P. Langer et al.
FULL PAPER
colourless, viscous oil. H NMR (300 MHz, CDCl3): δ = 2.20 (br.
1
(0.310 g, 1.6 mmol) in CH2Cl2 (3 mL) and silyl enol ether 3j
(0.454 g, 1.5 mmol), 5ad was isolated (0.135 g, 31%) by column
chromatography (silica gel, n-heptane/EtOAc = 30:1Ǟ20:1) as a
reddish solid (m.p. 119–121 °C). 1H NMR (300 MHz, CDCl3): δ =
2.25 (br. s, 3 H, CH3), 3.01 (s, 3 H, COOCH3), 6.88 (dd, 3J =
6.6 Hz, 4J = 0.7 Hz, 1 H, CHNaph), 7.17 (dd, 3J = 7.0 Hz, 4J =
4
s, 3 H, CH3), 3.38 (s, 3 H, COOCH3), 6.77 (d, JH,F = 6.4 Hz, 1
H, CHAr), 6.96–7.01 (m, 2 H, CHFPh), 7.04–7.09 (m, 2 H, CHFPh),
10.57 (s, 1 H, OH) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.3 (d,
3J = 3.9 Hz, CH3), 50.8 (COOCH3), 109.0 (d, 3J = 1.7 Hz, CAr
-
COOCH3), 113.6 (d, 2J = 21.9 Hz, 2CHFPh), 118.1 (d, 3J = 4.4 Hz,
CHAr), 127.5 (d, 2J = 19.2 Hz, CCFAr), 129.4 (d, 4J = 1.7 Hz, 1.3 Hz, 1 H, CHNaph), 7.29–7.32 (m, 1 H, CHNaph), 7.35 (m, 1 H,
CHFPh), 129.6 (d, 4J = 1.1 Hz, CHFPh), 130.5 (d, 3J = 3.4 Hz, CHAr), 7.37–7.39 (m, 1 H, CHNaph), 7.41–7.44 (m, 1 H, CHNaph),
CFPh), 132.4 (d, 2J = 21.5 Hz, CArCH3), 150.7 (d, 1J = 233.8 Hz,
7.76–7.81 (m, 2 H, CHNaph), 10.82 (s, 1 H, OH) ppm. 13C NMR
CFAr), 156.6 (d, 4J = 1.7 Hz, COHAr), 161.1 (d, 1J = 244.3 Hz, (75 MHz, CDCl3): δ = 14.5 (d, 3J = 3.5 Hz, CH3), 50.6 (COOCH3),
CFFPh), 169.6 (d, 4J = 2.9 Hz, COOCH3) ppm. 19F NMR 109.7 (d, 3J = 2.3 Hz, CArCOOCH3), 118.4 (d, 3J = 3.5 Hz, CHAr),
(235 MHz, CDCl3): δ = –127.5 (CFAr), –115.5 (CFFPh) ppm. GC-
123.9, 124.1, 124.5, 125.0, 125.1, 126.6 (CHNaph), 126.7 (d, 2J =
15.7 Hz, CCFAr), 127.1 (CHNaph), 131.1, 132.1, 132.5 (CNaph),
MS (EI, 70 eV): m/z (%) = 278 (32) [M+], 246 (100), 218 (41), 201
(3), 189 (16), 170 (8), 151 (3), 133 (2), 85 (4). HRMS (EI): calcd. 132.7 (d, 2J = 12.2 Hz, FCCCH3,Ar), 151.1 (d, 1J = 233.8 Hz,
for C15H12F2O3 278.07490; found 278.07532.
CFAr), 156.9 (d, 4J = 2.3 Hz, COHAr), 169.6 (d, 4J = 2.9 Hz,
COOCH3) ppm. 19F NMR (235 MHz, CDCl3): δ = –125.6 (CFAr
)
Methyl 4Ј,6-Difluoro-3-hydroxy-4,5-dimethylbiphenyl-2-carboxylate
(5ab): Starting with bis(silyl enol ether) 4f (0.448 g, 1.6 mmol),
TiCl4 (0.310 g, 1.6 mmol) in CH2Cl2 (3 mL) and silyl enol ether 3i
(0.405 g, 1.5 mmol), 5ab was isolated (0.177 g, 40%) by column
chromatography (silica gel, n-heptane/EtOAc = 30:1Ǟ20:1) as a
ppm. IR (Nujol): ν = 1665 (m), 1463 (s), 1376 (s), 1335 (m), 1225
˜
(m), 1080 (w), 953 (w), 789 (m), 551 (w) cm–1. GC-MS (EI, 70 eV):
m/z (%) = 310 (38) [M+], 278 (100), 249 (18), 233 (8), 220 (15), 155
(3), 110 (10). HRMS (EI): calcd. for C19H15FO3 310.09997; found
310.10006.
