The Journal of Organic Chemistry
Note
CDCl3): δ 7.30−7.11 (m, 10H, 2Ph), 6.13−6.04 (m, 1H, CHCH2),
5.34 (dd, J = 11 Hz and J = 1 Hz, 1H, CHC HH), 5.15 (dd, J = 17 Hz
and J = 1 Hz, 1H, CHCHH), 3.73 (s, 4H, NCH2Ph), 1.78−1.50 (m,
8H, CH2). 13C NMR (75 MHz, CDCl3): δ 142.1 (Cq Ar), 140.4 (CH),
128.5, 127.8, 126.2 (CHAr), 114.3 (CH2), 72.0 (Cq), 56.0, 36.3, 22.8
(CH2). IR vmax: 3061, 3025, 2956, 2872, 1602, 1493, 1452, 1409, 1372,
1243, 1118, 1027, 914, 739, 695 cm−1. HRMS (TOF MSES positive
mode) m/z: calcd for C21H26N, 292.2065; found, 292.2062.
Dibenzyl-(1-vinyl-cyclohexyl)-amine 13. Overall yield: 69%, as a
colorless solid; mp 28 °C. Rf = 0.7 (pentane/EtOAc: 90/10). 1H NMR
(300 MHz, CDCl3): δ 7.41−7.10 (m, 10H, 2Ph), 5.90−5.80 (m, 1H,
CHCH2), 5.38 (dd, J = 12 Hz and J = 1 Hz, 1H, CHCHH), 5.20
(dd, J = 18 Hz and J = 1 Hz, 1H, CHCHH), 3.75 (s, 4H, NCH2Ph),
1.83−1.80 (m, 2H, CH2), 1.86−1.52 (m, 6H, CH2), 1.39−1.24 (m, 4H,
CH2). 13C NMR (75 MHz, CDCl3): δ 142.5 (CH), 141.0 (Cq Ar),
128.4, 127.7, 126.0 (CHAr), 115.4 (CH2), 61.9 (Cq), 53.6, 34.4, 26.1,
22.7 (CH2). IR vmax: 3083, 3061, 3025, 2932, 2853, 1601, 1493, 1451,
1409, 1120, 1069, 916, 739, 691 cm−1. HRMS (TOF MSES positive
mode) m/z: calcd for C22H28N, 306.2222; found, 306.2217.
NMR (300 MHz, CDCl3): δ 7.32−7.08 (m, 10H, ArH), 5.37 (b, 3H,
NCHPh, CHCH), 4.32 (b, 1H, NCH2Ph), 4.12 (d, J = 15.4 Hz, 1H,
NCH2Ph), 2.60 (bs, 2H, CH2-CHCH) 1.61 (d, J = 4.9 Hz, 3H,
CH3), 1.42 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3): δ 156.2 (C
O), 140.4, 139.7 (Cq Ar), 128.3, 128.1, 127.9, 127.6, 127.3, 126.5 (CH
Ar, CH), 79.8 ((CH3)3C), 58.9 (CH), 47.6, 34.8 (CH2), 28.3
((CH3)3C), 18.0 (CH3). IR vmax: 3028, 2973, 2930, 2852, 1685, 1495,
1451, 1401, 1364, 1247, 1159, 1073, 963, 868, 735, 696, 610 cm−1.
HRMS (TOF MSES positive mode) m/z: calcd for C23H29NO2Na,
374.2094; found, 374.2094.
(1R)-Benzyl-(3-hydroxy-1-phenyl-propyl)-carbamic Acid tert-
Butyl Ester 6. Compound 5 (70 mg, 0.2 mmol) was dissolved in 3/1
dioxane/H2O (2 mL). 2,6-Lutidine (0.05 mL, 0.4 mmol), OsO4 (0.157
M in H2O, 0.025 mL, 0.004 mmol), and NaIO4 (171 mg, 0.8 mmol)
were added to the solution. The mixture was stirred at rt for 45 min and
then diluted with CH2Cl2 and H2O. The phases were separated, and the
aqueous phase was extracted with CH2Cl2. The combined CH2Cl2
phases were dried over magnesium sulfate, filtered, and concentrated
under reduced pressure. The resulting residue was dissolved in MeOH
(2 mL), and NaBH4 (19 mg, 0.5 mmol) was added. The mixture was
stirred at rt for 15 min and then diluted with CH2Cl2. The solution was
washed with 0.25 N aqueous HCl solution and then with a saturated
aqueous NaCl solution. The organic phase was dried over magnesium
sulfate, filtered, and concentrated under reduced pressure. Purification
by flash chromatography (petroleum ether/ethyl acetate: 75/25) gave 6
as a colorless oil (40 mg, 0.12 mmol, 58%). Rf = 0.22 (pentane/EtOAc:
(1R)-Benzyl-(1-phenyl-pent-3-enyl)-amine 2 (Following the
Conditions of Table 1, entry 6). To a solution of sublimed t-BuOK
(179 mg, 1.6 mmol) and diisopropylamine (0.22 mL, 1.6 mmol) in dry
THF (5 mL) at −78 °C was added butyllithium (1.4 M solution in
hexanes, 1.7 mL, 2.4 mmol) dropwise. The reaction mixture was stirred
for 0.5 h at −78 °C before adding a solution of allylamine 1 (100 mg,
0.4 mmol) in THF (3 mL) dropwise. After the solution was stirred at
−78 °C for 3 h (dark red solution), the reaction was quenched with
methanol-d4 (0.5 mL) and allowed to reach rt. Brine was added to the
reaction mixture, and the aqueous layer was extracted with ethyl
acetate. The combined organic layers were dried over magnesium
sulfate, filtered, and concentrated under reduced pressure. Purification
by using flash chromatography (pentane/ethyl acetate 95/5 + 1%
NEt3) gave (R)-2 as a colorless oil (85 mg, 0.34 mmol, 85%). Rf = 0.24
75/25). [α]2D0 +61 (c 1.2, CH2Cl2). H NMR (300 MHz, CDCl3): δ
1
7.25−6.92 (m, 10H, ArH), 5.57 (b, 1H, NCHPh), 4.23 (d, J = 14.6 Hz,
1H, NCH2Ph), 3.79 (d, J = 14.6 Hz, 1H, NCH2Ph), 3.50−3.42 (m, 2H,
CH2OH), 2.85 (bs, 1H, OH), 2.05−1.93 (m, 1H, CHCH2), 1.86−1.79
(m, 1H, CHCH2), 1.37 (s, 9H, 3CH3). 13C NMR (75 MHz, CDCl3): δ
139.4 (Cq Ar), 128.7, 128.6, 128.5, 128.1, 127.7, 127.4, 126.8 (CH Ar),
80.8 ((CH3)3C), 58.8 (CH2OH), 54.7 (CH), 46.9 (NCH2), 33.5
(CH2), 28.3 (CH3). IR vmax: 3438, 3060, 3030, 2974, 2925, 2876, 1683,
1661, 1495, 1452, 1404, 1365, 1248, 1157, 1121, 1028, 871, 735, 697
cm−1. HRMS (TOF MSES positive mode) m/z: calcd for
C21H27NO3Na, 364.1889; found, 364.1890.
(pentane/EtOAc: 95/5). [α]2D0 +42 (c 1.9, CH2Cl2). H NMR (300
1
MHz, CDCl3): δ 7.41−7.24 (m, 10H, 2Ph), 5.59−5.48 (m, 1H, CH
CH-CH3), 5.41−5.31 (m, 1H, CH2−CHCH), 3.73−3.53 (m, 3H,
NCHPh, NCH2Ph), 2.39−2.34 (m, 2H, CH2-CHCH), 1.67 (d, J =
6.3 Hz, 3H, CH3). 13C NMR (75 MHz, CDCl3): δ 144.1, 140.7 (Cq
Ar), 128.3, 128.3, 128.1, 127.9, 127.3, 126.9, 126.8 (CH Ar, CH),
62.1 (CH), 51.5, 41.9 (CH2), 17.9 (CH3). IR vmax: 3061, 3024, 2914,
2840, 2797, 1601, 1493, 1452, 1114, 1027, 967, 731, 696, 618 cm−1.
HRMS (TOF MSES positive mode) m/z: calcd for C18H22N,
252.1752; found, 252.1752.
(1R)-3-Benzylamino-3-phenyl-propan-1-ol (R)-7. Compound 6
(35 mg, 0.10 mmol) was dissolved in CH2Cl2 (2.7 mL), and the
solution was cooled in an ice bath. Trifluoroacetic acid (0.3 mL) was
added, and the mixture was stirred at 0 °C for 30 min and then at rt for
2 h. The mixture was diluted with toluene and concentrated under
reduced pressure. The residue was taken up in EtOAc and washed with
a saturated aqueous NaHCO3 solution. The organic phase was dried
over magnesium sulfate, filtered, and concentrated under reduced
pressure. Purification via flash chromatography (CH2Cl2/MeOH 95/5)
gave (R)-7 as a colorless oil (21 mg, 0.08 mmol, 87%). Rf = 0.33
(CH2Cl2/MeOH: 95/5). [α]2D0 +38 (c 0.16 MeOH) (lit.8 [α]2D0 −37 (c
(1R,5S)-Benzyl-(5-methyl-1-phenyl-hept-3-enyl)-amine 4.
Following the procedure reported above for 2 but with a 6/6/9
tBuOK/iPr2NH/BuLi molar ratio with respect to starting 3 (0.4 mmol)
and a reaction time of 1 h at −78 °C, and 6.5 h at −65 °C, the title
compound was obtained as an oil that crystallized upon standing (72
mg, 61%). Mp 35 °C. Rf = 0.2 (pentane/EtOAc: 90/10). [α]2D0 +54 (c
1
0.06 MeOH) for (S)-7). H NMR (300 MHz, CDCl3): δ 7.34−7.16
1
(m, 10H, ArH), 3.81 (dd, J = 3.2, 9.6 Hz, 1H, NCHPh), 3.74−3.72 (m,
2H, CH2OH), 3.59 (d, J = 12.8 Hz, 1H, NCH2Ph), 3.52 (d, J = 12.8 Hz,
1H, NCH2Ph), 3.27 (bs, 2H, OH, NH), 1.98−1.86 (m, 1H, CHCH2)
1.78−1.72 (m, 1H, CHCH2). 13C NMR (75 MHz, CDCl3): δ 137.6,
134.1 (Cq Ar), 129.3, 129.0, 128.9, 128.7, 128.5, 127.4 (CH Ar), 62.9
(CH), 61.1 (CH2OH), 49.9 (NCH2), 36.9 (CH2). IR vmax: 3287, 3064,
3026, 2923, 2848, 1674, 1602, 1493, 1452, 1360, 1200, 1063, 1027, 743,
696, 617 cm−1. HRMS (TOF MSES positive mode) m/z: calcd for
C16H20NO, 242.1545; found, 242.1550.
1.1, CH2Cl2). H NMR (300 MHz, CDCl3): δ 7.41−7.24 (m, 10H,
2Ph), 5.38−5.20 (m, 2H, CHCH trans), 3.72−3.63 (m, 2H, NCHα,
NCHHPh), 3.52 (d, AB syst., J = 13 Hz, 1H, NCHHPh), 2.39−2.35
(m, 2H, NCHαCH2), 2.01−1.92 (m, 1H, CHCH3), 1.33−1.17 (m, 2H,
CH3CH2), 0.93 (d, 3H, J = 7 Hz, 3H, CH3), 0.81 (t, J = 7 Hz, 3H,
CH3). 13C NMR (75 MHz, CDCl3): δ 139.9 (CH), 128.7, 128.3, 128.2,
127.4, 126.9, 126.8 (CHAr), 124.9, 62.0 (CH), 51.4, 42.0 (CH2), 38.5
(CH), 29.7 (CH2), 20.3, 11.9 (CH3). IR vmax: 3026, 2966, 2950, 2922,
2896, 2866, 1492, 1452, 1437, 1372, 1104, 1070, 962, 752, 729 cm−1.
HRMS (TOF MSES positive mode) m/z: calcd for C21H28N,
294.2222; found, 294.2210. Data have been deposited at the
Cambridge Crystallographic Data Centre and have been allocated the
deposition number CCDC 1052073.
Procedures for the Preparation of Compounds 10 and 11. (1-
Dibenzylamino-cyclopentyl)methanol 10. A solution of compound
8
16 (2 g, 10 mmol) in a mixture of ethanol (46 mL) and sulfuric acid
(23 mL) was refluxed overnight. After cooling to 0 °C, the reaction
mixture was poured very slowly onto an ice cold saturated hydrogen
carbonate aqueous solution with stirring. The aqueous layer was
extracted with dichloromethane. The combined organic layers were
dried over magnesium sulfate, filtered, and concentrated under reduced
pressure. Purification by flash chromatography (pentane/ethyl acetate:
90/10) gave the corresponding ethyl ester as a colorless oil (1.023 g,
4.14 mmol, 41%). A suspension of potassium carbonate (2.09 g, 15.15
mmol) in DMF (10 mL) containing the above ester (0.75 g, 10 mmol)
Procedure for the Chemical Correlation of Homoallylamine
2 to (R)-7. (1R)-Benzyl-(1-phenyl-pent-3-enyl)-carbamic Acid tert-
Butyl Ester 5. Compound 2 (200 mg, 0.8 mmol) was dissolved in
MeCN (5 mL), and Boc2O (347 mg, 1.6 mmol) was added. The
mixture was stirred at rt for 3 days, and then concentrated under
reduced pressure. Purification by flash chromatography (petroleum
ether/ethyl acetate: 99/1) gave 5 as a colorless oil (248 mg, 0.71 mmol,
88%). Rf = 0.52 (pentane/EtOAc: 95/5). [α]2D0 +55 (c 1.1, CH2Cl2). 1H
D
J. Org. Chem. XXXX, XXX, XXX−XXX