Molybdenum(VI) dichloride

Article abstract of DOI:10.1055/s-0028-1083273

A novel and efficient method for the one-pot transformation of β-hydroxycarbonyl compounds to a-brominated 1,3-dicarbonyl compounds is achieved with MoO₂Cl₂ in the presence of N-bromosuccinimide. All the reactions were carried out un

Full text of DOI:10.1055/s-0028-1083273

306
PAPER
Molybdenum(VI) Dichloride Dioxide Catalyzed Conversion of b-Hydroxy-
carbonyls into a-Bromo 1,3-Dicarbonyls by N-Bromosuccinimide
Conversionof
b
-H
a
ydroxycarb
n
onyls into
a
-
B
rom
o
1,3-D
a
icarbonylssamy Jeyakumar, Dillip Kumar Chand*
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600 036, India
Fax +91(44)22574202; E-mail: dillip@iitm.ac.in
Received 2 September 2008; revised 15 September 2008
Dedicated to the 70th birthday anniversary of Prof. Gopa B. Behera
OH
O
O
O
O
O
step I
step II
Abstract: A novel and efficient method for the one-pot transforma-
tion of b-hydroxycarbonyl compounds to a-brominated 1,3-dicar-
bonyl compounds is achieved with MoO2Cl2 in the presence of N-
bromosuccinimide. All the reactions were carried out under mild
conditions and provide good yields of the products. No bromination
occurs at benzylic and allylic positions.
R1
R2
R1
R2
R1
R2
oxidation
bromination
Br
step III
oxidation and bromination
Key words: b-hydroxycarbonyl compounds, oxidation, bromina-
tion, molybdenum, N-bromosuccinimide
Scheme 1
ence of Lewis acid.5e Thus, it should be possible to devel-
op and optimize a combination of NBS and a catalyst
suitable for both oxidation of alcohols and bromination of
active methylene carbons. In this paper, we wish to report
an application of MoO2Cl2 as a catalyst for the one-pot
conversion of b-hydroxycarbonyl compounds into a-bro-
minated 1,3-dicarbonyl compounds in the presence of
NBS.
Multi-coupling reagents such as 1,3-diketones and b-keto
esters possess electrophilic and nucleophilic centers and
hence can be derivatized to obtain a variety of functional-
ized organic molecules.1 Two major routes are available
for the synthesis of 1,3-dicarbonyl compounds, namely,
oxidation of b-hydroxycarbonyl compounds2 and the re-
action of enolates with acylating reagents such as esters,
acid halides, and acylimidazoles.3 Oxidation methods pro-
vide 1,3-dicarbonyl compounds in better yields as com-
pared to acylation methods.2 The a-brominated 1,3-
dicarbonyl compounds are valuable building blocks for
the synthesis of various organic molecules,4 which are
usually achieved by the bromination of 1,3-dicarbonyl
compounds using various brominating reagents.5
Initially, we studied the fate of ethyl 3-hydroxy-3-phenyl-
propanoate (1) when treated with various combinations of
MoO2Cl2 and NBS at ca. 30 °C (Table 1). The optimum
yield of ethyl 2-bromo-3-oxo-3-phenylpropanoate (9) was
observed with 2.5 equivalents of NBS in the presence of
15 mol% MoO2Cl2 in dichloromethane at ca. 30 °C
(Table 1, entry 3). Further, various b-hydroxycarbonyl
compounds were oxidized to the corresponding a-bromi-
nated 1,3-dicarbonyl compounds and the results are sum-
marized in Table 2.
Although, several methods are available for the oxidation
of b-hydroxycarbonyl compounds (Scheme 1, Step I)2
and bromination of 1,3-dicarbonyl compounds
(Scheme 1, Step II),5 to the best of our knowledge there is
no report on the one pot conversion of b-hydroxycarbonyl
compounds into a-brominated 1,3-dicarbonyl compounds
(Scheme 1, Step III).
Table 1 Oxidation of Ethyl 3-Hydroxy-3-phenylpropanoate Fol-
lowed by Brominationa
The role of MoO2Cl2 as a catalyst for various organic
transformations has gained considerable interest during
the past few years.6 We have also developed MoO2Cl2 as
a mild and selective catalyst for the oxidation of sulfides,7a
aerobic oxidation of alcohols,7b ring-opening reactions of
epoxides,7c and C–H insertion of ethyl diazoacetate into
aldehydes.7d Recently, N-bromosuccinimide (NBS) is em-
ployed as a convenient co-oxidant for metal-catalyzed ox-
idation of alcohols,8 and epoxides and aziridines.9 N-
Bromosuccinimide is also used as an efficient reagent for
the bromination of 1,3-dicarbonyl compounds in the pres-
MoO2Cl2 (15 mol%)
NBS
O
OH
O
O
OEt
OEt
Ph
Ph
solvent, 30 °C
Br
1
9
Entry
Solvent
MeCN
MeCN
CH2Cl2
toluene
NBS (equiv)
Time (h) Yield (%)b
1
2
3
4
1.1
2.5
2.5
2.5
5
5
5
5
30
72
89
50
a A mixture of b-hydroxy ester (1 mmol), MoO2Cl2 (15 mol%), and
NBS (as indicated) was stirred in the solvent (10 mL) at ca. 30 °C.
b Isolated yield.
SYNTHESIS 2009, No. 2, pp 0306–0310
Advanced online publication: 12.12.2008
DOI: 10.1055/s-0028-1083273; Art ID: Z20308SS
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
.2
0
0
8

