990 J . Org. Chem., Vol. 62, No. 4, 1997
Nayyar et al.
193.9; mass spectrum m/ e 240 (M+ + 1); IR (KBr) 2942, 1642
4-Oxo-1-(4-m et h oxyb en zyl)-2-m et h yl-4,5,6,7-t et r a h y-
d r oin d ole (45) was prepared starting from 40b in 49% yield
as a colorless solid after chromatography: mp 96-98 °C: Rf
0.46 (SiO2, 1:1 hexanes/EtOAc); 1H NMR δ 2.07-2.13 (m, 2H,
CH2), 2.13 (s, 3H, CH3), 2.45 (t, J ) 6.9 Hz, 2H, CH2), 2.63 (t,
J ) 6.2 Hz, CH2), 3.77 (s, 3H, OCH3), 4.95 (s, 2H, NCH2), 6.23
(s, 1H, CH), 6.84 (s, 4H, ArH); 13C NMR δ 11.8, 21.8, 23.5,
37.4, 46.4, 55.0, 103.2, 103.3, 114.0, 119.6, 126.7, 128.3, 130.4,
143.7, 158.7, 193.8; mass spectrum m/ e 269 (M+); IR (KBr)
2990, 1649, 1609, 1512 cm-1; HRMS calcd for C17H20NO2
270.1494, found 270.1500.
4-Oxo-1-(4-n it r op h en et h yl)-2-m et h yl-4,5,6,7-t et r a h y-
d r oin d ole (46) was prepared starting from 41b in 67% yield
as a yellow solid after chromatography (hexanes/EtOAc, 2:8):
mp 137-139 °C: Rf 0.36 (SiO2, 2:8 hexanes/EtOAc); 1H NMR
δ 1.95 (m, 2H, CH2), 2.13 (s, 3H, CH3), 2.31-2.39 (m, 4H, 2 ×
CH2), 3.04 (t, J ) 6.8 Hz, 2H, CH2), 4.03 (t, J ) 6.8 Hz, 2H,
NCH2), 6.28 (s, 1H, CH), 7.11 (d, J ) 9.5 Hz, 2H, ArH), 8.12
(d, J ) 8.4 Hz, 2H, Ar-H); 13C NMR δ 11.7, 21.6, 23.3, 36.3,
37.3, 44.3, 103.5, 103.6, 119.3, 123.4, 129.6, 129.7, 143.1, 145.1,
146.5, 193.4; mass spectrum m/ e 299 (M+ + 1); IR (KBr) 2947,
1635, 1597, 1513, 1345 cm-1; HRMS calcd for C17H19N2O3
299.1396, found 299.1389.
4-Oxo-1-(3,4-dim eth oxyben zyl)-2-m eth yl-4,5,6,7-tetr ah y-
d r oin d ole (47) was prepared starting from 42b in 45% yield
as a yellow solid after chromatography (hexanes:EtOAc, 2:8):
mp 107-109 °C: Rf 0.46 (SiO2, 2:8 hexanes/EtOAc); 1H NMR
δ 2.09 (dd, J ) 6.0, 6.5 Hz, 2H, CH2), 2.14 (s, 3H, CH3), 2.45
(dd, J ) 6.1, 6.7 Hz, 2H, CH2), 2.63 (t, J ) 6.1 Hz, 2H, CH2),
3.79 and 3.84 (two s, 6H, 2 × OCH3), 4.96 (s, 2H, CH2Ph), 6.32
(s, 1H, CH), 6.38 (d, J ) 8.1 Hz, 1H, ArH), 6.44 (s, 1H, ArH),
6.78 (d, J ) 8.2 Hz, 1H, ArH); 13C NMR δ 11.2, 21.2, 23.0,
36.9, 45.9, 55.0, 55.1, 102.6, 102.7, 108.2, 108.3, 110.7, 116.9,
118.9, 128.5, 129.9, 143.2, 147.5, 148.5, 193.0; mass spectrum
m/ e 299 (M+ + 1); IR (KBr) 2938, 1647 cm-1; HRMS calcd for
C18H22NO3 300.1600, found 300.1604.
cm-1; HRMS calcd for C16H18NO 240.1388, found 240.1383.
