12174 J. Am. Chem. Soc., Vol. 123, No. 49, 2001
Charette et al.
(m, 1H), 1.15 (dd, J ) 9, 5 Hz, 1H), 0.61 (t, J ) 5 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 147.5, 128.2, 127.1, 125.7, 63.4, 27.7, 24.7, 20.4,
18.6; HRMS calcd for C11H14O1 (M) 162.1045, found 162.1033. The
enantiomeric ratio was determined by GC of the TFAA derivative
(cyclodex-G-TA, 100 °C, 0.32 mm × 30 m, 25 psi) Tr(minor) 10.8
min, Tr(major) 11.2 min (er 94:6).
the desired cyclopropylmethanol (160 mg, 90%): mp 47-49 °C; Rf
0.24 (30% EtOAc/Hexanes); [R]D +71.9 (c 1.2, CHCl3); 1H NMR (400
MHz, CDCl3) δ 7.03-6.99 (m, 2H), 6.83-6.79 (m, 2H), 3.78 (s, 3H),
3.64 (dd, J ) 11, 7 Hz, 1H), 3.59 (dd, J ) 11, 7 Hz, 1H), 1.47 (s (br),
1H), 1.49-1.35 (m, 1H), 0.93-0.85 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 157.6, 134.2, 126.8, 113.7, 66.6, 55.2, 24.6, 20.4, 13.2; HRMS
calcd for C11H14O2 (M) 178.0994, found 178.0999. The enantiomeric
ratio was determined by GC of the TFAA derivative (cyclodex-G-TA,
117 °C, 0.32 mm × 30 m, 25 psi) Tr(minor) 25.3 min, Tr(major) 26.2
min (er 96:4).
(+)-(1S,2S)-1-Methyl-2-phenylcyclopropylmethanol (entry 5, Table
4). The cyclopropanation of (E)-2-methyl-3-phenyl-2-propenol (148 mg,
1.00 mmol) was performed according to the previously described
procedure (reaction time 3 h). The residue was purified by flash
chromatography on silica gel (30% EtOAc/Hexanes) to produce the
desired cyclopropylmethanol (130 mg, 80%): Rf 0.14 (20% EtOAc/
(+)-(1S,2S)-2-(p-Chlorophenyl)cyclopropylmethanol (entry 10,
Table 4). The cyclopropanation of (E)-3-(p-chlorophenyl)-2-propenol
(141 mg, 0.836 mmol) was performed according to the previously
described procedure (reaction time 1.5 h). The residue was purified by
flash chromatography on silica gel (35% EtOAc/Hexanes) to produce
the desired cyclopropylmethanol (86 mg, 56%): Rf 0.21 (30% EtOAc/
1
Hexanes); [R]D +13.9 (c 1.8, CHCl3); H NMR (400 MHz, CDCl3) δ
7.31-7.26 (m, 2H), 7.22-7.17 (m, 3H), 3.57 (d, J ) 11 Hz, 1H), 3.53
(d, J ) 11 Hz, 1H), 2.06 (dd, J ) 9, 6 Hz, 1H), 1.57 (s (br), 1H), 0.94
(dd, J ) 9, 5 Hz, 1H), 0.89 (s, 3H), 0.87 (t, J ) 5 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ 138.7, 129.0, 127.9, 125.8, 71.6, 26.6, 25.0, 15.6,
15.0; HRMS calcd for C11H14O1 (M) 162.1045, found 162.1047. The
enantiomeric ratio was determined by GC of TFAA derivative
(cyclodex-G-TA, 110 °C, 0.32 mm × 30 m, 25 psi) Tr(minor) 8.6 min,
Tr(major) 8.8 min (er 75:25).
1
Hexanes); [R]D +69.8 (c 3.4, CHCl3); H NMR (400 MHz, CDCl3) δ
7.25-7.21 (m, 2H), 7.03-6.98 (m, 2H), 3.63 (d, J ) 7 Hz, 2H), 1.84-
1.78 (m, 1H), 1.51 (s (br), 1H), 1.48-1.37 (m, 1H), 0.99-0.90 (m,
2H); 13C NMR (100 MHz, CDCl3) δ 141.0, 131.1, 128.3, 127.1, 66.1,
25.2, 20.7, 13.8; HRMS calcd for C10H11O1Cl1 (M) 182.0498, found
182.0501. The enantiomeric ratio was determined by HPLC (chiralcel-
OD: 2% iPrOH/Hexanes) Tr(major) 20.9 min, Tr(minor) 23.3 min (er
91:9).
