1
IR (DRA): 3271, 1607, 1570, 1522 cm−1; H NMR (500 MHz,
[α]2D5 = +222 (c 1.22, CHCl3); IR (ATR): 1720, 1665,
1
CDCl3): δ 4.97 (s, 1H), 4.80 (bs, 1H), 3.79–3.72 (m, 1H),
2.36 (dd, J = 16.1 Hz, J = 4.8 Hz, 1H), 2.25 (dd, J = 16.1 Hz,
J = 13.2 Hz, 1H), 2.20–2.12 (m, 2H), 1.54 (quint., J = 7.4 Hz,
2H), 1.30 (d, J = 6.5 Hz, 3H), 1.36–1.20 (m, 12H), 0.88 (t, J =
6.9 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 192.7, 165.9,
98.3, 49.1, 43.2, 35.2, 31.8, 29.4, 29.3, 29.2, 29.1, 27.6, 22.6,
20.4, 14.1; HRMS (ESI, m/z): Calcd for C15H27NONa:
260.1990, found [M + Na]+: 260.1988.
1592 cm−1; H NMR (500 MHz, CDCl3): δ 7.42–7.34 (m, 5H),
5.41 (s, 1H), 5.26 (AB, JAB = 12.1 Hz, 1H), 5.22 (AB, JAB
=
12.1 Hz, 1H), 4.92–4.87 (m, 1H), 3.02–2.97 (m, 1H), 2.81 (dd,
J = 17.1 Hz, J = 6.1 Hz, 1H), 2.32–2.26 (m, 1H), 2.24 (d, J =
17.1 Hz, 1H), 1.40–1.15 (m, 14H), 1.27 (d, J = 6.8 Hz, 3H),
0.88 (t, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 193.5,
158.3, 153.1, 135.2, 128.7, 128.7, 128.4, 111.8, 68.6, 52.2, 42.6,
35.8, 31.8, 29.4, 29.3, 29.2, 29.2, 28.0, 22.6, 16.6, 14.1;
HRMS (ESI, m/z): Calcd for C23H33NO3Na: 394.2358, found
[M + Na]+: 394.2357.
(2R,4S,6S)-2-Methyl-6-nonylpiperidin-4-ol (+)-1
In a 10 mL reactor equipped with a magnetic stirrer and a H2
funnel was placed substrate 7 (100 mg, 0.42 mmol, 1.0 eq) in
methanol (3 mL). 10% Pd/C (45 mg, 0.042 mmol, 0.1 eq) was
added and the suspension was stirred under H2 (8 bars) at room
temperature for 72 hours. The reaction mixture was filtered
through a Celite plug and the filtrate was concentrated under
reduced pressure. Column chromatography of the crude product
(silica gel, EtOAc–MeOH 1 : 1) afforded compound (+)-1 as a
white solid in 78% yield: mp = 108–109 °C (lit.12f mp =
108–109 °C); [α]D25 = +7.0 (c = 1.00, MeOH) [lit.12f [α]2D5 = +6.5
(c 2.00, MeOH)]; IR (DRA): 3267, 3181, 2958, 2918,
(2S,4R,6R)-2-Methyl-6-nonylpiperidin-4-ol (−)-1
The same hydrogenation procedure described above for
(+)-241D (+)-1 was followed to prepare (−)-1 starting from the
compound 10 (0.15 g, 0.40 mmol, 1.0 eq) in MeOH (3 mL),
10% Pd/C (43 mg, 0.040 mmol, 0.1 eq) and H2 (8 bars), rt,
6 days. Yield 70 mg (72%), white solid: mp = 108–109 °C
(lit.12a mp = 107 °C); [α]D25 = −6.5 (c 1.00, MeOH) [lit.12a
[α]2D5 = −6.5 (c 1.32, MeOH)]; HRMS (ESI, m/z): Calcd for
C15H32NO: 242.2484, found [M + H]+: 242.2484. Spectral data
are identical with those reported for (+)-1 and those reported in
the literature.12f
1
2848 cm−1; H NMR (500 MHz, CDCl3): δ 3.69–3.62 (m, 1H),
2.73–2.66 (m, 1H), 2.58–2.52 (m, 1H), 2.00–1.94 (m, 2H), 1.63
(bs, 2H), 1.50–1.20 (m, 16H), 1.13 (d, J = 6.2 Hz, 3H),
1.06–0.95 (m, 2H), 0.88 (t, J = 6.9 Hz, 3H); 13C NMR
(125 MHz, CDCl3): δ 69.4, 54.8, 50.2, 43.8, 41.7, 36.7, 31.9,
29.7, 29.5, 29.5, 29.3, 26.0, 22.7, 22.4, 14.1; HRMS (ESI, m/z):
Calcd for C15H32NO: 242.2484, found [M + H]+: 242.2485.
