Regioselective vinylation of kojic acid
785
Dimethyl (E)-2-[3-hydroxy-6-(hydroxymethyl)-4-oxo-
4H-pyran-2-yl]-2-butenedioate (5a, C12H12O8)
methoxy and methylene groups at d = 3.77 and 4.55 ppm,
two singlets for two vinyl protons of the 4H-pyrone ring
at d = 6.63 and 7.93 ppm, and two doublets for two
vinyl protons at approximately d = 5.54 and 7.67 ppm
(3JHH = 12.2 Hz) showing E geometry. The 13C NMR
spectrum of 7a contained ten sharp lines in agreement
with the proposed structure. The mass spectrum of 7a
contained the molecular ion peak at m/z = 226 (M?Á, 65).
Initial fragmentations involved loss of the side chains of
Yellow powder; yield 70%; m.p.: 181–184 °C; Rf = 0.2
(n-hexane–ethyl acetate 20:80, v/v); IR (KBr):vꢀ = 3,250
(OH), 1,750, 1,719, 1,698 (C=O) cm-1
;
1H NMR
(300.13 MHz, DMSO-d6): d = 3.70, 3.74 (6H, 2s,
2OCH3), 4.34 (2H, s, OCH2), 6.38, 6.68 (2H, 2s, 2CH),
5.6 (1H, bs, OH), 10.5 (1H, bs, OH) ppm; 13C NMR
(75.47 MHz, DMSO-d6): d = 52.1, 52.6 (2OCH3), 59.5
(OCH2), 108.7, 118.6 (2CH), 138.8, 139.0, 145.4, 173.9
(4C), 163.0, 163.7 (C=O, ester), 172.3 (C=O, ketone) ppm;
MS (70 eV): m/z = 284 (M?Á, 7), 253 (M?Á–OCH3, 55),
225 (M?Á–CO2Me, 100), 165 (M?Á–(2CO2Me ? H), 7),
113 (M?Á–(C6H5O ? CH2O), 7), 93 (M?Á–(CH2OH,
MeO2CCCCO2Me ? OH) ? 1, 30), 57 (C4H7?, 18).
1
the kojic acid system. The H and 13C NMR spectra of 7b
are similar to those of 7a except for the alkoxy group,
which gave characteristic signals with appropriate chem-
ical shifts.
In summary, the reaction between the zwitterionic
intermediate generated from acetylenic esters and nucleo-
philes such as triphenylphosphine and tert-butyl isocyanide
with kojic acid leads to vinylated kojic acid via a one-pot,
three component regioselective process. This procedure has
the advantage that not only is the reaction performed under
neutral conditions but also the substances can be mixed
without any activation or modification.
Diethyl (E)-2-[3-hydroxy-6-(hydroxymethyl)-4-oxo-
4H-pyran-2-yl]-2-butenedioate (5b, C14H16O8)
Yellow powder; yield 75%; m.p.: 124–126 °C; Rf = 0.3
(n-hexane–ethyl acetate 20:80, v/v); IR (KBr): vꢀ = 3,620
(OH), 1,744, 1,716, 1,695 (C=O) cm-1
;
1H NMR
3
(300.13 MHz, DMSO-d6): d = 1.21 (3H, t, JHH
7.1 Hz, CH3), 1.24 (3H, t, JHH = 7.1 Hz, CH3), 4.14
=
3
3
3
(2H, q, JHH = 7.1 Hz OCH2), 4.23 (2H, JHH = 7 Hz,
OCH2), 4.34 (2H, s, OCH2), 5.5 (1H, bs, OH), 6.39, 6.67
(2H, 2 s, 2CH), 10.5 (1H, bs, OH) ppm; 13C NMR
(75.47 MHz, DMSO-d6): d = 13.7, 14.0 (2CH3), 59.6,
60.9, 61.5 (OCH2), 108.7,119.0 (2CH), 139.1, 139.2, 145.5,
174.0 (4C), 164.1, 164.2 (2C=O, ester), 168.6 (C=O,
ketone) ppm; MS (70 eV): m/z = 312 (M?Á, 4), 267 (M?Á–
OEt, 53), 239 (M?Á–CO2Et, 100), 167 (M?Á–(CO2Et ?
