PAPER
Efficient Synthesis of 3,4-Diaryl-Substituted Pyrroles
3325
1H NMR (300 MHz, CDCl3): δ = 9.24 (br s, 1 H), 7.16 (d, J = 9 Hz,
2 H), 7.00–7.03 (m, 3 H), 6.81 (d, 2 H, J = 9 Hz), 6.72 (d, J = 9 Hz,
2 H), 3.79 (s, 3 H), 3.73 (s, 3 H), 3.69 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 161.5, 158.5, 158.0, 131.8, 129.5,
127.1, 126.5, 120.0, 119.4, 113.7, 113.1, 55.2, 55.1, 51.2.
127.5, 127.2, 124.6, 119.8, 114.4, 114.1, 113.8, 69.9, 55.5, 50.8.
MS: m/z = 637 (M+).
Removal of the Benzyl Group from 12 and 13;
General Procedure
A mixture of 12 (20 mg, 0.04 mmol) or 13 (12 mg, 0.019 mmol) and
Pd(OH)2 (10 mol%) in MeOH (0.5 M solution) was stirred over-
night under H2 atmosphere. After that, the resulting mixture was fil-
tered through Celite and the solvent was evaporated under reduced
pressure to afford the desired product in almost quantitative yield.
No further purification was performed.
MS: m/z = 337 (M+).
Methyl 3,4-Bis(4-methoxyphenyl)-1-[2-(4-methoxyphenyl)-2-
oxoethyl]-1H-pyrrole-2-carboxylate (11, Lamellarin O-Dimeth-
yl Ether)
A mixture of 10 (223 mg, 0.7 mmol), anhyd K2CO3 (773 mg, 5.6
mmol) 2-bromo-4′-methoxyacetophenone (321 mg, 1.4 mmol) in
anhyd acetone (50 mL) was heated under reflux for 3 h. The reac-
tion was cooled to r.t., followed by the addition of Celite, and re-
moval of the solvent. The supported crude mixture was fractionated
by FCC (SiO2, 30% EtOAc–hexanes) to afford 300 mg (88%) of the
desired product as yellow crystals; mp 68–72 °C (CH2Cl2–hexanes).
Methyl 3,4-Bis(4-hydroxyphenyl)-1H-pyrrole-2-carboxylate
(Lamellarin Q, 1)
Yield: 12.2 mg (quant); unstable yellow solid; mp 220–222 °C
(dec.).
IR (KBr): 3288, 3023, 2949, 1895, 1683, 1438, 1245 cm–1.
1H NMR (300 MHz, acetone-d6): δ = 10.91 (br s, 1 H), 8.25 (br s, 2
H), 7.14 (d, J = 3 Hz, 1 H), 7.05 (d, J = 8.7 Hz, 2 H), 6.95 (d, J = 8.7
Hz, 2 H), 6.75 (d, J = 8.7 Hz, 2 H), 6.66 (d, J = 8.7 Hz, 2 H), 3.64
(s, 3 H).
Note: When the 1H NMR spectra for compound 1 was acquired us-
ing a diluted sample (<10 mg), the signal at 8.25 ppm corresponding
to phenolic OH groups appeared as two simple signals at 8.25 and
8.18 ppm, and each signal integrated for 1 H (see spectra of com-
pound 1 in the Supporting Information).
IR (KBr): 3000, 2937, 2836, 2039, 1685, 1598, 1234, 1168 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.01 (d, J = 9 Hz, 2 H), 7.15 (d,
J = 9 Hz, 2 H), 6.99 (d, J = 9 Hz, 2 H), 6.98 (d, J = 9 Hz, 2 H), 6.92
(s, 1 H), 6.82 (d, J = 9 Hz, 2 H), 6.71 (d, J = 9 Hz, 2 H), 5.72 (s, 2
H), 3.88 (s, 3 H), 3.81 (s, 3 H), 3.73 (s, 3 H), 3.47 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 50.7, 55.1, 55.4, 55.5, 112.8, 113.5,
114.1, 119.7, 124.6, 126.9, 127.1, 127.8, 127.9, 129.4, 130.3, 131.1,
131.8, 157.8, 158.2, 162.3, 163.9, 191.8.
13C NMR (75 MHz, acetone-d6): δ = 161.9, 157.0, 156.5, 132.8,
130.2, 129.7, 127.4, 127.0, 126.8, 121.4, 120.0, 115.8, 115.2, 51.0.
MS: m/z = 309 (M+).
MS: m/z = 485 (M+).
Methyl 3,4-Bis(4-benzyloxyphenyl)-1H-pyrrole-2-carboxylate
(12)
This compound was prepared from the dibenzyl ether 9e according
to the procedure described for the synthesis of 10, to afford the anal-
ogous Fürstner intermediate 12 in 53% yield; foam.
