Green Synthesis of Haloformates from Olefins Using Formic Acid as Reactant, Protonic Acid, and Solvent

Article abstract of DOI:10.1055/s-0037-1610028

Bromoformates and iodoformates are successfully synthesized in high yields with regioselectivity and stereoselectivity by using ZnAl-BrO ₃^- layered double hydroxides (LDHs) and KX (X = Br, I) in the presence of formic acid (HCOOH). T

Full text of DOI:10.1055/s-0037-1610028

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2018, 29, A–F
letter
A
en
L. Wang et al.
Letter
Synlett
Green Synthesis of Haloformates from Olefins Using Formic Acid
as Reactant, Protonic Acid, and Solvent
ZnAl-BrO3–-LDHs
KI
ZnAl-BrO3–-LDHs
KBr
OCHO
OCHO
Ligeng Wang*
Hualong Zhang
Qin Yu
0
0
0
0
0-
0
0
2
5-
0
7
3
6-
2
8
1
R
R
R
R1
R1
R1
I
HCOOH, 25 °C
HCOOH, 40 °C
Br
10 examples
up to 90%
13 examples
up to 91%
Chun Feng
Jun Hu*
R = H, CH2OH, COOH,
COOCH3, Ph
High yield
High regioselectivity and stereoselectivity
College of Chemical Engineering, Zhejiang University of Technology,
Zhejiang 310014, P. R. of China
R
1 = Aryl, alkyl
wanglg@zjut.edu.cn
hjzjut@zjut.edu.cn
Received: 05.02.2018
Accepted after revision: 02.05.2018
Published online: 07.06.2018
follow during the design of a reaction,11 the preparation of
all these halogenating reagents inevitably involves liquid
bromine and solid iodine. Therefore, scientists are actively
engaged to explore nonpolluting and safer redox protocols.
Recently, bromoformates were prepared by using NH4Br
and Oxone with excellent diastereoselectivity.12 Subse-
quently, Chevella and co-workers synthesized iodoformates
with NH4I and Oxone in the presence of DMF.13 Obviously,
DMF is profoundly preferred by chemists because of its out-
standing solubility as well as nucleophilicity, being widely
applied to the type of reaction. Nonetheless, it is the inter-
solubility with H2O and organic solvents in any proportion
that cause the inefficient separation for organic products,
which stimulates the further research for a synthetic method
that is efficient, simple, and easy to handle.
DOI: 10.1055/s-0037-1610028; Art ID: st-2018-w0079-l
Abstract Bromoformates and iodoformates are successfully synthe-
sized in high yields with regioselectivity and stereoselectivity by using
–
ZnAl-BrO3 layered double hydroxides (LDHs) and KX (X = Br, I) in the
presence of formic acid (HCOOH). The protocol exploits the versatile
function of formic acid as solvent, nucleophilic reagent, and acidic me-
dium simultaneously, simplifying the reaction and separation of the
products.
Key words olefins, formic acid, bromoformates, iodoformates, regio-
selectivity, stereoselectivity
Halofunctionalization of olefins plays an important role
in organic synthesis.1 Compounds (halohydrins, β-halo-
esters) from this kind of reaction are prepared by adding
halogen and a valuable nucleophilic reagent to the carbon–
carbon double bond in a regioselective and stereoselective
manner.2 There are a number of vicinal halo-formyloxylated
synthons as precursors for many vital compounds which
can be applied to pharmaceuticals3 and organic synthesis,4
such as epoxides with high optical activity.5 Moreover,
halogen atoms can also be substituted by nucleophilic
reagents to transform other significant compounds6
through the SN1 or SN2 pathway.7
Chemists have increasingly paid attention to the vicinal
halo-formyloxylation of carbon–carbon double bond, ex-
ploring many protocols which are focused on the variety of
halogenating reagents. Only De Souza et al. reported the
iodoformyloxylation of olefins employing TCCA, NBSac.8
However, many other protocols based on bromoformyloxyl-
ation have constantly been put forward. For instance, NBS9
and TsNBr210 have been reported for performing simple and
efficient bromoformyloxylation. Even though trouble-free
strategies and user-friendliness should be the standard to
Formic acid (HCOOH), known as the simplest organic
carboxylic acid,14 possesses the property of dissolving or-
ganic and mineral salts simultaneously. As the target prod-
ucts are fleetly separated from the reaction system, formic
acid has been severed as reaction medium to promote or-
ganic synthetic transformations.15 In the meanwhile,
HCOO– dissociating from HCOOH has an ideal nucleophilici-
ty for formyloxylation reactions.16 Moreover, formic acid
creates a moderately acidic environment in which highly
–
active halogen sources generated from ZnAl-BrO3 -LDHs17/KX
(X = Br, I) react with substrates in situ.18 Herein, we report a
protocol of bromoformyloxylation and iodoformyloxylation
–
of olefins using ZnAl-BrO3 -LDHs and KX (X = Br, I) in the
presence of formic acid, providing a large amount of bro-
mide and iodine in a short time. In comparison with other
protocols, this method is not only a more exciting approach
slowly generating the halogen source in situ, but also pro-
vides a suitable chemical environment in which the full ad-
vantage of formic acid is taken with regard to acidity, solu-
bility, nucleophilicity.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

