Synthesis and application of novel carbohydrate-based ammonium and triazolium salts

Article abstract of DOI:10.1080/00397911.2019.1625403

The synthesis of nine new carbohydrate-based quaternary ammonium salts and two new triazolium salts starting from d-glucose has been accomplished. Our synthesis utilized the regio- and stereoselective ring opening reaction of 2,3-anhydro sugars by nucleop

Full text of DOI:10.1080/00397911.2019.1625403

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
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ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
Synthesis and application of novel carbohydrate-
based ammonium and triazolium salts
Tamás Nemcsok, Zsolt Rapi, Péter Bagi & Péter Bakó
To cite this article: Tamás Nemcsok, Zsolt Rapi, Péter Bagi & Péter Bakó (2019): Synthesis
and application of novel carbohydrate-based ammonium and triazolium salts, Synthetic
Communications, DOI: 10.1080/00397911.2019.1625403
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https://doi.org/10.1080/00397911.2019.1625403
Synthesis and application of novel carbohydrate-based
ammonium and triazolium salts
ꢀ
ꢀ
ꢀ
ꢀ
Tamas Nemcsok, Zsolt Rapi, Peter Bagi, and Peter Bako
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics,
Budapest, Hungary
ABSTRACT
ARTICLE HISTORY
Received 30 April 2019
The synthesis of nine new carbohydrate-based quaternary ammo-
nium salts and two new triazolium salts starting from D-glucose has
been accomplished. Our synthesis utilized the regio- and stereo-
selective ring opening reaction of 2,3-anhydro sugars by nucleophilic
reagents to afford the key intermediates. In these new types of
phase transfer catalysts, the ammonium and triazolium functions are
directly attached to the carbohydrate scaffold in different positions
(2-, 3-, 6-positions of the sugar). The efficiency of the altrose- and
glucose-based quaternary salts were tested in the alkylation of N-
(diphenyl) methylene glycine tert-butyl ester with benzyl bromide. To
our knowledge this is the first example when sugar-based quater-
nary ammonium or triazolium salts were used successfully as phase
transfer catalysts. The enantiomeric recognition ability of the synthe-
sized salts towards racemic Mosher’s acid silver salt was also investi-
gated by 19F NMR spectroscopy.
KEYWORDS
Carbohydrate-based quater-
nary salts; phase transfer
catalysis; enantiomeric
recognition
GRAPHICAL ABSTRACT
Introduction
Phase transfer catalysis has been long recognized as a powerful tool for organic synthe-
sis both in the industry and academia, as it offers several advantages, such as oper-
ational simplicity, mild reaction conditions, inexpensive and environmentally benign
reagents and solvents and suitability for large-scale synthesis.[1] Over more than the
past thirty years asymmetric phase transfer catalysis, based on chiral, non-racemic cata-
lysts has become an attractive protocol for the synthesis of optically active
ꢀ
ꢀ
CONTACT Peter Bako
pbako@mail.bme.hu
Department of Organic Chemistry and Technology, Budapest
University of Technology and Economics, PO Box 91, Budapest 1521, Hungary.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2019 Taylor & Francis Group, LLC

