Transformation of Sugars into Chiral Polyols over a Heterogeneous Catalyst

Article abstract of DOI:10.1002/anie.201803043

Transformation of sugars, while maintaining the intrinsic stereochemical structure, is desirable. However, such a transformation requires multistep synthesis with protection and deprotection of the OH groups. Herein, a new method for selective transformation of sugar derivatives into chiral building blocks and a diol synthon, with retention of the intrinsic configuration (stereo- and regioselectively), is demonstrated. The method is based on the selective recognition of cis-vicinal OH groups in sugars and leads to the one-pot removal of the cis-vicinal OH groups, without protection of OH groups (except the OH group of the hemiacetal group), over a heterogeneous CeO₂-supported ReO_x and Pd (ReO_x-Pd/CeO₂) catalyst by using H₂ as a reducing agent.

Full text of DOI:10.1002/anie.201803043

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Accepted Article
Title: Transformation of Sugars to Chiral Polyols over a Heterogeneous
Catalyst
Authors: Masazumi Tamura, Naoto Yuasa, Keiichi Tomishige,
Yoshinao Nakagawa, and Ji Cao
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201803043
Angew. Chem. 10.1002/ange.201803043
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10.1002/anie.201803043
Angewandte Chemie International Edition
COMMUNICATION
Transformation of Sugars to Chiral Polyols over a Heterogeneous
Catalyst
Masazumi Tamura*, Naoto Yuasa, Ji Cao, Yoshinao Nakagawa and Keiichi Tomishige*
Abstract: Transformation of sugars with maintaining the intrinsic
stereostructure is desirable to make full use of sugars, however,
there is no choice but to use multistep synthesis with protection
and deprotection of the OH groups due to the similar reactivities of
the OH groups. Herein, a new method for selective transformation
of sugar derivatives to chiral building blocks and a diol synthon with
retention of the intrinsic configuration (stereo- and regioselectively)
is demonstrated. The key to the success is based on the selective
recognition of cis-vicinal OH groups in sugars and one-pot
simultaneous removal of the cis-vicinal OH groups to the dideoxy
sugars without protection of OH groups except the OH group of the
hemiacetal group over heterogeneous CeO2-supported ReOx and
Pd (ReOx-Pd/CeO2) catalyst by using H2 as a reducing agent.
deprotection, leading to low yield and high cost11. De novo
synthesis method is also proposed as an alternative method
for the synthesis of deoxy sugars[13], which however suffers
from multistep synthesis, low yield and low availability of
starting materials. Recently, Gagné and co-workers
demonstrated an effective method for selective dissociation of
C-O bonds in silyl-protected polyols to chiral polyol synthons
with maintaining the stereocenters of polyols using B(C6F5)3
and tertiary silane[14-16], however, the method required the silyl
pre-protection of the OH groups and more than equivalent
amount of silane additives. Therefore, catalytic and selective
transformation of sugars without protection of OH groups to
deoxy sugars with maintaining the original stereostructure by
using cheap reductants such as H2 is ideal.
For the purpose, selective recognition of one or some OH
groups in sugars by catalysts is essential, and the unique cyclic
stereostructure of sugars will give an opportunity for the
selective recognition. However, the stability of the cyclic
structure of sugars is generally not so high, and methyl
glycosides are often used as synthons of sugars[17] because
they have more stable cyclic structure and can be easily
produced from sugars and methanol and restored to sugars.
