Cycloaddition Behavior of Carbonyl Ylides
J . Org. Chem., Vol. 62, No. 7, 1997 2009
solution of the magnesium dianion of hydrogen methyl mal-
onate at 0 °C. The solution was allowed to stir for 1 h and
was then quenched with a 1 N HCl solution. The mixture was
extracted with ether, dried over anhydrous MgSO4, and
concentrated under reduced pressure. The residue was sub-
jected to flash chromatography on silica gel to give 0.35 g (67%)
of 3-[3-methyl-2-oxo-1-(4-pentenyl)piperidin-3-yl]-3-oxopropi-
onic acid methyl ester as a colorless oil: IR (neat) 1739, 1716,
3.57 (d, 1H, J ) 16.2 Hz), 3.64 (s, 3H), 3.67 (d, 1H, J ) 16.2
Hz), 4.08 (q, 2H, J ) 7.1 Hz), 5.78 (d, 1H, J ) 15.7 Hz), and
6.88, (dt, 1H, J ) 11.3 and 5.1 Hz); 13C-NMR (CDCl3, 75 MHz)
δ 14.1, 19.8, 23.1, 25.3, 29.5, 30.9, 45.2, 47.4, 48.3, 51.4, 56.3,
61.1, 121.5, 148.0, 166.8, 167.6, 169.9, and 202.4. Anal. Calcd
for C17H25NO6: C, 60.16; H, 7.42; N, 4.13. Found: C, 60.04;
H, 7.24; N, 4.16.
Rh od iu m (II)-Ca ta lyzed Decom p osition of 3-[3-Meth yl-
2-oxo-1-(5-ca r b om et h oxy-4-p en t en yl)p ip er id in -3-yl]-2-
d ia zo-3-oxop r op ion ic Acid Eth yl Ester (14). Diazo trans-
fer of the above amido ester according to the general procedure
gave 14 as a yellow oil (70%) which was used immediately used
1626, and 1432 cm-1 1H-NMR (CDCl3, 300 MHz) δ 1.38 (s,
;
3H), 1.46-1.65 (m, 3H), 1.79 (dt, 2H, J ) 12.0 and 6.0 Hz),
2.02 (dd, 2H, J ) 14.5 and 6.8 Hz), 2.30-2.40 (m, 1H), 3.09-
3.43 (m, 4H), 3.64 (d, 1H, J ) 16.2 Hz), 3.67 (s, 3H), 3.73 (d,
1H, J ) 16.2 Hz), 4.92-5.02 (m, 2H), and 5.70-5.82 (m, 1H);
13C-NMR (CDCl3, 75 MHz) δ 19.9, 23.2, 26.0, 30.9, 31.0, 45.1,
47.5, 48.3, 52.2, 56.3, 115.1, 137.6, 168.0, 169.7, and 202.4.
Anal. Calcd for C15H23NO4: C, 64.04; H, 8.24; N, 4.98.
Found: C, 63.86; H, 7.95; N, 4.88.
in the next step: IR (neat) 2140, 1717, 1644, and 1312 cm-1
;
1H-NMR (CDCl3, 300 MHz) δ 1.21 (t, 3H, J ) 7.1 Hz), 1.45 (s,
3H), 1.50-2.10 (m, 5H), 2.13 (dd, 2H, J ) 14.6 and 7.4 Hz),
2.26 (dt, 1H, J ) 13.0 and 4.1 Hz), 3.10-3.20 (m, 1H), 3.23 (t,
2H, J ) 7.4 Hz), 3.56-3.65 (m, 1H), 3.66 (s, 3H), 4.13 (q, 2H,
J ) 7.1 Hz), 5.78 (d, 1H, J ) 15.6 Hz), and 6.91 (dt, 1H, J )
15.6 and 6.9 Hz); 13C-NMR (CDCl3, 75 MHz) δ 14.2, 19.6, 23.2,
25.0, 29.8, 30.9, 47.1, 47.9, 51.3, 54.4, 61.0, 121.1, 148.7, 160.9,
166.9, 171.5, and 192.0. Diazo amide 14 decomposed on
standing and was immediately subjected to the rhodium-
catalyzed reaction. All attempts to isolate an internal cycload-
duct from the decomposition of 14 failed to give any charac-
terizable product.