CO2 ? C2H4), 27), 142 (M?Á–EtO2CCCCO2Et, 15), 93
(M?Á–(CH2OH ? EtO2CCCCO2Et ? OH), 14).
Experimental
Dialkyl acetylenedicarboxylates, alkyl propiolates, tri-
phenylphosphine, tert-butyl isocyanide, and kojic acid
were obtained from Fluka (Buchs, Switzerland) and were
used without further purification. Melting points were
measured on an Electrothermal 9100 apparatus. H, 13C,
1
and 31P NMR spectra were measured with Bruker DRX-
500, 400, and 300 Avance spectrometers. Mass spectra
were recorded on a Finnigan-Matt 8430 mass spectrometer
operating at an ionization potential of 70 eV. IR spectra
were recorded on a Shimadzu IR-470 spectrometer. Ele-
mental analyses were performed using a Heraeus CHN–O
Rapid analyzer.
Di-tert-butyl 2-[3-hydroxy-6-(hydroxymethyl)-4-oxo-
4H-pyran-2-yl]-3-(1,1,1-triphenyl-k5-phosphanylidene)-
succinate (4c, C36H39O8P)
White powder; yield 90%; m.p.: 123–126 °C; Rf = 0.2
(n-hexane–ethyl acetate 20:80, v/v); IR (KBr): vꢀ = 3,481
(OH), 1,734, 1,726, 1,680 (C=O) cm-1
;
1H NMR
General procedure for the preparation of dialkyl (E)-2-
[3-hydroxy-6-(hydroxymethyl)-4-oxo-4H-pyran-2-yl]-
2-butenedioates (exemplified by 5a)
(400.13 MHz, CDCl3): d = 0.93, 1.51 (18H, 2s, 2CMe3),
3.68 (1H, d, 3JPH = 17.2 Hz, CH), 4.20 (1H, bs, OH), 4.22,
3
4.30 (2H, AB system, JHH = 14.8 Hz, OCH2), 6.34 (1H,
s, CH), 7.47–7.90 (15H, m, aromatic protons), 8.30 (1H, bs,
To a magnetically stirred solution of 0.284 g kojic acid
(2 mmol) and 0.524 g triphenylphosphine (2 mmol) in
10 cm3 THF, 2 mmol of dimethyl acetylenedicarboxylate
in 4 cm3 THF was added dropwise at -10 °C over
10 min. The mixture was stirred at room temperature for
24 h. The solvent was removed under reduced pressure
and the residue was purified by recrystallization from
ethyl acetate. The solvent was removed under reduced
pressure, and the products 5a, 5b, and 4c were obtained
as yellow powder.
OH) ppm; 13C NMR (100.61 MHz, CDCl3): d = 28.1,
28.3 (2CMe3), 40.6 (d, JPC = 132.8 Hz, P=C), 46.4 (d,
1
2JPC = 13.1 Hz, CH), 61.3 (OCH2), 78.2, 81.4 (2OCMe3),
1
109.0 (CH), 128.9 (d, JPC = 91.6 Hz, Cipso), 128.7 (d,
4
2JPC = 12.1 Hz, Cortho), 132.2 (d, JPC = 2.0 Hz, Cpara),
3
133.7 (d, JPC = 9.9 Hz, Cmeta), 150.8, 165.3, 174.9 (3C),
3
2
170.3 (d, JPC = 9.8 Hz, C=O), 170.9 (d, JPC = 13.7 Hz,
C=O) ppm; 31P NMR (161.97 MHz, CDCl3): d =
22.53 ppm; MS (70 eV): m/z = 630 (M?Á, 2), 369 (M?Á–
123