2228
D. Passarella et al. / Tetrahedron: Asymmetry 16 (2005) 2225–2229
(c 0.85, EtOH). Anal. Calcd for C H NO : C, 68.74;
H, 12.18; N, 8.91. Found: C, 68.79; H, 12.24; N, 8.88.
trated to give by flash column chromatography (hexane–
AcOEt, 4:1) 4a (206 mg, 43%) and 5a (131 mg, 28%).
1
3
25
3
1
Compound 4a: H NMR (400 MHz, CDCl ): d 0.95
3
4
.1.3. (+)-1-(1-Methyl-piperidin-2-yl)-propan-2-ol (N-
methylallosedridine), 11b. The treatment of 3b
115 mg, 0.47 mmol) with the same procedure described
for the preparation of 10b gave 11b (50 mg, 0.32 mmol,
(3H, d, J = 6.8 Hz), 1.14–1.22 (1H, m), 1.39–1.64 (7H,
m), 1.46 (9H, s), 1.67–1.78 (1H, m), 2.01 (dt, J = 12.3,
2 Hz), 2.69 (1H, td, J = 13, 2.5 Hz), 3.15–3.28 (1H, m),
(
3.82 (1H, br s), 3.91–4.01 (1H, m), 4.42–4.54 (1H, m);
C NMR (100.6 MHz, CDCl ): d 11.0, 19.9, 26.2,
1
13
6
J = 7.4 Hz), 1.22 (1H, ddd, J = 15.7, 4 Hz), 1.25–1.34
8%). H NMR (400 MHz, CDCl ): d 1.17 (3H, d,
3
3
29.1, 30.2, 30.3, 37.9, 40.0, 47.3, 69.5, 80.7; [a] =
D
(
(
(
7
1H, m), 1.42–1.58 (3H, m), 1.62–1.76 (2H, m), 1.84
1H, ddd, J = 15.7, 9.8, 9.5 Hz), 2.42 (3H, s), 2.44–2.50
1H, m), 2.60–2.66 (1H, m), 2.98 (1H, ddd, J = 11.7,
+37.7 (c 1, CHCl ). Compound 5a: mp 75 °C;
3
1
H
NMR (400 MHz, CDCl ):
d
0.97 (3H, d,
3
J = 7.6 Hz), 1.46 (9H, s), 1.38–1.66 (8H, m), 1.69–1.82
(2H, m), 2.85 (1H, t, J = 13 Hz), 3.53–3.62 (1H, m),
1
3
.5, 4 Hz), 3.92–3.99 (1H, m), 4.72 (1H, br s);
C
1
3
NMR (100.6 MHz, CDCl ): d 21.0, 23.0, 24.1, 25.6,
3.96 (1H, br d, J = 11.5 Hz), 4.34–4.40 (1H, m);
C
3
2
EtOH). Anal. Calcd for C H NO : C, 68.74; H,
9.7, 39.2, 40.0, 53.0, 60.9, 68.1; [a] = +67.5 (c 0.65,
NMR (100.6 MHz, CDCl ): d 10.1, 19.0, 25.5, 28.4,
D
3
29.5, 30.1, 37.7, 48.4, 71.6, 79.6; [a] = +53.3 (c 1,
1
3
25
3
D
1
2.18; N, 8.91. Found: C, 68.79; H, 12.24; N, 8.88.
CHCl3).
4
6
.1.4. 1-Piperidin-2-yl-propan-2-ol (sedridine), 6a or
b. TFA (1.04 mL, 13.6 mmol), was added to a solu-
4.1.7. Stereoselective synthesis of 5a or 5b. A solution
of Et Zn (1 M, 440 lL, 0.44 mmol) in toluene was added
2
tion of 2a or 2b (220 mg, 0.9 mmol) in CH Cl
2
at 0 °C to a solution of (ꢀ)-ephedrine (0.22 mmol) in tolu-
ene (3 mL). The solution was stirred for 15 min at 0 °C,
then a solution of 1a or 1b (50 mg, 0.22 mmol) in toluene
(1 mL) was added. The resulting solution was stirred for
24 h at room temperature. The mixture was washed with
1 M HCl, and extracted with AcOEt. The concentration
of the organic layer gave 5a {[a] = +51.4 (c 1, CHCl )}
2
(
10 mL) at 0 °C. The solution was warmed to room tem-
perature and left stirring for 3 h. The reaction was then
quenched with H O (2,5 mL) and 5 M NH OH to reach
pH 9. The concentration of the organic layer gave 6a or
2
4
1
6
b as a white crystalline solid (97 mg, 75%). H NMR
(
300 MHz, CDCl ): d 1.16 (3H, d, J = 5.6 Hz), 1.38–
3
D
3
1
2
.56 (4H, m), 1.58–1.68 (3H, m), 1.76–1.86 (1H, m),
.62 (1H, dt, J = 11.2, 3.7 Hz), 2.90–3.00 (1H, m), 3.12
or 5b {[a] = ꢀ48.7 (c 1, CHCl )} (65%).
