Cosolvent-Promoted O-Benzylation with Silver(I) Oxide: Synthesis of 1′-Benzylated Sucrose Derivatives, Mechanistic Studies, and Scope Investigation

Article abstract of DOI:10.1021/acs.joc.6b00144

A cosolvent-promoted O-benzylation strategy with Ag₂O was developed. The cosolvent consisting of CH₂Cl₂ and n-hexane can not only improve the reaction solubility for carbohydrates but also increase the benzylation efficiency. The formation of byproducts is greatly inhibited in the developed method. This method is simple, mild, and highly effective, and numerous 1′-benzylated sucrose derivatives were prepared including a photoreactive (trifluoromethyl)phenyldiazirine-based sucrose. The mechanisms of benzylation with primary and secondary benzyl bromides were also elaborated. Furthermore, the application scope with alcohols, glucose, and ribose derivatives was investigated.

Full text of DOI:10.1021/acs.joc.6b00144

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Article
Co-solvent Promoted O-Benzylation with Silver(I) Oxide: Synthesis of 1'-
Benzylated Sucrose Derivatives, Mechanistic Studies and Scope Investigation
Lei Wang, Yasuyuki Hashidoko, and Makoto Hashimoto
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00144 • Publication Date (Web): 05 May 2016
Downloaded from http://pubs.acs.org on May 12, 2016
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Co-solvent Promoted O-Benzylation with Silver(I) Oxide: Synthesis
of 1'-Benzylated Sucrose Derivatives, Mechanistic Studies and
Scope Investigation
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Lei Wang,* Yasuyuki Hashidoko, and Makoto Hashimoto*
Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita 9, Nishi 9,
Kita-ku, Sapporo 060-8589, Japan.
E-mail: lei870610@gmail.com; hasimoto@abs.agr.hokudai.ac.jp.
ABSTRACT
A co-solvent promoted O-benzylation strategy with Ag2O was developed. The co-solvent consisting of
CH2Cl2 and n-hexane can not only improve the reaction solubility for carbohydrates but also increase
the benzylation efficiency. The formations of by-products are greatly inhibited in the developed
method. This method is simple, mild, and highly effective. By which, numerous 1'-benzylated sucrose
derivatives were prepared including a photoreactive (trifluoromethyl)phenyldiazirine-based sucrose.
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The mechanisms of benzylation with primary and secondary benzyl bromides were also elaborated.
Furthermore, the application scope with alcohols, glucose and ribose derivatives were investigated.
INTRODUCTION
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Benzylation of hydroxyl groups has emerged as an important topic in synthetic chemistry and
carbohydrate field. The generated benzyl ether and its variants are important hydroxyl-protecting
groups because of its inherent stability, easy installation, compatibility with many reaction conditions
and numerous deprotection methods.1 Traditionally, sodium hydride (NaH)2 and silver (I) oxide
(Ag2O)3 are widely used as the reagents to mediate the O-benzylation of carbohydrates. Despite the
high efficiency of NaH in the benzylation process, its strong alkaline condition, substrate limitation
and tedious post-processing are major barriers to its wide application. Alternatively, Ag2O-mediated
O-benzylation strategy has been used as an indispensable strategy due to its mild condition, easy
post-processing and low environmental impact. Nonetheless, many reports suffered the excess use of
reagents, preparation of fresh Ag2O, poor solubility of the substrate, low reaction yields or long
reaction time.3d-e Furthermore, the reaction mechanisms still remain ambiguous. In view of the great
importance of Ag2O-mediated O-benzylation in carbohydrates field and synthetic chemistry, more
efficient improvements deserve to be carried out eagerly.
Sucrose, consisting of three primary hydroxyls and five secondary hydroxyls, serves as an
important starting platform for the preparation of surfactants, macrocyclic derivatives, functional
materials, food additives and pharmaceutical compounds.4 It is also the major form of transported
carbon in a lot of plant species and is transported through cell membranes in many tissue types.5 To
study sucrose carrier protein and the physiology of sucrose transport, modifications of 1'-postion of
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sucrose to construct nonnatural sucrose analogues are the widely used strategies.6 Meanwhile,
sucralose, fructooligosaccharides (1-kestose, nystose and 1-β-fructofuranosylnystose) and the
Achyranthes bidentata B1 polysaccharides7, isolated from a traditional Chinese herbal medicine
Achyranthes bidentata Blume, could all be regarded as the 1'-substituted sucrose, indicating that the
1'-position is tolerable for numerous modification. However, it has been reported that the more
sterically hindered 1'-hydroxyl of sucrose present the lowest reactivity among the primary hydroxyls
in many reactions8, which bring many trouble for the modification of 1'-position of sucrose. Herein,
we developed a co-solvent promoted O-benzylation strategy, which can not only improve the reaction
solubility but also increase the benzylation efficiency for 1'-sucrose. Furthermore, we
comprehensively elaborated the benzylation mechanisms for the first time and prepared a
3-(trifluoromethyl)-3-phenyldiazirine (TPD)9 coupled sucrose derivative based on aforementioned
strategy, which can be used as useful photoreactive component to study sucrose and its derivatives in
photoaffinity labelling10. Furthermore, many substrates including alcohols, glucose and ribose
derivatives were subjected into the reaction to further expand its application scope.
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RESULTS AND DISCUSSION
Initially, we would like to prepare the 1'-OH-heptaacetylsucrose 1 as a precursor for subsequent
benzylation. To conveniently obtain compound 1, we averted the tedious strategy by protection and
deprotection11 and chose a more efficient enzymatic method12 involving the hydrolysis of
commercially available octaacetylsucrose in the presence of Alcalase®. Next, sucrose 113 was reacted
with p-(trifluoromethyl)benzyl bromide 2a with Ag2O in CH2Cl2 which is the commonly used solvent
in carbohydrates field (Table 1). Temperature optimization indicated that 60 °C is ideal for the reaction
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(Table 1, entries 1-4), and 2 equiv of 2a and 3 equiv of Ag2O were selected as the optimial reagents
ratio (Table 1, entries 5-6). Any additive failed to improve the reaction yield (Table 1, entries 7-8) but
the N2 atmosphere made contribution to the reaction yield although only 23% yield was obtained
(Table 1, entry 9). Reagent amount screening showed that excess reagents (Table 1, entries 10-13) are
required to obtain the satisfactory yield. Despite of the good yield, this is not an effective strategy for
wide application especially for the benzylation with precious benzyl bromides. Based on the
significant solvent effect on nucleophilic substitution, we carried out the optimization of reaction
solvents (Table 2). Although there is no universal polarity scale for the sixteen solvents tested in this
study, we select dipole moment (µ) and dielectric constant (ε) as general indicator of solvent
polarity.14 Benzylation of 1 was evidently sensitive to solvent polarity. High-polarity solvents such as
MeCN, DMF and acetone failed to afford desired product (Table 2, entries 1-3). With low-polarity
solvents such as EtOAc and CHCl3 (Table 2, entries 6 and 7), 3a was obtained in 19% and 39%,
respectively. No desired product was obtained when THF or 1,4-dioxane was used as the solvent
(Table 2, entries 5 and 12). The desired products were obtained in moderate yield in other solvents
(Table 2, entries 8-11 and 13). Interestingly, when cylcohexane, n-hexane and n-pentane were used as
the solvents (Table 2, entries 14-16), the reaction yield drastically increased although these solvents
are not widely used in carbohydrates field because of their low solubility. These results indicated that
benzylation correlated more closely with the solvent’s dielectric constant (ε) than dipole moment (µ).
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Table 1. O-Benzylation of 1'-Sucrose with 2a in the Presence of Ag2Oa
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entry
1
2a (equiv)
Ag2O (equiv)
temp (ºC)
rt
time (h)
144
70
yield 3a (%)b
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trace
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8d
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aReaction conditions: 1 (0.1 mmol), 2a, Ag2O, CH2Cl2 (1 mL), MS 4Å (200 mg) in a sealed
tube under dark. bIsolated yield. cKI (0.01 equiv) was added. dn-Bu4NI (0.01 equiv) was added.
eUnder N2.
Table 2. Solvent Optimizationa
entry
1
solvent
MeCN
µb
3.2
3.8
2.9
1.8
1.8
1.7
1.1
1.3
1.2
0.4
0
εc
37.5
36.7
20.6
9.1
time (h)
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yield 3a (%)d
0
0
2
DMF
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acetone
CH2Cl2
THF
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0
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0
5
7.6
24
6
EtOAc
6.0
24
19
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CHCl3
4.8
24
8
Et2O
4.3
12
9
isopropyl ether
toluene
benzene
1,4-dioxane
3.9
12
10
11
12
2.4
20
2.3
16
0.4
2.2
24
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CCl4
0
2.2
2.0
1.9
1.8
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cyclohexane
n-hexane
n-pentane
0.3
0
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0
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a1 (0.1 mmol), 2a (2.0 equiv), Ag2O (3.0 equiv), solvent (1 mL), MS 4Å (200 mg), in a sealed tube
at 60 °C under N2. bDipole moment (debye). cDielectric constant (F/m). dIsolated yield.
