Cerium-catalyzed α-oxidation of β-dicarbonyl compounds with molecular oxygen

Article abstract of DOI:10.1055/s-2002-19331

β-Ketoesters and β-diketones are α-hydroxylated by molecular oxygen in the presence of 5 mol% CECl₃-7 H₂O in i-PrOH as solvent. The method is limited to substrates with an α-alkyl substituent. Optimal yields are achieved with cyclic

Full text of DOI:10.1055/s-2002-19331

LETTER
119
Cerium-catalyzed -Oxidation of -Dicarbonyl Compounds with Molecular
Oxygen
C
erium-ca
e
talyzed -O
n
xidation of
s
-Dicarbonyl Co
C
mpounds hristoffers,* Thomas Werner
Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany
Fax +49(711)6854269; E-mail: jchr@po.uni-stuttgart.de
Received 3 September 2001
tions. In the case of lactone 2d, unidentified, polar by-
products were removed by the mentioned simple filtration
through SiO2 (60%) or chromatography (78%), and the
yield obtained was improved to that achieved with Co-ca-
talysis. Main decomposition product of the ester 2e was
the acid 3,15 which was separable either by distillation, ex-
traction, or by chromatography. The yields obtained de-
pended on the workup procedure, but were about the same
as for Co-catalysis. Yields of the compounds 2f–i were
not satisfying. The products 2g–i had to be purified by
chromatography. In the cases of 2e and 2i the chloro de-
rivatives 4a16 and 4b were identified as by-products.
Abstract: -Ketoesters and -diketones are -hydroxylated by mo-
lecular oxygen in the presence of 5 mol% CeCl3 7 H2O in i-PrOH
as solvent. The method is limited to substrates with an -alkyl sub-
stituent. Optimal yields are achieved with cyclic starting materials.
Key words: catalysis, cerium -dicarbonyl compounds, oxidation,
oxygen
Procedures for the selective oxidation of functional
groups hold a central position in synthetic organic chem-
istry. -Hydroxy- -dicarbonyl compounds are prepared –
apart from some other methods1 – by oxidation of the par-
ent -dicarbonyl. Common electrophilic reagents for this
transformation are Pb(OAc)4,2 MoOPH,3 or peracids.4 Be-
sides, a sequence via the epoxide of the corresponding si-
lyl enol ether known as Rubottom oxidation is
established.5 Moreover, dialkyldioxiranes have been re-
ported for the selective oxidation of -dicarbonyl com-
pounds.6
With regard to ecological and economical concerns, mo-
lecular oxygen should be the oxidant of choice.7 The man-
Scheme Cerium-catalyzed -hydroxylation of -dicarbonyl com-
pounds
ganese-, cobalt- or cesium-catalyzed oxidations of
-
dicarbonyl compounds by O2 have been published recent-
ly. However, procedures are either inefficient (Mn),8 re-
quire toxic transition metals (Co),9 or an over
stoichiometric amount of Cs-salts.10,11 Herein we wish to
report on the oxidation of -ketoesters and -diketones
with molecular oxygen catalyzed by CeCl3 7 H2O.12 The
advantages are the use of the inexpensive and non-toxic
cerium salt and i-PrOH as the solvent.
Conversion of starting materials without an -alkyl sub-
stituent resulted in complex product mixtures, which were
only partly characterized and shall not be discussed in de-
tail here. On the other hand, malonates showed no conver-
sion under the reaction conditions.17 From a mechanistic
point of view, we presume formation of Ce(IV)-diketo-
nate complexes in situ undergoing intramolecular electron
transfer to give Ce(III) species and an oxidized dicarbonyl
intermediate, whose nature could be a radical. The latter
assumption is supported by the observation of halogenat-
ed by-products like 4a and 4b. Ce(III) species are reoxi-
dized by O2. Actually, the same catalytic activity is
observed with (NH4)2Ce(NO3)6.
Stirring of a 2–3 molar solution of starting materials 1 in
i-PrOH containing 5 mol% CeCl3 7 H2O under 1 atmos-
phere of O2 for 10–20 hours afforded the hydroxylated
products 2 (Scheme, Table). At least for the cyclic com-
pounds 2a–d the workup procedure was remarkably sim-
ple: Filtration through a small pad of SiO2 removed all
metal containing materials and gave analytically pure
products.13 In the case of cyclic oxoesters 2a–c the yields
were excellent and significantly improved compared to
Mn- (89% for 2a) and Co-catalysis (83% for 2a). Com-
pound 2b bearing the enantiopure (–)-menthyl moiety was
obtained as a 1:1 mixture of two diastereoisomers.14 Prod-
ucts 2d–i slowly decomposed under the reaction condi-
In summary, cyclic -dicarbonyl compounds are chemo-
selectively -hydroxylated by molecular oxygen. The
catalyst CeCl3 7 H2O is inexpensive and non-toxic, and
the solvent applied is i-PrOH. The workup procedure can
be as simple as filtration through some SiO2 yielding
analytically pure materials. We are presently working on
enlarging the scope of this method by optimizing the
yields of acyclic products.
Synlett 2002, No. 1, 28 12 2001. Article Identifier:
1437-2096,E;2002,0,01,0119,0121,ftx,en;G19201ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

