478
Vol. 51, No. 4
Ethyl 2,2-Dibromo-3,3-dimethylbutanoate (1f)6): Colorless oil. Yield 84%
(88—90 °C/3.0 mmHg). 1H-NMR (400 MHz, CDCl3) d: 1.33—1.38 (3H,
m), 1.36 (9H, s), 4.31 (2H, q, Jꢁ7 Hz). 13C-NMR (75 MHz, CDCl3) d: 13.9
(q), 27.3 (q), 43.4 (s), 58.5 (s), 63.7 (t), 165.8 (s). IR (Neat) cmꢀ1: 1739. EI-
MS m/z: 300 (Mꢂ), 302 (Mꢂꢂ2). HR-MS (EI) Calcd for C8H14Br2O2 (Mꢂ)
299.9361, Found: 299.9367.
Ethyl 2-Bromo-4-phenylbutanoate (4g): Colorless oil. Yield 62% (bulb-
to-bulb distillation, bp 160—180 °C at 2.0 mmHg). 1H-NMR (400 MHz,
CDCl3) d: 1.30 (3H, t, Jꢁ7 Hz), 2.25—2.42 (2H, m), 2.69—2.85 (2H, m),
4.16 (1H, dd, Jꢁ7, 8 Hz), 4.22 (2H, dq, Jꢁ2, 7 Hz), 7.17—7.32 (5H, m).
13C-NMR (100 MHz, CDCl3) d: 14.0 (q), 33.2 (t), 36.3 (t), 45.4 (d), 62.0 (t),
126.3 (d), 128.4 (d), 128.5 (d), 139.7 (s), 169.5 (s). IR (Neat) cmꢀ1: 1739.
EI-MS m/z: 270 (Mꢂ), 272 (Mꢂꢂ2). HR-MS (EI) Calcd for C12H15BrO2
(Mꢂ) 270.0255, Found: 270.0256.
Chart 6
method for aliphatic a,a-dibromo esters, precursors of yno-
lates, via bromination of lithium a-bromo ester enolates with
1,2-dibromo-1,1,2,2-tetrafluoroethane. We have also synthe-
sized trimethylsilyl dibromo esters via bromination of the
lithium ester enolate of trimethylsilylacetate, followed by
radical bromination in good yield. These results will con-
tribute to the utility of ynolate chemistry.
Ethyl 2,2-Dibromo-4-phenylbutanoate (1g)6): Colorless oil. Yield 74% (bp
121—123 °C/0.8 mmHg). 1H-NMR (400 MHz, CDCl3) d: 1.37 (3H, t,
Jꢁ7 Hz), 2.84—2.97 (4H, m), 4.33 (2H, q, Jꢁ7 Hz), 7.20—7.33 (5H, m).
13C-NMR (100 MHz, CDCl3) d: 13.8 (q), 33.9 (t), 48.8 (t), 59.6 (s), 63.7 (t),
126.3 (d), 128.4 (d), 128.4 (d), 139.4 (s), 165.8 (s). IR (Neat) cmꢀ1: 1733.
EI-MS m/z: 348 (Mꢂ), 350 (Mꢂꢂ2). HR-MS (EI) Calcd for C12H14Br2O2
(Mꢂ) 347.9361, Found: 347.9375.
Experimental
General 1H- and 13C-NMR spectra were obtained on a JEOL JNM-AL
400 and an AL 300 spectrometer. Signals are given in ppm using tetra-
methylsilane as an internal standard. IR spectra were recorded on JASCO
FT-IR 410. MS spectra were obtained on a JEOL JMS-DX303 and JMS-
SX102A.
Materials 1,2-Dibromo-1,1,2,2-tetrafluoroethane was purchased from
Tokyo Kasei Kogyo Co., Ltd. and purified by distillation. Anhydrous THF
and butyllithium were purchased from Kanto Chemical Co., Inc. and used
without further purification. a-Bromo esters were prepared according to the
literature5) except 4a.
Representative Procedure for a-Bromination of Esters. Ethyl 2,2-Di-
bromohexanoate (1a)5): To a solution of diisopropylamine (9.90 ml, 70.6
mmol) in THF (200 ml) was added a butyllithium solution (1.34 M in hexane,
52.7 ml, 70.6 mmol) at ꢀ78 °C and the reaction was stirred for 15 min. A so-
lution of ethyl 2-bromohexanoate (15.0 g, 67.2 mmol) in THF (20 ml) was
added dropwise. After 30 min, 1,2-dibromo-1,1,2,2-tetrafluoroethane (12.0
ml, 101 mmol) was added in one portion. After 30 min, the reaction mixture
was poured into a saturated NaHCO3 solution and the resulting mixture was
extracted with hexane. The organic phase was washed with water, saturated
NaCl solution, dried over MgSO4, filtered, and concentrated to afford a yel-
low oil, which was distilled (bp 85—90 °C at 2.0 mmHg) to yield 18.1 g
(89%) of 1a as a colorless oil.
Ethyl 2,2-Dibromo-2-(trimethylsilyl)acetate (1i)14): To a solution of diiso-
propylamine (4.5 ml, 32.2 mmol) in THF (70 ml) was added a butyllithium
solution (1.57 M in hexane, 20.5 ml, 32.2 mmol) at ꢀ78 °C and the reaction
was stirred for 15 min. A solution of ethyl trimethylsilylacetate (4.30 g,
26.8 mmol) in THF (10 ml) was added dropwise. After 30 min, 1,2-dibromo-
1,1,2,2-tetrafluoroethane (4.76 ml, 40.2 mmol) was added in one portion.
