2,3,6-Trisubstituted Piperidines
J. Am. Chem. Soc., Vol. 123, No. 50, 2001 12485
3-furyl-tri-n-butyltin26 (157 mg, 0.44 mmol, 2.2 equiv) and n-BuLi (1.53
M in hexanes, 0.26 mL, 0.40 mmol, 2.0 equiv) for 20 min at -78 °C.
In this case reverse addition was used for the addition of the second
nucleophile: the cationic diene solution was added into a solution of
3-furyllithium at -100 °C via cannula. After 1 min the reaction was
quenched with methanol (1 mL) at -100 °C. After chromatography
(10% ethyl acetate in hexanes, 15 × 2 cm), 23d was obtained as a
yellow solid (113 mg, 0.16 mmol, 82%), mp > 122 °C with
((CD3)CO, 100 MHz) δ 234.1, 233.7, 227.8, 227.7, 156.3, 155.1, 147.5,
147.3, 141.7, 141.5, 138.0, 137.9, 137.7, 137.2, 135.9, 129.23, 129.19,
129.1, 128.8, 128.7, 106.7, 106.4, 105.2, 105.04, 104.98, 100.2, 99.1,
85.6, 85.3, 76.3, 75.8, 67.9, 67.7, 66.2, 65.42, 65.36, 59.7, 58.9, 56.9,
56.65, 56.57, 56.3, 34.7, 32.4, 32.0, 31.8, 31.7, 30.8, 24.8, 24.7; IR
(CH2Cl2, KCl, cm-1) 2951, 2886, 2484, 1939, 1852, 1697, 1506, 1410,
1305, 1051. Anal. Calcd for C31H36BMoN7O7: C, 51.33; H, 5.00; N,
13.52. Found: C, 51.25; H, 5.08; N, 13.41.
1
decomposition (Et2O/hexanes). H NMR (CDCl3, 400 MHz): δ 8.53
Data for 23e: TLC (30% ethyl acetate in hexanes) Rf ) 0.19; mp
1
(d, J ) 1.6 Hz, 0.5 H), 8.50 (d, J ) 1.6 Hz, 0.5 H), 7.78 (d, J ) 1.2
Hz, 0.5 H), 7.77 (d, J ) 1.6 Hz, 0.5 H), 7.74 (s, 0.5 H), 7.71-7.65 (m,
3 H), 7.58 (s, 0.5 H), 7.49 (s, 1 H), 7.46-7.31 (m, 6 H), 6.67 (d, J )
0.8 Hz, 0.5 H), 6.48 (d, J ) 0.8 Hz, 0.5 H), 6.27-6.18 (m, 3 H), 5.59
(d, J ) 2.4 Hz, 0.5 H), 5.49 (d, J ) 2.4 Hz, 0.5 H), 5.45-5.32 (m, 1.5
H), 5.27-5.06 (m, 3 H), 4.80 (dd, J ) 9.8, 1.8 Hz, 0.5 H), 4.77 (d, J
) 8.8 Hz, 0.5 H), 4.69 (d, J ) 9.6 Hz, 0.5 H), 4.40 (dd, J ) 7.2, 2.8
Hz, 0.5 H), 4.34 (dd, J ) 7.2, 2.8 Hz, 0.5 H), 4.13 (d, J ) 7.2 Hz, 0.5
H), 4.12 (d, J ) 7.6 Hz, 0.5 H), 1.84 (s, 1.5 H), 1.79 (s, 1.5 H). 13C
NMR (CDCl3, 100 MHz): δ 232.1, 231.5, 226.7, 226.1, 154.8, 153.6,
146.6, 146.0, 145.9, 142.8, 142.7, 140.4, 140.2, 139.4, 139.1, 138.6,
136.65, 136.62, 136.5, 136.0, 134.3, 129.8, 129.7, 128.3, 128.1, 128.0,
127.9, 127.8, 127.6, 118.8, 118.2, 110.9, 110.7, 105.6, 105.25, 105.18,