120
J. Christoffers, T. Werner
LETTER
Table Products, Yields, and Workup Procedures
References
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Yield
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2a
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99%a,b
(4) Hubert, A. J.; Starcher, P. S. J. Chem. Soc. C 1968, 2500.
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2c
96%a
2d
2e
78%,c 54%,d 53%a
59%,d 38%c,e
(8) Christoffers, J. J. Org. Chem. 1999, 64, 7668.
(9) Baucherel, X.; Levoirier, E.; Uziel, J.; Juge, S. Tetrahedron
Lett. 2000, 41, 1385.
(10) Watanabe, T.; Ishikawa, T. Tetrahedron Lett. 1999, 40,
7795.
(11) Use of catalytic (10 mol%) amounts of Cs-salts resulted in
significantly lower yields.
2f
51%,d 46%c
(12) The combination of molecular oxygen and catalytic CeCl3 is
known for oxidation of benzyl alcohol to benzaldehyde in
the presence of Pt/C and Bi2(SO4)3: Oi, R.; Takenaka, S.
Chem. Lett. 1988, 1115.
2g
2h
2i
30%c,f
29%c
(13) Typical Procedure for 2c: Ester 1c (1.09 g, 6.40 mmol) was
added to a suspension of CeCl3 7 H2O (119 mg, 0.32 mmol)
in isopropanol (2.0 mL). The flask was evacuated twice to
ca. 500 mbar, flushed with oxygen, and the mixture was then
stirred for 16 h under 1 atm of O2. After filtration through
SiO2 (2 cm, washing with ethyl acetate) and removal of all
volatile materials from the filtrate in vacuo 1.14 g (96%, 6.12
mmol) of compound 2c were obtained as a colorless oil. 1H
NMR (CDCl3, 300 MHz): = 1.24–1.32 (m, 1 H), 1.33–1.58
(m, 2 H), 1.67–1.90 (m, 2 H), 1.91–2.05 (m, 1 H), 2.07–2.15
(m, 1 H), 2.27 (dd, J = 14.9 Hz, J = 10.6 Hz, 1 H), 2.59 (ddd,
J = 11.7 Hz, J = 7.0 Hz, J = 1.7 Hz, 1 H), 2.96 (td, J = 12.1
Hz, J = 2.9 Hz, 1 H), 3.67 (s, 3 H), 4.35 (s, 1 H) ppm. Anal.
Calcd for C9H14O4: C, 58.05; H, 7.58. Found: C, 58.27; H,
7.33.
44%c,g
a Filtration through 2 cm SiO2.
b Mixture of two diastereoisomers, ratio 1:1 by 1H NMR.
c Chromatography.
d Kugelrohr distillation.
e Acid 3 (28%) and chloro compound 4a (4%) were isolated as by-
products.
f Starting material was recovered (16%).
g By-product 4b was isolated in 7% yield.
(14) Selected data for new compounds, Menthyl Ester 2b: 1H
NMR (CDCl3, 300 MHz), diastereoisomer 1: = 0.71 (d,
J = 6.8 Hz, 3 H), 0.86 (d, J = 7.4 Hz, 3 H), 0.92 (d, J = 6.4
Hz, 3 H), 0.95 1.13 (m, 2 H), 1.33 1.56 (m, 2 H), 1.63
1.74 (m, 3 H), 1.88 2.17 (m, 5 H), 2.40–2.52 (m, 3 H), 3.86
(s, 1 H), 4.77 (dt, J = 10.5 Hz, J = 7.3 Hz, 1 H) ppm;
diastereoisomer 2: = 0.77 (d, J = 7.3 Hz, 3 H), 0.90 (d,
J = 6.5 Hz, 3 H), 0.92 (d, J = 6.4 Hz, 3 H), 0.95 1.13 (m, 2
H), 1.33 1.56 (m, 2 H), 1.63 1.74 (m, 3 H), 1.88 2.17 (m,
