Voituriez et al.
JOCArticle
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2.75-2.65 (m, 2H), 1.68-1.48 (m, 2H), 1.45 (s, 1H), 0.90-0.75
(m, 1H), 0.65-0.55 (m, 1H), 0.40-0.28 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 142.3, 128.6, 128.4, 125.9, 67.1, 36.0, 35.4, 21.5,
17.0, 9.9; IR νmax = 3326, 2995, 2920, 2855, 1603, 1495, 1454,
Rf 0.46 (10% EtOAc/hexanes); H NMR (400 MHz, CDCl3)
δ 7.37-7.25 (m, 5H), 7.00 (dt, J = 9.0, 2.1 Hz, 2H), 6.79 (dt, J =
8.7, 2.1 Hz, 2H), 4.55 (s, 2H), 3.76 (s, 3H), 3.52 (dd, J = 10.2, 6.6
Hz, 1H), 3.41 (dd, J = 10.2, 6.9 Hz, 1H), 1.80-1.71 (m, 1H),
1.43-1.31 (m, 1H), 0.95-0.83 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 157.8, 138.6, 134.7, 128.5, 127.8, 127.7, 127.1, 113.9,
73.8, 72.6, 55.4, 22.2, 20.9, 13.8; IR νmax = 2985, 2306, 1515,
1061, 1032, 1016, 742, 698, 631 cm-1
.
(2-Methyl-2-(4-methylpent-3-enyl)cyclopropyl)methanol (4d).22
The cyclopropanation of the commercially available geraniol 3d
(46 mg, 0.30 mmol) was performed according to the previously
described procedure. The residue was purified by flash chroma-
tography on silica gel (25% EtOAc/hexanes) to produce the
desired cyclopropane (47 mg, 93%): Rf 0.65 (30% EtOAc/
1455, 1265, 1177, 1033, 909, 754, 704, 630 cm-1
.
1-(2-(Benzyloxymethyl)cyclopropyl)-3-methoxybenzene (4i).
The cyclopropanation of (E)-1-(3-(benzyloxy)prop-1-enyl)-3-
methoxybenzene 3i26 (76 mg, 0.30 mmol) was performed accord-
ing to the previously described procedure. The residue was
purified by flash chromatography on silica gel (10% EtOAc/
hexane) to produce the desired cyclopropane (79 mg, 98%):
1
hexanes); H NMR (400 MHz, CDCl3) δ 5.12-5.05 (m, 1H),
3.69 (dd, J=11.2, 6.6 Hz, 1H), 3.47 (dd, J=11.2, 8.4 Hz, 1H),
2.10-1.98 (m, 2H), 1.66 (s, 3H), 1.63 (s, 1H), 1.60 (s, 3H),
1.40-1.32 (m, 1H), 1.18-1.10 (m, 1H), 1.08 (s, 3H), 0.95-0.85
(m, 1H), 0.48 (dd, J = 8.8, 4.8 Hz, 1H), 0.11 (t, J = 4.8 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 131.4, 124.7, 64.0, 41.2, 26.3,
25.8, 25.6, 20.0, 17.75, 17.69, 17.1; IR νmax = 3370, 2968, 2920,
1
Rf 0.46 (10% EtOAc/hexanes); H NMR (400 MHz, CDCl3)
δ 7.40-7.27 (m, 5H), 7.19 (t, J = 7.8 Hz, 1H), 6.75-6.63(m, 3H),
4.58(s, 2H), 3.80 (s, 3H), 3.56 (dd, J = 10.2, 6.3 Hz, 1H), 3.44 (dd,
J = 10.2, 6.6 Hz, 1H), 1.85-1.77 (m, 1H), 1.55-1.42 (m, 1H),
1.05-0.90 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 159.8, 144.5,
138.6, 129.4, 128.5, 127.8, 127.7, 118.4, 111.8, 110.9, 73.5, 72.6,
55.2, 22.8, 21.6, 14.3; IR νmax =3002, 2936, 2855, 1602, 1582,
1494, 1454, 1264, 1206, 1154, 1094, 1072, 1046, 773, 735,
694 cm-1; HRMS (ESI) calcd for C18H21O2 [M þ H]þ
269.1536, found 269.1525.