Hydrogenolysis of C-O bonds in methyl glycosides is one of
the options for removal of the OH groups, however, selective
hydrogenolysis of specific OH groups is so far quite difficult due
to the similar characteristic of the OH groups, resulting in a
variety of products (Scheme 1(A)). On the other hand,
deoxydehydration (DODH) is well-known as a method for
simultaneous removal of vicinal OH groups in polyols to olefin
groups[18-24]. Recently, we found that a combination method of
deoxydehydration-hydrogenation (DODH-HG) was effective
for one-pot simultaneous removal of vicinal OH groups in diols
to the corresponding dideoxy products[25,26]. In this method,
CeO2-supported ReOx modified with Pd (ReOx-Pd/CeO2) was
an efficient heterogeneous catalyst for the reaction by using
gaseous H2 as a reducing agent without dissociation of C-C
bonds. The detailed roles of each metal species of ReOx-
Pd/CeO2 in DODH reaction are shown in the supporting
information. The method can largely decrease the number of
products from sugars (Scheme 1(B)), and moreover focusing
on the cyclic structure of methyl glycosides, recognition of only
one of cis-vicinal or trans-vicinal OH groups by a catalyst will
enable more selective transformation of sugars. Herein, we
substantiated selective transformation of cis-vicinal OH groups
in methyl glycosides to the dideoxy glycosides by selective
recognition of cis-vicinal OH groups, and the produced dideoxy
glycosides could be transformed to useful chemicals such as
chiral building blocks and α,ω-diol synthons (Scheme 1(D)).
To clarify the potential of ReOx-Pd/CeO2 catalyst for
selective removal of cis-vicinal or trans-vicinal OH groups,
deoxydehydration-hydrogenation (DODH-HG) of methyl C6-
and C5-glycosides with cis-vicinal or trans-vicinal OH groups
was investigated as model substrates with ReOx-Pd/CeO2(Re:
Biomass is a promising renewable resource which can
replace fossil fuels because biomass is an only organic
resource among various renewable ones. Sugars are main
frameworks of biomass, and it is greatly desirable to develop
an innovative and effective method for transformation of
biomass-derived sugars to valuable chemicals on the
background of resource depletion and global climate change.
Selective transformation of sugars requires selective
dissociation of the C-O or C-C bonds, and it has been
intensively investigated with homogeneous, heterogeneous,
and enzymatic catalysts[1-3]. The most typical method for the
transformation of sugars is via formation of furfural and 5-
hydroxymethyl furfural because the furfurals can be easily
produced by dehydration of sugars in the presence of acid
catalysts (Scheme 1(C))[4-8]. The method via formation of sugar
alcohols is also proposed by combination of aqueous-phase
reforming, dehydration and/or hydrogenation (hydrogenolysis)
to produce alkanes and alkanols[9,10]
. However, such
transformation methods lose the unique stereostructure of
sugars. As for methods with retention of the stereostructure of
sugars, biocatalytic transformation of sugars to chiral
chemicals such as lactic acid is a well-known process, however
artificial catalytic transformation is very limited. To our best
knowledge, there are no reports on effective catalysts for the
one-pot selective removal of one or some OH groups from
unprotected sugars and sugar derivatives to produce deoxy
sugars in spite that deoxy sugars form the main frameworks of
natural products[11] and are used as a vital scaffold for
medicines[12]. Conventionally, synthesis of deoxy sugars needs
multistep synthesis with
a technique of protection and
[*]
Dr. M. Tamura, N. Yuasa, J. Cao, Dr. Y. Nakagawa, Prof. K. Tomishige,
Graduate School of Engineering, Tohoku University
Aoba 6-6-07, Aramaki, Aoba-ku, Sendai, Miyagi 980-8579 (Japan)
E-mail: mtamura@erec.che.tohoku.ac.jp
tomi@erec.che.tohoku.ac.jp
[**] This work was supported by a Grant-in-Aid for Challenging Exploratory
Research (16K14473) from JSPS
Supporting information for this article is given via a link at the end of the
document.((Please delete this text if not appropriate))
This article is protected by copyright. All rights reserved.

