Synthesis of Substituted Piperidines
J . Org. Chem., Vol. 64, No. 9, 1999 3331
NMR δ 34.6, 55.0, 62.9, 107.6, 126.9, 128.1, 129.1, 138.6, 146.7;
HRMS calcd for C13H17N 188.1439 (M + 1), found 188.1437
(M + 1).
2H), 2.05-2.20 (m, 2H), 3.04-3.09 (m, 2H), 3.20-3.27 (m, 2H),
3.34-3.41 (m, 2H), 6.65-6.68 (m, 1H), 6.97 (d, J ) 7.4 Hz,
2H); 13C NMR δ -0.6, 25.3, 28.9, 32.7, 46.5, 115.2, 125.9, 128.4,
1-(1-P h en ylet h yl)-4-ch lor op ip er id in e (2c). 1b reacted
with 4a to give 2c: yield 58%; 1H NMR δ 1.38 (d, J ) 6.7 Hz,
3H), 1.82-1.99 (m, 2H), 1.99-2.15 (m, 2H), 2.15-2.28 (m, 2H),
2.69-2.79 (m, 1H), 2.80-2.91 (m, 1H), 3.45 (q, J ) 6.7 Hz,
1H), 3.92-4.15 (m, 1H), 7.24-7.33 (m, 5H); 13C NMR δ 19.4,
35.9, 48.6, 57.8, 64.4, 126.9, 127.5, 128.2, 143.9. Anal. Calcd
for C13H18ClN: C, 69.78; H, 8.13; N, 6.26. Found: C, 69.75;
H, 8.35; N, 6.56.
1-(1-P h en yleth yl)-4-ch lor o-4-m eth ylp ip er id in e (2d ). 1b
reacted with 4b to give 2d and 5d . 2d : yield 68%; 1H NMR δ
1.60 (d, J ) 6.8 Hz, 3H), 1.83 (s, 3H), 1.94-2.20 (m, 4H), 2.58-
2.70 (m, 2H), 2.72-2.85 (m, 1H), 3.00-3.11 (m, 1H), 3.68 (q,
J ) 6.8 Hz, 1H), 7.43-7.55 (m, 5H); 13C NMR δ 19.5, 33.1,
41.1, 47.3 [46.3], 64.6, 70.0, 126.8, 127.5, 128.2, 144.3. Anal.
Calcd for C14H20ClN: C, 70.71; H, 8.50; N, 5.89. Found: C,
70.73; H, 8.72; N, 6.23.
140.6; MS m/z 345 (M+, 50), 258 (100). Anal. Calcd for C20H35
-
NSi2: N, 4.05. Found: N, 4.20.
9-Meth yl-1,7-bis[(tr im eth ylsilyl)m eth yl]-2,3,6,7-tetr ah y-
d r o-1H,5H-p yr id o[3,2,1-ij]qu in olin e (3b). 1f reacted with
4a to give 3b: yield 46%; 1H NMR δ 0.20 (s, 18H), 1.00 (dd, J
) 10.5, 14.8 Hz, 2H), 1.15 (dd, J ) 4.0, 11.0 Hz, 2H), 1.83-
1.87 (m, 2H), 2.08-2.23 (m, 2H), 2.33 (s, 3H), 2.97-3.09 (m,
2H), 3.09-3.22 (m, 2H), 3.24-3.33 (m, 2H), 6.80 (s, 2H); 13C
NMR δ -0.6, 20.5, 25.7, 29.3, 32.7, 46.9, 126.5, 126.6, 128.8,
138.2; MS m/z 359 (M+, 80), 272 (100). Anal. Calcd for C21H37
-
NSi2: C, 70.11; H, 10.39; N, 3.89. Found: C, 69.96; H, 10.26;
N, 4.26.
9-Met h oxy-1,7-b is[(t r im et h ylsilyl)m et h yl]-2,3,6,7-t et -
r a h yd r o-1H,5H-p yr id o[3,2,1-ij]qu in olin e (3c). 1g reacted
1
with 4a to give 3c: yield 78%; H NMR δ 0.20 (s, 18H), 1.02
(dd, J ) 10.5, 14.9 Hz, 2H), 1.17 (dd, J ) 3.8, 14.9 Hz, 2H),
1.78-1.90 (m, 2H), 2.10-2.22 (m, 2H), 2.98-3.07 (m, 2H),
3.07-3.17 (m, 2H), 3.20-3.29 (m, 2H), 3.88 (s, 3H), 6.62 (s,
2H); 13C NMR δ -0.6, 25.8, 29.6, 33.0, 47.3, 55.8, 112.0, 130.3,
135.8, 150.7; MS m/z 375 (M+, 100), 360 (40), 288 (90). Anal.
