Surfactant-mediated thioglycosylation of 1-hydroxy sugars in water

Article abstract of DOI:10.1039/d0ob02246b

Thioglycosides are an important class of sugars, since they can be used as non-ionic biosurfactants, biomimetic glycosides, and building blocks for carbohydrate synthesis. Previously, Br?nsted- or Lewis-acid-catalyzed dehydrative glycosylations between a 1-hydroxy sugar and a thiol have been reported to yield open-chain dithioacetal sugars as the major products instead of the desired thioglycosides. These dithioacetal sugars are by-products derived from the endocyclic bond cleavage of the thioglycosides. Herein, we report dehydrative glycosylation in water mediated by a Br?nsted acid-surfactant combined catalyst (BASC). Glycosylations between 1-hydroxy furanosyl/pyranosyl sugars and primary, secondary, and tertiary aliphatic/aromatic thiols in the presence of dodecyl benzenesulfonic acid (DBSA) provided the thioglycoside products in moderate to good yields. Microwave irradiation led to improvements in the yields and a shortening of the reaction time. Remarkably, open-chain dithioacetal sugars were not detected in the DBSA-mediated glycosylations in water. This method is a simple, convenient, and rapid approach to produce a library of thioglycosides without the requirement of anhydrous conditions. Moreover, this work also provides an excellent example of complementary reactivity profiles of glycosylation in organic solvents and water.

Full text of DOI:10.1039/d0ob02246b

Organic &
Biomolecular Chemistry
View Article Online
View Journal | View Issue
PAPER
Surfactant-mediated thioglycosylation of
1-hydroxy sugars in water†
Cite this: Org. Biomol. Chem., 2021,
19, 822
Trichada Ratthachag,a Supanat Buntasana,b Tirayut Vilaivan a and
b
Panuwat Padungros
*
Thioglycosides are an important class of sugars, since they can be used as non-ionic biosurfactants, bio-
mimetic glycosides, and building blocks for carbohydrate synthesis. Previously, Brønsted- or Lewis-acid-
catalyzed dehydrative glycosylations between a 1-hydroxy sugar and a thiol have been reported to yield
open-chain dithioacetal sugars as the major products instead of the desired thioglycosides. These
dithioacetal sugars are by-products derived from the endocyclic bond cleavage of the thioglycosides.
Herein, we report dehydrative glycosylation in water mediated by a Brønsted acid–surfactant combined
catalyst (BASC). Glycosylations between 1-hydroxy furanosyl/pyranosyl sugars and primary, secondary,
and tertiary aliphatic/aromatic thiols in the presence of dodecyl benzenesulfonic acid (DBSA) provided the
thioglycoside products in moderate to good yields. Microwave irradiation led to improvements in the
yields and a shortening of the reaction time. Remarkably, open-chain dithioacetal sugars were not
detected in the DBSA-mediated glycosylations in water. This method is a simple, convenient, and rapid
approach to produce a library of thioglycosides without the requirement of anhydrous conditions.
Moreover, this work also provides an excellent example of complementary reactivity profiles of glycosyla-
tion in organic solvents and water.
Received 11th November 2020,
Accepted 14th December 2020
DOI: 10.1039/d0ob02246b
rsc.li/obc
the ring-oxygen (O4) of the 1-dodecyl thiofuranoside 1a, fol-
lowed by endocyclic C1–O4 bond cleavage to form a thionium
Introduction
Thioglycosides are a valuable class of precursors for the chemi- intermediate. The second addition of 1-dodecanethiol to this
cal synthesis of carbohydrate polymers,1 and are widely uti- thionium intermediate gave the dithioacetal sugar 1b as the
lized in other applications such as non-ionic biosurfactants for major product.
the solubilization and reconstruction of membrane proteins2
Typically, the formation of dithioacetal sugars derived from
and biomimetic3 or bioactive thioglycosides.4 In the course of endocyclic bond cleavage has been used to protect the alde-
our synthesis of alkyl C-glycosides via Ramberg–Bäcklund ole- hyde/ketone functional groups of aldose/ketose sugars.8
fination,5 we first set out to generate a library of alkyl thio- Previous reports have thoroughly documented the challenges
furanosides by Fischer glycosylation6 using a perbenzylated of dehydrative glycosylation between armed pyranosyl/furano-
1-hydroxy sugar as an armed glycosyl donor (Scheme 1).7 syl donors and reactive nucleophiles, especially the combi-
Dehydrative glycosylation between the 1-hydroxy sugar 1 (2,3,5- nation of furanosyl donors and highly nucleophilic thiols.9 For
tri-O-benzyl-L-arabinofuranose) and 1-dodecanethiol in the example, dithioacetal sugars have been obtained during the
presence of catalytic HCl was first carried out. Analysis of the dehydrative glycosylation of 1-hydroxy sugars under catalysis
crude mixture indicated that 1-dodecyl thiofuranoside 1a was by Brønsted acids such as trifluoroacetic acid,10 HCl,11 and
obtained as a minor product along with the open-chain HBr.12 Products derived from the endocyclic bond cleavage
dithioacetal sugar 1b as a major product. The dithioacetal have also been observed under catalysis using Lewis acids,
sugar 1b was thought to be derived from the protonation of such as SnCl4,13 BF3·OEt2,14 B(OMe)3,14a and Me2BBr.15
Alternatively, armed perbenzylated 1-hydroxy sugar donors
can be converted into other glycosyl donors such as glycosyl
aOrganic Synthesis Research Unit, Department of Chemistry, Faculty of Science,
Chulalongkorn University, Phayathai Road, Pathumwan, Bangkok 10330, Thailand
bGreen Chemistry for Fine Chemical Productions STAR, Department of Chemistry,
Faculty of Science, Chulalongkorn University, Phayathai Road, Pathumwan,
Bangkok 10330, Thailand. E-mail: panuwat.p@chula.ac.th
trichloroacetimidates16 or glycosyl halides11e at the cost of
extra reaction steps. Less reactive glycosyl donors such as
peracylated 1-hydroxy sugars can be used as glycosyl donors.
However, they must be converted into a more reactive glycosyl
halide first, followed by the substitution of an acceptor. Strictly
anhydrous conditions are required for these processes to
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
d0ob02246b
822 | Org. Biomol. Chem., 2021, 19, 822–836
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
Scheme 1 Preliminary results for the Fischer glycosylation of 1-hydroxy sugar 1 yielded dithioacetal sugar 1b as the major product.
prevent hydrolysis of the glycosyl halide intermediates.17 presence of LASC was investigated, and the results are shown
Nevertheless, the direct synthesis of perbenzylated thioglyco- in Table 1.
sides from 1-hydroxy sugars is still highly desirable, and there
The dehydrative glycosylation reactions were carried out in
is no current methodology that allows such transformations water at 80 °C under microwave irradiation with catalytic Sc
without the substantial formation of dithioacetal sugar side (DBS)3 (scandium tris(dodecylbenzenesulfonate)) and Yb
products.
(DBS)3 (ytterbium tris(dodecylbenzenesulfonate)) (Table 1,
Water has become one of the most promising green sol- entries 1 and 2).26 Both LASCs gave only a trace amount of the
vents for modern organic synthesis as it is environmentally desired thioglycoside 1a accompanied by the unreacted
friendly, cheap, and often provides unique reactivity profiles 1-hydroxy sugar 1. Increasing the catalyst loading, reaction
that complement similar reactions performed in organic sol- time, and temperature did not result in any improvement of
vents.18 The growing interest in using water as a reaction the product yields. Cooperative catalyst systems with a LASC
medium motivated us to explore chemical glycosylation in and a Brønsted acid have previously been shown to enhance
water. Glycosylation reactions in water alone or in organic the rate of several chemical reactions in water.27 We reasoned
solvent/water mixtures19 have recently been demonstrated for that the addition of a Brønsted acid might accelerate the reac-
both unprotected and protected sugar substrates.20 The water tion by promoting the leaving ability of the OH group. The gly-
solubility of the rather hydrophobic protected sugars can be cosylation reactions were then performed using the combi-
enhanced by the aid of surfactants.18 Several surfactant nation of a water-tolerant Lewis acid and DBSA (entries 3–8).28
systems such as the Lewis acid–surfactant combined catalysts Significant improvements in the yield to the 56–67% range
(LASC)21 or the Brønsted acid–surfactant combined catalysts were indeed observed for all reactions with the formation of
(BASC) introduced by Kobayashi and co-workers22 and the both α- and β-anomers in comparable amounts. When the
designer nonionic surfactants of Lipshutz and co-workers have combination of Cu(OTf)2 and DBSA was used, the product 1a
proven to be powerful tools for performing chemical syntheses was obtained in only 15% yield (entry 9). Importantly, in all
in water without additional co-solvents.18b,23 We envisage that cases the crude reaction mixtures contained only the
the hydrophobicity of both protected 1-hydroxy sugars and ali- unreacted 1-hydroxy sugar 1 and the thioglycoside product 1a,
phatic thiols would make them suitable candidates for achiev- without any trace of the dithioacetal sugar 1b commonly
ing glycosylation in water assisted by the presence of a surfac- observed as the major by-product.
tant. Herein, we report the study of dehydrative glycosylation
between 1-hydroxy sugars and thiols in water in the presence plays
The results from Table 1 suggest that the Brønsted acid
crucial role in the dehydrative glycosylation of
a
of LASC, BASC, and designer surfactants.
1-hydroxy sugars.29 Next, the use of Brønsted acid–surfactant
combined catalysts (BASC) was investigated for the same glyco-
sylation (Table 2). Perfluoro-octanesulfonic acid (PFOS), per-
fluoro-octanoic acid (PFOA), and dodecyl benzenesulfonic acid
(DBSA) were applied in the reaction under microwave
irradiation at 80 °C (Table 2, entries 1–3). The PFOS-mediated
glycosylation gave a distinct two-layer heterogeneous mixture
and afforded only 48% conversion with low yield (entry 1).
However, the surfactants PFOA and DBSA provided well-dis-
persed turbid white emulsions during the course of the reac-
tion. Gratifyingly, both high conversions and yields of thiogly-
coside 1a were obtained in the PFOA- and DBSA-mediated gly-
cosylations (entries 2 and 3). In terms of anomeric selectivity,
DBSA (α/β = 7 : 93) provided higher β selectivity compared to
PFOA (α/β = 29 : 71). Thus, DBSA was preferred over PFOA as
Results and discussion
Lewis acid–surfactant combined catalysts (LASC) were first con-
sidered as surfactants for this study.22 Several water-tolerant
Lewis acids have been successfully employed as catalysts for
nucleophilic additions to carbonyl compounds in water, such
as Sc(OTf)3, Yb(OTf)3, La(OTf)3, Gd(OTf)3, Nd(OTf)3, Pr(OTf)3,
and Cu(OTf)2.24 The combination of water-tolerant Lewis acids
and anionic surfactants yields LASCs with both catalytic
activity and solubility in water.25 The dehydrative glycosylation
between the 1-hydroxy sugar 1 and 1-dodecanethiol in the
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 822–836 | 823

View Article Online
Paper
Organic & Biomolecular Chemistry
Table 1 Dehydrative thioglycosylation in water mediated by a Lewis acid–surfactant combined catalyst (LASC)
Entrya
Activator/surfactant
Conversionb
1a (yield)b,c
1a (α/β)d
e
1
2
3
4
5
6
7
8
9
Sc(DBS)3 e
<5%
<5%
ND
Trace
Trace
ND
ND
Yb(DBS)3
Sc(OTf)3/DBSAf
Yb(OTf)3/DBSAf
La(OTf)3/DBSAf
Gd(OTf)3/DBSAf
Nd(OTf)3/DBSAf
Pr(OTf)3/DBSAf
Cu(OTf)2/DBSAf
59% (ND)
63% (ND)
67% (99%)
64% (88%)
64% (83%)
56% (85%)
15% (ND)
50 : 50
44 : 56
39 : 61
41 : 59
40 : 60
42 : 58
40 : 60
ND
68%
73%
77%
66%
ND
a Standard conditions: 1-Dodecanethiol (1.2 equiv.), H2O, 80 °C by microwave irradiation (μwave), 5 h, [donor] = 0.50 M. b Conversions and yields
were determined from the isolated product and recovered 1-hydroxy sugar after column chromatography. c Yield in parentheses is based on recov-
ered starting materials (brsm). d Selectivities (α/β) were determined by 1H NMR integration. e LASC catalyst (10 mol%). f Lewis acid (10 mol%)/
DBSA (1 equiv.). DBS = dodecylbenzenesulfonate, DBSA = dodecylbenzenesulfonic acid, ND = not determined.