Methyl 3,4-Bis(4-hydroxyphenyl)-1-[2-(4-methoxyphenyl)-2-
oxoethyl]-1H-pyrrole-2-carboxylate (Lamellarin O, 3)
Yield: 8.5 mg (quant); unstable yellow solid; mp 255–260 °C (dec.).
IR (KBr): 3410, 3300, 3062, 3032, 2949, 2927, 1638, 1672, 1239
cm–1.
1H NMR (300 MHz, CDCl3): δ = 9.25 (br s, 1 H), 7.47–7.30 (m, 10
H), 7.19 (d, J = 9 Hz, 2 H), 7.04–6.99 (m, 3 H), 6.92 (d, J = 9 Hz, 2
H), 6.82 (d, J = 9 Hz, 2 H), 5.05 (s, 2 H), 4.99 (s, 2 H), 3.71 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 161.5, 157.8, 157.2, 137.1, 137,
131.9, 129.5, 129.4, 129.0, 128.5, 127.9, 127.6, 127.5, 127.3, 126.7,
126.4, 120.1, 119.2, 114.6, 114.0, 70.0, 69.9, 51.2.
IR (KBr): 3385, 3124, 3029, 2916, 2847, 2478, 1752, 1679, 1659,
1594, 1166 cm–1.
1H NMR (300 MHz, acetone-d6): δ = 8.24 (s, 1 H), 8.18 (s, 1 H),
8.08 (d, J = 9 Hz, 2 H), 7.18 (s, 1 H), 7.09 (d, J = 9 Hz, 2 H), 7.03
(d, J = 8.7 Hz, 2 H), 6.95 (d, J = 9 Hz, 2 H), 6.78 (d, J = 8.7 Hz, 2
H), 6.66 (d, J = 8.7 Hz, 2 H), 5.88 (s, 2 H), 3.91 (s, 3 H), 3.39 (s, 3
H).
13C NMR (75 MHz, acetone-d6): δ = 192.5, 164.7, 162.6, 156.8,
156.3, 132.5, 131.3, 130.9, 130.0, 129.0, 128.1, 127.9, 127.0, 124.9,
120.5, 115.6, 115.0, 114.7, 56.3, 55.9, 50.6.
MS: m/z = 489 (M+).
Methyl 3,4-Bis(4-benzyloxyphenyl)-1-[2-(4-methoxyphenyl)-2-
oxoethyl]-1H-pyrrole-2-carboxylate (13, Lamellarin O-Diben-
zyl Ether)
MS: m/z = 457 (M+).
Method A: Lamellarin O-dibenzyl ether was prepared from 12 in
85% yield according to the procedure described for compound 11.
Acknowledgment
We would like to thank Facultad de Química, National Autonomous
University of Mexico (UNAM) and DGAPA-UNAM for financial
support (Grant No. IN-204108). A. Ramirez and C. Jimenez thank
CONACYT for scholarships. The authors wish to thank Dr. J. M.
Muchowski for helpful discussions.
Method B: A mixture of 12 (150 mg, 0.3 mmol), K2CO3 (207 mg,
1.5 mmol), 18-crown-6 (80 mg, 0.03 mmol) and 2-bromo-4′-meth-
oxyacetophenone (138 mg, 0.6 mmol) in anhyd DMF (2 mL) was
heated at 100 °C under microwave irradiation (40 W, CEM-Discov-
ery 300 oven) for 30 min. After this time, the reaction was cooled to
r.t., diluted with 50% EtOAc–hexanes (150 mL), and washed suc-
cessively with H2O (5 × 30 mL), aq 10% LiCl (30 mL), brine (30
mL), and dried (Na2SO4). The solvent was removed in vacuo, and
the residue was purified by FCC (SiO2, 30% EtOAc–hexanes) to af-
ford 169 mg (88%) of a white-yellowish powder; mp 119–122 °C
(CH2Cl2–hexanes).
Supporting Information for this article is available online at
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References
IR (KBr): 3034, 2930, 1692, 1601, 1532, 1237, 1171 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.02 (d, J = 9 Hz, 2 H), 7.47–7.30
(m, 10 H), 7.17 (d, J = 8.7 Hz, 2 H), 7.02–6.97 (m, 4 H), 6.91 (s, 1
H), 6.90 (d, J = 8.7 Hz, 2 H), 6.79 (d, J = 9 Hz, 2 H), 5.72 (s, 2 H),
5.06 (s, 2 H), 4.99 (s, 2 H), 3.88 (s, 3 H), 3.45 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 191.8, 163.9, 162.3, 157.5, 157.1,
137.1, 137.0, 131.8, 131.0, 130.3, 129.4, 128.5, 128.2, 127.9, 127.6,
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3321–3326