(E)-1-Methoxy-3-(3-methoxyprop-1-enyl)benzene (3j). The
methylation of (E)-3-(3-methoxyphenyl)prop-2-en-1-ol (253 mg,
1.54 mmol) was performed according to a previously described
procedureusingNaH60%(1.2equiv) andMeI(1.2equiv) inTHF
(10 mL). Classical work up following by a purification by flash
chromatography on silica gel (10% EtOAc/hexanes) produce the
desired product 1f (230 mg, 84%): Rf 0.42 (10% EtOAc/hexanes);
1H NMR (400 MHz, CDCl3) δ7.22 (dd, J =8.1, 7.8Hz, 1H), 6.97
(d, J = 7.5 Hz, 1H), 6.92 (d, J = 2.4 Hz, 1H), 6.78 (dd, J = 8.1, 2.4
Hz, 1H), 6.57 (d, J = 15.9 Hz, 1H), 6.26 (dt, J = 15.9, 6.0 Hz, 1H),
4.07 (dd, J = 6.0, 5.7Hz, 1H), 3.79 (s, 3H), 3.36 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 159.9, 138.2, 132.3, 129.6, 126.4, 119.2,
113.4, 111.8, 73.1, 58.1, 55.2; IR νmax=2926, 2821, 1598, 1598,
1579, 1489, 1453, 1379, 1289, 1258, 1154, 1119, 1041, 967, 771, 689,
630 cm-1; HRMS (ESI) calcd for C11H14O2Ag [M þ Ag]þ
285.0039, found 285.0037.
1452, 1383, 1265, 1032, 738, 628 cm-1
.
(2-Cyclohexylcyclopropyl)methanol (4e).22 The cyclopropana-
tion of (E)-3-cyclohexylprop-2-en-1-ol 3e22 (36 mg, 0.26 mmol)
was performed according to the previously described procedure.
The residue was purified by flash chromatography on silica gel
(40% Et2O/hexanes) toproducethe desired cyclopropane(30mg,
76%): Rf 0.39 (40% Et2O/hexane)s; 1H NMR (400 MHz, CDCl3)
δ 3.40 (dd, J = 11.2, 7.2 Hz, 1H), 3.36 (dd, J = 10.8, 6.8 Hz, 1H),
1.80-1.64 (m, 4H), 1.62-1.52 (m, 2H), 1.20-0.95 (m, 5H),
0.89-0.78 (m, 1H), 0.60-0.48 (m, 1H), 0.44-0.35 (m, 1H),
0.34-0.26 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 67.4, 42.0,
33.2, 32.9, 26.6, 26.4, 24.1, 20.1, 8.8; IR νmax = 3329, 2919, 2849,
1447, 1049, 1028, 1013, 962, 868, 664 cm-1
.
(2-(Methoxymethyl)cyclopropyl)benzene (4f).9 The cyclopro-
panation of (E)-(3-methoxyprop-1-enyl)benzene 3f23,24 (44 mg,
0.30 mmol) was performed according to the previously de-
scribed procedure. The residue was purified by flash chroma-
tography on silica gel (10% EtOAc/hexanes) to produce the
desired cyclopropane (35 mg, 72%): Rf 0.55 (30% EtOAc/
1
hexanes); H NMR (400 MHz, CDCl3) δ 7.30-7.24 (m, 2H),
7.17 (tt, J=7.6, 1.2 Hz, 1H), 7.12-7.07 (m, 2H), 3.46 (dd, J=
10.2, 6.6 Hz, 1H), 3.40 (s, 3H), 3.39 (dd, J=10.4, 6.8 Hz, 1H),
1.83 (dt, J = 8.4, 4.8 Hz, 1H), 1.49-1.40 (m, 1H), 1.03-0.91 (m,
2H); 13C NMR (100 MHz, CDCl3) δ 142.7, 128.4, 125.9, 125.7,
76.2, 58.5, 22.5, 21.5, 14.1; IR νmax =3030, 2924, 2815, 1602,
1-Methoxy-3-(2-(methoxymethyl)cyclopropyl)benzene (4j). The
cyclopropanation of (E)-1-methoxy-3-(3-methoxyprop-1-enyl)-
benzene 3j (53 mg, 0.30 mmol) was performed according to the
previously described procedure. The residue was purified by flash
chromatography on silica gel (10% EtOAc/hexanes) to produce
the desired cyclopropane (57 mg, 99%): Rf 0.39 (10% EtOAc/
hexanes); 1H NMR (400 MHz, CDCl3) δ 7.18 (dd, J = 8.0, 7.6
Hz, 1H), 6.75-6.60 (m, 3H), 3.79 (s, 3H), 3.45-3.30 (m, 5H),
1498, 1463, 1200, 1105, 913, 748, 697 cm-1
.
