The Journal of Organic Chemistry
Note
58.0, 52.1, 45.9, 38.4, 34.0, 33.2, 30.0, 28.5, 23.2, 18.0, 14.3; HRMS
(ESI+) calcd for [C20H32N + H]+ 286.2529, found 286.2532.
rel-(2R,3S,4R)-3-Allyl-1-benzyl-4-isobutyl-2-methylpiperidine
1H), 5.79 (ddt, J = 17.5, 10.3, 7.5 Hz, 1H), 5.63 (ddd, J = 19.2, 10.2,
9.0 Hz, 1H), 5.07−4.96 (m, 4H), 4.08 (d, J = 13.5 Hz, 1H), 3.18 (d, J
= 13.6 Hz, 1H), 2.79 (dt, J = 11.8, 3.4 Hz, 1H), 2.31−2.25 (m, 2H),
2.25−2.15 (m, 1H), 2.05−1.93 (m, 2H), 1.53−1.41 (m, 2H), 1.35−
1.22 (m, 1H), 1.27 (d, J = 6.0 Hz, 3H); 13C NMR δ 143.2, 139.8,
135.5, 129.2, 128.3, 126.8, 116.5, 114.7, 59.3, 57.9, 51.9, 45.4, 44.7,
34.1, 31.9, 17.8; HRMS (ESI+) calcd for [C18H26N + H]+ 256.2060,
found 256.2066.
1
(2d): 44 mg, 78% yield; gum; H NMR δ 7.35−7.28 (m, 4H), 7.26−
7.21 (m, 1H), 5.80 (ddt, J = 17.3, 10.4, 7.2 Hz, 1H), 5.09−4.98 (m,
2H), 4.04 (d, J = 13.6 Hz, 1H), 3.26 (d, J = 13.4 Hz, 1H), 2.80 (dt, J =
11.6, 3.5 Hz,1H), 2.38−2.29 (m, 1H), 2.29−2.18 (m, 2H), 2.00 (dt, J
= 11.8, 2.8 Hz, 1H), 1.71−1.59 (m, 2H), 1.40 (ddd, J = 13.4, 10.3, 3.2
Hz, 1H), 1.35−1.23 (m, 1H), 1.27 (d, J = 6.0 Hz, 3H), 1.23−1.08 (m,
2H), 0.98 (ddd, J = 13.6, 10.1, 3.2 Hz, 1H), 0.90 (d, J = 6.6 Hz, 3H),
0.81 (d, J = 6.5 Hz, 3H); 13C NMR δ 139.5, 136.3, 129.2, 128.2, 126.8,
116.1, 59.7, 57.8, 51.8, 46.6, 43.4, 36.2, 34.0, 30.0, 24.9, 24.5, 21.4,
18.0; HRMS (ESI+) calcd for [C20H32N + H]+ 286.2529, found
286.2532.
rel-(2R,3S,4S)-3-Allyl-1-benzyl-4-cyclopentyl-2-methylpiperidine
1
(2k): 25 mg, 42% yield; gum; H NMR δ 7.35−7.27 (m, 4H), 7.25−
7.20 (m, 1H), 5.80 (ddt, J = 17.2, 10.2, 7.1 Hz, 1H), 5.07−4.97 (m,
2H), 3.95 (d, J = 13.6 Hz, 1H), 3.28 (d, J = 13.6 Hz, 1H), 2.80 (ddd, J
= 11.7, 4.2, 2.4 Hz,1H), 2.42−2.33 (m, 1H), 2.33−2.14 (m, 3H),
2.07−1.99 (m, 1H), 1.63−1.44 (m, 7H), 1.42−1.12 (m, 5H), 1.24 (d, J
= 6.3 Hz, 3H); 13C NMR δ 139.9, 136.8, 129.1, 128.2, 126.8, 116.0,
59.1, 58.2, 50.7, 44.5, 41.1, 40.5, 30.2, 27.0, 25.8, 25.7, 24.5, 17.2;
HRMS (ESI+) calcd for [C21H32N + H]+ 298.2529, found 298.2528.
