V. Barbier et al. / Tetrahedron xxx (2016) 1e6
5
4. Experimental section
6.37 (s, 1H), 2.50 (s, 3H). 13C NMR (75 MHz, CDCl3):
d
179.30,
178.25, 155.26, 147.16, 130.33, 127.80, 123.27, 100.91, 22.15. HRMS
m/z (ESI, TOF) calcd. For C11H9O3 (MþH)þ 189.0552, found
189.0554.
1H NMR (300 MHz) and 13C (75 MHz) spectra were recorded
€
with Bruker Avance 300 MHz spectrometers using tetramethylsi-
lane as an internal standard. Chemical shifts (d) are given in parts
per million and coupling constants are given as absolute values
expressed in Hertz. Electrospray ionization (ESI) mass spectra were
collected using a Q-TOF instrument supplied by WATERS. Samples
(solubilized in CH3CN at 1 mg mLꢀ1 and then diluted by 1000) were
introduced into the MS via an UPLC system whilst a Leucine En-
kephalin solution was co-injected via a micro pump. Infrared
spectra were recorded with a Nicolet iS10 Infrared FT ATR spec-
trometer. Thin-layer chromatography (TLC) was carried out on al-
uminium sheets precoated with silica gel 60 F254 (Merck). Column
chromatography separations were performed using Merck Kie-
selgel 60 (0.040e0.060 mm). Tetrahydrofuran and dichloro-
methane were dried immediately before use by distillation from
standard drying agents.
4.1.5. 5-(4-Chlorophenyl)furan-2,3-dione
(14e). Yellow
y
solid,
384.2 mg (82% yield); mp¼149e151 ꢁC; IR
(cmꢀ1): 3082, 1820,
1712, 1592, 1492, 1420, 1109, 1087, 805, 758. 1H NMR (300 MHz,
CDCl3):
d
7.88 (d, J¼8.6 Hz, 2H), 7.58 (d, J¼8.6 Hz, 2H), 6.42 (s, 1H).
13C NMR (75 MHz, CDCl3):
d
178.20, 177.92, 154.56, 141.94, 130.04,
128.83, 124.49, 101.74. HRMS m/z (ESI, TOF) calcd. For C10H5O3N-
aCl (MþNa)þ 230.9825, found 230.9834.
4.1.6. 5-(4-Fluorophenyl)furan-2,3-dione (14f). Yellow solid, 587.3 mg
(64% yield); mp¼137e139 ꢁC; IR
y
(cmꢀ1): 3100, 1820, 1715, 1590,
1485, 1418, 1105, 1084. 1H NMR (200 MHz, CDCl3):
d 7.94e7.85 (m,
1H), 7.21 (d, J¼8.6 Hz, 1H), 6.31 (s, 1H). 13C NMR (75 MHz, CDCl3):
d
178.15,177.97, 165.21, 154.69,130.38 (d, J¼9.7 Hz), 122.36,117.20 (d,
J¼22.5 Hz), 101.32 (d, J¼1.6 Hz). HRMS m/z (ESI, TOF) calcd. For
4.1. General procedure for
b-ketolactones synthesis
C
10H6O3F (MþH)þ 193.0301, found 193.0304.
To a solution of diethyl oxalate (1 equiv) in EtOH, NaH (1 equiv,
60% in oil) and the methylketone were successively added portion-
wise at 0 ꢁC under inert atmosphere. After 16 h of stirring at room
temperature, the reaction mixture was concentrated in vacuo. The
resulting sodium salt was washed several times with diethylether.
This sodium salt was dissolved and stirred 2 day at room tempera-
ture in a solution of HCl (40 equiv, 6M) and acetonitrile. The reaction
mixture was concentrated in vacuo and dissolved in dichloro-
methane. The media was treated with an aqueous solution of
NaHCO3 (until basic pH) and extracted three times. Then aqueous
phase was treated with HCl 6M (until acidic pH), filtered and dried to
4.1.7. 5-(4-Nitrophenyl)furan-2,3-dione (14g). Yellow solid, 632.7 mg
(68% yield); mp¼150e152 ꢁC; IR
y
(cmꢀ1): 3100, 1820, 1715, 1590,
1579,1485,1418,1390,1210,1084.1HNMR(300MHz,CDCl3):
d8.37(d,
J¼8.9 Hz, 2H), 8.04 (d, J¼8.8 Hz, 2H), 6.49 (s, 1H). 13C NMR (75 MHz,
CDCl3):
d
178.15, 177.97, 165.21, 154.69, 130.38 (d, J¼9.7 Hz), 122.36,
117.20, 101.32. Note that the two carbonyl resonances could not be
detected even after modification of the relaxation parameters. HRMS
m/z (ESI, TOF) calcd. For C10H5NO5Na (MþNa)þ 242.0065, found
242.0066.
4.1.8. 5-tert-Butylfuran-2,3-dione (14h). Prepared according to
get the resulting
b
-ketoacid as a solid. The
b
-ketoacid was dissolved
a reported procedure, see Ref. 9. 1H NMR (300 MHz, CDCl3): (62%)
in acetyl chloride at roomtemperature for 16 h. The reaction mixture
was concentrated under vacuum. The resulting power was washed
d 6.44 (s, 1H), 1.33 (s, 18H). HRMS m/z (ESI, TOF) calcd. For
C8H10O3Na (MþNa)þ 177.0528, found 177.0529.
with a small volume of cold ether to give
b
-ketolactones as a solid.