(2-(Benzyloxymethyl)cyclopropyl)benzene (4g).9 The cyclopro-
panation of (E)-(3-(benzyloxy)prop-1-enyl)benzene 3g9 (67 mg,
0.30 mmol) was performed according to the previously described
procedure. The residue was purified by flash chromatography on
silica gel (5% EtOAc/hexanes) to produce the desired cyclopropane
(68 mg, 95%): Rf 0.61 (30% EtOAc/hexanes); 1H NMR (400MHz,
CDCl3) δ 7.43-7.28 (m, 7H), 7.21 (tt, J = 7.6, 1.2 Hz, 1H), 7.15-
7.11 (m, 2H), 4.62 (s, 2H), 3.60 (dd, J=10.4, 6.4 Hz, 1H), 3.49 (dd,
J = 10.0, 6.8 Hz, 1H), 1.85 (dt, J = 9.2, 4.8 Hz, 1H), 1.55-1.50
(m, 1H), 1.10-0.95 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 142.7,
138.6, 128.5, 128.4, 127.8, 127.7, 125.9, 125.7, 73.6, 72.6, 22.7, 21.6,
14.3; IR νmax=3060, 3027, 2855, 1604, 1497, 1454, 1359, 1094, 1078,
1.84-1.77 (m, 1H), 1.47-1.40 (m, 1H), 1.02-0.92 (m, 2H); 13
C
NMR (100 MHz, CDCl3) δ 159.8, 144.4, 129.4, 118.4, 111.8,
110.9, 76.1, 58.5, 55.2, 22.6, 21.6, 14.2; IRνmax=2926, 2834, 1603,
1582, 1493, 1455, 1264, 1200, 1155, 1103, 1046, 773, 694 cm-1
;
HRMS (ESI) calcd for C12H16O2Ag [M þ Ag]þ 299.0195, found
299.0185.
1-(2-(Benzyloxymethyl)cyclopropyl)-4-chlorobenzene25 (4k).
The cyclopropanation of (E)-1-(3-(benzyloxy)prop-1-enyl)-4-
chlorobenzene 4k (66.5 mg, 0.257 mmol) was performed accord-
ing to the previously described procedure. The residue was
purified by flash chromatography on silica gel (5% Et2O/hexane)
to produce the desired cyclopropane (65 mg, 93%): Rf = 0.40
(10% Et2O/hexanes); 1H NMR (400 MHz, CDCl3) δ 7.41-7.29
(m, 5H), 7.24 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.4 Hz, 2H), 4.58
(s, 2H), 3.53 (dd, J = 10.4, 6.8 Hz, 1H), 3.50 (dd, J = 10.0, 6.4 Hz,
1H), 1.85-1.78 (m, 1H), 1.50-1.40 (m, 1H), 0.98(dd, J = 7.2, 6.8
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 141.3, 138.5, 131.2,
909, 735, 696 cm-1
.
1-(2-(Benzyloxymethyl)cyclopropyl)-4-methoxybenzene (4h).25
The cyclopropanation of (E)-1-(3-(benzyloxy)prop-1-enyl)-4-
methoxybenzene 3h9 (64 mg, 0.25 mmol) was performed accord-
ing to the previously described procedure. The residue was
purified by flash chromatography on silica gel (5% EtOAc/
hexanes) to produce the desired cyclopropane (61 mg, 91%):
(23) Barluenga, J.; Alonso-Cires, L.; Asensio, G. Tetrahedron Lett. 1981,
22, 2239.
(24) Huang, X.; Xu, X.-H. J. Chem. Soc., Perkin Trans. 1 1998, 3321.
(25) Charette, A. B.; Giroux, A. J. Org. Chem. 1996, 61, 8718.
(26) Takami, K.; Mikami, S.; Yorimitsu, H.; Shinokubo, H.; Oshima, K.
J. Org. Chem. 2003, 68, 6627.
J. Org. Chem. Vol. 75, No. 4, 2010 1249