B
L. Wang et al.
Letter
Synlett
The bromoformyloxylation reaction was initially stud-
ied by using styrene as a model substrate in the presence of
Table 1 Screening and Optimization of Bromoformyloxylationa
ZnAl-BrO3 -LDHs [1.0×10–3 mol (BrO3 )/g (ZnAl-BrO3 -LDHs)],17
KBr, HCOOH, and the outcome of the reaction was investi-
gated under different conditions by varying the tempera-
ture and volume of solvent. The corresponding results are
illustrated in Table 1. Apparently, styrene only provided the
bromoformyloxylation product in 53% yield at 25 °C, with
use of 10 mL of formic acid (entry 1). Moreover, nearly half
of the by-product was dibromination product, which was
determined by NMR spectroscopy. Because of the almost
equal nucleophilicity of HCOO– and Br–at relatively low
temperature, the system accessed the competitive nucleo-
philic reaction and produced dibromination and bromo-
formyloxylation products with the same probability. Yields
markedly improved as the temperature increased. Impor-
tantly, styrene could afford the corresponding product in
90% at 40 °C (entry 3) because then the nucleophilicity of
HCOO– absolutely surpassed that of Br– according to our
hypothesis. On the contrary, yields decreased by elevating
the temperature and the product was obtained in 85% at
45 °C and in 69% at 50 °C (entries 4–5). It is a small amount
of H2O that is produced from the interaction between
–
–
–
OCHO
KBr, ZnAl-BrO3–-LDHs
HCOOH
H
Br
2a
1a
Entry
Temp (°C)
HCO2H (mL)
Yield (%)b
1
2
3
4
5
6
7
25
35
40
45
50
40
40
10
10
10
10
10
8
53
77
90
85
69
86
73
6
a Reaction conditions: styrene (1a) (2 mmol), ZnAl-BrO3–-LDHs (0.8 g), KBr
(1.6 mmol).
b Isolated yields after column chromatography.
1-(naphthalen-2-yl)ethyl formate in 89 and 88% yield,
respectively (2b, 2c).
–
–
HCOOH and ZnAl-BrO3 -LDHs for BrO3 , which acts as a
kind of nucleophilic reagent to compete with other nucleo-
philic species, such as HCOO– and Br–, which directly gener-
ates bromohydrins.19 Similarly, the results indicate that the
yields decreased with decreasing volume of solvent and the
products were obtained in 86% with 8 mL and in 73% with 6
mL of solvent (entries 6–7). Probably the denseness of the
reaction mixture, which increased as the volume of solvent
decreased in the biphasic formic acid–hydrotalcite mixture,
prevented a proper homogeneity of the reaction. Further-
more, the reduction of the volume of formic acid from 10 to
6 mL directly led to the decline of acidity and concentration
of HCOO– in the whole solution, which ultimately impacted
the nucleophilicity of HCOO– and the redox reaction be-
tween BrO3– and Br–. Consequently, the reaction conditions
were eventually settled as 0.4 equivalents BrO3– (calculated
4-Chlorostyrene, 4-bromostyrene, 4-acetoxystyrene
bearing electron-withdrawing groups with inductive effect
reacted smoothly, yielding the corresponding vicinal bromo-
formates in similar yields (2d–f). Moreover, olefin deriva-
tives with substituents at the β-position of terminal styrene
were investigated. Unsatisfyingly, cinnamyl alcohol gave
the corresponding erythro-bromoformate product in only
73% yield (2g) along with obvious by-product. However, cis-
stilbene gave the threo-bromoformate product in 90% yield
(2h). α,β-Unsaturated olefins, such as 4-methycinnamic
acid and methyl trans-cinnamate, performed well to afford
the desired erythro-bromoformate products (2i, 2j). Simi-
larly, the reaction of indene also achieved the trans-
addition product in 88% yield (2k). Furthermore, 2-ethen-
ylpyridine and 3-methy-2-buten-1-ol furnished the desired
bromoformate in 87 and 89% yield (2l, 2m), which primely
proved that the protocol can be applied to olefins bearing a
heterocyclic ring and simple alkenes.