Calcd for C21H37NOSi2: N, 3.73. Found: N, 3.91.
1-(1-P h en yleth yl)-4-m eth ylen epiper idin e (5d): yield 21%;
1H NMR δ 1.55 (d, J ) 6.8 Hz, 3H), 2.30-2.42 (m, 4H), 2.52-
2.68 (m, 4H), 3.65 (q, J ) 6.7 Hz, 1H), 4.77 (s, 2H), 7.32-7.50
(m, 5H); 13C NMR δ 19.3, 34.8, 52.0, 64.2, 107.1, 126.7, 127.6,
128.1, 143.8, 147.0. Anal. Calcd for C14H19N: N, 6.96. Found:
N, 7.15.
9-Ch lor o-1,7-bis[(tr im eth ylsilyl)m eth yl]-2,3,6,7-tetr ah y-
d r o-1H,5H-p yr id o[3,2,1-ij]qu in olin e (3d ). 1h reacted with
4a to give 3d : yield 25%; 1H NMR δ 0.20 (s, 18H), 0.97 (dd, J
) 10.4, 14.8 Hz, 2H), 1.10 (dd, J ) 4.1, 15.0 Hz, 2H), 1.75-
1.87 (m, 2H), 2.08-2.16 (m, 2H), 2.96-3.01 (m, 2H), 3.16-
3.22 (m, 2H), 3.31-3.39 (m, 2H), 6.91 (s, 2H); 13C NMR δ -0.6,
25.1, 28.6, 32.9, 46.4, 119.6, 125.4, 130.0, 139.1; MS m/z 379
(M+, 90), 292 (100). Anal. Calcd for C20H34NClSi2: C, 63.19;
H, 9.03; N, 3.69. Found: C, 63.47; H, 9.10; N, 3.71.
1,7-Dim eth yl-1,7-bis[(tr im eth ylsilyl)m eth yl]-2,3,6,7-tet-
r a h yd r o-1H,5H-p yr id o[3,2,1-ij]qu in olin e (3e). 1e reacted
with 4b to give 3e (20%) and 12 (35%): 1H NMR δ 0.17 (s,
9H), 0.20 (s, 9H), 1.37 (dd, J ) 5.5, 14.8 Hz, 2H), 1.48 (dd, J
) 11.8, 16.6 Hz, 2H), 1.62 (s, 3H), 1.63 (s, 3H), 1.95-2.10 (m,
2H), 2.23-2.31 (m, 2H), 3.32-3.46 (m, 4H), 6.82-6.90 (m, 1H),
7.22-7.31 (m, 2H); 13C NMR δ 33.2 [32.1], 33.9 [33.3], 35.2
[35.1], 36.8 [36.7], 47.1 [46.9], 115.3 [115.4], 123.8, 124.3, 131.8;
MS m/z 373 (M+, 60), 358 (40), 286 (100). Anal. Calcd for
C22H39NSi2: C, 70.70; H, 11.54; N, 3.75. Found: C, 71.02; H,
11.13; N, 4.01.
1-(3-Meth yl-3-bu ten yl)-4-[(tr im eth ylsilyl)m eth yl]-1,2,3,4-
tetr a h yd r oqu in olin e (12): 1H NMR δ 0.22 (s, 9H), 1.35, 1.42
(AB, J ) 14.8 Hz, 2H), 1.62 (s, 3H), 2.09 (s, 3H), 1.95-2.20
(m, 2H), 2.50-2.62 (m, 2H), 3.58 (t, J ) 6.0 Hz, 2H), 3.69 (t,
J ) 7.7 Hz, 2H), 5.04 (s, 1H), 5.08 (s, 1H), 6.82-6.90 (m, 2H),
7.26-7.34 (m, 1H), 7.46 (d, J ) 7.4 Hz, 1H); 13C NMR δ 0.8,
22.8, 32.0, 32.4, 33.7, 34.8, 36.8, 45.6, 50.1, 110.5, 111.4, 115.3,
126.1, 126.7, 132.6, 143.4, 143.9. Anal. Calcd for C19H31NSi:
N, 4.65. Found: N, 4.69.
N -[4-(4-C h lo r o p ip e r id in o )p h e n y l]-N ,N -d im e t h y l-
a m in e (13). 1i reacted with 4a to give 13: yield 31%; mp 70.0-
72.0 °C; 1H NMR δ 2.12-2.26 (m, 2H), 2.30-2.44 (m, 2H), 3.03
(s, 6H), 3.03-3.10 (m, 2H), 3.45-3.58 (m, 2H), 4.25-4.36 (m,
1H), 6.90 (d, J ) 8.8 Hz, 2H), 7.08 (d, J ) 8.7 Hz, 2H); 13C
NMR δ 35.5, 41.5, 49.4, 57.3, 114.4, 119.0, 142.9, 145.9; HRMS
calcd for C13H19ClN2 238.1236, found 238.1139.
