Intermolecular Halogenation/Esterification of Alkenes with N-Halosuccinimide and Acetic Acid Catalyzed by 1,4-Diazabicyclo[2.2.2]octane

Article abstract of DOI:10.1002/adsc.201700117

1,4-Diazabicyclo[2.2.2]octane (DABCO) is a suitable Lewis base that acts as an organocatalyst in the activation of N-chlorosuccinimide (NCS) towards the chlorination of alkenes. The chloriranium ion formed from NCS and the alkene, can be intermolecularly opened by a nucleophile, such as acetic acid, to produce highly functionalized trans-chloro esters in high yields. The protocol is also applied to the synthesis of chlorohydrins and chloro ethers using water or methanol as nucleophiles instead of acetic acid. Brominated analogs can also be synthesized from alkenes and N-bromosuccinimide (NBS) in the presence of various basic catalysts. However, the reaction patterns seem to be remarkably different. The catalytic performance of bases in the bromoesterification of alkenes was found to be strongly affected by their Br?nsted basicity, suggesting that acetyl hypobromite, formed in situ from NBS and acetic acid, acts as a real brominating agent in these systems. (Figure presented.).

Full text of DOI:10.1002/adsc.201700117

Title: Intermolecular Halogenation/Esterification of Alkenes with N–
Halosuccinimide and Acetic Acid Catalyzed by DABCO
Authors: Laura S. Pimenta, Elena Gusevskaya, and Eduardo Alberto
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10.1002/adsc.201700117
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Intermolecular Halogenation/Esterification of Alkenes with N–
Halosuccinimide and Acetic Acid Catalyzed by DABCO
Laura S. Pimenta, Elena V. Gusevskaya and Eduardo E. Alberto*
Department of Chemistry, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil;
E-mail: albertoee@ufmg.br
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. DABCO (1,4-diazabicyclo[2.2.2]octane) is a However, the reaction pattern seems to be remarkably
suitable Lewis base that acts as an organocatalyst in the different. The catalytic performance of bases in the
activation of N–chlorosuccinimide (NCS) towards bromoesterification of alkenes was found to be strongly
chlorination of alkenes. The chloriranium ion formed from affected by their Brønsted-basicity, suggesting that acetyl
NCS and the alkene, can be intermolecularly opened by a hypobromite, formed in situ from NBS and acetic acid, acts
nucleophile, such as acetic acid, to produce highly as a real brominating agent in these systems.
functionalized trans-chloroesters in high yields. The protocol
is also applied to the synthesis of chlorohydrins and
chloroethers using water or methanol as nucleophiles instead
of acetic acid. Brominated analogs can also be synthesized
from alkenes and N–bromosuccinimide (NBS) in the
presence of various basic catalysts.
Keywords: Alkenes; Bromination; Chlorination;
Chloroester; N–Chlorosuccinimide; Organocatalysis
substrates to prepare various chlorohydrin derivatives
whose nature depends on the reaction conditions and
reagents used.[7] Alternatively, these compounds can
be synthesized from alkenes by treatment with
chlorinating agents such as acetyl hypochlorite
(AcOCl),[8] chromyl chloride in acetyl chloride,[9]
trichloroisocyanuric acid[10] or with PhICl2 in wet
DMF.[11] Oxidation of chloride salts by
(diacetoxyiodo)benzene in the presence of a phase
transfer catalyst has also been reported for alkene
chloroesterification.[12]
Despite the recent advent of potent chlorinating
agents such as CDSC (Et2SCl•SbCl6)[13] and
Palau’chlor®,[14] N-chlorosuccinimide (NCS) remains
to be a useful, inexpensive and reliable reagent for
the electrophilic chlorination of organic substrates.[15]
NCS is a mild chlorine transfer agent and in most
cases it is not capable to chlorinate alkenes in
Introduction
Catalytic halenium ion (e.g., Cl+, Br+) transfer to
an alkene followed by nucleophilic ring opening of
the haliranium ion is a powerful tool to produce
highly functionalized organic compounds.[1] In the