4-Oxo-1-ben zyl-4,5,6,7-tetr a h yd r oin d ole (21) was pre-
pared starting from 20b in 59% yield an off-white solid after
chromatography: mp 76-78 °C (lit.11 mp 80-81.3 °C): Rf 0.5
1
(SiO2, 2:8 hexanes/EtOAc); H NMR δ 2.11 (dd, J ) 6.2, 6.9
Hz, 2H, CH2), 2.45 (m, 2H, CH2), 2.64 (dd, J ) 6.1, 6.2 Hz,
2H, CH2), 5.04 (s, 2H, NCH2), 6.60 (m, 2H, CH), 6.98 (m, 2H,
CH and ArH), 7.26-7.43 9 (m, 3H, ArH); mass spectrum m/ e
225 (M+); IR (neat) 2944, 1654 cm-1
.
4-Oxo-1-ben zyl-2-(2-m eth ylpr opyl)-4,5,6,7-tetr ah ydr oin -
d ole (24) was prepared starting from 23b in 73% yield as a
light brown oil after chromatography (hexanes/EtOAc, 1:1): Rf
0.4 (SiO2, 7:3 hexanes/EtOAc); 1H NMR δ 0.88 (d, J ) 6.5 Hz,
6H, (CH3)2), 1.75-1.80 (m, 1H, CH), 2.06-2.10 (m, 2H, CH2),
2.29 (d, J ) 7.1 Hz, 2H, CH2), 2.46 (dd, J ) 6.1, 6.7 Hz, 2H,
CH2), 2.58 (t, J ) 6.1 Hz, 2H, CH2), 5.02 (s, 2H, NCH2), 6.36
(s, 1H, CH), 6.87 (d, J ) 7.1 Hz, 2H, ArH), 7.24-7.31 (m, 3H,
ArH); 13C NMR δ 21.8, 22.3, 23.5, 27.5, 35.2, 37.5, 46.8, 103.4,
119.8, 125.3, 127.3, 128.7, 134.3, 136.7, 143.7, 194.0; mass
spectrum m/ e 281 (M+); IR (CHCl3) 2958, 1644, 1476 cm-1
;
HRMS calcd for C19H24NO 282.1858, found 282.1865.
2,3,5,6,7,8-Hexah ydr o-8-oxo-1H-pyr r olo[1,2-a ]in dole (27)
was prepared starting from 26b in 51% yield as a cream-
colored solid after chromatography (hexanes/EtOAc): mp 77-
1
79 °C: Rf 0.33 (SiO2, 2:8 hexanes/EtOAc); H NMR δ 2.08-
2.16 (m, 2H, CH2), 2.43-2.55 (m, 4H, 2 × CH2), 2.71 (t, J )
6.2 Hz, 2H, CH2), 2.79-2.84 (m, 2H, CH2), 3.83 (dd, J ) 7.0,
7.1 Hz, 2H, NCH2), 6.18 (dd, J ) 1.1 Hz, 1H, CH); 13C NMR δ
21.6, 23.2, 23.5, 27.4, 37.4, 43.7, 95.6, 95.7, 123.8, 137.4, 138.6,
193.8; mass spectrum m/ e 175 (M+); IR (KBr) 2920, 1646, 1468
cm-1; HRMS calcd for C11H14NO 176.1075, found 176.1072.