Table 2 Dehydrative thioglycosylation in water mediated by Brønsted acid–surfactant combined catalysts (BASC), Brønsted acid/nonionic surfac-
tant combinations, and Brønsted acids alone
Entrya
Activator/surfactant
Temp
Conversionb
1a (yield)b,c
1a (α/β)d
1
2
3
4
5
6
7
8
PFOS (1 equiv.)
PFOA (1 equiv.)
DBSA (1 equiv.)
DBSA (1 equiv.)
DBSA (1 equiv.)
DBSA (1 equiv.)
CSA (0.1 equiv.)/Nok
p-TsOH (0.1 equiv.)/Nok
p-TsOH (0.1 equiv.)/Coolade
CSA (0.1 equiv.)/TPGS-750-M
p-TsOH (0.1 equiv.)/TPGS-750-M
p-TsOH (1 equiv.)/TPGS-750-M
p-TsOH (1 equiv.)/TPGS-750-M
p-TsOH (1 equiv.)
80 °C
80 °C
80 °C
40 °C
60 °C
100 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
120 °C
80 °C
80 °C
48%
78%
73%
44%
58%
80%
20%
31%
ND
15%
40%
ND
ND
ND
18% (37%)
71% (91%)
72% (99%)
44% (99%)
57% (99%)
64% (80%)
2% (10%)
18% (58%)
15% (ND)
8% (53%)
33% (83%)
56% (ND)
79% (ND)
17% (ND)
27% (ND)
30 : 70
29 : 71
7 : 93
8 : 92
8 : 92
6 : 94
0 : 100
0 : 100
0 : 100
0 : 100
0 : 100
10 : 90
24 : 76
20 : 80
12 : 88
9
10
11
12
13
14
15
p-HOC6H4SO3H (1 equiv.)
ND
a Standard conditions: 1-Dodecanethiol (1.2 equiv.), BASC or Brønsted acid (0.1 or 1 equiv.), H2O, heated by microwave irradiation (μwave), 5 h;
[donor] = 0.50 M; 2% w/w of the nonionic surfactant was used for entries 7–13. b Conversions and yields were determined from the isolated
product and recovered 1-hydroxy sugar by column chromatography. c Yield in parentheses is based on recovered starting materials (brsm).
d Selectivities (α/β) were determined by 1H NMR integration. PFOS = perfluoro-octanesulfonic acid, PFOA = perfluoro-octanoic acid, ND = not
determined.
the activator for this study since it provided higher selectivity the yield and selectivity of the product. Lowering the tempera-
and because of the health and environmental concerns arising ture to 40 °C and 60 °C gave inferior yields and conversion
from the persistency of PFOA in the environment.30
(entries 4 and 5). Increasing the temperature to 100 °C caused
The DBSA-mediated glycosylations were examined at some decomposition as evidenced by the formation of a brown
different temperatures to probe the effect of temperature on tar-like syrup, which resulted in a lower yield (entry 6). Efforts
824 | Org. Biomol. Chem., 2021, 19, 822–836
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
to reduce the amount of DBSA from 1 equivalent to a catalytic microwave irradiation (Table 3). Primary alkyl thioglycosides
amount resulted in lower yield, and less dispersion of the 1a and 2–6 with different chain lengths (C12, C8, C10, C14,
two substrates (1-hydroxy sugar 1 and 1-dodecanethiol) was C15, and C18) were obtained under the standard conditions in
noticed.
moderate to good yields (58–72%) with acceptable α/β selectiv-
The designer nonionic surfactants from the Lipshutz group ities (7 : 93 to 19 : 81). The superior results obtained using
have proven to be suitable media for many synthetically useful microwave heating were confirmed by performing the DBSA-
organic reactions in water.18 We were captivated by their poten- mediated thioglycosylation experiment under heating in an oil
tial and decided to evaluate these nonionic surfactants in our bath at 80 °C in a sealed tube for 48 hours, which gave the
study. Combinations of Lipshutz’s designer surfactants and desired alkyl thioglycoside 1a in lower yield (54%, α/β =
lipophilic sulfonic acids as a source of Brønsted acid were next 11 : 89). Delightfully, the formation of the dithioacetal sugar
investigated. When a mixture of 1-hydroxy sugar 1 and 1-dode- by-product was not observed in any of the reactions.
canethiol was treated with 10 mol% of camphorsulfonic acid
The glycosylation of 1-hydroxy sugar 1 with 2-phenyl etha-
(CSA) or p-toluenesulfonic acid (p-TsOH) with Nok surfactant nethiol yielded the expected thioglycoside 7 in moderate yield
(SPGS-550-M),31 thioglycoside 1a was produced in only a trace (42%) and selectivity (α/β = 38 : 62). Thioglycosides 8 and 9
amount (2% yield, α/β = 0 : 100; entry 7) or 18% yield (α/β = derived from a secondary aliphatic thiol (cyclohexanethiol)
0 : 100; entry 8). The combination of 10 mol% of p-TsOH and and a tertiary aliphatic thiol (tert-butylthiol) were obtained in
the surfactant Coolade32 also resulted in a poor yield of thio- moderate to low yields of 45% and 24%, respectively, and only
glycoside 1a (15%, α/β = 0 : 100; entry 9). Next, the surfactant the α anomers were detected. The steric hindrance and water
TPGS-750-M33 was examined (entries 10–13).33 The combi- solubility of tert-butylthiol could be the reasons for the lower
nation of a catalytic amount of CSA or p-TsOH with TPGS-750- yield of thioglycoside 9. In addition, aromatic thiols bearing
M still resulted in poor yield (8%, α/β = 0 : 100; entry 10 and both electron-donating and -withdrawing groups were tested.
33%, α/β = 0 : 100; entry 11). However, increasing the amount Gratifyingly, thioglycosides 10, 11, and 12 were all obtained in
of p-TsOH to 1 equivalent in the presence of TPGS-750-M pro- moderate yields. In general, β selectivities were observed in the
vided a higher yield of product 1a (56%, α/β = 10 : 90; entry 12). glycosylation of 1-hydroxy L-arabinofuranose 1 and thiols.
When the reaction temperature was raised to 120 °C, a con- However, bulky thiol nucleophiles seem to favor the formation
siderable improvement was observed, and product 1a was of α-products (8, 9, and 12). When the heterocyclic thiols
obtained in 79% yield with moderate selectivity (α/β = 24 : 76, 2-mercaptothiazoline and 2-mercaptobenzothiazole were exam-
entry 13) along with decomposition by-products. Ester-based ined as potential nucleophiles, the expected thioglycosides 13
nonionic surfactants might not be suitable for this particular and 14 were not formed, and 1-hydroxy sugar 1 was fully recov-
reaction since the conditions involve prolonged heating under ered.34 The crystal structures of 2-mercaptothiazoline and
acidic conditions, which may cause partial hydrolysis of the 2-mercaptobenzothiazole revealed that both heterocyclic thiols
ester linkages.18a Finally, performing the reactions using the preferentially exist as the thiocarbonyl tautomer instead of the
Brønsted acid alone (p-TsOH and p-hydroxybenzenesulfonic thiol form, thus reducing their nucleophilicity.35 The anomeric
acid) gave the product 1a in only low yields (entries 14 and 15) configurations of the L-thioarabinosides were determined
even when a full equivalent of the acid was used, which con- based on analysis of the coupling constant (J1,2) between the
clusively emphasized the necessity of the surfactant in the anomeric proton (H1) and H2. The coupling constants of the
reactions. It is noteworthy that in the DBSA-mediated thiogly- β-anomers and α-anomers were 4.8–5.0 Hz and 2.3–2.9 Hz,
cosylation, the ratios of the α and β thioglycosides 1a remain respectively, which is in line with previous reports.11e,36 The
almost the same over the whole temperature range examined NOESY spectrum of the β-anomer further confirmed the
(40, 60, 80, and 100 °C; entries 3–6). Moreover, conducting the assignment via the observation of strong NOE interactions
glycosylations at 80 °C using different Brønsted acids (entries between H1–H2 and H1–H4. It is important to note that this
1–3, 12, 14 and 15) gave different α/β selectivities ranging from newly developed protocol required only
a slight excess
7 : 93 to 30 : 70; thus, the α and β thioglycosides 1a were not in (1.2 equivalents) of the thiol to obtain acceptable to good
equilibrium, as otherwise the same selectivity would have yields of the thioglycosides. Conversely, traditional Fischer gly-
been observed. This implies that the selectivity for the for- cosylation often requires a large excess of the acceptor, often
mation of α and β thioglycosides 1a should be under kinetic as a solvent, to drive the equilibrium forward.37 The use of the
control. The results in Table 2 reveal that two conditions, malodorous thiol acceptor in large excess or as a solvent
namely DBSA (entry 3) and p-TsOH (1 equiv.)/TPGS-750-M hampers the full synthetic potential of Fischer glycosylation.
(entry 13), are capable of promoting the dehydrative thioglyco-
To test the compatibility of the reaction with various glyco-
sylation to form the thioglycoside 1a in comparable yields. syl donors, glycosylation reactions between 1-dodecanethiol
Nevertheless, DBSA was chosen as the Brønsted acid–surfac- and various glycosyl donors were examined (Table 4). Two
tant combined catalyst for further studies since it is less expen- L-arabinofuranosyl donors with different leaving groups at the
sive and does not require additional acids.
anomeric position, methyl 2,3,5-tri-O-benzyl-α-L-arabinofura-
The scope of the nucleophile, i.e., aliphatic, aromatic, and noside (15) and acetyl 2,3,5-tri-O-benzyl-L-arabinofuranoside
heterocyclic thiols, were next investigated in the DBSA- (16), were also compared to probe the effect of the leaving
mediated glycosylation of 1-hydroxy sugar 1 in water under group (Table 4, entries 1 and 2). The thioglycoside 1a was
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 822–836 | 825

View Article Online
Paper
Organic & Biomolecular Chemistry
Table 3 Scope of thiol nucleophiles in the DBSA-mediated dehydrative thioglycosylation of 1-hydroxy sugar 1 in watera,b
a Standard conditions: Thiol (1.2 equiv.), DBSA (1 equiv.), H2O, 80 °C by microwave irradiation (μwave), 5 h; [donor] = 0.50 M. b Isolated yield was
determined by column chromatography and selectivities (α/β) were determined by 1H NMR integration. c Reaction was performed under standard
conditions in a sealed tube and heating with an oil bath at 80 °C for 48 hours.
obtained in low yield (10%) for the glycosyl donor 15 and mod- tion.38 At the same time, the lipophilic thiol is also encapsu-
erate yield (60%) for the glycosyl donor 16. Thus, 1-hydroxy lated, resulting in very high local concentrations of both reac-
and 1-acetoxy sugars are more suitable glycosyl donors than tants. Next, dehydration followed by the addition of the thiol
1-methoxy sugars for the present DBSA-mediated dehydrative provides the desired thioglycoside.39 Inside the droplet, the
thioglycosylation in water.
equilibrium of the dehydration should favor the oxocarbenium
The glycosylation of 1-dodecanethiol by other perbenzylated compared to the environment outside the droplet, which con-
1-hydroxy furanosyl donors, namely D-arabinofuranose (17), tains a large excess of water. We hypothesize that the oxocarbe-
D-ribofuranose (18), and D-xylofuranose (19), provided the thio- nium intermediate could be stabilized by either the sulfur
glycosides 17a, 18a, and 19a in 66% (α/β = 16 : 84), 73% (α/β = atom of the encapsulated thiol or by the small amount of
17 : 83), and 73% (α/β = 69 : 31) yield, respectively (entries 3–5). water within the hydrophobic pocket, which is known as
Finally, 1-hydroxy pyranosyl sugars such as L-arabinopyranose hydrophobic hydration.38 For example, the hydrophobic
(20), D-galactopyranose (21), and D-glucopyranose (22) were interior of the sodium dodecylsulfate (SDS) micelle was pre-
also acceptable donors to yield the corresponding thioglyco- viously reported to stabilize the oxocarbenium intermediate
sides 20a, 21a, and 22a in 60% (α/β = 0 : 100), 32% (α/β = generated during a Prins cyclization in water.40 It should be
65 : 35), and 45% (α/β = 64 : 36) yield, respectively (entries 6–8).