rel-(2R,3S,4S)-3-Allyl-1-benzyl-4-cyclohexyl-2-methylpiperidine
rel-(2R,3S,4R)-3-Allyl-1-benzyl-4-tert-butyl-2-methylpiperidine
1
(2e): 43 mg, 75% yield; gum; H NMR δ 7.37−7.28 (m, 4H), 7.26−
7.20 (m, 1H), 5.75 (ddt, J = 17.1, 10.2, 7.0 Hz, 1H), 4.96−4.90 (m,
1H), 4.87−4.79 (m, 1H), 3.78 (d, J = 13.5 Hz, 1H), 3.46 (d, J = 13.2
Hz, 1H), 2.68 (ddd, J = 10.8, 6.5, 2.5 Hz,1H), 2.55−2.43 (m, 2H),
2.40−2.30 (m, 1H), 2.23−2.14 (m, 1H), 1.68−1.59 (m, 1H), 1.59−
1.46 (m, 1H), 1.39−1.30 (m, 1H), 1.19 (ddd, J = 12.6, 7.4, 5.3 Hz,
1H), 1.10 (d, J = 6.6 Hz, 3H), 0.93 (m, 9H); 13C NMR δ 140.2, 137.8,
129.1, 128.2, 126.8, 115.9, 59.6, 56.3, 49.5, 46.9, 42.5, 40.0, 33.8, 28.7,
23.8, 17.7; HRMS (ESI+) calcd for [C20H32N + H]+ 286.2529, found
286.2525.
1
(2l): 43 mg, 69% yield; gum; H NMR δ 7.35−7.27 (m, 4H), 7.27−
7.19 (m, 1H), 5.80 (ddt, J = 17.0, 10.1, 7.0 Hz, 1H), 5.10−4.99 (m,
2H), 4.05 (d, J = 13.6 Hz, 1H), 3.23 (d, J = 13.6 Hz, 1H), 2.83 (dt, J =
11.6, 3.5 Hz,1H), 2.36−2.14 (m, 3H), 1.98 (dt, J = 11.8, 2.6 Hz, 1H),
1.80−1.71 (m, 2H), 1.71−1.54 (m, 3H), 1.51−1.04 (m, 9H), 1.29 (d, J
= 6.3 Hz, 3H), 1.01−0.87 (m, 1H); 13C NMR δ 139.6, 136.2, 129.2,
128.2, 126.7, 116.0, 59.9, 58.0, 52.8, 44.1, 42.6, 38.0, 34.6, 33.3, 33.1,
27.5, 27.1, 26.5, 24.9, 18.2; HRMS (ESI+) calcd for [C22H34N + H]+
312.2686, found 312.2692.
rel-(2R,3S,4R)-3-Allyl-1-benzyl-2-methyl-4-phenethylpiperidine
1
(2f): 51 mg, 77% yield; gum; H NMR δ 7.37−7.21 (m, 7H), 7.21−
7.14 (m, 3H), 5.92 (ddt, J = 17.1, 10.0, 7.1 Hz, 1H), 5.07−4.96 (m,
2H), 4.05 (d, J = 13.6 Hz, 1H), 3.22 (d, J = 13.6 Hz, 1H), 2.87−2.78
(m, 1H), 2.70 (ddd, J = 13.7, 11.1, 5.0 Hz,1H), 2.48 (ddd, J = 13.6,
10.5, 5.9 Hz,1H), 2.38−2.15 (m, 3H), 2.06−1.87 (m, 2H), 1.78−1.68
(m, 1H), 1.52−1.40 (m, 1H), 1.40−1.21 (m, 3H), 1.27 (d, J = 6.1 Hz,
3H); 13C NMR δ 143.0, 139.6 (2 x C), 136.1, 129.2, 128.4, 128.2,
126.8, 125.8, 116.2, 59.7, 57.9, 51.9, 45.7, 38.1, 35.6, 33.9, 32.7, 29.9,
17.9; HRMS (ESI+) calcd for [C24H32N + H]+ 334.2529, found
334.2535.
rel-(2R,3S,4R)-3-Allyl-1-benzyl-2-methyl-4-phenylpiperidine (2m):
51 mg, 84% yield; gum; 1H NMR δ 7.40−7.16 (m, 10H), 5.75 (ddt, J
= 17.5, 10.4, 7.5 Hz, 1H), 4.99−4.93 (m, 1H), 4.90−4.82 (m, 1H),
4.16 (d, J = 13.6 Hz, 1H), 3.28 (d, J = 13.6 Hz, 1H), 2.89 (dt, J = 11.6,
3.5 Hz,1H), 2.49 (dt, J = 11.7, 4.1 Hz,1H), 2.33 (dq, J = 10.0, 6.1
Hz,1H), 2.21−2.11 (m, 1H), 2.13 (dt, J = 2.7, 11.9 Hz,1H), 1.95−1.85
(m, 1H), 1.83−1.71 (m, 2H), 1.70−1.63 (m, 1H), 1.35 (d, J = 6.0 Hz,
3H); 13C NMR δ 145.8, 139.7, 135.2, 129.2, 128.6, 128.3, 127.9, 126.8,
126.2, 116.6, 60.0, 57.8, 53.0, 47.0, 46.3, 34.3, 33.9, 17.9; HRMS (ESI
+) calcd for [C22H28N + H]+ 306.2216, found 306.2218.
