A Highly Efficient Magnetic Iron(III) Nanocatalyst for Ferrier Rearrangements

Article abstract of DOI:10.1055/s-0037-1611855

A novel and highly efficient magnetic Fe ₃ O ₄ &at;C&at;Fe(III) core-shell catalyst, in which the carbon shell was prepared from lotus leaf, was fabricated. This nanocatalyst was successfully applied in the synthesis of a series of 2,3-unsaturated O- glycosides in excellent yields and with high selectivity, especially in the case of 2-halo O- glycosides, which differ in reactivity from nonsubstituted O- glycosides, but which have scarcely been explored before. Moreover, the catalyst could be easily separated from the reaction by the application of an external magnetic force and reused a minimum of five times without any significant decrease in the yields of the products. In addition, the reaction proceeded readily on a gram scale, which provides a bright prospect for future applications.

Full text of DOI:10.1055/s-0037-1611855

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© Georg Thieme Verlag Stuttgart · New York
2019, 30, 1419–1426
letter
1419
en
Y. Dong et al.
Letter
Synlett
A Highly Efficient Magnetic Iron(III) Nanocatalyst for Ferrier
Rearrangements
Youxian Dong
Zekun Ding
synthesis, modification
FeCl3
Hong Guo
Le Zhou
Nan Jiang
waste lotus
leaf extract
Fe3O4
Fe3O4@C
Fe3O4@C@Fe(III)
Heshan Chen
Saifeng Qiu
Xiaoxia Xu
Jianbo Zhang*
Fe3O4@C@Fe(Ø)
(0.1 equiv.)
O
O
PGO
PGO
+
ROH
0
0
0
0-
0
0
0
3-3
7
2
6-4
2
3
X
OR
X
DCE, rt
X
School of Chemistry and Molecular Engineering, East China
Normal University, Shanghai 200241, P. R. of China
jbzhang@chem.ecnu.edu.cn
Mild condition
36 examples
Yield: 59%–98%
a/b: up to > 19:1
5 times recycle
X = H, Cl, Br, I
R = alkyl, aryl,
glycosyl
PG = protecting group
Received: 03.04.2019
Accepted after revision: 15.05.2019
Published online: 19.06.2019
unsaturated glycosides.20 A wide range of reagents have
been used to promote this reaction, including Bronsted
acids, Lewis acids, oxidants, etc.14,21–27 Although many
methods for performing Ferrier rearrangements have been
described in recent decades, most have involved Lewis acids
as catalysts; these are difficult to use in mass production
because they contain rare and expensive elements or are
not easily prepared. Consequently, the development of a
green and efficient strategy for the synthesis of 2,3-unsatu-
rated glycosides remains as a challenge.
Compared with common catalysts, most ferric salts are
harmless and inexpensive. In particular, ferric chloride has
been widely used in a variety of organic reactions because
of its superior and unique catalytic properties under ex-
tremely mild conditions; however, its characteristic mois-
ture absorption limits its further application.28–34 In recent
years, our group has introduced immobilized ferric cata-
lysts such as FeCl3·6H2O/C and FeCl3/C into glycosylation re-
actions, thereby reducing the catalyst cost and overcoming
the problem of moisture absorption.24–27,35 However, the
posttreatment separation and recycling performance of sol-
id-acid catalysts require further improvements. For this
reason, we recently reported a magnetic core–shell nano-
material, Fe3O4@C@SO3H, as novel Bronsted acid catalyst,
and we successfully employed it in a Ferrier rearrangement,
thereby solving the problems of isolation and recycling.28,36
Nevertheless, there is still scope for improving the
Fe3O4@C@SO3H catalyst, because it requires a reaction tem-
perature of 80 °C, which may be incompatible with some
heat-sensitive acceptors or donors. In our continuing search
for greener and more widely applicable catalysts for the
Ferrier rearrangement, we decided to fabricate a magnetic
Fe3O4@C@Fe(III) catalyst, the immobilized ferric ion of
DOI: 10.1055/s-0037-1611855; Art ID: st-2019-w0186-l
Abstract A novel and highly efficient magnetic Fe3O4@C@Fe(III) core–
shell catalyst, in which the carbon shell was prepared from lotus leaf,
was fabricated. This nanocatalyst was successfully applied in the syn-
thesis of a series of 2,3-unsaturated O-glycosides in excellent yields and
with high selectivity, especially in the case of 2-halo O-glycosides, which
differ in reactivity from nonsubstituted O-glycosides, but which have
scarcely been explored before. Moreover, the catalyst could be easily
separated from the reaction by the application of an external magnetic
force and reused a minimum of five times without any significant de-
crease in the yields of the products. In addition, the reaction proceeded
readily on a gram scale, which provides a bright prospect for future ap-
plications.
