564 J . Org. Chem., Vol. 64, No. 2, 1999
Brodney and Padwa
2-Hydr oxy-1,1,8-tr im eth yl-3-oxo-2,3,6,8,9,10-h exah ydr o-
1H,5H-p yr id o[3,2,1-ij]qu in olin e-2-ca r boxylic Acid Eth yl
Ester (32). A solution containing 0.1 g (0.3 mmol) of aldehyde
31 in 30 mL of acetonitrile was treated with 5 mg of p-
toluenesulfonic acid. The solution was heated at reflux for 6
h, and the solution was evaporated under reduced pressure.
The crude residue was subjected to flash silica gel chroma-
tography to afford 0.02 g (20%) of lactam 34 and 0.06 g (60%)
of 32 as a white solid: mp 67-68 °C; IR (neat) 3419, 1739,
1.47-1.60 (m, 2H), 1.68-1.76 (m, 2H), 2.17-2.22 (m, 1H),
3.86-3.89 (m, 2H), 4.38 (q, 2H, J ) 7.2 Hz), 5.16-5.30 (m,
2H), and 5.69-5.82 (m, 1H); 13C NMR (CDCl3, 75 MHz) δ 14.4,
20.9, 22.2, 26.2, 26.4, 28.3, 32.9, 36.6, 42.2, 44.7, 51.3, 61.8,
92.1, 96.0, 118.1, 133.2, 165.4, and 169.1; HRMS calcd for
C
18H27O4N 321.1940, found 321.1941.
A solution of 0.5 g (1.6 mmol) of the above cycloadduct in
35 mL of CH2Cl2 was cooled to -78 °C, and ozone was bubbled
through the solution for 20 min. The solution was quenched
with 0.6 mL (7.8 mmol) of dimethyl sulfide and was warmed
to room temperature. After 6 h of stirring at 25 °C, this
solution was added to 10 mL of H2O and extracted with ethyl
acetate, and the extracts were dried over Na2SO4. The solution
was concentrated under reduced pressure, and the resulting
residue was purified by flash silica gel chromatography to give
0.4 g (83%) of 35 as a clear oil: IR (neat) 1748, 1732, and 1116
1670, and 1112 cm-1 1H NMR (CDCl3, 300 MHz) δ 0.97 (s,
;
3H), 1.04 (d, 3H, J ) 7.2 Hz), 1.17 (t, 3H, J ) 6.9 Hz), 1.21 (s,
3H), 1.45-1.55 (m, 1H), 1.65-1.75 (m, 1H), 2.11-2.24 (m, 2H),
2.27-2.32 (m, 2H), 2.34-2.46 (m, 1H), 2.96-3.06 (m, 1H), 4.10
(dq, 2H, J ) 6.9 and 2.7 Hz), 4.44 (s, 1H), 4.57 (ddd, 1H, J )
12.5, 5.3, and 2.1 Hz), and 5.58 (d, 1H, J ) 3.6 Hz); 13C NMR
(CDCl3, 75 MHz) δ 14.1, 18.8, 19.7, 21.8, 24.3, 29.2, 33.2, 39.4,
39.9, 61.7, 79.1, 105.6, 118.3, 124.1, 126.7, 134.4, 167.3, and
169.5. Anal. Calcd for C18H25NO4: C, 67.69; H, 7.89; N, 4.39.
Found: C, 67.42; H, 7.97; N, 4.24.
1
cm-1; H NMR (CDCl3, 300 MHz) δ 0.94 (d, 3H, J ) 6.6 Hz),
0.87-0.90 (m, 1H), 0.96-0.99 (m, 1H), 1.08 (s, 3H), 1.17-1.23
(m, 1H), 1.26 (s, 3H), 1.36 (t, 3H, J ) 7.2 Hz), 1.37-1.42 (m,
1H), 1.69-1.80 (m, 2H), 1.89 (dd, 1H, J ) 12.3 and 6.0 Hz),
2.13-2.19 (m, 1H), 4.10 (s, 2H), 4.39 (q, 2H, J ) 7.2 Hz), and
9.57 (s, 1H); 13C NMR (CDCl3, 75 MHz) δ 14.5, 20.9, 22.1, 26.2,
26.4, 28.4, 32.9, 36.5, 44.8, 49.5, 50.9, 61.9, 92.1, 96.3, 165.0,
169.8, and 196.8; HRMS calcd for C17H25NO5 323.1733, found
323.1731.
N-Allyl-2-d ia zo-N-(3,7-d im eth yl-oct-6-en oyl)-m a lon a m -
ic Acid Eth yl Ester . To a solution containing 4.0 g (28 mmol)
of citronellic acid (7) in 125 mL of CH2Cl2 was added 6.8 g (42
mmol) of 1,1′-carbonyldiimidazole, and the solution was stirred
at room temperature for 2 h. The reaction mixture was then
charged with 3.2 g (56 mmol) of freshly distilled allylamine at
0 °C. The solution was allowed to warm to room temperature,
stirred for 10 h, and concentrated under reduced pressure. The
residue was subjected to flash silica gel chromatography to
give 4.6 g (78%) of 3,7-dimethyl-oct-6-enoic acid allyl amide
5-Hydr oxy-6,6,9-tr im eth yl-4-oxo-5,6,6a,7,8,9-h exah ydr o-
4H-p yr r olo-[3,2,1-ij]qu in olin e-5-ca r boxylic Acid Eth yl
Ester (37). A solution containing 0.1 g (0.3 mmol) of aldehyde
35 in 30 mL of acetonitrile was treated with 6 mg of p-
toluenesulfonic acid. The mixture was heated at reflux for 12
h, and the solution was concentrated under reduced pressure.