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For the solvents that failed to afford desired product (Table 2, entries 1-3, 5 and 12), we found
that sucrose 1 still remained but benzyl bromide 2a consumed completely.15 To clearly elucidate the
derivation of 2a and the factors affecting benzylation of 1, we carried out a series of control
experiments of which 2a was alone reacted with Ag2O in various solvents (Table 3). These results
indicated that in non-polar solvent such as n-hexane, the formation of di-benzyl ether and benzyl
alcohol (by-products for benzylation of 1) were greatly inhibited. Furthermore, the inertness of
n-hexane toward 2a also contributed to the benzylation of 1.
Table 3. Derivation of 2a with Ag2O in Different Solventsa
entry
solvent
MeCN
time (h)
4a/5a/others (%)c
4a/5a/others (%)d
1
15
4
10/62/28
10/57/33
e
e
2
DMF
-
-
3
acetone
THF
6
4/22/74
2/20/78
27/60/13
86/4/10
63/8/29
40/4/56
83/7/10
83/3/14
4/24/72
2/12/86
24/57/19
84/4/12
58/12/30
47/6/47
76/8/16
78/5/17
4
8
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1,4-dioxane
CH2Cl2
EtOAc
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13
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CHCl3
9
Et2O
10
isopropyl ether
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toluene
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61/2/37
71/1/28
90/1/9
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95/0/5
benzene
CCl4
cyclohexane
n-hexane
n-pentane
93/0/7
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96/0/4
aReaction conditions: 2a (0.2 mmol), Ag2O (1.0 equiv), solvent (0.5 mL), MS 4Å (100 mg), in
a sealed tube at 60 ºC under N2. bOthers: unidentified products. cRatios were determined by
1H-NMR for reaction mixtures. dRatios were determined by 19F-NMR for reaction mixtures.
eComplicated mixtures, ratios were not successfully determined.
Despite that n-hexane was the most effective solvent for the benzylation of 1 in present work, the
low solubility for carbohydrates severely limit its wide application. Co-solvents consisting of two or
more solvents have been utilized as a useful strategy in organic synthesis. Thus, we assumed that the
combination of n-hexane with other high-polarity solvent might improve the reaction solubility.
Initially, additive solvents were examined divided by their miscibility with n-hexane (Table 4, entries
1-7). Obviously, hexane-immiscible solvents failed to afford 3a (Table 4, entries 1-2) but
hexane-miscible solvents worked well (Table 4, entries 3-6). Composition screening revealed that the
combination of n-hexane and CH2Cl2 provided a dramatic increase of the reaction yield and reactants
were highly soluble in it (Table 4, entry 7). Co-solvent comprising cyclohexane and CH2Cl2 also
provided high benzylating efficiency (Table 4, entry 8). Tuning of the ratio of n-hexane and CH2Cl2
revealed 4:1 as the optimal volume ratio (Table 4, entry 9).
Table 4. Co-solvent Promoted O-Benzylation of 1 with Ag2Oa
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entry
solvent (volume ratio)
n-hexane/MeCN (4/1)
n-hexane/DMF (4/1)
n-hexane/THF (4/1)
time (h)
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yield 3a (%)b
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cyclohexane/CH2Cl2 (4/1)
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a1 (0.1 mmol), 2a (2.0 equiv), Ag2O (3.0 equiv), solvent (1 mL), MS 4Å (200 mg), in a
sealed tube at 60 °C under N2. bIsolated yield.
To highlight the efficiency of co-solvent in the benzylation of 1, we carried out a kinetic
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investigation of benzylation process in CD2Cl2 and deuterated co-solvent (cyclohexane-d12 and
CD2Cl2), respectively (Figure 1). As can be seen in the kinetic curve plot, when the reaction was
carried out in CD2Cl2 (Figure 1, a), benzyl bromide 2a consumed rapidly along with the formation of
desired product 3a and the major by-product 4a. Evidently, 4a was generated prior to the desired
product 3a, and benzyl bromide 2a was completely consumed within 15 h. While, when the reaction
was carried out in deuterated co-solvent (Figure 1, b), formation of the desired product 3a drastically
increased and the generation of by-product 4a was significantly inhibited. Meanwhile, 13% of benzyl
bromide 2a remained in the reaction mixture after 15 h.
Figure 1. Kinetic investigation of O-benzylation of
1
in CD2Cl2 and deuterated co-solventa
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a1 (0.1 mmol), 2a (2.0 equiv), Ag2O (3.0 equiv), solvent (a: CD2Cl2 1 mL, b: cyclohexane-d12/CD2Cl2 = 0.8 mL/0.2
mL), MS 4Å (200 mg), in a sealed tube at 60 °C under N2. Ratio was determined by 1H-NMR. (For detail, see
Supporting Information).
With the optimal condition in hand, we proceeded to investigate the co-solvent promoted
O-benzylation of 1 with other benzyl halides (Table 5). Primary benzyl bromides bearing
electron-deficient groups could give good yields as compared with that substituted with electron-rich
groups, indicating that the electronic nature of the aryl ring is crucial for the reaction. For benzyl
bromides that were substituted with electron-deficient groups such as -CF3 and -NO2 which are kinds
of meta-directors in electrophilic aromatic substitution, meta-substituted benzyl bromides (3b and 3d)
showed slight priority to react with 1 compared with para-substituted ones (3a and 3c). Opposite
results were obtained when the substituent was changed to -Cl and -Br, kinds of ortho/para-directors
in electrophilic aromatic substitution (3e and 3f, 3g and 3h). As for methyl substitution, the para- and
ortho-substituted benzyl bromide (3j and 3l) afforded the desired products in higher yield than that of
meta-substitution (3k). Compared with benzyl bromides, benzyl chlorides showed lower reactivity in
the benzylation of 1 (3i and 3j). Strong electron-rich substituent gave only a low yield of desired
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product (3m). Satisfactorily, p-TPD benzyl bromide17 could readily react with 1 giving a photoreactive
1'-sucrose derivative in 80% yield (3n).
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Table 5. Co-solvent Promoted O-benzylation of 1 with Other Benzyl Halidesa
a1 (0.1 mmol), isolated yield.
In addition, to gain more insight into the stereochemistry of the reaction, we carried out the
benzylation of 1 with secondary benzyl bromide 2o as shown in Scheme 1. Interestingly, the reaction
smoothly furnished 3o in excellent yield (95%) within 5 h. By using different enantioenriched 2o, the
reactions readily afford to 3o in the same enantiomer ratio. Furthermore, di-benzyl ether 4o was
detected with a dl- and meso-mixture in the ratio of 1/1. These results indicated that a planar benzyl
intermediate should be involved during the reaction.
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Scheme 1. O-Benzylation of 1 with Secondary Benzyl Bromide 2o
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Finally, all 1'-benzylated sucrose derivatives were subjected to deacetylation in methanolic
ammonia (Scheme 2). The corresponding desired products were obtained in good yields (up to 99%).
Furthermore, the photoreactivity of 6n in CH3OH were tested under the UV irradiation (Figure 2). The
half-life (t1/2) was calculated as 1.1 min indicating its good photoreactivity for the investigation of
sucrose in photoaffinity labeling. To clearly confirm the photoreactive product, we performed the
photoreaction of 6n in CH3OH and CD3OD respectively and analyzed the reaction mixtures by
ESI-HRMS (For detail, see Supporting Information).
Scheme 2. Deacylation of 1'-Benzylated Sucroses
Figure 2. (a) UV irradiation of 6n in CH3OH (b) UV-vis spectrum of 6n in CH3OH with a time
window of 0-10 min.
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To further expand the application scope of the co-solvent promoted O-benzylation strategy, many
substrates were tested as shown in Table 6. In consideration of the high benzylation efficiency and the
lower price, we chose 4-bromobenzyl bromide 2g as the benzylation reagent to perform the initial
study. As expected, both of the aliphatic and aromatic alcohols can be benzylated to afford desired
products in excellent yields with short time (8a-8j). When enantioenriched secondary benzyl alcohols
were used, the chiral purity of the desired products can be well remained (8k and 8l). Notably, other
carbohydrates such as glucose and ribose derivatives were also subjected into the developed strategy
and the reactions readily furnished corresponding products in good yields which indicating the good
application potentiality of the co-solvent promoted O-benzylation strategy (8m and 8n). Secondary
benzyl bromide 2o also worked well in this study (8o-8r). Furthermore, O-benzylation with polyols
were examined and the multi-benzylated products can be obtained in good isolated yields (8s and 8t).