–
according to the content of BrO3– intercalated in ZnAl-BrO3
-LDHs), 0.8 equivalents KBr, 10 mL of formic acid, at 40 °C.
A series of diverse derivatives were selected for explor-
ing the scope and generality of the bromoformyloxylation
process with the optimized reaction conditions established
from Table 1, and the results are shown in Scheme 1. Be-
cause alkyl and aryl groups activate the benzene ring, the
reactivity of the double bond at the para position increases
in a way. 2-Ethenylnaphthalene and 4-tert-butylstyrene
having an electron-donating group on the benzene ring
easily afforded the corresponding bromoformate products
2-bromo-1-(4-tert-butylphenyl)ethyl formate and 2-bromo-
Encouraged by the results of this vicinal bromoformy-
loxylation, we also considered iodoformyloxylation of ole-
fins under similar reaction conditions, because iodinated
organic compounds have significant applications. The iodo-
formyloxylation reaction was investigated by varying the
–
mass of ZnAl-BrO3 -LDHs with styrene being selected as a
model substrate at 25 °C, and the results are summarized in
Table 2. The iodoformyloxylation product of styrene was
obtained in only 38% yield (entry 1) with use of 0.35 g
–
ZnAl-BrO3 -LDHs which is the minimum mass when I– is
oxidized to I2 in an acidic environment.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

C
L. Wang et al.
Letter
Synlett
ZnAl-BrO3–-LDHs (0.4 equiv)
KBr (0.8 equiv)
OCHO
R
R
R1
R1
HCOOH, 40 °C
Br
1
2
R1 = aryl, alkyl
OCHO
OCHO
H
OCHO
OCHO
OCHO
H
H
H
H
Br
Br
Br
Br
Br
C4H9
Br
Cl
2a, 91%
2b, 89%
2c, 88%
2d, 85%
2e, 84%
OCHO
Br
OCHO
OCHO
OCHO
COOH
OCHO
H
COOCH3
OH
Br
Br
2j, 87% (J = 16)a
Br
Br
2i, 70% (J = 11.4)a
AcO
2f, 86%
2g, 73% (J = 15.9)a
2h, 90% (J = 4.6)a
OCHO
OCHO
Br
OCHO
N
H
OH
Br
Br
2k, 88% (J = 3.5)a
2l, 87%
2m, 89%
Scheme 1 Reaction conditions: substrate 1 (2 mmol), ZnAl-BrO3–-LDHs (0.8 g), KBr (1.6 mmol). Isolated yields after column chromatography. a J is the
coupling constant value of protons attached to the carbons bearing –OCHO and Br groups and was determined by 1H NMR spectroscopy.
Table 2 Screening and Optimization of Iodoformyloxylationa
this reaction system, optimal reaction conditions were
selected as 0.35 equivalents BrO3 , 1.1 equivalents KI, 10 mL
of formic acid, at 25 °C.
–
ZnAl-BrO3–-LDHs
KI (1.1 equiv)
OCHO
H
The protocol was examined for a range of styrene deriv-
atives and the results are shown in Scheme 2. The styrene
derivatives with electron-donating groups, such as methyl
and tert-butyl provided corresponding iodoformates in 88
and 90% yield (3b, 3c). In the meantime, 4-chlorostyrene, 4-
bromostyrene, and 4-acetoxystyrene, which bear electron-
withdrawing groups on the benzene ring, achieved the
products in 82, 87 and 85% yield, respectively (3d–f). In ad-
dition, olefin derivatives with substituents at the β-position
of terminal styrene also attained the corresponding iodo-
formates. Cinnamyl alcohol successfully gave the desired
erythro-iodoformate product in 76% yield (3g) and cis-stil-
bene provided the threo-iodoformate product in 79% yield
(3h). Indene classified as an internal aromatic olefin was
compatible with these reaction conditions, and the corre-
sponding product was obtained in 86% yield (3i).