1-P h en eth yl-4-ch lor op ip er id in e (2e). 1c reacted with 4a
to give 2e: yield 64%; H NMR δ 2.04-2.20 (m, 2H), 2.20-
2.39 (m, 2H), 2.39-2.58 (m, 2H), 2.70-2.82 (m, 2H), 2.88-
3.09 (m, 4H), 4.16-4.32 (m, 1H), 7.30-7.50 (m, 5H); 13C NMR
δ 33.8, 35.5, 51.2, 57.3, 60.3, 126.0, 128.4, 128.6, 140.2. Anal.
Calcd for C13H18ClN: C, 69.78; H, 8.13; N, 6.26. Found: C,
69.62; H, 8.37; N, 6.36.
1-(1-P h en yleth yl)-3-m eth yl-4-ch lor op ip er id in e (8). 1b
reacted with the mixture of 14a and 14b14 to give 8: yield
42%; 1H NMR δ 0.98 (d, J ) 6.3 Hz, 3H) [1.06 (d, J ) 6.3 Hz,
3H)], 1.37 (d, J ) 3.6 Hz, 3H) [1.39 (d, J ) 3.5 Hz, 3H)], 1.60-
2.20 (m, 5H), 2.78-2.88 (m, 1H), 2.96-3.08 (m, 1H), 3.38-
3.50 (m, 2H), 7.20-7.39 (m, 5H); 13C NMR δ 17.2 [17.3], 19.4,
36.7 [36.6], 40.1, 50.1 [50.4], 57.3 [57.6], 64.0 [63.9], 65.5 [65.4],
126.9, 127.5, 128.2, 143.6. Anal. Calcd for C14H20ClN: N, 5.89.
Found: N, 6.07.
1
2-Ben zyl-4a -ch lor od eca h yd r oisoqu in olin e (9). 1a re-
1
acted with 15 to give 9: yield 36%; H NMR δ 1.18-1.26 (m,
2H), 1.26-1.72 (m, 5H), 1.72-1.98 (m, 4H), 2.09 (t, J ) 11.0
Hz, 1H), 2.43 (dd, J ) 2.7, 11.0 Hz, 1H), 2.55 (td, J ) 4.2, 11.0
Hz, 1H), 2.71 (d, J ) 11.0 Hz, 1H), 3.48 (s, 2H), 7.15-7.27 (m,
5H); 13C NMR δ 21.7, 25.4, 25.7, 40.9, 41.1, 45.2, 49.4, 54.9,
63.0, 76.6, 127.0, 128.2, 129.1, 138.5; HRMS calcd for C16H22
-
ClN 264.1519 (M + 1), found 264.1504 (M + 1).
1-[(1S)-1-P h en yleth yl)-3-eth yl-4-ch lor op ip er id in e (10).
1d reacted with 16 to give 10 and 11 (in brackets): yield 58%;
1H NMR δ 0.90 (t, J ) 7.5 Hz, 3H) [0.81 (t, J ) 7.5 Hz, 3H)],
1.36 (d, J ) 5.4 Hz, 3H) [1.38 (d, J ) 6.6 Hz, 3H)], 1.60-1.80
(m, 3H), 1.85-2.20 (m, 4H), 2.72-3.14 (m, 2H), 3.40-3.50 (m,
1H), 3.50-3.63 (m, 1H), 7.20-7.38 (m, 5H); 13C NMR δ 10.9
[10.8], 19.7 [18.9], 24.0 [23.8], 36.3 [36.2], 45.9, 49.7 [49.8], 54.3
[54.2], 63.9 [63.7], 64.3, 126.8 [126.9], 127.4 [127.5], 128.2,
143.5. Anal. Calcd for C15H22ClN: C, 71.54; H, 8.82; N, 5.56.
Found: C, 71.26; H, 9.20; N, 5.74.
1,7-Bis[(tr im eth ylsilyl)m eth yl]-2,3,6,7-tetr ah ydr o-1H,5H-
p yr id o[3,2,1-ij]qu in olin e (3a ). 1e reacted with 4a to give
1
3a : yield 47%; H NMR δ 0.20 (s, 18H), 1.01 (dd, J ) 10.2,
14.8 Hz, 2H), 1.14 (dd, J ) 4.2, 14.9 Hz, 2H), 1.85-1.91 (m,
J O982356N