The Journal of Organic Chemistry
ARTICLE
CDCl3) δ 145.8, 128.3 (þ, 2C), 126.8 (þ, 2C), 125.7 (þ), 70.6 (ꢀ), 70.4
(ꢀ), 70.1 (ꢀ), 64.8 (þ), 49.6 (ꢀ), 49.3 (ꢀ), 32.2 (ꢀ), 26.2, 20.43 (ꢀ),
20.41 (ꢀ), 18.7 (þ), 14.0(þ);FTIR(cmꢀ1, film) 3321, 3059, 3024, 2957,
2928, 2872, 1670, 1603, 1578, 1541, 1497, 1458, 1447, 1377, 1348, 1323,
1292, 1246, 1173, 1121, 1095, 1055, 1028, 1013, 995, 951, 920, 872, 827,
762, 748, 698, 669, 650, 596, 534, 473, 409; HRMS (TOF ES) found
292.2271, calcd for C18H30NO2 (M þ H) 292.2277 (2.1 ppm).
(1R*,2S*)-N,N-Diethyl-2-(2-methoxyethoxy)-1-methylcy-
clopropanecarboxamide (26af): The title compound was pre-
pared according to typical procedure VI, employing bromocyclopropane
25a (117 mg, 1.00 equiv, 0.50 mmol) and ethylene glycol monomethyl
ether (57 mg, 1.0 equiv, 0.5 mmol). Preparative column chromatography
on silica gel afforded the title compound as a clear oil, Rf 0.40 (hexane/
EtOAc 3:1). Yield 102 mg (0.44 mmol, 89%). 1H NMR (400.13 MHz,
CDCl3) δ 3.72ꢀ3.56 (m, 2H), 3.53 (ddd, J = 10.9, 4.9, 3.5 Hz, 1H),
3.47ꢀ3.35 (m, 4H), 3.29 (s, 3H), 3.28ꢀ3.21 (m, 2H), 1.20ꢀ1.18 (m,
1H), 1.18 (s, 3H), 1.18 (t, J = 7.2 Hz, 3H), 1.04 (t, J = 7.1 Hz, 3H), 0.59
(ps t, J = 5.9 Hz, 1H); 13C NMR (100.67 MHz, CDCl3) δ 170.6, 71.6
(ꢀ), 69.6 (ꢀ), 63.2 (þ), 58.9 (þ), 41.0 (ꢀ), 38.5 (ꢀ), 27.6 (þ), 20.5,
18.2 (ꢀ), 13.9 (þ), 12.2 (þ); FT IR (cmꢀ1, film) 2968, 2934, 2874,
2824, 2737, 1722, 1634, 1518, 1427, 1379, 1364, 1348, 1323, 1304, 1259,
1219, 1200, 1167, 1128, 1101, 1067, 1030, 957, 920, 903, 860, 800, 760;
HRMS (TOF ES) found 229.1677, calcd for C12H23NO3 (Mþ)
229.1678 (0.4 ppm);
3-((1R*,2S*)-2-Methyl-2-phenylcyclopropoxy)propan-1-
amine (20aj): The title compound was prepared according to typical
procedure V, employing (2-bromo-1-methylcyclopropyl)benzene (18a)
(102 mg, 0.49 mmol, 1.0 equiv) and 3-aminopropan-1-ol (66 mg, 0.88
mmol, 1.7 equiv). Preparative column chromatography on silica gel
doped with triethylamine afforded the title compound as a pale orange
1
oil, Rf 0.50 (EtOAc/MeOH 1:1). Yield 80 mg (0.39 mmol, 81%). H
NMR (400.13 MHz, CDCl3) δ 7.33ꢀ7.28 (m, 2H), 7.24ꢀ7.18 (m, 3H),
3.71ꢀ3.66 (m, 2H), 3.70 (br s, 2H), 3.36 (dd, J = 6.9, 3.7 Hz, 1H), 2.94
(t, J = 6.6 Hz, 1H), 2.03ꢀ1.96 (m, 2H), 1.88 (quin, J = 6.5 Hz, 1H), 1.50
(s, 3H), 1.16 (app. t, J = 6.9, 6.1 Hz, 1H), 0.84 (dd, J = 6.1, 3.8 Hz, 1H);
13C NMR (100.67 MHz, CDCl3) δ 145.6, 128.3 (þ, 2C), 126.8 (þ, 2C),
125.8 (þ), 68.7 (ꢀ), 64.5 (þ), 38.2 (ꢀ), 30.2 (ꢀ), 26.0, 20.3 (ꢀ), 18.8
(þ); FT IR (cmꢀ1, film) 3354, 3292, 3057, 3024, 2955, 2928, 2872,
1558, 1539, 1497, 1404, 1362, 1339, 1294, 1250, 1169, 1092, 1028, 1013,
955, 922, 829, 698, 650, 536; HRMS (TOF ES) found 206.1547, calcd for
C13H20NO (M þ H) 206.1545 (1.0 ppm).
