(100.00). HRMS. Calcd for C13H14F2O2: 240.0962, Found
Synthesis of gem-difluoropropyl acetals and ketals
240.0925.
A typical procedure: under a nitrogen atmosphere, in a 10 ml
side-armed Pyrex tube with a magnetic stirring bar and a pres-
sure-equalized addition funnel, was placed acetal (1a) (1.82 g,
10.33 mmol), sodium fluoride (43 mg, 1.03 mmol) and diglyme
(1 ml). After heating the mixture to about 120 ЊC (bath), TFDA
(7.76 g, 30.98 mmol) was added dropwise. The mixture
was stirred at this temperature for 1 h. Then the reaction was
cooled to room temperature and directly purified by flash
chromatography on a silica gel column. Title product (2a)
(1.60 g, 68%) was obtained as a pale yellow liquid (eluent: pet-
roleum ether–ether = 10 : 1).
Compound 2g: liquid, IR (film) (cmϪ1): 2988, 1891, 1672,
1
1612, 1593, 1493, 1464, 1220, 1091, 1039. H NMR (CDCl3)
δ 1.35 (s, 3H), 2.07–2.15 (m, 1H), 2.87–2.94 (m, 1H), 3.91–4.06
(m, 4H), 7.12–7.33 (m, 4H). 19F NMR (CDCl3) δ Ϫ133.8 (dd,
J = 159.3, 15.2 Hz, 1 F), Ϫ136.5 (dd, J = 159.0, 14.1 Hz, 1 F).
MS m/z (relative intensity) 274 (Mϩ, 2.19), 259 (1.78), 209
(12.75), 165 (14.64), 101 (8.89), 87 (100.00). HRMS. Calcd for
C13H13ClF2O2: 274.0572, Found 274.0587.
Compound 2h: liquid, IR (film) (cmϪ1): 2989, 2895, 1614,
1519, 1466, 1250, 1180, 1037. 1H NMR (CDCl3) δ 1.55 (s, 3H),
2.03–2.11 (m, 1H), 2.85–2.93 (m, 1H), 3.79 (s, 3H), 3.92–4.06
Compound 2a: liquid, IR (film) (cmϪ1): 2893, 1679, 1504,
(m, 4H), 6.85–6.88 (m, 2 H), 7.14–7.17 (d, J = 8.7 Hz, 2 H). 19
F
1
1475, 1448, 1259, 1217, 1176, 1021, 1003. H NMR (CDCl3)
NMR (CDCl3) δ Ϫ135.0 (dd, J = 158.4, 14.7 Hz, 1 F), Ϫ137.5
(dd, J = 158.3, 13.8 Hz, 1 F). MS m/z (relative intensity) 270
(Mϩ, 1.12), 255 (1.96), 235 (1.58), 183 (3.99), 163 (6.84), 87
(100.00). HRMS. Calcd for C14H16F2O3: 270.1068, Found
270.1063.
δ 2.10–2.16 (m, 1H), 2.85–2.91 (m, 1H), 3.90–4.06 (m, 4H), 5.00
(d, J = 6.0 Hz, 1 H), 7.24–7.34 (m, 5H). 19F NMR (CDCl3)
δ Ϫ134.6 (dd, J = 163.3, 15.8 Hz, 1 F), Ϫ137.0 (dd, J = 164.4,
15.5 Hz, 1 F). MS m/z (relative intensity) 226 (Mϩ, 1.60), 207
(1.56), 183 (0.58), 164 (4.83), 153 (2.97), 133 (16.04), 77 (6.51),
73 (100.00). HRMS. Calcd for C12H12F2O2: 226.0805, Found
226.0805.
Compound 2i: pale yellow liquid, IR (film) (cmϪ1): 2988,
2891, 1522, 1466, 1410, 1378, 1328, 1278, 1244, 1221, 1172,
1039, 993. 1H NMR (CDCl3) δ 1.55 (s, 3H), 2.11 (dddd,
J = 14.7, 8.7, 1.2 Hz, 1H), 2.90 (dddd, J = 14.7, 9.0, 1.2 Hz, 1H),
3.90–4.07 (m, 4H), 7.3 (s, 4H). 19F NMR (CDCl3) δ Ϫ133.7 (dd,
J = 159.0, 14.7 Hz, 1F), Ϫ136.0 (dd, J = 157.4, 14.4 Hz, 1F). MS
m/z (relative intensity) 254 (Mϩ, 2.60), 239 (2.08), 189 (1.94),
167 (2.10), 147 (5.79), 115 (4.80), 87 (100.00). HRMS. Calcd for
C14H16F2O2: 254.1118, Found: 254.1102. Anal. Calcd for
C14H16F2O2: F, 14.94. Found: F, 15.14%.
