SPECIAL TOPIC
Vinylogous Michael Reaction of Deconjugated Butenolides
1645
HRMS (ESI+): m/z [M + Na]+ calcd for C19H16ClNNaO4: 380.0666;
found: 380.0667.
HRMS (ESI+): m/z [M + Na]+ calcd for C21H17NNaO4: 370.1055;
found: 370.1060.
(S)-5-[(S)-4-Methyl-1-nitropentan-2-yl]-5-p-tolylfuran-2(5H)-
one (3i)
(R)-3-[(S)-2-(3,4-Dimethylphenyl)-5-oxo-2,5-dihydrofuran-2-
yl]-1-phenylpyrrolidine-2,5-dione (5c)
Column chromatography (EtOAc–toluene, 1:3); brownish sticky
gel; yield: 25.2 mg (0.070 mmol, 54%).
Column chromatography (EtOAc–PE, 1:3); white solid; yield: 37
mg (0.123 mmol, 79%); mp 118–120 °C; [α]D21 –239.7 (c 1, CHCl3).
HPLC (Chiralpak AD-H column, n-hexane–EtOH, 75:25, 1.0
mL/min, 20 °C, 254 nm): tR = 6.2 min (major), 7.2 min (minor).
HPLC (Daicel Chiralpak AD-H column n-hexane–EtOH, 50:50, 1.0
mL/min, 20 °C, 254 nm): tR= 11.6 (minor), 14.1 min (major).
FT-IR (KBr): 3122 (w), 2924 (w), 1756 (s), 1552 (s), 1434 (w),
1383 (w), 1199 (w), 1109 cm–1 (w).
FT-IR (KBr): 3102 (w), 2924 (w), 1768 (m), 1715 (s), 1503 (w),
1386 (m), 1194 (m), 1100 cm–1 (w).
1H NMR (400 MHz, CDCl3): δ = 7.58 (d, J = 5.6 Hz, 1 H), 7.30–
7.21 (m, 4 H), 6.09 (d, J = 5.6 Hz, 1 H), 4.35 (dd, J = 4.5, 13.5 Hz,
1 H), 4.26 (dd, J = 7.5, 13.6 Hz, 1 H), 3.21–3.15 (m, 1 H), 2.35 (s,
3 H), 1.53–1.43 (m, 1 H), 1.29–1.19 (m, 2 H), 0.91 (d, J = 6.5 Hz, 3
H), 0.87 (d, J = 6.5 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.7, 158.1, 139.2, 134.0, 130.2,
125.0, 120.3, 92.3, 76.7, 43.2, 36.9, 26.5, 22.9, 22.1, 21.2.
1H NMR (400 MHz, CDCl3): δ = 8.40 (d, J = 5.7 Hz, 1 H), 7.44 (d,
J = 7.8 Hz, 2 H), 7.22–7.15 (m, 4 H), 7.03 (d, J = 7.8 Hz, 2 H), 6.18
(d, J = 5.6 Hz, 1 H), 3.37 (dd, J = 4.7, 8.6 Hz, 1 H), 3.04 (dd, J =
8.6, 18.9 Hz, 1 H), 2.96 (dd, J = 4.8, 19.1 Hz, 1 H), 2.25 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 174.4, 174.3, 158.7, 138.4, 138.0,
131.2, 130.6, 129.4, 129.2, 126.9, 126.7, 126.5, 123.3, 120.0, 89.4,
50.7, 31.1, 20.1, 19.6.
HRMS (ESI+): m/z [M + Na]+ calcd for C17H21NNaO4: 326.1368;
HRMS (ESI+): m/z [M + Na]+ calcd for C22H19NNaO4: 384.1212;
found: 326.1366.
found: 384.1210.
(R)-3-[(S)-5-Oxo-2-phenyl-2,5-dihydrofuran-2-yl]-1-phenyl-
pyrrolidine-2,5-dione (5a); Typical Procedure
(R)-3-[(S)-2-(Naphthalen-2-yl)-5-oxo-2,5-dihydrofuran-2-yl]-1-
phenylpyrrolidine-2,5-dione (5d)
Column chromatography (EtOAc–toluene, 1:3); off-white foam;
yield: 22.0 mg (0.072 mmol, 60%).
An oven-dried Schlenk tube was charged, under argon, with catalyst
II (1.4 mg, 0.0032 mmol, 0.02 equiv) and N-phenylmaleimide (4;
30.5 mg, 0.176 mmol, 1.1 equiv), followed by the addition of
CH2Cl2 (0.1 mL). The resulting soln was cooled to –41 °C under
positive argon pressure. A soln of 1a (25 mg, 0.16 mmol, 1.0 equiv)
in CH2Cl2 (0.22 mL) was added at –41 °C over 5 min. The resulting
mixture was allowed to stir at this temperature until completion of
the reaction (TLC monitoring, 6 h). The mixture was allowed to
warm up to r.t. and concentrated to a residue that was purified by
column chromatography (silica gel, 230–400 mesh, EtOAc–tolu-
ene, 1:3 ) to afford 5a (44.8 mg, 0.134 mmol, 84%) as an off-white
foam.
HPLC (Daicel Chiralpak AD-H column, n-hexane–EtOH, 50:50,
1.0 mL/min, 20 °C, 254 nm): tR = 23.6 (minor), 29.0 min (major).
FT-IR (KBr): 3059 (w), 2926 (m), 1773 (m), 1713 (s), 1499 (w),
1388 (m), 1193 (m), 1098 cm–1 (w).