(1S*,2R*)-2-(2-(Dimethylamino)ethoxy)-N,N-diethyl-1-methyl-
cyclopropanecarboxamide (26ag): The title compound was pre-
pared according to typical procedure VI, employing bromocyclopropane
25a (117 mg, 1.00 equiv, 0.50 mmol) and 2-N,N-dimethylaminoethanol
(67 mg 1.5 equiv, 0.75 mmol). Preparative column chromatography on
silica gel to afford the titled compound as a clear oil, Rf 0.20 (EtOAc).
1
Yield 97 mg (0.40 mmol, 80%). H NMR (400.13 MHz, CDCl3) δ
3.62ꢀ3.53 (m, 2H), 3.52ꢀ3.39 (m, 2H), 3.37ꢀ3.21 (m, 2H), 3.15 (dd,
J = 5.7, 3.7 Hz, 1H), 2.31 (t, J = 5.8 Hz, 2H), 2.11 (s, 6H), 1.11 (t, J = 7.1
Hz, 3H), 1.10 (s), 1.11ꢀ1.09 (m, 1H), 0.97(t, J = 7.1 Hz, 3H), 0.49 (t, J =
5.9 Hz, 1H); 13C NMR (100.67 MHz, CDCl3) δ 170.6, 68.7 (ꢀ), 63.1
(þ), 58.2 (ꢀ), 45.7 (þ, 2C), 41.0 (ꢀ), 38.5 (ꢀ), 27.4, 20.4 (þ), 18.1
(ꢀ), 13.9 (þ), 12.3 (þ); FT IR (cmꢀ1, film) 2970, 2934, 2874, 1637,
1462, 1427, 1381, 1364, 1348, 1323, 1304, 1219, 1200, 1167, 1128, 1101,
1067, 1030, 957, 903, 473; HRMS (TOF ES) found 243.2080, calcd for
C13H27N2O2 (M þ H) 243.2073 (2.9 ppm).
((1R*,2S*)-1-Methyl-2-(propa-1,2-dien-1-yloxy)cyclopropyl)-
benzene (20al): The title compound was prepared according to typical
procedure V, employing (2-bromo-1-methylcyclopropyl)benzene (105 mg,
0.50 mmol, 1.00 equiv) and propargyl alcohol (34 mg, 0.60 mmol,
1.2 equiv). The reaction was carried out at 80 °C for 3 h. Preparative
column chromatography of the residual oil on silica gel afforded the title
compound as a colorless oil, Rf 0.20 (hexane). Yield 76 mg (0.41 mmol,
82%). 1H NMR (400.13 MHz, CDCl3) δ 7.24ꢀ7.16 (m, 4H), 7.11 (tdd,
J = 6.6, 2.5, 1.8 Hz, 1H), 6.69 (t, J = 5.9 Hz, 1H), 5.38 (dd, J = 8.3, 6.1 Hz,
1H), 5.34 (dd, J = 8.6, 6.1 Hz, 1H), 3.48 (dd, J = 7.1, 3.8 Hz, 1H), 1.40 (s,
3H), 1.16 (t, J = 6.6 Hz, 1H), 0.87 (dd, J = 6.2, 3.7 Hz, 1H); 13C NMR
(100.67 MHz, CDCl3) δ 201.6, 145.2, 128.3 (þ, 2C), 126.9 (þ, 2C),
125.9 (þ), 121.5 (þ), 90.6 (ꢀ), 63.0 (þ), 25.8, 20.4 (ꢀ), 18.9 (þ); FT
IR (NaCl, cmꢀ1) 3059, 2932, 2378, 2291, 2253, 1798, 1730, 1686, 1628,
1603, 1578, 1541, 1528, 1508, 1497, 1483, 1464, 1448, 1375, 1364, 1267,
1171, 1121, 1109, 1094, 1070, 1041, 1030, 1011, 918, 808, 764, 700, 588;
HRMS (TOF ES) found 187.1119, calcd for C13H15O (M þ H)
187.1123 (2.1 ppm).
(1S*,2R*)-2-(Benzyloxy)-N,N-diethyl-1-methylcyclopropa-
necarboxamide (26ae): Typical Procedure VI: Bromocyclopro-
pane 25a (70.2 mg, 1.00 equiv, 0.30 mmol) was added to a mixture of
66.6 mg of t-BuOK (2.0 equiv, 0.60 mmol) and 7.8 mg of 18-crown-
6 ether (10%, 30 μmol). Then 49 mg of benzyl alcohol (1.5 equiv,
0.45 mmol) was added and the reaction mixture was stirred in anhydrous
THF (1 mL) overnight at 80 °C. The reaction mixture was partitioned
between water (10 mL), brine, and EtOAc (3 ꢁ 20 mL). The combined
organic phases were dried with Na2SO4, filtered, and concentrated. The
residue was filtered through a short bed of silica gel (EtOAc) to afford
the title compound as a colorless oil. Yield 74 mg (0.28 mmol, 95%). 1H
NMR (400.13 MHz, CDCl3) δ 7.36ꢀ7.24 (m, 5H), 4.58 (d, J = 12.1 Hz,
1H), 4.49 (d, J = 11.9 Hz, 1H), 3.69 (dq, J = 14.4, 7.3 Hz, 1H),
3.54ꢀ3.37 (m, 2H), 3.31 (dd, J = 5.8, 3.5 Hz, 1H), 3.31 (dq, J = 14.2, 7.1
Hz, 1H), 1.32 (dd, J = 5.8, 3.5 Hz, 1H), 1.24 (s, 3H), 1.22 (t, J = 7.3 Hz,
3H), 1.10 (t, J = 7.1 Hz, 3H), 0.66 (t, J = 5.9 Hz, 1H); 13C NMR (100.67
MHz, CDCl3) δ 170.7, 138.1, 128.2 (þ, 2C), 127.5 (þ, 2C), 127.4 (þ),
72.3 (ꢀ), 62.7 (þ), 41.1 (ꢀ), 38.6 (ꢀ), 27.8, 20.6 (þ), 18.5 (ꢀ), 14.0
(þ), 12.4 (þ); FT IR (cmꢀ1, film) 2990, 2980, 1713, 1623, 1433, 1364,
1259, 1223, 1159, 1132, 1090, 1047, 1003, 910, 733, 698, 648, 530;
HRMS (TOF ES) found 262.1817, calcd for C16H24NO2 (M þ H)
262.1807 (3.8 ppm).
