Direct conversion of olefins into α-bromo ketones using O-iodoxybenzoic acid and tetraethylammonium bromide

Article abstract of DOI:10.1055/s-0030-1259090

Utilizing full potential of IBX, a mild, selective, and facile method has been developed for the direct conversion of olefins into the corresponding α-bromo ketones by using 1.1 equivalents each of o-iodoxybenzoic acid and tetraethylammonium bromide. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1259090

LETTER
81
Direct Conversion of Olefins into a-Bromo Ketones Using O-Iodoxybenzoic
Acid and Tetraethylammonium Bromide
D
irec
t
Conver
w
sion of Olefins to
a-BromoK
p
etone
s
nil S. Deshmukh, Kiran H. Chaudhari, Krishnacharya G. Akamanchi*
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai 400019, India
Received 8 July 2010
R1
R2
O
R1
R2
Abstract: Utilizing full potential of IBX, a mild, selective, and fac-
ile method has been developed for the direct conversion of olefins
into the corresponding a-bromo ketones by using 1.1 equivalents
each of o-iodoxybenzoic acid and tetraethylammonium bromide.
IBX, TEAB
r.t., anhyd CH2Cl2
Br
1
2
Key words: o-iodoxybenzoic acid, tetraethylammonium bromide,
a-bromo ketone
Scheme 1 Direct conversion of olefin into a-bromo ketone with
IBX and TEAB
When cyclohexene (entry 2) was treated with 1.1 equiva-
lents of an equimolar ratio of IBX/TEAB in anhydrous
CH2Cl2 it gave a 75% yield of a-bromocyclohexanone
within 5 minutes. As illustrated in Table 1, using these re-
action conditions, a variety of olefins was successfully
converted into a-bromo ketones and the generality of the
reaction was established.16,17 A variety of substrates such
as aliphatic and alicyclic olefins, as well as allyl and vinyl
ethers underwent rapid direct oxidative transformation to
give a-bromo ketones in good yields.
Direct oxidative transformation of olefins to a-halo ke-
tones provides 1,2-difunctionalized synthons useful for
construction of heterocyclic rings such as imidazoles,1a
oxazoles,1b thiazoles,1c triazoles,2a benzofurans,2b 1,4-
benzodioxans,2c pyrazines,2d and others.3 The few meth-
ods available for direct conversion of olefins to a-halo ke-
tones include oxidative hydrolysis of vinyl bromides with
aqueous N-bromosuccinimide,4 treatment of enol ethers
and acetates with lead(IV) acetate in the presence of metal
halides,5 treatment of olefins with sodium bromite in ace-
tic acid,6 and vanadium-catalyzed bromination of olefins.7
The regioselectivity of the transformation was established
using terminal olefins when only a-bromo ketones were
obtained in the absence of the isomeric a-bromoaldehydes
as evidenced by 1H NMR analysis (entries 4–6, 8, 9). One
noteworthy result is the successful conversion of iminos-
tilbene into its bromo ketone derivative (entry 10), an in-
termediate for the antiepileptic drug oxcarbamazepine.
The lower yield (45%) for this conversion is due to com-
peting reaction with 5-carboxamide moiety to form imi-
nostilbene.12a
Recently, two new methods have emerged using hyperva-
lent iodine(V) reagent IBX in combination with NBS or
NIS8 and iodine.9 In the first cases, 2 equivalents of IBX
are required to achieve high yields of a-halo ketones and
avoid formation of diketones, whereas with the IBX and
iodine system, 1.1 equivalents were sufficient. IBX has
the potential to effect two sequential oxidations by step-
wise conversion to o-iodosobenzoic acid, a hypervalent
iodine(III) oxidant, and subsequently to the recyclable end
product o-iodobenzoic acid. Both these reported methods
do not make use of this potential of IBX and, instead, a
combination of oxidants has been used to effect the direct
transformation. Utilizing the full potential of IBX in ef-
fecting sequential oxidative transformations is highly de-
sirable and herein we describe the successful utilization of
the full potential of IBX in combination with TEAB for
facile and direct conversion of olefins into a-bromo ke-
tones under mild conditions in very good yields
(Scheme 1).
When the reaction was carried out with styrene, multiple
products including 1,2-dibromo-1-phenylethane and 2-
bromo-1-phenylethanol along with small amount of bro-
mo ketone were formed as evidenced by GC-MS analysis.
No satisfactory results were obtained even after change of
solvent or increase in reaction temperature.
In conclusion, a simple, high-yielding, and regioselective
method for direct transformation of olefins into a-bromo
ketones has been developed utilizing the full oxidizing po-
tential of IBX in combination with TEAB under mild con-
ditions.
Our research group is engaged in the development of syn-
thetic methodologies using hypervalent iodine(V) re-
agents and has used the IBX or DMP and TEAB Acknowledgment
combination to perform several transformations including
We sincerely thank the University Grant Commission (UGC) India
for financial Support. We are grateful to M/s Omkar Chemicals,
Badlapur, Thane, India, for a generous gift of IBX.
oxidative brominations,10 sulfoxidation,11 and one-carbon
dehomologative transformations.12
SYNLETT 2011, No. 1, pp 0081–0083
x
x.
x
x.
2
0
1
1
Advanced online publication: 07.12.2010
DOI: 10.1055/s-0030-1259090; Art ID: D18210ST
© Georg Thieme Verlag Stuttgart · New York