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To explore the benzylation mechanism, several control experiments have been carried out
(Scheme 3). The benzylation of 1 were conducted under the standard conditions in the presence of
2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) as a radical scavenger18. In the presence of 2 equiv of
TEMPO, the benzylation yield with 2a dropped to 55%, and the corresponding benzyl-TEMPO adduct
1
9a can be detected by H-NMR and ESI-HRMS. Although formation of 9a may indicate a radical
process, 10 equiv of TEMPO did not completely inhibit the reaction and no bibenzyl derivative 10a
(product derived from radical pathway19) was detected in these reactions. Besides, a control
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experiment of which 2a was directly treated with TEMPO readily afford to 9a in 76% yield. A
competition experiment indicated that benzylation of 1 with primary benzyl bromide bearing strong
electron-rich substituent (2m) proceeded much more slowly than for the other two substrates (2a and
2i). On the basis of above mentioned results, we proposed that a SN2 pathway is more reliable for
benzylation of 1 with primary benzyl bromides. Furthermore, addition of 2 equiv of TEMPO had no
significant effect on the benzylation of 1 with secondary benzyl bromide 2o although TEMPO adduct
9o was also detectable indicating a SN1 pathway may involve in the benzylation with secondary
benzyl bromide.
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Scheme 3. Control Experiments
Based on the result presented above, we outline the plausible benzylation mechanism (Scheme 4).
Initially, bromine of 2a is abstracted by Ag2O to form a long-chain intermediate A, which is further
attacked by 1'-hydroxyl of 1 giving desired product 3a. Meanwhile, intermediate A can convert to
silver-alkoxy20 intermediate B via self-cyclization following with the formation of 4a and 5a.
Furthermore, benzylation of 1 with secondary benzyl bromide 2o involve a halogenophilic attack by
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Ag2O, removal of bromine forming a planar benzylic carbocation C, the subsequent attack towards
two sides of C by 1 forming racemic products 3o. Meanwhile, di-benzyl ether 4o and alcohol 5o are
also formed during the process.
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Scheme 4. Mechanistic Hypothesis
CONCLUSIONS
In conclusion, we presented a comprehensive investigation of solvent effect on the O-benzylation
with Ag2O and developed a co-solvent promoted strategy that can not only improve the reaction
solubility but also increase the reaction yield. The co-solvent strategy could significantly inhibit the
formation of di-benzyl ether and alcohol which were major by-products in Ag2O-mediated benzylation
reaction. The benzylation yield can reach to 95% in the co-solvent promoted system despite of the
relatively low reactivity of 1'-hydroxyl of sucrose. Furthermore, benzylation mechanisms with primary
and secondary benzyl bromide were well elaborated for the first time. Involving which strategy, we
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successfully prepared photoreactive 1'-sucrose derivative which acts as a promising reagent to
investigate sucrose in photoaffinity labeling. The developed co-solvent promoted O-benzylation
strategy are successfully applied for the other substrates such as commonly used alcohols, glucose and
ribose derivatives that indicating its potential utility in both of carbohydrate field and synthetic
chemistry. Additional studies on the expansion of its scope and preparation of glycosides are currently
underway.
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EXPERIMENTAL SECTION
General Remarks. Chemical reagents and solvents were purchased and used without further
purification (Commercial available Ag2O was directly used without any treatment). Column
chromatography was performed using silica gel (200-400 mesh). HR-ESI mass spectra were recorded
with a UPLC ESI-TOF mass spectrometer.
Synthesis of 1'-OH-heptaacetylsucrose 1. To the solution of octaacetyl sucrose (1.00 g, 1.47
mmol) in 0.1 M phosphate buffer (50 mL, pH 7) containing a mixture of DMF and H2O (10 mL,
DMF:H2O=1:3), Alcalase® 2.4 L (2 mL) was added. The mixture was incubated at 37 °C for 24 h. The
mixture was extracted with ethyl acetate, concentrated under reduced pressure, then subjected to
column chromatography on silica gel (EtOAc:n-hexane, 10:1) to afford 1'-OH-heptaacetylsucrose 1
(0.25 g, 27.4%).
Co-solvent Promoted O-Benzylation of 1'-Sucrose in the Present of Ag2O. To a solution
of 1'-OH-heptaacetylsucrose 1 (0.1 mmol, 64 mg) in co-solvent (n-hexane/CH2Cl2, 0.8 mL/0.2 mL) in
a glass sealed tube, benzyl bromide 2 (2.0 equiv), Ag2O (3.0 equiv) and molecular sieves 4Å (200 mg)
were added, respectively. The reaction mixture was stirred at 60 °C under dark in the presence of N2.
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After the reaction was finished, the mixture was filtered by celite (or centrifugation) and concentrated,
and the residue was purified through silica gel column chromatography (EtOAc:Hexane=3:2) to afford
corresponding 1'-benzylated sucrose derivative.
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Preparation of Enantioenriched (R)-1-(1-bromoethyl)benzene (R)-2o and
(S)-1-(1-bromoethyl)benzene (S)-2o. To a stirred solution of (S)-1-phenyl ethanol or
(R)-1-phenyl ethanol (1.0 g, 8.2 mmol) in anhydrous hexane (30 mL) at 0 °C, PBr3 (0.5 equiv) was
added dropwise. The reaction was monorted by TLC analysis. After reaction for 15 min, the reaction
mixture was slowly poured into 50 mL ice-water. The organic phase was washed with saturated
NaHCO3 solution (30 mL×2), 1 M HCl (30 mL), and brine (30 mL×3), respectively, dried with
anhydrous MgSO4, and concentrated by evaporation. A: yield: 93%, [α]D = +41 (c 1, CHCl3); ratio:
(R)-2o/(S)-2o = 70/30 (by HPLC), Daicel Chiralpak AY-H, i-PrOH-hexane 0/100, flow rate 0.2
mL/min, tR: 23.80 min (R)-2o and 25.09 min (S)-2o, 210 nm detection. B: yield: 93%, [α]D = -41 (c 1,
CHCl3); ratio: (S)-2o/(R)-2o = 72/28 (by HPLC), Daicel Chiralpak AY-H, i-PrOH-hexane 0/100, flow
rate 0.2 mL/min, tR: 23.88 min (R)-2o and 25.19 min (S)-2o, 210 nm detection. C: For commercial
available (1-bromoethyl)benzene: [α]D = 0 (c 1, CHCl3); ratio: (R)-2o/(S)-2o = 49/51 (by HPLC),
Daicel Chiralpak AY-H, i-PrOH-hexane 0/100, flow rate 0.2 mL/min, tR: 23.85 min (R)-2o and 25.16
min (S)-2o, 210 nm detection.
Deacylation of 1'-Benzylated Sucrose Derivatives. To a solution of 1'-benzylated sucrose
derivative 3 (0.2 mmol) in methanol (4 mL), NH3 gas was bubbled. Then the mixture was stirred at room
temperature for 12 h. After removal of the solvent under vacuo, the residue was purified through silica
gel column chromatography (EtOAc:MeOH=5:1) to afford 1'-benzylated sucrose.
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Co-solvent Promoted O-Benzylation of Alcohols, Glucose and Ribose Derivatives in
the Present of Ag2O. To a solution of 7 (0.3 mmol) in co-solvent (n-hexane/CH2Cl2, 4/1) in a glass
sealed tube, benzyl bromide (2.0 equiv for 8a-8r, 4.0 equiv for 8s, 6.0 equiv for 8t), Ag2O (3.0 equiv
for 8a-8r, 6.0 equiv for 8s, 9.0 equiv for 8t) and molecular sieves 4Å were added, respectively. The
reaction mixture was stirred at 60 °C under dark in the presence of N2. After the reaction was finished,
the mixture was filtered by celite (or centrifugation) and concentrated, and the residue was purified
through silica gel column chromatography (CH2Cl2:Hexane=1:1 for 8a-8l, 8o-8p; EtOAc:hexane=1:2
for 8m-8n, 8q-8t) to afford corresponding products.
