1402
T. C. Rosen, G. Haufe / Tetrahedron: Asymmetry 13 (2002) 1397–1405
added to a suspension of LiAlH4 (0.11 g, 2.8 mmol)
in anhydrous diethyl ether (10 mL). The reaction
mixture was heated under reflux for 2 h and then
quenched with water. The resulting precipitate was
dissolved by adding sulfuric acid. The aqueous phase
was extracted with diethyl ether. The combined
organic layer was dried (Na2SO4) and concentrated.
( )-5 (0.60 g, 96%) was obtained as a colorless oil
which was further purified by column chromatogra-
phy (silica gel, pentane/diethyl ether 2:1). 1H NMR
(600 MHz):† d 1.15 (1H, dd, J=7.1; 9.5, CHBHA),
1.48 (1H, ddd, J=7.1; 11.0; 19.0, CHAHB), 1.67 (1H,
s, OH), 1.98 (1H, ddd, J=7.3; 8.3; 19.8, CH), 3.20
(1H, dd, J=8.3; 11.8, CH2OH), 3.33 (1H, ddd, J=
2.6; 7.3; 11.8, CH2OH), 7.30–7.50 (5H, m, Ph.). 13C
NMR: d 13.5 (J=11.4, CH2), 26.6 (J=14.0, CH),
61.2 (CH2OH), 82.2 (J=213.6, C-F), 128.0 (J=5.1,
Ph-CH), 128.6 (Ph-CH), 128.9 (J=3.8, Ph-CH),
134.8 (J=20.4, Ph-C). 19F NMR (564.3 MHz): d
−159.3 (m). GC/MS: m/z 148 (5), 135 (100), 133 (20),
125 (45), 122 (30), 115 (52), 109 (14), 77 (7), 63 (8),
51 (9), 39 (7). IR (film): 3601, 3553–3133, 3071, 3036,
2940, 2885, 1612, 1508, 1460, 1405, 1336, 1247, 1199,
1109, 1070, 1040, 889, 813, 772, 703 cm−1. Anal.
calcd for C10H11FO: C, 72.27; H, 6.67. Found: C,
71.84; H, 7.17%.
organic layer was dried (MgSO4) and concentrated.
The acetate ( )-7a (177 mg, 85%) was obtained after
column chromatography (silica gel, cyclohexane/ethyl
1
acetate 10:1) as a colorless oil. H NMR: d 1.21 (1H,
ddd, J=7.4; 7.4; 9.5, CHAHB), 1.55 (1H, ddd, J=7.4;
11.2; 19.1, CHAHB), 1.97 (3H, s, CH3), 2.00–2.10
(1H, m, CH), 3.63 (1H, dd, J=8.1; 11.9, CH2O), 3.76
(1H, ddd, J=2.2; 7.5; 11.9, CH2O), 7.35–7.43 (5H, m,
Ph). 13C NMR: d 14.0 (J=12.7, CH2), 20.6 (CH3),
22.9 (J=15.2, CH), 63.3 (CH2O), 82.1 (J=214.9, C-
F), 128.3 (J=3.8, Ph-CH), 128.5 (Ph-CH), 129.0 (Ph-
CH), 134.3 (J=20.3, Ph-C), 170.7 (CO2CH3). 19F
NMR: d −159.93 (ddd, J=9.5; 19.1; 19.1). GC/MS:
m/z 208 (2), 165 (2), 148 (86), 135 (15), 133 (28), 125
(11), 122 (29), 115 (21), 105 (29), 77 (8), 43 (100), 39
(5). IR (film): 2960, 1743, 1609, 1507, 1459, 1373,
1333, 1239, 1200, 1113, 1037, 998, 967, 906, 867, 768,
698, 475, 459, 445 cm−1. Anal. calcd for C12H13FO2:
C, 69.22; H, 6.29. Found: C, 68.91; H, 6.19%.
4.5. Preparation of trans-( )-(2-fluoro-2-phenylcyclo-
propyl)methyl acetate, ( )-6a
Analogous to the procedure described above ( )-6a
(184 mg, 88%) was synthesized using the correspond-
ing trans-alcohol ( )-4. 1H NMR: d 1.31–1.42 (2H,
m, CHAHB), 1.62–1.74 (1H, m, CH), 2.07 (3H, s,
CH3), 4.20 (1H, ddd, J=1.2; 8.3; 11.7, CH2O), 4.47
(1H, ddd, J=1.4; 6.5; 11.7, CH2O), 7.24–7.38 (5H, m,
Ph). 13C NMR: d 17.9 (J=12.7, CH2), 20.9 (CH3),
24.3 (J=11.4, CH), 62.7 (J=10.7, CH2O), 80.8 (J=
218.7, C-F), 124.5 (J=6.4, Ph-CH), 127.7 (Ph-CH),
128.5 (Ph-CH), 138.8 (J=20.3, Ph-C), 171.0
(CO2CH3). 19F NMR: d −192.28 (m). GC/MS: m/z
208 (1), 165 (2), 148 (100), 135 (16), 133 (33), 122
(33), 115 (22), 105 (32), 77 (9), 43 (100), 39 (6). IR
(film): 1741, 1607, 1501, 1453, 1375, 1236, 1036, 758,
700, 453 cm−1. Anal. calcd for C12H13FO2: C, 69.22;
H, 6.29. Found: C, 69.09; H, 6.44%.