5 H), 2.40 2.52 (m, 3 H), 3.86 (s, 1 H), 4.78 (dt, J = 10.9 Hz,
J = 7.3 Hz, 1 H) ppm. 13C{1H}-NMR (CDCl3, 75 MHz),
diastereoisomer 1: = 15.92 (CH3), 18.46 (CH2), 20.70
(CH3), 21.94 (CH3), 23.09 (CH2), 26.06 (CH), 31.36 (CH),
34.06 (CH2), 34.96 (CH2), 36.00 (CH2), 40.21 (CH2), 47.02
(CH), 76.85 (CH), 79.71 (C), 171.33 (C=O), 213.38 (C=O)
ppm; diastereoisomer 2: = 15.99 (CH3), 18.48 (CH2),
20.85 (CH3), 21.89 (CH3), 23.17 (CH2), 26.26 (CH), 31.33
(CH), 34.03 (CH2), 34.63 (CH2), 35.80 (CH2), 40.71 (CH2),
46.95 (CH), 76.90 (CH), 79.70 (C), 171.27 (C=O), 213.43
(C=O) ppm. Mol. mass calcd for C16H26O4: 282.1831.
Found: 282.1831 [M+]. Anal. Calcd: C, 68.06; H, 9.28.
3
4a
4b
Acknowledgement
We thank the Deutsche Forschungsgemeinschaft and the Fonds der
Chemischen Industrie for support of this work.
Synlett 2002, No. 1, 119–121 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Found: C, 67.97; H, 9.22. Ethyl 2-benzoyl-2-
Cerium-catalyzed -Oxidation of -Dicarbonyl Compounds
121
(CDCl3, 300 MHz): = 2.15 (s, 6 H), 3.42 (s, 2 H), 7.19–
7.22 (m, 2 H), 7.26–7.31 (m, 3 H) ppm. 13C{1H}-NMR
(CDCl3, 125 MHz): = 27.39 (CH3), 42.39 (CH2), 80.22
(C), 127.55 (CH), 128.37 (CH), 130.69 (CH), 133.88 (C),
201.09 (C=O) ppm. Mol. mass calcd for C12H13ClO2:
224.0604. Found: 224.0612 [M+].
hydroxypropanoate 2g: 1H NMR (CDCl3, 300 MHz):
= 1.15 (t, J = 7.2 Hz, 3 H), 1.74 (s, 3 H), 4.23 (q, J = 7.1
Hz, 2 H), 4.51 (s, 1 H), 7.42 7.48 (m, 2 H), 7.55 7.60 (m, 1
H), 7.97 8.00 (m, 2 H) ppm. 13C{1H}-NMR (CDCl3, 75
MHz): = 13.81 (CH3), 23.52 (CH3), 62.51 (CH2), 79.48
(C), 128.62 (CH), 129.47 (CH), 133.14 (C), 133.70 (CH),
172.31 (C=O), 195.94 (C=O) ppm. Mol. mass calcd for
C12H14O4: 222.0892. Found: 222.0876 [M+]. 3-Benzyl-3-
hydroxy-2,4-pentanedione 2i: 1H NMR (CDCl3, 300
MHz): = 2.23 (s, 6 H), 3.28 (s, 2 H), 4.69 (s, 1 H), 7.19–
7.28 (m, 5 H) ppm. 13C{1H}-NMR (CDCl3, 125 MHz):
= 25.66 (CH3), 41.88 (CH2), 91.06 (C), 127.58 (CH),
128.69 (CH), 130.05 (CH), 134.50 (C), 206.70 (C=O) ppm.
Mol. mass calcd for C12H14O3: 206.0943. Found: 206.0953
[M+]. 3-Benzyl-3-chloro-2,4-pentanedione 4b: 1H NMR
(15) Formation of by-product 3 was also observed with other
procedures.4,8
(16) (a) Brenner, J. E. J. Org. Chem. 1961, 26, 22. (b) Hussey,
C. W. T.; Pinder, A. R. J. Chem. Soc. 1962, 1517.
(c) Karrenbrock, F.; Schäfer, H. J. Tetrahedron Lett. 1978,
1521.
(17) The oxidative dehydrodimerization of malonates with
Ce(IV) or Mn(III) under ultrasonic conditions has been
reported: Linker, T.; Linker, U. Angew. Chem. Int. Ed. 2000,
39, 902.
Synlett 2002, No. 1, 119–121 ISSN 0936-5214 © Thieme Stuttgart · New York