2
T. NEMCSOK ET AL.
compounds.[2] The most common and efficient type of chiral phase transfer catalysts
are the quaternary ammonium salts. Cinchona alkaloid-derived, TADDOL-derived,
binaphthyl-based and many other types of ammonium salts have all been successfully
used in various reactions with excellent enantioselectivities.[3] More recently Ooi and
coworkers synthesized amino acid-derived 1,2,3-triazolium salts. These new types of
phase transfer catalysts generated high asymmetric induction in some alkylation reac-
tions.[4] Despite the numerous reported catalysts, the development of new and efficient
chiral phase transfer catalysts is still a challenging area in current organic chemistry.
Carbohydrate derivatives have been widely used for stereochemical control as chiral
auxiliaries,[5] ligands,[6] organocatalysts,[7] and phase transfer catalysts.[8] Building the
sugars into the chiral catalyst has several advantages: carbohydrates used as starting
materials are in most cases inexpensive and easily available commercial products; they
are biocompatible and available in enantiomerically pure form with known chiroptical
properties. Carbohydrates have functionalities which can be used to establish secondary
binding sites, as well as catalytic sites. These sugar-based compounds may be more
readily biodegradable, although the biological activity of most synthetic phase transfer
catalysts has not been tested. In our group monoaza-15-crown ethers annelated to dif-
ferent sugar units were synthesized and applied as phase transfer catalysts. These chiral
macrocycles proved to be highly enantioselective in some reactions.[9] In this work we
intended to spread the scope of our research to carbohydrate-based quaternary ammo-
nium salts.
In the literature only a limited number of articles are dealing with this type of com-
pounds. Most often the sugar-based quaternary ammonium salts are used as ionic
liquids.[10] Malhotra and coworkers synthesized isomannide-derived quaternary ammo-
nium salts and examined their chiral recognition ability towards racemic Mosher’s acid
silver salt by NMR spectroscopy.[11] Later, Reddy achieved remarkable chiral recognition
in the same experiment with a xylose-derived imidazolium-based ionic liquid.[12] Vo-
Thanh applied isosorbide-based ammonium salts in an aza-Diels-Alder reaction both as
solvent and as catalyst with moderate diastereoselectivity.[13] The synthesis and charac-
teristics of some other ionic liquids derived from glucose, arabinose, xylose and ribose
have also been reported.[14]
Sugar-based surfactants have aroused much attention due to the fact that they are
biodegradable, very mild to the skin, and are derived from renewable sources.
Surfactants derived from glucose, gluconamide and lactobionic acid have been synthe-
sized and their surface chemical and antibacterial properties were investigated.[15]
Dmochowska and coworkers tested the mutagenicity of some glucose-based quaternary
ammonium salts.[16] Triazolium salts derived from glucose and xylose have also been
synthesized and used as solvent in the amination of aryl halides.[17]
Up to now, there are no examples of using carbohydrate-based ammonium or triazo-
lium salts as catalyst, although some of the sugar-based ionic solvents had catalytic role
in certain reactions, but these compounds have been used in excess, as solvent, so these
ionic liquids cannot be considered as real catalysts. The aim of our research was to
design new phase transfer catalysts starting from cheap and naturally occurring mono-
saccharides and to investigate the catalytic properties of these compounds. In these mol-
ecules the catalytic center (ammonium or triazolium function) is connected directly to

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SYNTHETIC COMMUNICATIONSV
3
the carbohydrate scaffold, thus the enantioselectivity in the catalyzed reactions can be
influenced by the sugar unit. The possible effect arising from the chirality of the carbo-
hydrate was taken into consideration in the design, by placing the quaternary center at
various positions of the carbohydrate unit. Thus the synthesis of compounds having
ammonium or triazolium functions in positions 2, 3, and 6 were planned.
Results and discussion
Synthesis of sugar-based quaternary ammonium and triazolium salts
For the preparation of catalysts having ammonium function in position 2, methyl 2,3-
anhydro-4,6-O-benzylidene-a-D-allopiranoside (1) was selected as starting material,
which was synthesized in our laboratory in four steps starting from D-glucose in high
yields according to literature procedure.[18] The oxirane ring of allopyranoside 1 was
opened with three different amines (butylamine, 3,4-diethoxyphenylethylamine, and
morpholine, respectively) affording altropyranoside-derivatives 2a–c, following the pro-
cedure elaborated by Iglesias-Guerra (Scheme 1).[19] The reactions took place in a regio-
[20]
€
and stereoselective manner, according to the Furst–Plattner rule,
to provide the
products (2a–c) in good yields (78–91%) after recrystallization.
We assumed that the substituent in the third position of the sugar unit may have an
important role in the generation of asymmetric induction, because it is close to the qua-
ternary center. Therefore in two cases the third OH group was left free, and in some
cases it was alkylated with either ethyl bromide or benzyl bromide. The alkylation of
the OH group was performed with 2 equivalents of alkylating agent, in boiling THF or
DMF (70 ꢀC) using NaH as the base (Scheme 1) to afford products 3a–c in excellent
yields (91–98%). It is noteworthy that the reactions were completely selective for the O-
alkylation under these conditions. Formation of N-alkylated products could not be
observed, despite the fact that the alkylating agents were used in excess.
Intermediates 2a, 2c and 3a–c were further converted to tertiary amines and quater-
nized with methyl iodide in one step, in boiling acetonitrile in the presence of K2CO3
(Scheme 1). In most cases reactions were complete in 10 h; however, in the quaterniza-
tion of compound 2a and 2c full conversion was not achieved even after boiling for
40 h and further addition of methyl iodide (2 equivalents per day). These two products
were separated from the starting materials by aqueous extraction giving onium salts 4a
and 4d in moderate yield (75% and 66%, respectively). In all other cases no purification
was needed. The targeted ammonium salts (4b, 4c, 4e) were isolated in pure form after
standard work-up procedure in excellent yields (95–98%). We intended to synthesize
other derivatives of these compounds by using different alkylating agents (ethyl iodide,
benzyl bromide, allyl bromide), however, the quaternizations were unsuccessful, only
tertiary amines could be isolated, which can be explained by steric hindrance.
The starting material for the synthesis of altrose-based onium salts having the ammo-
nium function in position 3 was the methyl 2,3-anhydro-4,6-O-benzylidene-a-D-manno-
pyranoside (5), which was synthesized starting from D-glucose in four steps, in our
laboratory according to literature methods.[21] The ring opening of mannopyranoside 5
with amines, as expected,[22] resulted in 3-amino altropyranose derivatives. The reac-
tions were performed with butylamine and morpholine, in boiling acetonitrile, in the