(1S*,2R*)-N,N-Diethyl-1-methyl-2-(pent-4-enyloxy)cyclopro-
panecarboxamide (26ah:). The title compound was prepared
according to typical procedure VI, employing bromocyclopropane 25a
(117 mg 1.00 equiv, 0.50 mmol) and 4-pentene-1-ol (87 mg, 1.00 equiv,
0.50 mmol). Preparative column chromatography on silica gel to afford
the titled compound as a yellowish oil, Rf 0.50 (hexane/EtOAc 2:1). Yield
117 mg (0.49 mmol, 89%). 1H NMR (400.13 MHz, CDCl3) δ 5.75 (ddt,
J = 17.2, 10.1, 6.6 Hz, 1H), 4.97 (dq, J = 17.2, 1.7 Hz, 1H), 4.92 (ddt, J =
10.1, 2.0, 1.3 Hz, 1H), 3.63 (dq, J = 14.3, 7.1 Hz, 1H), 3.50ꢀ3.33 (m, 4H),
3.24 (dq, J = 13.6, 7.1 Hz, 1H), 3.20 (dd, J = 5.6, 3.5 Hz, 1H), 2.06ꢀ1.98
(m, 2H), 1.60ꢀ1.50 (m, 2H), 1.20 (t, J = 7.1 Hz, 3H), 1.19 (s, 3H), 1.17
(dd, J = 5.8, 3.5 Hz, 1H), 1.07 (t, J = 7.1 Hz, 3H), 0.57 (t, J = 5.8 Hz, 1H);
13C NMR (100.67 MHz, CDCl3) δ 170.7, 138.2 (þ), 114.6 (ꢀ), 69.4
(ꢀ), 62.9 (þ), 40.9 (ꢀ), 38.5 (ꢀ), 30.2 (ꢀ), 28.6 (ꢀ), 27.4, 20.5 (þ),
18.3 (ꢀ), 14.0 (þ), 12.3 (þ); FT IR (cmꢀ1, film) 3078, 2970, 2935,
2872, 1641, 1462, 1443, 1425, 1258, 1219, 1165, 1128, 1090, 1005, 960,
912, 636; HRMS (TOF ES) found 262.1774, calcd for C14H25NO2Na
(M þ Na) 262.1783 (3.4 ppm).
((1S*,2R*)-1-Methyl-2-(pent-4-enyloxy)cyclopropyl)-
(pyrrolidin-1-yl)methanone (26fh): The title compound was pre-
pared according to typical procedure VI, employing (2-bromo-1-
methylcyclopropyl)(pyrrolidin-1-yl)methanone (25f) (250 mg, 1.07
mmol) and pent-4-en-1-ol (138 mg, 1.61 mmol, 1.50 equiv). Preparative
column chromatography of a residue on silica gel afforded the title
compound as a yellow oil, Rf 0.30 (hexane/EtOAc 2:3). Yield 219 mg
(0.98 mmol, 92%). 1H NMR(400.13 MHz, CDCl3) δ 5.76 (ddt, J = 17.0,
10.3 Hz, 6.7 Hz, 1H), 4.97 (ddt, J = 17.2, 1.8, 1.5 Hz, 1H), 4.92 (ddt, J =
10.4, 2.2, 1.2 Hz, 1H), 3.83 (ddd, J = 10.1, 6.2, 3.7 Hz, 1H), 3.50ꢀ3.36
(m, 5H), 3.17 (dd, J = 5.8, 3.5 Hz, 1H), 2.02 (q, J = 7.3 Hz, 2H),
1.96ꢀ1.74 (m, 4H), 1.56 (quin, J = 7.0 Hz, 2H), 1.23 (s, 3H), 1.19 (dd,
J = 6.1, 3.5 Hz, 1H), 0.57 (dd, J = 6.1, 5.8 Hz, 1H); 13C NMR (100.67 MHz,
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dx.doi.org/10.1021/jo200368a |J. Org. Chem. 2011, 76, 3968–3986