10.1002/anie.201803043
Angewandte Chemie International Edition
COMMUNICATION
(A) Removal of single OH group
(B) Removal of vicinal OH groups
X
reach >99% conversion at 51 h
and the selectivity to 1 was 96%,
providing 1 in 96% yield. The
turnover frequency (TOF) and
turnover number (TON) based on
total Re amount were calculated
to be 4.9 h-1 and 77, respectively
by using the results at 0 and 4 h,
and that at 51 h. The values were
lower than the reported ones in
the case of 1,4-anhydroerythritol
(TOF=35 h-1, TON=600) over the
same catalyst at the same
reaction temperature and H2
O
HO
X
O
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
HO
HO
X
X
X
X
X
O
O
HO
HO
OCH3
+
+
Removal of
trans-vicinal OH groups
OH
X
X
OH
O
X
O
OH
X
X
cis-position
H2
O
HO
HO
HO
X
OH
O
OH
O
OCH3
OCH3
HO
HO
OCH3
(X = H, CH3, CH2OH)
Without
vicinal OH groups
OCH3
Removal of
cis-vicinal OH groups
trans-position
(X = H, CH2OH)
O
OCH3
OH
O
HO
X
OH
O
HO
O
OCH3
HO
Problem: Many possible products
(C) Conventional biomass transformation route
OH
OH
Without retention of original stereostructure
OH
O
O
HO
HO
HO
HO
OH
HO
O
O
Cellulose
Hemicellulose
O
O
pressure[25,26]
. Particularly, the
TOF was lower than those of 1,4-
anhydroerythritol and simple
Levulinic acid
Diols
OH
OH
OH
OH
O
O
HO
HO
etc..
Furfurals
OH OH
HO
OH
OH
Valuable
chemicals
OH
Sugars
Ethyleneglycol
Propyleneglycol
Alkanes
OH
OH
HO
diols[25,26]
, suggesting that the
HO
OH
OH OH
OH OH
etc..
reactivity of methyl glycosides is
low compared with simple diols.
Focusing on the selectivity at the
initial stage, methyl α-D-2,3-
dideoxy-erythro-hex-2-
Sugar alcohols
(D) This work: New biomass transformation route (selective removal of cis-vicinal OH groups in methyl glycosides
and further transformation to chiral polyol building blocks and α,ω-diol synthon)
With retention of original stereostructure
X
Cellulose
Hemicellulose
O
HO
enopyranoside (2) was observed
and the selectivity decreased
with increasing reaction time.
These results suggest that the
H2O
-CH3OH
OH
cis-position
Chiral polyol
building block
Methyl
glycosylation
X
X
OH
O
OH
O
2 H2, -2 H2O
H2O, H2
-CH3OH
Sugars
HO
HO
HO
X
OH
H2
ReOx-Pd/CeO2
OCH3
OCH3
(X = H, CH2OH)
OH
trans-position
X
-CH3OH
X
O
formation of
1 proceeds via
HO
HO
OH
hydrogenation of 2 and 2 is
produced by DODH reaction of
cis-C6 (Eq. 1). At longer reaction
α,ω-Diols
α,ω-Diol synthon
Scheme 1. Transformation methods of biomass-derived sugars and methyl glycosides.
2wt%, Pd/Re=1/4) catalyst, which is the optimized one in our
previous work[25,26] (Figure 1). Methyl C6-glycoside with
time (95 h), the selectivity to 1 decreased and that to others
including dehydration and/or hydrogenation products of 1
increased.
cis-vicinal OH groups, methyl α-D-mannopyranoside (cis-C6),
reacted to afford the corresponding dideoxy sugar, methyl α-
D-2,3-dideoxy-mannopyranoside (1), with high selectivity
(98%). On the other hand, methyl C6-glycoside without cis-
vicinal OH groups, methyl α-D-glucopyranoside (trans-C6),
hardly reacted, and no target deoxyglycoside was obtained. In
addition, the reaction with mixture of these C6-glycosides (cis-
C6+trans-C6) showed that only cis-C6 reacted in high
selectivity (97%), while the conversion was decreased by the
presence of trans-C6, which will be due to the competitive
adsorption of trans-C6 on the active site of ReOx-Pd/CeO2
catalyst. Similar tendency was observed in the case of methyl
C5-glycosides, although the reactivity of methyl C5-glycoside
with cis-vicinal OH groups, methyl β-D-ribofuranoside (cis-C5),
is higher than that of cis-C6. These results suggest that only
cis-vicinal OH groups in sugars can be selectively removed
even if other sugars with trans-vicinal OH groups coexist. In
addition, to compare the reactivity between cis-C6 and trans-
C6 more precisely, the reaction with trans-C6 at longer
reaction time of 24 h was carried out, providing 2% conversion
and no target product. The reactivity of cis-C6 is at least more
than 100-fold higher than that of trans-C6, indicating that
ReOx-Pd/CeO2 catalyst can selectivity recognize the structure
of cis-vicinal OH groups to achieve highly selective removal of
cis-vicinal OH groups in methyl glycosides.