4.3. Preparation of trans-( )-(2-fluoro-2-phenylcyclo-
propyl)methanol, ( )-4
Analogous to the procedure described above, ( )-4
(0.61 g, 98%) was synthesized using the corresponding
trans-ester ( )-3. 1H NMR (600 MHz):† d 1.17–1.39
(2H, m, CHAHB), 1.60–1.71 (1H, m, CH), 1.92 (1H,
s, OH), 3.80 (1H, dd, J=5.7; 11.5, CH2OH), 4.02
(1H, dd, J=8.4; 11.5, CH2OH), 7.24–7.35 (5H, m,
Ph). 13C NMR: d 17.8 (J=12.7, CH2), 28.0 (J=12.7,
CH), 61.5 (J=7.6, CH2OH), 81.5 (J=216.2, C-F),
124.4 (J=5.1, Ph-CH), 127.6 (Ph-CH), 128.9 (Ph-
CH), 139.2 (J=20.3, Ph-C). 19F NMR (564.3 MHz):
d −193.6 (m). GC/MS: m/z 166 (2), 148 (9), 136 (41),
135 (100), 133 (40), 125 (89), 122 (57), 115 (90), 109
(23), 96 (14), 77 (12), 63 (10), 51 (13), 39 (12). IR
(film): 3553–3108, 3068, 3036, 2938, 2886, 1610, 1503,
1461, 1409, 1301, 1241, 1148, 1120, 1075, 1036, 892,
881, 760, 698 cm−1. Anal. calcd for C10H11FO: C,
72.27; H, 6.67. Found: C, 71.82; H, 6.62%.
4.6. Preparation of cis-( )-(2-fluoro-2-phenylcyclo-
propyl)methyl propionate, ( )-7c
Analogous to the procedure described for the synthe-
sis of ( )-7a cis-( )-(2-fluoro-2-phenylcyclopropyl)-
methyl propionate (( )-7c) (180 mg, 80%) was
prepared using propionyl chloride. 1H NMR: d 1.08
(3H, t, J=7.6, CH3), 1.21 (1H, ddd, J=7.2; 7.2; 9.5
Hz, CHAHB), 1.57 (1H, ddd, J=7.2; 11.2; 19.1 Hz,
1H, CHAHB), 1.95–2.13 (1H, m, CH), 2.25 (2H, q,
J=7.6, OꢁCCH2), 3.61 (1H, dd, J=8.3; 11.9, CH2O),
3.81 (1H, ddd, J=2.4; 7.4; 11.9, CH2O), 7.33–7.47
(5H, m, Ph). 13C NMR: d 9.0 (CH3), 13.9 (J=12.7,
CH2), 22.9 (J=15.3, CH), 27.4 (OꢁCCH2), 63.1
(CH2O), 82.0 (J=214.9, C-F), 128.3 (J=3.8, Ph-CH),
128.4 (Ph-CH), 129.2 (J=2.5, Ph-CH), 134.2 (J=
20.3, Ph-C), 174.1 (CO2CH2). 19F NMR: d −160.00
(ddd, J=9.5; 19.1; 19.1). GC/MS: m/z 222 (1), 164
(3), 148 (100), 135 (9), 133 (26), 122 (25), 115 (12),
105 (26), 77 (4), 57 (59), 51 (2), 39 (2). IR (film):
3093, 3066, 3033, 2983, 2947, 2890, 1739, 1455,
4.4. Preparation of cis-( )-(2-fluoro-2-phenylcyclo-
propyl)methyl acetate, ( )-7a
Acetyl chloride (200 mg, 2.0 mol) in anhyd. diethyl
ether (1 mL) was slowly added to an ice-cold solution
of ( )-5 (166 mg, 1 mmol) and triethyl amine (200
mg, 2.5 mmol) in anhyd. diethyl ether (5 mL). After
45 min at 0°C the solution was stirred for an addi-
tional 6–7 h at room temperature. The reaction mix-
ture was then poured into water, and the aqueous
phase was extracted with diethyl ether. The combined
† Not all 1H,1H-coupling constants could be determined.