4
T. NEMCSOK ET AL.
Scheme 1. Synthesis of altrose-based quaternary ammonium salts 4a–e.
Scheme 2. Synthesis of altrose-based quaternary ammonium salts 7a–b.

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5
presence of LiClO4, giving intermediates 6a and 6c in good yields (88% and 89%,
respectively) after column chromatography (Scheme 2). Amino sugar 6a was then O-
alkylated with ethyl bromide applying the same method as mentioned before, giving
compound 6b with excellent yield (98%). In the final step compounds 6a and 6c were
methylated and quaternized with methyl iodide. As in the case of molecule 4d full con-
version was not reached in the alkylation of 6c even after 40 h of reflux and daily add-
ition of extra methyl iodide, therefore ammonium salt 7b had to be separated by
aqueous extraction from the starting material. This process afforded product 7b in mod-
erate yield (61%). Onium salt 7a could be obtained in pure form after standard work-
up procedure in good yield (92%).
We also envisioned the synthesis of a diammonium salt in which two altrose units
are linked via an ethylene bridge and the quaternary centers are in positions 2. To
accomplish that two altrose units were first connected by the ring opening reaction of
allopyranoside 1 with ethylenediamine. The reaction was performed in 2:1 stoichiometry
(anhydrosugar:amine) applying the same reaction conditions as before (Scheme 3).
Product 8 was obtained in 77% yield after column chromatography. Thereafter we
intended to perform methylation and quaternization of the nitrogen atoms in com-
pound 8 with methyl iodide, however, the solubility of compound 8 was poor even in
dipolar aprotic solvents, therefore, no quaternary product could be isolated. To improve
the solubility of compound 8 the free OH-groups were alkylated with ethyl bromide in
DMF (Scheme 3). Since no byproducts were observed, intermediate 9 was obtained in
excellent yield (97%) without any further purification. The methylation and quaterniza-
tion of diamine 9 was performed using the same conditions as before, applying large
excess of methyl iodide and refluxing the mixture for 40 h. The main product of the
1
reaction was isolated by column chromatography; however, the H NMR analysis clearly
demonstrated that instead of the expected bisquaternary product only the monoquater-
nary salt 10 was formed. Further attempts of using even larger excess of methyl iodide,
longer reaction time and applying DMF instead of acetonitrile all failed to provide the
desired diammonium salt, nevertheless onium salt 10 can also be used as catalyst.
The synthesis of the glucosamine-based ammonium salt 13 was also targeted. With
this compound we intended to study the role of the sugar unit in the catalysts. The
two hexopyranoses are of similar structure, only the configuration at C-2 and at C-3
Scheme 3. Synthesis of altrose-based quaternary ammonium salt 10.

6
T. NEMCSOK ET AL.
Scheme 4. Synthesis of glucose-based quaternary ammonium salt 13.
alters: in the a-D-glucopyranoside- and a-D-altropyranoside-units the C-centers men-
tioned can be described as 2R,3S, and 2S,3R, respectively, which may have a significant
influence on the effectiveness of the catalysts. For the preparation of ammonium salt 13
methyl-4,6-O-benzylidene-a-D-glucosamine (11) was chosen as starting material, which
was synthesized according to literature procedure.[23] First the OH group of compound
11 was alkylated with ethyl bromide, using the abovementioned method, in 99% yield
(Scheme 4). The alkylation was again completely selective for the OH group, despite
using an excess of the alkylating agent. Amino sugar 12 was then reacted with methyl
iodide in boiling acetonitrile affording quaternary salt 13 in a pure form, in good
yield (91%).
After the successful synthesis of the ammonium salts our attention turned toward
carbohydrate-based 1,2,3-triazolium salts. Recently increasing attention has been
focused on triazolium-based chiral phase transfer catalyst,[4] due their unique proper-
ties and easy accessibility via copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition of
terminal alkynes with organic azides, which represents one of the prime examples of
click chemistry.[24] For the preparation of triazolium salt 16 having the triazolium
function in position 2, oxirane ring of allopyranoside 1 was opened with NaN3.[25]
Azido sugar 14 was then reacted with phenylacetylene in the presence of CuSO4
and sodium ascorbate in DMF. The pure triazolium derivative 15 was formed in a
yield of 89% without any further purification after the work-up procedure. In the
final step intermediate 15 was alkylated with methyl iodide in boiling acetonitrile.
After 4 days of reflux and daily addition of extra methyl iodide the conversion was
not complete, therefore column chromatography was necessary to separate the prod-
uct from the starting compound. Triazolium salt 16 was obtained in 65% yield after
the purification (Scheme 5).
Finally, we intended to synthesize the glucose-based catalyst 19 having the triazolium
ring in position 6. Azido sugar 14 was synthesized according to literature procedure in
five steps starting from D-glucose,[26] which was then reacted with phenylacetylene in
the copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition, affording intermediate 18 in
good yield (84%). This compound was reacted with methyl iodide providing the tar-
geted triazolium salt 19 after chromatography in 59% yield (Scheme 6).

