860
K. Oh et al.
PRACTICAL SYNTHETIC PROCEDURES
quenched with sat. aq NH4Cl (10 mL), and the products were ex-
tracted with Et2O (3 × 15 mL). The combined organic layer was
washed with brine (20 mL) and dried (Na2SO4). After the solvent
was removed under reduced pressure, the residue was purified by
column chromatography (hexane–EtOAc, 20:1) to give 2Aa as a
colorless liquid; yield: 593 mg (93%).
purified by column chromatography (hexane–EtOAc, 30:1) to give
2Ak as a colorless liquid; yield: 555 mg (80%, two steps).
IR: 2958, 2871, 1741, 1726, 1275, 1217, 962, 708 cm–1.
1H NMR (500 MHz, CDCl3): d = 0.78 (t, J = 7.2 Hz, 3 H, CH3),
0.81–0.91 (m, 1 H, CH2), 1.04–1.29 (m, 3 H, CH2), 2.11 (dddd,
J = 14.0, 11.9, 4.4 Hz, JHF = 4.4 Hz, 1 H, CH2), 2.20 (s, 3 H,
CH3CO), 2.94 (dddd, J = 14.0, 12.2, 4.4 Hz, JHF = 3.4 Hz, 1 H,
CH2), 7.28–7.41 (m, 5 H, ArH).
13C NMR (126 MHz, CDCl3): d = 13.8, 21.6, 22.5, 25.8 (d, JCF = 2
Hz), 36.6 (d, JCF = 7 Hz), 84.1 (dd, JCF = 4, 2 Hz), 87.2 (dd,
JCF = 29, 23 Hz), 125.2, 127.7, 128.2, 141.4 (dd, JCF = 2, 2 Hz),
153.4 (dd, JCF = 297, 284 Hz), 168.6.
IR: 3028, 2949, 1747, 1731, 1282, 1221, 1026, 700 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.98–2.08 (m, 1 H, CH2), 2.07 (s,
3 H, CH3CO), 2.11–2.17 (m, 1 H, CH2), 2.58–2.62 (m, 2 H, CH2),
5.44 (dddd, J = 7.3, 7.3 Hz, JHF = 2.1, 2.1 Hz, 1 H, CH), 7.17 (dd,
J = 7.8, 0.8 Hz, 2 H, ArH), 7.21 (tt, J = 7.8, 0.8 Hz, 1 H, ArH), 7.29
(dd, J = 7.8, 7.8 Hz, 2 H, ArH).
13C NMR (126 MHz, CDCl3): d = 20.8, 31.1, 34.1, 68.3 (d, JCF = 3
Hz), 81.0 (dd, JCF = 35, 21 Hz), 126.3, 128.2, 128.6, 140.2, 154.2
(dd, JCF = 294, 289 Hz), 169.7.
19F NMR (470 MHz, CDCl3): d = 83.7 (ddd, JFF = 34 Hz, JFH = 4, 3
Hz, 1 F), 87.0 (d, JFF = 34 Hz, 1 F).
Anal. Calcd for C15H17BrF2O2: C, 51.87; H, 4.94. Found: C, 51.83;
H, 4.99.
19F NMR (470 MHz, CDCl3): d = 80.7 (br d, JFF = 27 Hz, 1 F), 82.3
(br d, JFF = 27 Hz, 1 F).
Anal. Calcd for C13H13BrF2O2: C, 48.92; H, 4.11. Found: C, 49.14;
H, 4.34.
1,1-Difluoro-3-phenylhepta-1,2-diene (3k)
The acetate 2Ak was converted into the corresponding difluoroal-
lene 3k by the same procedure as used for acetate 2Aa; yield: 85%.
IR: 2958, 2927, 1990, 1718, 1464, 1261, 1182, 769 cm–1.
1,1-Difluoro-5-phenylpenta-1,2-diene (3a)
n-BuLi (1.60 M in hexane; 0.12 mL, 0.19 mmol) was added to a
soln of acetate 2Aa (60 mg, 0.19 mmol) in hexane (2.6 mL) at 0 °C
under argon. The mixture was stirred for 1 min at that same temper-
ature, then the reaction was quenched with aq NH4Cl (3 mL), and
the products were extracted with Et2O (3 × 5 mL). The combined
organic layer was washed with brine (10 mL) and dried (Na2SO4).
After the solvent was removed under reduced pressure, the residue
was purified by column chromatography (pentane) to give 3a as a
colorless liquid; yield: 29 mg (87%).
1H NMR (500 MHz, CDCl3): d = 0.95 (t, J = 7.4 Hz, 3 H, CH3),
1.42 (tq, J = 7.5, 7.4 Hz, 2 H, CH2), 1.59 (tt, J = 7.5, 7.5 Hz, 2 H,
CH2), 2.69 (tt, J = 7.5 Hz, JHF = 5.7 Hz, 2 H, CH2), 7.33–7.40 (m, 3
H, ArH), 7.50–7.53 (m, 2 H, ArH).
13C NMR (126 MHz, CDCl3): d = 14.0, 22.2, 29.7 (d, JCF = 5 Hz),
33.0, 127.2, 128.5, 129.3, 134.8 (t, JCF = 6 Hz), 135.7, 152.6 (t,
JCF = 259 Hz), 166.2 (t, JCF = 36 Hz).
