jr. Sulfur Ylide; Academic Press: New
York, 1975.
(22) (a) Trost, B. M.; Shibata, T. J. Am. Chem. Soc. 1982, 104, 3225. (b) Trost,
B. M.; Martin, S. J. J. Am. Chem. Soc. 1984, 106, 4263. (c) Matsuyama,
H.; Nakamura, T.; Kamigata, N. J. Org. Chem. 1989, 54, 5218.
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