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7
Scheme 5. Synthesis of altrose-based triazolium salt 16.
Scheme 6. Synthesis of glucose-based triazolium salt 19.
Application of the sugar-based quaternary salts in the alkylation of glycine-
derived schiff base 20
The catalytic activity of the new carbohydrate-based ammonium and triazolium salts
were tested in the alkylation of glycine-derived Schiff base 20 with benzyl bromide. This
model reaction has been widely studied by different groups using cinchona alkaloids,
cyclohexyldiamine salts and TADDOL-based catalysts.[3a,b,27] The reactions were per-
formed at 0 ꢀC in a liquid–liquid two phase system, applying a mixture of toluene and
50% aqueous NaOH solution in the presence of 10 mol% catalyst. The crude products
were purified using preparative TLC in all cases. The enantiomeric excesses were deter-
mined using chiral HPLC analysis, in comparison with authentic racemic material. The
results are summarized in Table 1.
It can be seen from Table 1, that all synthesized quaternary salts proved to be effi-
cient phase transfer catalysts. Product 22 was obtained in moderate and good yields
(67–88%) in every case. The new catalysts favored the formation of the product with S
configuration, the enantioselectivity, however, was low (2–21% ee). The most promising
result was achieved with altrose-based ammonium salt 4e, which generated 21% asym-
metric induction. This example clearly demonstrate that carbohydrate-based quaternary
salts can be used as enantioselective phase transfer catalysts, although more experiments
have to be made in order to improve the achieved ee values. Further investigation of

8
T. NEMCSOK ET AL.
Table 1. Alkylation of glycine-derived Schiff base 20 with benzyl bromide catalyzed by carbohy-
drate-based ammonium and triazolium salts.
Entry
Catalyst
Time (h)
Yield (%)
ee (%)aa
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
6a
6b
10
13
16
19
6
5
5
7
5
5
7
8
8
6
5
67
75
78
69
86
81
76
77
73
82
88
4
2
4
3
21
6
3
9
5
5
9
10
11
5
aDetermined using chiral HPLC.
the catalytic activity of prepared quaternary salts in different reactions and optimization
of the reaction conditions is in progress in our laboratory.
The investigation of the enantiomeric recognition ability of the synthesized
quaternary salts by 19F NMR spectroscopy
Besides testing the new catalysts in asymmetric synthesis we also decided to study the
enantiomeric recognition ability of the new ammonium and triazolium salts by investi-
gating the diastereomeric interaction between racemic Mosher’s acid silver salt and the
new carbohydrate-based salts. The prepared iodide salts and racemic Mosher’s acid sil-
ver salt were dissolved in CD3CN and the mixture was stirred for 30 min, then the pre-
cipitated silver-iodide was filtered. The remaining solution was examined using 19F
NMR spectroscopy. The diastereomeric interaction between the ammonium and triazo-
lium cation and Mosher’s carboxylate resulted in the splitting of the CF3 signal. The dif-
ference, in chemical shift (Dd), of the two signals describes the enantiomeric
recognition ability of the applied salts. The results are summarized in Table 2.
It can be seen from Table 2 that the structure of the carbohydrate-based salts had a
significant effect on the Dd values. The highest Dd (9 Hz) was observed in case of com-
pound 4d. It is interesting, that analog 6b having the morpholino function in position 3
did not show enantiomeric recognition toward Mosher’s acid (Dd < 1 Hz). Another not-
able result is the 4.7 Hz chemical shift difference generated by ammonium salt 13, how-
ever, in all other cases the synthesized sugar-based salts showed poor enantiomeric
recognition. Compound 10 could not be tested in this experiment, because no precipita-
tion was formed after mixing iodide salt 10 and Mosher’s acid silver salt. Presumably
the tertiary amine function of salt 10 prevented the silver-iodide from precipitating by
complexation.