19F NMR (470 MHz, CDCl3): d = 60.0 (t, JFH = 6 Hz).
HRMS–FAB: m/z [M + H]+ calcd for C13H15F2: 209.1142; found:
IR: 3030, 2927, 2856, 2011, 1462, 1192, 744, 698 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.53–2.61 (m, 2 H, CH2), 2.81 (t,
J = 7.5 Hz, 2 H, CH2), 6.47 (tt, J = 6.1 Hz, JHF = 2.4 Hz, 1 H, =CH),
7.17–7.22 (m, 3 H, ArH), 7.30 (dd, J = 7.3, 7.3 Hz, 2 H, ArH).
13C NMR (126 MHz, CDCl3): d = 33.8, 33.8, 121.4 (t, JCF = 6 Hz),
126.2, 128.4, 128.5, 140.6, 152.8 (t, JCF = 261 Hz), 170.1 (t,
JCF = 36 Hz).
209.1130.
1,1-Difluoro-2-iodo-5-phenylpent-1-en-3-yl Acetate (2Ba);
Typical Procedure for Method B (from Aldehydes; Table 1,
Entry 1)
To a soln of (i-Pr)2NH (2.8 mL, 20 mmol) in THF (10 mL) was add-
ed n-BuLi (1.67 M in hexane; 12.0 mL, 20.0 mmol) over 10 min at
0 °C under argon. The resulting solution was allowed to stir for an
additional 15 min, and then cooled to –93 °C in a cold hexane bath.
To the cold LDA soln was added a soln of CF3CH2I (2.10 g, 10.0
mmol) in THF (5 mL) over 10 min, keeping the temperature be-
tween –93 °C and –85 °C. After the mixture was stirred for 20 min
at that same temperature, a soln of 3-phenylpropanal (1.34 g, 10.0
mmol) in THF (5 mL) was added over 5 min, while keeping the tem-
perature between –93 °C and –85 °C. The mixture was stirred for an
additional 30 min, then warmed to –30 °C over 90 min. After Ac2O
(1.23 g, 12.0 mmol) was added, the mixture was allowed to warm
to 0 °C over 2 h. The reaction was quenched with sat. aq NH4Cl
(20 mL), and the products were extracted with Et2O (3 × 20 mL).
The combined organic layer was washed with brine (20 mL) and
dried (Na2SO4). After the solvent was removed under reduced pres-
sure, the residue was purified by column chromatography (hexane–
EtOAc, 20:1). The acetate 2Ba was obtained as a colorless liquid;
yield: 3.01 g (82%).
19F NMR (470 MHz, CDCl3): d = 59.9 (td, JFH = 5, 2 Hz).
Anal. Calcd for C11H10F2: C, 73.32; H, 5.59. Found: C, 73.16; H,
5.77.
2-Bromo-1,1-difluoro-3-phenylhept-1-en-3-yl Acetate (2Ak);
Typical Procedure for Method A (from Ketones; Table 1,
Entry 11)
To a soln of 1,1-dibromo-2,2-difluoroethylene (442 mg, 2.0 mmol)
in Et2O (16 mL) was added a Et2O soln (2.0 mL) of n-BuLi (1.60 M
in hexane; 1.28 mL, 2.0 mmol) at –100 °C under argon. The mixture
was stirred for 15 min at that same temperature, then 1-phenylpen-
tan-1-one (0.30 mL, 2.0 mmol) in Et2O (3 mL) was added. The mix-
ture was stirred for an additional 1 h, and then allowed to warm to
–40 °C over 1 h. The reaction was quenched with sat. aq NH4Cl
(10 mL), and the products were extracted with Et2O (3 × 15 mL).
The combined organic layer was washed with brine (20 mL) and
dried (Na2SO4). After the solvent was removed under reduced pres-
sure, the residue was purified by column chromatography (hexane–
EtOAc, 10:1) to give 2-bromo-1,1-difluoro-3-phenylhept-1-en-3-
ol. To a soln of the alcohol in isopropenyl acetate (3 mL) was added
p-TsOH·H2O (5 mg, 0.03 mmol). The mixture was refluxed for 5 h,
then the reaction was quenched with sat. aq NaHCO3 (2 mL). The
products were extracted with Et2O (3 × 3 mL). The combined or-
ganic layer was washed with brine (3 mL) and dried (Na2SO4). After
the solvent was removed under reduced pressure, the residue was
IR: 3028, 2954, 1743, 1716, 1267, 1219, 1024, 698 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.87–1.93 (m, 1 H, CH2), 2.05–
2.17 (m, 1 H, CH2), 2.07 (s, 3 H, CH3CO), 2.58 (t, J = 7.2 Hz, 2 H,
CH2), 4.98 (t, J = 7.2 Hz, 1 H, CH), 7.17–7.22 (m, 3 H, ArH), 7.29
(dd, J = 7.3, 7.6 Hz, 2 H, ArH).
13C NMR (126 MHz, CDCl3): d = 20.9, 30.9, 36.0, 53.8 (dd,
JCF = 25, 26 Hz), 68.9 (d, JCF = 3 Hz), 126.2, 128.2, 128.5, 140.2,
154.0 (dd, JCF = 286, 286 Hz), 169.6.
Synthesis 2012, 44, 857–861
© Thieme Stuttgart · New York