2-(2-Br om oa llyl)-2-m eth ylm a lon ic Acid Dim eth yl Ester
(Ta ble 1, En tr y f). To a solution of dimethyl methylmalonate
(1.00 g, 6.84 mmol) in THF (20 mL), cooled to 0 °C was added
potassium tert-butoxide (921 mg, 8.2 mmol), and the solution
was stirred for 15 min. 2,3-Dibromopropene (1.00 mL, 8.20
mmol, 1.93 g/mL, 85% v/v) was added, and the solution was
stirred overnight at rt. The mixture was poured into water and
dichloromethane. The aqueous layer was extracted twice with
dichloromethane, and the combined organic layers were dried
with MgSO4 and concentrated. The crude product was purified
by flash chromatography on silica gel (hexanes/ether, 9/1) to
afford the vinyl bromide as an oil (1.2 g 80%): 1H NMR (300
MHz, CDCl3) δ 5.46 (s, 1H), 5.38 (br m, 1H), 3.53 (s, 6H), 2.95
(s, 2H), 1.29 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 171.4, 127.0,
121.6, 52.8, 52.6, 45.8, 19.1; IR (neat) 1736, 1625 cm-1; LRMS
(APCI+) m/z (relative intensity) 267 (100), 265 (98, MH+), 234
(56), 242 (56), 207 (52), 205 (53).
2-(Ben zh yd r ylid en ea m in o)-4-ch lor op en t -4-en oic Acid
Eth yl Ester (Ta ble 1, En tr y l). To a solution of 2,3-dichloro-
propene (830 mL, 9.0 mmol) in acetone (10 mL) was added
sodium iodide (1.6 g, 10.8 mmol), and the mixture was stirred
at rt for 4 h. The solution was filtered through Celite and
concentrated, and the crude iodide was used directly in the next
step.
J ) 7.2 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 169,6, 167.3, 136.6,
117.8, 65.3, 63.0, 41.7, 22.9, 14.1; IR (neat) 1743, 1633 cm-1
;
LRMS (APCI+) m/z (relative intensity) 294 (39), 292 (100, MH+),
252 (14), 250 (42).
Typ ica l P r oced u r e for Con ver sion of a Vin yl Ch lor id e
to a n r-Ch lor ok eton e. 2-Acetyla m in o-2-(3-ch lor o-2-oxo-
p r op yl)m a lon ic Acid Dieth yl Ester (Ta ble 1, En tr y k ). To
a solution of the vinyl chloride (530 mg, 2.40 mmol) in acetone
(10 mL) and acetic acid (4 mL), cooled to 0 °C, was added sodium
hypochlorite (1.15 mL, 2.40 mmol, 1.21 g/mL, 13% v/v) dropwise.
The solution was stirred for 1 h at 0 °C until the reaction was
complete as monitored by TLC. The solution was poured into
saturated sodium bicarbonate (50 mL) and diluted with dichlo-
romethane. The aqueous layer was extracted twice with dichlo-
romethane, and the combined organic layers were dried with
MgSO4 and concentrated in vacuo. The crude product was
purified by flash chromatography on silica gel (hexanes/ethyl
acetate, 1/1) to afford the R-chloroketone as a white solid: mp
1
70-72 °C (188 mg, 99%); H NMR (400 MHz, CDCl3) δ 7.05 (s,
1H), 4.14 (q, J ) 7.1 Hz, 4H), 4.03 (s, 2H), 3.75 (s, 2H), 1.93 (s,
3H), 1.15 (t, J ) 7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 199.3,
169.6, 166.5, 63.5, 62.9, 47.9, 43.0, 22.7, 13.7; IR (neat) 1743,
1664 cm-1; LRMS (APCI+) m/z (relative intensity) 310 (27), 308
(100, MH+), 266 (21), 102 (58).
