Novel catalytic bromolactonization of alkenoic acids using iodobenzene and Oxone

Article abstract of DOI:10.1002/jhet.617

The novel catalytic reaction for bromolactonization of alkenoic acids is reported. When iodobenzene is used as recyclable catalyst in combination with Oxone as terminal oxidant, the cyclization of various 4-pentenoic acids with sodium bromide is easily carried out in CF₃CH₂OH at room temperature and giving five-membered bromolactones in good yields.

Full text of DOI:10.1002/jhet.617

May 2011
Novel Catalytic Bromolactonization of Alkenoic Acids Using
695
R
Iodobenzene and OxoneV
Yan He,a Ye Pu,a Bo Shao,b and Jie Yana*
aCollege of Chemical Engineering and Materials Sciences, Zhejiang University of Technology,
Hangzhou 310032, People’s Republic of China
bCollege of Biological and Environmental Sciences, Zhejiang Shuren University,
Hangzhou 310015, People’s Republic of China
*E-mail: jieyan87@zjut.edu.cn
Received April 10, 2010
DOI 10.1002/jhet.617
Published online 22 February 2011 in Wiley Online Library (wileyonlinelibrary.com).
The novel catalytic reaction for bromolactonization of alkenoic acids is reported. When iodobenzene
R
is used as recyclable catalyst in combination with OxoneV as terminal oxidant, the cyclization of vari-
ous 4-pentenoic acids with sodium bromide is easily carried out in CF3CH2OH at room temperature and
giving five-membered bromolactones in good yields.
J. Heterocyclic Chem., 48, 695 (2011).
INTRODUCTION
reactions, a catalytic amount of iodoarene together with
a stoichiometric oxidant are used. Usually, iodobenzene
(PhI) is the most utilized iodoarene, m-chloroperbenzoic
Halolactonization serves as an important key reaction
in a variety of syntheses and has been studied exten-
sively [1]. Usually, alkenoic acids are used to construct
lactones in the reaction, which includes an electrophilic
addition of molecular halogens on the double bond, and
then following an intramolecular nucleophilic cycliza-
tion [2]. Molecular iodine is a nontoxic and easy to han-
dle solid, the iodolactonization is the most widespread
applied halolactonization. However, because molecular
bromine is a toxic, difficult to handle, low-boiling
lachrymatory liquid, and also a strong oxidant, the bro-
molactonization has some restrictions [3]. To improve
bromolactonization, N-bromosuccinimide in combination
with catalysts were used in place of molecular bromine
had been successful [4]; the complexes of bis(2,6-disub-
stitutedpyridine)bromonium triflates and dibromodiaryl-
selenium (IV) species were also used as the efficient
sources of positive bromine for bromolactonization [5];
NaBr and H2O2 with catalytic selenoxide, arylseleninic
acids, and organotellurides were found to be preferred
in the reactions [6]; Braddock et al. [7] reported a con-
venient method for the bromolactonization of 4-pentenoic
acid using hypervalent iodine reagent (diacetoxyiodo)-
benzene and lithium bromide.
R
acid, and OxoneV (KHSO4ꢀ2KHSO5ꢀK2SO4) are often
used as the terminal oxidants. In the catalytic reaction,
the oxidant generates the hypervalent iodine reagent
in situ, and after the oxidative transformation, the
reduced iodoarene is reoxidized.
Using catalytic hypervalent iodine reagents, some
new lactonizations have been reported: Liu and Tan [9]
investigated the iodobenzene-catalyzed iodolactonization
of alkenes in which sodium perborate monohydrate as
stoichiometric oxidant was used; Braddock et al. [10]
demonstrated that suitably ortho-substituted iodoben-
zenes can catalyze the intramolecular bromolactoniza-
tion of alkenes. Very recently, we found an efficient cat-
alytic sulfonyloxylactonization of alkenoic acids using
hypervalent iodine reagent [11]. To extend the catalytic
cyclization scope, we have investigated the catalytic
halolactonization of alkenoic acids. Herein, we would
like to report the novel catalytic bromolactonization of
R
alkenoic acids with iodobenzene as catalyst and OxoneV
as terminal oxidant.