Key words nanocatalyst, Ferrier rearrangement, haloglucals, iron
catalysis, catalyst recycling, magnetic catalyst
Glycoconjugates are involved in many biological pro-
cesses such as cell–cell communication, cell development,
viral infection, inflammation, and the immune response.
Consequently, they have become a focus theme in biochem-
istry and synthetic targets for pharmaceutical studies.1–9
Among the various reactions available for the synthesis of
glycoconjugates, the Ferrier rearrangement is an important
reaction for the synthesis of 2,3-unsaturated glycosides.10
The products of this transformation are versatile chiral in-
termediates for the synthesis of a variety of important bio-
logically active compounds and natural products.11–19 For
instance, the 2,3-unsaturated sugar derivatives of 5-(hy-
droxymethyl)furfural showed excellent antitumor activities
in our previous research, highlighting the significance of
exploring more-efficient method for the synthesis of 2,3-
© 2019. Thieme. All rights reserved. — Synlett 2019, 30, 1419–1426
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

1420
Y. Dong et al.
Letter
Synlett
which should readily catalyze the Ferrier reaction under
mild conditions. However, previous work on the immobili-
zation of metal Lewis acids on core–shell materials is rela-
tively scarce because difficulties in binding metal ions firm-
ly to a carbon shell can lead to poor recycling performance
of such composite when used as catalysts.37–45 After modifi-
cation, common carbon resources such as simple monosac-
charides or oligosaccharides can contain surfactant groups
(–COOH, –SO3H, –OH, etc.). To fabricate Fe3O4@C@Fe(III)
nanoparticles by surface modification of core–shell
Fe3O4@C with subsequent immobilization of the metal ions,
we focused on exploiting a biomass material containing
many polysaccharides.
well with the (111) planes of a cubic Fe3O4 structure. Fur-
thermore, the elemental composition of the Fe3O4@C sam-
ples was determined by energy-dispersive X-ray (EDX)
analysis [Figure 1(d)], which revealed that the as-prepared
products contained abundant Fe and C, and also confirmed
the nanocomposite structure of Fe3O4@C@Fe(III). In view of
the invisible external structure of the core–shell material,
the external Fe3+ content of the catalyst was determined by
complexometric titration.50,51 The load capacity of external
ferric ion was 1.25 × 10–3 mmol/mg, which fits well with
the results of our previous work.28
Although lotus leaves are rich in polysaccharides, fla-
vones, and proteins,46–49 they are generally discarded in the
autumn. To use them as a sustainable source of carbon and
to improve the efficiency of its preparation, we proposed
the novel catalyst-preparation route shown in Scheme 1.
Figure 1 (a) and (b) TEM images of Fe3O4@C@Fe(III); (c) HRTEM image
of Fe3O4@C@Fe(III); (d) EDX analysis.