The reusability of ReOx-Pd/CeO2 catalyst was studied in the
OH
OH
OH
OH
O
O
H2
H2
O
HO
HO
HO
(Eq. 1)
HO
-2 H2O
OCH3
OCH3
OCH3
cis-C6
2
1
OH
OH
O
OH
OCH3
O
OH
HO
OCH3
HO
O
O
HO
HO
HO
HO
OH
OH
OH
HO
OH
HO
OH
OCH3
HO
OCH3 HO
OCH3
OCH3
O
HO
O
OH
O
O
HO
+
+
HO
HO
OH
OCH3
OH
OCH3
HO
HO
Substrate
Figure 1. Comparison of reactivities of methyl glycosides with cis- or trans-
vicinal OH groups over ReOx–Pd/CeO2 catalyst. Conversion (blue bar) and
selectivity to the dideoxy sugars (orange bar) of various combination of
methyl C6- and C5-glycosides with cis- and trans-vicinal OH groups.
Reaction conditions: substrate 0.125 g or 0.125 + 0.125 g (for mixture
substrate), 1,4-dioxane 10 g, ReOx-Pd/CeO2(Re: 2wt%, Pd/Re=1/4) 150 mg
(100 mg for methyl C5-glycosides), 413 K, H2 8 MPa, 1 h.
The time-course of DODH-HG of methyl α-D-
mannopyranoside (cis-C6) over ReOx-Pd/CeO2 catalyst is
shown in Figure 2. The conversion increased smoothly to
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10.1002/anie.201803043
Angewandte Chemie International Edition
COMMUNICATION
OH
OH
OH
mannopyranoside from D-glucose with 6 steps[27,28], 40% total
yield of methyl-D-2,3-dideoxy riboside from halogenated
benzene with 7 steps[29] and 54% total yield for methyl-β-D-3,4-
O
O
2 H2
HO
HO
HO
+ 2 H2O
OCH3
ReOx-Pd/CeO2
1
OCH3
100
90
80
70
60
50
40
30
20
10
0
dideoxy
galactopyranoside
from
methyl
β-D-
galactopyranoside with 6 steps[30], Scheme S1). Judging from
the optimized catalyst amount and reaction time, the reactivity
of a methyl glycoside with a five-membered ring (entry 3) is
higher than those with a six-membered ring. This is the first
report on high-yield synthesis of dideoxy glycosides directly
from methyl glycosides without protection of OH groups except
the OH group of the hemiacetal group using H2 as a reducing
agent.
To expand the application of the method, further
transformation of the produced dideoxy glycoside to valuable
chemicals was investigated using methyl β-D-ribofuranoside
as a model substrate (Scheme 2(A)). After the DODH-HG of
methyl β-D-ribofuranoside, ReOx-Pd/CeO2 was removed by
filtration, and the produced dideoxy glycoside was easily
transformed to the corresponding dideoxy ribofuranose in high
yield of 97% only by addition of H2O under the conditions of
393 K and 4 h (hydration, Scheme 2(A)-(a)). On the other hand,
after the DODH-HG, water was added to the reaction mixture
without removal of ReOx-Pd/CeO2 catalyst and the mixture was
reacted at 393 K in 1,4-dioxane for 48 h, providing the (2S)-
1,2,5-pentanetriol in high yield of 97% and high ee of 96% with
maintaining the configuration of the original methyl β-D-
ribofuranoside (hydration+hydrogenation, Scheme 2(A)-(b)). In
addition, after the DODH-HG, ReOx-Pd/CeO2 was removed by
filtration, and Rh-ReOx/SiO2 and n-heptane were added into
the filtrate and the mixture was heated under H2 at 393 K for
24 h, providing tetrahydrofurfuryl alcohol (THFA) in high yield
of 91% (Scheme 2(A)-(c)), which will be produced by the
consecutive reactions of hydration, hydrogenation and
dehydration (Scheme S2). Considering that THFA can be
easily transformed by hydrogenolysis to 1,5-pentanediol in
0
10 20 30 40 50 60 70 80 90 100
Time / h
Figure 2. Time-course of DODH-HG of methyl α-D-mannopyranoside over
ReOx–Pd/CeO2 catalyst (: conversion, ꢀ: selectivity to 1, ꢁ: selectivity to
2, ꢂ: selectivity to others). Reaction conditions: methyl α-D-
mannopyranoside 0.25 g, ReOx–Pd/CeO2(Re: 2wt%, Pd/Re=1/4) 150 mg,
1,4-dioxane 10 g, 413 K, H2 8 MPa.