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SYNTHETIC COMMUNICATIONSV
9
Table 2. The enantiomeric recognition ability of carbohydrate-based
ammonium and triazolium salts toward racemic Mosher’s acid
studied using 19F NMR spectroscopy.
Entry
Quaternary salt
Dd (Hz)
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
6a
6b
10
13
16
19
1>
1>
3.2
9.0
1>
1>
1>
–
9
10
11
4.7
2.7
1>
Conclusion
The synthesis of a few new carbohydrate-based ammonium and triazolium salts was ela-
borated in several steps. The ammonium or triazolium functions were placed in differ-
ent positions of the altrose and glucose scaffold in order to examine structure-efficiency
relationship of the new catalysts. The synthesized quaternary salts promoted the alkyl-
ation of a glycine-derived Schiff base, although the achieved enantioselectivities were
low. However the 21% asymmetric induction generated by catalyst 4e demonstrates that
this type of compounds can be used as enantioselective catalyst, although further
research and optimization is needed to improve their efficiency. The 19F NMR study of
the sugar-based ammonium or triazolium Mosher’s carboxylate salts also confirmed
that some of these new compounds (4d and 13) have notable chiral recognition ability.
Experimental
General
Melting points were determined by using a Stuart SMP10 apparatus and are uncor-
rected. The specific rotation was measured on a Perkin Elmer 341LC polarimeter at
22 ꢀC. Nuclear magnetic resonance spectra were obtained on a Bruker (Billerica, MA)
DRX-500 or Bruker 300 instrument in CDCl3, DMSO-d6, CD3CN or CD3OD with
Me4Si as an internal standard. The exact mass measurements were performed by using
quadrupole time of flight mass spectrometer Premier mass spectrometer (Waters,
Milford, MA) in positive electrospray ionization mode. Analytical and preparative thin
layer chromatography (TLC) was performed on silica gel plates (60 GF 254, Merck,
Darmstadt, Germany), while column chromatography was carried out by using 70 to
230 mesh silica gel (Merck). The eluent rations are always given in vol/vol. The chemi-
cals were purchased from Aldrich Chemical (Milwaukee, WI).
General procedure for the ring opening reaction of anhydrosugars 1 and 5
The mixture of anhydrosugar 1 or 5, LiClO4 (2 equivalents), and the appropriate amine
(4 equivalents) was dissolved in dry CH3CN and refluxed for 8 h. After the completion

10
T. NEMCSOK ET AL.
of the reaction (followed by TLC) the solvent was evaporated in vacuum and the resi-
due was dissolved in CHCl3, washed with water, dried (Na2SO4) and concentrated. The
crude product was purified by either recrystallization from EtOH or column
chromatography.
General procedure for the O-ethylation of amino sugars 2a, 6a and 11
The appropriate amino sugar was dissolved in dry THF, and 2 equivalents of NaH was
added. After stirring the mixture for 30 min on 50 ꢀC, 2 equivalents of ethyl bromide
was added and the mixture was refluxed for further 10 h. After the completion of the
reaction water was added dropwise (3 equivalents to the amount of NaH) and the solv-
ent was removed under reduced pressure. The residue was dissolved in CHCl3, washed
with water, dried (Na2SO4) and concentrated, giving the O-alkylated products in
pure form.
General procedure for the O-alkylation of amino sugars 2a–b and 8
The appropriate amino sugar was dissolved in dry DMF, and 2 equivalents of NaH was
added. After stirring the mixture for 30 min on 50 ꢀC, 2 equivalents of the alkylating
agent (ethyl bromide or benzyl bromide) was added and the mixture was refluxed for
10 h. After the completion of the reaction water was added dropwise and the aqueous
phase was washed three times with EtOAc. The combined organic layers were dried
(Na2SO4) and concentrated, giving the O-alkylated products in pure form.
General procedure for the quaternization of amino sugars
The appropriate amino sugar was dissolved in dry CH3CN. Methyl iodide (tertiary
amines: 3 equivalents, secondary amines: 6 equivalents, primary amines: 9 equivalents)
and K2CO3 (tertiary amines: 0 equivalents, secondary amines: 2 equivalents, primary
amines: 4 equivalents) was added. The reaction mixture was refluxed for 1-4 days.
Additional amounts (2 equivalents) of methyl iodide were added every day. After the
reactions were complete (followed by TLC) the mixture was filtered and the solvent was
removed under reduced pressure. The purification processes of the different ammonium
salts altered from here on and are mentioned at the appropriate compounds below.
General procedure for the huisgen cycloaddition of azido sugars (14, 17) and
phenylacetylene
The appropriate azido sugar, phenylacetylene (1.1 equivalent), CuSO4ꢁ5H2O (0.08
equivalent) and sodium ascorbate (0.35 equivalent) was dissolved in DMF and the mix-
ture was stirred at ambient temperature. After the completion of the reaction (followed
by TLC) water was added and the product was extracted with EtOAc three times. The
combined organic layers were dried (Na2SO4) and concentrated.