rel-(2R,3S,4R)-3-Allyl-1-benzyl-4-(but-3-enyl)-2-methylpiperidine
1
(2g): 48 mg, 84% yield; gum; H NMR δ 7.37−7.27 (m, 4H), 7.27−
rel-(2R,3S,4R)-3-Allyl-1-benzyl-4-(4-chlorophenyl)-2-methylpiperi-
1
7.20 (m, 1H), 5.89−5.72 (m, 2H), 5.09−4.90 (m, 4H), 4.04 (d, J =
13.5 Hz, 1H), 3.22 (d, J = 13.5 Hz, 1H), 2.84−2.76 (m, 1H), 2.38−
2.07 (m, 4H), 2.04−1.89 (m, 2H), 1.75−1.58 (m, 2H), 1.36−1.14 (m,
4H), 1.26 (d, J = 6.1 Hz, 3H); 13C NMR δ 139.8, 139.3, 136.3, 129.2,
128.2, 126.8, 116.1, 114.4, 59.7, 58.0, 52.0, 45.9, 38.0, 34.0, 32.8, 30.6,
29.8, 18.0; HRMS (ESI+) calcd for [C20H30N + H]+ 284.2373, found
284.2374.
dine (2n): 63 mg, 93% yield; gum; H NMR δ 7.41−7.31 (m, 4H),
7.31−7.23 (m, 3H), 7.18−7.10 (m, 2H), 5.73 (ddt, J = 17.3, 10.3, 7.3
Hz, 1H), 5.02−4.94 (m, 1H), 4.91−4.82 (m, 1H), 4.16 (d, J = 13.6
Hz, 1H), 3.27 (d, J = 13.6 Hz, 1H), 2.88 (dt, J = 11.7, 3.4 Hz,1H), 2.48
(dt, J = 11.7, 4.2 Hz,1H), 2.38−2.28 (m,1H), 2.22−2.06 (m, 2H),
1.94−1.83 (m,1H), 1.79−1.59 (m, 3H), 1.35 (d, J = 6.2 Hz, 3H); 13C
NMR δ 144.3, 139.6, 134.9, 131.8, 129.2, 129.2, 128.7, 128.3, 126.9,
116.9, 59.9, 57.8, 52.8, 46.4, 46.2, 34.3, 33.9, 17.9; HRMS (ESI+) calcd
for [C22H27ClN + H]+ 340.1827, found 340.1834.
rel-(2R,3S,4R)-3-Allyl-1,4-dibenzyl-2-methylpiperidine (2h): 41
1
mg, 64% yield; gum; H NMR δ 7.34−7.22 (m, 7H), 7.22−7.16 (m,
1H), 7.16−7.11 (m, 2H), 5.92 (ddt, J = 17.3, 10.1, 7.2 Hz, 1H), 5.20−
5.10 (m, 2H), 4.06 (d, J = 13.6 Hz, 1H), 3.26 (d, J = 13.6 Hz, 1H),
3.16 (dd, J = 13.1, 3.4 Hz,1H), 2.75 (dt, J = 11.8, 3.7 Hz,1H), 2.57−
2.48 (m, 1H), 2.47−2.39 (m, 1H), 2.29 (ddd, J = 12.1, 9.4, 5.9 Hz,
1H), 2.17 (dd, J = 13.2, 10.3 Hz,1H), 1.92 (dt, J = 2.6, 13.6 Hz,1H),
1.55 (ddt, J = 21.9, 10.9, 3.9 Hz, 1H), 1.43−1.31 (m, 2H), 1.34 (d, J =
6.0 Hz, 3H), 1.27−1.15 (m, 1H); 13C NMR δ 141.1, 139.5, 136.0,
129.3, 129.2, 128.3, 128.2, 126.8, 125.8, 116.5, 59.6, 57.8, 51.9, 46.2,
40.8, 40.4, 34.1, 29.8, 18.1; HRMS (ESI+) calcd for [C23H30N + H]+
320.2373, found 320.2380.
