9120
J.T. Gupton et al. / Tetrahedron 66 (2010) 9113e9122
and 7.66 (d, J¼8.4 Hz, 2H); 13C NMR (CDCl3)
d
168.6, 156.2, 136.0,
procedure with the exception that 5-(4-methylbenzylidene)-4-p-
133.8, 130.1, 129.4, 129.1, 128.8, 128.0, 127.1, 122.0, 94.1, 41.1, 39.7,
31.5, 20.7, and 13.8; IR (neat) 3200 and 1667 cmꢁ1; HRMS (ES) m/z
calcd for C21H23ClNO2 356.1412, found 356.1406.
tolyl-5H-furan-2-one was used in the reaction in which case a solid
(87% yield) was obtained after flash chromatography and this ma-
terial exhibited the following physical properties: bp 79e80 ꢀC at
0.41 Torr; 1H NMR (CDCl3)
d
0.97 (t, J¼7.2 Hz, 3H), 1.39 (sextet,
4.1.33. 5-Benzyl-1-butyl-5-hydroxy-3,4-dimethoxyphenylpyrrol-2
(5H)-one (19d). This compound was prepared by the above pro-
cedure with the exception that 5-benzylidene-4-(3,4-dimeth-
oxyphenyl)-5H-furan-2-one was used in the reaction in which
case a solid (70% yield) was obtained after flash chromatographic
purification as previously described. This material exhibited the
following physical properties: mp 124e127 ꢀC; 1H NMR (CDCl3)
J¼7.2 Hz, 2H), 1.75 (m, 2H), 2.42 (s, 3H), 3.19 (d, J¼14.1 Hz, 1H), 3.29
(d, J¼14.1 Hz, 1H), 3.32 (m, 1H), 3.64 (m, 1H), 3.71 (s, 3H), 5.92 (s.
1H), 6.60 (br s, 4H), 7.22 (d, J¼8.1 Hz, 2H), and 7.62 (d, J¼8.1 Hz, 2H);
13C NMR (CDCl3)
d 169.1,158.4, 157.3, 140.1,130.5, 129.5, 128.9, 127.6,
126.2, 120.7, 113.3, 94.2, 55.1, 40.5, 39.6, 31.5, 21.4, 20.7, and 13.8; IR
(neat) 3500 and 1671 cmꢁ1; HRMS (ES) m/z calcd for C23H28NO3
366.2064, found 366.2138.
d
1.00 (t, J¼7.5 Hz, 3H), 1.44 (sextet, J¼7.5 Hz, 2H), 1.74 (m, 1H), 1.84
(m, 1H), 3.37 (m, 3H), 3.74 (m, 1H), 3.91 (s, 3H), 3.98 (s, 3H), 5.99 (s,
1H), 6.72 (d, J¼7.0 Hz, 2H), 6.95 (d, J¼8.0 Hz, 1H), 7.11 (m, 3H), 7.24
(d, J¼2.0 Hz, 1H), and 7.45 (dd, J¼2.0 Hz, J¼8.0 Hz 1H); 13C NMR
4.1.38. 5-(3,4-Dimethoxybenzyl)-1-(3,4-dimethoxyphenethyl)-5-
hydroxy-4-(3,4-dimethoxyphenyl)-pyrrol-2(5H)-one (19i). This com-
pound was prepared by the above procedure with the exception that
5-(3,4-dimethoxybenzylidene)-4-(3,4-dimethoxyphenyl)-5H-furan-
2-one and 3,4-dimethoxyphenethylamine were used in the reaction
in which case a solid (57% yield) was obtained after flash chro-
matographic purification as previously described. This material
exhibited the following physical properties: mp 170e172 ꢀC; 1H
(CDCl3)
d 169.0, 157.0, 150.7, 149.1, 134.0, 129.5, 127.9, 127.0, 124.5,
121.1, 120.1, 111.1, 110.5, 94.2, 56.0, 55.9, 41.3, 39.6, 31.7, 20.7, and
13.8; IR (neat) 3400 and 1662 cmꢁ1; HRMS (ES) m/z calcd for
C23H28NO4, 382.2013, found 382.2022.