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11
General procedure for the quaternization of triazolo sugars
The appropriate triazolo sugar was dissolved in dry CH3CN and methyl iodide (3 equiv-
alents) was added. The reaction mixture was kept at boiling temperature for 40 h.
Additional amounts (2 equivalents) of methyl iodide were added every day. After that
the mixture was filtered and the solvent was removed under reduced pressure. The
crude products were purified by column chromatography on silica gel.
General procedure for the benzylation of N-(diphenyl)methylene glycine tert-butyl
ester (20)
The mixture of N-(diphenyl)methylene glycine tert-butyl ester (20) (148 mg, 0.5 mmol),
the appropriate carbohydrate-based salt (0.05 mmol, 0.1 equivalent) in toluene (3 ml)
was treated sequentially with benzyl bromide (94 mg, 0.55 mmol) and 50% aq. NaOH
and the mixture was stirred for 5-8 h, at 0 ꢀC. The two phases were separated and the
organic layer was washed with water three times, dried on Na2SO4 and concentrated.
The crude product was purified on preparative TLC affording the desired product as
colorless oil. The enantiomeric excesses were determined by measuring the specific rota-
tion of the products and comparing it with data for the pure enantiomer obtained from
literature.[27]
19F NMR experiments
The racemic Mosher’s acid silver salt (0.015 mmol) and the appropriate sugar-based
quaternary salt (0.015 mmol) was dissolved in CD3CN. The mixture was stirred for
30 min, then filtered. The remaining solution was transferred to NMR tube and 19F
NMR spectrum was recorded.
Full experimental detail, characterization data of all compounds can be found via the
“Supplementary Content” section of this article’s webpage.
Funding
Supported by the UNKP-18-3 New National Excellence Program of the Ministry of Human
ꢀ
Capacities (UNKP-18-3-I-BME-102). Zsolt Rapi is grateful for the scholarship of the Varga
ꢀ
Jozsef Foundation.
References
[1] (a) Dehmlow, E. V.; Dehmlow, S. S. Phase Transfer Catalysis; VCH: Weinheim, 1993.(b)
Starks, C. M.; Liotta, C. L.; Halpern, M. Phase-Transfer Catalysis; Chapman & Hall: New
York, 1994. (c) Sasson, Y.; Neumann, R. Handbook of Phase-Transfer Catalysis; Blackie
Academic & Professional: London, 1997.(d) Halpern, M. E. Phase-Transfer Catalysis;
American Chemical Society: Washington, DC, 1997.
[2] (a) Donnell, M. I. O. Asymmetric Phase-Transfer Reactions. In Catalytic Asymmetric
Synthesis; Ojima, I., Eds.; Wiley-VCH: New York, 2000, pp. 231–280.(b) Marouka, K.
Asymmetric Phase Transfer Catalysis; Wiley-VCH Verlag GmbH & Co. KgaA: Weinheim,
2008.