1H NMR (400 MHz, CDCl3): δ = 8.53 (d, J = 5.7 Hz, 1 H), 7.97–
7.96 (m, 1 H), 7.87–7.84 (m, 2 H), 7.58–7.55 (m, 2 H), 7.52–7.45
(m, 2 H), 7.41–7.38 (m, 3 H), 6.98–6.95 (m, 2 H), 6.24 (d, J = 5.7
Hz, 1 H), 3.49 (dd, J = 4.8, 8.9 Hz, 1 H), 3.08 (dd, J = 8.9, 19.0 Hz,
1 H), 2.99 (dd, J = 4.9, 19.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 174.4, 173.9, 170.8, 158.4, 133.3,
133.1, 131.3, 131.2, 129.41, 129.39, 129.2, 128.5, 127.8, 127.5,
127.4, 126.7, 126.4, 125.8, 122.6, 120.5, 89.6, 50.7, 31.1.
HPLC (Daicel Chiralpak ID column, n-hexane–EtOH, 70:30, 1.0
mL/min, 20 °C, 210 nm): tR = 10.8 (minor), 12.4 min (major).
FT-IR (KBr): 3100 (w), 2926 (w), 1772 (s), 1714 (s), 1500 (m),
1387 (m), 1202 (m), 1104 cm–1 (w).
HRMS (ESI+): m/z [M + Na]+ calcd for C24H17NNaO4: 406.1055;
1H NMR (400 MHz, CDCl3): δ = 8.43 (d, J = 5.7 Hz, 1 H), 7.46–
7.40 (m, 8 H), 7.02–6.99 (m, 2 H), 6.22 (d, J = 5.7 Hz, 1 H), 3.41
(dd, J = 4.6, 9.0 Hz, 1 H), 3.06 (dd, J = 9.0, 19.0 Hz, 1 H), 2.96 (dd,
J = 4.6, 19.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 174.3, 174.0, 170.7, 158.3, 136.9,
133.9, 131.3, 129.7, 129.4, 129.2, 126.4, 126.0, 120.4, 89.3, 50.7,
31.1.
found: 406.1054.
(R)-3-[(S)-2-(4-Fluorophenyl)-5-oxo-2,5-dihydrofuran-2-yl]-1-
phenylpyrrolidine-2,5-dione (5e)
Column chromatography (EtOAc–toluene, 1:3); sticky gel; yield:
33.6 mg (0.096 mmol, 68%).
HPLC (Daicel Chiralpak AD-H column, n-hexane–EtOH, 50:50,
1.0 mL/min, 20 °C, 254 nm): tR = 11.8 (minor), 23.1 min (major).
HRMS (ESI+): m/z [M + Na]+ calcd for C20H15NNaO4: 356.0899;
found: 356.0894.
FT-IR (KBr): 3080 (w), 2926 (w), 1772 (m), 1714 (s), 1512 (m),
1387 (m), 1201 (m), 1114 (w), 1090 cm–1 (w).
(R)-3-[(S)-5-Oxo-2-(p-tolyl)-2,5-dihydrofuran-2-yl]-1-phenyl-
pyrrolidine-2,5-dione (5b)
Column chromatography (EtOAc–toluene, 1:3); sticky gel; yield:
40.4 mg (0.116 mmol, 83%).
1H NMR (400 MHz, CDCl3): δ = 8.38 (d, J = 5.7 Hz, 1 H), 7.46–
7.42 (m, 5 H), 7.13–7.09 (m, 2 H), 7.02 (d, J = 7.6 Hz, 2 H), 6.21
(d, J = 5.7 Hz, 1 H), 3.41 (dd, J = 4.5, 9.1 Hz, 1 H), 3.05 (dd, J =
9.2, 18.9 Hz, 1 H), 2.89 (dd, J = 4.5, 18.9 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 174.2, 173.8, 170.4, 164.4, 158.1,
131.2, 129.9, 129.4, 129.2, 128.1, 128.0, 126.6, 126.3, 120.5, 116.6,
116.4, 88.8, 50.5, 30.9.
HPLC (Daicel Chiralpak AD-H column, n-hexane–EtOH, 50:50,
1.0 mL/min, 20 °C, 254 nm): tR= 13.2 (minor), 15.1 min (major).
FT-IR (KBr): 3100 (w), 2926 (m), 1771 (s), 1714 (s), 1500 (m),
1387 (s), 1190 (m), 1095 cm–1 (m).
HRMS (ESI+): m/z [M + Na]+ calcd for C20H14FNNaO4: 374.0805;
1H NMR (400 MHz, CDCl3): δ = 8.41 (d, J = 5.6 Hz, 1 H), 7.47–
7.40 (m, 3 H), 7.33 (d, J = 7.7 Hz, 2 H), 7.21 (d, J = 7.6 Hz, 2 H),
7.03 (d, J = 7.3 Hz, 2 H), 6.20 (d, J = 5.5 Hz, 1 H), 3.39 (dd, J = 4.4,
8.4 Hz, 1 H), 3.05 (dd, J = 9.0, 19.1 Hz, 1 H), 2.95 (dd, J = 4.2, 18.9
Hz, 1 H), 2.36 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 174.3, 174.1, 170.8, 158.5, 139.8,
131.3, 130.9, 130.4, 130.1, 129.4, 129.2, 126.5, 125.8, 120.2, 89.4,
50.7, 31.1, 21.2.
found: 374.0804.
Acknowledgment
Generous financial support from Indian Institute of Science, Banga-
lore in the form of a start-up grant is gratefully acknowledged. This
research program is funded by the Department of Science and Tech-
nology (DST), New Delhi (Grant No. SR/FT/CS-90/2010) and the
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1641–1646