The coupling constant (J) values of the two protons at-
tached to the adjacent carbon atoms mainly depend on the
dihedral angle of the two protons in the 1H NMR spectrum,
being calculated by the Karplus empirical formula (based
on experimental data): J = A + B cos Φ + C cos 2Φ (A = 7, B =
–1, C = 5). Generally, the coupling constant J is greater than
8 Hz when the dihedral angle is 0/180°. In the meantime,
the coupling constant J is less than 7 at 60°. Therefore, after
stereoselective bromoformyloxylation and iodoformyloxy-
altion of 1,2-disubsituted olefins, the coupling constant J of
protons attached to the carbons bearing –OCHO and Br/I
I
HCOOH, 25 °C
1a
3a
Entry
ZnAl-BrO3–-LDHs (g)
Yield (%)b
1
2
3
4
5
6
7
0.35
0.45
0.55
0.65
0.70
0.75
0.80
30
59
64
78
86
86
85
a Reaction conditions: styrene (1a) (2 mmol), KI (2.2 mmol), HCO2H (10 mL).
b Isolated yields after column chromatography.
–
Moreover, the yields increased as the mass of ZnAl-BrO3 -
LDHs was increased, attaining 59, 64 and 78% (entries 3–4).
Essentially, the yields continuously increased as the degree
of oxidation that represents the content of I+ decreased.
–
Markedly, 0.7 g ZnAl-BrO3 -LDHs (the minimum mass when
I– is oxidized to I+ in acidic medium) gave the highest yield
of 86% (entry 5). Apparently, yields tended to be stable
–
when the mass of ZnAl-BrO3 -LDHs exceeded 0.7 g (entries
6–7). Therefore, we assumed that olefins reacted with
iodine based on I– being oxidized to I+ by BrO3– intercalated
in the hydrotalcite. Consequently, to evaluate the scope of
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

D
L. Wang et al.
Letter
Synlett
ZnAl-BrO3–-LDHs (0.35 equiv)
KI (1.1 equiv)
OCHO
R
R
R1
R1
HCOOH, 25 °C
I
1
3
R1 = aryl, alkyl
OCHO
I
OCHO
OCHO
OCHO
OCHO
H
H
H
H
H
I
I
I
I
C4H9
Cl
Br
3a, 86%
3b, 88%
3c, 90%
3d, 82%
OCHO
3e, 87%
OCHO
OCHO
OCHO
OCHO
H
I
OH
OH
I
I
I
I
AcO
3f, 85%
3g, 76% (J = 15.9)a
3h, 79% (J = 7)a
3i, 86% (J = 3.5)a
3j, 88%
Scheme 2 Reaction conditions: substrate 1 (2 mmol), ZnAl-BrO3–-LDHs (0.7 g), KI (2.2 mmol). Isolated yields after column chromatography. a J is the
coupling constant value of protons attached to the carbons bearing –OCHO and I groups and was determined by 1H NMR spectroscopy.
groups in the 1H NMR spectrum can prove that the bromo-
formyloxylation and iodoformyloxyaltion predominately
follow anti addition, which indirectly testifies that the reac-
tions proceed via a bromonium-ion or an iodonium-ion in-
termediate. Furthermore, the difference in electronegativi-
ty between –OCHO and Br/I directly causes the distinction
of the chemical shift (δ) values of the protons. In the regio-
selective bromoformyloxylation and iodoformyloxyaltion, it
can be certified that the –OCHO attaches to the α -position
(benzyl) and the Br/I locates at the β-position.
After the formation of the bromonium-ion or iodonium-
ion intermediate, a stable benzylic cation, which presents a
higher partial positive charge in α-position, is formed.
Consequently, the α-position is much more easily attacked
by HCOO– than the β-position, leading, therefore, to high
regioselectivity.
ation is shown in Scheme 4. What is different from the
mechanism of bromoformyloxylation is that I– is directly
oxidized to I+ species by BrO3 .