4.2. General procedure for isotetronic acid derivatives
synthesis
4.1.1. 5-Phenylfuran-2,3-dione (14a). Yellow solid, 0.24
g
(78%
yield) and perfectly fits analytic data described in Ref. 9.
mp¼133e135 ꢁC; IR
y
(cmꢀ1): 3062, 3026, 1785, 1712, 1592, 1492,
To a stirred solution of b-ketolatone (1 equiv), ethyl glyoxalate,
1450, 1411, 1366, 1310, 1291, 1277, 1165, 1129, 1109, 1087, 805, 758.
50% in toluene (Alfa Aesar) (1 equiv) in CDCl3 (1 mL), 1,3,5-
tris(isopropyl)benzene as an internal reference (1 equiv), is added
10 mol % of 4-PPY. After 24 h at RT, NMR analysis was performed
and yields were determined.
1H NMR (200 MHz, CDCl3):
d
7.65 (d, J¼8.3 Hz, 2H), 7.48e7.03 (m,
7H), 5.56 (dd, J¼5.7, 2.7 Hz, 1H), 3.38 (dd, J¼16.6, 5.7 Hz, 1H), 2.95
(dd, J¼16.6, 2.7 Hz, 1H), 2.43 (s, 3H).
4.1.2. 5-(2-Methoxyphenyl)furan-2,3-dione (14b). Orange solid,
4.2.1. Ethyl 3-benzoyl-4-hydroxy-5-oxo-2,5-dihydrofuran-2-
784.3 mg (85% yield); mp¼150e152 ꢁC; IR
y
(cmꢀ1): 3089, 1820,
carboxylate (18a). 70 % in CDCl3 and 47% in THF-d8 1H NMR
1715, 1592, 1583, 1487, 1421, 1080, 982. 1H NMR (300 MHz, CDCl3):
(300 MHz, CDCl3): d 7.67 (m, 2H), 7.55 (m, 3H), 5.87 (s, 1H), 4.24 (q,
d
7.98 (d, J¼7.9 Hz, 1H), 7.75e7.59 (m, 1H), 7.12 (dd, J¼16.9, 8.2 Hz,
J¼7.1 Hz, 2H), 1.23 (t, J¼7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3):
2H), 6.72 (s, 1H), 4.03 (s, 3H). 13C NMR (75 MHz, CDCl3):
d
179.76,
d 189.82, 168.18, 166.66, 149.15, 137.92, 136.53, 129.14, 128.34,
175.30, 161.47, 155.07, 136.70, 128.64, 121.11, 111.74, 106.85, 55.94.
HRMS m/z (ESI, TOF) calcd. For C11H8O4Na (MþNa)þ 227.0320,
found 227.0324.
120.38, 77.02, 62.74, 13.85. HRMS m/z (ESI, TOF) calcd. For C14H13O6
(MþH)þ 277.0712, found 277.0716.
4.2.2. Ethyl 4-hydroxy-3-(2-methoxybenzoyl)-5-oxo-2,5-
4.1.3. 5-(4-Methoxyphenyl)furan-2,3-dione (14c). Orange solid,
dihydrofuran-2-carboxylate (18b). 65 % in CDCl3 and 73% in THF-d8
855 mg (93% yield); mp¼140e142 ꢁC IR
y
(cmꢀ1): 3089, 1820, 1715,
1H NMR (300 MHz, CDCl3):
d
7.58 (t, J¼7.9 Hz, 1H), 7.51 (d, J¼6.6 Hz,
1592, 1583, 1487, 1421, 1080, 982. 1H NMR (200 MHz, CDCl3):
d
7.91
1H), 7.10 (t, J¼7.5 Hz, 1H), 7.04 (d, J¼8.5 Hz, 1H), 5.88 (s, 1H),
4.08e3.85 (m, 2H), 3.96 (s, 3H), 1.02 (t, J¼7.1 Hz, 3H). 13C NMR
(75MHz, CDCl3): 191.87,166.23,166.04,157.37,154.98,134.36,130.16,
127.09, 125.36, 121.21, 111.35, 76.28, 62.41, 55.63, 13.64. HRMS m/z
(ESI, TOF) calcd. For C15H15O7 (MþH)þ 307.0818, found 307.0826.
(d, J¼8.9 Hz, 1H), 7.07 (d, J¼8.9 Hz, 1H), 6.30 (s, 1H), 3.95 (s, 3H).).
13C NMR (75 MHz, CDCl3):
d
178.81, 177.77, 165.72, 155.78, 130.25,
118.16, 115.20, 99.92, 55.89. HRMS m/z (ESI, TOF) calcd. For C11H9O4
(MþH)þ 205.0501, found 205.0501.
4.1.4. 5-(4-Methylphenyl)furan-2,3-dione
(14d). Yellow solid,
(cmꢀ1): 3092, 1825,
4.2.3. Ethyl 4-hydroxy-3-(4-methoxybenzoyl)-5-oxo-2,5-
670.3 mg (74% yield); mp¼139e141 ꢁC; IR
y
dihydrofuran-2-carboxylate (18c). 51 % in CDCl3 and 38% in THF-d8
1710, 1593, 1584, 1485, 1418, 1320, 1268, 1005, 989. 1H NMR
1H NMR (300 MHz, CDCl3):
d
7.95 (d, J¼8.7 Hz, 1H), 7.02 (d, J¼8.7 Hz,
(200 MHz, CDCl3):
d
7.84 (d, J¼8.3 Hz, 2H), 7.40 (d, J¼8.0 Hz, 2H),
1H), 5.87 (s,1H), 4.22 (q, J¼7.2 Hz, 1H),1.21 (t, J¼7.1 Hz, 2H). 13C NMR