Cycloaddition Reaction of Mesoionic Betaines
J . Org. Chem., Vol. 63, No. 1, 1998 51
1
3054, 2855, 1652, and 1026 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 0.88 (t, 3H, J ) 7.4 Hz), 1.20 (t, 1H, J ) 7.0 Hz), 1.35 (ddd,
1H, J ) 12.0, 5.7 and 1.4 Hz), 1.51 (q, 2H, J ) 7.4 Hz), 1.62
(q, 1H, J ) 10.0 Hz), 1.99 (s, 3H), 2.17 (dd, 1H, J ) 12.3 and
6.5 Hz), 2.46 (dd, 1H, J ) 15.0 and 8.5 Hz), 2.86 (m, 1H), 3.90
(t, 2H, J ) 7.0 Hz), 4.06 (q, 1H, J ) 7.0 Hz), 6.43 (s, 1H), and
7.23-7.41 (m, 5H); 13C NMR (CDCl3, 75 MHz) δ 8.7, 14.0, 18.7,
26.8, 27.2, 28.4, 36.9, 40.3, 45.9, 60.2, 114.5, 115.1, 127.6, 128.3,
1614, 1588, 969, and 706 cm-1; H NMR (CDCl3, 300 MHz) δ
0.66 (t, 3H, J ) 7.4 Hz), 1.07-1.24 (m, 3H), 1.41 (m, 2H), 1.68
(s, 3H), 1.71-1.97 (m, 6H), 3.28 (m, 1H), 3.78 (dt, 1H, J )
15.0 and 3.0 Hz), 4.23 (s, 1H), and 7.06-7.27 (m, 5H); 13C NMR
(CDCl3, 75 MHz) δ 8.4, 19.4, 19.9, 25.9, 28.7, 30.0, 34.8, 39.9,
43.6, 45.4, 99.3, 113.7, 125.9, 127.1, 128.2, 136.7, 145.3, 170.9,
and 176.4. Anal. Calcd for C21H25NO2: C, 77.98; H, 7.79; N,
4.33. Found: C, 78.19; H, 7.80; N, 4.25.
128.4, 138.0, 150.3, 154.6, and 163.6. Anal. Calcd for C21H23
NO2: C, 78.47; H, 7.21; N, 4.35. Found: C, 78.39; H, 7.24; N,
4.42.
-
3-Eth yl-3-[(E)-4-ph en yl-3-bu ten yl]-2-piper idon e (30) was
prepared by a modification of the procedure of Schwarz.56
A
mixture of 1.0 g (3.9 mmol) of lactam 32, 218 mg (2.0 mmol)
of thiophenol, and 840 mg (5.1 mmol) of AIBN in 50 mL of
benzene was heated for 8 h in a sealed tube at 80 °C. Removal
of the solvent followed by chromatography on silica gel gave
lactam 30 in 92% as a colorless oil; IR (neat) 3281, 3205, 2899,
and 1650 cm-1; 1H NMR (CDCl3, 300 MHz) δ 0.91 (t, 3H, J )
7.5 Hz), 1.51-1.71 (m, 8H), 1.89-2.25 (m, 2H), 3.25 (s, 2H),
6.13-6.25 (m, 1H,), 6.34 (s, 1H), 6.38-6.48 (s, 1H), and 7.13-
7.31 (m, 5H); 13C NMR (CDCl3, 75 MHz) δ 8.6, 19.8, 28.0, 29.1,
31.1, 37.7, 42.5, 44.6, 125.8, 126.7, 128.4, 129.7, 130.7, 137.7,
and 176.9. Anal. Calcd for C17H23NO: C, 79.33; H, 9.01; N,
5.44. Found: C, 79.10; H, 9.10; N, 5.41.
2-Acetyl-7a-eth yl-6,7,7a,8,9,10-h exah ydr o-3-oxo-1-ph en -
yl-3H,5H-ben zo[ij]qu in olizin e (29) was prepared as a color-
less oil in 65% yield from lactam 25 in a manner similar to
that used for the conversion of 20 to 22; IR (neat) 3055, 2872,
1703, 1625, 1569, and 773 cm-1; 1H NMR (CDCl3, 300 MHz) δ
0.81 (t, 3H, J ) 7.5 Hz), 1.28-1.44 (m, 3H), 1.49-1.70 (m, 5H),
1.80-1.94 (m, 4H), 2.15 (s, 3H), 3.87 (m, 1H), 4.31 (pent, 1H,
J ) 7.5 Hz), 7.06 (m, 2H), and 7.29 (m, 3H); 13C NMR (CDCl3,
75 MHz) δ 7.1, 17.1, 17.8, 26.0, 27.9, 28.6, 31.3, 32.4, 36.8,
41.2, 111.5, 127.6, 127.7, 128.0, 128.8, 136.3, 149.8, 150.7,
159.6, and 202.4. Anal. Calcd for C22H25NO2: C, 78.77; H,
7.51; N, 4.18. Found: C, 78.81; H, 7.51; N, 4.22.
