2098
C. Jousse-Karinthi et al. / Tetrahedron 59 (2003) 2093–2099
calcd for C12H14N2O2: C, 66.04; H, 6.47; N, 12.84. Found:
C, 65.86; H, 6.60; N, 12.67.
(dd, J¼15.8, 9.5 Hz, 1H), 5.82 (d, J¼15.8 Hz, 1H), 4.73 (s,
1H), 4.70 (s, 1H), 4.15–4.07 (m, 4H), 3.84 (s, 1H), 3.73 (s,
3H), 2.61 (ddd, JHH¼14.0, 13.8 Hz, JPH¼7.5 Hz, 1H), 2.54
3.2.3. 1-Acetyl-2-methoxycarbonylmethyl-5-methylene-
cyclohexanecarboxylic acid methyl ester (7c). The
general procedure with methyl acetoacetate afforded triester
7c as a colorless oil in 70% yield; bp 90–1008C (0.05 Torr);
(t, J¼12.2 Hz, 1H), 2.38 (ddd, JHH¼13.7, 4.0 Hz, JPH¼
4.0 Hz, 1H), 2.08 (ddd, J¼12.2, 9.5, 3.0 Hz, 1H), 2.01 (dd,
J¼12.2, 3.0 Hz, 1H), 1.94 (ddd, JHH¼14.0, 4.0 Hz, JPH
¼
19.9 Hz, 1H), 1.36–1.30 (m, 9H); 13C NMR (CDCl3,
50 MHz) d 166.6 (C), 149.1 (CH), 144.6 (d, JCP¼16 Hz, C),
122.5 (CH), 109.2 (CH2), 69.9 (C), 62.6 (d, JCP¼7 Hz), 61.4
(d, JCP¼7 Hz), 52.8 (d, JCP¼16 Hz, CH), 51.4 (CH3), 45.8
(d, JCP¼134 Hz, CH), 35.9 (CH2), 30.9 (CH2), 27.9 (CH3),
16.3 (2CH2); HRMS (ESI) calcd for C16H27O6PNa
369.1396 [(MþNa)þ], found 369.1407. Further elution
provided 7f (Rf¼0.49) as colorless oil in 40% yield; IR
1
IR (neat) 1734, 1709, 1653, 1435 cm21; H NMR (CDCl3,
200 MHz) the presence of two diastereomers induces the
splitting of some signals d 4.70–4.60 (m, 2H), 3.69 and 3.68
(2s, 3H), 3.63 (s, 3H), 2.80–2.00 (m, 7H), 2.15 and 2.12 (2s,
3H), 1.95–1.40 (m, 2H); 13C NMR (CDCl3, 50 MHz) only
the major diastereomer is described d 203.9 (C), 172.8 (C),
171.5 (C), 143.7 (C), 110.3 (CH2), 65.3 (C), 52.4 (CH3),
51.4 (CH3), 37.6 (CH2), 36.3 (CH), 34.8 (CH2), 31.3 (CH2),
28.9 (CH2), 27.1 (CH3); HRMS (ESI) calcd for C14H20O5Na
291.1203 [(MþNa)þ], found 291.1194.