The crude residue was subjected to flash silica gel chroma-
tography to give 0.07 g (70%) of 37 as a colorless oil: IR (neat)
1743, 1715, and 1251 cm-1; 1H NMR (CDCl3, 300 MHz) δ 0.79
(t, 3H), 1.11 (s, 3H), 1.18 (d, 3H, J ) 6.9 Hz), 1.25 (t, 3H, J )
7.2 Hz), 1.28-1.38 (m, 1H), 1.69-1.73 (m, 1H), 1.84-1.91 (m,
1H), 2.05-2.21 (m, 1H), 2.59-2.66 (m, 1H), 2.94-3.00 (m, 1H),
4.10 (bs, 1H), 4.20-4.31 (m, 2H), 6.23 (d, 1H, J ) 3.3 Hz), and
7.20 (dd, 1H, J ) 3.3 and 0.9 Hz); 13C NMR (CDCl3, 75 MHz)
δ 14.3, 17.4, 21.0, 21.1, 24.0, 29.1, 33.1, 39.2, 44.9, 62.8, 83.2,
113.6, 116.4, 127.1, 130.5, 167.4, and 169.9; HRMS calcd for
as a colorless oil: IR (neat) 3289, 1653, and 1110 cm-1 1H
;
NMR (CDCl3, 300 MHz) δ 0.86 (d, 3H, J ) 6.0 Hz), 1.08-1.18
(m, 1H), 1.24-1.35 (m, 1H), 1.52 (s, 3H), 1.59 (s, 3H), 1.86-
1.96 (m, 4H), 2.10-2.20 (m, 1H), 3.79 (dt, 1H, J ) 5.6 and 1.0
Hz), 4.99-5.13 (m, 2H), 5.67-5.82 (m, 1H), and 6.40 (brs, 1H);
13C NMR (CDCl3, 75 MHz) δ 17.7, 19.6, 25.5, 25.7, 30.5, 37.0,
41.9, 44.3, 116.0, 124.4, 131.4, 134.6, and 172.7.
N-Malonylacylation was carried out on the above amide in
the normal manner to give 6.6 g (88%) of N-allyl-N-(3,7-
dimethyl-oct-6-enoyl)-malonamic acid ethyl ester as a colorless
oil: IR (neat) 1742, 1702, and 1190 cm-1 1H NMR (CDCl3,
;
300 MHz) δ 0.93 (d, 3H, J ) 6.6 Hz), 1.17-1.26 (m, 1H), 1.27
(t, 3H, J ) 7.1 Hz), 1.33-1.39 (m, 1H), 1.59 (s, 3H), 1.67 (s,
3H), 1.70-1.73 (m, 1H), 1.95-2.09 (m, 2H), 2.36 (dd, 1H, J )
16.4 and 8.4 Hz), 2.56 (dd, 1H, J ) 16.4 and 2.3 Hz), 3.86 (s,
2H), 4.19 (q, 2H, J ) 7.7 Hz), 4.35-4.45 (m, 2H), 5.05-5.10
(m, 1H), 5.17-5.23 (m, 2H), and 5.78-5.90 (m, 1H); 13C NMR
(CDCl3, 75 MHz) δ 14.3, 17.9, 19.9, 25.7, 25.9, 29.5, 37.0, 43.9,
46.1, 46.6, 61.5, 116.6, 124.4, 131.9, 132.7, 167.6, 168.6 and
175.6; HRMS calcd for C18H29NO4 323.2096, found 323.2082.
The above compound was subjected to the standard diazo
transfer conditions to give 4.5 g (70%) of N-allyl-2-diazo-N-
(3,7-dimethyl-oct-6-enoyl)-malonamic acid ethyl ester as a
yellow oil: IR (neat) 2128, 1720, 1695, and 1320 cm-1; 1H NMR
(CDCl3, 300 MHz) δ 0.87 (d, 3H, J ) 6.9 Hz), 1.10-1.19 (m,
1H), 1.23 (t, 3H, J ) 7.2 Hz), 1.28-1.36 (m, 1H), 1.52 (s, 3H),
1.60 (s, 3H), 1.57-1.63 (m, 1H), 1.86-1.99 (m, 1H), 2.27 (dd,
1H, J ) 15.9 and 7.8 Hz), 2.47 (dd, 1H, J ) 15.9 and 5.7 Hz),
4.19 (q, 2H, J ) 7.2 Hz), 4.22-4.30 (m, 2H), 4.99-5.03 (m,
1H), 5.09-5.22 (m, 2H), and 5.73-5.84 (m, 1H); 13C NMR
(CDCl3, 75 MHz) δ 14.5, 17.9, 19.9, 25.7, 25.9, 29.9, 37.1, 43.2,
48.2, 62.0, 72.9, 117.4, 124.5, 131.7, 133.4, 160.7, 166.4, and
175.0.