1
colourless, viscous oil. H NMR (300 MHz, CDCl3): δ = 2.11 (br.
s, 6 H, CH3), 3.32 (s, 3 H, COOCH3), 6.92–6.96 (m, 2 H, CHFPh),
6.99–7.03 (m, 2 H, CHFPh), 10.86 (s, 1 H, OH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 12.2 (d, 4J = 2.3 Hz, CH3), 12.5 (d, 3J =
Methyl 3-Fluoro-6-hydroxy-4,5-dimethyl-2-(1-naphthyl)benzoate
(5ae): Starting with bis(silyl enol ether) 4f (0.448 g, 1.6 mmol),
TiCl4 (0.310 g, 1.6 mmol) in CH2Cl2 (3 mL) and silyl enol ether
3j (0.454 g, 1.5 mmol), 5ae was isolated (0.180 g, 37%) by column
chromatography (silica gel, n-heptane/EtOAc = 30:1Ǟ20:1) as a
reddish solid (m.p. 88–91 °C). 1H NMR (300 MHz, CDCl3): δ =
2.12 (br. s, 3 H, CH3), 2.17 (br. s, 3 H, CH3), 2.92 (s, 3 H,
COOCH3), 7.10 (dd, 3J = 7.0 Hz, 4J = 1.1 Hz, 1 H, CHNaph), 7.19–
7.19 (m, 1 H, CHNaph), 7.30–7.32 (m, 2 H, CHNaph), 7.66–7.72 (m,
3 H, CHNaph), 11.15 (s, 1 H, OHAr) ppm. 13C NMR (75 MHz,
CDCl3): δ = 13.1 (d, 4J = 2.3 Hz, CH3), 13.4 (d, 3J = 5.8 Hz,
CCH3), 52.8 (COOCH3), 111.0 (d, 3J = 2.9 Hz, CCOOCH3Ar),
125.7 (d, 2J = 21.5 Hz, CCFAr), 126.2, 126.4, 126.7, 127.1
(CHNaph), 127.5 (d, 4J = 1.1 Hz, CHNaph), 127.9 (d, 3J = 3.4 Hz,
5.7 Hz, CCH3), 52.1 (COOCH3), 109.5 (d, 3J = 2.5 Hz, CAr
-
COOCH3), 114.9 (d, 2J = 21.4 Hz, 2 CHFPh), 125.7 (d, 2J =
20.4 Hz, CCFAr), 126.9 (d, 3J = 3.6 Hz, CFPh), 131.0 (d, 4J =
1.8 Hz, CHFPh), 131.1 (d, 4J = 1.2 Hz, CHFPh), 132.0 (d, 2J =
3
1
19.5 Hz, CArCH3), 132.4 (d, J = 3.5 Hz, CArCH3), 151.8 (d, J =
231.9 Hz, CFAr), 155.8 (d, 4J = 1.8 Hz, COHAr), 162.5 (d, 1J =
244.1 Hz, CFFPh), 171.6 (d, 4J = 3.1 Hz, COOCH3) ppm. 19F NMR
(235 MHz, CDCl3): δ = –126.5 (CFAr), –115.5 (CFFPh) ppm. IR
(KBr): ν = 2926 (m), 2875 (w), 1665 (s), 1616 (w), 1515 (s), 1440
˜
(s), 1334 (s), 1259 (m), 1219 (s), 1174 (m), 1096 (m), 1015 (m), 833
(m), 805 (m), 586 (m) cm–1. GC-MS (EI, 70 eV): m/z (%) = 292
(64) [M+], 260 (100), 245 (81), 231 (9), 217 (43), 183 (17), 170 (5),
151 (3). HRMS (EI): calcd. for C16H14F2O3 292.09055; found
292.09034.
2
CArCH3), 128.6, 129.3 (CHNaph), 133.1 (d, J = 19.8 Hz, CArCH3),
133.5, 134.4, 135.3 (CHNaph), 152.9 (d, 1J = 231.5 Hz, CFAr), 155.5
(d, 4J = 1.7 Hz, COHAr), 172.4 (d, 4J = 2.9 Hz, COOCH3) ppm.
19F NMR (235 MHz, CDCl3): δ = –124.0 (CF) ppm. IR (Nujol):
Ethyl 4-Ethyl-4Ј,6-difluoro-3-hydroxy-5-methylbiphenyl-2-carboxyl-
ate (5ac): Starting with bis(silyl enol ether) 4g (0.495 g, 1.6 mmol),
TiCl4 (0.310 g, 1.6 mmol) in CH2Cl2 (3 mL) and silyl enol ether
3i (0.405 g, 1.5 mmol), 5ac was isolated (0.170 g, 35%) by column
chromatography (silica gel, n-heptane/EtOAc = 30:1Ǟ20:1) as a
colourless, viscous oil. 1H NMR (300 MHz, CDCl3): δ = 0.69 (t,
3J = 7.2 Hz, 3 H, CH2CH3), 1.09 (t, 3J = 7.4 Hz, 3 H, CO-
OCH2CH3), 2.19 (br. s, 3 H, CH3), 2.69 (q, 3J = 7.4 Hz, 2 H,
CH2CH3), 3.88 (q, 3J = 7.0 Hz, 2 H, COOCH2CH3), 6.95–7.02 (m,
2 H, CHFPh), 7.04–7.11 (m, 2 H, CHFPh), 11.00 (s, 1 H, OH) ppm.
ν = 1664 (s), 1457 (s), 1377 (s), 1339 (s), 1260 (s), 1226 (s), 1098
˜
(m), 924 (w), 779 (s), 432 (w) cm–1. GC-MS (EI, 70 eV): m/z (%) =
324 (36) [M+], 292 (100), 277 (18), 249 (10), 233 (8), 220 (17), 162
(4), 110 (8). HRMS (EI): calcd. for C20H17FO3 324.11562; found
324.11546.