93.9, 93.3, 73.0, 72.8, 67.2, 60.1, 59.8, 59.5, 59.4, 46.1, 45.8, 24.5,
24.4. IR (CH2Cl2, KCl, cm-1): 2484, 1938, 1852, 1691, 1502, 1410,
1305, 1051. Anal. Calcd for C31H30BMoN7O5: C, 54.17; H, 4.40; N,
14.26. Found: C, 54.20; H, 4.48; N, 14.01.
) 93-95 °C with decomposition (ether/hexanes); H NMR (CDCl3,
400 MHz) δ 8.48 (s, 0.5 H), 8.44 (s, 0.5 H), 7.75 (s, 0.5 H), 7.74 (s,
0.5 H), 7.64-7.61 (m, 3 H), 7.46 (d, J ) 1.2 Hz, 1 H), 7.42-7.29 (m,
5 H), 6.24 (s, 1 H), 6.22 (s, 1 H), 6.16 (s, 1 H), 5.16-5.03 (m, 2 H),
4.91 (t, J ) 4.6 Hz, 0.5 H), 4.75 (t, J ) 4.6 Hz, 0.5 H), 4.52-4.47 (m,
1 H), 4.41-4.34 (m, 1 H), 4.22 (dd, J ) 7.6, 2.4 Hz, 0.5 H), 4.12 (dd,
J ) 7.6, 2.4 Hz, 0.5 H), 3.97-3.75 (m, 5 H), 2.28-2.13 (m, 1 H),
1.92 (s, 1.5 H), 1.87 (s, 1.5 H), 2.05-1.46 (m, 6.5 H), 1.41-1.25 (m,
4.5 H), 0.93 (t, J ) 7.2 Hz, 1.5 H), 0.84 (t, J ) 7.2 Hz, 1.5 H); 13C
NMR (CDCl3, 100 MHz) δ 232.3, 231.6, 227.4, 226.8, 155.1, 154.9,
146.6, 145.8, 139.6, 136.9, 136.6, 136.5, 135.8, 134.2, 128.6, 128.2,
128.1, 128.0, 127.7, 127.5, 105.5, 105.24, 105.16, 104.4, 104.1, 95.9,
95.4, 73.2, 73.0, 67.3, 67.0, 64.8, 64.7, 64.6, 63.04, 62.98, 55.6, 55.3,
51.82, 51.76, 40.8, 40.6, 33.7, 32.3, 32.00, 31.95, 31.6, 30.2, 27.2, 27.1,
24.6, 24.5, 22.6, 22.5, 14.1, 14.0; IR (CH2Cl2, KCl, cm-1) 2957, 2484,
1934, 1848, 1688, 1409, 1305, 1124, 1051. Anal. Calcd for C35H44-
BMoN7O6: C, 54.91; H, 5.79; N, 12.81. Found: C, 54.70; H, 5.84; N,
12.81.
(()-(2S,3R,6R)-Dicarbonyl[hydridotris(1-pyrazolyl)borato][(η-
3,4,5)-1-(benzyloxycarbonyl)-2-(3,3-(ethylenedioxy)propyl)-6-meth-
oxy-3-methyl-1,2,3,6-tetrahydropyridin-3-yl]molybdenum (22e) and
(()-(2S,3R,6R)-Dicarbonyl[hydridotris(1-pyrazolyl)borato][(η-3,4,5)-
1-(benzyloxycarbonyl)-2-(3,3-(ethylenedioxy)propyl)-3-methyl-6-n-
pentyl-1,2,3,6-tetrahydropyridin-3-yl]molybdenum (23e). R1M )
3,3-(ethylenedioxy)propylmagnesium bromide27 (0.36 M in THF, 0.83
mL, 0.30 mmol, 1.5 equiv); R2M ) n-pentylmagnesium bromide (2.0
M in ether, 0.15 mL, 0.30 mmol, 1.5 equiv). 22e was prepared by
following the general procedure and was dissolved in CH2Cl2 (1 mL)
and treated with Ph3CPF6 (77.6 mg, 0.20 mmol, 1.0 equiv) at -78 °C.