(neat), 1732, 1711, 1653, 1437 cm21 1H NMR (C6D6,
;
400 MHz) d 4.59 (s, 1H), 4.57 (s, 1H), 3.95–3.80 (m, 4H),
3.38 (dd, J¼16.7, 2.0 Hz, 1H), 3.33 (s, 3H), 3.20 (dd, J¼
16.7, 10.7. Hz, 1H), 3.11 (ddd, JHH¼13.8, 2.0 Hz, JCP
6.2 Hz, 1H), 2.76 (m, 1H), 2.53 (dd, JHH¼13.8 Hz, JCP
¼
¼
3.2.4. 1-Cyano-2-methoxycarbonylmethyl-5-methylene-
cyclohexanecarboxylic acid ethyl ester (7d). The general
procedure with ethyl cyanoacetate afforded compound 7d as
a colorless oil in 77% yield; IR (neat) 2243 (weak), 1735,
1656, 1438 cm21; 1H NMR (CDCl3, 200 MHz) the presence
of two diastereomers induced the splitting of most signals d
4.91, 4.89 4.82 and 4.78 (4s, 2H), 4.23 (q, J¼7.2 Hz, 2H),
3.64 and 3.65 (2s, 3H), 2.90–2.49 (m, 7H), 1.45 (m, 1H),
1.40 and 1.38 (2t, J¼7.2 Hz, 3H); 13C NMR (CDCl3,
50 MHz) the presence of two diastereomers induced the
splitting of some signals d 171.6 and 171.2 (C), 168.0 and
166.3 (C), 140.6 and 140.2 (C), 118.8 and 116.4 (C), 113.2
and 112.6 (CH2), 62.8 and 62.5 (CH2), 52.4 and 48.6 (C),
51.7 (CH3), 42.1 and 40.0 (CH2), 38.5 and 38.2 (CH), 37.0
and 34.8 (CH2), 32.8 and 31.0 (CH2), 29.6 and 27.7 (CH2),
13.8 (CH3); Anal. calcd for C14H19NO4: C, 63.37; H, 7.21;
N, 5.28. Found: C, 63.33; H, 7.05; N, 5.14.
10.0 Hz, 1H), 2.27 (s, 3H), 2.05 (m, 1H), 2.00–1.82 (m,
2H), 1.76 (dddd, J¼13.4, 12.2, 12.2, 5.3 Hz, 1H), 0.99 (q,
J¼7.2 Hz, 6H); 13C NMR (C6D6, 100 MHz) d 203.8 (C),
173.7 (C), 144.2 (d, JCP¼12.8 Hz, C), 110.6 (CH2), 62.9 (d,
JCP¼7.2 Hz, CH2), 62.3 (d, JC–P¼7.2 Hz, CH2), 61.7 (d,
JCP¼123 Hz, C), 50.9 (CH3), 40.2 (d, JCP¼5.8 Hz, CH2),
38.4 (d, JCP¼4.4 Hz, CH), 37.3 (CH2), 34.1 (CH2), 30.4 (d,
JCP¼11.2 Hz, CH2), 28.9 (CH3), 16.3 (2CH3); HRMS (ESI)
calcd for C16H27O6PNa 369.1396 [(MþNa)þ], found
369.1420.
3.2.7. (1-Benzyl-5-methylene-piperidin-2-yl)-acetic acid
methyl ester (28a). The general procedure with benzyla-
mine afforded piperidine 28a as pale yellow oil in 39%
1
yield; IR (neat) 1735, 1654, 1435 cm21; H NMR (CDCl3,
200 MHz) d 7.30 (m, 5H), 4.81 (s, 1H), 4.63 (s, 1H), 3.71 (d,
J¼13.3 Hz, 1H), 3.68 (s, 3H), 3.55 (d, J¼13.3 Hz, 1H), 3.28
(m, 1H), 3.21 (d, J¼13.4 Hz, 1H), 2.90 (d, J¼13.4 Hz, 1H),
2.78 (dd, J¼14.3, 6.2 Hz, 1H), 2.49 (dd, J¼14.3, 8.1 Hz,
1H), 2.42–2.19 (m, 2H), 1.94–1.78 (m, 1H), 1.68–1.55 (m,
1H); 13C NMR (CDCl3, 50 MHz) d 172.7 (C), 143.0 (C),
139.2 (C), 128.7 (2CH), 128.1 (2CH), 126.7 (CH), 109.5
(CH2), 56.6 (CH), 55.5 (CH2), 54.9 (CH2), 51.5 (CH3), 36.7
(CH2), 30.7 (CH2), 29.0 (CH2).