same reaction (Figure S1). The catalyst could be reused four
times without loss of activity and selectivity. The structure of
the catalyst was maintained after the reuse test, which was
confirmed by XRD (Figure S2), XANES (Figure S3) and
EXAFS (Figures. S4 and S5, and Tables S1 and S2) analyses.
From the ICP analysis of the filtrate, the leaching amount of Pd
and Re species was below the detection level and 1%,
respectively. Therefore, ReOx-Pd/CeO2 is
a
reusable
heterogeneous catalyst. The scope of methyl glycosides with
cis-vicinal OH groups was investigated using ReOx–Pd/CeO2
catalyst (Table 1). The cis-vicinal OH groups in the methyl
glycosides were selectively removed to afford the
corresponding dideoxy glycosides in high yields with high
selectivities by optimizing the catalyst amount and reaction
time, and the yields were much higher than those in the
previous reports (≤31% total yield of methyl-α-D-2,3-dideoxy
high yield (up to 94%) over Rh-ReOx or Ir-ReOx catalysts[31,32]
,
the transformation route can be a new production process of
α,ω-diols such as 1,5-pentanediol and 1,6-hexandiol
from biomass. In contrast, (2R)-1,2,5-pentanetriol
Table 1 Scope of methyl glycosides in DODH-HG over ReOx–Pd/CeO2 catalyst
Catalyst
t
Conv.
/%
Sel.
/%
Yielda
/%
was also obtained in high yield of 95% and high ee
of 95% with maintaining the configuration of the
original structure from methyl β-L-arabinopyranoside
via DODH-HG over ReOx-Pd/CeO2 catalyst, and
subsequent hydration and hydrogenation over Rh-
ReOx/SiO2 catalyst (Scheme 2(B)). Therefore,
enantiomers of 1,2,5-pentanetriol could be
individually synthesized from glycosides by changing
the starting materials.
Entry
Substrate
Product
amount
/mg
/h
OH
OH
OH
O
O
HO
HO
HO
1
2
150
300
51
72
99
94
97
94
96(91)
OCH3
Methyl α-D-mannopyranoside
OH
OCH3
OH
OH
O
O
88(84)
HO
OCH3
OH
OCH3
OCH3
Methyl β-D-galactopyranoside
OH
OCH3
HO
O
HO
O
3
100
24
>99
94
93(93)
OH
HO
Finally, one-pot transformation of D-ribose to (2S)-
Methyl β-D-ribofuranoside
1,2,5-pentanetriol was demonstrated by combination
of catalysts (Scheme 2(C)). D-Ribose easily
underwent glycosylation by methanol at room
temperature under air with Ir-ReOx/SiO2 catalyst to
provide mixture of methyl β-D-ribofuranoside and
methyl α-D-ribofuranoside (79% and 19%). After the
reaction, ReOx-Pd/CeO2 was added into the reaction
mixture without removal of Ir-ReOx/SiO2 catalyst, and
the mixture was reacted at 413 K under H2 for 4 h,
providing the corresponding dideoxy glycosides in
OH
O
O
HO
4
5
6
150
450
150
72
95
36
>99
97
93
83
92
93(88)
OH
OH
OCH3
OCH3
Methyl β-L-arabinopyranoside
OCH3
OCH3
OH
H3C
HO
O
OH
H3C
82(78)
O
OH
Methyl α-L-fucopyranoside
OCH3
OCH3
H3C
HO
O
>99
92(87)
H3C
HO
O
HO
OH
Methyl α-L-rhamnopyranoside
Reaction conditions: methyl glycoside 0.25 g, ReOx–Pd/CeO2(Re=2 wt%, Pd/Re=1/4), 1,4-
dioxane 10 g, 413 K, H2 8 MPa. aThe numbers outside and inside the parentheses are GC
and isolated yields, respectively.