After 1 min, the reaction mixture was slowly warmed to 0 °C over 5
min. Then methyl tert-butyl ether (MTBE) (8 mL) was added to
precipitate the formed cationic diene. The solvents were removed via
cannula (covered with a piece of filter paper to prevent removal of the
solid). The remaining solid was washed with MTBE (2 × 6 mL) and
then briefly dried under vacuum for a few minutes. The reaction mixture
was then cooled to -78 °C, dissolved in THF (1 mL), and treated with
the second nucleophile (R2M). After 15 min at -78 °C, the reaction
was quenched with methanol, brought to room temperature, and diluted
with ethyl acetate (2 mL) and brine (4 mL). The organic layer was
separated, dried over MgSO4, concentrated, and chromatographed (10%
ethyl acetate in hexanes, 15 × 2 cm) to give 23e as a yellow solid
(130 mg, 0.17 mmol, 85%).
Data for 22e: TLC (50% ethyl acetate in hexanes) Rf ) 0.26; mp
) 142-145 °C with decomposition (Et2O/hexanes); 1H NMR ((CD3)2-
CO, 400 MHz) δ 8.42 (s, 1 H), 7.95 (s, 0.5 H), 7.91 (d, J ) 1.6 Hz,
1.5 H), 7.81 (d, J ) 1.6 Hz, 1 H), 7.79 (s, 1 H), 7.68 (s, 1 H), 7.46-
7.31 (m, 5 H), 6.30-6.26 (m, 3 H), 5.63 (d, J ) 2.4 Hz, 0.5 H), 5.52
(d, J ) 2.8 Hz, 0.5 H), 5.17 (d, J ) 12.4 Hz, 0.5 H), 5.16 (d, J ) 12.4
Hz, 0.5 H), 5.07 (d, J ) 12.4 Hz, 0.5 H), 4.96 (d, J ) 12.4 Hz, 0.5 H),
4.82 (t, J ) 4.6 Hz, 0.5 H), 4.78-4.74 (m, 0.5 H), 4.45 (td, J ) 7.8,
3.6 Hz, 0.5 H), 4.32 (dd, J ) 7.2, 2.8 Hz, 0.5 H), 4.28 (dd, J ) 7.2,
2.8 Hz, 0.5 H), 4.06 (d, J ) 7.2 Hz, 0.5 H), 4.02 (d, J ) 7.2 Hz, 0.5
H), 3.92-3.84 (m, 2 H), 3.80-3.73 (m, 2 H), 3.39 (s, 1.5 H), 3.30 (s,
1.5 H), 2.16-2.08 (m, 1 H), 1.99-1.68 (m, 2 H), 1.94 (s, 1.5 H), 1.85
(s, 1.5 H), 1.61-1.56 (m, 0.5 H), 1.44-1.40 (m, 0.5 H); 13C NMR
(+)-(2S,3R,6R)- and (()-Dicarbonyl[hydridotris(1-pyrazolyl)-
borato][(η-3,4,5)-1-(benzyloxycarbonyl)-2-(3-benzyloxypropyl)-3-
methyl-6-n-pentyl-1,2,3, 6-tetrahydropyridin-3-yl]molybdenum (23f).