After 2.5 h, the reaction mixture was poured into saturated NH4Cl solution
and then the resulting mixture was extracted with hexane. The organic phase
was washed with water, saturated NaCl solution, dried over MgSO4, filtered,
and concentrated to afford an oil, which was distilled (bp 60—62 °C at
3 mmHg) to give 3.95 g (62%) of 4i15) as a colorless oil. To a solution of 4i
(3.0 g, 12.5 mmol) in CCl4 (50 ml) was added N-bromosuccinimide (3.35 g,
18.8 mmol) and a catalytic amount of benzoyl peroxide, and the resulting
suspension was refluxed for 21 h. After filtration, the filtrate was concen-
trated in vacuo to afford a brown oil, which was distilled (bp 73—77 °C at
1
3 mmHg) to yield 3.0 g (75%) of 1i as a colorless oil. H-NMR (400 MHz,
CDCl3) d: 0.34 (9H, s), 1.33 (3H, t, Jꢁ7 Hz), 4.30 (2H, q, Jꢁ7 Hz). 13C-
NMR (100 MHz, CDCl3) d: ꢀ2.4 (q), 14.0 (q), 51.5 (s), 63.5 (t), 167.6 (s).
IR (Neat) cmꢀ1: 1718, 1740. EI-MS m/z: 316 (Mꢂ), 318 (Mꢂꢂ2). HR-MS
(EI) Calcd for C7H14Br2O2Si (Mꢂ) 315.9130, Found: 315.9097.
Acknowledgement This work was supported in part by a Grant-in-Aid
for Scientific Research on Priority Areas (A) ‘Exploitation of Multi-Element
Cyclic Molecules’ from the Ministry of Education, Culture, Sports, Science
and Technology, Japan.
Ethyl 2,2-Dibromopropanoate (1b)6): Colorless oil. Yield 85% (49 °C/2.2
mmHg). 1H-NMR (300 MHz, CDCl3) d: 1.37 (3H, t, Jꢁ7 Hz), 2.65 (3H, s),
4.34 (2H, q, Jꢁ7 Hz). 13C-NMR (75 MHz, CDCl3) d: 13.6 (q), 37.2 (q), 52.1
(t), 63.5 (s), 166.5 (s). IR (Neat) cmꢀ1: 1737. EI-MS m/z: 258 (Mꢂ), 260
(Mꢂꢂ2). Anal. Calcd for C5H8Br2O2: C, 23.10; H, 3.10. Found: C, 23.19; H,
3.08.
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Ethyl 2,2-Dibromoheptanoate (1c)7): Colorless oil. Yield 86% (96—
102 °C/2.2 mmHg). 1H-NMR (300 MHz, CDCl3) d: 0.91 (3H, t, Jꢁ7 Hz),
1.29—1.42 (4H, m), 1.36 (3H, t, Jꢁ7 Hz), 1.59—1.64 (2H, m), 2.53—2.58
(2H, m), 4.33 (2H, q, Jꢁ7 Hz). 13C-NMR (75 MHz, CDCl3) d: 13.7 (q), 13.8
(q), 22.3 (t), 27.1 (t), 30.8 (t), 47.0 (t), 60.8 (s), 63.6 (t), 166.2 (s). IR (Neat)
cmꢀ1: 1735. EI-MS m/z: 314 (Mꢂ), 316 (Mꢂꢂ2). HR-MS (EI) Calcd for
C9H16Br2O2 (Mꢂ) 313.9517, Found: 313.9551.
Ethyl 2,2-Dibromocyclohexaneacetate (1d)9): Colorless oil. Yield 89%.
1H-NMR (300 MHz, CDCl3) d: 1.11—1.42 (5H, m), 1.35 (3H, t, Jꢁ7 Hz),
1.67—1.71 (1H, m), 1.78—1.99 (4H, m), 2.20 (1H, ddt, Jꢁ3, 3, 8 Hz), 4.34
(2H, q, Jꢁ7 Hz). 13C-NMR (100 MHz, CDCl3) d: 13.8 (q), 25.6 (t), 25.8 (t),
29.6 (t), 50.5 (d), 63.8 (t), 70.3 (s), 166.2 (s). IR (Neat) cmꢀ1: 1732, 1749.
EI-MS m/z: 326 (Mꢂ), 328 (Mꢂꢂ2). Anal. Calcd for C10H16Br2O2: C, 36.61;
H, 4.92. Found: C, 36.95; H, 4.94.
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Ethyl 2,2-Dibromo-3-methylbutanoate (1e)6): Colorless oil. Yield 91%
(53—60 °C/1.0 mmHg). 1H-NMR (400 MHz, at 50 °C in CDCl3) d: 1.15
(6H, d, Jꢁ6 Hz), 1.34 (3H, t, Jꢁ7 Hz), 2.63 (1H, hept, Jꢁ6 Hz), 4.33 (2H, q,
Jꢁ7 Hz). 13C-NMR (100 MHz, CDCl3) d: 13.9 (q), 19.6 (q), 41.4 (d), 63.8
(t), 71.3 (s), 166.0 (s). IR (Neat) cmꢀ1: 1735, 1751. EI-MS m/z: 286 (Mꢂ),
288 (Mꢂꢂ2). HR-MS (EI) Calcd for C7H12O2Br2 (Mꢂ) 285.9204, Found:
285.9206.
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