Rh od iu m -Ca ta lyzed Rea ction of 3-[3-Meth yl-2-oxo-1-
(4-p en ten yl)p ip er id in -3-yl]-2-d ia zo-3-oxop r op ion ic Acid
Meth yl Ester (12). Diazo transfer of the above amido ester
according to the general procedure gave 12 as a yellow oil
1
(70%): IR (neat) 2136, 1717, 1636, and 1312 cm-1; H-NMR
(CDCl3, 300 MHz) δ 1.46 (s, 3H), 1.30-2.10 (m, 7H), 2.26 (dt,
1H, J ) 13.0 and 4.2 Hz), 3.10-3.30 (m, 3H), 3.61 (dt, 1H, J
) 12.0 and 4.2 Hz), 3.68 (s, 3H), 4.86-4.98 (m, 2H), and 5.65-
5.79 (m, 1H); 13C-NMR (CDCl3, 75 MHz) δ 19.6, 23.3, 25.8,
30.9, 31.2, 47.1, 47.8, 51.9, 54.4, 114.7, 138.1, 161.2, 171.3, and
192.0. Diazo amide 12 decomposed on standing and was
immediately subjected to the rhodium-catalyzed reaction. All
attempts to isolate an internal cycloadduct from the decom-
position of 12 failed to give any characterizable product.
However, it was possible to isolate a bimolecular cycloadduct
using DMAD as the trapping agent. To a mixture of 21 µL
(0.17 mmol) of dimethyl acetylenedicarboxylate and 2 mg of
rhodium(II) acetate in 2 mL of benzene at reflux was added
30 mg (0.1 mmol) of 12 in 0.5 mL benzene over a period of 10
min. The mixture was heated at reflux for an additional 2 h,
cooled to rt, and concentrated under reduced pressure. The
residue was subjected to flash chromatography on silica gel
to give 35 mg (78%) of 2-(4-pentenyl)-6-methyl-7-oxo-11-oxa-
2-azatricyclo[6.2.1.01,6]undec-9-ene-8,9,10-tricarboxylic acid 8-m-
ethyl ester 9,10-dimethyl ester (13) as a bright yellow oil: IR
(neat) 1730, 1650, 1520, and 1330 cm-1; 1H-NMR (CDCl3, 300
MHz) δ 1.19 (s, 3H), 1.60-2.00 (m, 7H), 2.63 (t, 1H, J ) 13.1
Hz), 2.94-3.07, (m, 2H), 3.05-3.20 (m, 1H), 3.35 (dt, 1H, J )
11.5 and 5.6 Hz), 3.67 (s, 3H), 3.77 (s, 3H), 3.79 (s, 3H), 4.87-
4.96 (m, 2H), and 5.55-5.70 (m, 1H); 13C-NMR (CDCl3, 75
MHz) δ 18.9, 19.8, 26.6, 30.1, 34.1, 50.7, 52.0, 52.7, 52.8, 54.5,
57.1, 77.3, 102.3, 115.8, 115.9, 136.8, 158.8, 162.1, 165.9, 166.5,
and 198.6; HRMS calcd for C21H27NO8: 421.1736. Found:
421.1732.
3-Ca r beth oxy-1-(1′-oxo-4′-p en ten yl)-2-p ip er id on e (17).
To a stirred solution of 0.50 g (2.9 mmol) of 2-oxopiperidine-
3-carboxylic acid ethyl ester (16) in 20 mL of THF at -78 °C
was added 4.0 mL (6.4 mmol) of a 1.6 M n-butyllithium
solution in hexane and the mixture was allowed to stir while
warming to 0 °C. The solution was cooled to -78 °C and 0.38
g (3.2 mmol) of 4-pentenoic acid chloride in 1 mL of CH2Cl2
was added. The mixture was allowed to stir while warming
to rt over a period of 2 h. The reaction was quenched with
H2O, the organic layer was separated, and the aqueous layer
was extracted with CH2Cl2. The combined organic extracts
were washed with a saturated NaCl solution, dried over
anhydrous MgSO4, and concentrated under reduced pressure.
The residue was subjected to flash chromatography on silica
gel to give 0.44 g (60%) of 17 as a colorless oil: IR (neat) 1734,
1692, 1299, and 1148 cm-1; 1H-NMR (CDCl3, 300 MHz) δ 1.22
(t, 3H, J ) 7.1 Hz), 1.68-2.20 (m, 4H), 2.32 (dd, 2H, J ) 14.0
and 7.2 Hz), 2.94 (td, 2H, J ) 7.4 and 2.1 Hz), 3.45 (t, 1H, J
) 7.4 Hz), 3.55-3.75 (m, 2H), 4.16 (q, 2H, J ) 7.1 Hz), 4.80-
5.05 (m, 2H), and 5.70-5.85 (m, 1H); 13C-NMR (CDCl3, 75
MHz) δ 14.0, 20.6, 24.1, 28.8, 38.5, 43.5, 51.4, 61.7, 115.2,
137.2, 169.8, 176.0. Anal. Calcd for C13H19NO4: C, 61.64; H,
7.56; N, 5.53. Found: C, 61.48; H, 7.39; N, 5.52.