–
–
BrO3 + H+
KBr
H2O
OCHO
R
R1
Br Br
Br
–OOCH3
polarization
R1
Br–
Br
+
+Br Br–
R
R
R1
Scheme 3 Proposed mechanism for bromoformyloxylation
Scheme 3 shows a plausible mechanism which can ex-
plain the synthetic process of bromoformyloxylation with
regioselectivity and stereoselectivity. It is confirmed that
–
BrO3 + H+
–
–
BrO3 released from ZnAl-BrO3 -LDHs in acid medium re-
acts with KBr to generate the bromine source in the tran-
sient state of Br Br.20 Immediately, Br Br undergoes polar-
ization to the shape of Br+ Br– in strongly polar solvent. The
Br+ Br– species then reacts with a C=C double bond in situ,
forming a three-membered cyclic bromonium-ion interme-
diate21 and Br– that can recycle after redox reaction with
H2O
KI
OCHO
R
R1
I+
I
R1
I
+
–OOCH3
R
R1
R
–
Scheme 4 Proposed mechanism for iodoformyloxylation
BrO3 . Owing to the hard electrophilicity of the α-position,
formate as a kind of nucleophilic species attacks the α-posi-
tion from the anti side through the SN2 pathway. Subse-
quently, the three-membered ring is opened and the prod-
uct of bromoformyloxylation is obtained from the bromoni-
In conclusion, a new protocol for high-yielding bromo-
formyloxylation22 and iodoformyloxylation of olefins using
ZnAl-BrO3 -LDHs and KX (X = Br, I) in the presence of formic
–
um-ion intermediate simultaneously.
A
probable
mechanistic pathway for explaining the iodoformyloxyl-
acid has been reported and is provided with universal
adaptability for different types of substrates. It is notewor-
thy that the bromoformyloxylation and iodoformyloxyl-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

E
L. Wang et al.
Letter
Synlett
ation products exhibit excellent regioselectivity and stereo-
selectivity. The new manner of providing a halogen source
instead of using halogenating agents is in accordance with
the green chemical idea for inexpensive, flexible operation,
atom economy, and non-pollution. The concept reflected in
this study is that a kind of formic acid reagent has multiple
functions, which greatly simplifies the reaction and separa-
tion of the products.
(12) Mameda, N.; Peraka, S.; Macharla, A. K.; Marri, M. R.; Kodumuri,
S.; Nama, N. Tetrahedron Lett. 2014, 55, 3926.
(13) Chevella, D.; Mameda, N.; Macharla, A. K.; Peraka, S.; Marri, M.
R.; Kodumuri, S.; Nama, N. Synth. Commun. 2016, 13, 1133.
(14) (a) Niizato, H.; Ueno, Y.; Takemura, S. Chem. Pharm. Bull. 1972,
20, 2707. (b) Ueno, Y.; Yamasaki, A.; Terauchi, H.; Takemura, S.
Chem. Pharm. Bull. 1974, 22, 1646.
(15) (a) Ganboa, I.; Palomo, C. Synth. Commun. 1983, 13, 941. (b) Li,
X. K.; Ho, B.; Lim, D. S. W.; Zhang, Y. G. Green Chem. 2017, 19,
914. (c) Zhang, F.; Lu, Q.; Yue, X. X.; Zuo, B. Q.; Qin, M. D.; Li, F.;
Kaplan, D. L.; Zhang, X. G. Acta Biomater. 2015, 12, 139.
(d) Schettini, A. R. A.; Peres, R. C. D.; Soares, B. G. Synth. Met.
2009, 159, 1491. (e) Schueren, L. V. D.; Steyaert, I.;
Schoenmaker, B. D.; Clerck, K. D. Carbohydr. Polym. 2012, 88,
1221.
Acknowledgment
The center of forecasting and analysis in Zhejiang University of Tech-
nology is greatly appreciated. We thank Qingbao Song and Aimin
Chen for suggestions in this paper.
(16) (a) Kozar, L. G.; Clark, R. D.; Heathcock, C. H. J. Org. Chem. 1977,
42, 1386. (b) Kleinfelter, D. C.; Schleyer, P. v. R. Org. Synth. 1962,
42, 79. (c) Kaulen, J. Angew. Chem. Int. Ed. Engl. 1987, 26, 773.
(d) Wang, L.; Floreancig, P. E. Org. Lett. 2004, 6, 4207.
Supporting Information
(17) (a) Wang, L. G.; Zheng, F. X.; Jiang, C. X.; Ni, Z. M. J. Chin. Ceram.