Table 1 shows the results of the catalytic bromolacto-
nization of 4-pentenoic acid with 0.1 equiv. of iodoben-
zene at room temperature for 24 h, which indicates that
the yields of 5-(bromomethyl)-c-butyrolactone mainly
Recently, the catalytic utilization of hypervalent
iodine reagents is increasing in importance, with the
growing interest in the development of environmentally
benign synthetic transformations [8]. In these catalytic
depend on solvents and CF3CH2OH is the most effective
R
one (entries 4, 8–11). As a suitable oxidant, OxoneV is
the most preferred (entries 1–4). NaBr, KBr, and NH4Br
C
V
2011 HeteroCorporation

696
Y. He, Y. Pu, B. Shao, and J. Yan
Vol 48
Table 1
Results of the catalytic bromolactonization of 4-pentenoic acid with 0.1 equiv. of iodobenzene.
Entry
Brꢁ (1.5 equiv.)
Oxidant (1.0 equiv.)
Solvent
Yield (%)a
1
2
3
NaBr
NaBr
NaBr
NaBr
LiBr
NaBO3ꢀ4H2O
mCPBA
K2S2O8
CF3CH2OH
CF3CH2OH
CF3CH2OH
CF3CH2OH
CF3CH2OH
CF3CH2OH
CF3CH2OH
CH2Cl2
15
74
18
82
64
80
75
54
39
14
23
R
4
OxoneV
R
5
6
OxoneV
R
KBr
OxoneV
R
7
8
NH4Br
NaBr
NaBr
NaBr
NaBr
OxoneV
R
OxoneV
R
OxoneV
R
9
10
11
THF
CH3CN
DMF
OxoneV
R
OxoneV
a Isolated yield.
are efficient sources of bromine anion and usually NaBr
is the best choice (entries 4–7).
Under the optimum reaction conditions, the reactions of
found when 2-methyl-4-pentenoic acid was treated with
the hypervalent iodine reagent, the product was a mix-
ture of diastereomers, the ratios varied from 1.2 to
1.4:1. In our reaction protocol, we find when 1b is
used, the corresponding product is also a mixture of
diastereomers by examination of the 1H-NMR spectra
of bromolactones, the ratio is 2:1; while 3-methyl-4-
pentenoic acid (1c) is treated in the reaction, the ratio
for the obtained mixture of diastereomers is 58:42.
a series of 4-pentenoic acids (1) with equal equivalent of
R
OxoneV, 1.5 equiv. of NaBr, and 0.1 equiv. of iodoben-
zene in CF3CH2OH for 24 h are investigated (Scheme 1),
the results are summarized in Table 2.
It is shown from Table 2 that most reactions provide
good to excellent yields of five-membered bromolac-
tones (entries 1–4). When 2-cyclopentene-1-acetic acid
(1e) is used in the reaction, the corresponding product is
in middle yield due to the restrictive effect of the ring
(entry 5). Similar treatment of 3-butenoic acid and
trans-3-hexenoic acid, the reactions only obtain the
unsaturated lactones not the desired bromolactones
The proposed mechanism for the catalytic cycle of bro-
molactonization is depicted in Scheme 2, which includes
the electrophilic addition of hypervalent iodine reagent on
the double bond, then an intramolecular nucleophilic cy-
clization is happened, and another nucleophilic bromolac-
tonization is followed. The reduced by-product of PhI is
1
(entries 6 and 7). It is found by H-NMR technique that
regenerated into hypervalent iodine reagent by the oxida-
R
the desired five-membered lactones and four-membered
lactones are first formed, which then transformed into
the unsaturated lactones during workup procedure by
elimination. Efforts for preparation of the sex-membered
lactone of 6-bromomethyltetrahydropyran-2-one using
5-hexenoic acid are partially successful, and the desired
product is separated in only 27% of yield, which is
much lower than that of five-membered bromolactones.
