One-pot synthesis of 3-hydroxymaleic anhydrides by cyclization of 1,1-bis(trimethylsilyloxy)ketene acetals with oxalyl chloride

Article abstract of DOI:10.1055/s-2004-835668

Functionalized 3-hydroxymaleic anhydrides were prepared by cyclization of 1,1-bis(trimethylsilyloxy)ketene acetals with oxalyl chloride.

Full text of DOI:10.1055/s-2004-835668

2782
LETTER
One-Pot Synthesis of 3-Hydroxymaleic Anhydrides by Cyclization of
1,1-Bis(trimethylsilyloxy)ketene Acetals with Oxalyl Chloride
O
ne-Pot Synthe
h
sis of 3-Hyd
s
roxymalei
a
c
A
nhydrid
n
es Ullah, Peter Langer*
Institut für Chemie und Biochemie der Ernst-Moritz-Arndt-Universität Greifswald, Soldmannstr. 16, 17487 Greifswald, Germany
Fax +49(3834)864373; E-mail: peter.langer@uni-greifswald.de
Received 1 September 2004
wish to report a new method for the synthesis of 3-hy-
Abstract: Functionalized 3-hydroxymaleic anhydrides were pre-
droxymaleic anhydrides based on what are, to the best of
our knowledge, the first cyclization reactions of 1,1-
pared by cyclization of 1,1-bis(trimethylsilyloxy)ketene acetals
with oxalyl chloride.
bis(trimethylsilyloxy)ketene acetals with oxalyl chlo-
Key words: anhydrides, cyclizations, ketene acetals, oxalyl chlo-
ride, silyl enol ethers
ride.11–14 This methodology allows a convenient one-pot
synthesis of a variety of maleic anhydrides which are in
many cases not directly available by other methods.
Functionalized maleic anhydrides represent versatile
OSiMe3
building blocks for organic synthesis.1 For example,
O
Ph
Me3SiOTf
(0.5 equiv)
OSiMe3
pharmacologically relevant g-alkylidenebutenolides have
been prepared by Wittig reactions of maleic anhydrides.2
Maleic anhydrides have been transformed into
maleimides3 which represent key-intermediates for the
synthesis of 5-alkylidene-5H-pyrrol-2-ones.3 The em-
ployment of maleic anhydrides as dienophiles in [4+2],
[3+2] and [2+2] cycloaddition reactions allows the syn-
thesis of a variety of carba- and heterocyclic frameworks.4
Functionalized 3-alkanoylacrylic acids and naphtho-
quinones were prepared by Friedel–Crafts acylations
using maleic anhydrides as reagents. The reaction of
maleic anhydrides with enolates provides a convenient
approach to 4-alkylidenebutane-1,3-diones.5 A variety of
functionalized a,b-unsaturated carbonyl compounds were
prepared by reaction of maleic anhydrides with nucleo-
philes.6
Ph
HO
1a
2
O
O
O
Cl
O
CH2Cl2
+
78 °C to 20 °C
Cl
3a
_
_
Me3SiCl
Me3SiOTf
Me3SiCl
OSiMe3
_
Me3SiOTf
Ph
O
Cl
O
_
+
O
OTf
SiMe3
A
Scheme 1 Cyclization of 1,1-bis(trimethylsilyloxy)ketene acetal 1a
with oxalyl chloride.
Functionalized maleic anhydrides have been prepared by
conjugate addition of nucleophiles onto parent maleic an-
hydride and subsequent halogenation and elimination.7 2-
Methoxy-3-methylmaleic anhydride has been prepared by
base-mediated condensation of ethyl propionate with di-
ethyl oxalate8 and subsequent methylation.2a 2-Methoxy-
3-arylmaleic anhydrides are available by condensation of
arylacetonitriles with diethyl oxalate to give open-chained
pyruvates, subsequent methylation and treatment with
acid.9 3-Hydroxymaleic anhydrides are of potential
synthetic usefulness as precursors of enol triflates to be
employed in palladium-catalyzed cross-coupling reac-
tions. For example, the synthesis of (symmetrical) 2,3-di-
The known 1,1-bis(trimethylsilyloxy)ketene acetal 1a
was prepared by deprotonation of phenylacetic acid with
lithio-1,1,1,3,3,3-hexamethyldisilazane and subsequent
addition of trimethylchlorosilane to the dianion thus
formed.15 The reaction of 1a with oxalyl chloride (2) in
the presence of trimethylsilyl-trifluoromethanesulfonate
(Me3SiOTf) afforded the 3-hydroxymaleic anhydride 3a
in up to 70% yield (Scheme 1).16 The direct reaction of the
dianion of phenylacetic acid17 with oxalyl chloride or
diethyl oxalate resulted in the formation of complex
mixtures. In fact, the employment of 1,1-bis(trimethyl-
silyloxy)ketene acetal 1a, which can be regarded as a
masked dianion, proved mandatory to induce a clean cy-
clization. During the optimization, the following parame-
ters proved to be important: a) the employment of 0.5
equivalents of Me3SiOTf (the use of stoichiometric
amounts of TiCl4 resulted in the formation of complex
mixtures), b) the solvent (CH2Cl2), c) the reaction time
and d) the temperature. The formation of 3a can be
explained by Me3SiOTf-mediated attack of the carbon
atom of 1a onto 2 to give intermediate A and subsequent
cyclization via the oxygen atom.
hydroxymaleic
anhydride,10a
2,3-diacetoxymaleic
anhydride10b,c and 2,3-dimethoxymaleic anhydride10d has
been reported. In contrast, unsymmetrical 2,3-dihydroxy-