(+)-(1S,2S)-2-(3,5-Dimethylphenyl)cyclopropylmethanol (entry 6,
Table 4). The cyclopropanation of (E)-3-(3,5-dimethylphenyl)-2-
propenol (162 mg, 0.996 mmol) was performed according to the
previously described procedure (reaction time 1.5 h). The residue was
purified by flash chromatography on silica gel (25% EtOAc/Hexanes)
to produce the desired cyclopropylmethanol (151 mg, 86%): Rf 0.20
(+)-(1S,2S)-2-(para-Chlorophenyl)cyclopropylmethanol (entry 11,
Table 4). The cyclopropanation of (E)-3-(p-chlorophenyl)-2-propenol
(135 mg, 0.801 mmol) was performed according to the previously
described procedure (reaction time 3 h). The residue was purified by
flash chromatography on silica gel (35% EtOAc/Hexanes) to produce
the desired cyclopropylmethanol (118 mg, 81%): [R]D +72.4 (c 3.0,
CHCl3). The enantiomeric ratio was determined by HPLC (chiralcel-
OD: 2% iPrOH/Hexanes) Tr(major) 20.9 min, Tr(minor) 23.3 min (er
91:9).
(+)-(1S,2S)-2-Propylcyclopropylmethanol (entry 12, Table 4). The
cyclopropanation of (E)-2-hexenol (99 mg, 0.992 mmol) was performed
according to the previously described procedure (reaction time 3 h).
The residue was purified by flash chromatography on silica gel (25%
EtOAc/Hexanes) to produce the desired cyclopropylmethanol (77 mg,
68%): Rf 0.18 (20% EtOAc/Hexanes); [R]D +25.6 (c 3.2, CHCl3); 1H
NMR (300 MHz, CDCl3) δ 3.50-3.39 (m, 2H), 1.44-1.35 (m, 2H),
1.30-1.20 (m, 3H), 0.92 (t, J ) 7 Hz, 3H), 0.90-0.80 (m, 1H), 0.68-
0.58 (m, 1H), 0.40-0.29 (m, 2H); 13C NMR (100 MHz, CDCl3) δ
66.9, 35.8, 22.5, 19.9, 16.7, 13.8, 9.6. The enantiomeric ratio was
determined by 19F NMR of the Mosher ester derivative: -73.15 ppm
(major), -73.19 ppm (minor) (er 87:13).
(+)-(1S,2R)-2-Propylcyclopropylmethanol (entry 13, Table 4).
The cyclopropanation of (Z)-hexenol (76 mg, 0.759 mmol) was
performed according to the previously described procedure (reaction
time 3 h). The residue was purified by flash chromatography on silica
gel (25% EtOAc/Hexanes) to produce the desired cyclopropylmethanol
(75 mg, 87%): Rf 0.25 (20% EtOAc/Hexanes); [R]D +17.0 (c 2.0,
CHCl3);1H NMR (400 MHz, CDCl3) δ 3.66 (dd, J ) 11, 7 Hz, 1H),
3.58 (dd, J ) 11, 8 Hz, 1H), 1.49-1.37 (m, 3H), 1.32-1.18 (m, 2H),
1.15-1.05 (m, 1H), 0.94 (t, J ) 7 Hz, 3H), 0.98-0.83 (m, 1H), 0.71
(td, J ) 8, 5 Hz, 1H), -0.03 (dd, J ) 10, 5 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 63.3, 30.6, 23.1, 18.0, 15.8, 13.9, 9.3; HRMS calcd
for C7H14O1 (M) 114.1045, found 114.1038. The enantiomeric ratio
was estimated by 1H NMR of Mosher ester derivative: 4.44 ppm
(major), 4.49 ppm (minor) (er 74:26).
1
(20% EtOAc/Hexanes); [R]D +67.6 (c 0.94, CHCl3); H NMR (300
MHz, CDCl3) δ 6.82 (s, 1H), 6.71 (s, 2H), 3.63 (d, J ) 2 Hz, 1H),
3.61 (d, J ) 2 Hz, 1H), 2.30 (s, 6H), 1.80-1.74 (m, 1H), 1.76 (s (br),
1H), 1.50-1.42 (m, 1H), 1.00-0.88 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 142.2, 137.8, 127.3, 123.6, 66.6, 25.0, 21.2, 21.17, 21.06,
13.5; HRMS calcd for C12H17O1 (M + H) 177.1279, found 177.1275.
The enantiomeric ratio was determined by GC of the TFAA derivative
(cyclodex-G-TA, 110 °C, 0.32 mm × 30 m, 25 psi) Tr(minor) 20.2
min, Tr(major) 21.5 min (er 96:4).
(+)-(1S,2S)-2-Naphthylcyclopropylmethanol (entry 7, Table 4).
