An expedient protocol for conversion of olefins to α-bromo/iodoketones using IBX and NBS/NIS

Article abstract of DOI:10.1016/j.tetlet.2009.03.032

A variety of olefins have been shown to undergo conversion to the corresponding α-bromo/iodoketones when reacted with NBS/NIS and IBX in DMSO at room temperature. While the reaction is found to occur rapidly with e-rich arylolefins leading to the corresponding haloketones in 65-95% yields in 0.3-3.0 h, those containing e-withdrawing groups are found to yield diketones concomitantly, such that the latter are the exclusive products over extended duration of the reactions.

Full text of DOI:10.1016/j.tetlet.2009.03.032

Tetrahedron Letters 50 (2009) 2493–2496
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Tetrahedron Letters
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An expedient protocol for conversion of olefins to
IBX and NBS/NIS
a-bromo/iodoketones using
*
Jarugu Narasimha Moorthy , Kalyan Senapati, Nidhi Singhal
Department of Chemistry, Indian Institute of Technology Kanpur 208 016, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A variety of olefins have been shown to undergo conversion to the corresponding a-bromo/iodoketones
Received 30 January 2009
Revised 5 March 2009
Accepted 6 March 2009
Available online 13 March 2009
when reacted with NBS/NIS and IBX in DMSO at room temperature. While the reaction is found to occur
rapidly with e-rich arylolefins leading to the corresponding haloketones in 65–95% yields in 0.3–3.0 h,
those containing e-withdrawing groups are found to yield diketones concomitantly, such that the latter
are the exclusive products over extended duration of the reactions.
Ó 2009 Elsevier Ltd. All rights reserved.
a
-Haloketones are indispensable intermediates in organic syn-
protocol involving olefin conversion cost effective. Incidentally, the
number of procedures known for the conversion of olefins to -bro-
thesis. They are conveniently converted to a number of important
a
compounds. For example, they are transformed into (i) aldols ste-
mo/iodoketones is rather limited; a-iodoketones have been synthe-
reospecifically in the presence of Cr(II) salts,1 (ii)
a
-allyl carbonyl
sized by the reaction of olefins with I2/silver chromate,19 I2/
compounds by reacting with allyl gallium/indium reagents,2 (iii)
arylacetic acids through Ag-assisted rearrangement of the primary
pyridinium dichromate/molecular sieves,20 and IþðcollidineÞ2BF4ꢀ/
DMSO.21 Arylolefins such as styrenes have been converted to
a-iod-
or secondary
using EtZnCH2I.4 They are exploited in the conversion of vinylsil-
anes to ketones,5 ,b-unsaturated amides,6 etc.
-allylation of
In general, -haloketones are prepared from ketones or olefins.
Insofar as the synthesis of -bromoketones from ketones is con-
a
-bromo-alkylarylketones,3 and (iv) b-diketones
oacetophenones by UV irradiation in the presence of molecular io-
dine and oxygen.22 We are aware of only two procedures for the
c
a
preparation of
of olefins with sodium bromite in acetic acid has been reported to
afford
-bromoketones.23 Vanadium-catalyzed bromination of ole-
a-bromoketones directly from olefins; treatment
a
a
a
cerned, a variety of procedures have been reported in addition to
fins has been reported to afford a-bromoketones, but in very less
the protocol involving the reaction of ketones directly with Br2 in
yield.24 A common procedure that leads to both
ocarbonyl compounds is still scarce.
a-bromo and iod-
AcOH.7 For example,
a-bromoketones have been prepared by the
reaction of ketones with (i) silica gel-supported dioxane-dibromide
under microwave irradiation conditions,8 (ii) [hydroxy(tosyl-
oxy)iodo]benzene (HTIB) followed by MgBr2 under microwave
irradiation,9 (iii) N-methylpyrrolidin-2-one hydrotribromide
(MPHT),10 (iv) CuBr2 in ethyl acetate at reflux conditions,11 etc.
They have also been prepared by employing NBS in the presence
of trimethylsilyl trifluoromethanesulfonate (TMS-OTf).12 In a simi-
lar manner, a number of synthetic procedures are known for direct
In our continuing investigations on synthetic transformations
mediated by IBX,25 we recently reported that benzyl bromides
can be conveniently transformed into benzaldehydes by reacting
with IBX in DMSO.25c Mechanistically, we suggested that benzyl
bromides might undergo nucleophilic substitution with IBX
O
OH
conversion of ketones to their corresponding a-iodoketones, which
I
O
include the reaction of ketones with molecular iodine directly13a or
in combination with an additional reagent, for example, I2–ceric
ammonium nitrate (CAN),13b I2–HgCl2,14 I2–SeO2,15 I2/urea/
O
O
O
O
H
I
IBX
X
O
R
R
H2O2,16 I2–trimethylorthoformate,17 etc. As in the synthesis of
a-
DMSO
bromoketones, NIS has also been employed together with PTS for
the conversion of ketones to their
-halo derivatives.18
In general, direct conversion of olefins to -bromo/iodoketones
is synthetically advantageous than that involving ketones. Besides,
the fact that the olefins are less expensive than ketones renders the
a
OH
I
a
O
O
R
+
IBA
O
* Corresponding author. Tel.: +91 512 2597438; fax: +91 512 2597436.
E-mail address: moorthy@iitk.ac.in (J.N. Moorthy).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.03.032