maleic anhydrides, containing one free and one protected
hydroxy group, have not been prepared so far. Herein, we
SYNLETT 2004, No. 15, pp 2782–2784
0
7
.1
2
.2
0
0
4
Advanced online publication: 10.11.2004
DOI: 10.1055/s-2004-835668; Art ID: D26404ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
One-Pot Synthesis of 3-Hydroxymaleic Anhydrides
2783
OSiMe3
We currently study the functionalization of the 3-hy-
droxymaleic anhydrides by palladium-catalyzed cross-
coupling reactions of the corresponding enol triflates.
O
a
R
R
OSiMe3m
1a–n
OH
Acknowledgment
b
O
O
O
Cl
Financial support from the Deutsche Forschungsgemeinschaft is
gratefully acknowledged.
O
Cl
O
HO
R
3a–n
References
Scheme 2 Synthesis of 3a–n: a, (1) Li[N(SiMe3)2] (2.0 equiv),
THF, –78 °C, (2) Me3SiCl (2.2 equiv), –78 °C → 20 °C; b, Me3SiOTf
(0.5 equiv), CH2Cl2, –78 °C → 20 °C, 12 h, then 20 °C, 3 h.
(1) Reagents for Organic Synthesis; Paquette, L. A., Ed.; John
Wiley and Sons Ltd: Chichester, 1995, 3207.
(2) (a) Knight, D. W.; Pattenden, G. J. Chem. Soc., Perkin
Trans. 1 1979, 62. (b) Ingham, C. F.; Massy-Westropp, R.
A.; Reynolds, G. D.; Thorpe, W. D. Aust. J. Chem. 1975, 28,
2499. (c) Massy-Westropp, R. A.; Price, M. F. Aust. J.
Chem. 1980, 33, 333.
Table 1 Products and Yields
3
a
b
c
d
e
f
R
Yield (%)a
(3) James, G. D.; Mills, S. D.; Pattenden, G. J. Chem. Soc.,
Perkin Trans. 1 1993, 2581.
Ph
70
73
65
53
70
20
36
42
50
56
20
53
50
40
(4) For reviews, see for example: (a) Danishefsky, S. J.;
Kitahara, T.; Schuda, P. F.; Golob, D.; Dynak, J.; Stevens, R.
V. Org. Synth. 1983, 61, 147. (b) Kloetzel, M. C. Org.
React. 1948, 4, 1. (c) Alder, K. In Neuere Methoden der
Präparativen Organischen Chemie, Part 2; Foerst, W., Ed.;
Verlag Chemie: Berlin, 1953. (d) See also: Dauben, W. G.;
Kessel, C. R.; Takemura, K. H. J. Org. Chem. 1985, 50,
2576. (e) Kozikowski, A. P.; Huie, E.; Springer, J. P. J. Am.
Chem. Soc. 1982, 104, 2059.
(5) Murray, W. V.; Wachter, M. P. J. Org. Chem. 1990, 55,
3424.
(6) Jacobi, P.; Blum, C. A.; DeShimone, R. W.; Udodong, U. E.
S. J. Am. Chem. Soc. 1991, 113, 5384.
(7) Kaydos, J. A.; Smith, D. L. J. Org. Chem. 1983, 48, 1096.
(8) Schreiber, J. Annalen 1947, 2, 84.
(9) Edwards, R. L.; Gill, M. J. Chem. Soc., Perkin Trans. 1
1973, 1538.
(10) (a) Nef, J. U. Justus Liebigs Ann. Chem. 1910, 376, 115.
(b) Yalpani, M.; Wilke, G. Chem. Ber. 1985, 118, 661.
(c) Goodwin, S.; Witkop, B. J. Am. Chem. Soc. 1954, 76,
5599. (d) Stachel, H.-D.; Schachtner, J.; Seidel, J. Z.
Naturforsch. B 1996, 51, 409.
4-MeC6H4
4-ClC6H4
4-(MeO)C6H4
3,4-(MeO)2C6H3
Me
g
h
i
Et
n-Pr
n-Pent
n-Oct
j
k
l
Allyl
MeO
m
n
PhO
BnO
a Yields of isolated products.
(11) (a) For a review of silyl enol ethers, see: Brownbridge, P.
Synthesis 1983, 85. (b) For a review of 1,3-
bis(trimethylsilyloxy)-1,3-butadienes, see: Langer, P.
Synthesis 2002, 441.
To study the preparative scope, the substituents of the 1,1-
bis(trimethylsilyloxy)ketene acetal were systematically
varied (Scheme 2, Table 1). The cyclization of 1,1-bis(tri-
methylsilyloxy)ketene acetals 1a–e with oxalyl chloride
afforded the aryl-substituted 3-hydroxymaleic anhydrides
3a–e. The ketene acetals 1f–j were prepared from propi-
onic-, butanoic-, pentanoic-, heptanoic- and decanoic
acid, respectively. The cyclization of 1f–j with oxalyl
chloride afforded the alkyl-substituted 3-hydroxymaleic
anhydrides 3f–j. The cyclization of oxalyl chloride with
1k, prepared from pent-4-enoic acid, gave the allyl-substi-
tuted maleic anhydride 3k. The methoxy-, phenyloxy- and
benzyloxy-substituted 3-hydroxymaleic anhydrides 3l–n
were prepared from the corresponding 1,1-bis(trimethyl-
silyloxy)ketene acetals 1l–n. All cyclizations proceeded
in good to moderate yields and with very good regioselec-
tivity.
(12) (a) For the synthesis of a-hydroxy-g-alkylidenebutenolides
from 1,3-bis(trimethylsilyloxy)-1,3-butadienes, see:Langer,
P.; Schneider, T.; Stoll, M. Chem.–Eur. J. 2000, 6, 3204.
(b) For palladium-catalyzed functionalizations, see: Langer,
P.; Eckardt, T.; Schneider, T.; Göbel, C.; Herbst-Irmer, R. J.
Org. Chem. 2001, 66, 2222. (c) See also: Ahmed, Z.;
Langer, P. J. Org. Chem. 2004, 69, 3753.
(13) For the synthesis of 2,3-dihydro-2,3-diones from silyl enol
ethers, see: (a) Murai, S.; Hasegawa, K.; Sonoda, N. Angew.
Chem., Int. Ed. Engl. 1975, 14, 636; Angew. Chem. 1975, 87,
668. (b) Kappe, C. O.; Kollenz, G.; Wentrup, C.
Heterocycles 1994, 38, 779.
(14) For the synthesis of 4-hydroxy-2H-pyran-2-ones from silyl
enol ethers, see: Effenberger, F.; Ziegler, T.; Schonwalder,
K.-H.; Kesmarszky, T.; Bauer, B. Chem. Ber. 1986, 119,
3394.
Synlett 2004, No. 15, 2782–2784 © Thieme Stuttgart · New York