PAPER
Conversion of b-Hydroxycarbonyls into a-Bromo 1,3-Dicarbonyls
307
Table 2 Oxidation Followed by Bromination of b-Hydroxy Esters and Ketonesa
Entry
1
Substrate
Product
Time (h) Yield (%)b
OH
O
O
O
O
1
9
5
5
89
73
OEt
OEt
Br
OH
O
O
2
2
10
OEt
OEt
Br
O2N
Me
O2N
Me
O
O
O
OH
OH
O
3
4
3
4
11
12
12
12
49
63
OEt
OEt
OEt
OEt
Br
O
O
O
Me
Me
Me
Me
O
Br
O
Me
OH
5
6
5
6
13
14
12
5
65
81
Me
OEt
O
OEt
O
Et
Br
O
Et
OH
Me
Me
Br
O
O
O
OH
O
O
7
8
7
8
15
16
5
5
70
78
Me
Me
Br
O2N
O2N
OH
O
Ph
Ph
Br
a A mixture of b-hydroxy carbonyl compound (1 mmol), MoO2Cl2 (15 mol%), and NBS (2.5 mmol) was stirred in CH2Cl2 (10 mL) at ca. 30 °C.
b Isolated yield.
Aryl-substituted b-hydroxy esters (Table 2, entries 1 and
MoO2Cl2 (15 mol%)
NBS (1.1 equiv)
O
O
O
O
2) were smoothly converted into the corresponding mono-
a-brominated b-keto esters in 73–89% yields at room tem-
perature within 5 hours. However, aliphatic b-hydroxy es-
ters took 12 hours and the corresponding mono a-
brominated b-keto esters were obtained in 49–65% yields
(Table 2, entries 3–5). Further, the oxidation of b-hydroxy
ketones was examined under similar conditions to obtain
70–81% of corresponding mono a-brominated diketones
(Table 2, entries 6–8).
R1
R2
R1
R2
CH2Cl2, 30 °C
Br
Scheme
MoO2Cl2 and NBS
2
Bromination of 1,3-dicarbonyl compounds using
1,3-diketones were also performed where 69–91% of
monobrominated diketones were obtained (Table 3, en-
tries 6–8).
We have also separately investigated the a-bromination of
various 1,3-dicarbonyl compounds using 15 mol% of
MoO2Cl2 with 1.1 equivalents of NBS in dichloromethane
(Scheme 2) and the results are summarized in Table 3.
In order to determine the scope of this methodology, we
have studied the bromination of benzylic and allylic sub-
stituted b-keto esters using the MoO2Cl2 and NBS system
(Table 4). It is interesting to note that, benzylic (Table 4,
entries 1–3) and allylic (Table 4, entry 4) positions were
tolerated while active methylene carbons were brominat-
ed in 74–89% yields.
The a-unsubstituted b-keto esters were selectively mono-
brominated within 5 minutes to give 71–95% of yields
(Table 3, entries 1–3). In the case of a-alkyl substituted b-
keto esters (Table 3, entries 4 and 5) bromination was
quantitative, however, within 45 minutes. Bromination of
Synthesis 2009, No. 2, 306–310 © Thieme Stuttgart · New York