noted that a second protonation of the initially formed thiogly-
In the Brønsted acid–surfactant combined catalytic system coside product to yield a thionium intermediate is also poss-
in this study, we hypothesize that emulsion droplets are gener- ible at the acidic surface of the droplets. Since the majority of
ated by DBSA during the course of the reaction. The perbenzy- the lipophilic thiol would be trapped inside the droplet, the
lated 1-hydroxy sugar is encapsulated within the droplets and chance of it undergoing a second addition to the thionium
undergoes protonation at the surface of the emulsion droplets. intermediate is minimized. As a result, the dithioacetal sugar
The anionic surface of the DBSA accumulates a high concen- was not generated as has usually been observed when the gly-
tration of hydronium ions, thus increasing the rate of dehydra- cosylation is performed under conventional organic solvent
826 | Org. Biomol. Chem., 2021, 19, 822–836
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
Table 4 Scope of furanosyl/pyranosyl donors in the DBSA-mediated dehydrative thioglycosylation with 1-dodecanethiol in watera,b
Entry
1
Glycosyl donor (α/β)
Product/Yield (α/β)
Entry
5
Glycosyl donor (α/β)
Product/Yield (α/β)
2
3
6
7
4
8
a Standard conditions: Thiol (1.2 equiv.), DBSA (1 equiv.), H2O, 80 °C by microwave irradiation (μwave), 5 h; [donor] = 0.50 M. b Isolated yields
were determined by column chromatography and selectivities (α/β) were determined by 1H NMR integration.
conditions.41 With regards to stereoselectivity, we propose that sition state (TS2) caused by the eclipsed conformation of C1
the five-membered ring oxocarbenium intermediate adopts an and C2.
envelope conformation in which the carbon at position 3 (C3)
Control experiments and gram-scale synthesis were next
is placed at the top (3E conformer) or bottom (E3 conformer) of examined (Scheme 3). It is important to note that the kinetic
the envelope and the oxocarbenium moiety aligns on the product (β-thiofuranoside) is amenable to an epimerization to
plane, as depicted in Scheme 2.
yield the thermodynamically more stable α-thiofuranoside via
At equilibrium, conformer II (E3) is favored over conformer endocyclic bond cleavage/recyclization or reversible elimin-
I (3E) since all the substituents are pseudoequatorial, in con- ation/addition of the thiol.44 Isomerization of pure
trast to the all-pseudoaxial orientation of the substituents in β-thioglycoside 1a was investigated by heating under micro-
conformer I. The destabilization of conformer I is caused by a wave irradiation in the presence of DBSA (1 equiv.) at 80 °C
syn-butanol interaction between the benzyloxy group at C2 and (Scheme 3, eqn (1)). The starting material was completely con-
the benzyloxymethyl substituent at C4 of the furanose ring.42 sumed and the α-thioglycoside 1a was isolated in 45% yield
Based on this conformational analysis, the stereochemical with exclusive α-selectivity along with 46% yield of the
outcome could be explained using Woerpel’s model.43 The 1-hydroxy sugar 1 resulting from the competing hydrolysis
nucleophilic addition would be possible from either side of reaction.
conformer II. However, the thiol attack “inside” the envelope,
When pure α-thioglycoside 1a was subjected to the same
in which the substituents on both C1 and C2 are staggered, conditions, only the hydrolysis product, 1-hydroxy sugar 1, was
should lead to a lower energy transition state (TS1) compared obtained in 78% yield without the formation of β-thioglycoside
to the “outside” attack pathway. The “inside” attack via 1a (eqn (2)). These results supported the hypothesis that
TS1 would yield β-thiofuranoside as the kinetic product. β-thioglycoside is the kinetic product and could epimerize to
Conversely,
the “outside”
attack
leading
to
the the thermodynamic α-thioglycoside upon prolonged heating.
α-thiofuranoside product would result in a higher energy tran- This finding was well aligned with the preference for
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 822–836 | 827

View Article Online
Paper
Organic & Biomolecular Chemistry
Scheme 2 Proposed mechanism of the dehydrative thioglycosylation of 1a in water mediated by DBSA.
Scheme 3 Control experiments and gram-scale synthesis of 1-dodecyl thioglycoside 1a.
α-thioglycoside formation when bulky thiol nucleophiles were 1 in only 10% yield (eqn (3)). The presence of 1-dodecanethiol
used (Table 3, products 8, 9, and 12); in such cases, the epi- in the reaction clearly suppressed the hydrolysis (compared to
merization of the β-thioglycoside would be highly favorable. the 46% yield of the hydrolysis product in eqn (1)) as well as
Next, treatment of thioglycoside 1a (α/β = 7 : 93) with 1.2 equiva- the epimerization of the β-thioglycoside 1a to the more stable
lents of 1-dodecanethiol under the same conditions resulted α-thioglycoside. The epimerization could proceed through the
in the recovery of thioglycoside 1a in 88% yield with partial thionium intermediate or reversible elimination/addition of
epimerization (α/β = 19 : 81) along with the hydrolysis product the thiol to the oxocarbenium intermediate (Scheme 2). The
828 | Org. Biomol. Chem., 2021, 19, 822–836
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
latter pathway would be consistent with the suppression of epi- plates with a 0.5 mm thickness coating of silica gel 60 GF254
merization by excess thiol. from Merck. Chemical spots on the TLC plates were observed
Lastly, the practicality of the developed method was demon- by visualization under 254 nm UV light or staining with p-ani-
strated through a gram-scale synthesis of dodecyl thioglycoside saldehyde staining solution. Silica gel 60 (70–230 mesh)
1a (eqn (4)). The DBSA-mediated thioglycosylation of 1-hydroxy from Merck was used for purification by column chromato-
sugar 1 (1.04 g, 2.49 mmol) proceeded smoothly under the graphy. Solvents for NMR experiments were purchased from
standard conditions to provide thioglycoside 1a in 66% Cambridge Isotope Laboratories or Euriso-top. Milli-Q water
yield (75% brsm yield) with α/β
= 7 : 93 after column was obtained from an ultrapure water system with a 0.22 μm
chromatography. Interestingly, we were able to isolate the Millipak® 40 filter unit, Millipore (USA). Microwave irradiation
α,α-disaccharide 2345 derived from dimerization of hydroxy was carried out in a sealed vessel at 218 psi employing a CEM
sugar 1 as a side-product in 7% yield. No open-chain dithioa- microwave reactor, model Discover Labmate. Functional group
cetal sugar could be isolated from this larger-scale reaction.
determinations were confirmed by infrared (IR) spectroscopy
on a Nicolet 6700 instrument. Chemical structure characteriz-
ation was conducted using nuclear magnetic resonance (NMR)
spectroscopy on a Bruker Avance 400 NMR spectrometer
operating at 400 MHz for 1H NMR and 101 MHz for 13C{1H}
Conclusions
A large selection of thioglycosides was successfully synthesized NMR or a JEOL JNM-ECZ500R/S1 spectrometer operating at
by dehydrative thioglycosylation between 1-hydroxy sugars and 500 MHz for 1H NMR and 126 MHz for 13C{1H} NMR. Exact
thiols in water. The reactions were performed in the presence masses of all products were determined by high resolution
of DBSA as a Brønsted acid–surfactant combined catalyst mass spectrometry (HRMS) using
a
JEOL SpiralTOF™
(BASC). The glycosylation reactions between 1-hydroxy furano- MALDI-TOF Mass Spectrometer or
a
Bruker Daltonics-
syl and pyranosyl sugars (both D- and L-sugars) and only a micrOTOF-QII-ESI-Qq-TOF Mass Spectrometer.
slight excess of a primary, secondary, or tertiary aliphatic or
General procedure A: DBSA-mediated glycosylation of
1-hydroxy sugar in water
aromatic thiol provided the expected thioglycoside products as
a mixture of α and β anomers in moderate to good yields and
selectivity. The moderate anomeric selectivity is not a concern In a typical procedure, the 1-hydroxy sugar (0.24 mmol) and
for many applications of the thioglycosides, such as use as thiol (0.29 mmol, 1.2 equivalents) were added to a microwave
bio-surfactants or further transformation via the Ramberg– vessel, followed by the addition of an aqueous solution of
Bäcklund reaction. The use of readily available perbenzylated 0.5 M DBSA (0.24 mmol, 0.5 mL, 1 equivalent). The reaction
1-hydroxy sugars as the glycosyl donor and the ability to mixture was placed in the microwave reactor and irradiated at
perform the reaction in water are the major advantages of the 80 °C for 5 h. The reaction was monitored using thin-layer
present methodology. In addition, the present DBSA-mediated chromatography. After 5 h, the reaction was quenched by
glycosylation of 1-hydroxy sugars did not yield the open-chain adding saturated aqueous NaHCO3 solution (2.5 mL), extracted
dithioacetal sugar by-products, as is often observed when with ethyl acetate (5 × 2.5 mL), and washed with brine (3 mL).
similar glycosylations are performed in organic solvents. By The combined organic layer was dried over anhydrous MgSO4
taking advantage of the hydrophobic environment inside the and concentrated to dryness in a rotary evaporator. The crude
emulsion droplets, this work provides a unique chemo- product was purified by column chromatography on silica gel
selectivity preference for the formation of thioglycoside over using gradient elution with ethyl acetate : hexanes.
dithioacetal sugar. Moreover, this method also offers a con-
Dodecyl 2,3,5-tri-O-benzyl-1-thio-L-arabinofuranoside (1a).
venient and rapid approach to generate a library of thioglyco- The glycosylation was carried out as described in general pro-
sides, which are not only valuable as synthetic intermediates cedure A using 2,3,5-tri-O-benzyl-L-arabinofuranoside 1 (α/β =
and thioglycosyl donors for oligomerization, but also impor- 53 : 47, 100 mg, 0.24 mmol), 1-dodecanethiol (70 μL,
tant in their own right as bioactive thioglycosides, non-ionic 0.29 mmol), and an aqueous solution of 0.5 M DBSA
biosurfactants, and biomimetic glycosides. The thioglycosides (0.24 mmol, 0.5 mL). The reaction was monitored by TLC
are currently being used as precursors for the synthesis of (ethyl acetate : hexanes = 1 : 4; p-anisaldehyde, Rf = 0.40). The
alkyl C-glycosides in our laboratory.46
crude mixture was purified by column chromatography using
gradient elution with ethyl acetate : hexanes from 0 : 1 to 3 : 7
as the eluent. Thiofuranoside 1a was obtained as a yellow
syrup (105 mg, 72%, α/β = 7 : 93). β-Anomer: 1H NMR
(400 MHz, CDCl3) δH 7.34–7.23 (m, 15H), 5.38 (d, J = 4.9 Hz,
Experimental section
All chemicals and solvents were purchased from Acros, Merck, 1H, anomeric proton), 4.66–4.44 (m, 6H), 4.17–4.11 (m, 2H),
Sigma-Aldrich, TCI, or RCI Lab Scan. Solvents were dried with 4.04 (t, J = 4.0 Hz, 1H), 3.72 (dd, J = 9.9, 6.4 Hz, 1H), 3.64 (dd,
3 Å molecular sieves for anhydrous reactions. Reaction moni- J = 9.9, 6.5 Hz, 1H), 2.69–2.60 (m, 2H), 1.62–1.57 (m, 2H),
toring by thin layer chromatography (TLC) was performed 1.51–1.21 (m, 18H), 0.88 (t, J = 6.6 Hz, 3H). 13C{1H} NMR
using silica gel 60 F254 0.2 mm pre-coated aluminium plates (101 MHz, CDCl3) δC 138.2, 137.9, 137.6, 128.4, 128.4, 127.9,
purchased from Merck. Preparative TLC was carried out using 127.8, 127.8, 127.8, 127.6, 87.2 (anomeric carbon), 84.4, 83.9,
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 822–836 | 829

View Article Online
Paper
Organic & Biomolecular Chemistry
82.1, 73.4, 72.4, 71.9, 71.4, 32.0, 30.9, 30.0, 29.7, 29.7, 29.7, (99 mg, 65%, α/β = 19 : 81). β-Anomer: 1H NMR (400 MHz,
29.6, 29.6, 29.4, 29.3, 29.2, 29.0, 22.7, 14.1. HRMS CDCl3) δH 7.35–7.22 (m, 15H), 5.38 (d, J = 4.9 Hz, 1H, anomeric
(MALDI-TOF): m/z calcd for C38H52O4SNa [M + Na+] 627.3484, proton), 4.64–4.42 (m, 6H), 4.18–4.10 (m, 2H), 4.04 (t, J =
found 627.3484.
