A Cascade Aza-Cope/Aza-Prins Cyclization
dard chemical shifts were considered for the reference signal. IR
spectra were obtained on a Perkin–Elmer Spectrum One FT-IR
spectrometer. Optical rotations were measured with a Jasco P-2000
polarimeter using the sodium D line (589 nm). HRMS were re-
corded by using a Micromass: Q-Tof micro (YA-105) spectrometer
and were obtained by positive electrospray ionization using the
TOF method. Homoallylamines 1 were prepared by following a
literature procedure.[21] The spectroscopic data of 1a–1f, 1i, 1j, 1l,
and 1n–1w matched well with the chiral ones prepared by us.[16]
For new compounds, the data is given below.
1-(Benzo[d][1,3]dioxol-5-yl)-N-[(S)-1-phenylethyl]but-3-en-1-amine
(1y): Colorless oil (diastereomeric mixture of syn/anti, 1:1.3). 1H
NMR (500 MHz, CDCl3): δ = 1.26 (d, J = 6.8 Hz, 3 H), 1.32 (d,
J = 6.6 Hz, 3 H), 2.25 (t, J = 6.2 Hz, 2 H), 2.34–2.46 (m, 2 H),
3.27 (t, J = 7.0 Hz, 1 H), 3.48 (q, J = 6.7 Hz, 1 H), 3.66–3.73 (m,
2 H), 4.99–5.07 (m, 4 H), 5.56–5.61 (m, 2 H), 5.93 (s, 2 H), 5.95
(dd, J = 3.5, 1.5 Hz, 2 H), 6.60–6.81 (m, 6 H), 7.14–7.33 (m, 10
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 22.3, 24.7, 42.1, 43.4,
54.4, 54.6, 58.6, 59.4, 100.7, 107.1, 107.3, 107.8, 107.82, 117.2,
117.3, 120.3, 120.4, 126.5, 126.65, 126.7, 128.23, 128.3, 135.3,
135.5, 137.9, 138.2, 145.6, 145.9, 146.2, 146.3, 147.6, 147.7 ppm.
N-[1-(4-Methoxyphenyl)but-3-enyl]aniline (1g): Colorless oil. 1H
NMR (400 MHz, CDCl3): δ = 2.52–2.69 (m, 2 H), 3.84 (s, 3 H),
4.40 (dd, J = 7.7, 5.3 Hz, 1 H), 5.20–5.27 (m, 2 H), 5.78–5.88 (m,
1 H), 6.57 (d, J = 8.1 Hz, 2 H), 6.71 (t, J = 7.3 Hz, 1 H), 6.92 (d,
J = 6.6 Hz, 2 H), 7.14 (t, J = 7.9 Hz, 2 H), 7.34 (d, J = 8.6 Hz, 2
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 43.2, 55.1, 56.5, 113.5,
113.9, 117.3, 118.1, 127.3, 129.0, 134.7, 135.3, 147.2, 158.5 ppm.
IR (CHCl ): νmax = 3079, 3021, 2976, 1638, 1502, 1487, 1441, 1375,
˜
3
1101, 1042, 995, 910, 811, 735, 650 cm–1. HRMS (ESI-TOF): calcd.
for [C19H21NO2 + H]+ 296.1645; found 296.1640.
(S)-2-[1-(Benzo[d][1,3]dioxol-5-yl)but-3-enylamino]-2-phenylethanol
1
(1z): H NMR (500 MHz, CDCl3): δ = 2.36–2.43 (m, 1 H), 2.44–
2.52 (m, 1 H), 3.51 (dd, J = 10.7, 7.1 Hz, 1 H), 3.62 (t, J = 6.6 Hz,
1 H), 3.75 (dd, J = 10.8, 4.6 Hz, 1 H), 3.82 (dd, J = 7.0, 4.6 Hz, 1
H), 4.99–5.06 (m, 2 H), 5.61–5.69 (m, 1 H), 5.91 (dd, J = 3.3,
1.5 Hz, 2 H), 6.62 (dd, J = 8.0, 1.6 Hz, 1 H), 6.69–6.70 (m, 2 H),
7.19–7.23 (m, 2 H), 7.24–7.31 (m, 3 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 41.2, 59.5, 61.3, 65.5, 100.8, 107.2, 107.8, 117.3, 120.3,
127.1, 127.3, 128.4, 134.8, 137.6, 141.0, 146.4, 147.5 ppm. IR
IR (CHCl ): νmax = 3415, 3053, 3009, 2955, 2934, 2837, 1638, 1604,
˜
3
1509, 1464, 1302, 1248, 1180, 1107, 1035, 921, 828, 693, 669 cm–1.