To a solution of glycine ethyl ester benzophenone imine (1.00
g, 6.84 mmol)8 in THF (25 mL) cooled to 0 °C was added
potassium tert-butoxide (921 mg, 8.20 mmol), and the solution
was stirred at rt for 15 min. The 2-chloro-3-iodopropene prepared
as decribed above was added, and the solution was stirred at rt
overnight. The mixture was poured into water and ether. The
aqueous layer was extracted twice with ether, and the combined
organic layers were dried with MgSO4 and concentrated. The
crude product was purified by flash chromatography on silica
gel (hexanes/ether, 9/1) to afford the vinyl chloride as an oil (1.6
g, 63%): 1H NMR (400 MHz, CDCl3) δ 7.10-7.60 (m, 10H), 5.15
(s, 1H), 5.09 (s, 1H), 4.30 (dd, J ) 8.00, 3.00 Hz, 1H), 4.08 (m,
2H), 2.91 (m, 2H) 1.15 (t, J ) 5.1 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ 171.7, 171.0, 139.5, 138.5, 137.5, 135.8, 130.3, 129.8,
128.8, 128.6, 128.2, 128.1, 127.9, 127.1, 115.2, 62.7, 61.1, 43.3,
14.1; IR (neat) 1737, 1625 cm-1; LRMS (APCI+) m/z (relative
intensity) 344 (41), 342 (100, MH+).
1-(2-Ch lor oa llyl)-2-oxocycloh exa n eca r boxylic Acid Eth -
yl Ester (Ta ble 1, En tr y i). To a solution of ethyl cyclohexanone
carboxylate (1.48 g, 9.25 mmol) in THF (20 mL) cooled to 0 °C
was added potassium tert-butoxide (1.24 g, 11.1 mmol) and the
solution was stirred for 15 min. 2-Chloro-3-iodopropene prepared
as described above (11.1 mmol) was added, and the solution was
stirred at rt overnight. The mixture was poured into water and
dichloromethane. The aqueous layer was extracted twice with
dichloromethane and the combined organic layers were dried
over MgSO4 and concentrated. The crude product was purified
by flash chromatography on silica gel (hexanes/ether, 9/1) to
afford the vinyl chloride as an oil (1.30 g, 58%): 1H NMR (400
MHz, CDCl3) δ 5.11 (s, 1H), 5.03 (s, 1H), 4.05 (q, J ) 7.1 Hz,
2H), 2.93 (d, J ) 14.8 Hz, 1H), 2.54-2.61 (m, 2H), 2.26-2.37
(m, 2H), 1.94 (m, 1H), 1.60-1.80 (m, 2H), 1.30-1.60 (m, 2H),
1.12 (t, J ) 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 205.7,
170.0, 137.3, 116.5, 61.3, 59.7, 43.5, 40.6, 35.1, 27.3, 22.1, 13.7;
IR (neat) 1716, 1631 cm-1; LRMS (APCI+) m/z (relative intensity)
247 (35), 245 (98, MH+), 209 (100).
2-(Ben zh ydr yliden eam in o)-5-ch lor o-4-oxopen tan oic Acid
Eth yl Ester (Ta ble 1, En tr y l). Purified by flash chromatog-
raphy on silica gel (hexanes/ethyl acetate/triethylamine, 80/18/
2) to afford the R-chloroketone as an oil (52%): 1H NMR (400
MHz, CDCl3) δ 7.21-7.51 (m, 10H), 4.52 (dd, J ) 6.4, 8.0 Hz,
1H), 4.05 (m, 4H), 3.25 (dd, J ) 6.4, 18.8 Hz, 1H), 3.04 (dd, J )
8.1, 18.8 Hz, 1H), 1.20 (t, J ) 7.9 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 199.7, 172.1, 170.7, 139.2, 135.9, 130.5, 130.5, 128.7,
128.4, 128.0, 127.8, 61.4, 61.3, 48.7, 43.0, 14.0; IR (neat) 1732,
1712 cm-1; LRMS (APCI+) m/z (relative intensity) 360 (35), 358
(100, MH+).
2-(3-Ch lor o-2-oxop r op yl)cycloh exa n on e (Ta ble 1, En tr y
g). The crude product was purified by flash chromatography on
silica gel (hexanes/ether, 1/1) to afford the R-chloroketone as a
yellow oil (66%): 1H NMR (400 MHz, CDCl3) δ 4.14 (s, 2H) 2.86
(m, 2H), 1.92-2.41 (m, 6H), 1.27-1.90 (m, 3H); 13C NMR (100
MHz, CDCl3) δ 210.9, 200.9, 48.6, 46.9, 41.3, 39.3, 33.5, 27.4,
24.8; IR (neat) 1735, 1706 cm-1; LRMS (APCI+) m/z (relative
intensity) 191 (34), 189 (100, MH+).