95% yield (methyl β-D-2,3-dideoxy-ribofuranoside
This article is protected by copyright. All rights reserved.

10.1002/anie.201803043
Angewandte Chemie International Edition
COMMUNICATION
(A)
HO
O
OH
substantiated in high total yield (93%) and high ee (96%) by
combination of ReOx-Pd/CeO2 and Ir-ReOx/SiO2 catalysts.
H2O, -CH3OH
Removal of
ReOx-Pd/CeO2
(a)
(b)
(c)
8 MPa H2, H2O
1,4-dioxane, 393 K, 4 h
dideoxy ribofuranose
Total Yield 97%
OCH3
HO
O
H2O, -CH3OH, H2
OCH3
2 H2, -2H2O
HO
OH
Keywords: Sugar, Deoxydehydration, hydrogenation,
HO
O
ReOx-Pd/CeO2
8 MPa H2, H2O
1,4-dioxane,
393 K, 48 h
ReOx-Pd/CeO2
8 MPa H2
1,4-dioxane
413 K, 25 h
OH
(2S)-1,2,5-pentanetriol
HO
methyl β-D-
ribofuranoside
Conversion >99%
OH
heterogeneous catalyst, Rhenium, Cerium oxide
methyl β-D-2,3-
dideoxy-ribofuranoside
Total yield 97% (a94%)
96% ee
HO
O
H2, -CH3OH
Rh-ReOx/SiO2
8 MPa H2
[1] J. J. Bozell, G. R. Peterson, Green Chem. 2010, 12, 539-554.
[2] J. N. Chheda, G. W. Huber, J. A. Dumesic, Angew. Chem. Int. Ed. 2007,
46, 7164-7183.
Removal of
ReOx-Pd/CeO2
1,4-dioxane + n-heptane
393 K, 24 h
tetrahydrofurfuryl alcohol
Total yield 91%
[3] J. C. Serrano-Ruiz, J. A. Dumesic, Energy Environ. Sci. 2011, 4, 83-99.
[4] Y. Román-Leshkov, J. N. Chheda, J. A. Dumesic, Science 2006, 312,
1933-1937.
H2
HO
OH
Hydrogenolysis
Established technique
1,5-pentanediol
yield~up to 94%
(B)
OH
[5] G. W. Huber, J. N. Chheda, C. J. Barrett, J. A. Dumesic, Science 2005,
308, 1446-1450.
O
O
2 H2, -2H2O
H2O, -CH3OH, H2
HO
Rh-ReOx/SiO2
8 MPa H2, H2O
1,4-dioxane
393 K, 1 h
OH
OH
ReOx-Pd/CeO2
8 MPa H2
1,4-dioxane
413 K, 72 h
HO
OH
OH
[6] J. Q. Bond, D. M. Alonso, D. Wang, R. M. West, J. A. Dumesic, Science
2010, 327, 1110-1114.
OCH3
(2R)-1,2,5-pentanetriol
Total yield 95%
95% ee
OCH3
methyl β-L-3,4-dideoxy-
arabinopyranoside
methyl β-L-
arabinopyranoside
Conversion >99%
[7] H. Zhao, J. E. Holladay, H. Brown, Z. C. Zhang, Science 2007, 316, 1597-
1600.
(C)
HO
[8] R.-J. van Putten, J. C. van der Waal, E. de Jong, C. B. Rasrendra, H. J.
Heeres, J. G. de Vries, Chem. Rev. 2013, 113, 1499-1597.
[9] G. W. Huber, R. D. Cortright, J. A. Dumesic, Angew. Chem. Int. Ed. 2004,
43, 1549-1551; Angew. Chem. 2004, 116, 1575–1577.
[10] R. R. Davda, J. W. Shabaker, G. W. Huber, R. D. Cortright, J. A.
Dumesic, Appl. Catal. B 2005, 56, 171-186.