4.0 Hz, 1H), 3.72 (dd, J = 9.9, 6.3 Hz, 1H), 3.64 (dd, J = 9.9,
Octyl 2,3,5-tri-O-benzyl-1-thio-L-arabinofuranoside (2). The 6.6 Hz, 1H), 2.65 (td, J = 7.4, 1.9 Hz, 2H), 1.64–1.58 (m, 2H),
glycosylation was carried out as described in general procedure 1.38–1.19 (m, 22H), 0.88 (t, J = 6.7 Hz, 3H). 13C{1H} NMR
A using 2,3,5-tri-O-benzyl-L-arabinofuranoside 1 (α/β = 53 : 47, (101 MHz, CDCl3) δC 138.3, 137.9, 137.6, 128.4, 128.4, 128.4,
100 mg, 0.24 mmol), 1-octanethiol (50 μL, 0.29 mmol), and an 128.4, 128.0, 127.9, 127.8, 127.8, 127.8, 127.6, 87.2 (anomeric
aqueous solution of 0.5 M DBSA (0.24 mmol, 0.5 mL). The carbon), 84.4, 83.9, 82.1, 73.4, 72.4, 71.9, 71.4, 32.00, 30.9,
reaction was monitored by TLC (ethyl acetate : hexanes = 1 : 4; 30.0, 29.8, 29.7, 29.7, 29.7, 29.6, 29.4, 29.3, 29.0, 22.7, 14.1.
p-anisaldehyde, Rf = 0.40). The crude mixture was purified HRMS (MALDI-TOF): m/z calcd for C40H56O4SNa [M + Na+]
by column chromatography using gradient elution with 655.3797, found 655.3788.
ethyl acetate : hexanes from 0 : 1 to 3 : 7 as the eluent.
Pentadecyl 2,3,5-tri-O-benzyl-1-thio-L-arabinofuranoside (5).
Thiofuranoside 2 was obtained as a yellow syrup (94 mg, 71%, Glycosylation was carried out as described in general pro-
α/β = 14 : 86). β-Anomer: 1H NMR (400 MHz, CDCl3) δH cedure A using 2,3,5-tri-O-benzyl-L-arabinofuranoside 1 (α/β =
7.35–7.22 (m, 15H), 5.38 (d, J = 4.9 Hz, 1H, anomeric proton), 53 : 47, 100 mg, 0.24 mmol), 1-pentadecanethiol (83 μL,
4.63–4.46 (m, 6H), 4.17–4.12 (m, 2H), 4.04 (t, J = 4.0 Hz, 1H), 0.29 mmol), and an aqueous solution of 0.5 M DBSA
3.72 (dd, J = 9.9, 6.4 Hz, 1H), 3.64 (dd, J = 9.7, 6.4 Hz, 2H), 2.65 (0.24 mmol, 0.5 mL). The reaction was monitored by TLC
(dt, J = 8.4, 4.1 Hz, 2H), 1.64–1.58 (m, 2H), 1.38–1.20 (m, 10H), (ethyl acetate : hexanes = 1 : 4; p-anisaldehyde, Rf = 0.42). The
0.88 (t, J = 6.7 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) crude mixture was purified by column chromatography using
δC 138.3, 137.9, 137.6, 128.5, 128.5, 128.4, 128.4, 128.0, 127.9, gradient elution with ethyl acetate : hexanes from 0 : 1 to 3 : 7
127.8, 127.8, 127.8, 127.6, 87.2 (anomeric carbon), 84.4, 83.9, as the eluent. Thiofuranoside 5 was obtained as a yellow syrup
82.1, 73.4, 72.4, 71.9, 71.4, 31.9, 30.9, 30.0, 29.6, 29.6, 29.4, (90 mg, 58%, α/β = 8 : 92). β-Anomer: 1H NMR (400 MHz,
29.3, 29.1, 29.0, 22.7, 14.1. HRMS (MALDI-TOF): m/z calcd for CDCl3) δH 7.35–7.19 (m, 15H), 5.38 (d, J = 4.9 Hz, 1H, anomeric
C34H44O4SNa [M + Na+] 571.2858, found 571.2859.
Decyl 2,3,5-tri-O-benzyl-1-thio-L-arabinofuranoside
proton), 4.65–4.45 (m, 6H), 4.18–4.10 (m, 2H), 4.04 (t, J =
(3). 4.0 Hz, 1H), 3.72 (dd, J = 9.9, 6.4 Hz, 1H), 3.64 (dd, J = 9.9, 6.5
Glycosylation was carried out as described in general pro- Hz, 1H), 2.65 (td, J = 7.3, 1.9 Hz, 2H), 1.64–1.60 (m, 2H),
cedure A using 2,3,5-tri-O-benzyl-L-arabinofuranoside 1 (α/β = 1.38–1.19 (m, 24H), 0.87 (t, J = 7.0 Hz, 3H). 13C{1H} NMR
53 : 47, 100 mg, 0.24 mmol), 1-decanethiol (61 μL, 0.29 mmol), (101 MHz, CDCl3) δC 138.2, 137.9, 137.6, 128.5, 128.5, 128.4,
and an aqueous solution of 0.5 M DBSA (0.24 mmol, 0.5 mL). 128.3, 128.0, 127.9, 127.8, 127.8, 127.7, 127.6, 87.2 (anomeric
The reaction was monitored by TLC (ethyl acetate : hexanes = carbon), 84.4, 83.9, 82.1, 73.4, 72.4, 71.9, 71.4, 31.9, 30.9, 30.0,
1 : 4; p-anisaldehyde, Rf = 0.40). The crude mixture was purified 29.7, 29.7, 29.6, 29.6, 29.4, 29.3, 29.0, 29.0, 22.7, 14.1. HRMS
by column chromatography using gradient elution with (MALDI-TOF): m/z calcd for C41H58O4SNa [M + Na+] 669.3953,
ethyl acetate : hexanes from 0 : 1 to 3 : 7 as the eluent. found 669.3957.
Thiofuranoside 3 was obtained as a yellow syrup (91 mg, 67%,
Octadecyl 2,3,5-tri-O-benzyl-1-thio-L-arabinofuranoside (6).
α/β
=
14 : 86). β-Anomer: 1H NMR (400 MHz, CDCl3) Glycosylation was carried out as described in general pro-
δH 7.35–7.23 (m, 15H), 5.38 (d, J = 4.9 Hz, 1H, anomeric cedure A using 2,3,5-tri-O-benzyl-L-arabinofuranoside 1 (α/β =
proton), 4.64–4.44 (m, 6H), 4.17–4.14 (m, 2H), 4.04 (t, J = 53 : 47, 100 mg, 0.24 mmol), 1-octadecanethiol (83 μL,
4.0 Hz, 1H), 3.71 (dd, J = 9.9, 6.4 Hz, 1H), 3.68–3.57 (m, 1H), 0.29 mmol), and an aqueous solution of 0.5 M DBSA
2.65 (dt, J = 8.4, 4.1 Hz, 2H), 1.64–1.58 (m, 2H), 1.40–1.18 (m, (0.24 mmol, 0.5 mL). The reaction was monitored by TLC
14H), 0.87 (t, J = 6.7 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) (ethyl acetate : hexanes = 1 : 4; p-anisaldehyde, Rf = 0.48). The
δC 138.2, 137.9, 137.6, 128.4, 128.4, 127.9, 127.8, 127.8, 127.8, crude mixture was purified by column chromatography using
127.6, 87.2 (anomeric carbon), 84.4, 83.9, 82.1, 73.4, 72.4, 71.9, gradient elution with ethyl acetate : hexanes from 0 : 1 to 3 : 7
71.4, 31.8, 30.9, 30.0, 29.7, 29.3, 29.2, 29.0, 22.7, 14.1. HRMS as the eluent. Thiofuranoside 6 was obtained as a yellow syrup
(MALDI-TOF): m/z calcd for C36H48O4SNa [M + Na+] 599.3171, (104 mg, 63%, α/β = 9 : 91). β-Anomer: 1H NMR (400 MHz,
found 599.3161.
CDCl3) δH 7.35–7.23 (m, 15H), 5.38 (d, J = 4.9 Hz, 1H, anomeric
Tetradecyl 2,3,5-tri-O-benzyl-1-thio-L-arabinofuranoside (4). proton), 4.63–4.46 (m, 6H), 4.18–4.11 (m, 2H), 4.04 (t, J =
Glycosylation was carried out as described in general pro- 4.0 Hz, 1H), 3.72 (dd, J = 9.9, 6.4 Hz, 1H), 3.64 (dd, J = 9.9, 6.5
cedure A using 2,3,5-tri-O-benzyl-L-arabinofuranoside 1 (α/β = Hz, 1H), 2.65 (td, J = 7.4, 2.0 Hz, 2H), 1.64–1.58 (m, 2H),
53 : 47, 100 mg, 0.24 mmol), 1-tetradecanethiol (79 μL, 1.38–1.22 (m, 30H), 0.88 (t, J = 6.7 Hz, 3H). 13C{1H} NMR
0.29 mmol), and an aqueous solution of 0.5 M DBSA (101 MHz, CDCl3) δC 136.1, 135.8, 135.5, 126.3, 126.3, 126.2,
(0.24 mmol, 0.5 mL). The reaction was monitored by TLC 125.8, 125.7, 125.6, 125.5, 125.4, 85.0 (anomeric carbon), 82.2,
(ethyl acetate : hexanes = 1 : 4; p-anisaldehyde, Rf = 0.41). The 81.7, 79.9, 71.2, 70.2, 69.8, 69.3, 29.8, 28.8, 27.8, 27.6, 27.6,
crude mixture was purified by column chromatography using 27.5, 27.4, 27.3, 27.2, 27.1, 26.9, 20.6, 12.0. HRMS
gradient elution with ethyl acetate : hexanes from 0 : 1 to 3 : 7 (MALDI-TOF): m/z calcd for C44H64O4SNa [M + Na+] 711.4423,
as the eluent. Thiofuranoside 4 was obtained as a yellow syrup found 711.4414.
830 | Org. Biomol. Chem., 2021, 19, 822–836
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
2-Phenylethyl 2,3,5-tri-O-benzyl-1-thio-L-arabinofuranoside NMR (101 MHz, CDCl3) δC 138.2, 137.8, 137.7, 128.4, 128.3,
(7). Glycosylation was carried out as described in general pro- 128.3, 128.2, 127.9, 127.8, 127.7, 127.7, 127.6, 127.5, 89.5
cedure A using 2,3,5-tri-O-benzyl-L-arabinofuranoside 1 (α/β = (anomeric carbon), 86.0, 83.5, 79.8, 73.3, 72.2, 72.1, 69.3, 31.5.
53 : 47, 100 mg, 0.24 mmol), 2-phenylethanethiol (34 μL, HRMS (MALDI-TOF): m/z calcd for C30H36O4SNa [M + Na+]
0.29 mmol), and an aqueous solution of 0.5 M DBSA 515.2232, found 515.2239.
