An efficient synthesis and regioselective hydrogenolysis of dioxolane-type of carbohydrates

Article abstract of DOI:10.1016/j.tet.2016.04.068

Carbohydrates, inexpensive chiral sources, are very useful for many syntheses of chiral bioactive compounds. We have chosen to synthesize benzyl α-d-mannofuranosides and d-lyxofuranosides with dioxolane-type, 2,3-O-isopentylidene and 2,3-O-benzylidene acetals from d-mannose. Interestingly, we have discovered new knowledge about the cleavage of dioxolane-type using two catalysts, Cu(OTf)₂/BH₃·THF and TiCl₄/Et₃SiH. The results showed that the regioselectivity of the benzylidene acetal ring opening was affected by the adjacent hydroxy (OH) group and was not directed by the stereochemistry of the acetal center. The substrates containing OH groups at position 5 can be cleaved by Cu(OTf)₂/BH₃·THF in tetrahydrofuran to exclusively provide the 2-O-benzyl-3-hydroxy compounds. When the substrates bore the OH group at position 6, using TiCl₄/Et₃SiH in dichloromethane gave a similar pattern. If the substrates lacked the OH group at position 5 or 6, the reactions did not proceed or gave low selectivity. Our discovery is very useful for dioxolane-type ring opening of carbohydrate synthesis.

Full text of DOI:10.1016/j.tet.2016.04.068

Tetrahedron 72 (2016) 3296e3304
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
An efficient synthesis and regioselective hydrogenolysis of
dioxolane-type of carbohydrates
*
Boonsong Kongkathip , Nutthawat Chuanopparat, Ngampong Kongkathip
Natural Products and Organic Synthesis Research Unit (NPOS), Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of
Science, Kasetsart University, Chatuchak, Bangkok 10900, Thailand
a r t i c l e i n f o
a b s t r a c t
Article history:
Carbohydrates, inexpensive chiral sources, are very useful for many syntheses of chiral bioactive com-
Received 17 November 2015
Received in revised form 12 April 2016
Accepted 22 April 2016
pounds. We have chosen to synthesize benzyl
a-
D-mannofuranosides and
D-lyxofuranosides with
dioxolane-type, 2,3-O-isopentylidene and 2,3-O-benzylidene acetals from
D-mannose. Interestingly, we
have discovered new knowledge about the cleavage of dioxolane-type using two catalysts, Cu(OTf)2/
BH3$THF and TiCl4/Et3SiH. The results showed that the regioselectivity of the benzylidene acetal ring
opening was affected by the adjacent hydroxy (OH) group and was not directed by the stereochemistry of
the acetal center. The substrates containing OH groups at position 5 can be cleaved by Cu(OTf)2/BH3$THF
in tetrahydrofuran to exclusively provide the 2-O-benzyl-3-hydroxy compounds. When the substrates
bore the OH group at position 6, using TiCl4/Et3SiH in dichloromethane gave a similar pattern. If the
substrates lacked the OH group at position 5 or 6, the reactions did not proceed or gave low selectivity.
Our discovery is very useful for dioxolane-type ring opening of carbohydrate synthesis.
Ó 2016 Elsevier Ltd. All rights reserved.
Available online 25 April 2016
Keywords:
D
-mannose
Dioxolane
Benzylidene acetal
TiCl4/Et3SiH
Cu(OTf)2/BH3$THF
1. Introduction
and demonstrated that the hydroxy group directed the cleavage of
acetal by coordination with boron reagents. However, the reaction
Carbohydrates play an important role as components of various
biologically active natural compounds, but also as inexpensive
chiral sources for the synthesis of many chiral compounds.1 The
selective protection of hydroxy groups is necessary for organic
synthesis utilizing carbohydrates. The reductive ring-opening re-
action of the benzylidene acetal has been used frequently for
regioselective protection and/or transformation of the diol func-
tion. Generally, the regioselective reductive ring opening of 4,6-O-
benzylidene acetals in 4,6-O-benzylidenehexopyranosides, has
been shown to give either the corresponding 4-O-benzyl-6-
hydroxy or 6-O-benzyl-4-hydroxy derivative with high selectivity
and in good yield.2,3
details for the reductive opening of the dioxolane ring of carbo-
hydrates derivatives containing hydroxy groups have never been
reported.
The reductive ring opening of five-membered ring acetals
(dioxolanes) of hexopyranoses was first investigated by the Lip-
tak4,5 and Garegg groups.6 They reported that the direction of the
ring-cleavage of dioxolane-type benzylidene (1) and (3) by
LiAlH4eAlCl3 and BH3$NMe3/AlCl3 reagents, respectively, are de-
termined by the configuration of the acetal carbon (Scheme 1).
Saito et al.7 investigated the reductive ring opening of simple
dioxolane benzylidene acetals using BH3$SMe2/BF3$OEt2 reagents
OMe
OMe
O
b
O
BnO
BnO
BnO
O
OH
O
4
3
H
Ph
* Corresponding author. Tel.: þ66 2 5625444x2235; fax: þ66 2 5625444x2119;
Scheme 1. Ring cleavage of the 2,3-O-benzylidene acetal of hexopyranoses. Reagents
and conditions: (a) LiAlH4, AlCl3, CH2Cl2eEt2O, rt. (b) BH3$NMe3, AlCl3, THF or toluene.
e-mail address: fscibsk@ku.ac.th (B. Kongkathip).
http://dx.doi.org/10.1016/j.tet.2016.04.068
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

B. Kongkathip et al. / Tetrahedron 72 (2016) 3296e3304
3297
During our study on the synthesis of Tamiflu,8 we found that the
regiochemistry of the reductive ring opening of 2,3-O-iso-
pentylidene-a-D-mannofuranose (8) to 19 depends on the free
hydroxy group at C-5 (Table 1, entry 6). This finding prompted us to
investigate the reductive ring opening reaction of dioxolane-
containing sugars containing free hydroxy groups in more detail.
regioselective ring opening of 3,4-benzylidene acetal of arabino-
pyranosides.9 Treatment of acetoxy compound 9 with TiCl4/Et3SiH
either at ꢀ78 ꢁC or 0 ꢁC afforded poor selectivity (21:22¼1:1)
(entries 1 and 2) (Table 1). Better regioselectivity was observed
when the parent compound 8, containing a hydroxy group at C-5
was treated with this catalyst to give 19 and 20 in the ratio of 2.7:1
(entry 4). These results indicated that the direction of ring cleavage
might be influenced by the OH substitution at C-5. In order to in-
vestigate the effect of the functional group at C-5, the aldehyde
analogue 7, silyl ether 10 and tosylate 11 were also examined.
Moreover, Cu(OTf)2 was also assessed as this has been reported to
be an effective catalyst for the regioselective ring opening of the
4,6-O-benzylidene acetal in hexopyranosides systems.3 It was
found that when using Cu(OTf)2/BH3$THF in CH2Cl2 with alcohol 8,
only the hydrolyzed product was observed (entry 5), whereas the
reactions of tosylate 11 did not proceed either using Cu(OTf)2/
BH3$THF or TiCl4/Et3SiH (entries 10 and 11). The same result was
obtained when aldehyde 7 was treated with Cu(OTf)2/Et3SiH in
CH3CN, the reaction did not occur, only the starting material was
recovered (entry 7). In the case of 7, it might be due to Cu(OTf)2
being a weaker Lewis acid than TiCl4. Therefore Cu(OTf)2 was used
with BH3$THF, a stronger reducing agent than Et3SiH. The result
showed that reductive ring opening of 7 gave 2-isopentyl ether
product 19 (60%) along with alcohol 8 (entry 8). The results in-
dicated that aldehyde 7 was first reduced to alcohol 8 and then
acetal ring opening led to 19. Similar results were observed when
the acetate 9 and silyl ether 10 were examined (entries 3 and 9).
Thin Layer Chromatography monitoring of the reaction revealed
2. Results and discussion
Cleavage of dioxolane-type acetals of hexo- and pentofurano-
sides was investigated using the model systems, 2,3-O-iso-
pentylidene and benzylidene acetal
D
-mannofuranosides,
D-
lyxofuranosides and their derivatives, containing a hydroxy group
at the C-5 position. Therefore new carbohydrates, manno- and
lyxofuranosides with a dioxolane were synthesized. The 2,3:5,6-di-
O-isopentylidene acetal 5 was prepared from
method described in our previous paper.8 Mild acid treatment re-
moved the 5,6-acetal group of to give benzyl 2,3-O-iso-
pentylidene- -mannofuranoside (6) in good yield. Oxidation of
D-mannose by the
5
a-D
the 5,6-dihydroxyl of 6 with sodium periodate provided the in-
termediate aldehyde compound 7 which was then reduced with
sodium borohydride to give benzyl 2,3-O-iso-pentylidene-a-D-lyx-
ofuranoside (8). Acetylation of 8 gave acetate 9 and treatment of 8
with Me3SiCl and TsCl provided silyl ether 10 and tosylate 11, re-
spectively in good yield (Scheme 2).