308
K. Jeyakumar, D. K. Chand
PAPER
Table 3 Direct Bromination of 1,3-Dicarbonyl Compoundsa
Entry
1
Substrate
Product
Time (min)
5
Yield (%)b
O
O
O
17
9
90
95
OEt
O
2
18
10
5
OEt
O2N
O
O
O
O
3
4
19
20
11
12
45
45
71
92
Me
Me
OEt
OEt
Me
O
O
5
6
21
22
13
14
45
15
90
91
Me
OEt
O
Et
O
Me
O
O
O
7
8
23
24
15
16
15
15
92
92
Me
O2N
O
Ph
a A mixture of 1,3-dicarbonyl compound (1 mmol), MoO2Cl2 (15 mol%), and NBS (1.1 mmol) was stirred in CH2Cl2 (10 mL) at ca. 30 °C.
b Isolated yield.
tored by TLC. After completion, CH2Cl2 was evaporated and the
crude mixture was diluted with H2O (15 mL). The product was ex-
tracted with EtOAc (2 × 15 mL) and the combined organic extracts
were dried (Na2SO4). The EtOAc was evaporated and the residue
was purified by flash column chromatography (silica gel 60–120
mesh, EtOAc–hexane) to give the pure a-brominated 1,3-dicarbon-
yls 9–16.
In conclusion, we have developed a novel and efficient
method for the one-pot transformation of b-hydroxycar-
bonyl compounds to a-brominated 1,3-dicarbonyl com-
pounds. All the reactions were carried out under mild
conditions with good yields. It is also interesting to note
that benzylic and allylic positions are tolerant to bromina-
tion.
Bromination of 1,3-Dicarbonyl Compounds; General Proce-
dure B
Alcohols, 1–8 were prepared using literature methods.10 MoO2Cl2,
NBS, and b-keto esters, 17–28 were purchased from Aldrich. The
A mixture of 1,3-dicarbonyl compound (1 mmol), NBS (0.195 g,
1.1 mmol) and 15 mol% MoO2Cl2 (0.030 g, 0.15 mmol) was stirred
in CH2Cl2 (10 mL) at ca. 30 °C. The conversion was monitored by
TLC. After completion, CH2Cl2 was evaporated and the crude mix-
ture was diluted with H2O (15 mL). The product was extracted with
EtOAc (2 × 15 mL) and the combined organic extracts were dried
(Na2SO4). The EtOAc was evaporated and the residue was purified
by flash column chromatography (silica gel 60–120 mesh, EtOAc–
hexane) to give the pure a-brominated 1,3-dicarbonyls 9–16 and
29–32.
1
products were characterized by H and 13C NMR, IR, and melting
points using Bruker 400 MHz NMR spectrometer, Jasco FT/IR 660
plus, and Toshnival-India melting point apparatus, respectively.
The spectral data for products are comparable with the literature da-
ta: 9,5b 11,5b 12–13,11a 14–16,5b 29,11b 30,5f 31–32.5b The product 10
is reported,12 however, we could not find any spectral data for com-
parison. Thus, analytical data for 10 is provided in this work.
Oxidation of 3-Hydroxycarbonyl Compounds; General Proce-
dure A
A mixture of 3-hydroxycarbonyl compound (1 mmol), NBS (0.443
g, 2.5 mmol) and 15 mol% MoO2Cl2 (0.030 g, 0.15 mmol) was
stirred in CH2Cl2 (10 mL) at ca. 30 °C. The conversion was moni-
Ethyl 2-Bromo-3-(4-nitrophenyl)-3-oxopropanoate (10)
Prepared by using the general procedure A or B; yield: 73%; solid;
mp 85 °C.
Synthesis 2009, No. 2, 306–310 © Thieme Stuttgart · New York

PAPER
Conversion of b-Hydroxycarbonyls into a-Bromo 1,3-Dicarbonyls
309
Table 4 Regioselective Bromination of Allylic and Benzylic b-Keto Estersa
Entry
1
Substrate
Product
Time (h) Yield (%)b
O
O
O
O
25
29
10
30
80
89
OEt
OEt
Br
Me
Me
Me
O
O
O
O
2
26
30
Me
OEt
OEt
Br
O
Ph
Ph
O
O
O
O
3
4
27
28
31
32
15
10
81
74
Me
Me
OBn
Me
Me
OBn
O
Br
Br
O
O
O
O
a A mixture of b-keto ester (1 mmol), MoO2Cl2 (15 mol%), and NBS (1.1 mmol) was stirred in CH2Cl2 (10 mL) at ca. 30 °C.
b Isolated yield.
IR (neat): 1725 cm–1.
(4) (a) Larock, R. C. Comprehensive Organic Transformations,
2nd ed.; VCH Publishers Inc.: New York, 1999, 715–719.
(b) Misra, A. P.; Raj, K.; Bhaduri, A. P. Synth. Commun.
1999, 29, 3227. (c) Coats, S. J.; Wasserman, H. H.
Tetrahedron Lett. 1995, 36, 7735. (d) Yoshida, J.; Yano, S.;
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(e) Kaye, P. T.; Meakins, G. D.; Smith, A. K.; Tirel, M. D. J.
Chem. Soc., Perkin Trans. 1 1983, 1677.
1H NMR (400 MHz, CDCl3/TMS): d = 8.35 (d, J = 8.5 Hz, 2 H),
8.17 (d, J = 8.5 Hz, 2 H), 5.61 (s, 1 H), 4.31 (q, J = 7.2 Hz, 2 H),
1.26 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3/TMS): d = 186.8, 166.4, 150.8, 137.9,
130.3, 123.9, 63.6, 46.0, 13.8.
MS (ESI): m/z = 338 and 340 (M + Na+).
(5) (a) Stotter, P. L.; Hill, K. A. Tetrahedron Lett. 1972, 13,
4067. (b) Khan, A. T.; Ali, M. A.; Goswami, P.; Choudhury,
L. H. J. Org. Chem. 2006, 71, 8961. (c) Curran, D. P.;
Bosch, E.; Kaplan, J.; Newcomb, M. J. Org. Chem. 1989, 54,
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67, 7429. (f) Das, B.; Venkateswarlu, K.; Mahender, G.;
Mahender, I. Tetrahedron Lett. 2005, 46, 3041.
Acknowledgment
This study was supported by a grant-in-aid for scientific research
from the CSIR, (No. 01(2108)/07/EMR-II New Delhi, India.). K.J.
thanks CSIR, New Delhi for a Senior Research Fellowship.
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