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1'-OH-heptaacetylsucrose (1).12 Colorless oil (0.25 g, 27.4%): [α]D +50 (c 0.2 CHCl3) (lit12a.: +43,
c 2.0 CHCl3); 1H NMR (270 MHz, CDCl3) δ 5.67 (d, J = 3.7 Hz, 1H), 5.49 – 5.42 (m, 3H), 5.09 (t, J =
9.7 Hz, 1H), 4.93 (dd, J = 10.4, 3.7 Hz, 1H), 4.33 – 4.11 (m, 6H), 3.71 (d, J = 12.6 Hz, 1H), 3.59 (d, J
= 12.6 Hz, 1H), 2.19 (s, 3H), 2.12 (s, 3H), 2.09 (s, 6H), 2.08 (s, 3H), 2.04 (s, 3H), 2.02 (s, 3H); 13C
NMR (68 MHz, CDCl3) δ 170.82, 170.78, 170.6, 170.3, 170.1(2C), 169.6, 105.2, 89.8, 78.7, 76.4,
74.7, 70.1, 69.7, 68.4, 68.2, 63.6, 63.5, 61.7, 20.5 (7C); HRMS-ESI (m/z) [M + Na]+ calcd for
C26H36O18Na 659.1799, found 659.1822.
1'-[p-(trifluoromethyl)benzyl]heptaacetylsucrose (3a). Colorless oil (72.3 mg, 91%): [α]D +55
(c 1 CHCl3); 1H NMR (270 MHz, CDCl3) δ 7.62 (d, J = 8.1 Hz, 2H), 7.47 (d, J = 8.1 Hz, 2H), 5.71 –
5.69 (m, 2H), 5.48 – 5.39 (m, 2H), 5.08 (t, J = 9.7 Hz, 1H), 4.86 (dd, J = 10.3, 3.8 Hz, 1H), 4.65 (s,
2H), 4.32 – 4.12 (m, 6H), 3.64 (d, J = 10.5 Hz, 1H), 3.44 (d, J = 10.5 Hz, 1H), 2.13 (s, 3H), 2.12 (s,
3H), 2.08 (s, 3H), 2.04 (s, 6H), 2.01 (s, 3H), 1.94 (s, 3H); 13C NMR (68 MHz, CDCl3) δ 170.5, 170.4,
170.0, 169.8, 169.6, 169.4, 141.6, 129.8 (q, J = 32.1 Hz), 127.5, 125.2 (d, J = 3.5 Hz), 124.0 (q, J =
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272.5 Hz), 104.1, 89.4, 78.3, 75.4, 74.3, 72.5, 70.1, 70.0, 69.5, 68.1, 68.0, 63.1, 61.4, 20.2 and 20.0
(7C); 19F-NMR (470 MHz, CDCl3): δ = -62.53 ppm; HRMS-ESI (m/z) [M + Na]+ calcd for
C34H41F3O18Na 817.2143, found 817.2161.
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1'-[m-(trifluoromethyl)benzyl]heptaacetylsucrose (3b). Colorless oil (75.4 mg, 95%): [α]D +52
(c 1 CHCl3); 1H NMR (270 MHz, CDCl3) δ 7.62 – 7.49 (m, 4H), 5.72 – 5.69 (m, 2H), 5.48 – 5.40 (m,
2H), 5.08 (t, J = 8.9 Hz, 1H), 4.86 (dd, J = 10.3, 3.7 Hz, 1H), 4.65 (s, 2H), 4.31 – 4.11 (m, 6H), 3.66
(d, J = 10.5 Hz, 1H), 3.46 (d, J = 10.5 Hz, 1H), 2.13 (s, 3H), 2.12 (s, 3H), 2.08 (s, 3H), 2.04 (s, 6H),
2.01 (s, 3H), 1.95 (s, 3H); 13C NMR (68 MHz, CDCl3) δ 170.8, 170.7, 170.3, 170.10, 170.06, 169.9,
169.7, 138.7, 130.91 (q, J = 32.5 Hz), 130.86, 129.0, 124.7 (q, J = 3.7 Hz), 124.3 (q, J = 3.7 Hz),
124.1 (q, J = 271.7 Hz), 104.3, 89.6, 78.5, 75.6, 74.4, 72.9, 70.5, 70.2, 69.7, 68.3, 68.2, 63.4, 61.6,
20.5 and 20.4 and 20.3 (7C); 19F-NMR (470 MHz, CDCl3): δ = -62.64 ppm; HRMS-ESI (m/z) [M +
Na]+ calcd for C34H41F3O18Na 817.2143, found 817.2166.
1'-(p-nitrobenzyl)heptaacetylsucrose (3c). Colorless oil (57.8 mg, 75%): [α]D +54 (c 1 CHCl3);
1H NMR (270 MHz, CDCl3) δ 8.23 (d, J = 8.7 Hz, 2H), 7.54 (d, J = 8.7 Hz, 2H), 5.72 – 5.69 (m, 2H),
5.49 – 5.41 (m, 2H), 5.09 (t, J = 9.7 Hz, 1H), 4.86 (dd, J = 10.3, 3.7 Hz, 1H), 4.70 (s, 2H), 4.33 – 4.13
(m, 6H), 3.70 (d, J = 10.5 Hz, 1H), 3.49 (d, J = 10.5 Hz, 1H), 2.15 (s, 3H), 2.12 (s, 3H), 2.09 (s, 3H),
2.06 (s, 3H), 2.04 (s, 3H), 2.01 (s, 3H), 1.98 (s, 3H); 13C NMR (68 MHz, CDCl3) δ 170.8, 170.7, 170.3,
170.02 (2C), 169.95, 169.6, 147.7, 145.1, 127.9, 123.8, 104.3, 89.6, 78.5, 75.6, 74.4, 72.4, 70.9, 70.3,
69.7, 68.3, 68.2, 63.3, 61.6, 20.51 and 20.46 and 20.39 (7C); HRMS-ESI (m/z) [M + Na]+ calcd for
C33H41NO20Na 794.2120, found 794.2119.
1'-(m-nitrolbenzyl)heptaacetylsucrose (3d). Colorless oil (65.6 mg, 85%): [α]D +60 (c 1 CHCl3);
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1H NMR (270 MHz, CDCl3) δ 8.23 (s, 1H), 8.17 (d, J = 8.1 Hz, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.55 (t,
J = 8.1 Hz, 1H), 5.72 – 5.69 (m, 2H), 5.48 – 5.41 (m, 2H), 5.08 (t, J = 9.7 Hz, 1H), 4.86 (dd, J = 10.4,
3.7 Hz, 1H), 4.70 (s, 2H), 4.34 – 4.12 (m, 6H), 3.70 (d, J = 10.4 Hz, 1H), 3.50 (d, J = 10.4 Hz, 1H),
2.14 (s, 3H), 2.13 (s, 3H), 2.09 (s, 3H), 2.06 (s, 3H), 2.04 (s, 3H), 2.01 (s, 3H), 1.99 (s, 3H); 13C NMR
(68 MHz, CDCl3) δ 170.8, 170.7, 170.3, 170.08, 170.06, 170.0, 169.7, 148.6, 139.9, 133.4, 129.6,
122.9, 122.3, 104.2, 89.6, 78.5, 75.6, 74.4, 72.4, 70.9, 70.2, 69.7, 68.3, 68.2, 63.3, 61.6, 20.5 and 20.4
(7C); HRMS-ESI (m/z) [M + Na]+ calcd for C33H41NO20Na 794.2120, found 794.2135.
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1'-(p-chlorobenzyl)heptaacetylsucrose (3e). Colorless oil (70.1 mg, 92%): [α]D +54 (c 1 CHCl3);
1H NMR (270 MHz, CDCl3) δ 7.33 (d, J = 8.6 Hz, 2H), 7.28 (d, J = 8.6 Hz, 2H), 5.69 – 5.67 (m, 2H),
5.48 – 5.38 (m, 2H), 5.08 (t, J = 9.7 Hz, 1H), 4.86 (dd, J = 10.4, 3.7 Hz, 1H), 4.55 (s, 2H), 4.32 – 4.11
(m, 6H), 3.60 (d, J = 10.5 Hz, 1H), 3.41 (d, J = 10.5 Hz, 1H), 2.13 (s, 3H), 2.12 (s, 3H), 2.09 (s, 3H),
2.04 (s, 6H), 2.01 (s, 3H), 1.96 (s, 3H); 13C NMR (68 MHz, CDCl3) δ 170.8, 170.6, 170.2, 170.1 (2C),
169.8, 169.6, 136.0, 133.7, 129.1, 128.7, 104.4, 89.6, 78.4, 75.6, 74.5, 72.8, 70.2, 70.0, 69.7, 68.2 (2C),
63.4, 61.6, 20.5 and 20.4 and 20.3 (7C); HRMS-ESI (m/z) [M + Na]+ calcd for C33H41Cl35O18Na
783.1879, found 783.1882 or calcd for C33H41Cl37O18Na 785.1850, found 785.1863.
