Ibara C, et al. Sci China Chem August (2012) Vol.55 No.8
1631
glass sintered filter with a Celite pad to remove the piperi-
dinium salt. The filtrate was evaporated and chromato-
graphed on silica gel flash column (hexane:ethyl acetate =
1:1) to afford 1b (2.95 g, 9.48 mol) in 92% overall yield.
1b: mp: 110–114 °C; Rf = 0.52 (hexane/ethyl acetate =
2/1); 1H NMR (500 MHz, CDCl3): δ 0.83 (t, J=7.1 Hz, 3H),
1.17–1.62 (m, 4H), 1.60 (m, 2H), 4.20 (t, J=6.6 Hz, 2H),
6.17 (m, 1H), 6.71 (td, J=2.7 Hz, 1.7, 1H), 7.08 (td, J=2.7
Hz, 1.4, 1H), 7.21–7.28 (m, 3H), 7.41 (t, J=1.8 Hz, 1H)
7.42 (t, J=1.6 Hz, 1H), 7.89 (s,1H), 9.79 (s, 1H); 13C NMR
(125 MHz, CDCl3): δ 13.8, 22.1, 27.8, 28.1, 65.5, 111.2,
119.3, 126.1, 128.11, 128.6, 129.0, 129.3, 130.1, 130.9,
131.8, 133.1, 142.4, 165.3, 183.7; IR (KBr) : 3275, 2935,
2860, 1701(CO), 1612(CO), 1546, 1406, 1255, 740 cm–1;
Hz, 12.7, 5.3, 2H), 4.26 (s, 1H), 6.05 (t, J=1.8 Hz, 1H), 7.08
(dd, J=7.6, 1.6 Hz, 2H), 7.18 (m, 3H), 7.34 (t, J=2.5 Hz,
1H), 10.9 (br, 1H); 13C NMR (125 MHz, CDCl3) : δ13.8,
22.0, 27.5, 27.8, 28.7, 29.9, 38.5, 50.9, 64.9, 71.3, 107, 127,
128.0, 128.6, 129, 134, 134, 138, 153, 170, 189, 208; IR
(KBr): 3292, 2957, 1718(CO), 1676(CO), 1406, 1375, 1271,
1203, 765.7 cm–1; HRMS(ESI): m/z: calcd for [MH]+
+
C23H28NO4 : 382.20194, found: 382.20126.
We succeeded in obtaining 2b in 87% yield when the re-
action was stopped at Nazarov cyclization and isolated from
the reaction mixture.
2b: mp: 99–103 °C; Rf = 0.34 (hexane/ethyl acetate =
2/1); 1H NMR (500 MHz, CDCl3): δ 0.91 (t, J=7.1 Hz, 3H),
1.35 (dt, J=11.5, 4.2 Hz, 4H), 1.71 (dd, J=6.9, 7.3 Hz, 2H),
3.82 (d, J=3.2 Hz, 1H), 4.22 (m, 2H), 4.78 (d, J=3.2 Hz,
1H), 6.13 (t, J=2.1 Hz, 1H), 7.22 (d, J=8.2 Hz, 2H), 7.26
(td, J=6.6, 1.7 Hz, 1H), 7.33 (t, J=7.3 Hz, 2H), 7.39 (t,
J=2.7 Hz, 1H), 11.1 (brs,1H); 13C NMR (125 MHz, CDCl3):
δ 13.9, 22.2, 27.9, 28.2, 44.1, 65.7, 68.3, 106.5, 127.1,
127.2, 128.8, 132.8, 134.4, 141.6, 155.2, 169.4, 184.4; IR
(KBr):3221, 2956, 2872, 1726(CO), 1685(CO), 1450, 1400,
1319, 1161, 777cm–1; HRMS(ESI): m/z: calcd for [MH]+
+
HRMS(ESI): m/z: calcd for [MH]+ C19H22NO3 : 312.15942,
found: 312.15915
Using benzyl alcohol in the first step, benzyl etser 1c was
also prepared in 87% yield (two steps).
4.5 Benzyl (E)-2-benzylidene-3-oxo-3-(1H-pyrrol-2-yl)
propanoate (1c)
mp: 99–104 °C; 1H NMR (400 MHz, CDCl3): δ 4.70 (s, 1H),
5.25 (s, 2H), 6.15–6.18 (brs, 1H), 6.65–6.70 (brs, 1H),
7.00–7.05 (brs, 1H), 7.20–7.30 (brs, 1H), 7.20–7.03 (m,
6H), 7.30–7.45 (m, 4H), 7.90–7.95 (brs, 1H); 13C NMR
(125 MHz, CDCl3): δ 66.89, 111.3, 127.6, 128.0, 128.4,
128.6, 130.2, 130.3, 130.5, 131.8, 133.0, 135.7, 143.0,
165.1, 190.2; IR (KBr): 3269, 1718(CO), 1612(CO), 1545,
1496, 1406, 1251, 1190, 1122, 771 cm–1; HRMS(ESI): m/z:
+
C19H22NO3 : 312.16006, found: 312.15912.