2784
E. Ullah, P. Langer
LETTER
The residue was purified by chromatography (silica gel,
(15) For the synthesis of 1,1-bis(trimethylsilyloxy)ketene acetals,
see: (a) Ainsworth, C.; Kuo, Y.-N. J. Organomet. Chem.
1972, 46, 73. (b) Wissner, A. J. Org. Chem. 1979, 44, 4617.
(c) Takai, K.; Heathcock, C. H. J. Org. Chem. 1985, 50,
3247.
(16) To a CH2Cl2 solution (17.8 mL) of oxalyl chloride (0.20 mL,
2.3 mmol) and 1a (0.50 g, 1.8 mmol) was added a CH2Cl2
solution (5 mL) of TMSOTf (0.16 mL, 0.9 mmol) at 78 °C.
The temperature of the solution was allowed to rise to 20 °C
during 12 h. After stirring for 3 h at 20 °C, an aq solution of
HCl (10%) was added. The organic and the aqueous layer
were separated and the latter was extracted three times with
CH2Cl2. The combined organic layers were dried (Na2SO4),
filtered and the solvent of the filtrate was removed in vacuo.
hexane–EtOAc) to give 3a as a yellow solid (240 mg, 70%),
mp 164 °C. 1H NMR (300 MHz, CDCl3): d = 7.42–7.50 (m,
3 H, Ar), 8.05–8.08 (m, 2 H, Ar). 13C NMR (75 MHz,
CDCl3): d = 112.0 (C), 126.9 (C), 128.8 (CH), 129.1 (CH),
130.3 (CH), 149.4 (C), 163.4 (C), 163.5 (C). IR (neat): 3244
(s), 3123 (w), 1840 (s), 1760 (s), 1673 (s), 1393 (s), 1262 (s),
939 (s), 762 (s) cm–1. MS (EI, 70 eV): m/z (%) = 190 (43)
[M+], 162 (100), 145 (22), 118 (27), 105 (15), 89 (81), 77 (8).
Anal. Calcd for C10H6O4: C, 63.16; H, 3.18. Found: C, 62.87;
H, 3.63.
(17) For a review of dianions of carboxylic acids, see: Petragnani,
N.; Yonashiro, M. Synthesis 1982, 521.
Synlett 2004, No. 15, 2782–2784 © Thieme Stuttgart · New York