1-(3-Ch lor o-2-oxop r op yl)-2-oxocycloh exa n eca r b oxylic
Acid Eth yl Ester (Ta ble 1, En tr y i). The crude product was
purified by flash chromatography to afford the R-chloroketone
as a yellow oil (81%): 1H NMR (360 MHz, CDCl3) δ 4.14-4.21
(m, 4H), 2.76-2.88 (m, 3H), 2.37 (m, 2H), 2.00 (m, 1H), 1.57-
1.73 (m, 4H), 1.23 (t, J ) 7.0 Hz, 3H); 13C NMR (90 MHz, CDCl3)
d 207.2, 199.4, 171.3, 61.6, 60.0, 48.4, 44.0, 40.2, 37.1, 26.8, 21.7,
13.8; IR (neat) 1731, 1710 cm-1; LRMS (APCI+) m/z (relative
intensity) 263 (2), 261 (5, MH+), 245 (37), 244 (15), 243 (100),
135 (38), 102 (24).
Typ ica l P r oced u r e for Con ver sion of a Vin yl Br om id e
to a n r-Br om ok eton e. 2-(3-Br om o-2-oxop r op yl)-2-m eth yl-
m a lon ic Acid Dim eth yl Ester (Ta ble 1, En tr y f). To a
solution of sodium hydroxide (2.0 g, 50.0 mmol) in water (25 mL)
at 0 °C was slowly added bromine (0.85 mL, 16.6 mmol).2 The
solution was stirred for 15 min and used immediately. To a
solution of the vinyl bromide (300 mg, 1.13 mmol) in acetone
(10 mL) and acetic acid (4 mL) cooled to 0 °C was added dropwise
the sodium hypobromite solution (1.70 mL, 1.13 mmol, 0.664
M). The solution was stirred for 1 h at 0 °C as the progress of
the reaction was monitored by TLC. The solution was poured
into saturated sodium bicarbonate solution and diluted with
dichloromethane. The aqueous layer was extracted twice with
dichloromethane and the combined organic layers were dried
with MgSO4 and concentrated. The crude product was purified
by flash chromatography on silica gel (hexanes/ether, 7/3) to
afford the known R-bromoketone1 as an oil (290 mg, 87%): 1H
NMR (300 MHz, CDCl3) δ 3.88 (s, 2H), 3.65 (s, 6H), 3.19 (s, 2H),
1.46 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 198.5, 171.3, 52.7,
51.6, 45.0, 34.0, 20.3; IR (neat) 1734 cm-1; LRMS (APCI+) m/z
2-Acetyla m in o-2-(2-ch lor oa llyl)m a lon ic Acid Dieth yl Es-
ter (Ta ble 1, En tr y k ). To a solution of diethyl acetamidoma-
lonate (2.00 g, 10.31 mmol) in THF (25 mL) cooled to 0 °C was
added potassium tert-butoxide (1.15 mg, 10.31 mmol), and the
solution was stirred for 15 min. 2-Chloro-3-iodopropene (10.31
mmol), prepared as described above, was added, and the solution
was stirred at rt overnight. The mixture was poured into water
and dichloromethane. The aqueous layer was extracted twice
with dichloromethane, and the combined organic layers were
dried with MgSO4 and concentrated. The crude product was
purified by flash chromatography on silica gel (hexanes/ethyl
acetate, 2/1) to afford the vinyl chloride as an oil (1.80 g, 67%):
1H NMR (300 MHz, CDCl3) δ 6.86 (s, 1H), 5.06 (s, 1H), 4.96 (s,
1H), 4.03 (q, J ) 6.5 Hz, 4H), 3.24 (s, 2H), 1.82 (s, 3H), 1.05 (t,
J . Org. Chem, Vol. 68, No. 8, 2003 3325