Scheme 1 Fabrication of magnetic Fe3O4@C@Fe(III) core–shell catalyst
from waste lotus leaves
The results described above showed that the prepared
core–shell Fe3O4@C@Fe(III) particles are of nanometer-level
sizes and therefore might be expected to show better per-
formance as solid-acid catalysts. To examine their catalytic
activity, a Ferrier rearrangement reaction was conducted
with D-glucal triacetate and benzyl alcohol (Table 1). First,
we examine whether the newly prepared nanoFe3O4-modi-
fied core–shell Fe3O4@C material with -COOH, -SO3H, -OH,
and other groups, after sulfonation with H2SO4 as a Bronst-
ed acid, contained an abundance of surface groups and
would combine firmly with ferric ions (Table 1, entries 1–
4). The presence of a Fe3O4 coating on the carbon shell was
shown to be essential for catalytic performance (entries 1–
4), a result that is consistent with our previous work.28
Compared with FeCl3/C, the core–shell microspheres pro-
duced a superior reaction rate due their smaller particle
size (entries 5 and 6). These results encouraged us to fur-
ther study and optimize the conditions for the Ferrier reac-
tion. On increasing the reaction temperature, the yield fell
due to the increased production of byproducts (entries 6–
Compared with reported methods, our method success-
fully simplified the two-step process of carbonization and
sulfonation by performing it in one pot with concentrated
sulfuric acid as both a carbonization and sulfonation
agent.42
The morphology and structure of the resulting nano-
composites were analyzed by transmission electron micros-
copy (TEM). As shown in Figures 1(a) and 1(b), the nano-
composites had a cubic shape with an average size of 50–60
nm. The dark/light contrast shown in Figure 1(b) suggest a
composition consisting of different phases and confirmed
the formation of Fe3O4@C core–shell nanostructures. It was
clearly shown that the Fe3O4 nanoparticles were completely
coated with carbon shells, and that the diameter of the
Fe3O4 cores encapsulated within the carbon shells was
about 50–60 nm. The high-resolution TEM (HRTEM) image
shown in Figure 1(c) provides detailed structural informa-
tion about the Fe3O4@C nanoparticles. The lattice fringe, as
calculated from the HRTEM image, is 0.48 nm, which fits
© 2019. Thieme. All rights reserved. — Synlett 2019, 30, 1419–1426

1421
Y. Dong et al.
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Synlett
8). Next, we examined various solvents commonly used in
Ferrier reactions (DCE, CH2Cl2, MeCN, Et2O, and 1,4-diox-
ane) (entries 6 and 9–12). The reaction rate at room tem-
perature was slow in solvents other than DCE or CH2Cl2, and
therefore DCE was identified as the optimal solvent in
terms of the reaction time and yield. Next, the loading of
the Fe3O4@C@Fe(III) catalyst in this system was explored
(entries 6 and 13–15). When the number of equivalents
was reduced from 0.3 to 0.1 equivalents, the glucal triace-
tate was completely consumed in ten minutes and the yield
reached 93% (entry 13). However, when 0.5 equivalents of
catalyst were used, the yield fell slightly and the reaction
time was extended to 15 minutes (entry 14). Therefore, the
optimal reaction conditions were room temperature with
0.1 equivalents of catalyst in DCE.
Encouraged by these results, we explored the substrate
scope of the rearrangement reaction with a range of alco-
hols, phenols, and saccharides 2a–r as glycosyl acceptors
(Scheme 2). Various alcohols, including primary, secondary,
benzylic, allylic, propargylic, and halogenated alcohols
showed good anomeric selectivities in producing products
3a–i in high yields. It is noteworthy that when tert-butanol
was used as the nucleophile, the expected product 3e was
obtained in high yield despite its high degree of steric hin-
drance. The reaction of the significant platform compound
5-(hydroxymethyl)furural (HMF; 2j) with our catalytic sys-
tem gave a higher yield of the corresponding product 3j
than that produced with FeCl3/C in our previous work. This
result shows the advantages of Fe3O4@C@Fe(III) in exploring
more-bioactive HMF derivatives. The complex biomolecules
cholesterol (2l) and menthol (2m) also reacted reacted in
excellent yields and with high selectivities. Moreover, vari-
ous disaccharides were obtained smoothly when monosac-
charides were used as the acceptors, and the desired 2,3-
unsaturated glycoside products 3n and 3o were obtained in
high yields and with moderate selectivities. With phenolic
acceptors, the Ferrier rearrangement proceeded with in the
presence of 0.01 equivalents of catalyst, due to the acidity
of the phenols. Phenol (2p), 4-methoxyphenol (2q), and 4-
bromophenol (2r) provided the corresponding Ferrier
products in yields that reflected the substituent effect to
some extent. Both 3,4,6-tri-O-acetyl-D-glucal and 3,4-di-O-
acetyl-L-rhamnal were studied as representative glycosyl
donors. The latter reacted with HMF and 4-methoxyphenol
as representative alcoholic and phenolic acceptors, respec-
tively, giving the corresponding products 4a and 4b in
yields of 82% and 60% with higher stereoselectivities.
