Synthesis and Comparison of the Reactivity of Allyl Fluorides and ...

197
Chapter Six
6.5.20 Preparation of 2,2-difluoro-1-(4-(trifluoromethyl)phenyl)but-3-enyl 4-fluoro
benzoate (171)
The title compound was prepared using a method
outlined by Nakamura et al. [7] A 100 cm 3 , two-necked
round-bottomed flask was equipped with a magnetic
stirring bar, and Rotaflo tap and attached to a Schlenk
line. After flame-drying under high vacuum, the flask
was cooled and filled with nitrogen. The reaction flask
was charged with 2,2-difluoro-1-(4-(trifluoromethyl)
phenyl)but-3-en-1-ol (42 mg, 0.17 mmol) and pyridine (0.5 cm 3 ) and cooled to 0 ºC. 4-
Fluorobenzoyl chloride (0.02 cm 3 , 0.17 mmol) was added and the reaction mixture warmed
to room temperature and stirred for 2 h. After which the reaction was quenched with brine
(6 cm 3 ) and diethyl ether (5 cm 3 ). The organic layer was then separated and washed with
HCl (1 cm 3 , 5 % aqueous solution), saturated brine (10 cm 3 ), saturated NaHCO3 (10 cm 3 )
and saturated brine (10 cm 3 ) successively, then dried over magnesium sulphate. After
removal of solvent in vacuo the crude product was purified by column chromatography
[chloroform: hexane (50:50)], affording the product as an oil (39 mg, 63%). δH 5.48 (1H,d,
3 JHH = 11.0 Hz, Hb), 5.64(1H, dt, 3 JHH = 17.6 Hz, 4 JHF = 2.3 Hz, Ha), 5.85 (1H, ddt, 3 JHH =
17.6 Hz, 3 JHF = 12.5 Hz, 3 JHH = 11.0 Hz, Hc), 6.08 (1H, dd, 3 JHF = 11.3 Hz, 3 JHF = 9.0 Hz,
CHO), 7.08 (2H, tm, 3 JHH = 9.0 Hz, ArH-3’), 7.53 (2H, d, 3 JHH = 8.6 Hz, ArH-3), 7.57 (2H,
d, 3 JHH = 8.6 Hz, ArH-2), 8.04 (2H, ddm, 3 JHH = 9.0 Hz, 4 JHF = 5.5 Hz ArH-2’); δC 75.3 (t,
2 JCF = 30.2 Hz, CHCF2), 115.9 (d, 2 JCF = 21.4 Hz, ArCH-3’), 117.9 (t, 1 JCF = 246.5 Hz,
CF2), 122.6 (t, 3 JCF = 8.8 Hz, CHCH2), 123.8 (q, 1 JCF = 271.6 Hz, ArCF3), 125.2 (d, 4 JCF =
2.5 Hz, ArC-1’), 125.4 (q, 3 JCF = 3.8 Hz, ArCH-3), 128.6 (ArCH-2), 129.3 (t, 2 JCF = 25.2
Hz, CHCH2), 131.4 (q, 2 JCF = 32.7 Hz, ArCH-4), 132.6 (d, 3 JCF = 8.8 Hz, ArCH-2’), 137.1
(ArC-1), 163.7 (C=O), 166.3 (d, 1 JCF = 255.3 Hz, ArCF’); δF -62.8 (3F, s, CF3), -103.8 (1F,
s, CF), -105.8 (d, 2 JFF = 254.3 Hz, CF), -109.4 (d, 2 JFF = 250.4 Hz, CF). m/z (EI + ) 374
([M] + , 13 %), 297 ([M-CF2CH=CH2] + , 76 %), 123 ([M-CHO(C6H4CH3) CF2CH=CH2] + , 100
%). HRMS (EI) 374.07384 (C18H12O2F6 requires 374.07385).