(0.24 mmol, 0.5 mL). The reaction was monitored by TLC
4-Methylphenyl 2,3,5-tri-O-benzyl-1-thio-L-arabinofuranoside
(ethyl acetate : hexanes = 1 : 4; p-anisaldehyde, Rf = 0.35). The (10). Glycosylation was carried out as described in general pro-
crude mixture was purified by column chromatography using cedure A using 2,3,5-tri-O-benzyl-L-arabinofuranoside 1 (α/β =
gradient elution with ethyl acetate : hexanes from 0 : 1 to 3 : 7 53 : 47, 100 mg, 0.24 mmol), 4-methylbenzenethiol (36 μL,
as the eluent. Thiofuranoside 7 was obtained as a yellow syrup 0.29 mmol), and an aqueous solution of 0.5 M DBSA
(54 mg, 42%, α/β = 38 : 62). Mixture of α and β-anomer: 1H (0.24 mmol, 0.5 mL). The reaction was monitored by TLC
NMR (400 MHz, CDCl3) δH 7.45–7.06 (m, 20H), 5.37 (d, J = (ethyl acetate : hexanes = 1 : 4; p-anisaldehyde, Rf = 0.36). The
5.0 Hz, β-anomeric proton), 5.33 (d, J = 2.4 Hz, α-anomeric crude mixture was purified by column chromatography using
proton), 4.64–4.39 (m, 6H), 4.29 (q, J = 4.9 Hz, 0.4H), 4.19–4.11 gradient elution with ethyl acetate : hexanes from 0 : 1 to 3 : 7
(m, 1.2H), 4.04 (t, J = 4.0 Hz, 0.6H), 3.97 (t, J = 4.9 Hz, 0.8H), as the eluent. Thiofuranoside 10 was obtained as a yellow
3.74–3.58 (m, 2H), 2.96–2.89 (m, 4H). 13C{1H} NMR (101 MHz, syrup (52 mg, 41%, α/β = 16 : 84). β-Anomer: 1H NMR
CDCl3) δC 138.1, 138.0, 137.8, 137.7, 137.4, 128.6, 128.6, 128.4, (400 MHz, CDCl3) δH 7.50–7.15 (m, 17H), 7.09 (d, J = 7.8 Hz,
128.3, 128.0, 127.9, 127.8, 127.8, 127.8, 127.6, 126.3, 126.3, 2H), 5.60 (d, J = 4.9 Hz, 1H, anomeric proton), 4.69–4.48 (m,
88.8 (α-anomeric carbon), 87.7 (β-anomeric carbon), 87.2, 84.3, 6H), 4.25 (t, J = 4.2 Hz, 1H), 4.21–4.16 (m, 1H), 4.09 (t, J =
83.7, 82.1, 80.0, 73.4, 73.4, 72.4, 72.2, 72.0, 71.9, 71.4, 69.2, 3.7 Hz, 1H), 3.77 (dd, J = 9.9, 6.2 Hz, 1H), 3.69 (dd, J = 10.1,
36.6, 36.4, 32.6, 32.1. HRMS (MALDI-TOF): m/z calcd for 7.0 Hz, 1H), 2.31 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3)
C34H36O4SNa [M + Na+] 563.2232, found 563.2285.
Cyclohexyl 2,3,5-tri-O-benzyl-1-thio-α-L-arabinofuranoside 127.9, 127.9, 127.8, 127.8, 127.7, 127.6, 90.4 (anomeric
δC 138.2, 137.8, 137.4, 137.0, 131.6, 129.7, 128.4, 128.4, 128.3,
(8). Glycosylation was carried out as described in general pro- carbon), 84.3, 83.5, 82.4, 73.4, 72.5, 71.9, 71.1, 21.1. HRMS
cedure A using 2,3,5-tri-O-benzyl-L-arabinofuranoside 1 (α/β = (MALDI-TOF): m/z calcd for C33H34O4SNa [M + Na+] 549.2075,
53 : 47, 100 mg, 0.24 mmol), cyclohexanethiol (35 μL, found 549.2092.
0.29 mmol), and an aqueous solution of 0.5 M DBSA
4-Chlorophenyl 2,3,5-tri-O-benzyl-1-thio-L-arabinofuranoside
(0.24 mmol, 0.5 mL). The reaction was monitored by TLC (11). Glycosylation was carried out as described in general pro-
(ethyl acetate : hexanes = 1 : 4; p-anisaldehyde, Rf = 0.35). The cedure A using 2,3,5-tri-O-benzyl-L-arabinofuranoside 1 (α/β =
crude mixture was purified by column chromatography using 53 : 47, 100 mg, 0.24 mmol), 4-chlorobenzenethiol (34 μL,
gradient elution with ethyl acetate : hexanes from 0 : 1 to 3 : 7 0.29 mmol), and an aqueous solution of 0.5 M DBSA
as the eluent. Thiofuranoside 8 was obtained as a yellow syrup (0.24 mmol, 0.5 mL). The reaction was monitored by TLC
(56 mg, 45%, α/β = 100 : 0). α-Anomer: [α]2D5 45.0° (c 0.11, (ethyl acetate : hexanes = 1 : 4; p-anisaldehyde, Rf = 0.35). The
CHCl3). 1H NMR (400 MHz, CDCl3) δH 7.42–7.13 (m, 15H), 5.45 crude mixture was purified by column chromatography using
(d, J = 2.4 Hz, 1H, anomeric proton), 4.73–4.37 (m, 6H), gradient elution with ethyl acetate : hexanes from 0 : 1 to 3 : 7
4.31–4.29 (m, 1H), 3.97 (dd, J = 7.8, 2.6 Hz, 2H), 3.75–3.46 (m, as the eluent. Thiofuranoside 11 was obtained as a yellow
2H), 2.90 (ddd, J = 10.4, 6.7, 3.7 Hz, 1H), 2.13–1.84 (m, 2H), syrup (57 mg, 43%, α/β = 14 : 86). β-Anomer: 1H NMR
1.82–1.49 (m, 2H), 1.48–1.10 (m, 6H). 13C{1H} NMR (101 MHz, (400 MHz, CDCl3) δH 7.50–7.13 (m, 19H), 5.62 (d, J = 4.8 Hz,
CDCl3) δC 138.2, 137.9, 137.6, 89.2 (anomeric carbon), 86.5, 1H, anomeric proton), 4.67–4.42 (m, 6H), 4.30–4.24 (m, 1H),
83.6, 80.7, 73.3, 72.2, 72.0, 69.2, 45.3, 37.4, 30.8, 25.8. HRMS 4.23–4.13 (m, 1H), 4.09 (t, J = 3.7 Hz, 1H), 3.74 (dd, J = 9.9, 6.2
(MALDI-TOF): m/z calcd for C32H38O4SNa [M + Na+] 541.2388, Hz, 1H), 3.66 (dd, J = 10.0, 6.8 Hz, 1H). 13C{1H} NMR
found 541.2384.
(101 MHz, CDCl3) δC 138.1, 137.7, 137.2, 132.3, 129.0, 128.5,
tert-Butyl 2,3,5-tri-O-benzyl-1-thio-α-L-arabinofuranoside (9). 128.4, 128.4, 128.4, 128.0, 127.9, 127.8, 127.8, 127.8, 127.6,
Glycosylation was carried out as described in general pro- 89.8 (anomeric carbon), 84.3, 83.2, 82.6, 73.4, 72.6, 71.9, 70.9.
cedure A using 2,3,5-tri-O-benzyl-L-arabinofuranoside 1 (α/β = HRMS (MALDI-TOF): m/z calcd for C32H31ClO4SNa [M + Na+]
53 : 47, 100 mg, 0.24 mmol), tert-butylthiol (34 μL, 0.29 mmol), 569.1529, found 569.1531.
and an aqueous solution of 0.5 M DBSA (0.24 mmol, 0.5 mL).
1-Naphthyl
2,3,5-tri-O-benzyl-1-thio-L-arabinofuranoside
The reaction was monitored by TLC (ethyl acetate : hexanes = (12). Glycosylation was carried out as described in general pro-
1 : 4; p-anisaldehyde, Rf = 0.35). The crude mixture was purified cedure A using 2,3,5-tri-O-benzyl-L-arabinofuranoside 1 (α/β =
by column chromatography using gradient elution with 53 : 47, 100 mg, 0.24 mmol), 1-naphthalenethiol (40 μL,
ethyl acetate : hexanes from 0 : 1 to 3 : 7 as the eluent. 0.29 mmol), and an aqueous solution of 0.5 M DBSA
Thiofuranoside 9 was obtained as a yellow syrup (28 mg, 24%, (0.24 mmol, 0.5 mL). The reaction was monitored by TLC
α/β = 100 : 0). α-Anomer: [α]2D5 68.8° (c 0.15, CHCl3). 1H NMR (ethyl acetate : hexanes = 1 : 4; p-anisaldehyde, Rf = 0.30). The
(400 MHz, CDCl3) δH 7.42–7.15 (m, 15H), 5.53 (d, J = 2.9 Hz, crude mixture was purified by column chromatography using
1H, anomeric proton), 4.65–4.38 (m, 6H), 4.31–4.27 (m, 1H), gradient elution with ethyl acetate : hexanes from 0 : 1 to 3 : 7
4.00–3.95 (m, 2H), 3.66–3.60 (m, 2H), 1.40 (s, 9H). 13C{1H} as the eluent. Thiofuranoside 12 was obtained as a yellow solid
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 822–836 | 831

View Article Online
Paper
Organic & Biomolecular Chemistry
(64 mg, 47%, α/β = 86 : 14). α-Anomer: 1H NMR (400 MHz,
Dodecyl 2,3,5-tri-O-benzyl-1-thio-D-xylofuranoside (19a).
CDCl3) δH 8.52–8.40 (m, 1H), 7.89–7.73 (m, 3H), 7.59–7.37 (m, Glycosylation was carried out as described in general pro-
3H), 7.33–7.24 (m, 15H), 5.60 (d, J = 2.5 Hz, 1H, anomeric cedure A using 2,3,5-tri-O-benzyl-D-xylofuranoside 19 (α/β =
proton), 4.69–4.39 (m, 6H), 4.24 (t, J = 3.0 Hz, 1H), 4.04 (dd, J = 50 : 50, 100 mg, 0.24 mmol), 1-dodecanethiol (70 μL,
6.8, 3.3 Hz, 1H), 3.67–3.60 (m, 3H). 13C{1H} NMR (101 MHz, 0.29 mmol), and an aqueous solution of 0.5 M DBSA
CDCl3) δC 138.1, 137.8, 137.4, 131.7, 128.6, 128.5, 128.5, 128.4, (0.24 mmol, 0.5 mL). The reaction was monitored by TLC
128.4, 128.3, 128.3, 128.0, 128.0, 127.9, 127.9, 127.8, 127.8, (ethyl acetate : hexanes = 1 : 4; p-anisaldehyde, Rf = 0.40). The
127.8, 127.8, 127.7, 127.6, 127.6, 126.6, 126.2, 125.7, 125.5, crude mixture was purified by column chromatography using
90.6 (anomeric carbon), 88.8, 83.8, 80.9, 73.3, 72.3, 72.2, 69.2. gradient elution with ethyl acetate : hexanes from 0 : 1 to 3 : 7
HRMS (MALDI-TOF): m/z calcd for C36H34O4SNa [M + Na+] as the eluent. Thiofuranoside 19a was obtained as a yellow
585.2075, found 585.2066.
syrup (105 mg, 73%, α/β = 69 : 31). α-Anomer: 1H NMR
Dodecyl 2,3,5-tri-O-benzyl-1-thio-D-arabinofuranoside (17a). (400 MHz, CDCl3) δH 7.37–7.25 (m, 15H), 5.54 (d, J = 5.1 Hz,
Glycosylation was carried out as described in general pro- 1H, anomeric proton), 4.65–4.42 (m, 6H), 4.14 (dd, J = 5.2,
cedure A using 2,3,5-tri-O-benzyl-D-arabinofuranoside 17 (α/β = 2.8 Hz, 1H), 4.08 (dd, J = 5.1, 2.8 Hz, 1H), 3.99 (t, J = 3.9, 1H),
22 : 78, 100 mg, 0.24 mmol), 1-dodecanethiol (70 μL, 3.77–3.63 (m, 2H), 2.68–2.62 (m, 2H), 1.66–1.57 (m, 2H),
0.29 mmol), and an aqueous solution of 0.5 M DBSA 1.30–1.25 (m, 18H), 0.88 (t, J = 6.4 Hz, 3H). 13C{1H} NMR
(0.24 mmol, 0.5 mL). The reaction was monitored by TLC (101 MHz, CDCl3) δC 138.3, 138.0, 137.6, 128.5, 128.4, 128.4,
(ethyl acetate : hexanes = 1 : 4; p-anisaldehyde, Rf = 0.40). The 128.3, 127.9, 127.9, 127.9, 127.8, 127.6, 127.6, 87.3 (anomeric
crude mixture was purified by column chromatography using carbon), 84.1, 82.2, 80.9, 73.4, 72.8, 72.2, 68.1, 31.9, 31.7, 30.8,
gradient elution with ethyl acetate : hexanes from 0 : 1 to 3 : 7 30.0, 29.9, 29.7, 29.6, 29.6, 29.6, 29.4, 29.3, 29.2, 29.0, 29.0,
as the eluent. Thiofuranoside 17a was obtained as a yellow 22.7, 14.1. HRMS (MALDI-TOF): m/z calcd for C38H52O4SNa [M
syrup (96 mg, 66%, α/β = 16 : 84). β-Anomer: 1H NMR + Na+] 627.3484, found 627.3463.