1'-(m-chlorobenzyl)heptaacetylsucrose (3f). Colorless oil (68.6 mg, 90%): [α]D +56 (c 1 CHCl3);
1H NMR (270 MHz, CDCl3) δ 7.35 (s, 1H), 7.30 – 7.20 (m, 3H), 5.71 – 5.68 (m, 2H), 5.47 – 5.39 (m,
2H), 5.08 (t, J = 9.6 Hz, 1H), 4.86 (dd, J = 10.4, 3.8 Hz, 1H), 4.56 (s, 2H), 4.31 – 4.11 (m, 6H), 3.62
(d, J = 10.5 Hz, 1H), 3.43 (d, J = 10.5 Hz, 1H), 2.14 (s, 3H), 2.12 (s, 3H), 2.09 (s, 3H), 2.05 (s, 3H),
2.03 (s, 3H), 2.01 (s, 3H), 1.97 (s, 3H); 13C NMR (68 MHz, CDCl3) δ 170.8, 170.7, 170.2, 170.1 (2C),
169.9, 169.7, 139.7, 134.5, 129.8, 128.1, 127.7, 125.7, 104.4, 89.6, 78.5, 75.6, 74.5, 72.8, 70.2 (2C),
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69.7, 68.2 (2C), 63.4, 61.6, 20.51 and 20.47 and 20.3 (7C); HRMS-ESI (m/z) [M + Na]+ calcd for
C33H41Cl35O18Na 783.1879, found 783.1899 or calcd for C33H41Cl37O18Na 785.1850, found 785.1870.
1'-(p-bromobenzyl)heptaacetylsucrose (3g). Colorless oil (73.4 mg, 91%): [α]D +56 (c 1 CHCl3);
1H NMR (270 MHz, CDCl3) δ 7.48 (d, J = 8.2 Hz, 2H), 7.23 (d, J = 8.2 Hz, 2H), 5.69 – 5.67 (m, 2H),
5.47 – 5.38 (m, 2H), 5.08 (t, J = 9.6 Hz, 1H), 4.86 (dd, J = 10.3, 3.7 Hz, 1H), 4.53 (s, 2H), 4.31 – 4.11
(m, 6H), 3.60 (d, J = 10.6 Hz, 1H), 3.40 (d, J = 10.6 Hz, 1H), 2.13 (s, 3H), 2.12 (s, 3H), 2.09 (s, 3H),
2.04 (s, 6H), 2.01 (s, 3H), 1.96 (s, 3H); 13C NMR (68 MHz, CDCl3) δ 170.8, 170.7, 170.3, 170.1 (2C),
169.9, 169.7, 136.6, 131.7, 129.5, 121.9, 104.4, 89.6, 78.5, 75.6, 74.5, 72.9, 70.2, 70.0, 69.7, 68.2 (2C),
63.4, 61.6, 20.5 and 20.3 (7C); HRMS-ESI (m/z) [M + Na]+ calcd for C33H41Br79O18Na 827.1374,
found 827.1390 or calcd for C33H41Br81O18Na 829.1353, found 829.1377.
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CHCl3); H NMR (270 MHz, CDCl3) δ 7.50 (s, 1H), 7.43 (dt, J = 7.2, 1.8 Hz, 1H), 7.29 – 7.20 (m,
2H), 5.71 – 5.68 (m, 2H), 5.47 – 5.39 (m, 2H), 5.08 (t, J = 9.6 Hz, 1H), 4.86 (dd, J = 10.4, 3.8 Hz, 1H),
4.56 (s, 2H), 4.32 – 4.11 (m, 6H), 3.62 (d, J = 10.5 Hz, 1H), 3.42 (d, J = 10.5 Hz, 1H), 2.13 (s, 3H),
2.12 (s, 3H), 2.09 (s, 3H), 2.05 (s, 3H), 2.04 (s, 3H), 2.01 (s, 3H), 1.97 (s, 3H); 13C NMR (68 MHz,
CDCl3) δ 170.8, 170.7, 170.2, 170.1 (2C), 169.9, 169.6, 137.0, 131.0, 130.6, 130.1, 126.2, 122.6,
104.4, 89.6, 78.5, 75.6, 74.5, 72.8, 70.22, 70.15, 69.7, 68.2 (2C), 63.4, 61.6, 20.50 and 20.47 and 20.3
(7C); HRMS-ESI (m/z) [M + Na]+ calcd for C33H41Br79O18Na 827.1374, found 827.1400 or calcd for
C33H41Br81O18Na 829.1353, found 829.1381.
1'-benzylheptaacetylsucrose (3i).21 Colorless oil (50.1 mg, 69%): [α]D +56 (c 1 CHCl3); 1H NMR
(270 MHz, CDCl3) δ 7.36 – 7.29 (m, 5H), 5.72 – 5.68 (m, 2H), 5.47 – 5.38 (m, 2H), 5.07 (t, J = 9.7 Hz,
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1H), 4.86 (dd, J = 10.3, 3.7 Hz, 1H), 4.59 (s, 2H), 4.32 – 4.10 (m, 6H), 3.60 (d, J = 10.6 Hz, 1H), 3.41
(d, J = 10.6 Hz, 1H), 2.11 (s, 6H), 2.08 (s, 3H), 2.03 (s, 6H), 2.00 (s, 3H), 1.94 (s, 3H); 13C NMR (68
MHz, CDCl3) δ 170.8, 170.7, 170.2, 170.1 (2C), 169.9, 169.7, 137.6, 128.5, 127.9, 127.8, 104.5, 89.6,
78.3, 75.6, 74.6, 73.6, 70.2, 69.8 (2C), 68.24, 68.18, 63.5, 61.7, 20.52 and 20.46 and 20.2 (7C);
HRMS-ESI (m/z) [M + Na]+ calcd for C33H42O18Na 749.2269, found 749.2257.
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1'-(p-methylbenzyl)heptaacetylsucrose (3j). Colorless oil (40.7 mg, 55%): [α]D +51 (c 1 CHCl3);
1H NMR (270 MHz, CDCl3) δ 7.22 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 5.71 – 5.67 (m, 2H),
5.47 – 5.37 (m, 2H), 5.07 (t, J = 9.6 Hz, 1H), 4.86 (dd, J = 10.4, 3.8 Hz, 1H), 4.54 (s, 2H), 4.31 – 4.10
(m, 6H), 3.56 (d, J = 10.6 Hz, 1H), 3.39 (d, J = 10.6 Hz, 1H), 2.34 (s, 3H), 2.11 (s, 6H), 2.08 (s, 3H),
2.03 (s, 6H), 2.00 (s, 3H), 1.95 (s, 3H); 13C NMR (68 MHz, CDCl3) δ 170.9, 170.7, 170.3, 170.2 (2C),
169.9, 169.7, 137.7, 134.5, 129.2, 128.0, 104.6, 89.6, 78.4, 75.6, 74.6, 73.5, 70.2, 69.8, 69.6, 68.3,
68.2, 63.5, 61.7, 21.0, 20.54 and 20.48 and 20.3 (7C); HRMS-ESI (m/z) [M + Na]+ calcd for
C34H44O18Na 763.2425, found 763.2428.
1'-(m-methylbenzyl)heptaacetylsucrose (3k). Colorless oil (28.9 mg, 39%): [α]D +56 (c 1
CHCl3); 1H NMR (270 MHz, CDCl3) δ 7.27 – 7.21 (m, 1H), 7.14 – 7.09 (m, 3H), 5.73 – 5.68 (m, 2H),
5.47 – 5.38 (m, 2H), 5.07 (t, J = 9.7 Hz, 1H), 4.86 (dd, J = 10.4, 3.7 Hz, 1H), 4.55 (s, 2H), 4.31 – 4.10
(m, 6H), 3.58 (d, J = 10.6 Hz, 1H), 3.40 (d, J = 10.6 Hz, 1H), 2.35 (s, 3H), 2.12 (s, 3H), 2.11 (s, 3H),
2.08 (s, 3H), 2.03 (s, 6H), 2.00 (s, 3H), 1.94 (s, 3H); 13C NMR (68 MHz, CDCl3) δ 170.8, 170.7, 170.3,
170.2, 170.1, 169.8, 169.7, 138.2, 137.5, 128.7, 128.6, 128.4, 124.9, 104.5, 89.6, 78.4, 75.6, 74.6, 73.7,
70.1, 69.8, 69.7, 68.23, 68.15, 63.5, 61.7, 21.2, 20.51 and 20.46 and 20.3 (7C); HRMS-ESI (m/z) [M +
Na]+ calcd for C34H44O18Na 763.2425, found 763.2452.