D
3
(
1H, br d, J = 11.2 Hz), 3.74 (2H, br s), 4.05–4.16 (1H,
4.1.8. (+)-1-Piperidin-2-yl-butyl-2-ol (ethylnorlobelol),
8a. The treatment of 4a (200 mg, 0.78 mmol) with
the same procedure described for the preparation of 6a
1
3
m); C NMR (75.4 MHz, CDCl ): d 23.4, 24.1, 25.0,
3
EtOH). Anal. Calcd for C H NO: C, 67.09; H, 11.96;
3
0.8, 43.2, 46.3, 54.5, 64.4; 6a [a] = +26.2 (c 0.85,
D
or 6b gave 8a (75 mg, 67%) as a white crystalline solid.
0.82 (3H, t,
8
17
1
N, 9.78. Found: C, 67.15; H, 11.89; N, 9.80; 6b
a] = ꢀ25.6 (c 0.95, EtOH). Anal. Calcd for
H
NMR (400 MHz, CDCl3):
d
[
C H NO: C, 67.09; H, 11.96; N, 9.78. Found: C,
J = 7.2 Hz), 1.35–1.52 (6H, m), 1.53–1.62 (3H, m),
1.77–1.82 (1H, m), 2.57 (1H, dt, J = 11.8, 3 Hz), 2.85–
2.92 (1H, m), 3.02–3.08 (1H, m), 3.70 (2H, br s), 3.72–
D
8
17
6
7.16; H, 11.90; N, 9.72.
1
3
3
.82 (1H, br s); C NMR (100.6 MHz, CDCl ): d 9.9,
3
4
7
.1.5. 1-Piperidin-2-yl-propan-2-ol (allosedridine), 7a and
b. The treatment of 3a or 3b (200 mg, 0.82 mmol)
24.6, 25.9, 30.5, 31.5, 41.6, 46.7, 54.7, 70.2; mp63 °C;
[a] = +17.5 (c 0.80, EtOH). Anal. Calcd for
D
with the same procedure described for the preparation
of 6a or 6b gave 7a or 7b (69 mg, 59%). H NMR
C H NO: C, 68.74; H, 12.18; N, 8.91. Found: C,
68.78; H, 12.16; N, 8.95.
9
19
1
(
400 MHz, CDCl ): d 1.06–1.12 (1H, m), 1.13 (3H, s),
3
0
1.22–1.33 (2H, m), 1.45–1.52 (2H, m), 1.53–1.65 (2H,
m), 1.77–1.84 (1H, m), 2.54–2.62 (1H, m), 2.71 (1H, tt,
J = 10.7, 2.6 Hz), 3.03 (1H, dq, J = 13.5, 2 Hz), 3.95–
4
2
4.1.9. (ꢀ)-1-Piperidin-2-yl-butyl-2-ol (2 -epi-ethylnor
lobelol), 9a. The treatment of 5a (130 mg, 0.51 mmol)
with the same procedure described for the preparation
1
3
.03 (1H, m); C NMR (100.6 MHz, CDCl ): d 23.8,
of 6a or 6b gave 9a (35 mg, 48%) as a white crystalline
solid. H NMR (400 MHz, CDCl ): d 0.90 (3H, t,
3
1
4.5, 27.4, 34.4, 44.6, 46.0, 58.1, 68.9. Compound 7a
3
[
C H NO: C, 67.09; H, 11.96; N, 9.78. Found: C,
a] = ꢀ16.4 (c 0.80, MeOH). Anal. Calcd for
J = 7.5 Hz), 1.11–1.22 (1H, m), 1.23–1.55 (7H, m),
1.57–1.70 (1H, m), 1.76–1.84 (1H, m), 2.62 (1H, dt,
J = 12.2, 3 Hz), 2.76 (1H, tt, J = 10.7, 2.5 Hz), 3.04–
D
8
17
6
0
1
7.14; H, 11.92; N, 9.80. Compound 7b [a] = +15.5 (c
D
1
3
.95, EtOH). Anal. Calcd for C H NO: C, 67.09; H,
1.96; N, 9.78. Found: C, 67.21; H, 11.99; N, 9.76.
3.10 (1H, m), 3.67–3.75 (1H, m), 4.10 (2H, br s);
C
8
17
NMR (100.6 MHz, CDCl ): d 10.3, 24.9, 27.3, 31.6,
3
3
4.4, 42.5, 46.5, 58.7, 74.7; [a] = ꢀ6.6 (c 0.80, EtOH).
D
4
.1.6. 2-(2-Hydroxy-butyl)-piperidine-1-carboxylic acid
tert-butyl ester, 4a and 5a. A solution of EtMgBr
1 M, 3.7 mL, 3.7 mmol) in Et O was added dropwise
to a solution of 1a (420 mg 1.85 mmol) in THF
4.1.10. 2-Allyl-piperidine-1-carboxylic acid tert-butyl
ester, 12a. BuLi (1.9 mL, 3.04 mmol) was added to a
(
2
+
ꢀ
suspension of Ph P CH I (1.23 g, 3.04 mmol) in THF
3 3
(
15 mL) at ꢀ78 °C. The solution was allowed to warm
(15 mL) cooled at 0 °C. The mixture was allowed to stir
for 15 min at 0 °C after which a solution of 1a (300 mg,
1.32 mmol) in THF (5 mL) was added. The reaction
mixture was warmed to room temperature and stirred
for 3 h. The reaction was quenched with a saturated
upto ꢀ20 °C and left stirring for 5 h. The reaction mix-
ture was quenched with a saturated solution of NH Cl
4
(10 mL) and extracted with CH Cl . The organic layer
2 2
was washed with brine, dried over Na SO , and concen-
2
4