4.1.34. 5-Benzyl-1-hexyl-5-hydroxy-4-p-tolylpyrrol-2(5H)-one
(19e). This compound was prepared by the above procedure with
the exception that n-hexylamine was used in the reaction in which
case a solid (96% yield) was obtained after flash chromatography
and this material exhibited the following physical properties: mp
NMR (CDCl3)
d
2.97 (m, 1H), 3.12 (d, J¼13.8 Hz, 1H), 3.19 (d,
J¼13.8 Hz, 1H), 3.22 (m, 1H), 3.47 (m, 1H), 3.56 (s, 3H), 3.78 (s, 3H),
3.85 (s, 3H), 3.86 (s, 3H), 3.87 (s, 3H), 3.94 (s, 3H), 3.98 (m, 1H), 5.93
(s, 1H), 6.08 (d, J¼2.1 Hz, 1H), 6.28 (dd, J¼2.1 Hz, J¼8.4 Hz, 1H), 6.58
(d, J¼8.4 Hz, 1H), 6.80 (m, 3H), 6.90 (d, J¼8.7 Hz, 1H), 7.18 (d,
J¼2.1 Hz, 1H), and 7.37 (dd, J¼2.1 Hz, J¼8.4 Hz 1H); 13C NMR (CDCl3)
107e110 ꢀC; 1H NMR (CDCl3)
d
0.92 (t, J¼6.6 Hz, 3H), 1.35 (br s, 6H),
1.72 (m, 2H), 2.52 (s, 3H), 3.31 (m, 3H), 3.65 (m, 1H), 5.95 (s, 1H),
d 169.1, 157.3, 150.7, 149.1, 149.0, 148.1, 148.0, 147.7, 132.1, 126.3, 124.3,
6.70 (d, J¼7.2 Hz, 2H), 7.10 (m, 3H), 7.25 (d, J¼8.1 Hz, 2H), and 7.63
121.6, 121.2, 120.9, 119.5, 112.7, 112.3, 111.4, 111.0, 110.6, 110.3, 93.7,
56.0, 55.9, 55.8, 55.7, 55.5, 41.9, 41.0, and 34.0; IR (neat) 3200 and
1658 cmꢁ1; HRMS (ES) m/z calcd for C31H36NO8 550.2441, found
550.2452. Additional NMR experiments including NOESY, HMBC,
HSQC, APT, and COSY were carried out in order to allow for complete
assignment of all proton and carbon absorptions.
(d, J¼8.1 Hz, 2H); 13C NMR (CDCl3)
d 169.2, 157.4, 140.0, 134.2, 129.5,
129.0, 128.5, 127.9, 127.6, 126.9, 120.6, 94.1, 41.5, 39.9, 31.6, 29.3,
27.3, 22.7, 21.4, and 14.1; IR (neat) 3300 and 1662 cmꢁ1; HRMS (ES)
m/z calcd for C24H30NO2 364.2271, found 364.2282.
4.1.35. 5-Benzyl-1-(2,4-dimethoxybenzyl)-5-hydroxy-4-p-tol-
ylpyrrol-2(5H)-one (19f). This compound was prepared by the
above procedure with the exception that 2,4-dimethoxybenzyl-
amine was used in the reaction in which case a solid (95% yield) was
obtained after flash chromatography and this material exhibited
the following physical properties: mp 136e138 ꢀC; 1H NMR (CDCl3)
4.1.39. (Z)-5-Benzylidene-1-butyl-4-p-tolylpyrrol-2(5H)-one (20a).