In our initial studies, a highly selective catalyst protocol (TiCl4/
Et3SiH) reported by Gilead was used with the acetate derivative 9,
which was previously employed in our recent study on the
Table 1
Reductive ring opening (Hydrogenolysis) of dioxolane type, 2,3-O-isopentylidene (7e11) and 2,3-O-benzylidene (15) of carbohydrates
Entry
Compound
Lewis acid, reducing agent, condition
Quantity of Lewis acid
Product (% yield)
19
20
21
22
23
8
1
2
3
4
5
6
7
8
9
9
9
8
8
8
7
7
TiCl4, Et3SiH, CH2Cl2, ꢀ78 ꢁC, 5 min
TiCl4, Et3SiH, CH2Cl2, 0 ꢁC, 5 min
Cu(OTf)2, BH3$THF, THF, rt, 10 min
TiCl4, Et3SiH, CH2Cl2, 0 ꢁC, 5 min
Cu(OTf)2, BH3$THF, CH2Cl2, rt, 5 min
Cu(OTf)2, BH3$THF, THF, rt, 2 h
Cu(OTf)2, Et3SiH, MeCN, rt, 2 h
Cu(OTf)2, BH3$THF, THF, rt, 2 h
Cu(OTf)2, BH3$THF, THF, rt, 10 min
Cu(OTf)2, BH3$THF, THF, rt, 2 h
TiCl4, Et3SiH, CH2Cl2, 0 ꢁC, 5 min
Cu(OTf)2, BH3$THF, THF, rt, 2 h
1.0 equiv
1.0 equiv
0.1 equiv
1.0 equiv
0.1 equiv
0.1 equiv
0.1 equiv
0.1 equiv
0.1 equiv
0.1 equiv
1.0 equiv
0.1 equiv
d
d
d
d
15
20
18
d
d
20
20
d
d
d
d
d
d
d
d
30
d
d
55
40
Hydrolysis
75
No reaction
60
d
d
d
d
9.8
d
d
d
d
d
d
d
d
19.8
30.5
9
10
11
11
59.1
10
11
12
No reaction
No reaction
d
15 exo/endo
d
d
d
75

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B. Kongkathip et al. / Tetrahedron 72 (2016) 3296e3304
Scheme 2. Synthesis of 2,3-O-isopentylidene of benzyl a-D-mannofuranosides (6), a-D-lyxofuranosides (8) and derivatives (9, 10, 11). Reagents and conditions: (a) 3-pentanone,
DMF, H2SO4, rt, overnight; (b) i) NaH, BnCl, DMF, rt, 4 h; ii) concd HCl, MeOH, rt, 3 h; (c) i) NaIO4, EtOHeH2O, rt, 1 h, d) NaBH4, EtOH, 0 ꢁCdrt, 2 h. 90% for two steps; (e) Ac2O, py,
CH2Cl2, rt, 2 h. 80%; (f) TMSCl, Et3N, CH2Cl2, rt, 24 h. 90%; (g) TsCl, py, CH2Cl2, rt, 2 h. 95%.
that the acetoxy and silyl groups were removed under the reaction
conditions to give the corresponding alcohol 8, which then un-
derwent acetal ring opening. To prove our assumption, alcohol 8
was subjected to catalytic ring opening under the same conditions.
It is true that only isomer 19 was exclusively obtained from the
reaction (entry 6). From the above results it is clear that the OH at C-
5 is crucial for the reaction and also essential for the direction of
Fig. 1. A bidentate copper complex of 5-hydroxy-2,3-O-iso-pentylidene carbohydrates.
ring cleavage when Cu(OTf)2/BH3$THF is used.
In order to compare the above results with five-membered
benzylidene acetals, the 2,3-O-benzylidene analogue 15 was pre-
pared as a mixture of exo- and endo-isomers from -mannose
Surprisingly, the reaction of the 5,6-dihydroxy-containing 6
with Cu(OTf)2, BH3$THF did not proceed (Table 2, entry 1).
Unreacted starting material remained after 2 h. On the other hand
treatment of 6 with TiCl4, Et3SiH, CH2Cl2 at 0 ꢁC provided exclu-
sively 24 in moderate yield (52%) (entry 2). The above results
suggest that the copper catalyst can form a complex with the
dihydroxy groups, causing a loss of activity, whereas titanium can
coordinate with one of the two hydroxy groups and the adjacent
acetal oxygen of the compound 6 which undergoes ring opening. To
test this hypothesis, monoprotection of the diol 6 was prepared.
Treatment of 6 with TBDPSCl and TBDMSCl gave 16a and 16b, re-
spectively in good yield. The free OH at position 5 of 16b was then
D
(Scheme 3) using a modified method described by Florent.10 It was
earlier reported that the cleavage of the five-membered benzyli-
dene-type acetal ring is directed by the stereochemistry of the
acetal center.4,11 However upon treatment of 15 exo/endo with
Cu(OTf)2, BH3$THF in THF at room temperature for 2 h the 2-O-
benzyl ether 23 was exclusively obtained in good yield (Table 1,
entry 12). This observation indicated that under Cu(OTf)2/BH3$THF
catalysis the direction of benzylidene acetal ring opening was not
directed by the stereochemistry of the acetal center but by the
presence of the 5-OH group.
Scheme 3. Synthesis of 2,3-O-benzylidene of benzyl
a
-D-mannofuranosides (13) and
a
-D-lyxofuranosides (14 and 15). Reagents and conditions: (a) i) NaH, BnCl, DMF, rt, 4 h; ii)
concd HCl, MeOH, rt, 3 h; (b) NaIO4, EtOHeH2O, rt, 1 h 90%, (c) NaBH4, EtOH, 0 ꢁC, rt, 2 h. 98%.
This regioselectivity is attributed to the preferential complexa-
tion of the 5-hydroxy group and the adjacent acetal oxygen with
the copper reagent to form a bidentate complex (Fig. 1), which
would favor C3eO bond cleavage to give O-benzyl-2-O-iso-
benzylated to give 17 in good yield. Selective removal of silyl pro-
tecting group in 17 by treatment with TBAF at room temperature
afforded the 5-OBn compound 18 in good yield as shown in Scheme
4. No reaction was observed when treating 16a with either
Cu(OTf)2/BH3$THF or TiCl4/Et3SiH (Table 2, entries 3 and 4). This
pentylidene-5-a-D-lyxofuranoside (19).

B. Kongkathip et al. / Tetrahedron 72 (2016) 3296e3304
3299
Table 2
Reductive ring opening (Hydrogenolysis) of dioxolane type, 2,3-O-isopentylidene of carbohydrates containing 5,6-dihydroxyl (6) and mono protected compounds (16, 18)
Entry
Compound
Lewis acid, reducing agent, condition
Quantity of Lewis acid
Product (% yield)
24
25
26
1
2
3
4
5
6
6
16a
16a
18
Cu(OTf)2, BH3$THF, THF, rt, 2 h
TiCl4, Et3SiH, CH2Cl2, 0 ꢁC, 5 min
Cu(OTf)2, BH3$THF, THF, rt, 2 h
TiCl4, Et3SiH, CH2Cl2, 0 ꢁC, 5 min
TiCl4, Et3SiH, CH2Cl2, 0 ꢁC, 5 min
0.1 equiv
1.0 equiv
0.1 equiv
1.0 equiv
1.0 equiv
No reaction
52
No reaction
No reaction
d
d
d
32
21
could be explained by the presence of the bulky TBDPS group (at C-
6) next to the free OH at C-5 which hindered coordination of the OH
to the metal catalyst. However when alcohol 18 (free OH at C-6)
reacted with TiCl4/Et3SiH in CH2Cl2 at 0 ꢁC, acetal ring opening
reaction occurred to give 2-pentyl ether 25 as a major product
along with the regioisomer 26 (Table 2, entry 5) in the ratio of 3:2.
The results of this reaction and that one obtained from compound 6
(Table 2, entry 2) clearly concluded that TiCl4 is capable to co-
ordinate with OH at C-6 in the substrates 6 and 18.
4. Experimental
4.1. General
Proton nuclear magnetic resonance (1H NMR) spectra and car-
bon nuclear magnetic resonance (13C NMR) spectra were recorded
on a Varianutity INOVA 400 MHz and Bruker Avance III HD spec-
trometers. Chemical shifts were recorded as
d values in ppm.
Spectra were acquired in CDCl3 unless otherwise stated. The peak
due to residual CHCl3 (7.26 ppm for 1H and 77.23 ppm for 13C) was
used as the internal reference. Coupling constants (J) are given in
Hz, and multiplicity is defined as follows: br¼broad, s¼singlet,
d¼doublet, dd¼doublet of doublets, dt¼doublet of triplets,
t¼triplet, q¼quartet, m¼multiplet. Infrared (IR) spectra were
recorded in cmꢀ1 on a PerkineElmer 2000 FTIR spectrophotometer
at the Chemistry Department, Faculty of Science, Kasetsart Uni-
versity. Samples were analyzed either as a thin film on sodium
chloride disks or as KBr disks. Accurate mass spectra (HRMS) were
obtained on Q-TOF2 hybrid quadrapole time-of-flight mass spec-
trometer. Optical rotations were calculated using a JASCO P-2000
polarimeter at the Government Pharmaceutical Organization.
Melting points (mp) were determined on a MEL-TEMP capillary
melting point apparatus at the Chemistry Department, Kasetsart
University and are reported uncorrected in ꢁC. All chemicals and
solvents were purchased from the Fluka Co. Ltd. as analytical grade
and solvents were purified by general methods before being used.
Scheme 4. Protection of hydroxy groups at position 5 or 6 of 2,3-O-isopentylidene
benzyl
a-D-mannofuranoside (6). Reagents and conditions: (a) TBDPSCl, imidazole,
DMAP, CH2Cl2, 0 ꢁC, 1 h. 85%; (b) TBDMSCl, imidazole, DMAP, CH2Cl2, 0 ꢁC to rt, 1 h.
80%; (c) BnBr, NaH, THF, rt, 2 h, 70%; (d) TBAF, THF, rt, 12 h. 80% for two steps.