(400 MHz, CDCl3) δH 7.35–7.21 (m, 15H), 5.38 (d, J = 4.9 Hz,
Dodecyl
2,3,4-tri-O-benzyl-1-thio-β-L-arabinopyranoside
1H, anomeric proton), 4.68–4.35 (m, 6H), 4.18–4.11 (m, 2H), (20a). Glycosylation was carried out as described in general
4.04 (t, J = 4.0 Hz, 1H), 3.68 (dd, J = 9.8, 6.4 Hz, 1H), 3.64 (dd, procedure A using 2,3,5-tri-O-benzyl-L-arabinopyranoside 20 (α/
J = 9.9, 6.5 Hz, 1H), 2.67–2.61 (m, 2H), 1.64–1.55 (m, 2H), β = 37 : 63, 100 mg, 0.24 mmol), 1-dodecanethiol (70 μL,
1.43–1.18 (m, 18H), 0.88 (t, J = 6.7 Hz, 3H). 13C{1H} NMR 0.29 mmol), and an aqueous solution of 0.5 M DBSA
(101 MHz, CDCl3) δC 138.2, 137.9, 137.6, 128.4, 128.3, 128.0, (0.24 mmol, 0.5 mL). The reaction was monitored by TLC
127.9, 127.8, 127.8, 127.7, 127.6, 87.2 (anomeric carbon), 84.4, (ethyl acetate : hexanes = 1 : 4; p-anisaldehyde, Rf = 0.40). The
83.9, 82.9, 73.4, 72.4, 71.9, 71.4, 31.9, 31.3, 30.9, 30.0, 29.8, crude mixture was purified by column chromatography using
29.7, 29.7, 29.6, 29.6, 29.4, 29.3, 29.0, 29.0, 22.7, 14.1. HRMS gradient elution with ethyl acetate : hexanes from 0 : 1 to 3 : 7
(MALDI-TOF): m/z calcd for C38H52O4SNa [M + Na+] 627.3484, as the eluent. Thiopyranoside 20a was obtained as a yellow
found 627.3466.
syrup (86 mg, 60%, α/β = 0 : 100). β-Anomer: 1H NMR
Dodecyl 2,3,5-tri-O-benzyl-1-thio-D-ribofuranoside (18a). (400 MHz, CDCl3) δH 7.28–7.16 (m, 15H), 5.13 (d, J = 3.8 Hz,
Glycosylation was carried out as described in general pro- 1H, anomeric proton), 4.67–4.41 (m, 6H), 3.93 (dd, J = 7.7,
cedure A using 2,3,5-tri-O-benzyl-D-ribofuranoside 18 (α/β = 3.9 Hz, 1H), 3.87 (dd, J = 11.7, 2.7 Hz, 1H), 3.73 (dt, J = 5.6,
53 : 47, 100 mg, 0.24 mmol), 1-dodecanethiol (70 μL, 2.8 Hz, 1H), 3.69–3.51 (m, 2H), 2.61 (t, J = 7.4 Hz, 2H),
0.29 mmol), and an aqueous solution of 0.5 M DBSA 1.69–1.59 (m, 2H), 1.31–1.13 (s, 18H), 0.80 (q, J = 7.4, 6.8 Hz,
(0.24 mmol, 0.5 mL). The reaction was monitored by TLC 3H). 13C{1H} NMR (101 MHz, CDCl3) δC 137.6, 137.4, 137.3,
(ethyl acetate : hexanes = 1 : 4; p-anisaldehyde, Rf = 0.40). The 127.4, 127.3, 127.0, 126.8, 126.7, 126.7, 126.6, 126.6, 82.7
crude mixture was purified by column chromatography using (anomeric carbon), 76.2, 75.1, 72.5, 72.0, 72.0, 70.7, 61.3, 38.3,
gradient elution with ethyl acetate : hexanes from 0 : 1 to 3 : 7 30.9, 29.5, 28.8, 28.7, 28.6, 28.6, 28.6, 28.5, 28.5, 28.3, 28.2,
as the eluent. Thiofuranoside 18a was obtained as a yellow 28.2, 27.9, 27.5, 21.7, 13.1. HRMS (MALDI-TOF): m/z calcd for
syrup (105 mg, 73%, α/β = 17 : 83). β-Anomer: 1H NMR C38H52O4SNa [M + Na+] 627.3484, found 627.3485.
(400 MHz, CDCl3) δH 7.34–7.24 (m, 15H), 5.21 (d, J = 4.0 Hz,
Dodecyl
2,3,4,6-tetra-O-benzyl-1-thio-D-galactopyranoside
1H, anomeric proton), 4.66–4.49 (m, 6H), 4.27–4.25 (m, 1H), (21a). Glycosylation was carried out as described in general
4.01 (t, J = 5.4 Hz, 1H), 3.86 (t, J = 4.5, 1H), 3.60–3.56 (m, 2H), procedure A using 2,3,4,6-tetra-O-benzyl-D-galactopyranoside
2.67–2.58 (m, 2H), 1.64–1.55 (m, 2H), 1.30–1.25 (m, 18H), 21 (α/β = 66 : 34, 100 mg, 0.24 mmol), 1-dodecanethiol (70 μL,
0.89 (t, J = 6.4 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δC 0.29 mmol), and an aqueous solution of 0.5 M DBSA
138.3, 137.8, 137.7, 128.4, 128.4, 128.3, 128.2, 128.1, 128.0, (0.24 mmol, 0.5 mL). The reaction was monitored by TLC
128.0, 127.9, 127.9, 127.8, 127.7, 127.7, 127.6, 127.6, 86.3 (ethyl acetate : hexanes = 1 : 4; p-anisaldehyde, Rf = 0.32). The
(anomeric carbon), 81.7, 81.0, 78.3, 73.5, 73.4, 72.3, 70.9, crude mixture was purified by column chromatography using
31.9, 31.2, 31.0, 30.1, 29.9, 29.7, 29.7, 29.6, 29.6, 29.5, 29.4, gradient elution with ethyl acetate : hexanes from 0 : 1 to 3 : 7
29.3, 29.2, 29.1, 29.0, 29.0, 22.7, 14.1. HRMS (MALDI-TOF): as the eluent. Thiopyranoside 21a was obtained as a yellow
m/z calcd for C38H52O4SNa [M + Na+] 627.3484, found syrup (56 mg, 32%, α/β = 65 : 35). Mixture of α and β-anomer:
627.3463.
1H NMR (400 MHz, CDCl3) δH 7.49–7.06 (m, 20H), 5.46 (d, J =
832 | Org. Biomol. Chem., 2021, 19, 822–836
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
5.5 Hz, 0.5H, α-anomeric proton), 4.96–4.38 (m, 8H), 4.42 (d, 3H). 13C{1H} NMR (126 MHz, CDCl3) δC 137.1, 136.8, 136.4,
J = 9.2 Hz, 0.5H, β-anomeric proton), 4.34–4.19 (m, 1H), 3.94 127.4, 127.4, 127.3, 127.0, 126.9, 126.8, 126.7, 126.6, 87.8
(dd, J = 9.2, 2.8 Hz, 0.5H), 3.80 (dd, J = 9.8, 2.9 Hz, 0.5H), (anomeric carbon), 86.5, 82.6, 78.9, 72.3, 71.2, 71.0, 68.1, 30.9,
3.66–3.37 (m, 4H), 2.80–2.61 (m, 1H), 2.60–2.35 (m, 1H), 30.3, 28.6, 28.6, 28.5, 28.3, 28.2, 27.9, 21.7, 13.1. HRMS
1.73–1.44 (m, 2H), 1.38–1.21 (m, 18H), 0.88 (t, J = 6.7 Hz, 3H). (ESI-QTOF): m/z calcd for C38H52O4SNa [M + Na+] 627.3484,
13C{1H} NMR (101 MHz, CDCl3) δC 137.6, 137.4, 137.3, 128.4, found 627.3481.
128.4, 128.4, 128.3, 128.3, 128.2, 128.2, 128.0, 128.0, 127.9,
Control experiment Scheme 3, eqn (2). Dodecyl 2,3,5-tri-O-
127.8, 127.6, 127.6, 127.6, 127.5, 127.3, 127.4, 85.6 (β-anomeric benzyl-1-thio-α-L-arabinofuranoside 1a (α/β = 100 : 0, 7.5 mg,
carbon), 84.1, 83.7 (α-anomeric carbon), 79.6, 78.6, 76.7, 76.5, 0.01 mmol) was added to a microwave vessel followed by the
76.3, 75.3, 74.8, 74.4, 73.7, 73.6, 73.3, 73.4, 72.8, 72.5, 69.7, addition of an aqueous solution of 0.5 M DBSA (0.02 mmol,
69.1, 68.9, 32.2, 31.9, 30.7, 29.9, 29.7, 29.6, 29.6, 29.5, 29.4, 0.04 mL, 2 equivalents). The reaction mixture was placed in
29.3, 29.0, 26.4, 23.4, 22.7, 14.1. HRMS (MALDI-TOF): m/z the microwave reactor and irradiated at 80 °C for 5 h. The reac-
calcd for C46H60O5SNa [M + Na+] 747.4059, found 747.4084.
Dodecyl 2,3,4,6-tetra-O-benzyl-1-thio-D-glucopyranoside and monitored by TLC (ethyl acetate : hexanes = 1 : 4; p-anisal-
tion was then carried out as described in general procedure A
(22a). Glycosylation was carried out as described in general dehyde, Rf = 0.15). The crude mixture was purified by column
procedure A using 2,3,4,6-tetra-O-benzyl-D-glucopyranoside 22 chromatography using ethyl acetate : hexanes = 3 : 7 as the
(α/β = 50 : 50, 100 mg, 0.24 mmol), 1-dodecanethiol (70 μL, eluent to remove DBSA. The yield of 2,3,5-tri-O-benzyl-L-arabi-
0.29 mmol), and an aqueous solution of 0.5 M DBSA nofuranose 1 was determined by 1H NMR integration to be
(0.24 mmol, 0.5 mL). The reaction was monitored by TLC 78%.
(ethyl acetate : hexanes = 1 : 4; p-anisaldehyde, Rf = 0.32). The
Control experiment Scheme 3, eqn (3). Dodecyl 2,3,5-tri-O-
crude mixture was purified by column chromatography using benzyl-1-thio-L-arabinofuranoside 1a (α/β = 7 : 93, 167 mg,
gradient elution with ethyl acetate : hexanes from 0 : 1 to 3 : 7 0.28 mmol) and 1-dodecanethiol (0.08 mL, 0.33 mmol,
as the eluent. Thiopyranoside 22a was obtained as a yellow 1.2 equivalents) were added to a microwave vessel, followed by
syrup (78 mg, 45%, α/β = 64 : 36). Mixture of α and β-anomer: the addition of an aqueous solution of 0.5
M DBSA
1H NMR (400 MHz, CDCl3) δH 7.45–7.07 (m, 20H), 5.37 (d, J = (0.28 mmol, 0.56 mL, 1 equivalent). The reaction mixture was
4.9 Hz, 0.5H, α-anomeric proton), 5.20–4.51 (m, 7.5H), 4.45 placed in the microwave reactor and irradiated at 80 °C for 5 h.
(dt, J = 11.6, 5.3 Hz, 2H), 4.19 (d, J = 9.9 Hz, 0.5H, β-anomeric The reaction was then carried out as described in general pro-
proton), 3.90–3.51 (m, 4H), 3.50–3.33 (m, 0.5H), 2.62–2.38 (m, cedure A and monitored by TLC (ethyl acetate : hexanes = 1 : 4;
2H), 1.71–1.49 (m, 2H), 1.37–1.21 (m, 18H), 0.88 (t, J = 6.7 Hz, p-anisaldehyde, Rf = 0.40). The crude mixture was purified by
3H). 13C{1H} NMR (101 MHz, CDCl3) δC 138.8, 138.6, 138.4, column chromatography using gradient elution with ethyl
138.3, 138.1, 138.1, 138.0, 138.0, 128.4, 128.4, 128.4, 128.1, acetate : hexanes from 0 : 1 to 3 : 7 as the eluent. Dodecyl 2,3,5-
128.0, 128.0, 127.8, 127.8, 127.8, 127.8, 127.7, 127.7, 127.6, tri-O-benzyl-1-thio-L-arabinofuranoside 1a was recovered as a
127.6, 86.7, 85.3 (β-anomeric carbon), 83.5, 82.6 (α-anomeric yellow syrup (147 mg, 88%, α/β = 19 : 81) and 2,3,5-tri-O-benzyl-
carbon), 81.9, 79.7, 79.2, 78.1, 77.6, 75.7, 75.7, 75.5, 75.0, 73.5, L-arabinofuranose 1 was obtained as a white solid (12 mg,
72.4, 72.1, 70.5, 69.6, 69.2, 68.7, 31.9, 30.9, 30.0, 29.8, 29.7, 10%).