Koser et al. [12] in 1988 reported a lactonization
using the hypervalent iodine reagent, [hydroxyl
((bis(phenyloxy)phosphoryl)oxy)iodo]benzene, and they
tion of OxoneV and used in the cycle.
In summery, we have successfully developed an effi-
cient catalytic bromolactonization of alkenoic acids
R
using catalyst of PhI and OxoneV as terminal oxidants,
which has some advantages such as mild reaction condi-
tions, simple procedure, and good yields for five-mem-
bered bromolactones. Furthermore, the scope of catalytic
use of hypervalent iodine reagents in organic synthesis
could be extended.
EXPERIMENTAL
Scheme 1
General procedure for the catalytic bromolactonization
of alkenoic acids.. To CF3CH2OH (2 mL), alkenoic acid 1
R
(0.3 mmol), OxoneV (0.3 mmol), sodium bromide (0.45
mmol), and iodobenzene (0.03 mmol) are added. The mixture
is stirred at room temperature for 24 h and then separated on a
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R
May 2011
Novel Catalytic Bromolactonization of Alkenoic Acids Using Iodobenzene and OxoneV
697
Table 2
Results of the catalytic bromolactonization of alkenoic acids.
Entry
1
Alkenoic acids (1)
Bromolactones (2)
Yield (%)a
82
2
3
4
96
95
95
5
6
63
23
38
7
a Isolated yield.
Scheme 2
silica gel plate using (3:2 hexane-ethyl acetate) as eluent to
give 2 in good to excellent yields.
5-(Bromomethyl)-c-butyrolactone (2a). Oil [7]. 1H-NMR
(500 MHz, CDCl3): 4.78–4.73 (m, 1H), 3.59–3.52 (m, 2H),
2.69–2.63 (m, 1H), 2.61–2.54 (m, 1H), 2.49–2.42 (m, 1H),
2.15–2.11 (m, 1H). 13C-NMR (125 MHz, CDCl3): 176.1, 77.9,
34.0, 28.3, 26.2. IR (film): m ¼ 2962, 1777, 1168, 1023, 917
cmꢁ1. MS (EI, m/z, %): 179 (13), 181 (14), 99 (100).
2-Methyl-5-(bromomethyl)-c-butyrolactone (2b). Oil [13].
1H-NMR (500 MHz, CDCl3): 4.78–4.73 (2b1) and 4.61–4.55
(2b2) (m, 1H), 3.60–3.57 (2b1) and 3.54–3.50 (2b2) (m, 2H),
2.86–2.81 (2b1) and 2.78–2.71 (2b2) (m, 1H), 2.66–2.60 (2b1)
and 2.44–2.38 (2b2) (m, 1H), 2.13–2.07 (2b1) and 1.75–1.68
(2b2) (m, 1H), 1.31 (d, J ¼ 7.0 Hz, 3H), 13C-NMR (125 MHz,
CDCl3): 179.1, 178.4, 75.9, 75.8, 35.6, 35.5, 34.0, 33.8, 33.7,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

698
Y. He, Y. Pu, B. Shao, and J. Yan
Vol 48
Nicolaou, K. C.; Seitz, S. P.; Sipio, W. J.; Blount, J. F. J Am Chem
Soc 1979, 101, 3884; (d) Yoshida, M.; Suzuki, T.; Kamigata, N. J
Org Chem 1992, 57, 383.
33.5, 16.1, 15.0. IR (film): m ¼ 2975, 1775, 1182, 1157, 1016,
927 cmꢁ1. MS (EI, m/z, %): 193 (100), 195 (93).
3-Methyl-5-(bromomethyl)-c-butyrolactone (2c). Oil [14].