Table 1 Optimizing the Conditions for the Ferrier Rearrangement of D-
Glucal Triacetate with Benzyl Alcohol
Next, we attempted to employ our catalyst to promote
more-challenging reactions with other glucal donors.
Among the various substituted glycals, 2-haloglycals have
recently become recognized as new entries to 2C-function-
alized glycals, and are widely used as important synthons in
organic chemistry.52–54 Thus, 2-iodo- and 2-bromoglycals
and the corresponding 2,3-unsaturated 2-haloglycosides
have been used in the synthesis of 2C-arylglycosides, the
oxadecalin core of phomactin A, and biologically active
scaffolds such as chromans and isochromans.55–57
Substitution at C-2 position has a marked influence on
the reactivity of glycals, especially in the case of halogen
substituents, which have both an electron-donating induc-
tive effect and an electron-withdrawing conjugation effect.
However, previous research on 2-haloglycals and the corre-
sponding reaction activity is inadequate. Our interest was
intrigued by the activity of 2-haloglycals and the efficiency
of the core–shell metal Lewis acid catalyst. Based on our
previous preparation of 2-haloglycals, we employed tri-O-
acetyl-2-iodoglucal (5a) to explore the optimal condition
for Ferrier rearrangement reactions with ethanol in the
presence of Fe3O4@C@Fe(III) catalyst. First, we used 1.0
equivalent of catalyst to promote the reaction at 25 °C, but
no product was detected (Table 2, entry 1). When the tem-
perature was increased to 40 °C, the reaction rate improved
and product 7a was obtained in 70% yield in 60 minutes
(entry 2). At 60 °C, we obtained the product in 95% yield af-
ter 20 min (entry 3) and 80 °C, it was formed in 88% yield
after 10 min. However, at these higher temperatures the
formation of byproducts also increased and, therefore, the
OAc
O
OAc
O
solvent/catalyst
AcO
AcO
AcO
BnOH
+
OBn
1a
(1 equiv.)
2a
3a
(1.2 equiv.)
Entry Catalyst
Temp Equiv of Solvent
Time
(min) (%)
Yieldb
(°C)
Catalysta
1
2
Fe3O4
Fe3O4
25
80
25
80
25
25
40
80
25
25
25
25
25
25
25
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.1
0.5
0.05
DCE
>720
>720
>720
10
NRc
DCE
NR
NR
76
85
89
84
82
80
60
63
NR
93
88
91
3
Fe3O4@C@SO3Hd
Fe3O4@C@SO3Hd
FeCl3/C
DCE
4
DCE
5
DCE
10
6
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
DCE
10
7
DCE
10
8
DCE
10
9
CH2Cl2
MeCN
Et2O
30
10
11
12
13
14
15
240
360
1,4-dioxane >720
DCE
DCE
DCE
10
15
10
a Fe3+ content of the catalyst as determined by complexometric titration.50
b Isolated yield.
c NR = no reaction.
d Core–shell microparticles of Fe3O4@C modified with –SO3H and –COOH
groups.28
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Y. Dong et al.