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1'-(o-methylbenzyl)heptaacetylsucrose (3l). Colorless oil (37.0 mg, 50%): [α]D +55 (c 1 CHCl3);
1H NMR (270 MHz, CDCl3) δ 7.31 – 7.29 (m, 1H), 7.22 – 7.17 (m, 3H), 5.69 – 5.66 (m, 2H), 5.48 –
5.36 (m, 2H), 5.07 (t, J = 9.7 Hz, 1H), 4.86 (dd, J = 10.3, 3.7 Hz, 1H), 4.58 (dd, J = 20.0, 12.0 Hz, 2H),
4.31 – 4.10 (m, 6H), 3.63 (d, J = 10.5 Hz, 1H), 3.43 (d, J = 10.5 Hz, 1H), 2.33 (s, 3H), 2.11 (s, 6H),
2.09 (s, 3H), 2.03 (s, 3H), 2.01 (s, 6H), 1.96 (s, 3H); 13C NMR (68 MHz, CDCl3) δ 170.8, 170.7, 170.3,
170.2 (2C), 169.8, 169.7, 136.9, 135.4, 130.4, 128.8, 128.1, 125.8, 104.6, 89.7, 78.5, 75.7, 74.7, 72.0,
70.2, 70.0, 69.8, 68.3, 68.2, 63.5, 61.7, 20.5 and 20.4 and 20.3 (7C), 18.60; HRMS-ESI (m/z) [M +
Na]+ calcd for C34H44O18Na 763.2425, found 763.2441.
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1'-(p-methoxylbenzyl)heptaacetylsucrose (3m). Colorless oil (8.3 mg, 11%): [α]D +56 (c 1
CHCl3); 1H NMR (270 MHz, CDCl3) δ 7.26 (d, J = 8.5 Hz, 2H), 6.88 (d, J = 8.5 Hz, 2H), 5.71 – 5.67
(m, 2H), 5.47 – 5.37 (m, 2H), 5.07 (t, J = 9.5 Hz, 1H), 4.86 (dd, J = 10.3, 3.8 Hz, 1H), 4.51 (s, 2H),
4.31 – 4.10 (m, 6H), 3.81 (s, 3H), 3.55 (d, J = 10.6 Hz, 1H), 3.38 (d, J = 10.6 Hz, 1H), 2.11 (s, 3H),
2.09 (s, 3H), 2.03 (s, 6H), 2.01 (s, 3H), 1.96 (s, 3H); 13C NMR (68 MHz, CDCl3) δ 170.8, 170.7, 170.3,
170.2 (2C), 169.9, 169.7, 159.5, 129.5, 113.9, 104.6, 89.6, 78.4, 75.6, 74.6, 73.3, 70.2, 69.8, 69.4, 68.3,
68.2, 63.5, 61.7, 55.2, 20.6 and 20.5 and 20.4 (7C); HRMS-ESI (m/z) [M + Na]+ calcd for
C34H44O19Na 779.2374, found 779.2380.
1'-[p-(trifluorodiazirinyl)benzyl]heptaacetylsucrose (3n). Colorless oil (66.7 mg, 80%): [α]D
+53 (c 1 CHCl3); 1H NMR (270 MHz, CDCl3) δ 7.39 (d, J = 8.2 Hz, 2H), 7.20 (d, J = 8.2 Hz, 2H), 5.70 –
5.68 (m, 2H), 5.47 – 5.39 (m, 2H), 5.08 (t, J = 9.3 Hz, 1H), 4.86 (dd, J = 9.9, 4.1 Hz, 1H), 4.60 (s, 2H),
4.32 – 4.11 (m, 6H), 3.60 (d, J = 10.5 Hz, 1H), 3.41 (d, J = 10.5 Hz, 1H), 2.13 (s, 3H), 2.12 (s, 3H),
2.09 (s, 3H), 2.04 (s, 6H), 2.01 (s, 3H), 1.94 (s, 3H); 13C NMR (68 MHz, CDCl3) δ 170.7, 170.6, 170.2,
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170.0 (2C), 169.8, 169.6, 139.4, 128.6, 128.0, 126.6, 122.1 (q, J = 275.3 Hz), 104.3, 89.5, 78.4, 75.5,
74.4, 72.7, 70.1 (2C), 69.7, 68.2, 68.1, 63.3, 61.6, 28.2 (q, J = 39.9 Hz), 20.5 and 20.4 and 20.2 (7C);
19F-NMR (470 MHz, CDCl3): δ = -65.28 ppm; HRMS-ESI (m/z) [M + Na]+ calcd for C35H41N2O18F3Na
857.2204, found 857.2191.
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1'-((1-methyl)benzyl)heptaacetylsucrose (3o). Colorless oil (70.3 mg, 95%, mixture of (R)- and
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(S)-isomers): [α]D +54 (c 1 CHCl3); H NMR (270 MHz, CDCl3) δ 7.34 – 7.27 (m, 5H), 5.76 – 5.63
(m, 2H), 5.46 – 5.29 (m, 2H), 5.10 – 5.01 (m, 1H), 4.84 (dd, J = 10.3, 3.8 Hz, 1H), 4.50 – 4.41 (m,
1H), 4.33 – 4.05 (m, 6H), 3.49 – 3.42 (m, 1H), 3.27 – 3.17 (m, 1H), 2.18 – 1.86 (m, 21H), 1.46 – 1.43
(m, 3H); 13C NMR (68 MHz, CDCl3) δ 170.8 – 169. 7 (7C), 143.1 and 142.8, 128.64 and 128.59,
127.9 and 127.8, 126.3, 104.8 and 104.7, 89.8 and 89.5, 79.3, 79.2 and 79.0, 78.3, 75.7 and 75.5, 75.2
and 74.7, 70.2 and 70.1, 69.8 and 69.7, 68.3 and 68.20, 68.15 and 68.1, 63.54 and 63.48, 61.6, 23.9
and 23.7, 20.6 – 20.2 (7C); HRMS-ESI (m/z) [M + Na]+ calcd for C34H44O18Na 763.2425, found
763.2443.
1'-[p-(trifluoromethyl)benzyl]sucrose (6a). White solid (96.0 mg, 96%): mp 90–92 °C; [α]D +57
(c 1 CH3OH); 1H NMR (270 MHz, CD3OD) δ 7.66 (d, J = 8.1 Hz, 2H), 7.58 (d, J = 8.1 Hz, 2H), 5.41
(d, J = 3.8 Hz, 1H), 4.76 (d, J = 12.5 Hz, 1H), 4.69 (d, J = 12.5 Hz, 1H), 4.27 (d, J = 8.5 Hz, 1H), 4.11
– 4.03 (m, 1H), 3.86 – 3.61 (m, 9H), 3.41 (dd, J = 6.4, 3.3 Hz, 1H), 3.37 (s, 1H); 13C NMR (68 MHz,
CD3OD) δ 144.3, 130.8 (q, J = 31.9 Hz), 129.0 (d, J = 2.0 Hz), 126.3 (d, J = 2.6 Hz), 125.8 (q, J =
272.1 Hz), 105.2, 94.0, 83.5, 78.6, 75.3, 74.7, 74.3, 73.7, 73.1, 71.4 (2C), 63.3, 62.2; 19F-NMR (470
MHz, CD3OD): δ = -64.00 ppm. HRMS-ESI (m/z) [M + Na]+ calcd for C20H27F3O11Na 523.1403,
found 523.1423.
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1'-[m-(trifluoromethyl)benzyl]sucrose (6b). White solid (93.0 mg, 93%): mp 91–93 °C; [α]D
+55 (c 1 CH3OH); 1H NMR (270 MHz, CD3OD) δ 7.61 – 7.44 (m, 4H), 5.32 (d, J = 3.8 Hz, 1H), 4.67
(d, J = 12.5 Hz, 1H), 4.60 (d, J = 12.5 Hz, 1H), 4.17 (d, J = 8.6 Hz, 1H), 4.05 – 3.95 (m, 1H), 3.77 –
3.62 (m, 7H), 3.57 (t, J = 10.7 Hz, 2H), 3.33 (dd, J = 6.2, 3.5 Hz, 1H), 3.29 (d, J = 2.5 Hz, 1H); 13C
NMR (68 MHz, CD3OD) δ 141.2, 132.4, 131.8 (q, J = 32.0 Hz), 130.3, 125.8 (q, J = 271.4 Hz), 125.4
(q, J = 3.8 Hz), 125.2 (q, J = 3.8 Hz), 105.2, 94.0, 83.5, 78.6, 75.3, 74.7, 74.3, 73.8, 73.1, 71.4 (2C),
63.3, 62.2; 19F-NMR (470 MHz, CD3OD): δ = -64.08 ppm. HRMS-ESI (m/z) [M + Na]+ calcd for
C20H27F3O11Na 523.1403, found 523.1395.