3-[3-Ca r beth oxy-2-oxo-1-(1′-oxo-4′-p en ten yl)p ip er id in -
3-yl]-2-d ia zo-3-oxop r op ion ic Acid Eth yl Ester (18). To a
stirred solution of 0.13 g (0.5 mmol) of imide 22 in 20 mL of
THF at 0 °C was added 0.30 mL (0.6 mmol) of a 2.0 M solution
of n-butylmagnesium chloride in THF. The solution was
allowed to stir at 0 °C for 1 h and then 0.20 g (1.1 mmol) of
ethyl 2-diazomalonyl chloride was added. The solution was
allowed to stir at 0 °C for 2 h and was then quenched with
H2O. The organic layer was separated and the aqueous layer
was extracted with ether. The combined organic extracts were
washed with a saturated NaCl solution, dried over anhydrous
MgSO4, and concentrated under reduced pressure. The resi-
due was subjected to flash chromatography on silica gel to give
0.11 g (55%) of 18 as a yellow oil which was immediately used
in the next step as a consequence of its lability: IR (neat) 2140,
1736, 1703, 1696, and 1637 cm-1; 1H-NMR (CDCl3, 300 MHz)
δ 1.26 (t, 3H, J ) 7.1 Hz), 1.27 (t, 3H, J ) 7.1 Hz), 1.60-2.00
(m, 2H), 2.30-2.45 (m, 3H), 2.63 (dt, 1H, J ) 9.2 and 4.2 Hz),
2.80-3.05 (m, 2H), 3.66-3.89 (m, 2H), 4.20 (q, 2H, J ) 7.1
Hz), 4.28 (q, 2H, J ) 7.1 Hz), 4.92-5.05 (m, 2H), and 5.72-
5.85 (m, 1H);13C-NMR (CDCl3, 75 MHz) δ 13.9, 14.2, 20.4, 28.2,
28.9, 37.9, 43.5, 61.9, 62.8, 69.9, 115.1, 137.3, 160.7, 166.6,
168.4, 176.3, and 186.9.
3-[3-Meth yl-2-oxo-1-(5-ca r bom eth oxy-4-p en ten yl)p ip -
er id in -3-yl]-3-oxop r op ion ic Acid Eth yl Ester . To a stirred
solution containing 0.13 g (0.4 mmol) of 3-[3-methyl-2-oxo-1-
(4-pentenyl)piperidin-3-yl]-3-oxopropionic acid ethyl ester in
CH2Cl2 at -78 °C was added O3 until the solution became light
blue. Oxygen was then bubbled through the solution to
remove the excess O3. To this solution was added 0.12 g (2.0
mmol) of dimethyl sulfide and the solution was allowed to
warm to rt while stirring over a period of 12 h. The solution
was concentrated under reduced pressure to remove the excess
dimethyl sulfide and the crude aldehyde was taken up in CH2-
Cl2. To this solution was added 0.21 g (0.6 mmol) of (car-
bomethoxymethylene)triphenylphosphorane and the solution
was allowed to stir at rt for 2 h. The mixture was quenched
by pouring into H2O, the organic phase was separated, and
the aqueous phase was extracted with CH2Cl2. The combined
CH2Cl2 extracts were washed with a saturated NaCl solution,
dried over anhydrous MgSO4, and concentrated under reduced
pressure. The residue was subjected to flash chromatography
on silica gel to give 0.80 g (54%) of 3-[3-methyl-2-oxo-1-(5-
carbomethoxy-4-pentenyl)piperidin-3-yl]-3-oxopropionic acid
ethyl ester as a colorless oil: IR (neat) 1770, 1750, 1670, 1640,
9,10b-Ep oxy-3,8-d ioxod eca h yd r op yr id o[3,2,1-ij]qu in o-
lin e-7a ,9-d ica r boxylic Acid Dieth yl Ester (19). To a 50
mg (0.12 mmol) sample of diazo amide 18 in 0.5 mL of benzene
was added 2 mg of rhodium(II) acetate. The mixture was
heated at 50 °C in an oil bath for 4 h. The mixture was
1500, and 1475 cm-1 1H-NMR (CDCl3, 300 MHz) δ 1.23 (t,
;
3H, J ) 7.1 Hz), 1.35 (s, 3H), 1.45-1.78 (m, 5H), 2.15 (dd, 2H,
J ) 13.9 and 7.1 Hz), 2.26-2.35 (m, 1H), 3.19-3.40 (m, 4H),