Benzyl ester 3c and 2c were obtained using the same
protocol.
3c: mp: 155–160 °C; 1H NMR (500 MHz, CDCl3) δ 2.95
(s, 3H), 2.43–2.48 (m, 1H), 2.56–2.65 (m, 2H), 2.80–2.85
(m, 1H), 4.30 (d, J=15.0 Hz, 1H), 4.37 (s, 1H), 4.49 (d,
J=15.0 Hz, 1H), 6.11 (s, 1H), 7.01–7.03 (m, 2H), 7.15–7.16
(m, 2H), 7.22–7.25 ( m, 6H ), 7.33–7.35 (m, 1H), 11.0 (s,
+
calcd for [M+H]+ C21H18NO3 : 332.12874, found:
3
NH,1H): C NMR (125 MHz, CDCl3): δ 28.7, 30.0, 38.4,
332.12126.
51.0, 66.2, 71.4, 106.5, 127.5, 127.6, 127.8, 127.9, 128.1,
128.3, 128.5, 128.9, 129.2, 134.0, 134.1, 135.2, 138.1,
152.6, 170.1, 188.2, 207.8; IR (KBr): 3244, 3030, 2955,
1734(CO), 1681(CO), 1495, 1456, 1402, 1371, 1259, 1220,
1155, 744 cm–1; HRMS(ESI): m/z: calcd for [MH]+
4.6 Synthesis of 3b through one pot Nazarov cycliza-
tion/Michael reaction
+
To a mixture of Fe(ClO4)3·Al2O3(19 mg, 5.0 mol% for
Fe3+, 0.01 mmol) in [bmim][NTf2] (0.4 mL) was added 1b
(62 mg, 0.20 mmol) at rt and the mixture was stirred at
80 °C for 4 h. The reaction mixture was cooled to rt after
confirmation that the starting 1b had been consumed and 2b
produced, then 2 eq. of 1-buten-3-one (0.03 mL, 0.40 mmol)
was added to the reaction mixture at rt and stirred for 6 h at
60 °C. After being cooled to rt, the reaction was extracted
with a mixed solvent of hexane and ether (2:1). The com-
bined organic layers were evaporated to dryness and silica
gel thin layer chromatography (TLC) (hexane:ethyl acetate
= 3:2) gave 3b (59.5 mg, 0.156 mmol) in 78% yield as a
white solid. Ionic liquid layer was dried under reduced
pressure at 60 °C for 30 min, feeding of substrate 1b (62 mg)
and conducted next reaction.
C25H24NO4 : 402.17062, found: 402.17126.
2c: 155–160 °C; 1H NMR (400 MHz, CDCl3): 3.88 (d,
J=3.25 Hz, 1H), 4.78 (d, J=3.2 Hz, 1H), 5.27 (d, J=3.6 Hz,
2H), 6.20–6.30 (brs, 1H), 7.16 (d, J=7.3 Hz, 1H), 7.23–7.45
(m, 10H), 11.1 (s, NH, 1H); 13C NMR (125 MHz, CDCl3):
44.04, 67.09, 68.09, 106.5, 127.20, 127.23, 127.38,
128.00, 128.05, 128.10, 128.30, 128.40, 128.77, 129.0,
132.7, 134.6, 135.6, 141.4, 155.2, 169.2, 184.1; IR(KBr):
3244, 2955, 1734(CO), 1681(CO), 1495, 1402, 1371, 1259,
1220, 1155, 744 cm–1; HRMS(ESI): m/z: calcd for [MH]+
+
C21H18NO3 : 332.12874, found: 332.12826.
The present work was supported by a Grant-in-Aid for Scientific Research
in a Priority Area, “Science of Ionic Liquids”, from the Ministry of Educa-
tion, Culture, Sports, Science and Technology of Japan.
3b: mp: 139–142 °C; Rf = 0.11(hexane/ethyl acetate =
2/1); 1H NMR (500 MHz, CDCl3): δ 0.73(t, J=7.3 Hz, 3H),
0.97 (dt, J=15.3, 4.1 Hz, 2H), 1.14 (m, 4H), 2.09 (s, 3H),
2.35 (m, 1H), 2.52 (m, 2H), 2.75 (m, 1H), 3.31 (ddt, J=68.6
1
2
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