3. Conclusion
4.2. Preparation of benzyl-2,3-O-isopentylidene-and 2,3-O-
In conclusion, among the tested Lewis acids, we discovered that
Cu(OTf)2/BH3$THF in THF gave the best result for the highly
regioselective ring opening of both 2,3-O-isopentylidene and 2,3-
benzylidene-
a-D-mannofuranosides
4.2.1. General procedures. A solution of
D-mannose (1.00 g,
O-benzylidene acetal
D
-lyxofuranosides bearing
a
5-hydroxyl.
5.55 mmol) in dry DMF (11 mL) was mixed with 3-pentanone
(5.50 mL) or benzaldehyde (5.50 mL). The mixture was cooled to
0
ture. The reaction was stirred for 12 h then it was neutralized with
aqueous NaHCO3. The mixture was extracted with CH2Cl2. The or-
ganic layer was collected, dried over Na2SO4, filtered and the filtrate
was concentrated by evaporation under reduced pressure. The
residue was used in the next step without further purification.
These conditions resulted in the corresponding 2-O-pentyl and 2-
O-benzyl ethers with the substituted 3-hydroxyl. The use of TiCl4/
Et3SiH in CH2Cl2 provided a similar ring cleavage pattern in mod-
ꢁC and concd H2SO4 (0.28 mL) was added dropwise to the mix-
erate yield when the 2,3-O-isopentyli-dene acetal
D-mannofur-
anosides contain a 6-hydroxyl. Moreover our investigation revealed
that when the compounds contain an adjacent hydroxyl group, the
regioselective ring opening of the benzylidene acetal was not al-
tered by the adjacent hydroxyl group which could coordinate with
either the copper or titanium catalyst to form a bidentate metal-
complex intermediate.
A solution of crude 2,3:5,6-di-O-acetal D-mannofuranose (1.10 g)
in dry DMF (5 mL) was added into a cooled mixture of 60% sodium
hydride (0.33 g, 8.36 mmol), washed with THF, in DMF (5 mL) under

3300
B. Kongkathip et al. / Tetrahedron 72 (2016) 3296e3304
a nitrogen atmosphere. Benzyl chloride (1.28 mL, 11.1 mmol) was
slowly added into the mixture and the mixture was stirred for 4 h at
the room temperature. Then CH2Cl2 was added into the solution
and the mixture was extracted with water. The organic layer was
collected, dried over Na2SO4, filtered and the filtrate was concen-
trated by evaporation under reduced pressure. The residue was
used in the next step without further purification.
5.80 (s, H-endo-benzylidene), 5.65 (s, H-endo-benzylidene), 5.32 (s,
H-1), 5.31 (s, H-1), 5.30 (s, H-1), 4.99 (m, H-3), 4.85 (m, H-3),
4.81e4.56 (m, H-benzylic), 4.48e4.22 (m, H-4), 4.21e4.02 (m, H-5,
H-6), 3.88e3.73 (m, H-6); 13C NMR (CDCl3, 100 MHz)
d: 139.2,138.8,
138.7, 138.6, 138.3, 138.0, 131.5, 130.1, 129.9, 129.8, 129.5, 129.2,
129.1, 128.9, 128.7, 128.5, 128.4, 127.8, 127.6, 127.5, 127.4, 127.1, 126.8,
106.7, 106.2, 104.6, 104.2, 102.2, 97.9, 85.8, 85.7, 81.9, 81.6, 81.4, 80.5,
79.2, 74.8, 74.2, 73.9, 73.3, 69.5, 69.1, 68.6, 68.5, 61.4; HRMS (ESIþ)
m/z [MþNa]þ, calcd for C27H26NaO6: 469.1622, found: 469.1627.
To a cooled solution of crude benzyl 2,3:5,6-di-O-acetal
D-
mannofuranose- -mannofuranoside (1.40 g) in MeOH (23 mL)
a-D
was added concd HCl (0.28 mL). This solution was diluted with
water until the solution turned turbidity. The solution was stirred at
room temperature about 3 h, then this solution was neutralized by
adding 30% NH4OH solution. The solvent was removed and the
residue was extracted with CH2Cl2 and water. The organic layer was
collected, dried over Na2SO4, filtered and the filtrate was concen-
trated by evaporation under reduced pressure. The residue was
purified by flash column chromatography on silica gel eluting with
EtOAc:hexane, 2:3.
4.2.6. Benzyl
2,3-O-isopentylidene-5-a-D-mannofuranoside
(6).8 Colorless oil (0.55 g, 34% for three steps); Rf (40% EtOAc/
25
hexane) 0.25; [
a
]
þ9.8 (c¼4.18, CHCl3); FTIR (neat), ymax, 3417,
D
3089, 3031, 2971, 2939,1462,1454 cmꢀ1; 1H NMR (CDCl3, 400 MHz)
d
: 7.21e7.29 (m, 5H, aromatic), 5.05 (s, 1H, H-1), 4.76 (dd, J¼3.6,
6.0 Hz, 1H, H-3), 4.58 (d, J¼6.0 Hz, 1H, H-2), 4.54 (d, J¼11.9 Hz, 1H,
eOCH2Ph), 4.42 (d, J¼11.9 Hz, 1H, eOCH2Ph), 3.99e3.97 (m, 1H, H-
5), 3.74 (dd, J¼3.6, 8.1 Hz, 1H, H-4), 3.74 (dd, J¼2.9, 11.4 Hz, 1H, H-6),
3.58 (dd, J¼3.6, 11.4 Hz, 1H, H-6), 2.09, 2.81 (2ꢂ br s, 2ꢂ 1H, eOH),
1.64, 1.51 (q, J¼7.5 Hz, 2ꢂ 2H, H-8, H-9), 0.84, 0.80, (t, J¼7.5 Hz, 2ꢂ
4.2.2. 2,3:5,6-Di-O-isopentylidene-5-
a
-
D
-mannofuranose (5).8 Pale
20
yellow oil (1.14 g, 65%); Rf (20% EtOAc/hexane) 0.50; [
a]
þ1.0
3H, H-10, H-11); 13C NMR (CDCl3, 100 MHz)
d: 137.4, 128.4, 128.0,
D
(c¼0.25, CHCl3); FTIR (neat), ymax, cmꢀ1: 3429, 2973, 2942, 2883,
127.9, 127.8, 116.9, 105.9, 85.2, 80.4, 79.5, 70.3, 69.2, 64.4, 28.8, 28.7,
8.7, 7.7; HRMS (ESIþ) m/z [MþNa]þ, calcd for C18H26NaO6: 361.1627,
found: 361.1613.
1463; 1H NMR (CDCl3, 400 MHz)
d
: 5.28 (d, J¼2.4 Hz, 1H, H-1), 4.71
(dd, J¼3.4, 5.9 Hz, 1H, H-3), 4.52 (d, J¼5.9 Hz, 1H, H-2), 4.34 (dd,
J¼6.4 Hz, 13.1 Hz, 1H, H-5), 4.08 (dd, J¼3.4, 6.4 Hz, 1H, H-4), 4.03
(dd, J¼6.4, 8.4 Hz,1H, H-6), 3.88 (dd, J¼6.4, 8.4 Hz,1H, H-6), 3.52 (br
s, 1H, eOH), 1.49e1.65 (m, 8H,eCH2e), 0.78e0.86 (m, 12H, eCH3);
4.2.7. Benzyl 2,3-O-benzylidene-5-a-D-mannofuranoside (13exo/
13endo). Colorless oil (0.50 g, 25% for three steps, the ratio of 13exo/
13endo¼2:3); Rf (40% EtOAc/hexane) 0.12; FTIR (neat), ymax, 3441,
13C NMR (CDCl3, 100 MHz)
d: 116.8, 112.8, 101.4, 85.9, 80.0, 77.3,
72.8, 67.2, 28.6, 7.9, 7.8, 7.7, 7.6; HRMS (ESIþ) m/z [MþNa]þ, calcd for
3112, 3065, 2935, 1455, 1399 cmꢀ1 1H NMR (400 MHz, CDCl3)
; d:
C
16H28NaO6: 339.1784, found: 339.1783.
7.51e7.28 (m, 20H, aromatic), 5.93 (s, 1H, H-7 exo), 5.76 (s, 1H, H-7
endo), 5.28 (s, 1H, H-1), 5.26 (s, 1H, H-1), 4.95 (dd, J¼5.5, 2.1 Hz, 1H,
H-3), 4.90 (dd, J¼6.1, 2.1 Hz, 1H, H-3), 4.80 (d, J¼6.0 Hz, 1H, CH2Ph),
4.72 (d, J¼6.0 Hz, 1H, CH2Ph), 4.67 (d, J¼6.0 Hz, 1H, CH2Ph), 4.64 (d,
J¼6.0 Hz, 1H, CH2Ph), 4.55 (d, J¼2.1 Hz, 1H, H-2), 4.52 (d, J¼2.1 Hz,
1H, H-2), 4.11e3.97 (m, 4H, H-4, H-4, H-5, H-5), 3.87e3.78 (m, 2H,
H-6), 3.67 (dt, J¼11.3, 5.6 Hz, 2H, H-6), 3.21 (s, 4H, eOH); 13C NMR
4.2.3. 2,3:5,6-Di-O-benzylidene-5-
a
-
D
-mannofuranoside
(12exo/
12endo). Pale yellow oil (1.26 g, 51%); FTIR (neat), ymax, cmꢀ1: 3435,
3067, 3015, 2948, 1701, 1459, 1401, 1219; 1H NMR (400 MHz, Ace-
tone) d: 7.55e7.46 (m, H-aromatic), 7.44e7.34 (m, H-aromatic), 5.97
(s, H-exobenzylidene), 5.96 (s, H-exobenzylidene), 5.94 (s, H-exo-
benzylidene), 5.79 (s, H-endobenzylidene), 5.78 (s, H-endobenzyli-
dene), 5.78e5.77 (s, H-endobenzylidene), 5.73 (s, H-
endobenzylidene), 5.53 (s, H-anomeric), 5.51 (s, H-anomeric), 5.50
(s, H-anomeric), 5.47 (s, H-anomeric), 5.01e4.90 (m, H-3),
4.78e4.68 (m, H-2), 4.66e4.52 (m, H-4), 4.33 (m, H-5), 4.25e4.13
(CDCl3, 100 MHz) d; 138.6, 137.6, 130.3, 130.1, 129.0, 128.9, 128.8,
128.3, 127.8, 127.5, 106.3, 106.2, 105.9, 86.0, 85.2, 81.6, 80.8, 80.7,
80.3, 69.9, 69.2, 69.1, 64.9, 64.8; HRMS (ESIþ) m/z [MþNa]þ, calcd
for C20H22NaO6: 381.1309, found: 381.1309.