1H-NMR (500 MHz, CDCl3): 4.72–4.69 (2c1) and 4.30–4.27
(2c2) (m, 1H), 3.63–3.44 (m, 2H), 2.84–2.50 (m, 2H), 2.34
(dd, J ¼ 17.0, 3.5 Hz, 2c1) and 2.25 (dd, J ¼ 18.0, 8.0 Hz,
2c2) (1H), 1.23 (d, J ¼ 7.0 Hz, 2c1) and 1.17 (d, J ¼ 7.0 Hz,
2c2) (3H). 13C-NMR (125 MHz, CDCl3): 175.6, 175.3, 84.5,
80.9, 37.2, 36.6, 34.1, 34.0, 32.5, 32.3, 28.6, 19.6, 18.3, 13.0.
IR (film): m ¼ 2969, 1781, 1156, 998, 940 cmꢁ1. MS (EI, m/z,
%): 193 (12), 195 (13), 71 (100).
[2] (a) Anaral, L.; Melo, S. C. J Org Chem 1973, 38, 800; (b)
Cambie, R. C.; Rutledge, P. S.; Somerville, R. F.; Woodgate, P. D.
Synthesis 1988, 1009.
[3] (a) Budaxari, S.; O’Neil, M. J.; Smith, A.; Heckelman, P.
E.; Kinneary, J. F., Eds. The Merck Index, 12th ed.; Merck: Rahway,
1996; (b) Goehring, R. R. In Encyclopaedia of Reagents for Organic
Synthesis; Paquette, L. A., Ed.; Wiley: New York, 1995; Vol. 1, p
679.
[4] (a) Mellegaard, S. R.; Tunge, J. A. J Org Chem 2004, 69,
8979; (b) Mellegaard-Waetzig, S. R.; Wang, C.; Tunge, J. A. Tetrahe-
dron 2006, 62, 7191; (c) Ahmad, S. M.; Braddock, D. C.; Cansella,
G.; Hermitage, S. A. Tetrahedron Lett 2007, 48, 915; (d) Ahmad, S.
M.; Braddock, D. C.; Cansella, G.; Hermitage, S. A.; Redmonda, J.
M.; White, A. J. P. Tetrahedron Lett 2007, 48, 5948.
[5] (a) Cui, X.-L.; Brown, R. S. J Org Chem 2000, 65, 5653;
(b) Leonard, K. A.; Zhou, F.; Detty, M. R. Organometallics 1996, 15,
4285.
2, 2-Dimethyl-5-(bromomethyl)-c-butyrolactone (2d). Oil
[15]. 1H-NMR (500 MHz, CDCl3): 4.67–4.61 (m, 1H), 3.57
(dd, J ¼ 10.5, 5.0 Hz, 1H), 3.50 (dd, J ¼ 11.0, 6.5 Hz, 1H),
2.28 (dd, J ¼ 13.0, 6.5 Hz, 1H), 1.94 (dd, J ¼ 13.0, 10.0 Hz,
1H), 1.30 (s, 3H), 1.10 (s, 3H), 0.89 (s, 3H). 13C-NMR (125
MHz, CDCl3): 180.9, 74.6, 41.9, 40.5, 33.6, 24.9 (d, J ¼ 3.8
Hz). IR (film): m ¼ 2971, 1773, 1206, 1139, 1111, 1026, 915
cmꢁ1. MS (EI, m/z, %): 207 (100), 209 (96).
[6] (a) Goodman, M. A.; Detty, M. R. Organometallics 2004,
23, 3016; (b) Bennett, S. M.; Tang, Y.; McMaster, D.; Bright, F. V.;
Detty, M. R. J Org Chem 2008, 73, 6849; (c) Drake, M. D.; Bateman,
M. A.; Detty, M. R. Organometallics 2003, 22, 4158; (d) Detty, M.
R.; Higgs, D. E.; Nelen, M. I. Org Lett 2001, 3, 349.
[7] Braddock, D. C.; Cansella, G.; Hermitage, S. A. Synlett
2004, 461.