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OAc
O
OAc
Fe3O4@C@Fe(Ø)
DCE, 25 °C
ROH
+
O
AcO
AcO
AcO
OR
2
1a
(1 equiv)
3
(1.2 equiv)
OAc
O
OAc
O
OAc
O
OAc
O
AcO
AcO
AcO
AcO
AcO
O
O
6
O
O
3a 10 min 93%, 5:1
3b 10 min, 96%, 6:1
3c 10 min, 98%, 8:1
3d 15 min, 92%, 7:1
OAc
O
OAc
O
OAc
O
OAc
O
AcO
AcO
AcO
O
O
O
O
3e 90 min, 83%, >19:1
3f 20 min, 88%, 8:1
3g 10 min, 95%, 8:1
3h 10 min, 94%, 7:1
OAc
O
OAc
H
OAc
O
O
CHO
Cl
Cl
AcO
AcO
AcO
O
AcO
H
H
O
O
Cl
O
3j 10 min, 88%, 5:1
3l 20 min, 92%, >19:1
3i 30 min, 89%, >19:1
OAc
OAc
O
OAc
O
O
AcO
AcO
O
O
O
O
O
BzO
BzO
BnO
BnO
BzO
BnO
OMe
OCH3
OMe
Br
3n 10 min, 86%, 10:1
3o 10 min, 88%, 10:1
3m 10 min, 93%, >19:1
OAc
OAc
OAc
O
O
O
AcO
AcO
AcO
O
O
O
3pa 10 min, 68%, 10:1
3qa 5 min, 77%, 10:1
3ra 10 min, 74%, 10:1
O
O
OCH3
O
O
O
AcO
AcO
CHO
4ba 10 min, 60%, >19:1
4a 10 min, 82%, 7:1
a equiv(cat.)=0.01 equiv
Scheme 2 Scope of the Ferrier rearrangement under the optimized conditions
optimal temperature was 60 °C. Next, we tried different
solvent (entries 5–8) apart from DCE, the optimal solvent
for the Ferrier reaction of 2-unsubstituted glucals, and we
found that DCE remained the best choice. To reduce the use
of catalyst, gradient dosages from 1.0 to 0.1 equivalents
were tested (entries 3 and 9–11), and we found that 1.0
equivalents of catalyst rapidly and efficiently promoted this
reaction. Therefore, the optimal reaction conditions are
60 °C with 1.0 equivalent of catalyst in DCE.
Having established the optimal reaction conditions, we
turned our attention to exploring the substrate scope of the
Ferrier rearrangement reaction of 5a and 8a with a series of
O-nucleophiles 6a–n (Scheme 3). In all cases, the reaction
proceeded smoothly and with good to excellent yields and
-selectivity, demonstrating that our catalyst can be used in
the presence of not only common or complex bioactive al-
cohols, phenols, and glycosyl acceptors, but also with 2-
iodo-, 2-bromo, and 2-chloroglucal donors.
We then examined the differences in the reactivities of
2-unsubstituted and 2-halogenated tri-O-acetylglucals un-
der the same mild conditions. We chose tri-O-acetylglucal
(1a),tri-O-acetyl-2-iodoglucal (5a), 2-bromo-tri-O-acetyl-
glucal (8a), and 2-chloro-tri-O-acetylglucal (10a) as donors
and ethanol as the acceptor with 0.3 equivalents of the cat-
alyst. A comparison of the reaction time, conversion rate,
and yield for the various reactions showed that tri-O-
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Y. Dong et al.
