Molecular sieves as an efficient and recyclable catalyst for bromolactonization and bromoacetoxylation reactions

Article abstract of DOI:10.1016/j.tetlet.2010.04.113

Bromolactonization of unsaturated acids and bromoacetoxylation of olefins proceeded smoothly in the presence of molecular sieves and N-bromosuccinimide. The molecular sieves can be recycled and reused, and the halogen carrier can be recovered effectively.

Full text of DOI:10.1016/j.tetlet.2010.04.113

Tetrahedron Letters 51 (2010) 3433–3435
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Tetrahedron Letters
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Molecular sieves as an efficient and recyclable catalyst for
bromolactonization and bromoacetoxylation reactions
*
Feng Chen, Xiaojian Jiang, Jun Cheng Er, Ying-Yeung Yeung
3 Science Drive 3, Department of Chemistry, National University of Singapore, Singapore 117543, Singapore
a r t i c l e i n f o
a b s t r a c t
Article history:
Bromolactonization of unsaturated acids and bromoacetoxylation of olefins proceeded smoothly in the
presence of molecular sieves and N-bromosuccinimide. The molecular sieves can be recycled and reused,
and the halogen carrier can be recovered effectively.
Received 18 March 2010
Revised 20 April 2010
Accepted 27 April 2010
Available online 14 May 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Electrophilic bromination of alkenes is a fundamental transfor-
mation in organic synthesis. The reactions are typically conducted
in aqueous base using bromine or N-bromosuccinimide (NBS) as
the halogen source.1 An important research direction is the devel-
opment of a solid base or acid as a green and recyclable catalyst.
Attempts to catalyze the same reaction with recycled molecular
sieves were successful without significant loss of reactivity (Table
1, entries 8 and 9).
In addition to 4-pentenoic acid (1), we also examined the lact-
onization of several unsaturated acids and good yields of the ex-
pected products were obtained (Table 2). An exo-mode of
cyclization was favored under kinetic conditions, in which the cis
3
Some methods such as SiO2/NBS,2 Tl2CO3/Br2 and Amberlyst/
NBS4 have been reported. However, recent studies have shown that
the resource demands and amount of waste produced by many
new halogenation methods are significantly higher than the stan-
dard process, especially if recycling of the halogen-carrying agent
(e.g., succinimide) is not efficient.5 Herein we describe a resource
efficient process for bromolactonization and bromoacetoxylation
using molecular sieves (MS) and NBS.
Table 1
Bromolactonization of 4-pentenoic acid (1) catalyzed by various molecular sieves
O
O
Molecular sieves are commonly used to absorb water and other
small molecules.6 To our delight, we found that molecular sieves
were able to catalyze bromolactonization and bromoacetoxylation
reactions. Initially, the bromolactonization of 4-pentenoic acid (1)
with NBS was carried out at room temperature. Without any cata-
lyst, the reaction was complete in 54 h (Table 1, entry 1). In the
presence of 3 Å molecular sieves (400 mg per mmol), the bromol-
actonization reaction proceeded to completion in just 5 min (Table
1, entry 2).7 Upon further examination, we were able to reduce the
catalyst loading to 20 mg per mmol of 1, producing lactone 2 in
98% yield in 4.5 h (Table 1, entry 7).8 It is important to note that
the lactonization still proceeded smoothly on 1.0 g scale (Table 1,
entry 10).9 In addition, in the absence of solvent the reaction was
complete in 3 h in 92% yield.10 Among the molecular sieves exam-
ined (3 Å, 4 Å, 5 Å, and 13 X), 3 Å MS gave the best results (Table 1,
entries 12–14).
NBS, molecular sieves
CH2Cl2, rt, dark
OH
O
Br
1
2
Entry
Molecular sieves
Loading (mg/mmol)
Time
Yielda (%)
1
2
3
4
5
6
7
None
3 Å
3 Å
3 Å
3 Å
3 Å
3 Å
3 Å
3 Å
3 Å
3 Å
4 Å
5 Å
13 X
0
400
300
200
100
40
20
20
20
20
54 h
99
99
99
98
98
99
98
97
92
93
92
97
90
93
5 min
10 min
20 min
30 min
75 min
4.5 h
4.5 h
4.5 h
9 h
8b
9c
10d
11e
12
13
14
20
20
20
20
3
10 h
23 h
7.5 h
The work-up procedure was extremely simple, involving filtra-
tion of the MS, precipitation of the succinimide, and removal of the
solvent by distillation. The isolated product and the recycled
halogen carrier were extremely pure (>99% purity by 1H NMR).
a
b
c
Isolated yields.
Reaction using first time recycled molecular sieves.
Reaction using second time recycled molecular sieves.
Reaction conducted using 1.0 g (10 mmol) of the substrate.
Reaction conducted without using solvent.
d
e
* Corresponding author. Tel.: +65 65167760; fax: +65 67791691.
E-mail address: chmyyy@nus.edu.sg (Y.-Y. Yeung).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.04.113

3434
F. Chen et al. / Tetrahedron Letters 51 (2010) 3433–3435
Table 2
Bromolactonization of unsaturated acids 3–6
NBS, 3 Å MS,
CH2Cl2, rt, dark
Products 7-10
Substrates 3-6
Entrya
Substrate
Product
Cat. loading (mg/mmol)
Time (h)
Yieldb (%)
O
O
OH
Br
O
1
20
7
94
7
3
OH
H
O
2
3
100
9
9
83
93
O
4
O
Br
H
8
O
OH
OH
Ph
Ph
O
20
20
O
O
Ph
Br
5
9
O
O
4
8
91
Me
Ph
Me
6
Br
10
a
Reaction conditions: substrate (0.5 mmol), NBS (89 mg, 0.5 mmol), 3 Å MS (10 mg), CH2Cl2 (2 mL, 0.25 M).
Isolated yield.
b
stereochemistry at the ring junction of the bridged (Table 2, entry
1) and fused (Table 2, entry 2) lactones was preserved.11 The ste-
reocontrol in entry 4 (Table 2) could be attributed to the five-mem-
bered ring transition state in which the less bulky methyl group
remained at the pseudo-axial position.12
Examination of intermolecular bromoacetoxylation reactions of
various olefins confirmed the effectiveness of this protocol (Table
3).13 In entries 3 and 4, Markovnikov-type addition was observed.
In general, the intermolecular bromoacetoxylation required higher
MS loading in order to achieve a reasonable reaction rate.
Table 3
Bromoacetoxylation of olefins 11–16
NBS, 3 Å MS,
CH2Cl2, rt, dark
Products 17-22
Substrates 11-16 + AcOH
Entrya
Substrate
Product
Cat. loading (mg/mmol)
Time (h)
2
Yieldb (%)
96
Br
1
200
200
OAc
11
17
Br
2c
16
99
OAc
12
Ph
18
OAc
3d
400
400
12
12
90
80
Br
Br
13
Ph
Ph
19
Ph
Ph
4d
Ph
14
OAc
20

F. Chen et al. / Tetrahedron Letters 51 (2010) 3433–3435
3435
Table 3 (continued)
Entrya
Substrate
Ph
Product
Cat. loading (mg/mmol)
Time (h)
24
Yieldb (%)
Ph
OAc
Ph
Ph
21
5
400
400
90
67
15
Br
Br
OAc
22a
C4H9
16
OAc
Br
C4H9
(1 : 1)
C4H9
6
12
22b
a
Reaction conditions: substrate (1.0 mmol), NBS (178 mg, 1.0 mmol), AcOH (57 lL, 1.0 mmol), CH2Cl2 (4 mL, 0.25 M).
Isolated yield.
cis:trans ratio was 2:1.
4 equiv of AcOH were used.
b
c
d
28, 207; (c) Schmid, G. H.; Garrat, D. G. In The Chemistry of Double Bonded
Functional Groups; Patai, S., Ed.; Wiley: New York, 1977; p 725. Suppl. A; Part 2.
2. Konishi, H.; Aritomi, K.; Okano, T.; Kiji, J. Bull. Chem. Soc. Jpn. 1989, 62,
591–593.
3. Cambie, R. C.; Rutledge, P. S.; Somerville, R. F.; Woodgate, P. D. Synthesis 1988,
1009–1011.
4. Goldberg, Y.; Alper, H. J. Mol. Catal. 1994, 88, 377–383.
5. Eissen, M.; Lenoir, D. Chem. Eur. J. 2008, 14, 9830–9841.
6. Fieser; Fieser. In Reagents for Organic Synthesis; Wiley & Sons: New York, 1967;
Vol. 1. p 730.
7. The molecular sieves were purchased from Aldrich and used as received
without further treatment. Molecular sieves from other companies including
Alfa and Acros worked equally well.
Towards a mechanistic understanding of the reaction, we spec-
ulate the origin of the catalytic ability is due to the mild basicity of
the molecular sieves. A simple basicity test showed approximately
pH 9–10 for all the molecular sieves.14 We rationalize that the MS
deprotonate the carboxylic acid to provide a nucleophilic carboxyl-
ate, which facilitates the lactonization and bromoacetoxylation.
Nevertheless, base-sensitive esters and lactones tolerate the reac-
tion conditions. In addition, b-bromolactone 10, which has been
known to readily undergo dehydrobromination under mildly basic
conditions, was isolated in high yield.13
In summary, we have developed an efficient, column- and
extraction-free bromolactonization of unsaturated carboxylic acids
using NBS and 3 Å MS. The protocol can also be applied to the
intermolecular bromoacetoxylation of olefinic substrates. The cat-
alyst and the halogen carrying agent can be recycled effectively
thereby demonstrating a resource efficient halogenation process.
The application of this procedure to other reactions is under
investigation.15
8. Representative procedure for the bromolactonization: to
a solution of 4-
pentenoic acid (1) (102 L, 1.0 mmol) and 3 Å molecular sieves (20 mg) in
l
CH2Cl2 (4 mL) was added N-bromosuccinimide (178 mg, 1.0 mmol) at room
temperature. The resulting suspension was stirred vigorously for 4.5 h and
filtered. The residue was washed with CH2Cl2 to recover the molecular sieves.
The combined filtrate was concentrated under reduced pressure. The white
solid paste obtained was diluted with n-hexanes (10 mL), filtered, and
concentrated under reduced pressure to give lactone 2 (178 mg, 99%). The
residue was dried to yield succinimide (121 mg, 99%).
9. The longer reaction time was due to the unoptimized rate of stirring the
suspension.
10. A shaker was used instead of a magnetic stirrer as the reaction suspension was
sticky.
11. Ranganathan, S.; Muraleedharan, K. M.; Vaish, N. K.; Jayaraman, N. Tetrahedron
2004, 60, 5273–5308.
12. Garnier, J. M.; Robin, S.; Rousseau, G. Eur. J. Org. Chem. 2007, 20,
3281–3291.
13. All the products were characterized and the physical data were in full
accordance with literature values.
Acknowledgment
We thank the FRC grant (No. 143-000-384-133) from the Na-
tional University of Singapore.
References and notes
14. pH values were measured by stirring the suspension of molecular sieves in
water for 10 min before testing using pH paper.
1. (a) de la Mare, P. B. D.; Bolton, R. Electrophilic Additions to Unsaturated Systems,
2nd Ed.; Elsevier: New York, 1982; (b) Ruasse, M.-F. Adv. Phys. Org. Chem. 1993,
15. Preliminary results indicated that 5 Å MS catalyzed the bromoetherification of
4-penten-1-ol in 66% yield.