2494
J. N. Moorthy et al. / Tetrahedron Letters 50 (2009) 2493–2496
O
leading to monoalkoxyperiodinane, which collapses to the alde-
hyde and iodosobenzoic acid (IBA) (Scheme 1). In extension of
these studies, we envisaged that the halonium species derived
from the reaction of olefins with NBS/NIS could be attacked by
IBX, as shown in Scheme 2, leading to alkoxyperiodinanes, which
N
I
I
R2
O
R2
R1
O
R1
DMSO
collapse to
a-halocarbonyl compounds. Herein, we report that
the olefins do undergo consecutive halogenation and oxidation
IBX
NH
reactions to afford
yields.
a-halocarbonyl compounds in excellent isolated
O
path b
path a
In our initial experiments with 2-methylstyrene, the reaction
was conducted in DMSO at room temperature with 1.1 and 1.0–
1.5 equiv of NBS/NIS and IBX, respectively. While the formation
of 2-halopropiophenone was readily observed, incomplete conver-
sion of the olefin was noted even after 1–2 h of the reaction. Ex-
tended reaction times to ensure complete conversion of the
starting olefin were found to lead to the slow formation of the
diketone, which was reasoned to arise as a result of Kornblum oxi-
dation mediated by the DMSO solvent.26 The use of excess IBX was
found to minimize the formation of the diketone product and yield
O
O
O
O
I
I
I
O
O
O
O
R2
H
R1
R1
H
R2
I
a
-halocarbonyl compound quantitatively. Evidently, the excess IBX
OH
I
O
O
reagent leads to rapid conversion of the olefin, whereby rather
slow formation of diketone product is minimized. Thus, by
employing 2.0 equiv of IBX and 1.1 equiv of NBS/NIS, the conver-
R2
+
R1
I
O
IBA
sion of a variety of olefins to the corresponding
a-halocarbonyl
compounds was investigated.27 The results of consecutive haloge-
nation and oxidation reactions of olefins with NBS/NIS and IBX in
DMSO are given in Table 1.
Scheme 2.
Table 1
Results of conversion of olefins to the corresponding a
-bromo/iodoketones with IBX and NBS/NISa
Entry
1
Substrate
Reagent
Time (h)
Product
Yield (%)
83
O
Me
Me
NBS
1.1
0.7
0.3
0.2
4.0
2.5
0.4
0.3
Br
O
Me
O
2
3
4
5
6
7
8
NIS
84
I
Me
Me
Me
NBS
NIS
92
Br
MeO
MeO
MeO
Br
O
70b
84c
61c
88
I
O
Me
Me
NBS
NBS
NBS
NIS
O
Br
O
Me
Me
O2N
O
O2N
O
O
Br
I
95