3.2.5. (2-Nitro-2-methyl-4-methylene-cyclohexyl)-acetic
acid methyl ester (2e). The general procedure with nitro-
ethane afforded nitro ester 2e as a colorless oil in 62%
yield; IR (neat) 1736, 1670, 1535 cm21; 1H NMR (CDCl3,
200 MHz) the presence of two diastereomers induced the
splitting of some signals d 4.85–4.70 (m, 2H), 3.64 and 3.65
(2s, 3H), 3.00–2.80 (m, 2H), 2.50–1.60 (m, 6H), 1.58 and
1.40 (2s, 3H), 1.16 (qd, J¼13.0, 4.4 Hz, 1H); 13C NMR
(CDCl3, 50 MHz) major diastereomer d 171.6 (C), 142.4
(C), 112.1 (CH2), 92.0 (C), 51.6 (CH3), 47.0 (CH2), 40.1
(CH), 35.3 (CH2), 33.1 (CH2), 29.3 (CH2), 16.5 (CH3),
minor diastereomer d 172.6 (C), 142.4 (C), 111.9 (CH2),
90.7 (C), 51.6 (CH3), 43.2 (CH2), 40.3 (CH), 34.1 (CH2),
31.1 (CH2), 27.9 (CH2), 25.6 (CH3); Anal. calcd for
C11H17NO4: C, 58.13; H, 7.54; N, 6.16. Found: C, 58.22;
H, 7.58; N, 6.04.
3.2.8. 9,12-Dimethyl-3-methylene-9,12-diazatricyclo-
[5.3.3.01,6]tridecane-8,10,11,13-tetraone (22) and
2-methyl-7-methylene-1,3-dioxo-octahydro-isoquino-
line-8a-carboxylic acid methylamide (23). The general
procedure with 1,3-dimethylbarbituric acid 20 and carbo-
nate 14 gave a 1:2 mixture of tricyclic imide 22 and amide
23. Chromatographic purification on silica gel (hexane/ethyl
acetate, 1:1) afforded tricyclic imide 22 (Rf¼0.6) as
colorless crystals (18%); mp 197–1988C; IR (neat): 1716,
1688, 1651, 1419 cm21; 1H NMR (CDCl3, 400 MHz) d 4.99
(d, J¼1.6 Hz, 1H), 4.88 (d, J¼1.6 Hz, 1H), 3.95 (d, J¼
2.7 Hz, 1H), 3.65 (dd, J¼14.1, 1.3 Hz, 1H), 3.17 (s, 3H),
3.16 (s, 3H), 2.66 (ddd, J¼13.4, 4.2, 2.7 Hz, 1H), 2.37 (dddd
J¼13.6, 4.2, 2.1, 2.1 Hz, 1H), 2.21 (dd, J¼14.1, 1.4 Hz,
1H), 2.07 (broad t, J¼13.6 Hz, 1H), 1.96 (m, 1H), 1.31 (qd,
J¼13.6, 4.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 168.9
(C), 166.9 (C), 166.1 (C), 165.6 (C), 141.0 (C), 114.2 (CH2),
54.6 (CH), 54.5 (C), 37.7 (CH2), 36.5 (CH), 32.7 (CH2),
28.5 (CH2), 27.7 (CH3), 27.3 (CH3); MS (70 eV) m/z: 276
3.2.6. [2-Acetyl-2-(diethoxy-phosphoryl)-4-methylene-
cyclohexyl]-acetic acid methyl ester (7f) and 3-[3-(di-
ethoxy-phosphoryl)-2-hydroxy-2-methyl-5-methylene-
cyclo-hexyl]-acrylic acid methyl ester (15). The general
procedure with (2-oxopropyl)-phosphonic acid diethyl ester
2f afforded a mixture of the keto-phosphonate 7f and the
hydroxy phosphonate 15. Chromatographic purification on
silica gel (ethyl acetate) afforded first hydroxy phosphonate
15 (Rf¼0.57) as a colorless oil in 15% yield; IR (neat) 3424,
1721, 1653, 1434 cm21; 1H NMR (CDCl3, 400 MHz) d 7.08