The cyclopropanation of (E)-3-(2-naphthyl)-2-propenol (183 mg, 0.995
mmol) was performed according to the previously described procedure
(reaction time 1.5 h). The residue was purified by flash chromatography
on silica gel (25% EtOAc/Hexanes) to produce the desired cyclopro-
pylmethanol (160 mg, 81%): Rf 0.28 (25% EtOAc/Hexanes); [R]D
1
+62.4 (c 1.1, CHCl3); H NMR (400 MHz, CDCl3) δ 7.82-7.75 (m,
3H), 7.55-7.40 (m, 3H), 7.20 (dd, J ) 8, 2 Hz, 1H), 3.68-3.66 (m,
2H), 2.02-1.97 (m, 1H), 1.83 (s (br), 1H), 1.59-1.54 (m, 1H), 1.11-
1.07 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 139.8, 133.4, 131.9,
127.9, 127.5, 127.2, 126.0, 125.0, 124.6, 124.0, 66.4, 25.2, 21.4, 13.7;
HRMS calcd for C14H14O1 (M: 198.1044, found 198.1039. The
enantiomeric ratio was determined by HPLC (chiralcel-OD: 4% iPrOH/
Hexanes) Tr(major) 32.3 min, Tr(minor) 43.1 min (er 96:4).
(+)-(1S,2S)-1-Naphthylcyclopropylmethanol (entry 8, Table 4).
The cyclopropanation of (E)-3-(1-naphthyl)-2-propenol (184 mg, 0.996
mmol) was performed according to the previously described procedure
(reaction time 3 h). The residue was purified by flash chromatography
on silica gel (25% EtOAc/Hexanes) to produce the desired cyclopro-
pylmethanol (158 mg, 80%): Rf 0.35 (40% EtOAc/Hexanes); [R]D
+13.9 (c 2.4, CHCl3); 1H NMR (300 MHz, CDCl3) δ 8.42 (dd, J ) 7,
1 Hz, 1H), 7.88 (dd, J ) 7, 1 Hz, 1H), 7.75 (d, J ) 8 Hz, 1H), 7.60-
7.52 (m, 2H), 7.41 (t, J ) 8 Hz, 1H), 7.30 (m, 1H), 3.84 (d, J ) 3 Hz,
1H), 3.81 (d, J ) 3 Hz, 1H), 2.38-2.27 (m, 1H), 1.93 (s, 1H), 1.57-
1.46 (m, 1H), 1.10-0.97 (m, 2H); 13C NMR (100 MHz, CDCl3) δ
137.7, 133.5, 133.2, 128.5, 126.8, 125.8, 125.6, 125.4, 124.2, 123.9,
66.7, 22.8, 19.1, 11.2; HRMS calcd for C14H14O1 (M) 198.1044, found
198.1050. The enantiomeric ratio was determined by HPLC (chiralcel-
OD: 4% iPrOH/Hexanes) Tr(major) 28.5 min, Tr(minor) 33.7 min (er
92:8).
(+)-(1S,2S)-2-(2-Phenylethyl)cyclopropylmethanol (entry 14, Table
4). The cyclopropanation of (E)-5-phenyl-2-pentenol (162 mg, 1.00
mmol) was performed according to the previously described procedure
(reaction time: 3 h). The residue was purified by flash chromatography
on silica gel (25% EtOAc/Hexanes) to produce the desired cyclopro-
pylmethanol (111 mg, 63%): Rf 0.28 (20% EtOAc/Hexanes); [R]D
1
+14.8 (c 2.2, CHCl3); H NMR (400 MHz, CDCl3) δ 7.31-7.17 (m,
(+)-(1S,2S)-2-(p-Methoxyphenyl)cyclopropylmethanol (entry 9,
Table 4). The cyclopropanation of (E)-3-(p-methylphenyl)-2-propenol
(164 mg, 0.997 mmol) was performed according to the previously
described procedure (reaction time 1.25 h). The residue was purified
by flash chromatography on silica gel (35% EtOAc/Hexanes) to produce
5H), 3.47-30.32 (m, 2H), 2.77-2.64 (m, 2H), 1.70-1.48 (m, 2H),
1.16 (s (br), 1H), 0.88-0.80 (m, 1H), 0.67-0.59 (m, 1H), 0.41-0.32
(m, 2H); 13C NMR (100 MHz, CDCl3) δ 142.1, 128.4, 128.2, 125.7,
66.9, 35.8, 35.3, 21.3, 16.8, 9.7; HRMS calcd for C12H15 (M - OH)
159.1174, found 159.1169. The enantiomeric ratio was determined