12
T. NEMCSOK ET AL.
[3] (a) Ooi, T.; Maruoka, K. Angew. Chem. Int. Ed. 2007, 46, 4222–4266. - DOI: 10.1002/
anie.200601737.(b) Maruoka, K.; Shirakawa, S. Angew. Chem. Int. Ed. 2013, 52,
€
4312–4348. - DOI: 10.1002/anie.201206835.(c) Schorgenhumer, J.; Tiffner, M.; Waser, M.
Beilstein J. Org. Chem. 2017, 13, 1753–1769. DOI: 10.3762/bjoc.13.170.
[4] (a) Ohmatsu, K.; Kiyokawa, M.; Ooi, T. J. Am. Chem. Soc. 2011, 133, 1307–1309. DOI:
10.1021/ja1102844.(b) Ohmatsu, K.; Goto, A.; Ooi, T. Chem. Commun. 2012, 48,
7913–7915. DOI: 10.1039/c2cc32398b.(c) Ohmatsu, K.; Ando, Y.; Ooi, T. J. Am. Chem.
Soc. 2013, 135, 18706–18709. DOI: 10.1021/ja411647x.(d) Ohmatsu, K.; Furukawa, Y.;
Nakaguro, D.; Ooi, T. Chem. Lett. 2015, 44, 1350–1352. DOI: 10.1246/cl.150581.
[5] (a) Kunz, H.; Ruck, K. Angew. Chem. Int. Ed. Engl. 1993, 32, 336–358. DOI: 10.1002/
anie.199303361.(b) Boysen, M. M. K. 2013, Carbohydrates – Tools for Stereoselective
Synthesis; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim.
€
[6] (a) Lehnert, T.; Ozu€duru, G.; Grugel, H.; Albrecht, F.; Telligmann, S. M.; Boysen,
M. M. K. Synthesis 2011, 17, 2685–2708. DOI: 10.1055/s-0030-1260143.(b) Henderson,
A. S.; Bower, J. F.; Galan, M. C. Org. Biomol. Chem. 2016, 14, 4008–4017. DOI: 10.1055/s-
0030-1260143.
[7] Phillips, A. M. F. Eur. J. Org. Chem. 2014, 2014, 7291–7303. DOI: 10.1002/ejoc.201402689.
ꢀ
[8] (a) Bako, P.; Keglevich, G.; Rapi, Z.; Toke, L. Coc. 2012, 16, 297–304. DOI: 10.2174/
ꢀ
138527212799499877.(b) Bako, P.; Keglevich, G.; Rapi, Z. Loc. 2010, 7, 645–656. DOI:
ꢀ
10.2174/138527212799499877.(c) Bako, P.; Rapi, Z.; Keglevich, G. Period. Polytech. Chem.
Eng. 2015, 59, 51–58. DOI: 10.3311/PPch.7308.
ꢀ
}
ꢀ
ꢀ
[9] (a) Rapi, Z.; Demuth, B.; Keglevich, G.; Grun, A.; Drahos, L.; Soti, P. L.; Bako, P.
Tetrahedron: Asymmetr. 2014, 25, 141–147. DOI: 10.1016/j.tetasy.2013.12.007.(b) Rapi, Z.;
ꢀ
ꢀ €
€
ꢀ
Nemcsok, T.; Palvolgyi, A.; Keglevich, G.; Grun, A.; Bako, P. Chirality 2017, 6, 257–252.
ꢀ
DOI: 10.1002/chir.22678.(c) Rapi, Z.; Gru€n, A.; Keglevich, G.; Stirling, A.; Bako, P. New J.
Chem. 2016, 40, 7856–7865. DOI: 10.1039/C6NJ02030E.(d) Rapi, Z.; Nemcsok, T.; Gru€n,
ꢀ
ꢀ €
ꢀ
ꢀ
A.; Palvolgyi, A.; Samu, G.; Hessz, D.; Kubinyi, M.; Kallay, M.; Keglevich, G.; Bako, P.
Tetrahedron 2018, 74, 3512–3526. DOI: 10.1016/j.tet.2018.04.087.
[10] (a) Marra, A.; Chiappe, C.; Mele, A. Chimia. (Aarau) 2011, 65, 76–80. DOI: 10.2533/chi-
ꢀ
mia.2011.76.(b) Thruong, T.-K.-T.; Van Buu, O. N.; Aupoix, A.; Pegot, B.; Vo-Thanh, G.
Cos. 2012, 9, 53–64. DOI: 10.2174/157017912798889143.
[11] (a) Kumar, V.; Olsen, C. E.; Schaffer, S. J. C.; Parmar, V. S.; Malhotra, S. V. Org. Lett.
2007, 9, 3905–3908. DOI: 10.1021/ol071390y.(b) Kumar, V.; Pei, C.; Olsen, C. E.; Schaffer,
S. J. C.; Parmar, V. S.; Malhotra, S. V. Tetrahedron: Asymmetr. 2008, 19, 664–671. DOI:
10.1016/j.tetasy.2008.02.009.
[12] Jayachandra, R.; Reddy, S. R. RSC Adv. 2016, 6, 39758–39761. DOI: 10.1039/C6RA02792J.
[13] Van Buu, O. N.; Vo-Thanh, G. Loc. 2007, 4, 158–167. DOI: 10.2174/157017807780737219.
[14] (a) Poletti, L.; Chiappe, C.; Lay, L.; Pieraccini, D.; Polito, L.; Russo, G. Green Chem. 2007,
9, 337–341. DOI: 10.1039/b615650a.(b) Plaza, P. G. J.; Bhongade, B. A.; Singh, G. Synlett
2008, 19, 2973–2976. DOI: 10.1055/s-0028-1087343.(c) Pernak, J.; Czerniak, K.; Biedziak,
A.; Marcinkowska, K.; Praczyk, T.; Erfurt, K.; Chrobok, A. RSC Adv. 2016, 6,
52781–52789. DOI: 10.1039/C6RA06703D.
[15] (a) Nyuta, K.; Yoshimura, T.; Tsuchiya, K.; Ohkubo, T.; Sakai, H.; Abe, M.; Esumi, K.
Langmuir 2006, 22, 9187–9191. DOI: 10.1021/la061688h.(b) Torigoe, K.; Tasaki, A.;
Yoshimura, T.; Sakai, K.; Esumi, K.; Takamatsu, Y.; Sharma, S. C.; Sakai, H.; Abe, M.
Colloid Surface A 2008, 326, 184–190. DOI: 10.1016/j.colsurfa.2008.05.036.(c) Gan, C.;
Wang, H.; Zhao, Z.; Yin, B. J. Surfact. Deterg. 2014, 17, 465–470. DOI: 10.1007/s11743-
014-1562-9.(d) Parus, A.; Framski, G. Turk. J. Chem. 2018, 42, 1095–1104. DOI: 10.3906/
kim-1711-35.
ꢀ
[16] (a) Dmochowska, B.; Piosik, J.; Woziwodzka, A.; Sikora, K.; Wisniewski, A.; WeRgrzyn, G.
J. Hazard. Mater. 2011, 193, 272–278. DOI: 10.1016/j.jhazmat.2011.07.064.(b)
ꢀ
Dmochowska, B.; Sikora, K.; Woziwodzka, A.; Piosik, J.; Podgorska, B. Beilstein J. Org.
Chem. 2016, 12, 1434–1439. DOI: 10.3762/bjoc.12.138.