R1M ) (3-(benzyloxy)propyl)magnesium bromide (0.40 M in THF,
0.75 mL, 0.30 mmol, 1.5 equiv);28 R2M ) n-pentylmagnesium bromide
(2.0 M in ether, 0.15 mL, 0.30 mmol, 1.5 equiv). Following the general
procedure starting from (+)-9, (+)-23f (111 mg, 0.13 mmol, 67%,
>99% ee) was obtained after chromatography (10% ethyl acetate in
hexanes, 15 × 2 cm), [R]D +136.0 (c ) 0.5, CH2Cl2). (()-23f
was prepared in the same manner starting from (()-9. TLC (30%
ethyl acetate in hexane): Rf ) 0.60; mp ) 88-90 °C with decom-
position (Et2O/hexanes). 1H NMR (CDCl3, 400 MHz): δ 8.49 (s,
0.5 H), 8.45 (s, 0.5 H), 7.74 (d, J ) 4.8 Hz, 1 H), 7.62 (s, 3 H), 7.46
(s, 1 H), 7.42-7.20 (m, 10 H), 6.22 (d, J ) 12.4 Hz, 2 H), 6.17 (s, 1
H), 5.14 (t, J ) 13.0 Hz, 1.2 H), 5.04 (t, J ) 13.0 Hz, 0.8 H), 4.58-
4.45 (m, 2 H), 4.45-4.32 (m, 2 H), 4.22 (dd, J ) 7.3, 2.2 Hz, 0.5 H),
4.13 (dd, J ) 7.3, 2.2 Hz, 0.5 H), 3.88 (d, J ) 6.3 Hz, 1 H), 3.62-
3.46 (m, 1 H), 3.44-3.28 (m, 1 H), 2.28-2.10 (m, 1 H), 1.92 (s, 1.5
H), 1.87 (s, 1.5 H), 2.00-1.14 (m, 11 H), 0.93 (t, J ) 6.8 Hz, 1.5 H),
0.84 (t, J ) 6.8 Hz, 1.5 H). 13C NMR (CDCl3, 100 MHz): δ 232.4,
231.7, 227.6, 226.9, 155.2, 155.0, 146.6, 145.9, 145.8, 139.7, 138.8,
138.6, 137.0, 136.7, 136.5, 135.8, 134.2, 105.5, 105.3, 105.2, 96.5,
95.9, 73.1, 73.0, 72.52, 72.46, 70.4, 70.1, 67.2, 67.0, 63.0, 62.9, 55.8,
55.6, 51.9, 51.8, 40.9, 40.7, 36.7, 36.5, 32.0, 31.7, 28.1, 28.0, 27.22,
27.16, 24.64, 24.55, 22.6, 22.5, 14.1, 14.0. IR (CH2Cl2, KCl, cm-1):
3054, 1933, 1847, 1418, 1269, 1265, 1259. Anal. Calcd for C40H48-
BMoN7O5: C, 59.05; H, 5.95; N, 12.05. Found: C, 58.75; H, 5.90; N,
11.85.
Demetalation of (Dihydropyridinyl)molybdenum Complexes.
(()-(2R,3S,6S)-1-(Benzyloxycarbonyl)-2-(3,3-(ethylenedioxy)pro-
pyl)-3-methyl-6-n-pentyl-1,2,3,6-tetrahydropyridine (24). To
a
solution of 23e (0.20 g, 0.26 mmol, 1.0 equiv) in DME (2 mL) at -15
°C was added NOPF6 (136 mg, 0.78 mmol, 3.0 equiv) as a solid in
one portion. The reaction was slowly warmed to 0 °C over 30 min,
and a solution of NaCNBH3 in THF (1.0 M, 1.30 mL, 1.30 mmol, 5.0
equiv) was added. The mixture was stirred at room temperature for 1
h. Then ethyl acetate (10 mL) and water (10 mL) were added. The
(26) Pinhey, J. T.; Roche, E. G. J. Chem. Soc., Perkin Trans. 1 1988,
2415.
(27) To a suspension of Mg turnings (486 mg, 20 mmol, 2.0 equiv;
ground to generate fresh surface) in THF (20 mL) was added 2-(2-
bromoethyl)-1,3-dioxolane (1.17 mL, 1.81 g, 10 mmol, 1.0 equiv) via
syringe at room temperature over 5 min. After 4 h the Grignard reagent
was transferred to a Sure-Seal bottle and stored in a refrigerator. The
concentration was measured to be ca. 0.36 M by titration of an aqueous
solution of the quenched Grignard reagent with 0.10 M HCl solution.
(28) To a suspension of Mg turnings (0.486 g, 20 mmol, 2.0 equiv;
ground to generate a fresh surface) in THF (20 mL) was added benzyl
3-bromopropyl ether (1.77 mL, 2.29 g, 10 mmol, 1.0 equiv) via syringe at
room temperature over 5 min. After 2 h at room temperature, the Grignard
reagent was transferred to a Sure-Seal bottle and stored in a refrigerator.
The concentration was measured to be ca. 0.40 M by titration of an aqueous
solution of the quenched Grignard reagent with 0.10 M HCl solution.