Soc. 2015, 43, 672. (b) Yang, M. S.; Gu, L. H.; Yang, B.; Wang, L.;
Sun, Z. Y.; Zheng, J. Y. Appl. Surf. Sci. 2017, 426, 185. (c) Djebbi,
M. A.; Elabed, A.; Bouaziz, Z.; Sadiki, M.; Elabed, S.; Namour, P.;
Jaffrezic-Renault, N.; Amare, A. B. H. Int. J. Pharm. 2016, 515,
422.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610028.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
References and Notes
(18) (a) Veeraiah, T.; Sondu, S. Int. J. Chem. Sci. 2007, 5, 911. (b) Imbri,
D.; Netz, N.; Kucukdisli, M.; Kammer, L. M.; Jung, P.;
Kretzschmann, A.; Opatz, T. J. Org. Chem. 2014, 79, 11750.
(c) Karama, U.; Mahfouz, R.; Al-Othman, Z.; Warad, I.;
Almansour, A. Synth. Commun. 2013, 43, 893. (d) Solladié, N.;
Gross, M. Tetrahedron Lett. 1999, 40, 3359.
(19) (a) Song, S.; Huang, X. Q.; Liang, Y. F.; Tang, C. H.; Li, X. W.; Jiao,
N. Green Chem. 2015, 17, 2727. (b) Dong, J. J.; Fernández-Fueyo,
E.; Li, J. B.; Guo, Z.; Renirie, R.; Wever, R.; Hollmann, F. Green
Chem. 2017, 53, 6207. (c) Lodh, R. S.; Borah, A. J.; Phukan, P.
Indian. J. Chem. 2014, 53B, 1425.
(1) (a) Dewkar, G. K.; Narina, S. V.; Sudalai, A. Org. Lett. 2003, 5,
4501. (b) Damin, B.; Garapon, J.; Sillion, B. Synthesis 1981, 362.
(c) Damin, B.; Garapon, J.; Sillion, B. Tetrahedron Lett. 1980, 21,
1709.
(2) (a) Macharla, A. K.; Nappunni, R. C.; Nama, N. Tetrahedron Lett.
2012, 53, 1401. (b) Phukan, P.; Chakraborty, P.; Kataki, D. J. J. Org.
Chem. 2006, 71, 7533. (c) Taber, D. F.; Liang, J. L. J. Org. Chem.
2007, 72, 431. (d) Yeung, Y. Y.; Gao, X.; Corey, E. J. J. Am. Chem.
Soc. 2006, 128, 9644.
(3) (a) Tripathy, N. k. Georg G. I. 2004, 45, 5309. (b) Buynak, J. D.;
Mathew, J.; Rao, M. N. J. Chem. Soc., Chem. Commun. 1986, 12,
941. (c) Thiem, J.; Gerken, M. J. Carbohydr. Chem. 1982, 1, 229.
(d) Liang, J.; Moher, E. D.; Moore, R. E.; Hoard, D. W. J. Org. Chem.
2000, 65, 3143.
(4) (a) Anderson, J. C.; Headley, C.; Stapleton, P. D.; Taylor, P. W. Tet-
rahedron 2005, 61, 7703. (b) Li, L.; Chan, T. H. Org. Lett. 2001, 3,
739. (c) Larivée, A.; Unger, J. B.; Thomas, M.; Wirtz, C.; Dubost,
C.; Handa, S.; Fürstner, A. Angew. Chem. Int. Ed. 2011, 50, 304.
(5) Kolb, H. C.; Sharpless, K. B. Tetrahedron 1992, 48, 10515.
(6) (a) Hamm, S.; Henning, L.; Findeisen, M.; Müller, D.; Welzel, P.
Tetrahedron 2000, 56, 1345. (b) Suginome, H.; Wang, J. B. Bull.
Chem. Soc. Jpn. 1989, 62, 193.
(7) (a) Glukhovtsev, M. N.; Pross, A.; Radom, L. J. Am. Chem. Soc.
1995, 117, 9012. (b) Xiao, M. Y.; Ren, D. D.; Xu, L. B.; Li, S. S.; Yu,
L. P.; Xiao, J. Org. Lett. 2017, 19, 5724. (c) Ortiz, R.; Herrera, R. P.
Molecules 2017, 22, 574. (d) Zhu, Y.; Mei, H. B.; Han, J. L.;
Soloshonok, V. A.; Zhou, J.; Pan, Y. J. Org. Chem. 2017, 82, 13663.