R
SYNTHETIC COMMUNICATIONSV
13
[17] (a) Jha, A. K.; Jain, N. Tetrahedron Lett. 2013, 54, 4738–4741. DOI: 10.1016/j.tetlet.
2013.06.114.(b) Ferlin, N.; Gatard, S.; Van Nhien, A. N.; Courty, M.; Bouquillon, S.
Molecules 2013, 18, 11512–11525. DOI: 10.3390/molecules180911512.
[18] Richtmeyer, N. K. Methods Carbohydr. Chem. 1962, I, 107.
[19] Vega-Perez, J. M.; Candela, J. I.; Vega, M.; Iglesias-Guerra, F. Carbohyd. Res. 1995, 279,
C5–C8. DOI: 10.1016/0008-6215(96)83597-X.
[20] Fu€rst, A.; Plattner, P. A. Hca. 1949, 32, 275–283. DOI: 10.1002/hlca.19490320139.
[21] Hicks, D. R.; Fraser-Reid, B. Synthesis 1974, 1974, 203–204. DOI: 10.1055/s-1974-23284.
[22] Willams, N. R. Adv. Carbohyd. Chem. Bi. 1970, 25, 109–179. DOI: 10.1016/S0065-
2318(08)60427-8.
[23] Goyal, N.; Cheuk, S.; Wang, G. Tetrahedron 2010, 66, 5962–5971. DOI: 10.1016/
j.tet.2010.05.071.
[24] (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem. Int. Ed. 2001, 40, 2004–2021.
DOI: 10.1002/1521-3773(20010601)40:11 < 2004::AID-ANIE2004 > 3.0.CO;2-5.(b) Wu, P.;
Fokin, V. V. Aldrichim. Acta 2007, 40, 7–19. http://www.scopus.com/inward/record.
url?scp=33947526772&partnerID=8YFLogxK.(c) Moses, J. E.; Moorhouse, A. D. Chem.
Soc. Rev 2007, 36, 1249–1262. DOI: 10.1039/B613014N.
ꢀ
ꢀ
[25] Walvoort, M. T. C.; Moggre, G.-J.; Lodder, G.; Overkleeft, H. S.; Codee, J. D. C.; van der
Marel, G. A. J. Org. Chem. 2011, 76, 7301–7315. DOI: 10.1021/jo201179p.
[26] (a) Fuller, T. S.; Stick, R. V. Aust. J. Chem. 1980, 30, 2509–2515. DOI: 10.1071/
ꢀ
CH9802509.(b) Agoston, K.; Fu€gedi, P. Carbohyd. Res 2014, 389, 50–56. DOI: 10.1016/
j.carres.2013.12.026.
[27] (a) Corey, E. J.; Xu, F.; Noe, M. C. J. Am. Chem. Soc. 1997, 119, 12414–12415. DOI:
10.1021/ja973174y.(b) Ooi, T.; Kameda, M.; Maruoka, K. J. Am. Chem. Soc. 1999, 121,
6519–6520. DOI: 10.1021/ja991062w.(c) Gratzer, K.; Waser, M. Synthesis. (Stuttg) 2012,
44, 3661–3670. doi: 10.1055/s-0032-1316804