29.6, 29.6, 29.4, 29.3, 29.0, 22.7, 14.1. HRMS (MALDI-TOF): m/z
Gram-scale synthesis of dodecyl 2,3,5-tri-O-benzyl-1-thio-L-
arabinofuranoside (1a) Scheme 3, eqn (4). 2,3,5-Tri-O-benzyl-L-
calcd for C46H60O5SNa [M + Na+] 747.4059, found 747.4035.
Control experiment Scheme 3, eqn (1). Dodecyl 2,3,5-tri-O- arabinofuranose 1 (α/β = 53 : 47, 1.04 g, 2.49 mmol) and
benzyl-1-thio-β-L-arabinofuranoside 1a (α/β = 0 : 100, 56 mg, 1-dodecanethiol (0.71 mL, 2.98 mmol, 1.2 equivalents) were
0.09 mmol) was added to a microwave vessel followed by the added to a microwave vessel followed by the addition of an
addition of an aqueous solution of 0.5 M DBSA (0.09 mmol, aqueous solution of 0.75 M DBSA (2.50 mmol, 3.35 mL, 1 equi-
0.18 mL, 1 equivalent). The reaction mixture was placed in the valent). The reaction mixture was placed in the microwave
microwave reactor and irradiated at 80 °C for 5 h. The reaction reactor and irradiated at 80 °C for 5 h. The reaction was moni-
was then carried out as described in general procedure A and tored by thin-layer chromatography. After 5 h, the reaction was
monitored by TLC (ethyl acetate : hexanes = 1 : 4; p-anisalde- quenched by adding saturated aqueous NaHCO3 solution
hyde, Rf = 0.50). The crude mixture was purified by column (15 mL), extracted with ethyl acetate (5 × 20 mL), and washed
chromatography using gradient elution with ethyl acetate : with brine (15 mL). The combined organic layer was dried over
hexanes from 1 : 19 to 3 : 7 as the eluent. Dodecyl 2,3,5-tri- anhydrous Na2SO4 and concentrated to dryness in a rotary
O-benzyl-1-thio-α-L-arabinofuranoside 1a was obtained as a evaporator. The crude product was purified by column
yellow syrup (25 mg, 45%, α/β = 100 : 0) and 2,3,5-tri-O-benzyl- chromatography on silica gel using gradient elution with
L-arabinofuranose 1 was obtained as a white solid (18 mg, ethyl acetate : hexanes from 1 : 19 to 3 : 7 as the eluent.
46%). Dodecyl 2,3,5-tri-O-benzyl-1-thio-α-L-arabinofuranoside Thiofuranoside 1a was obtained as a yellow syrup (988 mg,
1
1a: H NMR (500 MHz, CDCl3) δH 7.45–7.14 (m, 15H), 5.34 (d, 66%, α/β = 7 : 93), α,α-disaccharide (23) was obtained as a
J = 2.3 Hz, 1H, anomeric proton), 4.67–4.42 (m, 6H), 4.30–4.25 colorless syrup (70 mg, 7%), and 1-hydroxy sugar 1 was recov-
(m, 1H), 3.93 (2H), 3.62 (dd, J = 10.9, 3.7 Hz, 2H), 2.62 (d, J = ered as a white solid (125 mg, 12%). The coupling had 88%
6.7 Hz, 2H), 1.74–1.49 (m, 2H), 1.46–1.10 (m, 18H), 0.84 (s, conversion and 75% yield based on recovered starting
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 822–836 | 833

View Article Online
Paper
Organic & Biomolecular Chemistry
materials. 2,3,5,2′,3′,5′-Hexa-O-benzyl-α,α-L-arabinofuranoside Pacharalita Hansakunathai and Chompunud Yuenamporn for
(23):45 1H NMR (500 MHz, CDCl3) δH 7.49–7.14 (m, 30H), 5.51 the preliminary study on this research.
(s, 2H, 2 anomeric protons), 4.64–4.46 (m, 12H), 4.26 (dt, J =
8.3, 3.0 Hz, 2H), 4.13–4.08 (m, 2H), 3.96 (dd, J = 7.1, 3.3 Hz,
2H), 3.65 (qd, J = 10.8, 4.7 Hz, 4H). 13C{1H} NMR (126 MHz,
CDCl3) δC 138.2, 138.0, 137.6, 128.6, 128.5, 128.5, 128.2, 128.1,
References
128.0, 128.0, 127.9, 127.9, 127.9, 127.7, 102.2 (anomeric
carbon), 88.0, 83.9, 81.3, 73.5, 72.3, 72.0, 69.9, 32.0, 31.7, 29.8,
29.8, 29.7, 29.7, 29.7, 29.6, 29.5, 29.4, 22.8, 22.8, 14.3. HRMS
(ESI-QTOF): m/z calcd for C52H54O9Na [M + Na+] 845.3666,
found 845.3659.
1 (a) M. Panza, S. G. Pistorio, K. J. Stine and
A. V. Demchenko, Chem. Rev., 2018, 118, 8105–8150;
(b) C. Kinnaert, M. Daugaard, F. Nami and M. H. Clausen,
Chem. Rev., 2017, 117, 11337–11405; (c) M. Mende,
C. Bednarek, M. Wawryszyn, P. Sauter, M. B. Biskup,
U. Schepers and S. Bräse, Chem. Rev., 2016, 116, 8193–
8255; (d) K. Wangpaiboon, P. Padungros, S. Nakapong,
T. Charoenwongpaiboon, M. Rejzek, R. A. Field and
General procedure B: Brønsted acid/nonionic surfactant-
mediated glycosylation of 1-hydroxy sugar in water
R.
Pichyangkura,
Sci.
Rep.,
2018,
8,
8340;
In a typical procedure, a nonionic surfactant (TPGS-750-M,
Nok, and Coolade) was prepared as a 2% w/w aqueous solu-
tion. The 1-hydroxy sugar (0.24 mmol), thiol (0.29 mmol,
1.2 equivalents), and Brønsted acid (0.1 or 1.0 equivalent) were
added to a microwave vessel, followed by the addition of the
2% w/w nonionic surfactant, and the final concentration was
adjusted to 0.5 M based on the 1-hydroxy sugar. The reaction
mixture was placed in the microwave reactor and irradiated at
80 °C for 5 h. The reaction was monitored by thin-layer chrom-
atography. After 5 h, the reaction was quenched by adding
saturated aqueous NaHCO3 solution (2.5 mL), extracted with
ethyl acetate (5 × 2.5 mL), and washed with brine (3 mL). The
combined organic layer was dried over anhydrous Na2SO4 and
concentrated to dryness in a rotary evaporator. The crude
product was purified by column chromatography on silica gel
using gradient elution with ethyl acetate : hexanes.
Dodecyl 2,3,5-tri-O-benzyl-1-thio-L-arabinofuranoside (1a)
Table 2 entry 13. The glycosylation was carried out as
described in general procedure B, except that the vessel was
irradiated under microwave at 120 °C. 2,3,5-Tri-O-benzyl-L-ara-
binofuranose 1 (α/β = 53 : 47, 101 mg, 0.24 mmol), 1-dodeca-
nethiol (70 μL, 0.29 mmol), p-TsOH·H2O (41 mg, 0.24 mmol)
and a 2% w/w aqueous solution of TPGS-750-M (0.50 mL) were
combined in a vessel and irradiated under microwave at
120 °C for 5 h. The reaction was monitored by TLC (ethyl
acetate : hexanes = 1 : 4; p-anisaldehyde, Rf = 0.40). The crude
mixture was purified by column chromatography using gradi-
ent elution with ethyl acetate : hexanes from 1 : 19 to 3 : 7 as
the eluent. Thiofuranoside 1a was obtained as a yellow syrup
(115 mg, 79%, α/β = 24 : 76).
(e) T. N. Y. Nguyen, P. Padungros, P. Wongsrisupphakul,
N. Sa-Ard-Iam, R. Mahanonda, O. Matangkasombut,
M. K. Choo and P. Ritprajak, Sci. Rep., 2018, 8, 17123;
(f) T. Chivangkul, S. Pengprecha, P. Padungros,
K. Siraleartmukul, S. Prasongsuk and N. Muangsin,
Carbohydr. Polym., 2014, 108, 224–231.
2 (a) S. Saito and T. Tsuchiya, Chem. Pharm. Bull., 1985, 33,
503–508; (b) M. Chami, G. Pehau-Arnaudet, O. Lambert,
J.-L. Ranck, D. Lèvy and J.-L. Rigaud, J. Struct. Biol., 2001,
133, 64–74; (c) L. Z. Szabó, D. J. Hanrahan, E. M. Jones,
E. Martin, J. E. Pemberton and R. Polt, Carbohydr. Res.,
2016, 422, 1–4.
3 (a) T. Ziegler, R. Dettmann, M. Duszenko and V. Kolb,
Carbohydr. Res., 1996, 295, 7–23; (b) R. Dettmann and
T. Ziegler, Carbohydr. Res., 2011, 346, 2348–2361;
(c) A. Roux, S. Loffredo, L. A. Ferrara and V. P. Murphy, Pure
Appl. Chem., 2019, 91, 1257–1276.
4 (a) F. Castaneda, A. Burse, W. Boland and R. K. H. Kinne,
Int. J. Med. Sci., 2007, 4, 131–139; (b) Y. Gao, G. Zhao,
W. Liu, Y. Wang, W. Xu and J. Wang, Chin. J. Chem., 2010,
28, 605–612; (c) Z. Wang, G. Zhao, W. Liu, Y. Wang,
H. Shao, W. Xu and L. Tian, Chin. J. Org. Chem., 2010, 30,
849–859; (d) C. S. Kim, J. Oh, L. Subedi, S. Y. Kim,
S. U. Choi and K. R. Lee, J. Nat. Prod., 2018, 81, 2129–2133.
5 (a) F. K. Griffin, V. P. Murphy, D. E. Paterson and
R. J. K. Taylor, Tetrahedron Lett., 1998, 39, 8179–8182;
(b) M. L. Alcaraz, F. K. Griffin, D. E. Paterson and
R. J. K. Taylor, Tetrahedron Lett., 1998, 39, 8183–8186;
(c) D. E. Paterson, F. K. Griffin, M. L. Alcaraz and
R. J. K. Taylor, Eur. J. Org. Chem., 2002, 1323–1336;
(d) R. J. K. Taylor, G. D. McAllister and R. W. Franck,
Carbohydr. Res., 2006, 341, 1298–1311.
6 (a) F. Jérôme, S. Marinkovic and B. Estrine, ChemSusChem,
2018, 11, 1395–1409; (b) A. Karam, K. De Oliveira Vigier,
S. Marinkovic, B. Estrine, C. Oldani and F. Jérôme, ACS
Catal., 2017, 7, 2990–2997; (c) W. G. Ramdani, A. Karam,
K. De Oliveira Vigier, S. Rio, A. Ponchel and F. Jérôme, Mol.
Catal., 2019, 468, 125–129.
7 (a) D. Gin, J. Carbohydr. Chem., 2002, 21, 645–665;
(b) S. O’Neill, J. Rodriguez and M. A. Walczak, Chem. –
Asian J., 2018, 13, 2978–2990; (c) C. Gallo-Rodriguez and
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
This research is supported financially by the Thailand
Research Fund (MRG5680133 for P. P.). We would like to thank
834 | Org. Biomol. Chem., 2021, 19, 822–836
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
G. A. Kashiwagi, in Selective Glycosylations: Synthetic
Methods and Catalysts, ed. C. S. Bennett, Wiely-VCH,
Weinheim, Germany, 2017, pp. 297–326, DOI: 10.1002/
9783527696239.ch14; (d) P. Sriwarom, P. Padungros and
T. Vilaivan, J. Org. Chem., 2015, 80, 7058–7065.
314; (c) A. Sakakura, Y. Koshikari, M. Akakura and
K. Ishihara, Org. Lett., 2012, 14, 30–33; (d) G. Pelletier,
A. Zwicker, C. L. Allen, A. Schepartz and S. J. Miller, J. Am.
Chem. Soc., 2016, 138, 3175–3182; (e) T. J. Wadzinski,
A. Steinauer, L. N. Hie, G. Pelletier, A. Schepartz and
S. J. Miller, Nat. Chem., 2018, 10, 644–652.
8 (a) S. Hanessian, Preparative carbohydrate chemistry,
Dekker, New York, Basel, Hong Kong, 1997; 21 S. Kobayashi, Y. Mori, S. Nagayama and K. Manabe, Green
(b) M. Funabashi, S. Arai and M. Shinohara, J. Carbohydr.