Letter
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OAc
O
OAc
O
Fe3O4@C@Fe(Ø)
DCE, 60 °C
AcO
AcO
AcO
ROH
+
OR
X
X
5a X = I
8a X = Br
10a X = Cl
6
7
9
11
OAc
O
OAc
O
OAc
O
AcO
AcO
AcO
AcO
AcO
AcO
O
O
O
I
I
I
7a 20 min, 95%, >19:1
7b 20 min, 93%, 10:1
7c 12 h, 60%, >19:1
OAc
O
OAc
O
OAc
O
Cl
Cl
O
O
O
Cl
I
I
I
7e 15 min, 91%, >19:1
7f 20 min, 81%, 5:1
7d 30 min, 89%, 14:1
OAc
O
OAc
OAc
O
H
O
O
CHO
AcO
AcO
AcO
AcO
H
H
O
O
O
I
I
I
7i 12 h, 59%, >19:1
7h 20 min, 85%, 5:1
OAc
7g 30 min, 86%, >19:1
OAc
O
O
AcO
O
O
O
I
O
I
BnO
BnO
BzO
BzO
BnO
BzO
OMe
OMe
7j 15 min, 86%, >19:1
7k 20 min, 89%, >19:1
Br
OAc
O
OAc
O
OAc
O
AcO
AcO
AcO
O
O
O
I
I
I
7l 30 min, 69%, >19:1
7ma 20 min, 71%, >19:1
7n 60 min, 67%, >19:1
OAc
O
OAc
O
OAc
O
AcO
AcO
AcO
O
O
O
BnO
BnO
O
Br
Br
Cl
BnO
9b 15 min, 87%, >19:1
OMe
9a 20 min, 90%, >19:1
11a 20 min, 89%, >19:1
a equiv(cat.)=0.1 equiv.
Scheme 3 Scope of the Ferrier rearrangement reaction under the optimized conditions
acetylglucal (1a) has the highest reactivity and that the ac-
tivities of the tri-O-acetyl-2-haloglucals decrease with de-
creasing atomic number of the halogen (Table 3).
washed with CH2Cl2 to remove any adsorbed products,
dried under vacuum, and reused in a subsequent reaction.
As shown in in Scheme 5, in a test over five reaction cycles
there was only a slight decrease in the activity of the cata-
lyst. Because the crude extract of lotus leaf is rich in poly-
saccharides, we suspect that these polysaccharides play a
significant role in the carbonization and immobilization
process. We therefore examined lotus-leaf polysaccharides
obtained by alcohol sedimentation as a shell carbon re-
source to determine whether the polysaccharides alone
could provide enough active groups for immobilization of
ferric ions.43,48,49 However, the catalyst with the polysaccha-
ride-derived carbon shell gave inferior results.
On the basis of reports in the literature,58–60 we conclud-
ed that the substituent at C-2 position has a remarkable ef-
fect, and that electron-withdrawing groups reduce the elec-
tron density of the oxocarbenium intermediate (Scheme 4).
Recycling of the Fe3O4@C@Fe(III) catalyst was studied
for the model reaction of tri-O-acetyl-D-glucal with benzyl
alcohol. After reaction, the Fe3O4@C@Fe(III) catalyst was
dispersed in the reaction system but could be easily collect-
ed by using an external magnet. The liquid was then re-
moved from the mixture to leave the catalyst, which was
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1424
Y. Dong et al.
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Table 3 Reactivities of Tri-O-acetylglucal and 2-Halo-tri-O-acetylglucals
rides or flavonoids individually. We postulate that after car-
bonization, polysaccharides provide sufficient carbon re-
sources and incomplete carbonization of flavonoid residues
results in improved binding of ferric ions, thereby improv-
ing the ability of the material to immobilize ferric ions.48,49
Because the Ferrier reaction of 2-haloglucals proceeds
at 60 °C, which is a fairly high temperature for Ferrier rear-
rangements in general, we tested the recycling perfor-
mance of the catalyst by using reaction of tri-O-acetyl-2-io-
doglucal (5a) with ethanol as a model reaction to examine
whether the ferric ion remained tightly bound to the core–
shell Fe3O4@C under heated conditions. The product was
still obtained in 86% yield, even after the catalyst had been
cycled five times, demonstrating that our catalyst is suit-
able for use under harsh conditions, thereby significantly
broadening its the range applications under recycling con-
ditions.
As shown by the above experiments, our catalyst has
outstanding catalytic activity and recycling performance.