Gen er a l P r oced u r e for th e Nick el Bor id e Ca ta lyzed
Hyd r ogen a tion . The alkynyl-substituted lactams were re-
duced according the procedure of Brown and Ahuja.55 To a
homogeneous solution of 0.18 equiv of Ni(OAc)2‚4H20 in
absolute ethanol (1 mL/1 mmol of alkyne) at 25 °C was added
0.18 equiv of NaBH4 (1 M solution in absolute ethanol). The
flask was alternatively evacuated (aspirator) and filled with
hydrogen, and the catalyst was stirred over 1 atm of hydrogen.
Ethylenediamine (0.37 equiv) was added dropwise via syringe
followed by a solution of the appropriate alkyne in absolute
ethanol (10 mL/1 g alkyne). The mixture was stirred at 25 °C
until hydrogenation to the cis-alkene was complete. The
solvent was removed under reduced pressure, and the residue
was dissolved in CH2Cl2. This solution was filtered through
a plug of florisil, the solvent was removed under reduced
pressure, and the crude product was purified by flash silica
gel chromatography.
2-Acetyl-7a -eth yl-1(â),2(â),5,6,7,7a (r),8,9-octa h yd r o-1-
p h en yl-3H-cyclop en ta [ij]qu in olizin -3-on e (31) was ob-
tained as a colorless oil from lactam 30 in 63% yield in a
manner similar to that used for the conversion of 20 to 22; IR
1
(neat) 3010, 2877, 1712, 1680, 1645, and 706 cm-1; H NMR
(CDCl3, 300 MHz) δ 0.91 (t, 3H, J ) 7.4 Hz), 1.21-1.60 (m,
4H), 1.69-1.80 (m, 4H), 1.95-2.14 (m, 3H), 2.21-2.40 (m, 1H),
2.25 (s, 1H,) 2.88-3.01 (m, 1H), 3.51 (s, 1H), 3.96 (s, 1H), 4.01-
4.04 (m, 1H), and 7.21-7.50 (m, 5H); 13C NMR (CDCl3, 75
MHz) δ 8.7, 19.5, 26.2, 27.7, 28.7, 32.5, 36.1, 39.6, 41.9, 45.4,
65.7, 117.7, 127.0, 127.1, 128.9, 140.4, 140.6, 166.7, and 201.5.
Anal. Calcd for C21H25NO2: C, 77.98; H, 7.79; N, 4.33.
Found: C, 78.03; H, 7.74; N, 4.29.
The 2,4-DNPH derivative of 31 was prepared in the follow-
ing fashion. To a solution of 30 mg of 2,4-dinitrophenylhy-
drazine in 0.50 mL of methanol and 50 µL of H2SO4 was added
20 mg of 31 in 200 µL of methanol. After stirring for 10 min,
a few drops of concentrated H2SO4 was added to the mixture
and an orange precipitate appeared. Filtration gave the 2,4-
DNPH of 31 in 63% yield as an orange solid, mp 187-188 °C;
3-Eth yl-3-[(Z)-4-ph en yl-3-bu ten yl]-2-piper idon e (32) was
obtained as a colorless oil in 96% yield from lactam 24 in a
manner similar to that used for the conversion of 20 to 22; IR
(neat) 3283, 3195, 2866, and 1651 cm-1; 1H NMR (CDCl3, 300
MHz) δ 0.84 (t, 3H, J ) 7.4 Hz), 1.41-1.87 (m, 8H), 2.19-
2.42 (m, 2H), 3.16 (brs, 2H), 5.59 (dt, 1H, J ) 11.4 and 7.4
Hz), 6.35 (d, 1H, J ) 11.4 Hz), 6.95 (brs, 1H), and 7.13-7.31
(m, 5H), 13C NMR (CDCl3, 75 MHz) δ 8.4, 19.6, 23.4, 28.7, 30.9,
38.0, 42.2, 44.4, 126.2, 127.9, 128.4, 128.6, 132.4, 137.3, and
176.9. Anal. Calcd for C17H23NO: C, 79.33; H, 9.01; N, 5.44.
Found: C, 79.13; H, 9.05; N, 5.39.