82
S. S. Deshmukh et al.
LETTER
Table 1 Oxidative Bromination of Olefines by Using IBX and TEABa
Entry
1
Substrate
Productb
Time (min)
5
Yield (%)c
O
74
Br
O
2
3
5
5
75
70
Br
O
Br
O
4
5
5
5
92
90
Br
O
Br
O
6
7
5
91
65
Br
O
O
10
O
Br
O
O
O
Br
8
9
15
15
74
74
O
O
O
Br
Cl
Cl
O
Br
10
180
45
N
N
O
NH2
O
NH2
a Reactions were carried out on 5 mmol scale at r.t. except for entry 10 which was carried out at 40 °C.
b All the products were characterized by IR and NMR.
c Isolated yield.
(7) Moriuchi, T.; Yamaguchi, M.; Kikushima, K.; Hirao, T.
Tetrahedron Lett. 2007, 48, 2667.
(8) Moorthy, J. S.; Senapati, K.; Singhal, N. Tetrahedron Lett.
2009, 50, 2493.
(9) Yadav, J. S.; Reddy, B. V. S.; Singh, A. P.; Basak, A. K.
Tetrahedron Lett. 2008, 49, 5880.
References and Notes
(1) (a) Marek, A.; Kulhanek, J.; Ludwig, M.; Bures, F.
Molecules 2007, 12, 1183. (b) Loughlin, W. A. Aust. J.
Chem. 1998, 51, 875. (c) Hantzsch, A.; Weber, J. H. Ber.
Dtsch. Chem. Ges. 1887, 20, 3118.
(2) (a) Cho, J.; Kim, K. J. Heterocycl. Chem. 1992, 29, 1433.
(b) Reddy, V. V.; Sampath, R. P.; Ashok, D. Synth.
Commun. 2000, 30, 1825. (c) Habermann, J.; Ley, S. V.;
Scicinski, J. J.; Scott, J. S. J. Chem. Soc., Perkin Trans. 1
1999, 2524. (d) Waly, M. A. Acta Chim. Slov. 2008, 55, 343.
(3) Katritzky, A. R.; Pozharskii, A. F. Handbook of
Heterocyclic Chemistry, 2nd ed.; Pergamon: New York,
2000.
(10) Ramnarayanan, G. V.; Shukla, V. G.; Akamanchi, K. G.
Synlett 2002, 2059.
(11) Shukla, V. G.; Salgaonkar, P. D.; Akamanchi, K. G. J. Org.
Chem. 2003, 68, 5422.
(12) (a) Bhalerao, D. S.; Mahajan, U. S.; Chaudhari, K. H.;
Akamanchi, K. G. J. Org. Chem. 2007, 72, 662. (b)Bellale,
E. V.; Bhalerao, D. S.; Akamanchi, K. G. J. Org. Chem.
2008, 73, 9473.
(13) (a) Dictionary of Organic Compounds, 6th ed.; Chapman
and Hall Electronic Publishing House: London, 1996.
(b) Dubois, J.-E.; El-Alaoui, M.; Toullec, J. J. Am. Chem.
Soc. 1981, 103, 5393.
(4) Morton, H. E.; Leanna, M. R. Tetrahedron Lett. 1993, 34,
4481.
(5) Motohanshi, S.; Satomi, M.; Fujimoto, Y.; Tatsuno, T.
Synthesis 1982, 1021.
(6) Kageyama, T.; Tobito, Y.; Katoh, A.; Ueno, Y.; Okawara,
M. Chem. Lett. 1983, 12, 1481.
Synlett 2011, No. 1, 81–83 © Thieme Stuttgart · New York