(m, H-6), 4.11e3.95 (m, H-6); 13C NMR (CDCl3, 100 MHz)
d: 138.6,
4.3. Oxidative cleavage of benzyl-5,6-dihydroxy-2,3-acetal-
a-
138.0, 137.6, 130.3, 130.1, 129.0, 128.9, 128.8, 128.5, 128.3, 127.8,
106.3, 106.2, 105.9, 86.0, 85.2, 81.6, 80.7, 80.3, 69.9, 69.2, 69.1, 64.9,
64.8; HRMS (ESIþ) m/z [MþNa]þ, calcd for C20H20NaO6: 379.1152,
found: 379.1150.
D
-mannofuranoside
4.3.1. General procedure. To a solution of NaIO4 (1.2 equiv) in water
(2.70 mL/mmol) was added a solution of benzyl 2,3-O-acetal-
a-D-
mannofuranoside (1 equiv) in EtOH (2.70 mL/mmol) at the room
temperature. The resulting mixture was stirred for 1 h. The white
precipitate was filtered and then a few drops of ethylene glycol
were added into the filtrate. The white precipitate was filtered
again and the filtrate was concentrated under reduce pressure.
Then EtOH was added into the residue and the white precipitate
was filtered and repeated until no precipitation occurred. The
combined filtrates were concentrated under reduced pressure to
give pale-yellow oil. The residue was purified by flash column
chromatography on silica gel eluting with EtOAc:hexane, 1:4.
4.2.4. Benzyl
2,3:5,6-di-O-isopentylidene-5-a-D-manno-fur-
anoside.8 Pale yellow oil (1.03 g, 70%); Rf (7% EtOAc/hexane) 0.16;
25
[
a]
þ61.4 (c¼0.09, CHCl3); FTIR (neat), ymax, cmꢀ1: 3088, 3064,
D
3031, 2973, 2940, 2881, 1462; 1H NMR (CDCl3, 400 MHz)
d:
7.20e7.28 (m, 5H, aromatic), 5.00 (s, 1H, H-1), 4.69 (dd, J¼3.4,
5.9 Hz, 1H, H-3), 4.57 (d, J¼5.9 Hz, 1H, H-2), 4.54 (d, J¼11.6 Hz, 1H,
eCH2Ph), 4.40 (d, J¼11.6 Hz, 1H, eCH2Ph), 4.34 (dd, J¼6.4, 13.8 Hz,
1H, H-5), 4.03 (dd, J¼8.4, 6.4 Hz,1H, H-4), 3.90 (dd, J¼7.2, 3.4 Hz,1H,
H-6), 3.81 (dd, J¼8.4, 3.4 Hz, 1H, H-6), 1.47e1.64 (m, 8H, eCH2e),
0.77e0.87 (m, 12H, eCH3); 13C NMR (CDCl3, 100 MHz)
d: 137.3,
128.4, 127.9, 127.7, 116.8, 112.8, 105.9, 85.4, 80.8, 79.9, 73.1, 69.0,
67.4, 29.6, 29.2, 28.8, 8.3, 8.1, 7.9, 7.7; HRMS (ESIþ) m/z [MþNa]þ,
calcd for C23H34NaO6: 429.2253, found: 429.2253.
4.3.2. Benzyl-2,3-O-isopentylidene-5-
(7).8 Colorless oil (0.44 g, 90%); Rf (20% EtOAc/hexane) 0.37; [
þ47.0 (c¼0.14, CH2Cl2); FTIR (neat), ymax, 3089, 3064, 3031, 2972,
2881, 2363, 1739, 1462 cmꢀ1; 1H NMR (CDCl3, 400 MHz)
: 9.63 (d,
a-D-aldomannofuranoside
25
a
]
D
d
4.2.5. Benzyl
2,3:5,6-di-O-benzylidene-5-
a
-
D
-manno-furanoside
J¼1.1 Hz, 1H, H-5), 7.21e7.29 (m, 5H, aromatic), 5.22 (s, 1H, H-1),
5.01 (dd, J¼4.2, 5.9 Hz, 1H, H-3), 4.62 (d, J¼5.9 Hz, 1H, H-2), 4.62 (d,
J¼11.7 Hz, 1H, eOCH2Ph), 4.45 (d, J¼11.7 Hz, 1H, eOCH2Ph), 4.36 (d,
J¼4.2 Hz, 1H, H-4), 1.64, 1.51 (q, J¼7.5 Hz, 2ꢂ 2H, H-8, H-9), 0.79,
(exo/endo). Pale yellow oil (0.89 g, 70%); Rf (5% EtOAc/hexane) 0.18;
FTIR (neat), ymax, cmꢀ1: 3089, 3033, 2944, 2882, 1728, 1458, 1397,
1091, 1071; 1H NMR (400 MHz, Acetone)
d: 7.60e7.15 (m, H-aro-
matic), 5.98 (s, H-exo-benzylidene), 5.95 (s, H-exo-benzylidene),
0.77 (t, J¼7.5 Hz, 2ꢂ 3H, H-10, H-11); 13C NMR (CDCl3, 100 MHz)
d:

B. Kongkathip et al. / Tetrahedron 72 (2016) 3296e3304
3301
197.5, 136.8, 128.5, 117.7, 105.8, 85.0, 84.5, 81.2, 69.3, 29.0, 28.6, 8.3,
7.4; HRMS (ESIþ) m/z [MþH]þ, calcd for C17H23O5: 307.1545, found:
307.1545.
30 min at room temperature then acetic anhydride (0.21 mL,
2.27 mmol) was dropped into the solution which was then stirred
for 2 h at room temperature. Removal of solvent afforded a syrup
which was purified by column chromatography on silica gel using
4.3.3. Benzyl-2,3-O-benzylidene-5-
a
-
D
-aldolyxofuranoside (14exo/
a mixture of EtOAc:hexane, 10:90 as eluent to give 9 (0.32 g, 80%) as
25
14endo). Colorless oil (0.42 g, 90%, the ratio of 14exo/14endo¼3:7);
a colorless oil; Rf (15% EtOAc/hexane) 0.25; [
a
]
þ74.8 (c¼0.79,
D
25
Rf (20% EtOAc/hexane) 0.30; FTIR (neat), ymax, 3089, 3065, 2941,
CHCl3); (lit. [
a]
þ74.75 (c¼0.79, CHCl3)); FTIR (neat), ymax, 3031,
D
1737, 1455, 1218 cmꢀ1
;
1H NMR (400 MHz, Acetone-d6)
d: 9.81 (s,
2972, 1744 cmꢀ1 1H NMR8 (CDCl3, 400 MHz)
; d: 7.35e7.25 (m, 5H,
1H, H-5), 9.71 (s, 1H, H-5), 7.52e7.26 (m, 20H, aromatic), 5.94 (s, 1H,
H-6 exo), 5.78 (s, 1H, H-6 endo), 5.43 (s, 1H, H-1), 5.42 (s, 1H, H-1),
5.39 (dd, J¼5.2, 4.5 Hz, 1H, H-3), 5.30 (dd, J¼5.2, 4.2 Hz, 1H, H-3),
4.84 (d, J¼5.2 Hz, 1H, H-2), 4.81 (d, J¼5.2 Hz, 1H, H-2), 4.75 (d,
J¼4.0 Hz, 2H, CH2Ph), 4.73 (d, J¼4.0 Hz, 2H, CH2Ph), 4.62 (d,
J¼4.5 Hz, 1H, H-4), 4.59 (d, J¼4.2 Hz, 1H, H-4); 13C NMR (CDCl3,
aromatic), 5.12 (s, 1H, H-1), 4.72 (dd, J¼3.5, 5.9 Hz, 1H, H-3), 4.67 (d,
J¼11.8 Hz, 1H, eOCH2Ph), 4.64 (d, J¼5.9 Hz, 1H, H-2), 4.48 (d,
J¼11.8 Hz, 1H, eOCH2Ph), 4.28 (dd, J¼3.0, 11.76 Hz, 1H, H-5), 4.17
(dd, J¼7.7, 10.56 Hz, 1H, H-5), 4.48 (ddd, J¼3.6, 5.4, 4.7 Hz, 1H, H-4),
2.09 (s, 3H, eC(O)CH3), 1.67, 1.53 (2ꢂ q, J¼7.8 Hz, 2ꢂ 2H, H-8, H-9),
0.88, 0.83 (2ꢂ t, J¼7.4 Hz, 2ꢂ 3H, H-10, H-11); 13C NMR (CDCl3,
100 MHz)
d
: 197.6, 196.9, 138.3, 137.3, 136.9, 130.5, 130.3, 129.1,
100 MHz) d: 170.7, 137.3, 128.4, 127.9, 127.7, 117.0, 105.9, 85.3, 80.0,
128.9, 128.5, 127.9, 127.5, 107.0, 106.6, 106.3, 106.0, 85.9, 85.7, 85.0,
78.1, 69.0, 62.8, 29.1, 28.7, 20.8, 8.3, 7.5; HRMS (ESIþ) m/z [MþNa]þ,
84.8, 82.2, 80.9, 69.6, 69.5; HRMS (ESIþ) m/z [MþH]þ, calcd for
calcd for C19H26NaO6: 373.1622, found: 373.1638.
