Monohydroxylation of cyclic and acyclic β-keto esters with molecular oxygen catalyzed by cobalt(II) chloride in neutral conditions

Article abstract of DOI:10.1016/S0040-4039(99)02275-3

Cyclic and acyclic α-alkyl-α-hydroxy-β-keto esters 2 were obtained with 50-100% isolated yields from the corresponding β-keto esters 1 by oxidation with molecular oxygen in a mixture of CH₃CN/i-PrOH and in the presence of cobalt(II) chloride. (

Full text of DOI:10.1016/S0040-4039(99)02275-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 1385–1387
Monohydroxylation of cyclic and acyclic β-keto esters with
molecular oxygen catalyzed by cobalt(II) chloride in neutral
†
conditions
∗
Xavier Baucherel, Eric Levoirier, Jacques Uziel and Sylvain Juge
Unité mixte Université de Cergy-Pontoise /ESCOM-“Synthèse Organique Sélective et Chimie Organométallique”,
EP CNRS 1822-5 mail Gay Lussac-95031 Cergy-Pontoise Cedex, France
Received 28 October 1999; accepted 6 December 1999
Abstract
Cyclic and acyclic α-alkyl-α-hydroxy-β-keto esters 2 were obtained with 50–100% isolated yields from the
corresponding β-keto esters 1 by oxidation with molecular oxygen in a mixture of CH3CN/i-PrOH and in the
presence of cobalt(II) chloride. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: oxygen; hydroxylation; catalysis; keto esters.
The α-hydroxy-β-keto ester moiety 2 is used as a starting material or an intermediate for the synthesis
1
,2
of natural products. It is also present in the structure of biologically active molecules such as indolic
3
alkaloids.
The shortest way for the preparation of compounds 2 is the oxidation of the corresponding β-
dicarbonyl compounds 1 in basic conditions or via the enol derivatives. Various oxidants were already
4
3b
5
6
7
8
used, including Pb(OAc) , H O , m-CPBA, singlet oxygen, molecular oxygen, dimethyldioxirane
4
2
2
2
a,c
or oxaziridine derivatives.
9
Iqbal et al. have described catalytic oxidation of alcohols and epoxidation of olefins by oxygen, using
ethyl 2-oxocyclopentane carboxylate as reductant. During this reaction, the β-keto ester is converted into
the corresponding α-hydroxylated derivative.
In order to achieve a general synthesis of α-hydroxy-β-keto esters 2 by aerobic oxidation, we studied
the monohydroxylation reaction in the presence of isopropanol as a reductant. We report herein a very
simple method that uses a catalytic amount of CoCl in a mixture of acetonitrile/isopropanol (Scheme
2
1).
This procedure was applied to various cyclic β-keto esters or to a lactone derivative (Table 1, entries
–4) to afford the corresponding α-hydroxy-β-keto esters 3–6 in 60–100% isolated yields. The above
1
∗
†
Corresponding author. Fax: 33 1 34 25 70 67; e-mail: sylvain.juge@chim.u-cergy.fr (S. Juge)
Presented as part of a communication at the BIOTRANS 99, Giardini, Naxos, Italy, September 26–October 1, 1999.
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02275-3
tetl 16203

1
386
Scheme 1.
reaction conditions were also successful in the case of the less reactive acyclic β-keto esters (entries 5
1
0
and 6).
Table 1
α-Hydroxylated β-keto esters
In conclusion, in this paper we propose a simple and efficient method of aerobic monohydroxylation in
neutral conditions, leading to various α-hydroxy-β-keto esters, which can be obtained in an enantiopure
form by kinetic resolution by using baker’s yeast.11
References
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1
0. Typical procedure: Anhydrous cobalt(II) chloride (0.35 mmol) was heated at 60°C in acetonitrile (44 mL) and isopropanol
26 mL) under 1 atmosphere of oxygen. The β-keto ester 1 (7 mmol) was then added in the reaction mixture. At the end of
the reaction (monitored by TLC) the solvent was evaporated in vacuo and the residue was purified by flash chromatography
(