LETTER
Direct Conversion of Olefins to a-Bromo Ketones
83
(14) (a) Kajigaeshi, S.; Kakinami, T.; Okamoto, T.; Fujisaki, S.
Bull. Chem. Soc. Jpn. 1987, 60, 1159. (b) Gerta, C.;
Williams, J. M. J. Synlett 2003, 124.
(60 MHz, CDCl3): d = 1.25–2.51 (m, 8 H), 3.82–4.13 (dd,
J = 1.92 Hz, 1 H).
2-Bromocyclooctanone (Entry 3)
(15) (a) Illig, C.; Subasinghe, N.; Hoffman, J.; Wilson, K.;
Rudolph, M.; Marugan, J. US 2002/37915 (A1), 2002.
(b) Andrew, P. T.; Allott, C. P.; Gibson, K. H.; Major, J. S.;
Masek, B. B.; Oldham, A. A.; Ratcliffe, A. H.; Roberts, D.
A.; Russell, S. T.; Thomason, D. A. J. Med. Chem. 1992, 35,
877. (c) Roland, H. Helv. Chim. Acta 1987, 70, 1955.
(16) General Experimental Procedure for Direct Conversion
of Olefins into a-Bromo Ketones
Liquid.13b IR (neat): nmax = 1730, 685 cm–1. 1H NMR (60
MHz, CDCl3): d = 1.25–1.59 (m, 8 H), 2.17–2.52 (m, 4 H),
4.08–4.17 (t, J = 2.9 Hz, 1 H).
1-Bromoocta-2-one (Entry 4)
Liquid.14a IR (neat): nmax = 1730, 686 cm–1. 1H NMR (300
MHz, CDCl3): d = 0.91–1.10 (t, J = 9.6 Hz, 3 H), 2.26–2.00
(m, 10 H), 3.74 (s, 2 H).
1-Bromo-3,3-dimethylbutan-2-one (Entry 6)
Liquid.14b IR (neat): nmax = 1730, 690 cm–1. 1H NMR (300
MHz, CDCl3) d = 1.14 (s, 9 H), 3.69 (s, 2 H).
1-Bromo-3-phenoxypropan-2-one (Entry 8)
Liquid.15a IR (neat): nmax = 1737, 668 cm–1. 1H NMR (60
MHz, CDCl3): d = 4.46 (s, 2 H), 5.10 (s, 2 H), 6.99–7.34 (m,
5 H).
1-Bromo-3-(4-chlorophenoxy)propan-2-one (Entry 9)
Liquid.15b IR (neat): nmax = 1738, 668 cm–1. 1H NMR (300
MHz, CDCl3): d = 4.46 (s, 2 H), 5.10 (s, 2 H), 7.03 (dd,
J = 8.1 Hz, 2 H), 7.38 (dd, J = 6.4 Hz, 2 H).
10-Bromo-11-oxo-10,11-dihydro-5H-
To a stirred suspension of IBX (5.5 mmol) and TEAB (5.5
mmol) in anhydrous CH2Cl2 was added the olefine (5
mmol). Within 5–15 min the reaction mixture turned from
yellow to colorless and homogeneous, indicating completion
of reaction (monitored by TLC). The reaction mixture was
diluted with CH2Cl2 (25 mL) and washed with sat. NaHCO3
(2 × 25 mL), followed by NaHSO3 (25 mL), and brine (25
mL). The organic layer was separated, dried over anhyd
Na2SO4, filtered, and solvent was evaporated under reduced
pressure to give the crude bromo ketone. The crude product
was purified by column chromatography using silica gel
(60–120), eluting with EtOAc–PE (1:99).
dibenzo[b,f]azepine-5-carboxamide (Entry 10)
Solid; mp 89 °C.15c IR (KBr): nmax = 3377, 3325, 3020,
1726, 1696, 744 cm–1. 1H NMR (60 MHz, CDCl3): d = 6.59
(s, 1 H), 6.99–7.92 (m, 8 H).
(17) Spectroscopic Data for Selected a-Bromo Ketones
2-Bromocyclohexanone (Entry 2)
Liquid.13a IR (neat): nmax = 1731, 740, 680 cm–1. 1H NMR
Synlett 2011, No. 1, 81–83 © Thieme Stuttgart · New York