352
M.-X. Wang et al. / Tetrahedron: Asymmetry 15 (2004) 347–354
COOH), 1692 cmꢀ1; MS (EI) m=z 198 (Mþ, 4%), 178
(100), 153 (39), 133 (66), 105 (53), 77 (38). Anal. Calcd
for C10H8F2O2: C, 60.61; H, 4.07. Found: C, 60.74; H,
4.08. HPLC analysis: Chiralpak AD, hexane–isopropa-
120.0, 110.3, 62.4, 55.5, 37.2, 36.3; IR (KBr) 2200–3240
(br, COOH), 1712 cmꢀ1; MS (EI) m=z 262 (Mþ+2, 1),
260 (Mþ, 1%), 227 (10), 226 (34), 225 (27), 224 (100), 209
(49), 189 (21), 181 (22), 179 (25), 135 (83), 115 (57), 77
(51). Anal. Calcd for C11H10Cl2O3: C, 50.60; H, 3.86.
Found: C, 50.78; H, 4.12. HPLC analysis: Chiralpak
AD, hexane–isopropanol 9:1, flow rate 0.8 mL/min,
nol 9:1, flow rate 0.8 mL/min,
¼ 8.557 min.
t
¼ 6.975 min,
ðþÞ
t
ðꢀÞ
())-(1R,3R)-2,2-Difluoro-3-phenylcyclopropanecarbonit-
D
HPLC); identical spectra data as that of racemic 1a were
t
¼ 7.263 min, t ¼ 8.754 min.
ðꢀÞ
ðþÞ
25
rile 1a: Oil; ½aꢁ ¼ )12 (c 0.675, CHCl3); ee 6% (Chiral
( )-trans-2,2-Dichloro-3-(2-methoxylphenyl)cyclopro-
25
D
obtained. HPLC analysis: Chiralpak AD, hexane–iso-
propanol 9:1, flow rate 0.4 mL/min, t ¼ 13.572 min,
panecarbonitrile 1c: Mp 81–82 °C; ½aꢁ ¼ 0; identical
spectra data as that of racemic 1c were obtained. HPLC
analysis: Chiralcel OD, hexane–isopropanol 9:1, flow
rate 0.8 mL/min, 14.242 min, 22.364 min.
ðꢀÞ
t
¼ 14.946 min.
ðþÞ
5.3.2. Enzymatic hydrolysis of racemic trans-2,2-dichloro-
3-phenylcyclopropanecarbonitrile 1b. (+)-(1R,3R)-2,2-
5.3.4. Enzymatic hydrolysis of racemic trans-2,2-dibro-
mo-3-phenylcyclopropanecarbonitrile 1d. (+)-(1R,3R)-
2,2-Dibromo-3-phenylcyclopropanecarboxamide 2d: Mp
Dichloro-3-phenylcyclopropanecarboxylic
acid
3b:
25
D
1
½aꢁ ¼ +52 (c 1.25, CHCl3); ee 72% (Chiral HPLC); H
25
NMR (300 MHz, CDCl3) d 10.15 (br s, 1H, COOH),
7.28–7.45 (m, 5H, Ar-H), 3.54 (d, 1H, J ¼ 8.4, CH), 2.93
(d, 1H, J ¼ 8.3, CH); 13C NMR (75 MHz, CDCl3) d
172.8 (COOH), 132.1, 128.7, 128.6, 128.3, 62.2, 40.9,
37.0; IR (KBr) 2400–3500 (br, COOH), 1715 cmꢀ1; MS
(EI) m=z 230 (Mþ, <2%), 194 (23%), 185 (8), 160 (34),
149 (18), 131 (22), 116 (37), 115 (100), 105 (29). Anal.
Calcd for C10H8Cl2O2: C, 51.98; H, 3.49. Found: C,
51.83; H, 3.33. HPLC analysis: Chiralpak AD, hexane–
59–161 °C; ½aꢁ ¼ +68.4 (c 0.95, CHCl3); ee 95% (Chiral
D
1
HPLC); H NMR (300 MHz, CDCl3) d 7.19–7.34 (m,
5H, Ar-H), 6.06 (br s, 2H, NH2), 3.51 (d, 1H, J ¼ 7.8,
CH), 2.79 (d, 1H, J ¼ 8.1, CH); 13C NMR (75 MHz,
CDCl3) d 167.4 (CONH2), 134.6, 129.1, 128.8, 128.4,
40.0, 38.8, 29.2; IR (KBr) 3420, 3187 (NH2), 1660 cmꢀ1
;
MS (EI) m=z 276 (Mþ)41, 2%), 237 (Mþ)HBr, 3%), 235
(2), 105 (100), 77 (68). Anal. Calcd for C10H9Br2NO:
C, 37.65; H, 2.84; N, 4.39. Found: C, 37.77; H, 2.77;
N, 4.19. HPLC analysis: Chiralcel OD, hexane–isopro-
isopropanol 9:1, flow rate 0.8 mL/min, t ¼ 14.433 min,
ðþÞ
t
¼ 7.942 min.
panol 9:1, flow rate 0.8 mL/min, t ¼ 21.585 min,
ðꢀÞ
ðþÞ
t
¼ 19.214 min.