past years, much effort has been devoted toward the
monohalogenation of alkenes. Perhaps, the most
studied transformation is the intramolecular
halolactonization and haloetherification of organic
substrates employing haloimide-based reagents (e.g.,
N-halosucciminide, N-halophthalimide).[2] These
processes have been extensively explored and
nowadays represent a consolidated method for the
alkene functional group transformation, even in an
asymmetric fashion.[3]
The intermolecular version of these reactions
delivers halohydrin, haloether or haloester derivatives. uncatalyzed reactions. This feature opens up the
Collectively, these substances represent a class of
privileged natural and synthetic compounds, which
find broad application in chemical and biological
processes.[4] Even though new approaches and
methodologies for the synthesis of bromohydrin and
related compounds have been well explored,[5] the
research for efficient ways to produce chlorinated
analogs still has plenty of room for improvement. For
instance, chloroester derivatives are most commonly
prepared by the catalytic ring opening of epoxides
with acid chlorides.[6] Diols can also be used as
possibility to better control the regio-, diastereo-, and
stereochemical outcome of the process by the
activation of NCS with an appropriate organocatalyst
(Lewis acid or base).[3b] Surprisingly just a few
reports in the literature account for the chlorination
and intermolecular functionalization of alkenes with
NCS:
products
such
as
chlorohydrins,[16]
chloroethers[17] and chloroamides[18] have been
prepared using this approach.
Accordingly, as part of our interest in the
halofunctionalization of organic substrates,[19] we
1
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10.1002/adsc.201700117
Advanced Synthesis & Catalysis
describe herein a simple, straightforward and efficient
protocol for the synthesis of chloroester starting from
alkenes. The method consists of the treatment of
starting materials with NCS in acetic acid in the
presence of catalytic amounts of DABCO. The
protocol can also be applied to the synthesis of
chlorohydrins, chloroethers and bromoesters from
alkenes (using in this case N-bromosuccinimide as a
source of bromine).
Entry
catalyst
AcOH
(equiv.) (%)[b]
Yield
(mol–%)
1
2
3
4
5
6
Ph3P (10)
Ph3PS (10)
Ph3PSe (10)
Pyridine (10)
2,4,6-Trimethylaniline (10)
DMAP (10)
2
2
2
2
2
2 ± 0
3 ± 0
NR[c]
NR[c]
NR[c]
6 ± 0
Results and Discussion
As a model reaction, the chloroesterification of
cyclohexene 1a was investigated using N–
chlorosuccinimide, acetic acid as the nucleophile and
10 mol–% of different Lewis bases as organocatalysts.
Representative results are shown in Table 1. All
experiments were performed in the dark at 20 ± 2 ºC
employing dichloromethane as the solvent. The
progress of the reaction was monitored by gas
chromatography using undecane as the internal
standard. Initially, a set of phosphorus, sulfur and
2
7
8
9
10
11[d]
12[e]
13[e]
4-Methylmorpholine
Triethylamine
DABCO (10)
DABCO (10)
DABCO (10)
DABCO (20)
None
2
2
2
5
5
10
10
4 ± 0
11 ± 1
46 ± 1
64 ± 0
76 ± 1
95 ± 1
NR[c]
[a]
Reaction conditions: cyclohexene (1.0 mmol), NCS (1.0
selenium-based
organocatalysts
was
tested.
mmol), AcOH (2.0 – 10.0 mmol), catalyst (10.0 – 20.0
mol–%, related to cyclohexene), undecane (internal
standard, 0.5 mmol) and dichloromethane (5.0 mL).
Reactions were performed during two hours, in the dark (in
an amber flask wrapped with an aluminium foil) at 20 ± 2
Unfortunately none of them was effective to promote
the desired conversion (Entries 1–3). Next, we turned
out our attention to nitrogen-based catalysts. Pyridine,
2,4,6-trimethylaniline,
4-methylmorpholine,
triethylamine and DMAP (4-dimethylamino-pyridine)
were tested and again, little if any catalytic activity
was observed after two hours of reaction (Entries 4–
8).
ºC (water bath). [b] GC yield (average for duplicate runs). [c]
[d]
NR = no reaction within two hours.
reaction. Reaction with 1.2 mmol of NCS. DMAP = 4-
dimethylamino-pyridine;
diazabicyclo[2.2.2]octane.