Compound 2b: liquid, IR (film) (cmϪ1): 2894, 1683, 1500,
1400, 1260, 1176, 1093, 1004. 1H NMR (CDCl3) δ 2.05–2.14 (m,
1H), 2.81–2.97 (m, 1H), 3.90–4.06 (m, 4H), 4.46 (d, J = 8.1 Hz,
0.31 H), 4.99 (d, J = 5.7 Hz, 0.69 H), 7.17–7.39 (m, 4H). 19F
NMR (CDCl3) δ Ϫ134.6 (dd, J = 163.3, 15.8 Hz, 1 F), Ϫ137.0
(dd, J = 164.4, 15.5 Hz, 1 F). MS m/z (relative intensity) 260
(Mϩ, 0.55), 225 (1.76), 187 (3.67), 165 (17.66), 137 (10.63), 131
(50.33), 103 (25.60), 73 (100.00). HRMS. Calcd for
C12H11ClF2O2: 260.0416, Found 260.0371. Anal. Calcd for
C12H11F2O2: C, 55.29; H, 4.25; F, 14.58. Found: C, 55.49; H,
4.24; F, 14.36%.
Compound 2j: liquid, IR (film) (cmϪ1): 2990, 1620, 1468,
1
1169, 1127, 1068. H NMR (CDCl3) δ 1.55 (s, 3H), 2.15–2.23
(m, 1H), 2.95–3.03 (m, 1H), 3.92–4.09 (m, 2H), 7.34–7.60 (m,
4H). 19F NMR (CDCl3) δ Ϫ62.5 (s, 3F), Ϫ133.3 (dd, J = 161.0,
14.4 Hz, 1F), Ϫ136.7 (dd, J = 160.5, 13.5 Hz, 1F). MS m/z
(relative intensity) 308 (Mϩ, 1.68), 293 (6.87), 243 (100.00), 199
(49.54), 171 (18.43), 145 (11.73), 87 (93.49). Anal. Calcd for
C19H18F2O3: C, 68.67; H, 5.46; F, 11.43. Found: C, 68.67; H,
5.42; F, 11.61%.
Compound 2c: pale yellow liquid, IR (film) (cmϪ1): 2897,
1614, 1519, 1251, 1178, 1033. 1H NMR (CDCl3) δ 2.04–2.10 (m,
1H), 2.79–2.87 (m, 1H), 3.78 (s, 3H), 3.90–4.08 (m, 4H), 4.49
(d, J = 8.1 Hz, 0.32 H), 4.97 (d, J = 6.3 Hz, 0.68 H), 6.84–6.87
(m, 2H), 7.16–7.36 (m, 2H). 19F NMR (CDCl3) δ Ϫ122.5 (dd,
J = 165.3, 14.4 Hz, 0.32 F), Ϫ134.9 (dd, J = 159.0, 13.5 Hz, 0.68
F), Ϫ137.1 (dd, J = 163.6, 13.5 Hz, 0.68 F), Ϫ145.8 (d, J = 165.0
Hz, 0.32 F). MS m/z (relative intensity) 256 (Mϩ, 1.73), 183
(4.48), 139 (49.32), 77 (8.52), 73 (100.00). Anal. Calcd for
C13H14F2O3: C, 60.93; H, 5.51; F, 14.83. Found: C, 60.59; H,
6.02; F, 14.55%.
Compound 2k: white solid, mp 59–60 ЊC. IR (film) (cmϪ1):
2895, 1654, 1513, 1460, 1421, 1285, 1245, 1152, 1046. 1H NMR
(CDCl3) δ 2.26–2.33 (m, 1H), 3.09–3.17 (m, 1H), 3.76 (s, 3H),
3.83–4.18 (m, 4H), 6.79–6.83 (m, 2H), 7.05–7.09 (m, 2H). 19F
NMR (CDCl3) δ Ϫ133.3 (dd, J = 158.1, 14.5 Hz, 1F), 136.7 (dd,
J = 158.3, 14.3 Hz, 1F). MS m/z (relative intensity) 332 (Mϩ,
1.11), 238 (2.30), 210 (16.79), 205 (4.99), 149 (100.00), 105
(31.77), 77 (21.96). Anal. Calcd for C19H18F2O3: C, 68.67; H,
5.46; F, 11.43. Found: C, 68.67; H, 5.42; F, 11.61%.