(e) Miralles, N.; Gomez, J. E.; Kleij, A. W.; Fernandez, E. Org. Lett.
2017, 19, 6096.
(8) De Souza, A. V. A.; Mendonca, G. F.; Bernini, R. B.; De Mattos, M.
C. S. J. Braz. Chem. Soc. 2007, 18, 1575.
(9) Dalton, D. R.; Smith, R. C. J.; Jones, D. G. Tetrahedron 1970, 26,
575.
(20) (a) Adimurthy, S.; Ghosh, S.; Patoliya, P. U.; Ramachandraiah, G.;
Agrawal, M.; Gandhi, M. R.; Upadhyay, S. C.; Ghosh, P. K.; Ranu,
B. C. Green Chem. 2008, 10, 232. (b) Cortes, C. E. S.; Faria, R. B.
Inorg. Chem. 2004, 43, 1395.
(21) (a) Zheng, C. Y.; Slebocka-Tilk, H.; Nagoraski, R. W.; Alvarado, L.;
Brown, R. S. J. Org. Chem. 1993, 58, 2122. (b) Heasley, V. L.;
Shellhamer, D. F.; Iskilian, J. A.; Street, D. L. J. Org. Chem. 1978,
43, 3139. (c) Vardhan, H. B.; Bach, R. D. J. Org. Chem. 1992, 57,
4948. (d) Slebocka-Tilk, H.; Nagorski, S. M. R. W.; Brown, P. T. R.
S.; McDonald, R. J. Am. Chem. Soc. 1995, 117, 8769. (e) Chiappe,
C.; Rubertis, A. D.; Jaber, A.; Lenoir, D.; Wattenbach, C.; Pomelli,
C. S. J. Org. Chem. 2002, 67, 7066. (f) McClendon, E.; Omollo, A.
O.; Valente, E. J.; Hamme, A. T. Tetrahedron Lett. 2009, 50, 533.
(22) Representative Procedure for the Synthesis of Bromofor-
mate 2f
Substrate (1f, 324.4 mg, 2 mmol), KBr (190.4 mg, 1.6 mmol),
formic acid (10 mL) were added to a 50 mL three-necked flask,
and KBr was absolutely dissolved in the mixture with proper
stirring at room temperature. After ZnAl-BrO3–-LDHs (0.8 g) was
added to the mixture, the reaction system was stirred at 40 °C
with use of a reflux condenser in a water bath until the sub-
strate completely disappeared (monitored by TLC). The molecu-
lar bromine was treated with sodium bisulfite solution right
away. The solid phase ZnAl-BrO3–-LDHs was removed by cen-
trifugation. Furthermore, the dichloromethane (3 × 5 mL) used
for washing the ZnAl-BrO3–-LDHs was merged into the liquid
mixture after centrifugation. Then, the products were extracted
(10) Saikia, I.; Krishna, K. R.; Phukan, P. Tetrahedron Lett. 2012, 53,
758.
(11) Podgoršek, A.; Eissen, M.; Fleckenstein, J.; Stavber, S.; Zupan, M.;
Iskra, J. Green Chem. 2009, 11, 120.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

F
L. Wang et al.
Letter
Synlett
into the organic phase with dichloromethane (3 × 10 mL) and
H2O (30 mL). The organic phase was dried with sodium sulfate
and concentrated in vacuum. The crude product was purified by
column chromatography on silica gel.
δ = 8.15 (s, 1 H), 7.42–7.39 (m, 2 H), 7.14–7.12 (m, 2 H), 6.11
(dd, J = 8.3, 4.5 Hz, 1 H), 3.68 (dd, J = 11.0, 8.4 Hz, 1 H), 3.61 (dd,
J = 11.0, 4.5 Hz, 1 H), 2.31 (s, 3 H) ppm. 13C NMR (126 MHz,
CDCl3): δ = 169.16, 159.52, 151.09, 134.49, 127.84, 122.00,
74.04, 33.51, 21.07 ppm. HRMS (ESI): m/z calcd for C11H11BrO4
[M + H]+: 286.9919; found: 286.9917.
2-Bromo-1-(4-acetoxylphenyl)ethyl formate (2f)
Yield: 493.8 mg, 86%. Colorless oil. 1H NMR (500 MHz, CDCl3):
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F