J. N. Moorthy et al. / Tetrahedron Letters 50 (2009) 2493–2496
2495
Table 1 (continued)
Entry
Substrate
Reagent
NBS
Time (h)
3.0
Product
Yield (%)
79
O
O
9
10
11
12
13
14
15
16
17
18
19
20
21
Br
NIS
NBS
NIS
NBS
NIS
NBS
NIS
NBS
NIS
NBS
NIS
NBS
NIS
3.0
1.0
3.0
1.0
1.0
3.0
2.5
0.5
1.5
3.0
1.5
0.5
0.5
69
93
84
91
76d
88e
90
88
86
72
83
65f
82
I
O
Br
O
I
O
Me
Br
Me
O
I
Me
O
Br
O
O
I
Br
Me
Me
Me
Me
O
O
O
I
Me
Me
O
O
Br
O
I
O
Br
O
I
22
a
All the reactions were conducted on 1–2 mmol of olefin at room temperature (25–35 °C) by employing 1.1 and 2.0 equiv of NBS/NIS and IBX, respectively.
b
c
d
e
f
From 1H NMR analysis of the reaction mixture, a rearranged aldehyde (cf. Eq. 1) was found to be formed in ca. 25%.
The reaction was run at 60–65 °C to ensure complete conversion of the olefin.
The diketone product was isolated in 10% yield.
Conversion was 67%.
Conversion was 83%.
As can be seen in Table 1, a variety of olefins, with the exception
of p-bromo- and p-nitro-2-methylstyrenes (entries 5 and 6), react
with NBS/NIS and IBX at room temperature to yield
iodoketones in 65–95% isolated yields; for the bromo- and
a
-bromo/

2496
J. N. Moorthy et al. / Tetrahedron Letters 50 (2009) 2493–2496
nitro-substituted 2-methylstyrenes, the diketone was found to be
formed concomitantly with the formation of -haloketones (en-
Acknowledgments
a
tries 5 and 6). A similar scenario was observed for their reaction
with NIS as well. Thus, the reaction in these cases was run at 60–
J.N.M. is thankful to the Department of Science and Technology
(DST), India for financial support. K.S. is grateful to UGC for a senior
research fellowship.
65 °C until the initially formed
the diketone. Evidently, the e-withdrawing substituents remark-
ably modify the reactivity of -haloketones with DMSO. It is note-
a-haloketone was converted to
a
References and notes
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substituents.26 Otherwise, a comparison of the results of 2-methyl-
styrene with those of the p-methoxy-substituted derivative (en-
tries 1–4) suggests that e-rich olefins lead to haloketones quite
rapidly and in excellent isolated yields.
The reactions of 2-methylstyrene and cyclohexene with NIS/IBX
in DMSO-d6 were monitored directly by 1H NMR spectroscopy. In
particular, the formation of regioisomeric haloketone, cf. path b,
Scheme 2, was found to be completely absent in the case of 2-
methylstyrene. In a similar manner, for all the aryl or alkyl olefins,
the crude product mixtures were analyzed by 1H NMR to establish
the lack of formation of the regioisomeric product.
While our investigations were in progress, Yadav et al. re-
ported that olefins as well as terminal alkynes can be converted
to
applicable only to the preparation of
a
-haloketones with I2/IBX in water.28 While this protocol is
a-iodoketones, we have
found that the procedure is of limited substrate-scope in that
it does not work well for olefins that are substituted. For exam-
ple, the reaction of 2-methylstyrene under the reported condi-
tions of the reaction, that is, I2 (1.0 equiv)/IBX (1.2 equiv)/H2O,
rt, 4 h, was found to lead to as many as four products as re-
vealed by 1H NMR spectroscopy (Eq. 1). In contrast, the proce-
dure disclosed herein is not only convenient, but also enables
the accessibility of both
a-bromo and iodoketones in high yields
with a common procedure.
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27. Representative procedure: To a clear solution of IBX (2 mmol) in 2–3 mL of
DMSO was added the olefin (1 mmol) followed by NXS (1.1 mmol). The
reaction mixture was stirred for the duration mentioned in Table 1.
Subsequently, the reaction was poured into water and extracted with
chloroform. After the usual work-up, the product was isolated by rapid
silica-gel column chromatography.
O
O
O
CH3
CH3
CH3
+
+
I
CH3
I2 / IBX
ð1Þ
CH3
CHO
H2O
O
Although IBX was discovered a century ago, its true potential in
accomplishing diverse synthetic transformations has begun to be
explored only in recent times. The facile conversion of olefins to
haloketones reported herein, albeit limited to e-rich olefins, will
undoubtedly expand the ambit of synthetic transformations med-
iated by IBX.
28. Yadav, J. S.; Reddy, B. V. S.; Singh, A. P.; Basak, A. K. Tetrahedron Lett. 2008, 49,
5880–5882.