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Russian Chemical Bulletin, International Edition, Vol. 50, No. 2, pp. 324326, February, 2001
Selective reduction of the acyl group in cyclic α-acyl-β-dicarbonyl
compounds with sodium cyanoborohydride.
Efficient synthesis of cyclic α-alkyl-β-dicarbonyl compounds
F. S. Pashkovsky,« I. P. Lokot´, and F. A. Lakhvich
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus,
5/2 ul. Kuprevicha, 220141 Minsk, Republic of Belarus.
Fax: +7 (017) 263 7132. E-mail: evk@ns.iboch.ac.by
Efficient synthesis of cyclic α-alkyl-β-dicarbonyl compounds of the cyclopentane, cyclo-
hexane, tetronic acid, and α-pyrone series from the corresponding cyclic α-acyl-β-dicarbonyl
compounds under the action of NaBH3(CN) in a THFHCl system is described.
Key words: cyclic α-acyl-β-dicarbonyl compounds, sodium cyanoborohydride, selective
reduction, cyclic α-alkyl-β-dicarbonyl compounds.
2-Alkylcyclopentane-1,3-diones, 2-alkylcyclohexane-
convenient medium for this reaction. In this system,
tricarbonyl compounds 1 are reduced chemoselectively
to form products 2 in 7596% yield (Table 1). In the
case of arylmethylideneacyl derivatives, the whole enone
fragment undergoes reduction, as in the ionic hydroge-
nation. However, the reduction of furfurylideneacyl de-
rivatives is more selective and results in rather unstable
(2-furyl)alkyl derivatives even when a large excess of a
reducing agent is used. The work-up of the reaction
mixtures according to the proposed modification is mark-
edly simplified and allows more complete extraction of
the reaction products.
1,3-diones, 3-alkyltetronic acids, and 3-alkyl-3,4-
dihydro-2Í-pyran-2,4-diones are widely used in the
synthesis of natural compounds and their biologically
active analogs.14
We have previously proposed a method for the prepa-
ration of 2-alkylcycloalkane-1,3-diones and their het-
erocyclic analogs by the selective reduction of the acyl
group in the corresponding α-acyl derivatives of
β-dicarbonyl compounds under the action of Et3SiH in
CF3COOH in the presence of catalytic amounts of
5
6,7
BF3Et2O or LiClO4
(ionic hydrogenation). This
method makes it possible to synthesize the target α-
alkyl-β-dicarbonyl compounds in 6698% yield from
accessible 2-acylcyclopentane-1,3-diones, 2-acylcyclo-
hexane-1,3-diones, 3-acyltetronic acids, and 3-acyl-3,4-
dihydro-2Í-pyran-2,4-diones. In the case of arylmethyl-
ideneacyl derivatives of cyclic β-didicarbonyl compounds,
the conjugated double bond is reduced along with the
carbonyl group.6 The double bonds of the furan ring in
the furfurylideneacyl derivatives are also reduced.5,7
In 1980, the chemoselective reduction was described
of the carbonyl group of the acyl substituent in
acyl derivatives of the Meldrum acid, barbituric ac-
ids, 4-hydroxycoumarins, and dehydroacetic acid by
NaBH3(CN) in AcOH to form the corresponding alkyl
derivatives in high yields.8
We showed for particular examples that this proce-
dure can also be applied to compounds of the cyclohex-
ane, cyclopentane, and tetronic acid series (1) to form
α-alkyl-β-dicarbonyl compounds (2). However, the
method is experimentally inconvenient because of diffi-
culties associated with the isolation of the products from
the reaction mixtures containing AcOH, which decreases
noticeably their yields.
O
O
O
NaBH3(CN)/THFHCl
R
R
X
X
aq
7596%
O
O
1ag
2ag
Thus, reduction by sodium cyanoborohydride in the
THFHCl system is a preparatively convenient method
for the selective transformation of cyclic α-acyl-β-
dicarbonyl compounds of the cyclopentane, cyclohex-
ane, tetronic acids, and α-pyrone series into the corre-
sponding α-alkyl-β-diketones. In combination with ionic
hydrogenation, this procedure allows the flexible trans-
formation of furfurylideneacyl derivatives into compounds
with different degrees of saturation of the furfuryl-
ideneacyl fragment.
Experimental
Melting points were measured on a Boetius heating stage.
1Í NMR spectra were recorded on a Bruker AC-200 spectrom-
eter (200.13 MHz) in CDCl3 using Me4Si as an internal stan-
We found that a mixture of approximately equal
volumes of THF and 2M aqueous HCl is the most
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 309311, February, 2001.
1066-5285/00/5002-324 $25.00 © 2001 Plenum Publishing Corporation