C
19H19O5: 327.1227, found: 327.1232.
4.6. Benzyl 2,3-O-isopentylidene-5-O-trimethylsilyl-a-D-lyx-
4.4. Reduction of 2,3-acetal-5-aldolyxofuranoside
ofuranoside (10)8
4.4.1. General procedure. To a solution of benzyl 2,3-O-acetal-5-a-
Trimethylsilylchloride (0.2 mL, 0.99 mmol) was dropped into
a cooled solution of 8 (0.20 g, 0.65 mmol) and Et3N (0.22 mL,
1.63 mmol) in CH2Cl2 (1.5 mL) under nitrogen atmosphere. The
reaction was warmed to room temperature and stirred for 24 h.
The solution was washed with brine and the organic layers were
collected and dried over Na2SO4 and filtered. Removal of the sol-
vent afforded a syrup which was purified by column chromatog-
raphy on silica gel using a mixture of EtOAc:hexane, 5:95 as eluent
to give 10 (0.22 g, 90%) as a colorless oil; Rf 2(510% EtOAc/hexane)
D-aldolyxofuranoside (1 equiv) in EtOH (2.70 mL/mmol) was added
sodium borohydride (1.2 equiv). The solution was stirred for 2 h.
The solution was cooled to 0 ꢁC and acetone was added, then the
solvent was removed. The residue was extracted with CH2Cl2 and
water, and combined extracts were dried over Na2SO4 and filtered.
After removal of the solvent under vacuo, the crude product was
purified by flash column chromatography on silica gel eluting with
EtOAc:hexane, 1:3.
0.25;
[
a
]
D
25þ74.6 (c¼0.35, CHCl3); (lit.
[
a]
þ74.58 (c¼0.35,
D
4.4.2. Benzyl
2,3-O-isopentylidene-5-a-D-lyxofuranoside
CHCl3)); FTIR (neat), ymax, cmꢀ1: 3031, 2972; 1H NMR8 (CDCl3,
400 MHz) d: 7.27e7.16 (m, 5H, aromatic), 5.02 (s, 1H, H-1), 4.62
(8).8 Started from 7 (0.40 g, 1.57 mmol): colorless oil (0.46 g, 98%);
23
25
Rf (20% EtOAc/hexane) 0.12; [
þ72.27 (c¼0.96, CHCl3)); FTIR (neat), ymax, 3435, 3031, 2972,
1089 cmꢀ1 1H NMR8 (CDCl3, 400 MHz)
: 7.28e7.17 (m, 5H, aro-
a
]
þ72.3 (c¼0.96, CHCl3); (lit. [
a]
D
D
(dd, J¼3.4, 5.9 Hz, 1H, H-3), 4.60 (d, J¼11.7 Hz, 1H, eOCH2Ph), 4.55
(d, J¼5.9 Hz, 1H, H-2), 4.38 (d, J¼11.8 Hz, 1H, eOCH2Ph), 4.48 (ddd,
J¼3.4, 6.6, 5.3 Hz, 1H, H-4), 3.90 (dd, J¼3.3, 10.9 Hz, 1H, H-5), 3.80
(dd, J¼6.7, 10.9 Hz, 1H, H-5), 1.61, 1.48 (2ꢂ q, J¼7.8 Hz, 2ꢂ 2H, H-8,
H-9), 0.81, 0.77 (2ꢂ t, J¼7.4 Hz, 2ꢂ 3H, H-10, H-11), 0.09 (s, 3ꢂ 3H,
;
d
matic), 5.06 (s, 1H, H-1), 4.68 (dd, J¼3.5, 5.9 Hz, 1H, H-3), 4.60 (d,
J¼11.8 Hz, 1H, eOCH2Ph), 4.58 (d, J¼5.9 Hz, 1H, H-2), 4.40 (d,
J¼11.7 Hz, 1H, eOCH2Ph), 4.03 (ddd, J¼3.6, 5.4, 5.4 Hz, 1H, H-4),
3.90e3.88 (m, 2H, H-5), 2.39 (br s, 1H, eOH), 1.62, 1.48 (2ꢂ q,
J¼7.6 Hz, 2ꢂ 2H, H-8, H-9), 0.83, 0.78 (2ꢂ t, J¼7.4 Hz, 2ꢂ 3H, H-10,
eSiMe3); 13C NMR (CDCl3, 100 MHz),
d: 137.5, 128.3, 128.0, 127.7,
116.6, 105.6, 85.4, 81.0, 79.9, 68.8, 60.6, 28.8, 28.3, 8.3, 7.1, ꢀ0.4;
HRMS (ESIþ) m/z [MþNa-SiMe3]þ, calcd for C17H24NaO5: 331.1516,
found: 331.1525.
H-11); 13C NMR (CDCl3, 100 MHz)
d: 137.2, 128.4, 116.9, 105.5, 85.5,
80.1, 79.8, 68.8, 61.5, 28.4, 8.3, 7.6; HRMS (ESIþ) m/z [MþNa]þ, calcd
for C17H24NaO5: 331.1521, found: 331.1522.
4.7. Benzyl 2,3-O-isopentylidene-5-O-toluenesulfonyl-a-D-
4.4.3. Benzyl-2,3-O-benzylidene-5-
a-D
-lyxofuranoside (15exo/15en-
lyxofuranoside (11)
do). Started from 14exo/endo (0.40 g, 1.23 mmol): colorless oil
(0.39 g, 98%, the ratio of 15exo/15endo¼3:2); Rf (20% EtOAc/hexane)
0.12; FTIR (neat), ymax, 3474, 3015, 2928, 1459, 1399, 1217 cmꢀ1; 1H
Compound 8 (0.20 g, 0.65 mmol) was dissolved in dry pyridine
(0.1 mL, 1.30 mmol) and dry CH2Cl2 (2 mL). The solution was stirred
for 30 min at room temperature then toluenesulfonyl chloride
(0.25 g,1.31 mmol) was dropped into the solution which was stirred
for 2 h at room temperature. Removal of solvent afforded a syrup
which was purified by column chromatography on silica gel using
a mixture of EtOAc:hexane, 10:90 as eluent to give 11 (0.26 g, 95%)
NMR (400 MHz, Acetone) d: 7.60e7.25 (m, 20H, aromatic), 5.88 (s,
1H, H-6 exo), 5.77 (s, 1H, H-6 endo), 5.23 (s, 1H, H-1), 5.20 (s, 1H, H-
1), 4.94 (dd, J¼5.5, 3.6 Hz, 1H, H-3), 4.90 (d, J¼6.1, 3.5 Hz, 1H, H-3),
4.77 (d, J¼5.0 Hz, 1H, CH2Ph), 4.74 (d, J¼5.0 Hz, 1H, CH2Ph), 4.71 (d,
J¼5.0 Hz, 2H, CH2Ph), 4.56 (d, J¼1.4 Hz, 1H, H-2), 4.53 (d, J¼1.5 Hz,
1H, H-2), 4.26e4.22 (m, 1H, H-4), 4.22e4.17 (m, 1H, H-4), 4.01e3.93
as a colorless oil; Rf (15% EtOAc/hexane) 0.25; [
CHCl3); FTIR (neat), ymax, 3031, 2972, 2884 cmꢀ1
400 MHz)
aromatic, eSO2PhMe), 4.98 (s, 1H, H-1), 4.59 (dd, J¼3.4, 5.9 Hz, 1H,
H-3), 4.54 (d, J¼11.7 Hz, 1H, eOCH2Ph), 4.53 (d, J¼5.9 Hz, 1H, H-2),
4.35 (d, J¼11.7 Hz,1H, eOCH2Ph), 4.30 (dd, J¼4.28,10.2 Hz,1H, H-5),
4.11e4.20 (m, 2H, H-4, H-5), 2.09 (s, 3H, eSO2CH3), 1.49, 1.41 (2ꢂ q,
J¼7.5 Hz, 2ꢂ 2H, H-8, H-9), 0.74, 0.69 (2ꢂ t, J¼7.5 Hz, 2ꢂ 3H, H-10,
a
]
;
25 þ50.3 (c¼0.66,
D
(m, 2H, H-5), 3.88 (m, 2H, H-5); 13C NMR (CDCl3, 100 MHz)
d: 138.6,
1H NMR (CDCl3,
138.0, 137.6, 130.3, 130.1, 129.0, 128.9, 128.7, 128.3, 127.8, 127.5,
106.5,106.0,105.6, 86.3, 85.4, 82.0, 81.7, 81.3, 80.5, 69.0, 60.6; HRMS
(ESIþ) m/z [MþNa]þ, calcd for C19H20NaO5: 351.1203, found:
351.1203.
d
: 7.75 (d, J¼8.36 Hz, 2H, eSO2PhMe), 7.18e7.27 (m, 7H,
4.5. Benzyl 2,3-O-isopentylidene-5-O-acetyl-a-D-lyxo-furano-
side (9)8
H-11); 13C NMR (CDCl3, 100 MHz)
d: 146.7, 137.2, 136.0, 128.4, 127.9,
127.8, 117.0, 105.8, 87.1, 82.2, 80.8, 69.3, 65.2, 25.8, 25.6, 9.3, 8.3, 7.5;
HRMS (ESIþ) m/z [MþH]þ, calcd for C24H31O7S: 463.1790, found:
463.1812.