Six hours of
[e]
DABCO
=
1,4-
An encouraging result was obtained using 10 mol–
% of DABCO (1,4-diazabicyclo[2.2.2]octane) and
two equivalents of acetic acid: trans–chloroacetate 2a
was obtained in 46% yield (Entry 9). Increasing the
amount of acetic acid to five equivalents related to
cyclohexene as well as extending the reaction time to
6 hours resulted in higher yields of product (Entries
10 and 11). It can be seen that the reaction occurs
faster in the presence of increased amounts of AcOH
(Entries 9 and 10). The best reaction condition to
obtain chloroester 2a was achieved with 20 mol–% of
DACBO, a slight excess of NCS and 10 equivalents
of acetic acid. After a two-hour reaction, product 2a
was obtained in 95% yield (Entry 12). In a control
experiment under identical conditions, but without
the catalyst, no substrate conversion and no formation
of product 2a were detected (Entry 13). Other
catalysts and solvents were also screened, but
unfortunately, chloroacetate 2a was produced in
lower yields (the results are presented in the
supporting information). Noteworthy is that the
catalytic activity of organic bases in the
chloroesterification of cyclohexene did not correlate
at all with their Brønsted basicity. For example,
DMAP and pyridine showed much lower activity
than DABCO (Entries 4, 6 and 7).
With the optimized reaction conditions in hands,
control experiments were designed to better
understand the reaction mechanism (Scheme 1). It
was observed that after two hours of reaction the
experiments conducted in the dark or under the
daylight gave essentially the same yield of
chloroacetate 2a: 95% and 94%, respectively. A
similar result was obtained in the presence of 0.2
equivalents of BHT (butylated hydroxytoluene),
which is a radical inhibitor, suggesting that the
process involves the formation of ionic rather than
radical intermediates. These results point out for a
process that occurs mainly by an ionic pathway.
As the reaction occurs in acidic media and is
accelerated by DABCO, which can also act as a
Brønsted base and deprotonate acetic acid, one can
speculate that the chlorine transfer agent could be
acetyl hypochloride (AcOCl)[8] formed in situ from
NCS and the acetate ion, as shown in Scheme 1
(dotted box A). To check this hypothesis, we
swapped the organocatalyst/base DABCO by cesium
carbonate, an inorganic base strong enough to
deprotonate acetic acid and soluble in the reaction
media. However, in the reaction conducted with
Cs2CO3 instead of DABCO, no formation of product
2a was detected at all. This result suggests that acetyl
Table 1. Optimization of the reaction conditions for the
synthesis of chloroacetate 2a.[a]
2
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10.1002/adsc.201700117
Advanced Synthesis & Catalysis
hypochloride is not the real chlorinating agent acting
in our reaction.
The remaining nitrogen’s lone pair on 3 could act as a
Lewis base [21] and attack the chlorine atom of NCS to
produce succinimide and intermediate 4, the actual
chlorinating agent in the process. [22] The formation of
the chloroester can be rationalized by the subsequent
attack of the nucleophile (acetate or acetic acid) on
the chloriranium ion formed between 4 and the
alkene, delivering the final product and DABCO to
resume the catalytic cycle.
Another plausible explanation for the reaction
outcome could be the activation of NCS by the
interaction with a protonated DABCO species as
shown in Scheme 1 (dotted box B). The difference in
the pKa values of the compounds involved in the
reaction allows the formation, in appreciable
concentrations, only of the monoprotonated DABCO
derivative (pka of AcOH = 4.8 vs 3.0 and 8.8 for
protonated DABCO species). On the other hand, the
use of a stronger acid such as trifluoroacetic acid (pKa
of TFA = – 0.3) would permit the protonation of both
nitrogen atoms in the DABCO molecule making it
even more effective in the activation of NCS by this
manner. To verify this supposition, we performed the
reaction in the presence of various amounts of TFA.
At
equimolar
TFA/DABCO
concentration,
chloroester 2a was formed in a yield considerable
lower than in the absence of TFA.[20] Moreover,
further increase in the TFA concentration virtually
shouted down the chloroesterification of cyclohexene
catalyzed by DABCO. These results ruled out the
assumption that the activation of NCS could occur by
the interaction of N-chlorosuccinimide’s oxygen
atoms with the protonated molecule of the catalyst.