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1'-(p-nitrobenzyl)sucrose (6c). White solid (85.9 mg, 90%): mp 93–95 °C; [α]D +53 (c 1 CH3OH);
1H NMR (270 MHz, CD3OD) δ 8.26 (d, J = 8.7 Hz, 2H), 7.65 (d, J = 8.7 Hz, 2H), 5.42 (d, J = 3.7 Hz,
1H), 4.83 (d, J = 13.3 Hz, 1H), 4.75 (d, J = 13.3 Hz, 1H), 4.27 (d, J = 8.5 Hz, 1H), 4.12 – 4.02 (m,
1H), 3.87 – 3.64 (m, 9H), 3.41 (dd, J = 8.6, 4.8 Hz, 1H), 3.37 (s, 1H); 13C NMR (68 MHz, CD3OD) δ
149.0, 147.7, 129.3, 124.6, 105.3, 94.1, 83.7, 78.7, 75.4, 74.8, 74.4, 73.4, 73.2, 71.6, 71.5, 63.4, 62.3;
HRMS-ESI (m/z) [M + Na]+ calcd for C19H27NO13Na 500.1380, found 500.1382.
1'-(m-nitrobenzyl)sucrose (6d). White solid (85.9 mg, 90%): mp 91–93 °C; [α]D +53 (c 1
CH3OH); 1H NMR (270 MHz, CD3OD) δ 8.26 (s, 1H), 8.16 (dd, J = 7.9, 1.2 Hz, 1H), 7.79 (d, J = 7.9
Hz, 1H), 7.60 (t, J = 7.9 Hz, 1H), 5.39 (d, J = 3.8 Hz, 1H), 4.77 (d, J = 13.0 Hz, 1H), 4.71 (d, J = 13.0
Hz, 1H), 4.23 (d, J = 8.5 Hz, 1H), 4.07 – 4.01 (m, 1H), 3.85 – 3.60 (m, 9H), 3.38 (dd, J = 6.6, 3.1 Hz,
1H), 3.34 (d, J = 3.3 Hz, 1H); 13C NMR (68 MHz, CD3OD) δ 150.0, 142.4, 134.9, 130.8, 123.6, 123.3,
105.3, 94.1, 83.6, 78.7, 75.3, 74.7, 74.4, 73.4, 73.2, 71.5 (2C), 63.3, 62.3; HRMS-ESI (m/z) [M + Na]+
calcd for C19H27NO13Na 500.1380, found 500.1382.
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1'-(p-chlorobenzyl)sucrose (6e). White solid (88.7 mg, 95%): mp 90–92 °C; [α]D +55 (c 1
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CH3OH); H NMR (270 MHz, CD3OD) δ 7.38 – 7.25 (m, 4H), 5.37 (d, J = 3.8 Hz, 1H), 4.62 (d, J =
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12.2 Hz, 1H), 4.55 (d, J = 12.2 Hz, 1H), 4.20 (d, J = 8.5 Hz, 1H), 4.05 – 3.99 (m, 1H), 3.82 – 3.55 (m,
9H), 3.37 (dd, J = 5.8, 4.0 Hz, 1H), 3.34 (s, 1H); 13C NMR (68 MHz, CD3OD) δ 138.6, 134.6, 130.5,
129.6, 105.3, 94.1, 83.6, 78.8, 75.4, 74.8, 74.4, 73.8, 73.3, 71.5, 71.2, 63.4, 62.3; HRMS-ESI (m/z) [M
+ Na]+ calcd for C19H27Cl35O11Na 489.1140, found 489.1116 or calcd for C19H27Cl37O11Na 491.1110,
found 491.1086.
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1'-(m-chlorobenzyl)sucrose (6f). White solid (81.3 mg, 87%): mp 90–92 °C; [α]D +59 (c 1
CH3OH); 1H NMR (270 MHz, CD3OD) δ 7.39 (s, 1H), 7.33 – 7.26 (m, 3H), 5.38 (d, J = 3.8 Hz, 1H),
4.64 (d, J = 12.2 Hz, 1H), 4.57 (d, J = 12.2 Hz, 1H), 4.22 (d, J = 8.5 Hz, 1H), 4.11 – 4.00 (m, 1H),
3.83 – 3.56 (m, 9H), 3.38 (dd, J = 6.3, 3.4 Hz, 1H), 3.34 (s, 1H); 13C NMR (68 MHz, CD3OD) δ 142.2,
135.5, 131.1, 128.84, 128.76, 127.1, 105.3, 94.1, 83.6, 78.7, 75.4, 74.8, 74.4, 73.8, 73.2, 71.5, 71.3,
63.4, 62.3; HRMS-ESI (m/z) [M + Na]+ calcd for C19H27Cl35O11Na 489.1140, found 489.1158 or calcd
for C19H27Cl37O11Na 491.1110, found 491.1137.
1'-(p-bromobenzyl)sucrose (6g). White solid (101.2 mg, 99%): mp 89–91 °C; [α]D +59 (c 1
CH3OH); 1H NMR (270 MHz, CD3OD) δ 7.49 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 5.37 (d, J
= 3.7 Hz, 1H), 4.61 (d, J = 12.2 Hz, 1H), 4.54 (d, J = 12.2 Hz, 1H), 4.20 (d, J = 8.5 Hz, 1H), 4.05 –
3.99 (m, 1H), 3.82 – 3.55 (m, 9H), 3.38 (dd, J = 5.8, 4.0 Hz, 1H), 3.34 (s, 1H); 13C NMR (68 MHz,
CD3OD) δ 139.1, 132.7, 130.8, 122.5, 105.3, 94.1, 83.6, 78.8, 75.4, 74.8, 74.4, 73.8, 73.3, 71.5, 71.2,
63.4, 62.3; HRMS-ESI (m/z) [M + Na]+ calcd for C19H27Br79O11Na 533.0634, found 533.0652 or
calcd for C19H27Br81O11Na 535.0614, found 535.0634.
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1'-(m-bromobenzyl)sucrose (6h). White solid (92.0 mg, 90%): mp 90–92 °C; [α]D +52 (c 1
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CH3OH); H NMR (270 MHz, CD3OD) δ 7.55 (s, 1H), 7.42 (d, J = 7.6 Hz, 1H), 7.34 (d, J = 7.6 Hz,
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1H), 7.26 (d, J = 7.6 Hz, 1H), 5.37 (d, J = 3.8 Hz, 1H), 4.63 (d, J = 12.3 Hz, 1H), 4.56 (d, J = 12.3 Hz,
1H), 4.22 (d, J = 8.5 Hz, 1H), 4.11 – 4.00 (m, 1H), 3.83 – 3.55 (m, 9H), 3.38 (dd, J = 6.2, 3.6 Hz, 1H),
3.34 (s, 1H); 13C NMR (68 MHz, CD3OD) δ 142.5, 131.9, 131.8, 131.4, 127.6, 123.5, 105.3, 94.1,
83.6, 78.7, 75.4, 74.8, 74.4, 73.8, 73.3, 71.5, 71.3, 63.4, 62.3; HRMS-ESI (m/z) [M + Na]+ calcd for
C19H27Br79O11Na 533.0634, found 533.0663 or calcd for C19H27Br81O11Na 535.0614, found 535.0632.
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1'- benzylsucrose (6i).21 White solid (78.7 mg, 91%): mp 78–80 °C; [α]D +57 (c 1 CH3OH); H
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NMR (270 MHz, CD3OD) δ 7.39 – 7.25 (m, 5H), 5.38 (d, J = 3.8 Hz, 1H), 4.64 (d, J = 12.0 Hz, 1H),
4.57 (d, J = 12.0 Hz, 1H), 4.22 (d, J = 8.5 Hz, 1H), 4.07 – 3.98 (m, 1H), 3.83 – 3.56 (m, 9H), 3.38 (dd,
J = 5.8, 3.9 Hz, 1H), 3.35 (s, 1H); 13C NMR (68 MHz, CD3OD) δ 139.6, 129.6, 129.0, 128.9, 105.3,
94.1, 83.6, 78.8, 75.4, 74.8, 74.7, 74.4, 73.3, 71.5, 71.2, 63.3, 62.3; HRMS-ESI (m/z) [M + Na]+ calcd
for C19H28O11Na 455.1529, found 455.1538.