1
387
on silica gel. Compound 3:7c,8 IR: 3471, 2981, 1757, 1725, 1260; H NMR (250 MHz, CDCl
1H, s), 2.28 (3H, m), 1.93 (3H, m), 1.11 (3H, t, J=6.9); 13C NMR (62.9 MHz, CDCl
): δ 213.4, 171.5, 79.6, 62.2, 35.7,
: 172.0735; found: 172.0727; anal. calcd: C, 55.81; H, 6.98; found: C, 55.73; H,
1
): δ 4.05 (2H, q, J=6.9), 3.95
3
(
3
6
3
8 12 4
4.7, 18.2, 13.8; HRMS calcd for C H O
.96. Compound 4:5 IR: 3455, 2945, 1721, 1253; H NMR (CDCl
,7c
1
): δ 4.24 (1H, s), 4.19 (2H, q, J=7.2), 2.65–2.40 (3H,
): δ 207.3, 170.0, 80.6, 62.0, 38.8, 37.6, 27.0,
9 14 4
H O : 186.0892; found: 186.0901; anal. calcd: C, 58.06; H, 7.53; found: C, 58.21; H, 7.61.
3
1
3
m), 1.95 (1H, m), 1.80–1.50 (4H, m), 1.21 (3H, t, J=7.2); C NMR (CDCl
1.9, 14.0; HRMS calcd for C
3
2
6
1
Compound 5: mp 68°C; IR: 3464, 1737, 1678, 1269; H NMR (CDCl
.5), 7.38 (1H, t, J=7.5), 7.31 (1H, d, J=7.5), 4.26 (1H, s), 3.68 (3H, s), 3.07 (2H, m), 2.66 (1H, dt, J=13.6, 5.0), 2.20 (1H,
): δ 194.6, 171.2, 144.1, 134.5, 130.2, 129.0, 128.3, 127.1, 77.7, 53.1, 32.8, 25.6;
HRMS calcd for C12 : 221.0813; found: 221.0807; anal. calcd: C, 65.45; H, 5.49; found: C, 65.03; H, 5.50. Compound
): δ 4.50–4.35 (2H, m), 4.21 (1H, s), 2.64 (1H, ddd, J=13.5, 7.2, 4.7), 2.34 (1H,
ddd, J=13.5, 8.1, 7.5), 2.29 (3H, s); C NMR (CDCl ): δ 205.9, 175.1, 81.5, 66.3, 34.1, 24.8; HRMS calcd for C
3
): δ 8.10 (1H, dd, J=7.8, 1.5), 7.57 (1H, td, J=7.5,
1
13
ddd, J=13.6, 8.8, 6.5); C NMR (CDCl
3
13 4
H O
8
1
6
: IR: 3427, 1771, 1716; H NMR (CDCl
3
13
3
6 9 4
H O :
12
1
1
2
45.0501; found: 145.0498. Compound 7: IR: 3459, 1724, 1263; H NMR (CDCl
.21 (3H, s), 1.53 (3H, s), 1.22 (3H, t, J=7.2); 13C NMR (CDCl
): δ 205.1, 171.2, 80.8, 63.7, 24, 21.6, 13.7; HRMS calcd
: 161.0814; found: 161.0814. Compound 8: IR: 3472, 3031, 1722, 1272; H NMR (CDCl
3
): δ 4.17 (2H, q, J=7.2), 4.13 (1H, s),
3
1
for C
4
1
7
H
13
O
4
3
): δ 7.3–7.2 (5H, m),
): δ 204.4, 171.3, 134.9,
14 4
H O : 223.0970; found: 223.0965.
1
3
.07 (1H, s), 3.79 (3H, s), 3.43 (1H, d, J= 14.7), 3.18 (1H, d, J=14.7), 2.3 (3H, s); C NMR (CDCl
30.5, 128.7, 126.6, 84.8, 53.8, 41.4, 21.7; HRMS calcd for C12
3
1
1
1. Buisson, D.; Baucherel, X.; Levoirier, E.; Jugé, S. Tetrahedron Lett. 2000, 41, 1389–1392.
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