Chem., 1999, 18, 333–341.
9 (a) S. Oscarson, in Glycoscience: Chemistry and Chemical
Chem., 1999, 1, 175–177.
22 T. Kitanosono, K. Masuda, P. Xu and S. Kobayashi, Chem.
Rev., 2018, 118, 679–746.
Biology I–III, ed. B. O. Fraser-Reid, K. Tatsuta and J. Thiem, 23 (a) B. S. Takale, R. R. Thakore, E. S. Gao, F. Gallou and
Springer Berlin Heidelberg, Berlin, Heidelberg, 2001, pp.
643–671, DOI: 10.1007/978-3-642-56874-9_20; (b) S. Mikkola
and M. Oivanen, ARKIVOC, 2009, 39–53, DOI: 10.3998/
ark.5550190.0010.306; (c) S. Manabe and Y. Ito, Pure Appl.
Chem., 2017, 89, 899–909.
B. H. Lipshutz, Green Chem., 2020, 22, 6055–6061;
(b) B. S. Takale, R. R. Thakore, F. Y. Kong and
B. H. Lipshutz, Green Chem., 2019, 21, 6258–6262;
(c) M. Cortes-Clerget, S. E. Spink, G. P. Gallagher,
L. Chaisemartin, E. Filaire, J.-Y. Berthon and
B. H. Lipshutz, Green Chem., 2019, 21, 2610–2614;
(d) H. Pang, F. Gallou, H. Sohn, J. Camacho-Bunquin,
M. Delferro and B. H. Lipshutz, Green Chem., 2018, 20,
130–135.
10 Y.-K. Chang, B.-Y. Lee, D. J. Kim, G. S. Lee, H. B. Jeon and
K. S. Kim, J. Org. Chem., 2005, 70, 3299–3302.
11 (a) L. Bellon, J. L. Barascut and J. L. Imbach, Nucleosides
Nucleotides, 1992, 11, 1467–1479; (b) J. A. Secrist, W. B. Parker,
K. N. Tiwari, L. Messini, S. C. Shaddix, L. M. Rose, 24 (a) S. Kobayashi and I. Hachiya, J. Org. Chem., 1994, 59,
L. L. Bennett and J. A. Montgomery, Nucleosides Nucleotides,
1995, 14, 675–686; (c) J. Wirsching and J. Voss, Eur. J. Org.
3590–3596; (b) S. Kobayashi, S. Nagayama and T. Busujima,
J. Am. Chem. Soc., 1998, 120, 8287–8288.
Chem., 1999, 691–696; (d) J.-Y. Hasegawa, M. Hamada, 25 S. Kobayashi and T. Wakabayashi, Tetrahedron Lett., 1998,
T. Miyamoto, K. Nishide, T. Kajimoto, J.-I. Uenishi and 39, 5389–5392.
M. Node, Carbohydr. Res., 2005, 340, 2360–2368; (e) B. Ayers, 26 (a) I. V. Vasilenko, H. Y. Yeong, M. Delgado, S. Ouardad,
H. Long, E. Sim, I. A. Smellie, B. L. Wilkinson and
A. J. Fairbanks, Carbohydr. Res., 2009, 344, 739–746.
12 A. T. Khan and M. M. Khan, Carbohydr. Res., 2010, 345,
2139–2145.
F. Peruch, B. Voit, F. Ganachaud and S. V. Kostjuk, Angew.
Chem., Int. Ed., 2015, 54, 12728–12732; (b) I. V. Vasilenko,
F. Ganachaud and S. V. Kostjuk, Macromolecules, 2016, 49,
3264–3273.
13 J. Braanalt, I. Kvarnstroem, G. Niklasson, S. C. T. Svensson, 27 (a) M. V. Deaton and M. A. Ciufolini, Tetrahedron Lett.,
B. Classon and B. Samuelsson, J. Org. Chem., 1994, 59,
1783–1788.
14 (a) T. Inazu, Noguchi Kenkyusho Jiho, 1987, 11–15;
(b) F. P. Boulineau and A. Wei, J. Org. Chem., 2004, 69,
3391–3399.
1993, 34, 2409–2412; (b) M. A. Ciufolini, M. V. Deaton,
S. Zhu and M. Chen, Tetrahedron, 1997, 53, 16299–16312;
(c) K. Manabe, Y. Mori, S. Nagayama, K. Odashima and
S. Kobayashi, Inorg. Chim. Acta, 1999, 296, 158–163.
28 K. Manabe, S. Iimura, X.-M. Sun and S. Kobayashi, J. Am.
Chem. Soc., 2002, 124, 11971–11978.
15 (a) M. Prévost, O. St-Jean and Y. Guindon, J. Am. Chem.
Soc., 2010, 132, 12433–12439; (b) O. St-Jean, M. Prevost and 29 (a) I. Solic, P. Seankongsuk, J. K. Loh, T. Vilaivan and
Y. Guindon, J. Org. Chem., 2013, 78, 2935–2946.
16 R. R. Schmidt and M. Stumpp, Liebigs Ann. Chem., 1983,
1249–1256, DOI: 10.1002/jlac.198319830717.
R. W. Bates, Org. Biomol. Chem., 2018, 16, 119–123;
(b) I. Solic, H. X. Lin and R. W. Bates, Tetrahedron Lett.,
2018, 59, 4434–4436.
17 (a) T. Ghosh, A. Santra and A. K. Misra, Beilstein J. Org. 30 S. Harrad, N. Wemken, D. S. Drage, M. A.-E. Abdallah and
Chem., 2013, 9, 974–982; (b) S. S. Weng, K. Y. Hsieh and
Z. J. Zeng, J. Chin. Chem. Soc., 2017, 64, 464–473.
A.-M. Coggins, Environ. Sci. Technol., 2019, 53, 13449–
13457.
18 (a) B. H. Lipshutz and S. Ghorai, Green Chem., 2014, 16, 31 P. Klumphu and B. H. Lipshutz, J. Org. Chem., 2014, 79,
3660–3679; (b) B. H. Lipshutz, F. Gallou and S. Handa, ACS 888–900.
Sustainable Chem. Eng., 2016, 4, 5838–5849; 32 N. R. Lee, M. Cortes-Clerget, A. B. Wood, D. J. Lippincott,
(c) B. H. Lipshutz, S. Ghorai and M. Cortes-Clerget, Chem. –
Eur. J., 2018, 24, 6672–6695.
H. Pang, F. A. Moghadam, F. Gallou and B. H. Lipshutz,
ChemSusChem, 2019, 12, 3159–3165.
19 (a) T. Tomonari, M. Takeshi, N. Masato, K. Atsushi and 33 B. H. Lipshutz, S. Ghorai, A. R. Abela, R. Moser,
S. Shin-ichiro, Chem. Lett., 2009, 38, 458–459;
(b) N. Yoshida, M. Noguchi, T. Tanaka, T. Matsumoto,
T. Nishikata, C. Duplais, A. Krasovskiy, R. D. Gaston and
R. C. Gadwood, J. Org. Chem., 2011, 76, 4379–4391.
N. Aida, M. Ishihara, A. Kobayashi and S.-I. Shoda, Chem. – 34 (a) A. V. Demchenko, N. N. Malysheva and C. De Meo,
Asian J., 2011, 6, 1876–1885.
20 (a) A. Naohiro and K. Shu, Chem. Lett., 2006, 35, 238–239;
(b) S. Shirakawa and S. Kobayashi, Org. Lett., 2007, 9, 311–
Org. Lett., 2003, 5, 455–458; (b) A. V. Demchenko,
P. Pornsuriyasak, C. De Meo and N. N. Malysheva, Angew.
Chem., Int. Ed., 2004, 43, 3069–3072.
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 822–836 | 835

View Article Online
Paper
Organic & Biomolecular Chemistry
35 (a) H. T. Flakus, A. Miros and P. G. Jones, Spectrochim. Acta, 39 Y. Chevalier and T. Zemb, Rep. Prog. Phys., 1990, 53, 279–
Part A, 2002, 58, 225–237; (b) R.-F. Zhang, L.-L. Qiu, F. Li
and C.-L. Ma, Chin. J. Chem., 2004, 22, 768–773.
36 (a) T. Kametani, K. Kawamura and T. Honda, J. Am. Chem.
371.
40 D. L. Aubele, C. A. Lee and P. E. Floreancig, Org. Lett., 2003,
5, 4521–4523.
Soc., 1987, 109, 3010–3017; (b) N. Oka, A. Mori and 41 L. Leclercq, G. Douyère and V. Nardello-Rataj, Catalysts,
K. Ando, Eur. J. Org. Chem., 2018, 6355–6362; (c) G.-L. Zhao, 2019, 9, 163.
Z.-Y. Yu, Y. Li, L.-N. Pang and J.-W. Wang, Chin. J. Chem., 42 (a) K. Ohno, H. Yoshida, H. Watanabe, T. Fujita and
2008, 26, 158–164; (d) M. Weïwer, T. Sherwood and
R. J. Linhardt, J. Carbohydr. Chem., 2008, 27, 420–427;
(e) S.-K. Seo and A. Wei, Org. Biomol. Chem., 2008, 6, 3362–
H. Matsuura, J. Phys. Chem., 1994, 98, 6924–6930;
(b) C. H. Larsen, B. H. Ridgway, J. T. Shaw, D. M. Smith and
K. A. Woerpel, J. Am. Chem. Soc., 2005, 127, 10879–10884.
3365; (f) A. Kitowski, E. Jiménez-Moreno, M. Salvadó, 43 (a) D. M. Smith and K. A. Woerpel, Org. Lett., 2004, 6,
J. Mestre, S. Castillón, G. Jiménez-Osés, O. Boutureira and
G. J. L. Bernardes, Org. Lett., 2017, 19, 5490–5493.
37 (a) L. F. Bornaghi and S. A. Poulsen, Tetrahedron Lett., 2005,
46, 3485–3488; (b) N. Shaikh, L. Russo, L. Cipolla and
2063–2066; (b) S. R. Shenoy, D. M. Smith and
K. A. Woerpel, J. Am. Chem. Soc., 2006, 128, 8671–8677;
(c) P. Szcześniak, E. Maziarz, S. Stecko and B. Furman,
J. Org. Chem., 2015, 80, 3621–3633.
F. Nicotra, Mol. Diversity, 2011, 15, 341–345; (c) L. Williams, 44 M. Goswami, A. Ellern and N. L. B. Pohl, Angew. Chem., Int.
N. Schunck, K. H. Gotz, M. Ringwald and M. S. Schmidt, Ed., 2013, 52, 8441–8445.
Carbohydr. Res., 2019, 486, 107841; (d) J. Aronow, 45 T. Yamanoi, R. Inoue, S. Matsuda, K. Iwao, Y. Oda,
C. Stanetty, I. R. Baxendale and M. D. Mihovilovic,
A. Yoshida and K. Hamasaki, Heterocycles, 2009, 77, 445–
Monatsh. Chem., 2019, 150, 11–19.
460.
38 (a) B. Svens and B. Rosenholm, J. Colloid Interface Sci., 46 (a) P. Padungros, R.-H. Fan, M. D. Casselman, G. Cheng,
1973, 44, 495–504; (b) R. Hargreaves, D. T. Bowron and
K. Edler, J. Am. Chem. Soc., 2011, 133, 16524–16536;
(c) J. A. Long, B. M. Rankin and D. Ben-Amotz, J. Am. Chem.
Soc., 2015, 137, 10809–10815.
H. R. Khatri and A. Wei, J. Org. Chem., 2014, 79, 4878–4891;
(b) P. Padungros, L. Alberch and A. Wei, J. Org. Chem.,
2014, 79, 2611–2624; (c) P. Padungros, L. Alberch and
A. Wei, Org. Lett., 2012, 14, 3380–3383.
836 | Org. Biomol. Chem., 2021, 19, 822–836
This journal is © The Royal Society of Chemistry 2021