(2R)-tert-Butyl 2-methyl-4-oxo-1,2,3,4-tetrahydro-6-undecyl-pyridine-
1-carboxylate (11)
The same procedure described above for compound 5 was fol-
lowed to prepare the amino-ynone precursor of 11 starting from
1-tridecyne (1.9 mL, 8.12 mmol, 4 eq) in THF (12 mL), BuLi
2.5 M in hexane (3.1 mL, 7.71 mmol, 3.8 eq) and Weinreb
amide obtained from Boc-D-Ala-OH (0.5 g, 2.03 mmol, 1.0 eq)
in THF (7 mL). The deprtonation step for 11 was performed
from −78 °C to −20 °C over 1 h. Yield 0.65 g (87%), clear oil:
[α]2D5 = +1.5 (c 1.03, CHCl3); IR (ATR): 3349, 2211, 1694,
(S)-Benzyl 4-oxopentadec-5-yn-2-ylcarbamate (9)
The same procedure described above for compound 5 was fol-
lowed to prepare
9 starting from 1-undecyne (1.7 mL,
8.56 mmol, 4.0 eq) in THF (8 mL), BuLi 2.5 M in hexane
(3.2 mL, 8.13 mmol, 3.8 eq), Weinreb amide obtained from
Z–Ala–OH (0.6 g, 2.14 mmol, 1 eq) in THF (7 mL). Yield
0.71 g (89%), clear oil: [α]2D5 = +1.8 (c 1.14, CHCl3); IR (ATR):
1
1670 cm−1; H NMR (500 MHz, CDCl3): two conformers in a
90/10 ratio δ 4.78 (bs, 0.9H) and 4.40 (bs, 0.1H), 4.20–4.01
(m, 1H), 2.81 (dd, J = 16.2 Hz, J = 5.3 Hz, 1H), 2.66 (dd, J =
16.1 Hz, J = 6.0 Hz, 1H), 2.36 (t, J = 7.2 Hz, 2H), 1.58 (quint.,
J = 7.3 Hz, 2H), 1.44 (s, 9H), 1.41–1.23 (m, 16H), 1.21 (d, J =
6.7 Hz, 3H), 0.88 (t, J = 6.9 Hz, 3H); 13C NMR (125 MHz,
CDCl3): δ 186.0, 155.0, 95.3, 81.0, 79.3, 51.4, 43.5, 31.9, 29.6,
29.4, 29.3, 29.0, 28.9, 28.4, 27.7, 22.7, 20.5, 19.0, 14.1;
HRMS (ESI, m/z): Calcd for C22H39NO3Na: 388.2828, found
[M + Na]+: 388.2829.
The same procedure described above for compound 6 was
followed to prepare 11 starting from the corresponding amino
ynone (0.5 g, 1.37 mmol, 1 eq) in 1,2-dichoroethane (6 mL),
PPh3AuCl (34 mg, 0.068 mmol, 5 mol%) and AgSbF6 (23.5 mg,
0.068 mmol, 5 mol%). Yield 0.44 g (82%), pale yellow oil: [α]D25
1
3326, 2210, 1697, 1669 cm−1; H NMR (500 MHz, CDCl3): δ
7.38–7.29 (m, 5H), 5.16–5.00 (m, 3H), 4.21–4.13 (m, 1H), 2.83
(dd, J = 16.3 Hz, J = 4.4 Hz, 1H), 2.71 (dd, J = 16.3 Hz, J = 5.8
Hz, 1H), 2.34 (t, J = 7.1 Hz, 2H), 1.56 (quint., J = 7.3 Hz, 2H),
1.42–1.34 (m, 2H), 1.34–1.20 (m, 10H), 1.24 (d, J = 6.9 Hz,
3H), 0.88 (t, J = 6.9 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ
185.8, 155.4, 136.5, 128.5, 128.1, 128.0, 95.6, 80.9, 66.6, 51.1,
43.9, 31.8, 29.3, 29.2, 29.0, 28.8, 27.6, 22.6, 20.4, 18.9, 14.1;
HRMS (ESI, m/z): Calcd for C23H33NO3Na: 394.2358, found
[M + Na]+: 394.2359.
(2S)-Benzyl 2-methyl-6-nonyl-4-oxo-1,2,3,4-tetrahydro-pyridine-
1-carboxylate (10)
= −229 (c 0.97, CHCl3); IR (ATR): 1711, 1665, 1589 cm−1
;
1H NMR (500 MHz, CDCl3): δ 5.37 (s, 1H), 4.81–4.76 (m, 1H),
3.09–3.03 (m, 1H), 2.81 (dd, J = 16.9 Hz, J = 6.2 Hz, 1H),
2.30–2.24 (m, 1H), 2.22 (d, J = 16.9 Hz, 1H), 1.54 (s, 9H),
1.48–1.20 (m, 21H), 0.88 (t, J = 6.9 Hz, 3H); 13C NMR
(125 MHz, CDCl3): δ 193.7, 158.7, 152.2, 111.0, 82.7, 52.1,
42.7, 36.0, 31.9, 29.6, 29.5, 29.4, 29.3, 29.2, 28.1, 27.9, 22.6,
The same procedure described above for compound 6 was fol-
lowed to prepare 10 starting from the amino ynone 9 (0.5 g,
1.35 mmol, 1 eq) in 1,2-dichoroethane (6 mL), PPh3AuCl
(33 mg, 0.067 mmol,
5 mol%) and AgSbF6 (23 mg,
0.067 mmol, 5 mol%). Yield 0.44 g (88%), pale yellow oil:
5544 | Org. Biomol. Chem., 2012, 10, 5541–5546
This journal is © The Royal Society of Chemistry 2012