To further demonstrate the mass production of glycosides,
we tested the catalyst in large-scale Ferrier rearrangement
reactions (Scheme 6). When 5 mmol of tri-O-acetyl-D-glu-
cal (1a) or di-O-acetyl-L-rhamnal (1b) was treated with
benzyl alcohol (2a) under the optimal conditions (0.1 equiv
catalyst, DCE, rt), the corresponding products 3a and 4c
were obtained in excellent yields in 10 minutes through
simple magnetic separation and column chromatography.
Fe3O4@C@Fe(III)
0.3 equiv.
OAc
O
OAc
O
AcO
AcO
AcO
EtOH
+
DCE, 60 °C
OEt
X
X
1 equiv.
1.2 equiv.
Entry
X
Time (min)
Conversion (%) Yield (%)
1
2
3
4
H
10
90
90
90
100
100
91
92
83
79
72
I
Br
Cl
85
OR2
X
O
O
O
R1O
R1O
R1O
R1O
HOR2
R1O
R1O
X
X
LG:
Scheme 4 Plausible mechanism
OAc
O
OAc
O
Fe3O4@C@Fe(III)
0.1 equiv.
AcO
AcO
AcO
BnOH
+
DCE, 25 °C
OBn
1a
2a
3a
(1.36g, 5 mmol)
(6 mmol)
yield = 95%
Fe3O4@C@Fe(III)
0.1 equiv.
OBn
O
O
BnOH
AcO
+
AcO
DCE, 25 °C
OAc
2a
(6 mmol)
4c
yield = 91%
1b
(1.07g, 5mmol)
Scheme 6 Ferrier rearrangement reactions on a large scale
In summary, we have developed a green synthesis of
magnetic Fe3O4@C@Fe(III) core–shell microspheres from lo-
tus leaf as a carbon resource; this is the first report of the
immobilization of Fe(III) on a carbon shell as a Lewis acid
catalyst. Our Fe3O4@C@Fe(III) catalyst was successfully ap-
plied in Ferrier rearrangement reactions, including those of
2-haloglycals.61 This core–shell magnetic catalyst is not
only superior to Fe3O4@C-SO3H in terms of the reaction
conditions and the substrate scope, but also overcomes the
problems of reuse and moisture absorption associated with
FeCl3. Compared with recently developed Lewis acid cata-
Scheme 5 Recycling experiments of Fe3O4@C@Fe(III). Reaction condi-
tions: 1a (0.2 mmol, 54.4 mg), BnOH (0.224 mmol, 24 μL),
Fe3O4@C@Fe(III) (16 mg), DCE (2 mL), 10 min, rt.
Next, and as a comparison, another important ex-
tractive component, flavonoids, were tested as a carbon re-
source,48 but, as shown in Scheme 5, the total crude extract
as a carbon resource was superior to lotus-leaf polysaccha-
© 2019. Thieme. All rights reserved. — Synlett 2019, 30, 1419–1426

1425
Y. Dong et al.
Letter
Synlett
Table 2 Optimization of the Conditions for the Ferrier Rearrangement
Tri-O-acetyl-2-iodoglucal with Ethanol
Acknowledgment
We sincerely thank the analytic center of East China Normal Universi-
ty for data measurements. We also thank Mr. Guosheng Sun for help-
ful discussion.
OAc
OAc
solvent/catalyst
O
O
AcO
AcO
AcO
EtOH
+
OEt
I
I
Supporting Information
5a
(1 equiv.)
6a
7a
(1.2 equiv.)
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611855.