OCH3
O
HO
O
HO
O
OH
CH3OH, -H2O
+
OCH3
OH
Ir-ReOx/SiO2
CH3OH
r.t., 24 h, air
HO OH
D-ribose
Conversion >99%
HO
HO
OH
Yield (%)
79
19
OCH3
2H2, -2H2O
HO
O
HO
O
Ir-ReOx/SiO2 + ReOx-Pd/CeO2
CH3OH
+
OCH3
OH
[11] Deoxy sugars: occurrence and synthesis; R. M. De Lederkremer, C.
Marino, in Advances in Carbohydrate Chemistry and Biochemistry,
Derek Horton Ed. Elsevier: 2007, vol. 61, pp. 143-216.
[12] V. Křen T. Řezanka, FEMS Microbiol. Rev. 2008, 32, 858-859 (2008).
[13] T. G. Frihed, M. Bols, C. M. Pedersen, Chem. Rev. 2015, 115, 3615-
3676.
Yield (%)
81
14
413 K, 4 h
H2O, -CH3OH, H2
HO
Ir-ReOx/SiO2 + ReOx-Pd/CeO2
H2O, CH3OH
OH
(2S)-1,2,5-pentanetriol
Total yield 93%
96% ee
393 K, 4 h
Scheme 2. Synthesis of chiral building blocks and α,ω-diol synthon. (A)
Formation of dideoxy ribofuranose, (2S)-1,2,5-pentanetriol and
tetrahydrofurfuryl alcohol from methyl β-D-ribofuranoside. (B) Formation of
(2R)-1,2,5-pentanetriol from methyl β-L-arabinopyranoside. (C) Formation of
(2S)-1,2,5-pentanetriol from D-ribose. See supplementary materials for
detailed procedures.
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81% + methyl α-D-2,3-dideoxy-ribofuranoside 14%). The
produced reaction mixture with water was heated, affording
(2S)-1,2,5-pentanetriol in 93% yield with 96% ee. This is first
example of one-pot transformation of sugars to chiral alcohols
in high yield and high ee without protection of OH groups
except the OH group of the hemiacetal group.
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In conclusion, we found that ReOx-Pd/CeO2 was an effective
heterogeneous catalyst for the direct and selective
transformation of methyl glycosides with cis-vicinal OH groups
to dideoxy glycosides without protection of OH groups except
the OH group of the hemiacetal group by deoxydehydration
and subsequential hydrogenation using gaseous H2 as a
reductant. The key for the selective transformation is
recognition of cis-vicinal OH groups in the methyl glycosides
by ReOx-Pd/CeO2 catalyst, leading to selective conversion of
the cis-vicinal OH groups to C=C bond by deoxydehydration.
Various methyl glycosides with cis-vicinal OH groups were
converted to the corresponding dideoxy glycosides in high
isolated yields (78-93%) with maintaining the intrinsic structure.
Furthermore, we demonstrated that the produced dideoxy
glycoside can be selectively transformed to the chiral polyols
in high yield and high ee by hydration and hydrogenation, and
both enantiomers of 1,2,5-pentanetriol can be individually
synthesized by changing the starting substrate of methyl
glycosides. Tetrahydrofurfuryl alcohol, a diol synthon of 1,5-
pentanediol, was also synthesized in high yield by hydration
and hydrogenation of the produced dideoxy sugar. One-pot
transformation of D-ribose to (2S)-1,2,5-pentanetriol was
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This article is protected by copyright. All rights reserved.

10.1002/anie.201803043
Angewandte Chemie International Edition
COMMUNICATION
COMMUNICATION
Sugar transformation: This is the first report on the single step transformation of
sugars to dideoxy sugars in high stereoselectivity and regioselectivity without
protecting OH groups except the OH group of the hemiacetal group using
heterogeneous CeO2-supported ReOx and Pd (ReOx-Pd/CeO2) catalyst and H2 as a
reducing agent.
Masazumi Tamura*, Naoto Yuasa, Ji
Cao, Yoshinao Nakagawa and Keiichi
Tomishige*
Page No. – Page No.
Transformation of Sugars to Chiral
Polyols over a Heterogeneous
Catalyst
This article is protected by copyright. All rights reserved.