Compound 8 (0.35 g, 1.14 mmol) was dissolved in dry pyridine
(0.27 mL) and dry CH2Cl2 (2 mL). This solution was stirred for

3302
B. Kongkathip et al. / Tetrahedron 72 (2016) 3296e3304
4.8. Benzyl-2,3-O-isopentylidene-5-hydroxy-6-O-tert-butyl
diphenylsilyl- -mannofuranoside (16a)
was collected, dried over Na2SO4, filtered and the filtrate was
concentrated by evaporation. The residue was purified by flash
column chromatography eluting with EtOAc:hexane, 2:98 to give
a-D
To a solution of 6 (0.20 g, 0.59 mmol) in CH2Cl2 (3 mL) was
added imidazole (0.08 g, 1.92 mmol) and 4-N,N-dimethylamino-
pyridine (0.03 g, 0.30 mmol). The mixture was cooled to 0 ꢁC and
tert-butyldiphenylsilyl chloride (0.18 mL, 0.72 mmol) was added.
The reaction mixture was warmed to room temperature and stirred
for 5 h. This mixture was washed with saturated aqueous NH4Cl,
the organic layers were collected, dried over Na2SO4 and filtered.
The solvent of the filtrate was removed and the residue was puri-
fied by flash column chromatography on silica gel eluting with
the product (0.405 g, 70%) as a colorless oil; Rf (2% EtOAc/hexane)
25
0.37; [
a
]
D
þ22.1 (c¼2.25, CHCl3); FTIR (neat), ymax, 3089, 3032,
2930, 1462, 1360, 1253 cmꢀ1 1H NMR (400 MHz, CDCl3)
; d:
7.44e7.17 (m, 10H, aromatic), 5.09 (s, 1H, H-1), 4.84 (dd, J¼5.9,
3.3 Hz, 1H, H-3), 4.83 (d, J¼11.1 Hz, 1H, CH2Ph), 4.70 (d, J¼11.1 Hz,
1H, CH2Ph), 4.64 (d, J¼5.9 Hz, 1H, H-2), 4.63 (d, J¼12.0 Hz, 1H,
CH2Ph), 4.47 (d, J¼12.0 Hz, 1H, CH2Ph), 4.03 (dd, J¼9.2, 3.3 Hz, 1H,
H-4), 3.96 (d, J¼2.0 Hz, 1H, H-6), 3.90 (dd, J¼9.3, 2.1 Hz, 1H, H-5),
3.72 (dd, J¼10.7, 5.6 Hz, 1H, H-6), 1.78e1.66 (m, 2H, H-8), 1.61 (q,
J¼7.5 Hz, 2H, H-9), 0.94 (s, J¼1.7 Hz, 9H, eSitBuMe2), 0.95e0.88 (m,
3H, H-10), 0.11 (s, J¼1.0 Hz, 3H, H-11), 0.10 (s, 6H, eSitBuMe2); 13C
EtOAc:hexane, 6:94 to afford 16a as a colorless oil (0.29 g, 85%); Rf
25
(30% EtOAc/hexane) 0.67; [
a
]
þ57.5 (c¼0.61, CHCl3); FTIR (neat),
D
ymax, 3435, 3031, 2972 cmꢀ1
;
1H NMR (CDCl3, 400 MHz)
d:
NMR (CDCl3, 100 MHz) d: 139.0, 137.6, 128.3, 128.1, 128.0, 127.9,
7.76e7.69 (m, 6H, eSiPh2), 7.40e7.26 (m, 9H, aromatic, eSiPh2),
4.95 (s, 1H, H-1), 4.83 (dd, J¼2.7, 5.9 Hz, 1H, H-3), 4.61 (d, J¼5.9 Hz,
1H, H-2), 4.52 (d, J¼12.0 Hz, 1H, eOCH2Ph), 4.33 (d, J¼12.0 Hz, 1H,
eOCH2Ph), 4.27e4.26 (m, 1H, H-5), 3.96 (dd, J¼3.56, 8.12 Hz, 1H, H-
4), 3.87 (dd, J¼3.56, 11.1 Hz, 1H, H-6), 3.76 (dd, J¼1.6, 11.1 Hz, 1H, H-
6), 1.49, 1.44 (q, J¼7.4 Hz, 2ꢂ2H, H-8, H-9), 1.00 (s, 9H, etBu), 0.73,
127.6, 127.4, 116.2, 106.0, 85.1, 80.2, 78.6, 77.9, 73.5, 68.8, 64.3, 29.1,
28.8, 25.9, 18.3, 8.5, 7.7, ꢀ5.3; HRMS (ESIþ) m/z [MþNa]þ, calcd for
C31H46NaO6Si: 565.2956, found: 565.2954.
4.11. Benzyl-2,3-O-isopentylidene-5-O-benzyl-6-hydroxy-a-D-
mannofuranoside (18)
0.66 (t, J¼7.4 Hz, 2ꢂ 3H, H-10, H-11); 13C NMR (CDCl3, 100 MHz)
d:
137.4, 137.2, 136.0, 135.5, 129.3, 128.4, 128.0, 127.9, 127.8, 116.2,
105.9, 85.3, 80.1, 79.6, 72.3, 68.9, 65.1, 28.8, 28.7, 27.0, 26.9, 26.9,
19.5, 19.3, 8.2, 7.2; HRMS (ESIþ) m/z [MþNa]þ, calcd for
To a cooled solution of 17 (0.30 g, 0.70 mmol) in tetrahydro-
furan (7.7 mL) was slowly added 1 M tetra-n-butylammonium
fluoride (0.84 mL, 0.84 mmol). The reaction was warmed up to
room temperature under N2 atmosphere. After 24 h, the solvent
was removed by evaporation under reduced pressure. The residue
was purified by flash column chromatography eluting with
EtOAc:hexane, 10:90 to give 18 (0.27 g, 90%) as a colorless oil; Rf
C
34H44NaO6Si: 599.2805, found: 599.2811.
4.9. Benzyl 2,3-O-isopentylidene-5-hydroxy-6-O-tert-butyl
dimethylsilyl- -mannofuranoside (16b)
a-D
(10% EtOAc/hexane) 0.12; [
a]
25 þ154.4 (c¼0.52, CHCl3); FTIR (neat),
D
To a solution of 6 (0.20 g, 0.59 mmol) in CH2Cl2 (3 mL) was
added imidazole (80 mg, 1.18 mmol) and 4-N,N-dimethylamino-
pyridine (0.03 g, 0.29 mmol). The mixture was cooled to 0 ꢁC and
tert-butyldimethylsilyl chloride (107 mg, 0.71 mmol) was added.
The reaction mixture was warmed to room temperature and stirred
for 5 h. This mixture was washed with saturated ammonium
chloride, the organic layers were collected and the solvent was
removed. The solvent was removed and the residue was extracted
with dichloromethane and water. The organic layer was collected
and the solvent was removed. The residue was purified with flash
column chromatography (EtOAc:hexane, 6:94) to afford 16b as
ymax, 3473, 3088, 3031, 2971, 2939, 1497, 1455, 1206 cmꢀ1; 1H NMR
(400 MHz, CDCl3) d: 12.41e7.18 (m, 10H, aromatic), 5.10 (s, 1H, H-
1), 4.83 (dd, J¼5.9, 3.3 Hz, 1H, H-3), 4.74 (d, J¼11.2 Hz, 1H, CH2Ph),
4.69 (d, J¼11.8 Hz, 1H, CH2Ph), 4.67 (d, J¼5.9 Hz, 1H, H-2), 4.64 (d,
J¼11.8 Hz, 1H, CH2Ph), 4.49 (d, J¼11.8 Hz, 1H, CH2Ph), 4.08 (dd,
J¼9.0, 3.3 Hz, 1H, H-4), 3.98e3.92 (m, 1H, H-5), 3.86 (dd, J¼11.7,
4.1 Hz, 1H, H-6), 3.71 (dd, J¼11.7, 4.2 Hz, 1H, H-6), 1.92 (s, 1H, OH),
1.78e1.66 (m, 2H, H-8), 1.61 (q, J¼7.5 Hz, 2H, H-9), 0.92 (t,
J¼7.5 Hz, 3H, H-10), 0.90 (t, J¼7.5 Hz, 3H, H-11); 13C NMR (CDCl3,
100 MHz) d: 138.3, 137.4, 128.4, 128.3, 128.0, 127.8, 127.7, 116.5,
105.8, 85.1, 80.0, 79.4, 76.5, 72.9, 69.0, 62.6, 29.1, 28.8, 8.5, 7.7;
HRMS (ESIþ) m/z [MþNa]þ, calcd for C25H32NaO6: 451.2091, found:
451.2103.