HRMS (ESI-TOF): calcd. for [C17H19NO + H]+ 254.1530; found
254.1533.
N-Allyl-1-(4-methoxyphenyl)but-3-en-1-amine (1h): Colorless oil.
1H NMR (400 MHz, CDCl3): δ = 2.38 (t, J = 6.3 Hz, 2 H), 2.97–
3.14 (m, 2 H), 3.64 (t, J = 6.9 Hz, 1 H), 3.79 (s, 3 H), 5.02–5.16
(m, 4 H), 5.65–5.76 (m, 1 H), 5.77–5.90 (m, 1 H), 6.86 (d, J =
8.7 Hz, 2 H), 7.21 (d, J = 8.6 Hz, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 42.8, 49.8, 55.1, 61.0, 113.6, 115.8, 117.4, 128.2, 135.4,
(CHCl ): ν
= 3434, 2929, 1639, 1500, 1488, 1442, 1246, 1094,
˜
3
max
1042, 909, 650 cm–1. HRMS (ESI-TOF): calcd. for [C19H21NO3 +
H]+ 312.1594; found 312.1596.
General Procedure to Synthesize 3a–3f, 3ab, 3ac, and 3ad: (Tables 1
and 2). To a solution of homoallylamine 1 (1.0 mmol) in CH3CN
(1.0 mL) were sequentially added formalin (37% solution in H2O,
0.8 mL, 10 mmol) and TFA (92 μL, 1.2 mmol). The reaction mix-
ture was stirred at room temperature for the specified time. It was
then treated with saturated aqueous NaHCO3 (2.0 mL), and the
resulting mixture was extracted with CH2Cl2 (3ϫ 10 mL). The
combined organic layers were washed with brine, dried with
Na2SO4, and concentrated. The residue was purified by column
chromatography (petroleum ether/EtOAc, 1:4) to deliver piper-
idines 3a–3f. For 3ab and 3ac, Lewis acids FeCl3, SnCl4, or ZnBr2
(1.0 equiv.) in CH3CN/H2O (1:1) were used instead of TFA. For
3ad, 1-phenyl-1H-tetrazole-5-thiol (2.0 equiv.) was used.
136.7, 158.6 ppm. IR (CHCl ): νmax = 3416, 3078, 3012, 2956, 2933,
˜
3
2837, 1640, 1611, 1586, 1509, 1462, 1442, 1419, 1354, 1302, 1243,
1178, 1102, 1037, 995, 921, 832, 810, 668 cm–1. HRMS (ESI-TOF):
calcd. for [C14H19NO + H]+ 218.1539; found 218.1533.
N-Benzyl-1-(3,4,5-trimethoxyphenyl)but-3-en-1-amine (1k): Color-
1
less oil. H NMR (400 MHz, CDCl3): δ = 2.36–2.51 (m, 2 H), 3.53
(d, J = 13.3 Hz, 1 H), 3.56 (dd, J = 13.7, 5.9 Hz, 1 H), 3.70 (d, J
= 13.3 Hz, 1 H), 3.87 (s, 9 H), 5.05–5.12 (m, 2 H), 5.65–5.75 (m, 1
H), 6.62 (s, 2 H), 7.23–7.33 (m, 5 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 42.8, 50.9, 55.4, 60.1, 61.3, 103.3, 117.1, 126.3, 127.6,
127.8, 134.9, 136.2, 139.1, 140.0, 152.7 ppm. IR (CHCl ): ν
=
˜
3
max
3511, 3065, 3016, 2839, 1640, 1594, 1508, 1464, 1421, 1327, 1130,
1005, 921, 757, 700, 667 cm–1. HRMS (ESI-TOF): calcd. for
[C20H25NO3 + Na]+ 350.1727; found 350.1726.