IR (KBr) 3317, 3100, 2900, 1663, 1615, 1503, and 1334 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 0.65 (t, 3H, J ) 7.4 Hz), 1.21-
1.36 (m, 3H), 1.54-1.62 (m, 1H), 1.77-1.79 (m, 2H), 1.96-
2.05 (m, 3H), 2.18 (s, 3H), 2.26-2.38 (m, 1H), 3.02-3.09 (m,
1H), 3.57 (s, 1H), 3.95 (s, 1H), 4.00-4.05 (m, 1H), 7.01-7.32
(m, 5H), 7.91 (d, 1H, J ) 10.0 Hz), 8.31 (dd, 1H, J ) 10.0 and
2.0 Hz), 9.12 (d, 1H, J ) 2.0 Hz), and 11.09 (s, 1H); 13C NMR
(CDCl3, 75 MHz) δ 8.9, 15.0, 19.8, 26.7, 29.3, 32.8, 36.5, 41.2,
42.1, 45.7, 60.0, 116.3, 116.6, 123.7, 123.7, 127.3, 127.4, 129.3,
130.2, 138.4, 140.7, 140.9, 145.2, 153.0, and 167.5; HRMS
Calcd for C27H29N5O5: 503.2168. Found: 503.2166.
2-Acetyl-7a -eth yl-1(â),2(â),5,6,7,7a (â),8,9-octa h yd r o-1-
p h en yl-3H-cyclop en ta [ij]qu in olizin -3-on e (33) was ob-
tained as a white solid from lactam 32 in 61% yield in a
manner similar to that used for the conversion of 20 to 22,
mp 97-98 °C; IR (KBr) 3005, 2862, 1716, 1688, 1645, and 706
3-E t h yl-3-[4-(2′-n it r op h en yl)-3-b u t yn yl]-2-p ip er id on e
(41) was prepared in 73% yield as a yellow solid from lactam
26 and 2-nitro-1-bromobenzene, mp 93-94 °C, IR (KBr) 3553,
3289, 2863, 2211, 1646, and 1522 cm-1; 1H NMR (CDCl3, 300
MHz) δ 0.87 (t, 3H, J ) 7.3 Hz), 1.53 (m, 1H), 1.68-1.88 (m,
6H), 2.02 (m, 1H), 2.51 (t, 2H, J ) 7.0 Hz), 3.26 (m, 2H), 6.45
1
cm-1; H NMR (CDCl3, 300 MHz) δ 0.83 (t, 3H, J ) 7.4 Hz),
1.17 (m, 1H), 1.38-1.56 (m, 3H), 1.60-1.79 (m, 3H), 1.86 (dd,
1H, J ) 7.0 and 3.5 Hz), 1.90 (dd, 1H, J ) 7.0 and 3.5 Hz),
2.04 (m, 1H), 2.04 (s, 3H), 2.95 (m, 1H), 3.82 (d, 1H, J ) 13.5
Hz), 3.88 (dt, 1H, J ) 13.5 and 3.9 Hz); 4.09 (d, 1H, J ) 13.5
Hz), and 7.05-7.23 (m, 5H); 13C NMR (CDCl3, 75 MHz) δ 8.7,
19.1, 27.2, 28.3, 31.7, 32.0, 35.5, 41.0, 41.7, 45.4, 61.3, 116.0,
126.7, 127.9, 128.3, 140.0, 140.2, 167.7, and 204.3. Anal.
Calcd for C21H25NO2: C, 77.98; H, 7.79; N, 4.33. Found: C,
78.11; H, 7.84; N, 4.29.
(brs, 1H), 7.25-7.54 (m, 3H), and 7.92 (d, 1H, J ) 8.1 Hz); 13
C
NMR (CDCl3, 75 MHz) δ 8.4, 15.4, 19.6, 29.1, 30.3, 30.6, 36.5,
42.4, 44.4, 75.8, 99.2, 119.1, 124.2, 127.9, 132.6, 134.7, and
176.5. Anal. Calcd for C17H20N2O3: C, 67.98; H, 6.71; N, 9.33.
Found: C, 67.81; H, 6.77; N, 9.27.
2-Acetyl-7a -eth yl-5,6,7,7a ,8,9-h exa h yd r o-1-(2-n itr op h e-
n yl)-3H-cyclop en ta [ij]qu in olizin -3-on e (42) was obtained
from lactam 41 in 77% yield in a manner similar to that used
for the conversion of 20 to 22 as 1:1-mixture of diastereomers
which could be separated by silica gel chromatography. One
of the diastereomers showed the following properties: mp
7a -E t h yl-2-(1-h yd r oxyet h ylid en e)-1(â),5,6,7,7a (â),8,9-
h e p t a h yd r o-1-p h e n yl-3H -cyclop e n t a [ij]q u in olizin -3-
on e (34) was also obtained (31% yield) as a white solid in a
manner similar to 33 and was purified by silica gel column
chromatography, mp 138-139 °C; IR (KBr) 3025, 2855, 1702,
156-157 °C; IR (neat) 2963, 2864, 1639, 1526, and 1343 cm-1
;
(55) Brown, C. A.; Ahuja, V. K. J . Chem. Soc., Chem. Commun. 1973,
553.
(56) Schwarz, M.; Graminski, G. F.; Waters, R. M. J . Org. Chem.
1986, 51, 260.