a colorless oil (0.21 g, 80%); Rf (10% EtOAc/hexane) 0.25; [
a
]
25 þ85.7
D
(c¼0.51, CHCl3); FTIR (neat), ymax, cmꢀ1: 3432, 3031, 2974; 1H NMR
(CDCl3, 400 MHz) d: 7.34e7.27 (m, 5H, aromatic), 5.08 (s, 1H, H-1),
4.85 (dd, J¼3.4, 5.9 Hz, 1H, H-3), 4.64 (d, J¼5.9 Hz, 1H, H-2), 4.62 (d,
J¼11.8 Hz, 1H, eOCH2Ph), 4.45 (d, J¼11.8 Hz, 1H, eOCH2Ph),
4.03e4.00 (m, 1H, H-5), 3.95 (dd, J¼3.4, 8.3 Hz, 1H, H-4), 3.82 (dd,
J¼3.5, 10.2 Hz, 1H, H-6), 3.69 (dd, J¼5, 10.2 Hz, 1H, H-6), 2.79 (d,
J¼6.2 Hz, 1H, OH), 1.70, 1.58 (q, J¼6.8 Hz, 2ꢂ 2H, H-8, H-9), 0.91 (s,
9H, eSitBu), 0.91, 0.86 (t, J¼6.8 Hz, 2ꢂ 3H, H-10, H-11), 0.09 (s, 6H,
4.12. Regioselective reductive ring opening of various iso-
pentylidene and benzylidene acetals
4.12.1. General procedure. Method A: A solution of the starting
material (1 equiv) in dry CH2Cl2 (1.5 mL/mmol) was cooled to
eSiMe2); 13C NMR (CDCl3, 100 MHz)
d
: 137.4, 128.3, 128.0, 127.8,
ꢀ78 ꢁC or
0
ꢁC under nitrogen atmosphere. Triethylsilane
127.7, 116.7, 105.9, 85.3, 80.5, 79.2, 69.5, 68.9, 64.5, 29.1, 28.8, 25.8,
(1.35 equiv) was added, then a solution of TiCl4 (1.0 equiv) in dry
CH2Cl2 (0.5 mL) was dropped slowly into the reaction mixture and
stirred for 5 min. The reaction mixture was washed with water and
saturated aqueous NaHCO3, then the organic layers were collected,
dried over Na2SO4, filtered and the solvent of filtrate was removed
under vacuum. The residue was purified by flash column chroma-
tography on silica gel.
25.7, 18.2, 18.0, 8.2, 7.2, ꢀ0.4; HRMS (ESIþ) m/z [MþNa]þ, calcd for
C
24H40NaO6Si: 474.6381, found: 474.6403.
4.10. Benzyl-2,3-O-isopentylidene-5-O-benzyl-6-O-tert-bu-
tyldimethylsilyl- -mannofuranoside (17)
a-D
Sodium hydride (60% in mineral oil, 0.07 g, 1.66 mmol) was
washed with tetrahydrofuran under N2 atmosphere. A solution of
16b (0.50 g, 1.10 mmol) in tetrahydrofuran (3 mL) was slowly added
into the suspension mixture of washed sodium hydride in tetra-
hydrofuran (1.6 mL) and the mixture was stirred for 10 min. Benzyl
bromide (0.16 mL, 1.33 mmol) was added to the mixture and it was
further stirred for 1 h. After the completion, the water was added to
the mixture and extracted with dichloromethane. The organic layer
Method B: A solution of the starting material (1 equiv) in 1 M
BH3$THF complex (3 equiv) was cooled to 0 ꢁC or room temperature
under nitrogen atmosphere. Cu(OTf)2 (0.1 equiv) was added into
the solution and stirred for 30 min to 2 h. The reaction mixture was
washed with saturated aqueous NaHCO3 then the organic layers
were collected, dried over Na2SO4, filtered and the solvent removed
under vacuum. The residue was purified by flash column chroma-
tography on silica gel.

B. Kongkathip et al. / Tetrahedron 72 (2016) 3296e3304
3303
4.12.2. Benzyl-2-O-isopentylidene-3-hydroxy-5-
a
-
D
-lyxofura noside
100 MHz) d: 137.3,136.7, 128.5,128.4,128.3,128.1, 127.8, 127.7, 127.6,
(19).8 From 8 (0.10 g, 0.32 mmol); colorless oil (0.04 g, 40% for
127.4, 126.8, 103.9, 82.5, 79.2, 73.0, 71.7, 69.4; HRMS (ESIþ) m/z
[MþNa]þ, calcd for C19H22NaO5: 353.1359, found: 353.1375.
Method A and 0.08 g, 75% for Method B); Rf (40% EtOAc/hexane)
0.32; [
a]
25 þ67.2 (c¼0.77, CHCl3); (lit. [
a
]
25 þ67.24 (c¼0.77, CHCl3));
D
D
FTIR (neat), ymax, 3434, 1101, 1021 cmꢀ1; 1H NMR (CDCl3, 400 MHz)
4.12.6. Benzyl-2-O-isopentylidene-3-hydroxy-5,6-dihydroxy-a-D-
d
: 7.32e7.20 (m, 5H, aromatic), 4.99 (d, J¼1.3 Hz, 1H, H-1), 4.67 (d,
lyxofuranoside (24). As described in general Method A; started
from 6 (0.10 g, 0.29 mmol); colorless oil (0.05 g, 52%); Rf (70%
J¼11.8 Hz, 1H, eOCH2Ph), 4.42 (d, J¼11.8 Hz, 1H, eOCH2Ph), 4.43
(ddd, J¼5.6, 7.0, 5.6 Hz, 1H, H-3), 4.10 (ddd, J¼4.0, 5.7, 2.8 Hz, 1H, H-
4), 3.87 (dd, J¼1.3, 5.4 Hz, 1H, H-2), 3.81e3.80 (m, 2H, H-5), 3.28 (qt,
J¼5.8 Hz, 1H, H-7), 3.08 (d, J¼7.1 Hz, 1H, eOH), 2.62 (br s, 1H, eOH),
1.51, 1.40 (m, 4H, H-8, H-9), 0.82, 0.79 (2ꢂ t, J¼7.4 Hz, 2ꢂ 3H, H-10,
EtOAc/hexane) 0.25; [
a
]
D
25 þ57.9 (c¼0.64, CHCl3); FTIR (neat),
ymax,
: 7.33e7.26 (m,
3434, 1101, 1021 cm-1; 1H NMR (CDCl3, 400 MHz)
d
5H, aromatic), 5.05 (d, J¼2.2 Hz, 1H, H-1), 4.70 (d, J¼11.8 Hz, 1H,
eOCH2Ph), 4.49 (d, J¼11.8 Hz, 1H, eOCH2Ph), 4.43 (m, 1H, H-3),
4.03e3.97 (m, 3H, H-2, H-4, H-5), 3.82 (dd, J¼2.7, 11.5 Hz, 1H, H-6),
3.67 (dd, J¼5.5, 11.5 Hz, 1H, H-6), 3.40 (br s, 1H, OH), 3.34 (qt,
J¼5.8 Hz, 1H, H-7), 1.57, 1.47 (m, 4H, H-8, H-9), 0.88, 0.85 (2ꢂ t,
H-11); 13C NMR (CDCl3, 100 MHz)
d: 137.4, 128.3, 127.8, 127.7, 104.5,
83.1, 81.1, 79.3, 71.6, 69.4, 61.5, 25.9, 25.7, 9.4, 9.3; HRMS (ESIþ) m/z
[MþNa]þ, calcd for C17H26NaO5: 333.1672, found: 333.1680.
J¼7.4 Hz, 2ꢂ 3H, H-10, H-11); 13C NMR (CDCl3, 100 MHz)
d: 137.4,
4.12.3. Benzyl-2-hydroxy-3-O-isopentylidene-5-
(20). From 8 (0.10 g, 0.32 mmol); colorless oil (0.02 g, 15% for
Method A); Rf (40% EtOAc/hexane) 0.25; [
CHCl3); FTIR (neat), ymax, 3434, 1101, 1021 cmꢀ1D
a-
D-lyxofura noside
128.3, 127.9, 127.8, 127.6, 105.5, 83.2, 89.6, 79.5, 71.1, 70.1, 69.7, 64.0,
26.0, 25.7, 9.4, 9.3; HRMS (ESIþ) m/z [MþNa]þ, calcd for
C18H28NaO6: 363.1789, found: 363.1806.
25
a
]
ꢀ79.4 (c¼1.27,
;
1H NMR (CDCl3,
400 MHz)
d
: 7.32e7.20 (m, 5H, aromatic), 4.97 (d, J¼4.24 Hz, 1H, H-
4.12.7. Benzyl-2-O-isopentylidene-3-hydroxy-5-O-benzyl-6-
1), 4.73 (d, J¼11.8 Hz, 1H, eOCH2Ph), 4.51 (d, J¼11.8 Hz, 1H,
eOCH2Ph), 4.23 (m, 1H, H-4), 4.10 (ddd, J¼5.64, 5.74, 5.52 Hz,1H, H-
3), 3.84 (dd, J¼4.24, 5.5 Hz, 1H, H-2), 3.82e3.77 (m, 2H, H-5), 3.29
(qt, J¼5.8 Hz, 1H, H-7), 3.05 (d, J¼7.4 Hz, 1H, eOH), 2.35 (br s, 1H,
eOH),1.54e1.46 (m, 4H, H-8, H-9), 0.86, 0.83 (2ꢂ t, J¼7.4 Hz, 2ꢂ 3H,
hydroxy-a-
D-mannofuranoside (25) and benzyl-2-hydroxy-3-O-iso-
pentylidene-5-O-benzyl-6-hydroxy-
a-D-mannofuranoside (26). As
described in general Method A; started from 18 (0.20 g, 0.47 mmol);
purification by flash column chromatography on silica gel eluting
with EtOAc:hexane, 1:4 afforded the product as a colorless oil
(0.10 g), 53% as two isomers (25:26¼3:2); Rf (70% EtOAc/hexane)
0.25; FTIR (neat), ymax, 3417, 3031, 2964, 2934, 1497, 1454,1209 cmꢀ1
H-10, H-11); 13C NMR (CDCl3, 100 MHz)
d 137.2, 128.2, 127.9, 127.6,
99.7, 82.7, 81.2, 77.7, 70.2, 69.3, 62.2, 25.9, 25.8, 9.3; HRMS (ESIþ) m/
z [MþNa]þ, calcd for C17H26NaO5: 333.1672, found: 333.1680.