1'-(p-methylbenzyl)sucrose (6j). White solid (79.5 mg, 89%): mp 85–87 °C; [α]D +58 (c 1
CH3OH); 1H NMR (270 MHz, CD3OD) δ 7.25 (d, J = 7.7 Hz, 2H), 7.15 (d, J = 7.7 Hz, 2H), 5.38 (d, J
= 3.7 Hz, 1H), 4.60 (d, J = 11.8 Hz, 1H), 4.53 (d, J = 11.8 Hz, 1H), 4.21 (d, J = 8.5 Hz, 1H), 4.08 –
4.00 (m, 1H), 3.83 – 3.54 (m, 9H), 3.39 (t, J = 4.8 Hz, 1H), 3.35 (brs, 1H), 2.33 (s, 3H); 13C NMR (68
MHz, CD3OD) δ 138.7, 136.5, 130.1, 129.2, 105.3, 94.0, 83.5, 78.8, 75.4, 74.7, 74.6, 74.3, 73.2, 71.4,
71.0, 63.3, 62.2, 21.1; HRMS-ESI (m/z) [M + Na]+ calcd for C20H30O11Na 469.1686, found 469.1693.
1'-(m-methylbenzyl)sucrose (6k). White solid (83.0 mg, 93%): mp 86–88 °C; [α]D +57 (c 1
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CH3OH); H NMR (270 MHz, CD3OD) δ 7.21 (t, J = 7.5 Hz, 1H), 7.17 (s, 1H), 7.14 (d, J = 7.5 Hz,
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1H), 7.08 (d, J = 7.5 Hz, 1H), 5.38 (d, J = 3.8 Hz, 1H), 4.60 (d, J = 11.8 Hz, 1H), 4.53 (d, J = 11.8 Hz,
1H), 4.21 (d, J = 8.5 Hz, 1H), 4.06 – 4.00 (m, 1H), 3.83 – 3.54 (m, 9H), 3.38 (dd, J = 5.8, 3.9 Hz, 1H),
3.35 (s, 1H), 2.33 (s, 3H); 13C NMR (68 MHz, CD3OD) δ 139.5, 139.3, 129.7, 129.53, 129.45, 126.1,
105.3, 94.1, 83.5, 78.8, 75.4, 74.8 (2C), 74.4, 73.3, 71.4, 71.1, 63.3, 62.3, 21.4; HRMS-ESI (m/z) [M
+ Na]+ calcd for C20H30O11Na 469.1686, found 469.1678.
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1'-(o-methylbenzyl)sucrose (6l). White solid (81.2 mg, 91%): mp 83–85 °C; [α]D +58 (c 0.2
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CH3OH); H NMR (270 MHz, CD3OD) δ 7.33 – 7.30 (m, 1H), 7.18 – 7.10 (m, 3H), 5.38 (d, J = 3.8
Hz, 1H), 4.65 (d, J = 11.7 Hz, 1H), 4.57 (d, J = 11.7 Hz, 1H), 4.21 (d, J = 8.5 Hz, 1H), 4.07 – 3.98 (m,
1H), 3.83 – 3.56 (m, 9H), 3.38 (dd, J = 6.1, 3.8 Hz, 1H), 3.34 (s, 1H), 2.34 (s, 3H); 13C NMR (68 MHz,
CD3OD) δ 138.2, 137.4, 131.3, 130.0, 129.1, 126.9, 105.4, 94.1, 83.6, 78.7, 75.5, 74.8, 74.4, 73.3,
73.1, 71.5, 71.1, 63.3, 62.3, 18.9; HRMS-ESI (m/z) [M + Na]+ calcd for C20H30O11Na 469.1686, found
469.1698.
1'-(p-methoxylbenzyl)sucrose (6m). White solid (83.2 mg, 90%): mp 83–85 °C; [α]D +59 (c 1
CH3OH); 1H NMR (270 MHz, CD3OD) δ 7.28 (d, J = 8.6 Hz, 2H), 6.89 (d, J = 8.6 Hz, 2H), 5.37 (d, J
= 3.8 Hz, 1H), 4.56 (d, J = 11.5 Hz, 1H), 4.49 (d, J = 11.5 Hz, 1H), 4.18 (d, J = 8.5 Hz, 1H), 4.06 –
3.96 (m, 1H), 3.85 – 3.52 (m, 9H), 3.78 (s, 3H), 3.37 (t, J = 4.6 Hz, 1H), 3.34 (s, 1H); 13C NMR (68
MHz, CD3OD) δ 161.1, 131.5, 130.8, 114.9, 105.3, 94.1, 83.6, 78.9, 75.5, 74.8, 74.41, 74.40, 73.3,
71.5, 70.9, 63.4, 62.3, 55.7; HRMS-ESI (m/z) [M + Na]+ calcd for C20H30O12Na 485.1635, found
485.1645.
1'-[p-(trifluorodiazirinyl)benzyl]sucrose (6n). White solid (98.3 mg, 91%): mp 73–75 °C; [α]D
+50 (c 1 CH3OH); 1H NMR (270 MHz, CD3OD) δ 7.50 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H),
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5.39 (d, J = 3.9 Hz, 1H), 4.70 (d, J = 12.7 Hz, 1H), 4.63 (d, J = 12.7 Hz, 1H), 4.23 (d, J = 8.5 Hz, 1H),
4.09 – 3.97 (m, 1H), 3.84 – 3.57 (m, 9H), 3.39 (dd, J = 5.7, 2.6 Hz, 1H), 3.35 (s, 1H); 13C NMR (68
MHz, CD3OD) δ 142.2, 129.4, 129.3, 127.7, 123.8 (q, J = 273.7 Hz), 105.2, 94.1, 83.6, 78.7, 75.4,
74.7, 74.4, 73.7, 73.2, 71.4, 71.3, 63.3, 62.3, 29.4 (q, J = 40.5 Hz); 19F-NMR (470 MHz, CD3OD): δ =
-67.15 ppm. HRMS-ESI (m/z) [M + Na]+ calcd for C21H27N2O11F3Na 563.1465, found 563.1488.
1'-((1-methyl)benzyl)sucrose (6o). White solid (87.5 mg, 98%, mixture of (R)- and (S)-isomers):
mp 60–62 °C; [α]D +53 (c 1 CH3OH); 1H NMR (270 MHz, CD3OD) δ 7.37 – 7.21 (m, 5H), 5.33 (d, J
= 3.8 Hz, 0.5H) and 5.30 (d, J = 3.8 Hz, 0.5H), 4.63 – 4.48 (m, 1H), 4.27 (d, J = 8.5 Hz, 0.5H) and
4.15 (d, J = 8.5 Hz, 0.5H), 4.01 (t, J = 7.9 Hz, 1H), 3.81 – 3.49 (m, 9H), 3.43 – 3.33 (m, 2H), 1.44 –
1.40 (m, 3H); 13C NMR (68 MHz, CD3OD) δ 145.1 and 145.0, 129.68 and 129.65, 128.7, 127.5 and
127.4, 105.6 and 105.1, 94.03 and 93.96, 83.7 and 83.6, 80.3 and 80.2, 79.2 and 78.6, 75.5 and 75.4,
74.9 and 74.7, 74.4 and 74.3, 73.3 and 73.2, 71.4, 70.1 and 69.2, 63.4 and 63.2, 62.2, 24.4 and 24.2;
HRMS-ESI (m/z) [M + Na]+ calcd for C20H30O11Na 469.1686, found 469.1687.
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1-bromo-4-(ethoxymethyl)benzene (8a).22 Colorless oil (63.2 mg, 98%): H NMR (270 MHz,
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CDCl3) δ 7.47 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 4.45 (s, 2H), 3.53 (q, J = 7.0 Hz, 2H),
1.24 (t, J = 7.0 Hz, 3H); 13C NMR (68 MHz, CDCl3) δ 137.8, 131.6, 129.4, 121.4, 71.9, 65.9, 15.1;
HRMS-ESI (m/z) [M + H]+ calcd for C9H10BrO 214.9895, found 214.9910.
1-bromo-4-(propoxymethyl)benzene (8b).23 Colorless oil (65.3 mg, 95%): H NMR (270 MHz,
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CDCl3) δ 7.47 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 4.45 (s, 2H), 3.42 (t, J = 6.7 Hz, 2H), 1.70
– 1.59 (m, 2H), 0.94 (t, J = 6.7 Hz, 3H); 13C NMR (68 MHz, CDCl3) δ 137.9, 131.5, 129.3, 121.4,
72.2, 72.0, 22.8, 10.5; HRMS-ESI (m/z) [M + H]+ calcd for C10H12BrO 229.0051, found 229.0046.
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