ðꢀÞ
())-(1S,3S)-2,2-Dichloro-3-phenylcyclopropanecarbonit-
25
rile 1b: Oil; ½aꢁ ¼ )3.4 (c 3.8, CHCl3); ee 29% (Chiral
())-(1S,3S)-2,2-Dibromo-3-phenylcyclopropanecarbonit-
D
HPLC); identical spectra data as that of racemic 1b were
25
rile 1d: Oil; ½aꢁ ¼ )27 (c 1.0, CHCl3); ee 72% (Chiral
D
HPLC); identical spectra data as that of racemic 1d were
obtained. HPLC analysis: Chiralcel OJ, hexane–iso-
propanol 9:1, flow rate 0.8 mL/min, t ¼ 18.262 min,
obtained. HPLC analysis: Chiralcel OJ, hexane–iso-
propanol 9:1, flow rate 0.8 mL/min, t ¼ 18.931 min,
ðþÞ
t
¼ 12.841 min.
ðꢀÞ
ðꢀÞ
t
¼ 32.626 min.
ðþÞ
5.3.3. Enzymatic hydrolysis of racemic trans-2,2-dichloro-
3-(2-methoxylphenyl)cyclopropanecarbonitrile 1c. (+)-
(1R,3R)-2,2-Dichloro-3-(2-methoxylphenyl)cyclopro-
5.3.5. Enzymatic hydrolysis of racemic trans-2,2-difluoro-
3-phenylcyclopropanecarboxamide 2a. ())-(1R,3R)-2,2-
Difluoro-3-phenylcyclopropanecarboxamide 2a: 15 min
25
panecarboxamide 2c: Mp 137–139 °C; ½aꢁ ¼ +23.5 (c
D
25
0.85, CHCl3); ee 60% (Chiral HPLC); 1H NMR
(300 MHz, CDCl3) d 6.85–7.25 (m, 5H, Ar-H), 6.10 (br
s, 2H, NH2), 3.83 (s, 3H, OCH3), 3.43 (d, 1H, J ¼ 8.5,
CH), 2.61 (d, 1H, J ¼ 8.6, CH); 13C NMR (75 MHz,
CDCl3) d 167.2 (CONH2), 158.9, 129.3, 128.3, 121.8,
120.0, 110.4, 62.1, 55.6, 37.7, 35.5; IR (KBr) 3437, 3156
(NH2), 1685 cmꢀ1; MS (EI) m=z 261 (Mþ+2, 1), 259
(Mþ, 1%), 241 (1), 221 (14), 206 (11), 181 (35), 135 (100),
77 (50). Anal. Calcd for C11H11Cl2NO2: C, 50.79; H,
4.26; N, 5.38. Found: C, 50.87; H, 4.16; N, 5.20. HPLC
analysis: Chiralcel OJ, hexane–isopropanol 9:1, flow
rate 0.8 mL/min, t ¼ 18.684 min, t ¼ 24.548 min.
(46% yield), mp 131–132 °C; ½aꢁ ¼ )112 (c 1.0, CHCl3);
D
ee > 99% (Chiral HPLC).
(+)-(1S,3S)-2,2-Difluoro-3-phenylcyclopropanecarboxy-
lic acid 3a: 15 min (51% yield), mp 105–107 °C;
25
½aꢁ ¼ +110 (c 1.5, CHCl3); ee 87% (Chiral HPLC).
D
5.3.6. Enzymatic hydrolysis of racemic trans-2,2-dichloro-
3-phenylcyclopropanecarboxamide 2b. (+)-(1R,3R)-2,2-
Dichloro-3-phenylcyclopropanecarboxamide 2b: 8 h (49%
25
yield), mp 152–153 °C; ½aꢁ ¼ +73 (c 1.0, CHCl3);
ðþÞ
ðꢀÞ
D
ee > 99% (Chiral HPLC); 1H NMR (300 MHz, CDCl3) d
7.26–7.40 (m, 5H, Ar-H), 6.08 (br s, 2H, NH2), 3.52 (d,
1H, J ¼ 8.2, CH), 2.74 (d, 1H, J ¼ 8.2, CH); 13C NMR
(75 MHz, CDCl3) d 166.7 (CONH2), 132.7, 128.7, 128.4,
128.0, 61.7, 39.1, 38.2; IR (KBr) 3476, 3206 (NH2),
1642 cmꢀ1; MS (EI) m=z 230 (Mþ, <2%), 212 (<1%), 188
(32), 187 (19), 186 (50), 153 (27), 151 (100), 149 (50), 115
(95), 105 (24). Anal. Calcd for C10H9Cl2NO: C, 52.20;
())-(1S,3S)-2,2-Dichloro-3-(2-methoxylphenyl)cyclo-
25
propanecarboxylic acid 3c: Mp 108–110 °C; ½aꢁ ¼ )30 (c
0.6, CHCl3); ee 93% (Chiral HPLC); 1DH NMR
(300 MHz, CDCl3) d 10.10 (br s, 1H, COOH), 6.99–7.41
(m, 5H, Ar-H), 3.99 (s, 3H, CH3), 3.59 (d, 1H, J ¼ 8.7,
CH), 2.90 (d, 1H, J ¼ 8.4, CH); 13C NMR (75 MHz,
CDCl3) d 172.6 (COOH), 158.7, 129.4, 128.2, 121.1,