Compound 2d: pale yellow liquid, IR (film) (cmϪ1): 2959,
2893, 1521, 1473, 1402, 1328, 1259, 1220, 1175, 1098, 1026,
1004. 1H NMR(CDCl3) δ 2.05–2.14 (m, 1H), 2.33 (s, 3H), 2.81–
2.88 (m, 1H), 3.90–4.07 (m, 4H), 4.98 (d, J = 6.0 Hz, 1H), 7.15
(s, 4H). 19F NMR (CDCl3) δ Ϫ134.3 (dd, J = 159.6 Hz, 15.2 Hz,
1F), Ϫ136.6 (dd, J = 159.3 Hz, 14.4 Hz, 1F). MS m/z (relative
intensity) 240 (Mϩ, 1.04), 225 (0.33), 167 (1.37), 147 (4.97), 73
(100.00). Anal. Calcd for C13H14F2O2: C, 64.99; H, 5.87; F,
15.82. Found: C, 65.07; H, 5.96; F, 15.84%.
Compound 2l: solid, mp 40–41 ЊC. IR (film) (cmϪ1): 2895,
1654, 1513, 1460, 1421, 1285, 1245, 1152, 1046. 1H NMR
(CDCl3) δ 2.30 (s, 3H), 2.31–2.37 (m, 1H), 3.11–3.19 (m, 1H),
3.83–4.18 (m, 4H), 7.03–7.08 (m, 4H), 7.33–7.41 (m, 3H), 7.54–
7.58 (m, 2H). 19F NMR (CDCl3) δ Ϫ132.3 (dd, J = 157.9, 14.7
Hz, 1F), Ϫ135.4 (dd, J = 158.5, 13.3 Hz, 1F). MS m/z (relative
intensity) 316 (Mϩ, 3.04), 266 (28.87), 239 (0.80), 194 (70.88),
149 (100.00), 105 (91.34), 77 (60.80). Anal. Calcd for
C19H18F2O2: C, 72.14; H, 5.74; F, 12.01. Found: C, 72.48; H,
5.92; F, 12.02%.
Compound 2e: yellow liquid, IR (film) (cmϪ1): 2964, 2897,
1686, 1623, 1584, 1525, 1476, 1413, 1329, 1262, 1169, 1127,
1
1070, 1021. H NMR(CDCl3) δ 2.12–2.22 (m, 1H), 2.89–2.97
(m, 1H), 3.83–4.10 (m, 4H), 7.35–7.60 (m, 4H). 19F NMR
(CDCl3) δ Ϫ134.1 (dd, J = 161.6 Hz, 13.0 Hz, 1F), Ϫ136.2 (dd,
J = 162.7, 13.8 Hz, 1F), Ϫ62.60 (s, 3F). MS m/z (relative inten-
sity) 294 (Mϩ, 0.55), 293 (0.61), 275 (2.23), 232 (1.78), 221
(1.73), 201 (6.48), 145 (2.24), 73 (100.00), 69 (2.03). Anal. Calcd
for C13H11F5O2: C, 53.07; H, 3.77; F, 32.29. Found: C, 52.60; H,
3.63; F, 32.53%.
Compound 2m: yellow liquid, 1H NMR (CDCl3) δ 2.33–2.41
(m, 1H), 3.15–3.23 (m, 1H), 3.81–4.18 (m, 4H), 7.15–7.66 (m,
10H). 19F NMR (CDCl3) δ Ϫ131.8 (dd, J = 159.9, 14.1 Hz, 1F),
Ϫ135.7 (dd, J = 161.9, 15.2 Hz, 1F). MS m/z (relative intensity)
302 (Mϩ, 4.70), 252 (3.29), 207 (14.47), 149 (45.39), 105
(100.00), 77 (57.90). HRMS Calcd. for C18H16F2O2: 302.1118.
Found: 302.1128.
Compound 2f: liquid, IR (film) (cmϪ1): 2989, 2891, 1670,
1609, 1504, 1446, 1327, 1221, 1039. 1H NMR (CDCl3)
δ 1.56 (s, 3H), 2.11–2.19 (m, 1H), 2.91–2.98 (m, 1H),
3.93–4.08 (m, 4H), 7.23–7.39 (m, 5H). 19F NMR (CDCl3)
δ Ϫ133.6 (dd, J = 159.3, 17.2 Hz, 1 F), Ϫ135.9 (dd, J = 162.2,
14.9 Hz, 1 F). MS m/z (relative intensity) 240 (Mϩ, 0.84), 225
(1.58), 190 (0.50), 175 (7.83), 133 (12.14), 87 (89.56), 43
1
Compound 2n: liquid. H NMR (CDCl3) δ 2.28–2.36 (m,
1H), 3.57–3.64 (m, 1H), 3.78–4.16 (m, 4H), 7.07–7.70 (m, 9H).
19F NMR (CDCl3) δ Ϫ131.9 (dd, J = 160.7, 13.8 Hz, 1F),
Ϫ135.3 (dd, J = 158.9, 13.5 Hz, 1F). MS m/z (relative
intensity) 336 (Mϩ, 5.18), 317 (0.53), 287 (16.09), 242 (11.29),
214 (40.56), 149 (100.00), 105 (94.22), 77 (35.81). Anal. Calcd
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 1 5 1 – 1 1 5 6
1154