A new synthetic route for 1,2-diketo compounds using unexpected C-C bond cleavage by PCC

Article abstract of DOI:10.1016/j.tetlet.2012.07.095

An efficient method has been established for the preparation of 1,2-diketones by unexpected C-C bond cleavage in 4-keto-2-hydroxy esters using pyridiniumchlorochromate (PCC).

Full text of DOI:10.1016/j.tetlet.2012.07.095

Tetrahedron Letters 53 (2012) 5327–5330
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Tetrahedron Letters
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A new synthetic route for 1,2-diketo compounds using unexpected C–C
bond cleavage by PCC
Shrikar M. Bhosale a, Aadil A. Momin a, Rupesh L. Gawade b, Vedavati G. Puranik b, Radhika S. Kusurkar a,
⇑
a Department of Chemistry, University of Pune, Pune 411 007, India
b National Chemical Laboratory, Pune, Pune 411 008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient method has been established for the preparation of 1,2-diketones by unexpected C–C bond
cleavage in 4-keto-2-hydroxy esters using pyridiniumchlorochromate (PCC).
Ó 2012 Elsevier Ltd. All rights reserved.
Received 2 May 2012
Revised 19 July 2012
Accepted 24 July 2012
Available online 27 July 2012
Keywords:
1,2-Diketones
PCC
C–C bond cleavage
O
1,2-Diketones are of great importance in organic chemistry
especially in the synthesis of pharmaceuticals. These compounds
are useful as intermediates in the synthesis of biologically active
heterocyclic compounds such as imidazoles, quinoxalines, and
indolone-N-oxide.1 Their industrial applications as corrosion inhib-
itors,2 photosensitive agents,3 and photoinitiators4 have also been
shown. Because of the wide variety of applications, there are vari-
ous synthetic routes available for 1,2-diketones, however practical
and efficient methods are limited.5 Traditionally, 1,2-diketones are
prepared by the oxidation of benzoins or hydrobenzoins in the
presence of excessive amounts of metal oxidants. It suffers from
several disadvantages, including heavy environmental pollution
and difficulty in accessing functionalized benzoins.6 Recent strate-
gies for the synthesis 1,2-diketones are direct oxidation of internal
alkynes7 and by the decarbonylation of 1,3-diketones with iodide
and base under irradiation of fluorescent light.8
OCH3
H3CO
O
5
OH
O
N
O
N
N
a
N
H
1
N
H
2
N
H
b
O
O
O
c
X
c
OH
OCH3
O
O
N
H
3
N
H
4
N
H
O
O
OCH3
5
Scheme 1. Reagents and conditions: (a) DMF, NCS, 3 h, Et3N, Methyl crotonate, 4 h.
(b) Raney Ni, H2, acidic buffer, methanol, 5 h, 89%. (c) PCC, DCM, 2 h, 80%.
PCC is a well-known oxidizing agent, for the conversion of alco-
hols to aldehydes and ketones with high efficiency.9 Several rear-
rangements and useful conversions are mediated by PCC.10,11
This makes PCC a versatile reagent in organic synthesis. We herein
report a new method for the synthesis of 1,2-diketo compounds by
PCC mediated unexpected C–C bond cleavage.
In our earlier endeavor of a total synthesis of a natural product,
there was
a
need of methyl-4-(1H-indol-3-yl)-3-methyl-2,
4-dioxobutanoate (4) as an intermediate. To achieve this, initially
2 was prepared using a 1,3-dipolar reaction of oxime 1 and methyl
crotonate (Scheme 1). In this reaction two regioisomers were
⇑
Corresponding author.
E-mail address: rsk@chem.unipune.ac.in (R.S. Kusurkar).
Figure 1. ORTEP diagram of compound 5.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.07.095

5328
S. M. Bhosale et al. / Tetrahedron Letters 53 (2012) 5327–5330
O
OCH3
OH
O
O
O
OH
O
O
OCH3
OCH3
PCC
O
N
H
N
H
N
H
3
O
O
Cr
Cl
O
N
H
O
O
O
O
Cr
O
OCH3
O
O
O
O
H
O
O
O
N
H
N
H
OCH3
N
H
O
Cr
OH
5
O
Scheme 2. Possible mechanism for the formation of diketo compound 5.
Table 1
Formation of 1,2-diketones using various 4-keto-2-hydroxy esters
Entry
Starting material
Product
Yield (%)
80
O
O
O
1
N
H
N
H
OH
OCH3
O
5
3
O
O
O
O
2
3
68
70
OH
5a
O
OCH3
3a
O
O
OH
Cl
Cl
5b
O
OCH3
3b
O
O
4
5
6
81
76
90
O
MeO
5c
MeO
OH
3c
EtO
O
O
O
NH
EtO
NH
O
5d
5e
OH
3d
O
O
O
O
O
OH
O
OC2H5
3e
O
7
8
93
95
O
OH
O
3f
5f
O
O
O
OH
5g
O
OC2H5
3g