Method A. Into a round bottom flask containing a magnetic stir bar
were placed 15 mL of chloroform, 5-benzyl-1-butyl-5-hydroxy-4-
p-tolylpyrrol-2(5H)-one (0.200 g, 0.600 mmol), and p-toluene sul-
fonic acid (0.017 g, 0.09 mmol) and the reaction mixture was stirred
at room temperature for 3 h. The reaction mixture was diluted with
additional chloroform (20 mL) and the resulting chloroform phase
was extracted with saturated aqueous bicarbonate solution
(3ꢂ20 mL) and brine (3ꢂ10 mL) and dried over anhydrous mag-
nesium sulfate. After removing the drying agent by filtration, the
filtrate was concentrated in vacuo to give a solid, which was
purified by flash chromatography on a Biotage SP-1 instrument,
equipped with a silica cartridge, and employing an ethyl acetate/
hexane gradient. The product (0.181 g, 96% yield) was eluted with 6
column volumes of eluant. The resulting solid exhibited the
following physical properties: mp 132e135 ꢀC; 1H NMR (CDCl3)
d
2.43 (s, 3H), 3.32 (d, J¼14.5 Hz,1H), 3.48 (d, J¼14.5 Hz,1H), 3.81 (s,
3H), 3.94 (s, 3H), 4.60 (d, J¼15.0 Hz, 1H), 4.82 (d, J¼15.0 Hz, 1H),
6.04 (s,1H), 6.50 (m, 2H), 6.72 (d, J¼7.0 Hz, 2H), 7.10 (m, 3H), 7.24 (d,
J¼8.0 Hz, 2H), 7.47 (d, J¼9.0 Hz, 1H), and 7.69 (d, J¼8.0 Hz, 2H); 13C
NMR (CDCl3)
d 169.5, 160.4, 157.7, 157.4, 140.1, 134.3, 132.0, 129.6,
129.5, 129.0, 127.9, 127.8, 126.9, 120.6, 118.8, 105.0, 98.8, 94.0, 55.7,
55.4, 42.4, 36.7, and 21.4; IR (neat) 1669 cmꢁ1; HRMS (ES) m/z calcd
for C27H28NO4 430.2013, found 430.1997.
4.1.36. 5-(4-Methylbenzyl)-1-butyl-5-hydroxy-4-p-tolylpyrrol-2
(5H)-one (19g). This compound was prepared by the above pro-
cedure with the exception that 5-(4-methylbenzylidene)-4-p-tolyl-
5H-furan-2-one was used in the reaction in which case a solid (95%
yield) was obtained after flash chromatography and this material
exhibited the following physical properties: mp 144e146 ꢀC; 1H
d
0.64 (t, J¼7.4 Hz, 3H), 0.88 (sextet, J¼7.4 Hz, 2H), 1.19 (pentet,
J¼7.7 Hz, 2H), 2.43 (s, 3H), 3.56 (t, J¼7.5 Hz, 2H), 6.19 (s, 1H), 6.40 (s,
1H), 7.28 (d, J¼6.0 Hz, 2H), 7.32 (m, 3H), and 7.38 (m, 4H); 13C NMR
(CDCl3)
d 171.2, 153.1, 139.3, 139.2, 135.0, 129.8, 129.3, 129.0, 128.0,
NMR (CDCl3)
d
0.98 (t, J¼7.5 Hz, 3H), 1.41 (sextet, J¼7.5 Hz, 2H), 1.71
127.8, 120.0, 115.1, 41.1, 30.3, 21.3, 19.6, and 13.5; IR (neat)
1689 cmꢁ1; HRMS (ES) m/z calcd for C22H24NO 318.1852, found
318.1868. Additional NMR experiments including NOESY, HMBC,
HSQC, and DQF-COSY were carried out in order to allow for com-
plete assignment of all proton and carbon absorptions and to es-
tablish the Z stereochemistry.
(m, 1H), 1.80 (m, 1H), 2.23 (s, 3H), 2.44 (s, 3H), 2.96 (s, 1H), 3.28 (m,
3H), 3.68 (m, 1H), 6.00 (s, 1H), 6.58 (d, J¼8.0 Hz, 2H), 6.88 (d,
J¼8.0 Hz, 2H), 7.25 (d, J¼8.0 Hz, 2H), and 7.66 (d, J¼8.0 Hz, 2H); 13C
NMR (CDCl3)
d 168.9, 157.0, 140.2, 136.5, 130.9, 129.6, 129.3, 128.7,
127.6, 120.9, 94.3, 40.7, 39.6, 31.7, 21.5, 21.0, 20.7, and 13.8; IR (neat)
3027 and 1651 cmꢁ1; HRMS (ES) m/z calcd for C23H28NO2 350.2115,
found 350.2129.
4.1.40. (Z)-5-Benzylidene-1-butyl-4-(4-methoxyphenyl)pyrrol-2
(5H)-one (20b). Method B. 5-Benzyl-1-butyl-5-hydroxy-4-meth-
oxyphenylpyrrol-2(5H)-one (0.200 g, 0.569 mmol) was placed in
a 10 mL microwave reaction tube along with a stir bar, p-toluene
4.1.37. 5-(4-Methoxybenzyl)-1-butyl-5-hydroxy-4-p-tolylpyrrol-2
(5H)-one (19h). This compound was prepared by the above