2826 J . Org. Chem., Vol. 66, No. 8, 2001
Bunce et al.
131.0, 128.5, 125.2, 52.5, 46.3, 42.7, 29.8; HRMS m/z calcd for
1 H), 3.76 (s, 3 H), 3.26 (m, 1 H), 2.21 (ddd, J ) 12.6, 5.7, 2.5
Hz, 1 H), 1.94 (dt, J ) 23.6, 11.0 Hz, 1 H), 1.52 (m, 2 H), 1.38
(m, 4 H), 0.93 (t, J ) 6.9 Hz, 3 H); 13C NMR δ 175.0, 144.6,
128.1, 127.9, 118.1, 117.4, 114.7, 52.0, 50.7, 43.9, 36.1, 32.5,
27.6, 22.7, 14.0; HRMS m/z calcd for C15H21NO2 247.1572,
found 247.1571.
C
12H13NO5 251.0793, found 251.0791.
Anal. Calcd for C12H13NO5: C, 57.37; H, 5.18. Found: C,
57.59; H, 5.23.
Meth yl (()-2-(2-n itr oph en yl)-4-oxo-4-ph en ylpen tan oate
(5b): mp 80-82 °C; 1.41 g (4.50 mmol, 89%); IR 1746, 1687,
1530, 1353 cm-1; 1H NMR δ 7.98 (m, 3 H), 7.57 (m, 3 H), 7.46
(m, 3 H), 4.91 (dd, J ) 7.8, 5.1 Hz, 1 H), 4.03 (dd, J ) 18.1, 7.8
Hz, 1 H), 3.69 (s, 3 H), 3.47 (dd, J ) 18.1, 5.1 Hz, 1 H); 13C
NMR δ 196.7, 172.4, 149.3, 136.2, 133.5 (2), 133.4, 131.0, 128.6,
Anal. Calcd for C15H21NO2: C, 72.87; H, 8.50; N, 5.67.
Found: C, 73.06; H, 8.52; N, 5.72.
Met h yl (()-(2S*,4S*)-2-ter t-b u t yl-1,2,3,4-t et r a h yd r o-
qu in olin e-4-ca r boxyla te (6d ): 588 mg (2.38 mmol, 93%); mp
76-79 °C; IR 3381, 1736 cm-1; 1H NMR δ 7.02 (t, J ) 8.0 Hz,
1 H), 6.93 (d, J ) 7.7 Hz, 1 H), 6.62 (t, J ) 7.6 Hz, 1 H), 6.53
(d, J ) 8.1 Hz, 1 H), 3.93 (dd, J ) 12.5, 5.3 Hz, 1 H), 3.84 (br
s, 1 H), 3.78 (s, 3 H), 3.00 (dd, J ) 11.5, 2.3 Hz, 1 H), 2.20
(ddd, J ) 12.5, 5.3, 2.3 Hz, 1 H) 1.93 (dt, J ) 24.0, 11.5 Hz, 1
H), 0.98 (s, 9 H); 13C NMR δ 175.2, 145.2, 127.9, 127.7, 118.2,
117.3, 114.8, 59.8, 52.0, 44.4, 33.3, 27.7, 25.8 (3); HRMS m/z
calcd for C15H21NO2 247.1572, found 247.1568.
128.5, 128.1, 125.2, 52.6, 42.8, 42.0; HRMS m/z calcd for C17H15
-
NO5 313.0950, found 313.0948.
Anal. Calcd for C17H15NO5: C, 65.18; H, 4.79. Found: C,
65.50; H, 4.84.
Meth yl (()-2-(2-n itr op h en yl)-4-oxoocta n oa te (5c): 1.04
g (3.55 mmol, 95%); IR 1744, 1715, 1527, 1354 cm-1; 1H NMR
δ 7.97 (d, J ) 8.1 Hz, 1 H), 7.58 (t, J ) 7.7 Hz, 1 H), 7.45 (d,
J ) 7.8 Hz, 1 H), 7.44 (t, J ) 7.3 Hz, 1 H), 4.70 (dd, J ) 8.4,
4.8 Hz, 1 H), 3.66 (s, 3 H), 3.44 (dd, J ) 18.1, 8.4 Hz, 1 H),
2.85 (dd, J ) 18.1, 4.8 Hz, 1 H), 2.45 (m, 2 H), 1.57 (quintet,
J ) 7.3 Hz, 2 H), 1.30 (sextet, J ) 7.4 Hz, 2 H), 0.89 (t, J )
7.3 Hz, 3 H); 13C NMR δ 207.8, 172.3, 148.7, 133.5 (2), 131.0,
128.4, 125.2, 52.5, 45.4, 42.7, 42.4, 25.8, 22.2, 13.8; HRMS m/z
calcd for C15H19NO5 293.1263, found 293.1260.
Anal. Calcd for C15H21NO2: C, 72.87; H, 8.50; N, 5.67.
Found: C, 73.08; H, 8.53; N, 5.65.
Meth yl (()-1,2,3,4-Tetr a h yd r oqu in olin e-4-ca r boxyla te
(9). A solution of 1.50 g (6.38 mmol) of 3e in 150 mL of MeOH
was treated with ozone, dimethyl sulfide and p-TsOH as
described for the preparation of 5a . The reaction was concen-
trated, diluted with ether, washed with NaHCO3 (2×) and
NaCl (1×) and dried (MgSO4). Evaporation of the ether gave
acetal 7 contaminated with a small amount of aldehyde 8. This
mixture was dissolved in 75 mL of THF and 75 mL of 3%
aqueous HClO4 was added dropwise at 0 °C.12 The solution
was stirred at 0 °C for 1 h and at room temperature for 6 h,
then extracted with CH2Cl2 (2×). The organic layer was
washed with NaHCO3 (2×) and NaCl (1×), dried (MgSO4) and
concentrated under vacuum to give 1.48 g (6.24 mmol, 98%)
of 8. This compound was used without further purification:
Anal. Calcd for C15H19NO5: C, 61.43; H, 6.48. Found: C,
61.75; H, 6.54.
Met h yl (()-5,5-d im et h yl-2-(2-n it r op h en yl)-4-oxoh ex-
a n oa te (5d ): 2.18 g (7.44 mmol, 92%); IR 1744, 1712, 1530,
1
1353 cm-1; H NMR δ 7.96 (d, J ) 8.1 Hz, 1 H), 7.57 (t, J )
7.6 Hz, 1 H), 7.45 (d, J ) 7.7 Hz. 1 H), 7.44 (t, J ) 7.3 H, 1 H),
4.66 (dd, J ) 8.5, 4.8 Hz, 1 H), 3.66 (s, 3 H), 3.48 (dd, J )
18.1, 8.5 Hz, 1 H), 2.96 (dd, J ) 18.1, 4.8 Hz, 1 H), 1.15 (s, 9
H); 13C NMR δ 212.7, 172.5, 148.7, 133.6, 133.4, 130.7, 128.4,
125.2, 52.4, 44.0, 42.8, 40.3, 26.3 (3); HRMS m/z calcd for
1
C
15H19NO5 293.1263, found 293.1262.
IR 2846, 2733, 1744, 1729, 1527, 1354 cm-1; H NMR δ 9.80
Anal. Calcd for C15H19NO5: C, 61.43; H, 6.48. Found: C,
61.69; H, 6.52.
(s, 1 H), 8.00 (dd, J ) 7.8, 1.4 Hz, 1 H), 7.58 (td, J ) 7.7, 1.4
Hz, 1 H), 7.47 (m, 2 H), 4.76 (dd, J ) 8.1, 5.1 Hz, 1 H), 3.65 (s,
3 H), 3.55 (dd, J ) 18.7, 8.1 Hz, 1 H), 2.97 (dd, J ) 18.7, 5.1
Hz, 1 H); 13C NMR δ 198.5, 171.8, 148.7, 133.6, 132.9, 130.9,
128.7, 125.4, 52.7, 46.6, 41.4; HRMS m/z calcd for C11H11NO5
237.0637, found 237.0636.
Rep r esen ta tive P r ep a r a tion of Tetr a h yd r oqu in olin e-
4-car boxylic Ester s: Meth yl (()-(2R*,4S*)-2-Meth yl-1,2,3,4-
tetr a h yd r oqu in olin e-4-ca r boxyla te (6a ). A solution of 750
mg (2.99 mmol) of 5a in 125 mL of MeOH containing 100 mg
of 5% Pd/C was shaken under 4 atm of H2 at 30 °C for 2.5 h.
The solvent was removed, the residue was diluted with ether,
and the solution was filtered through a pad of Celite topped
with a layer of anhydrous MgSO4 to separate the catalyst.
Concentration under vacuum gave 600 mg (2.93 mmol, 98%)
of 6a as a light yellow oil that crystallized on standing at -20
°C. This solid was triturated with 3% ether in hexane to give
To a solution of 550 mg (2.32 mmol) of 8 in 150 mL of MeOH
was added 125 mg of 5% Pd/C, and the mixture was shaken
under 4 atm of H2 at 30 °C for 8 h. The solvent was removed,
the residue was diluted with ether, and the solution was
filtered through
a pad of Celite topped with a layer of
anhydrous MgSO4 to separate the catalyst. Concentration
under vacuum gave 400 mg (2.09 mmol, 90%) of 9 as a light
yellow oil: IR 3403, 1729 cm-1; 1H NMR δ 7.10 (d, J ) 7.8 Hz,
1 H), 7.02 (t, J ) 8.0 Hz, 1 H), 6.63 (t, J ) 7.8 Hz, 1 H), 6.51
(d, J ) 8.0 Hz, 1 H), 3.78 (t, J ) 4.8 Hz, 1 H), 3.71 (s, 3 H),
3.69 (br s, 1 H), 3.43 (td, J ) 11.0, 3.2 Hz, 1 H), 3.27 (dt, J )
11.5, 4.8 Hz, 1 H), 2.27 (m, 1 H), 2.00 (m, 1 H); 13C NMR δ
174.9, 144.5, 130.3, 128.1, 117.0 (2), 114.8, 52.0, 41.5, 38.7,
24.4; HRMS m/z calcd for C11H13NO2 191.0946, found 191.0943.
Anal. Calcd for C11H13NO2: C, 69.11; H, 6.81; N, 7.32.
Found: C, 69.29; H, 6.85; N, 7.41.
6a as an off-white powder: mp 82-84 °C; IR 3395, 1737 cm-1
;
1H NMR δ 7.01 (t, J ) 8.1 Hz, 1 H), 6.97 (d, J ) 7.7 Hz, 1 H);
6.64 (t, J ) 7.6 Hz, 1 H), 6.50 (d, J ) 8.1 Hz, 1 H), 3.96 (dd, J
) 12.0, 5.9 Hz, 1 H), 3.76 (br s, 1 H), 3.76 (s, 3 H), 3.41 (m, 1
H), 2.15 (ddd, J ) 12.8, 5.9, 2.6 Hz, 1 H), 1.95 (dt, J ) 22.9,
12.8 Hz, 1 H), 1.23 (d, J ) 6.3 Hz, 3 H); 13C NMR δ 175.0,
144.7, 128.1, 127.3, 117.9, 117.6, 114.7, 52.0, 46.3, 43.9, 34.4,
22.3; HRMS m/z calcd for C12H15NO2 205.1103, found 205.1104.
Anal. Calcd for C12H15NO2: C, 70.24; H, 7.32; N, 6.83.
Found: C, 70.29; H, 7.33; N, 6.76.
Meth yl (()-(4a R*,6S*)-2,3,4,4a ,5,6-Hexa h yd r o-1H-ben -
zo[c]qu in olizin e-6-ca r boxyla te (12). A solution of 600 mg
(2.18 mmol) of 3f in 150 mL of MeOH was treated with ozone,
dimethyl sulfide and p-TsOH as described for the preparation
of 5a . The reaction was concentrated, diluted with ether,
washed with NaHCO3 (2×) and NaCl (1×) and dried (MgSO4).
Evaporation of the ether gave acetal 10 contaminated with a
small amount of aldehyde 11. This mixture was dissolved in
40 mL of THF and 40 mL of 3% aqueous HClO4 was added
dropwise at 0 °C. Stirring was continued for 1 h at 0 °C and
at room temperature for 3 h. Workup, as above, afforded 626
mg (2.04 mmol, 94%) of 11. This compound was used without
further purification: IR 2840, 2733, 1744, 1730, 1530, 1353
Meth yl (()-(2S*,4S*)-2-p h en yl-1,2,3,4-tetr a h yd r oqu in o-
lin e-4-ca r boxyla te (6b): 619 mg (2.32 mmol, 97%); mp 75-
1
78 °C; IR 3395, 1736 cm-1; H NMR δ 7.45-7.27 (complex, 5
H), 7.07 (t, J ) 8.1 Hz, 1 H), 7.03 (d, J ) 7.7 Hz, 1 H), 6.72 (t,
J ) 7.7 Hz, 1 H), 6.57 (d, J ) 8.1 Hz, 1 H), 4.42 (dd, J ) 10.2,
3.7 Hz, 1 H), 4.11 (dd, J ) 11.1, 6.5 Hz, 1 H), 4.10 (br s, 1 H),
3.71 (s, 3 H), 2.36 (m, 2 H); 13C NMR δ 174.5, 144.7, 143.2,
128.7, 128.3, 128.1, 127.9, 126.7, 117.8, 117.7, 114.9, 55.7, 52.0,
44.1, 35.2; HRMS m/z calcd for C17H17NO2 267.1259, found
267.1259.
Anal. Calcd for C17H17NO2: C, 76.40; H, 6.37; N, 5.24.
Found: C, 76.33; H, 6.34; N, 5.29.
1
Meth yl (()-(2R*,4S*)-2-bu tyl-1,2,3,4-tetr a h yd r oqu in o-
cm-1; H NMR δ 9.75 (t, J ) 1.4 Hz, 1 H), 7.97 (dd, J ) 8.0,
lin e-4-ca r boxyla te (6c): 625 mg (2.53 mmol, 99%); mp 53-
1.2 Hz, 1 H), 7.59 (td, J ) 7.4, 1.4 Hz, 1 H), 7.45 (m, 2 H), 4.71
(dd, J ) 8.8, 4.5 Hz, 1 H), 3.65 (s, 3 H), 3.42 (dd, J ) 17.9, 8.8
Hz, 1 H), 2.82 (dd, J ) 17.9, 4.5 Hz, 1 H), 2.66-2.43 (complex,
4 H), 1.92 (quintet, J ) 7.0 Hz, 2 H); 13C NMR δ 206.6, 201.7,
1
54 °C; IR 3393, 1736 cm-1; H NMR δ 7.02 (t, J ) 8.1 Hz, 1
H), 6.96 (d, J ) 7.7 Hz, 1 H), 6.64 (t, J ) 7.6 Hz, 1 H), 6.51 (d,
J ) 8.0 Hz, 1 H), 3.94 (dd, J ) 11.8, 5.7 Hz, 1 H), 3.80 (br s,