Ethyl 3-Ethyl-5-fluoro-2-hydroxy-4-methyl-6-(1-naphthyl)benzoate
(5af): Starting with bis(silyl enol ether) 4g (0.495 g, 1.6 mmol),
TiCl4 (0.310 g, 1.6 mmol) in CH2Cl2 (3 mL) and silyl enol ether
3j (0.454 g, 1.5 mmol), 5af was isolated (0.223 g, 42%) by column
chromatography (silica gel, n-heptane/EtOAc = 30:1Ǟ20:1) as a
reddish solid (m.p. 68–72 °C). 1H NMR (300 MHz, CDCl3): δ =
0.80 (t, 3J = 7.4 Hz, 3 H, CH2CH3), 1.16 (t, 3J = 7.5 Hz, 3 H,
COOCH2CH3), 2.56 (br. s, 3 H, CH3,Ar), 2.68 (q, 3J = 7.6 Hz, 2 H,
CH2CH3), 3.58 (q, 3J = 7.3 Hz, 2 H, COOCH2CH3), 7.11 (m, 1 H,
CHNaph), 7.21–7.26 (m, 4 H, CHNaph), 7.68–7.76 (m, 2 H, CHNaph),
11.10 (s, 1 H, OHAr) ppm. 13C NMR (75 MHz, CDCl3): δ = 11.9
(d, 3J = 5.6 Hz, CH3,Ar), 12.6 (CH2CH3,Ar), 13.5 (COOCH2-
CH3,Ar), 20.1 (d, 4J = 1.6 Hz, CH2CH3,Ar), 61.1 (COOCH2CH3,Ar),
3
13C NMR (75 MHz, CDCl3): δ = 11.8 (d, J = 2.3 Hz, CH3), 13.4
(CH2CH3), 13.5 (COOCH2CH3), 20.0 (d, 4J = 2.3 Hz, CH2CH3),
3
61.4 (COOCH2CH3), 109.8 (d, J = 1.7 Hz, CArCOOCH2CH3),
2
2
114.7, 115.7 (CHFPh), 125.9 (d, J = 20.4 Hz, CCFAr), 131.0 (d, J
= 1.1 Hz, CHFPh), 131.1 (d, 2J = 2.3 Hz, CHFPh), 131.3 (d, 2J =
20.4 Hz, CCFAr), 132.7 (d, 3J = 3.5 Hz, CFPh), 132.8 (d, 3J =
1
4
2.9 Hz, CCH2CHAr), 151.9 (d, J = 232.7 Hz, CFAr), 156.2 (d, J
1
4
= 1.7 Hz, COHAr), 162.5 (d, J = 243.7 Hz, CFFPh), 171.2 (d, J =
3.5 Hz, COOCH3) ppm. 19F NMR (235 MHz, CDCl3): δ = –126.1
(CFAr), –115.9 (CFFPh) ppm. GC-MS (EI, 70 eV): m/z (%) = 320
(64) [M+], 274 (88), 256 (100), 231 (34), 201 (24), 183 (23), 170 (6),
151 (4), 133 (3). HRMS (EI): calcd. for C18H18F2O3 320.17071;
found 320.12229.
3
2
110.4 (d, J = 2.3 Hz, CArCOOCH2CH3), 125.0 (d, J = 21.5 Hz,
CCFAr), 125.4 (d, 4J = 1.1 Hz, CHNaph), 125.8, 125.9, 126.2, 126.6,
2
127.7, 128.4 (CHNaph), 131.5 (d, J = 19.2 Hz, CArCH3), 132.9 (d,
3J = 2.9 Hz, CArCH2CH3), 133.1, 133.6 (CNaph), 134.8 (d, 4J =
Methyl 3-Fluoro-6-hydroxy-4-methyl-2-(1-naphthyl)benzoate (5ad): 1.1 Hz, CCH3Ar), 152.3 (d, 1J = 231.5 Hz, CFAr), 156.6 (d, 4J =
Starting with bis(silyl enol ether) 4a (0.426 g, 1.6 mmol), TiCl4
1.7 Hz, COHAr), 171.1 (d, 4J = 3.5 Hz, COOCH3,Ar) ppm. 19F
514
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Eur. J. Org. Chem. 2008, 503–518