1,2,3,4,6,7,8,9-Octa h yd r o-9-oxop yr id o[1,2-a ]in d ole (30)
was prepared starting from 29b in 61% yield as a colorless
solid after chromatography (hexanes/EtOAc, 4:6): mp 100-
1
102 °C: Rf 0.39 (SiO2, 2:8 hexanes/EtOAc); H NMR δ 1.78-
4-Oxo-1-(1-n a p h th ylm eth yl)-2-m eth yl-4,5,6,7-tetr a h y-
d r oin d ole (48) was prepared starting from 43b in 45% yield
after chromatography (hexanes:EtOAc, 3:7): mp 158-160
1.83 (m, 2H, CH2), 1.92-1.98 (m, 2H, CH2), 2.12 (p, J ) 6.3
Hz, 2H, CH2), 2.45 (dd, J ) 6.1, 6.7 Hz, 2H, CH2), 2.67 (t, J )
6.2 Hz, 2H, CH2), 2.75 (t, J ) 6.3 Hz, 2H, CH2), 3.78 (dd, J )
6.2, 6.2 Hz, 2H, NCH2), 6.20 (s, 1H, CH); 13C NMR δ 20.3, 20.8,
22.7, 23.0, 23.2, 37.4, 42.7, 100.3, 100.4, 119.1, 130.4, 142.0,
1
°C: Rf 0.32 (SiO2, 1:1 hexanes/EtOAc); H NMR δ 2.05-2.11
(m, 2H, CH2), 2.13 (s, 3H, CH3), 2.48 (dist t, J ) 5.7, 7.0 Hz,
2H, CH2), 2.60 (dist t, J ) 6.1 Hz, 2H, CH2), 5.47 (s, 2H, NCH2),
6.41 (d, J ) 10.8 Hz, 1H, ArH), 6.43 (s, 1H, CH), 7.35 (dd, J )
6.4, 9.0 Hz, 1H, ArH), 7.55-7.65 (m, 2H, ArH), 7.78 (d, J )
8.2 Hz, 1H, ArH), 7.93 (d, J ) 8.0 Hz, 1H, ArH), 7.98 (d, J )
8.1 Hz, 1H, ArH); 13C NMR δ 11.6, 21.5, 23.5, 37.5, 44.7, 103.5,
119.8, 121.7, 125.5, 125.6, 127.9, 128.8, 129.7, 130.8, 131.8,
133.2, 144.2, 194.1; mass spectrum m/ e 289 (M+); IR (KBr)
2939, 1648 cm-1; HRMS calcd for C20H20NO 290.1545, found
290.1549.
193.6; mass spectrum m/ e 189 (M+); IR (KBr) 2938, 1651 cm-1
;
HRMS calcd for C12H16NO 190.1232, found 190.1229.
2,3,5,6,7,8-Hexah ydr o-8-oxo-9-ph en yl-1H-pyr r olo[1,2-a ]-
in d ole (34) was prepared starting from 33b in 45% yield as
light yellow solid after chromatography (hexanes/EtOAc, 4:6):
mp 158-159 °C: Rf 0.4 (SiO2, 1:1 hexanes/EtOAc); 1H NMR δ
2.10-2.19 (m, CH2, 2H), 2.47-2.57 (m, 4H, 2 × CH2), 2.77 (t,
J ) 6.2 Hz, 2H, CH2), 2.95 (dd, J ) 7.1, 7.5 Hz, 2H, CH2), 3.89
(dd, J ) 7.0, 7.1 Hz, 2H, NCH2), 7.16-7.57 (m, 5H, ArH); 13
C
Dim et h yl 2,3-d ih yd r o-5-(5-h exyn yl)-1H -p yr r ozolin e-
6,7-d ica r boxyla te (53) The crude acid 51 (1 mmol) was
dissolved in Ac2O (1.3 mL) and then heated at 60-80 °C for
30 min, dimethyl acetylenenedicarboxylate (1.6 mmol) was
added, and the mixture was heated under reflux (120-125 °C
bath temperature) for 6-8 h. The mixture was concentrated
in vacuo, and the brown syrup was purified by column
chromatography (hexanes:EtOAc, 6:4) to give 53 in 98%
yield: Rf 0.53 (SiO2, 1:1 hexanes/EtOAc); 1H NMR δ 1.53-
1.73 (m, 4H, 2 × CH2), 1.93 (t, J ) 2.6 Hz, 1H, CH), 2.21 (dt,
J ) 6.7, 6.9 Hz, 2H, CH2), 2.45-2.55 (m, J ) 7.1, 7.5 Hz, 2H,
CH2), 2.75 (dd, J ) 7.2, 7.7 Hz, 2H, CH2), 3.03 (dd, J ) 7.3,
7.6 Hz, 2H, CH2), 3.77 and 3.82 (two s, 6H, 2 × OCH3), 3.90
(dd, J ) 7.1, 7.2 Hz, 2H, NCH2); 13C NMR δ 18.3, 25.5, 25.9,
26.7, 28.0, 28.6, 45.7, 51.3, 51.5, 68.9, 84.3, 106.5, 115.9, 134.4,
143.4, 164.9, 165.9; mass spectrum m/ e 303 (M+); IR (CHCl3)
NMR δ 22.2, 23.3, 23.8, 27.1, 38.8, 43.9, 114.6, 119.9, 125.3,
127.3, 128.5, 134.6, 135.5, 139.3, 193.2; mass spectrum m/ e
251 (M+); IR (KBr) 2929, 1637, 1604 cm-1; HRMS calcd for
C17H18NO 252.1388, found 252.1393.