S. M. Bhosale et al. / Tetrahedron Letters 53 (2012) 5327–5330
5329
Table 1 (continued)
Entry
Starting material
Product
Yield (%)
OMe
OMe
O
O
9
O
93
91
OH
OC2H5
MeO
O
MeO
5h
3h
O
O
O
10
O
5i
OH
EtO
3i
formed.12 Isomer 2 was identified by a downfield doublet of C5H in
1H NMR. Subsequently, N–O bond cleavage of 2 was carried out
using Raney nickel in the presence of hydrogen to give 4-keto-2-
hydroxy ester 3. Further, reaction of 3 with PCC (3 equiv) in DCM
at room temperature furnished a solid product. However, the spec-
tral data of this product were not consistent with the expected
structure 4.
2, 3833; (d) McKenna, J. M.; Halley, F.; Souness, J. E.; McLay, I. M.; Pickett, S. D.;
Collis, A. J.; Page, K.; Ahmed, I. J. Med. Chem. 2002, 45, 2173; (e) Deng, X.; Mani,
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In 1H NMR a singlet of methoxyl protons was absent and a singlet
at d 2.54 was seen which could be assigned to three protons of
–COCH3. 13C NMR showed one singlet at d 25.50 and only two car-
bonyl singlets at d 183.84 and 200.80. The spectral data suggested
structure 5 for this compound. Finally, structure 5 was confirmed
by single crystal X-ray analysis13 (Fig. 1). The same product was ob-
tained by using 1.5 equiv of PCC with less yield. The formation of this
product could be explained (Scheme 2) by initial PCC oxidation of
the secondary alcohol to the oxo species, which exists
predominantly in the enol tautomer. Nucleophilic attack of the enol
oxygen on chromiumwith the displacement of chloride gives a chro-
mate ester. Upon suffering a [2,3]-sigmatropic rearrangement, the
alpha carbon of the ketone is oxidized and undergoes subsequent
decomposition eliminating two equivalents of carbon monoxide
and one equivalent of methanol. The formation of carbon monoxide
was confirmed by gas evolution from the reaction and a color test.14
Thus, 1,2-diketone 515 resulted in an accidental finding, that
PCC in excess cleaved the C–C bond of 4-keto-2-hydroxy ester.
Considering this as a new observation and the importance of
1,2-diketo compounds in organic synthesis, we generalized this
observation using various 4-keto-2-hydroxy esters as shown in
Table 1, entry 1 to 10. The method used for the synthesis of ester
3 was applied for all other esters 3a–3i. In the PCC reactions, using
esters 3c–3i, yields were better than using esters 3a and 3b.
In conclusion, we have reported a new efficient route for the
preparation of 1,2-diketones by unexpected C–C bond cleavage
using PCC.
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Acknowledgements
We are grateful to Mrs. J. P Chaudhari for NMR spectra and Ms.
Deepanjali for IR spectra. S.M.B. is thankful to the CSIR, New Delhi
for financial support.
Supplementary data
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Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.
07.095.
References and notes
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Commun. 1988, 18, 1573; (n) Cossy, J.; Bouzbouz, S.; Lachgar, M.; Hakiki, A.;
Tabyaouic, B. Tetrahedron Lett. 1998, 39, 2561.
15. General procedure for the preparation of 1,2-diketones. To a stirred solution of
-hydroxy ester in dry DCM was added PCC (3 equiv) slowly at 0 °C. Reaction
a
12. Larsen, K. E.; Torssell, K. B. G. Tetrahedron 1984, 40, 2985.
mixture was stirred for the next 2 h at room temperature and was directly
poured onto the column using DCM or ethylacetate–hexane as an eluent for
purification to furnish 1,2-diketone.
13. Crystallographic data for structure 5 have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication nos. CCDC 878819.
Copies of the data can be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK, (fax: +44 (0)1223 336033 or e-mail:
deposit@ccdc.cam.ac.Uk).
14. The evolved carbon monoxide gas from the reaction mixture was passed
through a solution of PdCl2 in acetone–water. Black precipitate of metallic Pd
appeared which was confirmed by the addition of aqueous solution of
ammonium molybdate. A molybdenum blue color was observed.
1-(1H-Indol-3-yl)propane-1,2-dione (5): Mp 174–176 °C; 1H NMR (300 MHz,
CDCl3) 2.54 (s, 3H), 7.25–7.43 (m, 3H), 8.41–8.45 (d, 2H), 8.83 (br s, 1H); 13C
NMR (75 MHz, CDCl3) 25.50, 111.50, 122.51, 123.42, 124.37, 126.24, 135.85,
136.20, 183.84, 200.80; FT-IR(KBr cmÀ1) 3398,1734; Ms (70 eV) m/z 187; Anal.
Calcd for C11H9NO2: C, 70.58; H, 4.78%. Found: C, 70.39; H, 5.02.