6-Bromohexahydrocyclopenta[b]furan-2-one (2e). Oil [10].
1H-NMR (500 MHz, CDCl3): 5.08 (d, J ¼ 6.0 Hz, 1H), 4.54
(d, J ¼ 4.0 Hz, 1H), 3.19–3.14 (m, 1H), 2.88 (dd, J ¼ 18.5,
10.0 Hz, 1H), 2.50–2.00 (m, 4H), 1.63–1.58 (m, 1H). 13C-
NMR (125 MHz, CDCl3): 176.4, 90.5, 52.8, 36.0, 35.9, 33.1,
31.3. IR (film): m ¼ 2968, 1778, 1159, 1014, 875. MS
(EI, m/z, %): 205 (5), 207 (4), 79 (100).
[8] (a) Dohi, T.; Kita, Y. Kagaku 2006, 61, 68; (b) Richard-
son, R. D.; Wirth, T. Angew Chem Int Ed Engl 2006, 45, 4402; (c)
Dohi, T.; Minamitsuji, Y.; Maruyama, A.; Hirose, S.; Kita, Y. Org
Lett 2008, 10, 3559; (d) Ochiai, M. Chem Rec 2007, 7, 13; (e) Uya-
nik, M.; Ishihara, K. Chem Commun 2009, 2086; (f) Dohi, T.; Kita,
Y. Chem Commun 2009, 2073.
2(5H)-Furanone (2f). Oil [16]. 1H-NMR (500 MHz,
CDCl3): 7.61–7.59 (m, 1H), 6.19–6.17 (m, 1H), 4.93–4.92
(m, 2H). IR (film): m ¼ 3100, 1780, 1750, 1600, 1450, 1350,
1330, 1150, 1090, 1030 cmꢁ1
.
5-Ethyl-2(5H)-Furanone (2g). Oil [16]. 1H-NMR (500
MHz, CDCl3): 7.47–7.45 (m, 1H), 6.14–6.12 (m, 1H), 5.03–
5.00 (m, 1H), 1.88–1.82 (m, 1H), 1.77–1.70 (m, 1H), 1.02
(t, J ¼ 1.9 Hz, 3H). IR (film): m ¼ 3110, 2995, 1810, 1260,
[9] Liu, H.-G.; Tan, C.-H. Tetrahedron Lett 2007, 48, 8220.
[10] Braddock, D. C.; Cansella, G.; Hermitage, S. A. Chem
Commun 2006, 2483.
1170, 1150, 1110, 920 cmꢁ1
.
[11] Yan, J.; Wang, H.; Yang, Z.-P.; He, Y. Synlett 2009, 2669.
[12] Koser, G. F.; Lodaya, J. S.; Ray, D. G., III; Kokil, P. B. J
Am Chem Soc 1988, 110, 2987.
[13] Tamaru, Y.; Mizutani, M.; Furukawa, Y.; Kawamura, S.;
Yoshida, Z.; Yanagi, K.Minobe, M. J Am Chem Soc 1984, 106, 1079.
[14] Ireland, R. E.; Anderson, R. C.; Badoud, R.; Fitzsimmons,
B. J.; McGarvey, G. J.; Thaisrivongs, S.; Wilcox, C. S. J Am Chem
Soc 1983, 105, 1988.
Acknowledgment. Financial support from the Natural Science
Foundation of China (Project 21072176) is greatly appreciated.
[15] Rood, G. A.; DeHaan, J. M.; Zibuck, R. Tetrahedron Lett
1996, 37, 157.
REFERENCES AND NOTES
[16] Shah, M.; Taschner, M. J.; Koser, G. F.; Rach, N. L.
Tetrahedron Lett 1986, 27, 4557.
[1] (a) Bartlett, P. A.; Meyerson, J. J Am Chem Soc 1978, 100,
3950; (b) Haas, J.; Piguel, S.; Wirth, T. Org Lett 2002, 4, 297; (c)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet