Lebrun et al.
°C for 30 min and then at room temperature for 5 h. The reaction
mixture was quenched with water at room temperature and diluted
with EtOAc. The aqueous layer was washed with EtOAc (3×).
The combined organic layers were washed with brine, dried over
MgSO4, and concentrated. Purification was done by flash chroma-
tography using 15% EtOAc/hexanes as the eluent to afford the
desired sulfone 2b (1.53 g, 40% yield), while some starting material
(0.402 g) was recovered. The reaction was not pushed to completion
to avoid dibromo compound formation, which was previously
observed. Compound 2b was obtained as a white crystal after
corresponding alkenyl halides in good yields with excellent Z
stereoselectivities using the modified Julia olefination. The
R-halomethyl sulfones can be easily prepared in two or three
steps from commercially available reagents. Further investiga-
tions on substituent effects and mechanistic studies of these
reactions are currently underway.
Experimental Section
1
crystallization in ether/hexanes. H NMR (500 MHz, CDCl3): δ
Synthesis of Sulfone 2a. 5-[(Chloromethyl)sulfonyl]-1-phenyl-
1H-tetrazole (2a). Step 1: To a solution of 2-mercaptophenyltet-
razole (10 g, 56.1 mmol) in DMF (300 mL, 0.187 M) at -5 °C
was slowly added 60% sodium hydride (2.24 g, 56.1 mmol, 1
equiv). The reaction was stirred at -5 °C for 10 min. Chloro-
iodomethane (4.27 mL, 58.9 mmol, 1.05 equiv) diluted in ∼5 mL
of DMF was then slowly added, and the mixture was stirred at
room temperature for 1.5 h. The reaction mixture was quenched
with a saturated NH4Cl solution at room temperature and diluted
with EtOAc. The aqueous layer was washed with EtOAc (3×).
The organic layers were washed with water (3×) and brine, dried
over MgSO4, and concentrated. Purification was done by using a
silica gel plug filtration with 40% EtOAc/hexanes as the eluent,
which afforded the desired sulfide (11.27 g, 89% yield). The product
was directly oxidized to the sulfone. Step 2: To a solution of the
previous sulfide (3.8 g, 15.66 mmol) in ethanol (100 mL, 0.157
M) at 0 °C was added ammonium molybdate tetrahydrate (3.87 g,
3.13 mmol, 0.2 equiv), followed by 30% hydrogen peroxide (4.8
mL, 47 mmol, 3 equiv). The reaction was stirred at room
temperature overnight. The reaction mixture was quenched with a
sodium sulfite solution at room temperature and diluted with EtOAc.
The aqueous layer was washed with EtOAc (3×). The combined
organic layers were washed with brine, dried over MgSO4, and
concentrated. Purification was done by flash chromatography using
10-20% EtOAc/hexanes as the eluent to afford the corresponding
7.57-7.64 (m, 5H), 5.02 (s, 2H). 13C NMR (126 MHz, CDCl3): δ
151.3, 132.6, 131.8, 129.8, 125.2, 43.9. HRMS calcd for C8H8-
BrN4O2S: 302.9551. Found: 302.9550.
Representative Procedure for the Synthesis of Z Alkenyl
Halide (3a). To a solution of sulfone 2a (100 mg, 0.387 mmol)
and p-anisaldehyde (47 µL, 0.387 mmol, 1 equiv) in THF (1.5 mL,
0.258M) at room temperature was added HMPA (135 µL, 0.774
mmol, 2 equiv), followed by LiHMDS (774 µL, 0.774 mmol, 2
equiv) as a 1.0 M hexanes solution. The reaction was stirred at
room temperature for 30 min, after which it was filtered through a
silica gel cartridge (1.5 g), washed with 5% ether/pentane, and
evaporated. The crude NMR indicated a ratio of 10:90 favoring
the Z isomer. Purification was done by flash chromatography using
0-20% ether/pentanes to give alkenyl chloride 3a (62 mg, 95%
yield) as a colorless oil.
1
1-[(Z)-2-Chlorovinyl]-4-methoxybenzene (3a). H NMR (500
MHz, CDCl3): δ 7.69 (d, J ) 8.8 Hz, 2H), 6.94 (d, J ) 8.8 Hz,
2H), 6.60 (d, J ) 8.1 Hz, 1H), 6.19 (d, J ) 8.1 Hz, 1H), 3.86 (s,
3H). 13C NMR (126 MHz, CDCl3): δ 159.3, 130.7, 128.6, 126.8,
115.4, 113.6, 55.2. GC-MS calcd for C9H9ClO: 168.04. Found:
168. See ref 19 for compound 7.
1
1-[(Z)-2-Bromovinyl]-4-methoxybenzene (3b). H NMR (500
MHz, CDCl3): δ 7.71 (d, J ) 8.7 Hz, 2H), 7.03 (d, J ) 8.1 Hz,
1H), 6.94 (d, J ) 8.7 Hz, 2H), 6.34 (d, J ) 8.1 Hz, 1H), 3.86 (s,
3H). 13C NMR (126 MHz, CDCl3): δ 159.4, 131.6, 130.4, 127.5,
113.6, 104.1, 55.2. GC-MS calcd for C9H9BrO: 211.98. Found:
212. See ref 20 for compound 3c.
1
chloromethyl sulfone 2a (3.26 g, 81% yield) as a white solid. H
NMR (500 MHz, CDCl3): δ 7.57-7.66 (m, 5H), 5.12 (s, 2H). 13
C
NMR (126 MHz, CDCl3): δ 151.4, 132.6, 131.8, 129.8, 125.2,
58.6. HRMS calcd for C8H8ClN4O2S: 259.0056. Found: 259.0057.
1
2-[(Z)-2-Chlorovinyl]naphthalene (4a). H NMR (500 MHz,
Synthesis of Sulfone 2b. 5-[(Bromomethyl)sulfonyl]-1-phenyl-
1H-tetrazole (2b). Step 1: To a solution of 2-mercaptophenyltet-
razole (5.0 g, 28.1 mmol) in DMF (120 mL, 0.234 M) at 0 °C was
slowly added 60% sodium hydride (1.124 g, 28.1 mmol, 1 equiv).
The reaction was stirred at 0 °C for 20 min, then methyl iodide
(1.757 mL, 28.1 mmol) was introduced, and the reaction mixture
was stirred at room temperature for 2 h. The reaction mixture was
quenched with a saturated NH4Cl solution and diluted with EtOAc.
The aqueous layer was washed with EtOAc (3×). The combined
organic layers were washed with water (4×) and brine, dried over
MgSO4, and concentrated. Purification was done by flash chroma-
tography using a gradient of 10-40% EtOAc/hexanes to afford
the corresponding methyl sulfide (5.3 g, 99% yield). This compound
was used directly for the next step. Step 2: To a solution of the
previous methyl sulfide (3 g, 15.6 mmol) in ethanol (70 mL, 0.223
M) at 0 °C was added ammonium molybdate tetrahydrate (9.64 g,
7.8 mmol, 0.5 equiv), followed by 30% hydrogen peroxide (7.17
mL, 70.2 mmol, 4.5 equiv). The reaction was stirred at room
temperature overnight. The reaction mixture was quenched with a
sodium sulfite solution at room temperature and diluted with EtOAc.
The aqueous layer was washed with EtOAc (3×). The combined
organic layers were washed with brine, dried over MgSO4, and
concentrated. Purification was done by flash chromatography using
0-40% EtOAc/hexanes as the eluent to afford the corresponding
methyl sulfone (2.84 g, 81% yield) as a white solid that was used
directly for the next step. Step 3: To a solution of the previous
methyl sulfone (2.84 g, 12.67 mmol) in THF (250 mL, 0.051 M)
at -40 °C was added DBU (1.91 mL, 12.67 mmol, 1 equiv). The
reaction was cooled to -40 °C. NBS (2.255 g, 12.67 mmol, 1 equiv)
diluted in THF was then added, and the reaction was stirred at -40
CDCl3): δ 8.15 (s, 1H), 7.81-7.87 (m, 4H), 7.46-7.52 (m, 2H),
6.78 (d, J ) 8.1 Hz, 1H), 6.35 (d, J ) 8.1 Hz, 1H). 13C NMR (126
MHz, CDCl3): δ 133.1, 132.9, 131.6, 129.3, 128.8, 128.3, 127.8,
127.6, 126.7, 126.4, 126.2, 117.8. GC-MS calcd for C12H9ClO:
188.04. Found: 188.
1
2-[(Z)-2-Bromovinyl]naphthalene (4b). H NMR (500 MHz,
CDCl3): δ 8.15 (s, 1H), 7.75-7.87 (m, 4H), 7.44-7.53 (m, 2H),
7.18-7.27 (m, 1H), 6.50 (d, J ) 8.1 Hz, 1H). 13C NMR (126 MHz,
CDCl3): δ 133.1, 133.0, 132.4, 128.6, 128.3, 127.69, 127.66, 126.6,
126.39, 126.41, 126.3, 106.7. GC-MS calcd for C12H9BrO: 231.99.
Found: 232. See ref 20 for compound 3q.
1-[(Z)-2-Chlorovinyl]-2-methylbenzene (5a). 1H NMR (500
MHz, CDCl3): δ 7.62-7.65 (m, 1H), 7.19-7.24 (m, 3H), 6.77 (d,
J ) 7.9 Hz, 1H), 6.36 (d, J ) 7.9 Hz, 1H), 2.30 (s, 3H). 13C NMR
(126 MHz, CDCl3): δ 136.3, 133.0, 129.9, 129.0, 128.4, 128.0,
125.4, 118.8, 19.8. GC-MS calcd for C9H9Cl: 152.04. Found: 152.
See ref 19 for compound 11.
1-[(Z)-2-Bromovinyl]-2-methylbenzene (5b). 1H NMR (500
MHz, CDCl3): δ 7.58-7.62 (m, 1H), 7.22-7.29 (m, 3H), 7.19 (d,
J ) 7.9 Hz, 1H), 6.57 (d, J ) 7.9 Hz, 1H), 2.32 (s, 3H). 13C NMR
(126 MHz, CDCl3): δ 136.2, 134.3, 132.0, 130.0, 128.6, 128.1,
125.4, 108.4, 19.8. GC-MS calcd for C9H9Br: 195.99. Found: 196.
See ref 21 for compound 2c.
(19) Schlosser, M.; Ladenberger, V. Chem. Ber. 1967, 100, 3901.
(20) Kuang, C.; Yang, Q.; Senbokuc, H.; Tokudac, M. Tetrahedron 2005,
61, 4043.
(21) Uenishi, J.; Kawahama, R.; Yonemitsu, O. J. Org. Chem. 1998,
63, 8965.
2012 J. Org. Chem., Vol. 71, No. 5, 2006