3,7,7-Tr im et h yl-9-oxo-10-(2-oxo-et h yl)-11-oxa -10-a za -
tr icyclo-[6.2.1. 01,6]u n d eca n e-8-ca r boxylic Acid Eth yl Es-
ter (35). A solution of 3.4 g (9.8 mmol) of the above diazo imide
in 60 mL of CH2Cl2 at room temperature was treated with 5
mg of rhodium(II) perfluorobutyrate. The reaction mixture was
stirred for 24 h at room temperature and was concentrated
under reduced pressure. The resulting residue was purified
by flash silica gel chromatography to give 2.8 g (87%) of 10-
allyl-3,7,7-trimethyl-9-oxo-11-oxa-10-aza-tricyclo[6.2.1.01,6]-
undecane-8-carboxylic acid ethyl ester as a colorless oil: IR
(neat) 1754, 1722, 1403, and 1114 cm-1; 1H NMR (CDCl3, 300
MHz) δ 0.82-0.89 (m, 1H), 0.95 (d, 3H, J ) 6.3 Hz), 1.05 (s,
3H), 1.21 (s, 3H), 1.31-1.43 (m, 2H), 1.35 (t, 3H, J ) 7.2 Hz),
C
17H23NO4 305.1627, found 305.1625.
2-Dia zo-N-h ep t-6-en oyl-N-[2-(2-iod op h en yl)eth yl]-m a -
lon a m ic Acid Eth yl Ester (38). To a solution containing 1.9
g (14.4 mmol) of hept-6-enoic acid in 175 mL of CH2Cl2 was
added 2.4 g (15 mmol) of 1,1′-carbonyldiimidazole, and the
solution was stirred at room temperature for 2 h. The reaction
mixture was charged with 3.6 g (15 mmol) of 2-(2-iodo-phenyl)-
ethylamine. The solution was stirred for 8 h and concentrated
under reduced pressure. The residue was subjected to flash
silica gel chromatography to give 4.0 g (77%) of hept-6-enoic
acid [2-(2-iodophenyl)ethyl] amide as a white solid: mp 38-
39 °C; IR (neat) 3281, 1645, and 1552 cm-1; 1H NMR (CDCl3,
300 MHz) δ 1.29-1.39 (m, 2H), 1.53-1.63 (m, 2H), 2.00 (q,
2H, J ) 6.9 Hz), 2.10 (t, 2H, J ) 7.5 Hz), 2.90 (t, 2H, J ) 6.9
Hz), 3.46 (q, 2H, J ) 6.6 Hz), 4.92 (m, 2H), 5.67 (bs, 1H), 5.69-
5.80 (m, 1H), 6.84-6.89 (m, 1H), 7.15-7.24 (m, 2H), and 7.77
(d, 1H, J ) 8.1 Hz); 13C NMR (CDCl3, 75 MHz) δ 25.3, 28.7,
33.6, 36.7, 39.6, 40.4, 100.8, 114.9, 128.6, 128.7, 130.2, 138.6,
139.8, 141.8, and 173.2. Anal. Calcd for C15H20NOI: C, 50.43;
H, 5.64; N, 3.92. Found: C, 50.56; H, 5.70; N, 3.91.
N-Malonylacylation was carried out on the above amide in
the normal manner to give 4.9 g (97%) of N-hept-6-enoyl-N-
[2-(2-iodo-phenyl)ethyl]-malonamic acid ethyl ester as a color-
less oil: IR (neat) 1737, 1694, 1630, and 1190 cm-1; H NMR
1
(CDCl3, 300 MHz) δ 1.24 (t, 3H, J ) 7.2 Hz), 1.30 (quint, 2H,
J ) 7.5 Hz), 1.52 (quint, 2H, J ) 7.5 Hz), 1.99 (dd, 2H, J )
14.1 and 6.9 Hz), 2.44 (t, 2H, J ) 7.2 Hz), 2.99 (t, 2H, J ) 7.2
Hz), 3.79 (s, 2H), 3.86 (t, 2H, J ) 7.5 Hz), 4.16 (q, 2H, J ) 7.2
Hz), 4.89-4.98 (m, 2H), 5.66-5.79 (m, 1H), 6.89-6.92 (m, 1H),
7.25-7.26 (m, 2H), and 7.77 (d, 1H, J ) 7.8 Hz); 13C NMR
(CDCl3, 75 MHz) δ 14.3, 24.1, 28.4, 33.6, 36.6, 39.7, 44.6, 46.7,
61.4, 100.5, 114.9, 128.9, 129.0, 131.0, 138.4, 139.7, 141.2,
167.5, 169.0, and 176.0; HRMS calcd for C20H26NO4I 471.0908,
found 471.0899.