Scheme 2. Proposed reaction mechanism.
The proposed mechanism is additionally supported
by the observation that nitrogen-based compounds
which lack the second tertiary amine fragment (such
as 4-methylmorpholine and triethylamine, were
inefficient catalysts for this reaction (Table 1, Entries
7 and 8). Protonation by acetic acid seems to
inactivate these compounds toward the interaction
with NCS. It should also be mentioned that formation
of acetyl hypochlorite in the reaction solution cannot
be completely ruled out. However, the results
obtained indicate that the contribution of the reaction
pathway involving acetyl hypochlorite is not
significant under the conditions used.
To verify the substrate scope and limitations,
experiments with a set of different alkenes were
conducted under the conditions optimized for
cyclohexene. A small but important change in the
reaction conditions was made: instead of DCM, the
reactions were performed in glacial acetic acid, thus
avoiding the use of a strongly regulated chlorinated
solvent (Table 2). A two-hour reaction with
cyclohexene produced trans-chloroester 2a in 84%
yield. Methyl-cyclohexene, 1-octene and 2-hexene
(mixture of cis and trans) gave under the same
conditions the corresponding chloroacetates 2b, 2c
and 2d in a range of 53–95% yield. The product
derived from 1-octene was detected as a 3:1 mixture
of two regioisomers 2c and 2c’ isolated in a 95%
combined yield. On the hand, the reaction with 2-
hexene produced a complex mixture of isomers 2d.
Scheme 1. Effect of additives and/reaction conditions on
[a]
the chloroesterification of cyclohexene 1a.
reaction within two hours. BHT
hydroxytoluene; TFA = trifluoroacetic acid.
NR = no
butylated
=
Based on the obtained experimental evidences, we
proposed the following mechanism for the DABCO
catalyzed chloroesterification of alkenes with NCS
(Scheme 2). The first event in the sequence is
probably the Brønsted acid/base reaction between
DABCO and AcOH producing protonated species 3,
which seems to be the truly catalyst in this system.
Table 2. Substrate scope for the synthesis of chloroacetate
2.[a]
3
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10.1002/adsc.201700117
Advanced Synthesis & Catalysis
rotating opened carbocation rather than a cyclic
chloriranium ion as the preferred intermediate of the
electrophilic addition of chlorine to these substrates.
Additionally, E-stilbene was sparingly soluble in the
reaction media, even after the addition of DCM,
furnishing the product in a lower yield. A limitation
of the process was evidenced when an electron poor
alkene, methyl cinnamate, was tested as the starting
material: product 2k was not detected in the reaction
solution even after 24 hours. On the other hand, the
scope of this reaction can be extended to other
chlorohydrin derivatives by changing the solvent
(nucleophile) nature. Styrene gave the corresponding
chlorohydrin 2l and chloroether 2m in 71 and 82%
yields when the reaction was performed in aqueous
THF or in methanol, respectively. Preparative
reactions were successfully performed using 10 mmol
of styrene as starting material. Chlorinated products
2e, 2l and 2m were obtained in 63–74% yield.
Lastly, we investigated the bromoesterification of
cyclohexene with N–bromosuccinimide (NBS) and
AcOH[23] and compared the results with the
chlorination protocol. Cyclohexene was treated with
NBS in DMC solutions containing acetic acid and
catalytic amounts of various organic and inorganic
bases. In the blank reaction, without the catalyst
added, the main product detected after 60 minutes
was trans-1,2-dibromocyclohexane 6a obtained in
21% yield along with 4% of bromoacetate 5a (Table
3, Entry 1). The addition of catalytic amounts of
DMAP or DABCO (5 mol–%) resulted in drastic
changes in the reaction kinetics and product
distribution: after 15 minutes bromoacetate 5a was
obtained in 84% and 81% yields, respectively along
with small amounts of the dibrominated product 6a
(Entries 2 and 3). Pyridine, a less basic compound
than DMAP and DABCO, proved to be an inefficient
organocatalyst for this transformation showing nearly
the same results as the reaction without the catalyst
(Entries 4 vs. 1). The increase in the amount of
DABCO to 10 mol–% affected not only the reaction
rate, but also the product selectivity: bromoacetate 5a
was obtained in 93% yield along with only 1% of the
dibromide (Entry 5 vs. entry 3). On the other hand, in
a sharp contrast with the chlorination process, the
catalytic performance of cesium carbonate was
similar to those of DMAP and DABCO (cf. entry 6
with entries 2, 3 and 5). Moreover, sodium acetate,
sparingly soluble in the reaction mixture, was also
able to activate NBS and promote the formation of
bromoacetate 5a from cyclohexene in 55% yield
(Entry 7).