2,3,5,6,7,8-Hexa h yd r o-6,6-d im eth yl-8-oxo-1H-p yr r olo-
[1,2-a ]in d ole (38) was prepared starting from 37b in 56%
yield as a colorless solid after chromatography (hexanes/
EtOAc,4:6): mp 125-126 °C: Rf 0.5 (SiO2, 1:1 hexanes/EtOAc);
1H NMR δ 0.92 (s, 6H, 2 × CH3), 2.12 (s, 2H, CH2), 2.36 (m,
2H, CH2), 2.44 (s, 2H, CH2), 2.64 (dd, J ) 7.1, 7.3 Hz, 2H, CH2),
3.68 (dd, J ) 6.9, 7.1 Hz, 2H, NCH2), 5.96 (s, 1H, CH); 13C
NMR δ 23.0, 27.2, 28.2, 35.0, 35.5, 43.5, 51.595.2, 95.3, 122.4,
137.1, 137.4, 192.8; mass spectrum m/ e 203 (M+); IR (KBr)
2958, 1638 cm-1; HRMS calcd for C13H18NO 204.1388, found
204.1392.
4-Oxo-1-m eth yl-2-m eth yl-4,5,6,7-tetr a h yd r oin d ole (44)
was prepared starting from 39b in 39% yield as a light brown
solid after chromatography (hexanes/EtOAc, 3:7): mp 80-82
°C: Rf 0.5 (SiO2, 2:8 hexanes/EtOAc); 1H NMR δ 2.11-2.18
(m, 2H, CH2), 2.20 (s, 3H, CH3), 2.45 (dd, J ) 6.2, 6.6 Hz, 2H,
CH2), 2.71 (t, J ) 6.2 Hz, CH2), 3.42 (s, 3H, NCH3), 6.26 (s,
1H, CH); 13C NMR δ 11.7, 21.6, 23.3, 30.1, 37.3, 102.4, 102.5,
118.9, 130.3, 143.5, 193.5; mass spectrum m/ e 163 (M+); IR
(KBr) 2940, 1641 cm-1; HRMS calcd for C10H14NO 164.1075,
found 164.1077.
3307, 3021, 2950, 2117, 1709 cm-1; HRMS calcd for C17H22
NO4 304.1549, found 304.1554.
-
Eth yl 2,3-d ih yd r o-5-(5-h exyn yl)-1H-p yr a zolin eca r box-
yla te (54) was prepared starting from the acid 51 (1.0 mmol)
and ethyl propiolate (1.6 mmol) to give two regioisomers in
63% yield after chromatography (hexanes:EtOAc, 6:4): m a jor
r egioisom er in 47% yield: Rf 0.52 (SiO2, 85:15 hexanes/
1
EtOAc); H NMR δ 1.31 (t, J ) 7.1 Hz, 3H, CH3), 1.56-1.79
(m 4H, 2 × CH2), 1.95 (t, J ) 2.5 Hz, 1H, CH), 2.22 (m, 2H,
CH2), 2.51 (dd, J ) 6.7, 6.9 Hz, 4H, 2 × CH2), 3.05 (t, J ) 7.5