rel-(2R,3S,4R)-3-Allyl-1-benzyl-2-methyl-4-((trimethylsilyl)-
methyl)piperidine (2i): 56 mg, 89% yield; gum; 1H NMR δ 7.38−7.30
(m, 4H), 7.30−7.22 (m, 1H), 5.82 (ddt, J = 17.3, 10.2, 7.2 Hz, 1H),
5.12−4.99 (m, 2H), 4.07 (d, J = 13.5 Hz, 1H), 3.23 (d, J = 13.5 Hz,
1H), 2.78 (dt, J = 11.6, 3.3 Hz,1H), 2.43−2.33 (m, 1H), 2.31−2.16
(m, 2H), 2.01 (dt, J = 2.5, 13.5 Hz, 1H), 1.71−1.62 (m, 1H), 1.44−
1.33 (m, 1H), 1.33−1.11 (m, 2H), 1.30 (d, J = 5.9 Hz, 3H), 0.98 (dd, J
= 14.9, 2.6 Hz, 1H), 0.32 (dd, J = 14.8, 10.5 Hz, 1H), 0.03 (s, 9H); 13C
NMR δ 139.7, 136.5, 129.2, 128.2, 126.8, 115.9, 60.0, 58.0, 52.2, 49.0,
35.7, 34.2, 33.6, 21.9, 18.2, −0.3; HRMS (ESI+) calcd for [C20H34NSi
+ H]+ 316.2455, found 316.2461.
rel-3-((2R,3S,4R)-3-Allyl-1-benzyl-2-methylpiperidin-4-yl)-N,N-bis-
(trimethylsilyl)aniline (2o): 45 mg, 64% yield; gum; 1H NMR δ 7.38−
7.30 (m, 4H), 7.28−7.22 (m, 1H), 7.11 (t, J = 7.6 Hz, 1H), 6.90−6.87
(m, 1H), 6.75−6.70 (m, 2H), 5.75 (ddt, J = 17.4, 10.3, 7.4 Hz, 1H),
4.99−4.93 (m, 1H), 4.92−4.84 (m, 1H), 4.16 (d, J = 13.5 Hz, 1H),
3.28 (d, J = 13.5 Hz, 1H), 2.88 (dt, J = 11.8, 3.5 Hz,1H), 2.41 (dt, J =
11.8, 4.2 Hz, 1H), 2.30 (dq, J = 10.0, 5.9 Hz, 1H), 2.23−2.05 (m, 2H),
1.97−1.88 (m, 1H), 1.80−1.67 (m, 2H), 1.66−1.60 (m, 1H), 1.35 (d, J
= 6.2 Hz, 3H), 0.04 (s, 18H); 13C NMR δ 148.1, 146.1, 139.5, 135.3,
129.6, 129.3, 128.4, 128.3, 128.1, 126.9, 123.4, 116.6, 60.0, 58.0, 53.0,
46.8, 46.4, 34.4, 33.8, 17.9, 2.2; HRMS (ESI+) calcd for [C22H29N2 −
2SiMe3 + 3H]+ 321.2325, found 321.2328.
rel-(2R,3S,4R)-3-Allyl-1-benzyl-4-mesityl-2-methylpiperidine (2p):
1
58 mg, 83% yield; gum; H NMR δ 7.40−7.31 (m, 4H), 7.29−7.23
(m, 1H), 6.82 (s, 1H), 6.79 (s, 1H), 5.70 (ddt, J = 17.2, 10.0, 7.1 Hz,
1H), 4.95−4.89 (m, 1H), 4.80−4.72 (m, 1H), 4.12 (d, J = 13.6 Hz,
1H), 3.35 (d, J = 13.6 Hz, 1H), 2.98−2.86 (m, 2H), 2.45 (s, 3H),
2.38−2.15 (m, 5H), 2.29 (s, 3H), 2.24 (s, 3H), 2.06 (dq, J = 12.6, 3.6
Hz,1H), 1.98−1.88 (m, 1H), 1.50−1.42 (m, 1H), 1.36 (d, J = 5.4 Hz,
3H); 13C NMR δ 139.8, 137.7, 137.0, 136.1, 135.7, 135.1, 131.3, 129.6,
129.2, 128.3, 126.8, 116.5, 61.3, 57.3, 53.6, 43.5, 43.3, 34.4, 29.4, 22.2,
21.8, 20.8, 17.9; HRMS (ESI+) calcd for [C25H34N + H]+ 348.2686,
found 348.2691.
rel-(2R,3S,4R)-3-Allyl-1-benzyl-2-methyl-4-vinylpiperidine (2j): 52
1
mg, 51% yield; gum; H NMR δ 7.36−7.27 (m, 4H), 7.27−7.20 (m,
D
dx.doi.org/10.1021/jo300690h | J. Org. Chem. XXXX, XXX, XXX−XXX