Compound 25: 1H NMR (400 MHz, CDCl3)
d: 7.37e7.27 (m, 10H,
aromatic), 5.05 (s, 1H, H-1), 4.73 (d, J¼11.4 Hz, 1H, CH2Ph), 4.69 (d,
J¼11.8 Hz, 1H, CH2Ph), 4.61 (d, J¼11.4 Hz, 1H, CH2Ph), 4.50 (d,
J¼11.8 Hz, 1H, CH2Ph), 4.48e4.44 (m, 1H, H-3), 4.33 (dd, J¼7.3,
4.1 Hz, 1H, H-2), 4.05 (d, J¼4.9 Hz, 1H, H-4), 3.99e3.91 (m, 1H, H-5),
3.91e3.78 (m, 2H, 2ꢂ H-6) 3.38e3.31 (p, J¼5.9 Hz,1H, H-7), 2.50 (br
s, 2H, OH) 1.60e1.51 (m, 4H, H-8, H-9), 0.91e0.86 (t, J¼7.5 Hz, 3H,
H-10), 0.87e0.82 (t, J¼7.5 Hz, 3H, H-11); 13C NMR (CDCl3, 100 MHz)
4.12.4. Benzyl-2-O-isopentylidene-3-hydroxy-5-O-acetyl-
ofuranoside (21) and benzyl-2-hydroxy-3-O-isopentyli-dene-5-O-
acetyl- -lyxofuranoside (22). As described in general Method A;
started from benzyl 2,3-O-isopentylidene-5-O-acetyl- -lyxofur-
a-D-lyx-
a-D
a-D
anoside (0.05 g, 0.14 mmol), the residue was purified by flash col-
umn chromatography on silica gel eluting with EtOAc:hexane,
10:90 to give a 3:1 mixture of 21 and 22 (0.03 g, 60%) as a colorless
oil; Rf (20% EtOAc/hexane) 0.15; FTIR (neat), ymax, 3435, 3031, 2972,
d
: 137.7, 137.6, 137.5, 128.5, 128.4, 128.0, 127.9, 127.8, 106.6, 82.5,
79.6, 78.6, 73.3, 72.0, 69.4, 60.8, 25.8, 24.8, 9.5, 9.0; HRMS (ESIþ) m/z
[MþNa]þ, calcd for C25H34NaO6: 453.2248, found: 453.2256.
1742, 1738 cmꢀ1
Compound 21: 1H NMR (CDCl3, 400 MHz)
.
d: 7.34e7.26 (m, 5H,
Compound 26: 1H NMR (400 MHz, CDCl3)
d: 7.41e7.25 (m, 10H,
aromatic), 5.08 (d, J¼1.3 Hz, 1H, H-1), 4.70 (d, J¼11.8 Hz, 1H,
eOCH2Ph), 4.37 (m, 1H, H-2), 4.48 (d, J¼11.8 Hz, 1H, eOCH2Ph), 4.63
(m, 1H, H-3), 4.25e4.23 (m, 1H, H-5), 4.15e4.12 (m, 1H, H-5),
4.06e4.07 (m, 1H, H-4), 3.28 (qt, J¼5.8 Hz, 1H, H-7), 2.94 (br s, 1H,
OH), 2.07 (s, 3H, eC(O)CH3), 1.56e1.49 (m, 4H, H-8, H-9), 0.90, 0.86
(2ꢂ t, J¼7.4 Hz, 2ꢂ 3H, H-10, H-11).
aromatic), 5.08 (d, J¼2.6 Hz,1H, H-1), 4.77 (d, J¼11.4 Hz,1H, CH2Ph),
4.72 (d, J¼12.0 Hz, 1H, CH2Ph), 4.69 (d, J¼11.4 Hz, 1H, CH2Ph), 4.52
(d, J¼12.0 Hz, 1H, CH2Ph), 4.35 (dd, J¼5.1, 3.4 Hz, 1H, H-3), 4.15 (dd,
J¼7.8, 3.3 Hz, 1H, H-2), 4.04 (dd, J¼5.2, 2.6 Hz, 1H, H-4), 3.99e3.93
(m, 1H, H-5), 3.86 (dd, J¼11.7, 4.5 Hz, 1H, H-6), 3.72 (dd, J¼11.7,
4.2 Hz, 1H, H-6), 3.38 (p, J¼5.9 Hz, 1H, H-7), 2.42 (br s, 2H, OH)
1.62e1.47 (m, 4H, H-8, H-9), 0.91 (t, J¼7.5 Hz, 3H, H-10), 0.87 (t,
Compound 22: 1H NMR (CDCl3, 400 MHz)
d: 7.34e7.26 (m, 5H,
aromatic), 5.08 (d, J¼4.24 Hz, 1H, H-1), 4.75 (d, J¼12.4 Hz, 1H,
eOCH2Ph), 4.50 (d, J¼12.4 Hz,1H, eOCH2Ph), 4.47 (m,1H, H-3), 4.39
(d, J¼2.8 Hz, 1H, H-2), 4.34e4.32 (m, 1H, H-5), 4.25e4.23 (m, 1H, H-
5), 4.16e4.21 (m,1H, H-4), 3.31 (qt, J¼5.8 Hz,1H, H-7), 2.94 (br s,1H,
eOH), 2.07 (s, 3H, eC(O)CH3), 1.56e1.49 (m, 4H, H-8, H-9), 0.88,
0.85 (2ꢂ t, J¼7.4 Hz, 2ꢂ 3H, H-10, H-11).
J¼7.5 Hz, 3H, H-11); 13C NMR (CDCl3,100 MHz)
d: 138.3,137.5,128.4,
128.3, 127.9, 127.8, 127.7, 105.9, 83.1, 82.9, 79.5, 72.7, 70.6, 70.0, 69.4,
62.1, 25.8, 9.4, 9.3; HRMS (ESIþ) m/z [MþNa]þ, calcd for
C25H34NaO6: 453.2248, found: 453.2258.
Acknowledgements
Compound 21þ22: 13C NMR (CDCl3, 100 MHz)
d: 170.6, 170.4,
137.4,137.3,128.2,127.7,127.6,126.9,105.8, 81.9, 83.2, 78.2, 76.4, 76.2,
70.4, 69.1, 64.0, 63.1, 25.8, 25.7, 25.6, 25.2, 20.7, 9.2, 9.1; HRMS (ESIþ)
m/z [MþNa]þ, calcd for C19H28NaO6:375.1783, found: 375.1789.
N.C. is a Ph.D. student under the Royal Golden Jubilee Program of
the Thailand Research Fund (TRF). We are grateful for financial
support from the Thailand Research Fund and Kasetsart University
through the Royal Golden Jubilee Program. Financial support from
the Center of Excellence for Innovation in Chemistry (PERCH-CIC),
Commission on Higher Education, Ministry of Education and
Kasetsart University Research and Development Institute (KURDI)
are also gratefully acknowledged.
4.12.5. Benzyl-2-O-benzyl-3-hydroxy-5-a-D-lyxofuranoside (23). As
described in general Method A; started from 15 endo/exo (0.10 g,
0.30 mmol); colorless oil (0.08 g, 75%); Rf (20% EtOAc/hexane) 0.12;
25
[
a]
þ80.3 (c¼2.46, MeOH); FTIR (neat), ymax, 3431, 3088, 3063,
D
2929, 1496, 1454, 1024 cmꢀ1 1H NMR (400 MHz, CDCl3)
; d:
7.42e7.26 (m, 10H, aromatic), 5.16 (s, 1H, H-1), 4.74 (d, J¼11.8 Hz,
1H, CH2Ph), 4.66 (s, 2H, CH2Ph), 4.63e4.53 (m, 1H, H-3), 4.49 (d,
J¼11.8 Hz, 1H, CH2Ph), 4.18 (d, J¼4.6 Hz, 1H, H-2), 4.01 (d, J¼4.9 Hz,
1H, H-4), 3.97e3.80 (m, 2H, H-5), 2.84 (s, 2H, OH); 13C NMR (CDCl3,
Supplementary data
Supplementary data (1H and 13C NMR spectra for all new and
important known compounds) associated with this article can be

3304
B. Kongkathip et al. / Tetrahedron 72 (2016) 3296e3304
3. (a) Garegg, P. J. Acc. Chem. Res. 1992, 25, 575e580; (b) Shie, C.-R.; Tzeng, Z.-H.;
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1665e1668.
found in the online version, at http://dx.doi.org/10.1016/
j.tet.2016.04.068.
4. Liptak, A. Tetrahedron Lett. 1976, 17, 3551e3554.
5. Liptak, A.; Imre, J.; Harangi, J.; Nanasi, P.; Neszmelyi, A. Tetrahedron 1982, 38,
ꢀ
ꢀ
ꢀ
ꢀ
3721e3727.
6. Ek, M.; Garegg, P. J.; Haltberg, H.; Oscarson, S. J. Carbohydr. Chem.1983, 2, 305e311.
7. Saito, S.; Kuroda, A.; Tanaka, K.; Kimura, R. Synlett 1996, 231e233.
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