S
u
p
p
orit
n
gInformati
o
n
S
u
p
p
orit
n
gInformati
o
n
Entry Catalyst
Temp
(°C)
Equiv cat-Solvent Time Yieldb
alysta
(min) (%)
1
2
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
Fe3O4@C@Fe(III)
25
40
60
80
60
60
60
60
60
60
60
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.5
0.3
0.1
DCE
>720 trace
60 70
References and Notes
DCE
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CH2Cl2
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Et2O
THF
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>720 NRc
>720 NR
>720 NR
90 85
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8
9
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Funding Information
The project was supported by the Natural Science Foundation of
Shanghai (11ZR1410400), large instruments Open Foundation of East
China Normal University (20161043) and National Undergraduate
Training
Program
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1H NMR (500 MHz, CDCl3):  = 7.36 (d, J = 4.9 Hz, 5 H), 5.90 (d,
J = 10.4 Hz, 1 H), 5.87–5.83 (m, 1 H), 5.33 (dd, J = 9.4, 1.3 Hz, 1
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4,6-Di-O-acetyl-2,3-dideoxy-2-
Yellow oil; yield: 39.4 mg (85%). 1H NMR (500 MHz, CDCl3):
 = 9.63 (s, 1 H), 7.23 (d, J = 3.1 Hz, 1 H), 6.63 (d, J = 2.9 Hz, 1 H),
6.50 (s, 1 H), 5.31 (d, J = 8.6 Hz, 1 H), 5.10 (s, 1 H), 4.75 (ddd, J =
19.2, 13.5, 7.4 Hz, 2 H), 4.20 (ddd, J = 30.1, 16.3, 5.3 Hz, 3 H),
2.09 (d, J = 6.9 Hz, 6 H). 13C NMR (125 MHz, CDCl3):  = 177.85,
170.79, 170.11, 157.15, 152.98, 138.61, 121.97, 112.01, 99.17,
73.08, 67.21, 66.84, 62.93, 62.55, 20.99, 20.92. HRMS (ESI+): m/z
[M + Na]+ calcd for C16H17INaO6: 486.9866; found: 486.9860.
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Yellow oil; yield: 65.6 mg (87%). 1H NMR (500 MHz, CDCl3):
 = 7.36–7.28 (m, 15 H), 6.19 (s, 1 H), 5.32 (d, J = 8.7 Hz, 1 H),
5.15 (s, 1 H), 4.97 (d, J = 10.8 Hz, 1 H), 4.92 (d, J = 11.1 Hz, 1 H),
4.84–4.77 (m, 2 H), 4.66 (dd, J = 11.2, 8.5 Hz, 2 H), 4.59 (d, J = 3.0
Hz, 1 H), 4.19 (dd, J = 12.3, 5.1 Hz, 1 H), 4.13 (d, J = 10.9 Hz, 2 H),
4.01 (t, J = 9.2 Hz, 1 H), 3.89–3.81 (m, 2 H), 3.76 (d, J = 10.6 Hz, 1
H), 3.66 (t, J = 9.4 Hz, 1 H), 3.53 (dd, J = 9.7, 2.9 Hz, 1 H), 3.37 (s,
3 H), 2.08 (s, 3 H), 2.04 (s, 3 H). 13C NMR (125 MHz, CDCl3):
 = 170.81, 170.17, 138.87, 138.47, 138.24, 129.74, 128.60,
128.57, 128.54, 128.30, 128.19, 128.08, 127.88, 127.77, 122.54,
98.17, 97.80, 82.06, 80.01, 77.75, 75.93, 75.17, 73.54, 70.92,
66.93, 66.85, 66.57, 62.53, 55.37, 53.57, 21.00, 20.87. HRMS
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777.1881.
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Yellow oil; yield: 26.0 mg (89%). 1H NMR (500 MHz, CDCl3):
 = 5.98 (s, 1 H), 5.35 (d, J = 9.3 Hz, 1 H), 4.91 (s, 1 H), 4.25–4.14
(m, 3 H), 3.84 (dq, J = 14.3, 7.1 Hz, 1 H), 3.70–3.61 (m, 1 H), 2.09
(s, 3 H), 2.07 (s, 3 H), 1.28 (t, J = 7.1 Hz, 3 H). 13C NMR (125 MHz,
CDCl3):  = 170.80, 170.22, 132.85, 125.48, 96.65, 66.82, 66.25,
65.25, 62.62, 20.99, 20.86, 15.26. HRMS (ESI+): m/z [M + Na]+
calcd for C12H17ClNaO6: 315.0612; found: 315.0606.
© 2019. Thieme. All rights reserved. — Synlett 2019, 30, 1419–1426