[a] Reaction conditions: substrate (1.0 mmol), glacial acetic
acid (2.0 mL), DABCO (22 mg, 0.2 mmol) NCS (160 mg,
1.2 mmol) at 20 ± 2 ºC (water bath, under the daylight).
Reaction times are given in parenthesis and yields are of
[b]
pure, isolated products.
Product obtained as a 2/1
mixture of diastereoisomers. [c] Product obtained as a 2.5/1
mixture of diastereoisomers.
[d]
Starting material: E–
stilbene, solvent: DCM/AcOH (1/1 v/v; 4.0 mL total),
[e]
product ratio: syn/anti = 1/1.
Starting material: Z–
[f]
stilbene, product ratio: syn/anti = 1/1.
Solvent =
[g]
H2O/THF (1/1 v/v; 2.0 mL total). Solvent: MeOH (2.0
mL).
Styrene derivatives were also subjected to the
reaction producing the corresponding chloroacetates
2e–g in ca. 80–90 % yields. Cinnamyl chloride was
also a suitable substrate for the reaction. Highly
functionalized dichloride acetate 2h was isolated in
68% yield after 4 hours of reaction. An attempt to
employ isoeugenol as substrate did not show
encouraging results. Formation of numerous products
was observed by GC with low selectivity. Due to the
complexity of the reaction mixture these products
were not identified. We suppose that the concomitant
chlorination at the aromatic ring occurs along with
the desired oxidation of the alkene. Converting
isoeugenol to its O-benzoyl derivative allowed to
perform the oxidation of the olefinic bond with an
acceptable selectivity: product 2j was isolated in 59%
yield. Reactions with E and Z stilbenes were also
efficient. It is noteworthy that from both stilbenes a
1:1 mixture of the corresponding syn and anti–
chloroesters 2j was obtained suggesting a freely
Table 3. Optimization of the reaction conditions for the
synthesis of bromoacetate 5a.[a]
4
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10.1002/adsc.201700117
Advanced Synthesis & Catalysis
Yield (%)[b]
5a 6a
from O-benzoyl-isoeugenol. Differently from what
was observed in the chloroacetoxylation, electron
poor methyl cinnamate was effectively converted to
the corresponding bromoacetate. Although a longer
reaction time was required for the full conversion of
the starting material, product 5h was isolated in 93%
yield.
Entry catalyst (mol–%) Time (min)
1
2
3
4
5
6
7
none
60
15
15
15
15
15
15
4 ± 0 21 ± 1
84 ± 2 3 ± 0
81 ± 1 6 ± 1
5 ± 1 19 ± 0
93 ± 1 1 ± 0
76 ± 2 2 ± 1
55 ± 2 1 ± 0
DMAP (5)
DABCO (5)
Pyridine (5)
DABCO (10)
Cs2CO3 (10)
AcONa (10)
Table 4. Substrate scope for the synthesis of bromoacetate
5.[a]
[a]
Reaction conditions: cyclohexene (1.0 mmol), NBS (1.0
mmol), AcOH (2.0 mmol), catalyst (5.0 – 10.0 mol–%,
related to cyclohexene), undecane (internal standard, 0.5
mmol) and DCM (5.0 mL). Reactions were performed in
the dark (in an amber flask wrapped with an aluminium
[b]
foil) at 20 ± 2 ºC (water bath).
duplicate runs).