1-Benzylpiperidin-4-ol (3a): Colorless oil. 1H NMR (400 MHz,
CDCl3): δ = 1.54–1.63 (m, 2 H), 1.85–1.90 (m, 2 H), 2.05–2.12 (m,
2 H), 2.73–2.81 (m, 2 H), 3.50 (s, 2 H), 3.54–3.73 (m, 1 H), 7.24–
7.34 (m, 5 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 34.1, 50.9,
1
N-Benzyl-1-(4-chlorophenyl)-3-butenylamine (1m): Colorless oil. H
62.8, 67.5, 126.9, 128.0, 129.1, 137.8 ppm. IR (CHCl ): ν
=
˜
3
max
NMR (400 MHz, CDCl3): δ = 1.85 (br. s, 1 H), 2.31–2.43 (m, 2
H), 3.51 (d, J = 13.3 Hz, 1 H), 3.64–3.71 (m, 2 H), 5.03–5.07 (m,
2 H), 5.62–5.72 (m, 1 H), 7.21–7.32 (m, 9 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 43.2, 51.5, 61.1, 118.1, 127.1, 128.3, 128.6,
3376, 3064, 2941, 2809, 2766, 1653, 1454, 1363, 1300, 1240, 1102,
1066, 745, 700 cm–1. HRMS (ESI-TOF): calcd. for [C12H17NO +
H]+ 192.1383; found 192.1386.
1-(4-Methoxybenzyl)piperidin-4-ol (3b): Colorless oil. 1H NMR
(400 MHz, CDCl3): δ = 1.53–1.62 (m, 2 H), 1.85–1.90 (m, 2 H),
2.09 (t, J = 9.9 Hz, 2 H), 2.72–2.74 (m, 2 H), 3.44 (s, 2 H), 3.62–
3.71 (m, 1 H), 3.80 (s, 3 H), 6.84 (d, J = 8.6 Hz, 2 H), 7.21 (d, J =
8.6 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 33.8, 50.5,
128.7, 128.9, 132.7, 135.1, 140.5, 142.5 ppm. IR (CHCl ): ν
=
˜
3
max
3081, 3025, 2927, 2833, 1639, 1597, 1492, 1454, 1344, 1091, 1014,
920, 827, 699 cm–1. HRMS (ESI-TOF): calcd. for [C17H18NCl +
H]+ 272.1206; found 272.1199.
Ethyl 2-(Benzylamino)pent-4-enoate (1x): Colorless oil. 1H NMR
(400 MHz, CDCl3): δ = 1.26 (t, J = 7.1 Hz, 3 H), 2.42 (t, J =
6.8 Hz, 2 H), 3.33 (t, J = 6.5 Hz, 1 H), 3.65 (d, J = 13.0 Hz, 1 H),
3.82 (d, J = 13.0 Hz, 1 H), 4.16 (dq, J = 7.1, 2.2 Hz, 2 H), 5.06–
5.13 (m, 2 H), 5.71–5.82 (m, 1 H), 7.23–7.37 (m, 5 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 14.4, 37.7, 52.0, 60.2, 60.6, 117.9,
55.0, 61.9, 67.1, 113.3, 129.2, 130.4, 158.5 ppm. IR (CHCl ): ν
˜
3
max
= 3393, 3016, 2941, 2836, 1613, 1514, 1294, 1248, 1179, 1100, 1062,
1038, 911, 820, 668 cm–1. HRMS (ESI-TOF): calcd. for
[C13H19NO2 + H]+ 222.1489; found 222.1487.
1-Benzyl-4-chloropiperidine (3ab): Colorless oil. 1H NMR
(400 MHz, CDCl3): δ = 1.86–1.95 (m, 2 H), 2.05–2.14 (m, 2 H),
2.21–2.32 (m, 2 H), 2.71–2.82 (m, 2 H), 3.50 (s, 2 H), 4.01–4.10 (m,
127.1, 128.3, 128.4, 133.7, 139.7, 174.5 ppm. IR (CHCl ): ν
=
˜
3
max
3332, 3065, 3027, 2981, 2935, 2857, 1732, 1642, 1602, 1492, 1462,
1456, 1373, 1337, 1274, 1245, 1186, 1147, 1028, 996, 919, 699 cm–1. 1 H), 7.24–7.35 (m, 5 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
HRMS (ESI-TOF): calcd. for [C14H19NO2 + H]+ 234.1494; found
234.1499.
35.4, 51.1, 57.4, 62.8, 127.2, 128.3, 129.1, 137.9 ppm. IR (CHCl3):
= 3028, 2954, 2806, 2764, 1494, 1451, 1366, 1347, 1259, 1126,
ν
˜
max
Eur. J. Org. Chem. 2015, 2012–2022
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2017