GC yield (average for
These results indicate that differently from the
chloroesterification process, in the
bromoacetoxylation of alkenes with NBS and acetic
acid, the catalyst efficiency and product distribution
are directly related to the Brønsted-basicity of the
catalyst employed. The formation of bromoacetate 5a
seems to be the result of the reaction between
cyclohexene and acetyl hypobromite,[24] formed in
situ by the reaction between the acetate ion and NBS.
In other words, the role of the organocatalyst in the
bromination process more likely consists in the
deprotonation of acetic acid (thus favoring the
formation of acetyl hypobromite) rather than in the
direct participation in the halogen atom transfer from
NBS to alkene (Scheme 3).
[a] Reaction conditions: substrate (1.0 mmol), glacial acetic
acid (2.0 mL), DABCO (11 mg, 0.1 mmol) NBS (214 mg,
1.2 mmol) at 20 ± 2 ºC (water bath, in the dark: amber
flask wrapped with aluminum foil). Reaction times are
O
AcO
O
X = Br
X = Cl
H
N
N
N
X
N
N
– succinimide
– DABCO
OBr
given in parenthesis and yields are of pure, isolated
– succinimide
Cl
[b]
O
products.
Product obtained as a 5/1 mixture of
AcO
[c]
diastereoisomers. Product obtained as a 14/1 mixture of
diastereoisomers. [d] Product obtained as an 11/1 mixture of
diastereoisomers.
Scheme 3. Different activation types of NBS and NCS
with an organocatalyst (DABCO for instance) towards
haloesterification of alkenes.
Conclusion
Representative examples of brominated products
synthesized are depicted in Table 4. Likewise in the
reactions for the chlorination of alkenes, the use of
the strongly regulated chlorinated solvent DCM was
avoided. All the experiments were conducted in
glacial acetic acid solutions (substrate concentration
of 0.5 M) with 1.2 equivalents of NBS and 10 mol%
of the catalyst, in the dark at 20 ± 2 ºC. Trans-
bromoacetate 5a was isolated in 89% yield after the
oxidation of cyclohexene. The reaction with 1-octene
gave a 2/1 mixture of isomers 5b in 88% yield.
Styrene and its derivatives were successfully
converted to the corresponding bromoacetates 5c–e.
An interesting product, compound 5f, was obtained in
61% yield from cinnamyl chloride after a 4-hour
reaction. Product 5g was produced in a high yield
In summary, a simple and straightforward protocol
for the intramolecular chloro and bromoesterification
of alkenes employing acetic acid and N-
halosuccinimide was conceived. One of the
advantages of the developed procedure is the use of
acetic acid as solvent as well as the acetoxylating
reagent. In this regard, the use of an organic co–
solvent, particularly a chlorinated one can be avoided.
Among several organocatalysts tested, commercially
available DABCO proved to be a superior catalyst in
the chloroacetoxylation of cyclohexene. Control
experiments indicate that DACBO acts as a Lewis
base in the activation of NCS and is the “truly
chlorinating agent” in the process, participating
directly in the chlorine atom transfer from NCS to the
alkene molecule. The protocol can also be
5
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10.1002/adsc.201700117
Advanced Synthesis & Catalysis
conveniently extended to the preparation of
chloroethers or chlorohydrins by changing the solvent
by alcohols or water. On the other hand,
bromoesterification of alkenes using NBS is affected
to a greater extent by the Brønsted-basicity of the
catalyst, suggesting acetyl hypobromite as the real
brominating agent.
methanol (2.0 mL). No precautions were taken to
avoid light, oxygen or water on the reaction media.
The mixture was then stirred at 20 ± 2 ºC (water bath)
during 2 hours. The solvent was removed under
reduced pressure, and the product purified by silica
gel chromatography.
Optimization of the Bromoacetoxylation of
Cyclohexene: in an amber, screw capped 3 dram vial,
wrapped with aluminium foil, N-bromosuccinimide
(178 mg, 1.0 mmol) was added to a solution of
catalyst (0.05 – 0.10 mmol), undecane (107 µL, 0.5
mmol), glacial acetic acid (114 µL, 2.0 mmol) and
cyclohexene (101 µL, 1.0 mmol) in dichloromethane
(5.0 mL). The reaction was performed at 20 ± 2 ºC
(reaction vessel immersed in a water bath). No
precautions were taken to exclude oxygen or water
from the reaction media. After 15 minutes, the
reaction was quenched with NaHSO3 2M (0.5 mL).
The organic phase was separated, dried over MgSO4,
filtered and injected in the CG. The reported yields
represent an average of duplicate runs.
Experimental Section
Optimization of the Chloroacetoxylation of
Cyclohexene: in an amber, screw capped 3 dram vial,
wrapped with aluminium foil, N-chlorosuccinimide
(1.0 – 1.2 mmol) was added to a solution of catalyst
(0.1 – 0.2 mmol), undecane (107 µL, 0.5 mmol),
glacial acetic acid (2.0 – 10.0 mmol) and cyclohexene
(101 µL, 1.0 mmol) in dichloromethane (5.0 mL).
The reaction was performed at 20 ± 2 ºC (reaction
vessel immersed in a water bath). No precautions
were taken to exclude oxygen or water from the
reaction media. After two hours, the reaction was
quenched with NaHSO3 2M (0.5 mL). The organic
phase was separated, dried over MgSO4, filtered and
injected in the GC. The reported yields represent an
average of duplicate runs.
General Procedure for Bromoacetoxylation of
Alkenes: an amber, screw capped 3 dram vial,
wrapped with aluminium foil, was charged with
substrate (1.0 mmol), glacial acetic acid (2.0 mL),
DABCO (11 mg, 0.10 mmol) and N-
bromosuccinimide (214 mg, 1.2 mmol). The mixture
was then stirred at 20 ± 2 ºC (water bath) for the
appropriate amount of time (the progress of the
reaction was followed by gas chromatography). At
the end of the reaction, it was diluted with hexanes
(25 mL) and extracted with distilled water (3 x 10
mL). The organic phase was washed with Na2CO3
1M (1 x 10 mL), dried over MgSO4, filtered and the
solvents removed under reduced pressure. The
product was purified by silica gel chromatography.
Procedure for Chloroacetoxylation Of Alkenes: a
25 mL one-neck flask was charged with substrate (1.0
mmol), glacial acetic acid (2.0 mL), DABCO (22 mg,
0.2 mmol) and N-chlorosuccinimide (160 mg, 1.2
mmol). No precautions were taken to avoid light,
oxygen or water on the reaction media. The mixture
was then stirred at 20 ± 2 ºC (water bath) for the
appropriate amount of time (the progress of the
reaction was followed by gas chromatography). At
the end of the reaction, it was diluted with hexanes
(25 mL) and extracted with distilled water (3 x 10
mL). The organic phase was washed with Na2CO3
1M (1 x 10 mL), dried over MgSO4, filtered and the
solvents removed under reduced pressure. The Acknowledgements
product was purified by silica gel chromatography.
The authors are grateful to CNPq (grant number 303727/2014-4),
CAPES and FAPEMIG for financial support of this research.
Procedure for Chlorohydroxylation of Styrene: in
a 25 mL one-neck flask, N-chlorosuccinimide (160
mg, 1.2 mmol) was added to a mixture of DABCO
(22 mg, 0.2 mmol) and styrene (115 µL, 1.0 mmol) in
a mixture of distilled water (1.0 mL) and THF (1.0
mL). No precautions were taken to avoid light,
oxygen or water on the reaction media. The mixture
was stirred at 20 ± 2 ºC (water bath) during 2 hours.
The reaction mixture was then diluted with 30 mL of
AcOEt and washed with water (2 x 20 mL). The
combined organic phase was dried over MgSO4,
filtered and the solvents removed under reduced
pressure. The product was purified by silica gel
chromatography.
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10.1002/adsc.201700117
Advanced Synthesis & Catalysis
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7
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Advanced Synthesis & Catalysis
FULL PAPER
Intermolecular Halogenation/Esterification of
Alkenes with N–Halosuccinimide and Acetic Acid
Catalyzed by DABCO
Adv. Synth. Catal. Year, Volume, Page – Page
Laura S. Pimenta, Elena V. Gusevskaya and
Eduardo E. Alberto*
8
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