Additive-Free Gold(III)-Catalyzed Stereoselective Synthesis of 2-Deoxyglycosides Using Phenylpropiolate Glycosides as Donors

Article abstract of DOI:10.1002/asia.201900888

Stereoselective synthesis of deoxyglycosides has been achieved from benchtop stable and easily synthesizable deoxy-phenylpropiolate glycosides (D-PPGs) using gold(III) salt as catalyst under external additive-free conditions. Under a simple catalytic system, D-PPGs reacted with a variety of sugar and non-sugar acceptors to produce majorly α-stereoselective O/N-deoxyglycosides in good to excellent yields and regenerate easily separable and reusable phenylpropiolic acid. Deoxy-PPGs containing armed and disarmed groups survived well under the optimized reaction conditions. In addition, the orthogonal nature of D-PPGs was showcased, and 1,1′-linked trehalose-type sugar was also synthesized.

Full text of DOI:10.1002/asia.201900888

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Accepted Article
Title: Additive Free Gold(III)-Catalyzed Stereoselective Synthesis of 2-
Deoxyglycosides Using Phenylpropiolate Glycosides as Donors
Mukta Shaw, and Amit Kumar*
Authors: Amit Kumar and Mukta Shaw
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10.1002/asia.201900888
Chemistry - An Asian Journal
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Additive Free Gold(III)-Catalyzed Stereoselective Synthesis of 2-
Deoxyglycosides Using Phenylpropiolate Glycosides as Donors
Mukta Shaw, and Amit Kumar*
Abstract: Stereoselective synthesis of deoxyglycosides has been
achieved from the benchtop stable and easily synthesizable deoxy-
phenylpropiolate glycosides (D-PPGs) using gold(III) salt as catalyst
under external additive-free conditions. Under a simple catalytic
system, D-PPGs reacted with a variety of sugar and non-sugar
acceptors to produce majorly α-stereoselective O/N-deoxyglycosides
in good to excellent yields and regenerate easily separable and
reusable phenylpropiolic acid. Deoxy-PPGs containing armed and
disarmed groups survived well under the optimized reaction
conditions. In addition, the orthogonal nature of D-PPGs was
showcased and 1,1´-linked trehalose-type sugar was also
synthesized.
selectivity of such reactions strongly depend on the choice of the
leaving groups, which is present at the anomeric position.
Therefore, the glycosyl donor plays a very crucial role in
chemical glycosylation reactions, which motivates further design
and development of efficient and sustainable glycosyl donors.
Such strategies that satisfy the parameters of modern science is
a high research priority for contemporary organic chemists.
Introduction
There has been a sustained interest in the design of viable and
efficient synthetic method for making the glycosidic bond, where
one sugar unit is attached with another sugar unit or any other
molecules via carbon-oxygen (C‒O) bond, due to their
prevalence in the natural biopolymers, which play a critical role
in modulating the various biological processes.[1] Indeed, making
the glycosidic bond is arguably one of the most fundamental and
important
aspects of the glycosciences.[2] The 2-
deoxyglycosides (where C2‒hydroxyl group is replaced by
hydrogen atom) are ubiquitous carbohydrate scaffold present in
several biologically active natural products, for instance,
digitoxin, landomycin A, etc.[3]
Also, these classes of
compounds are frequently found in many important drugs such
as anticancer and antibiotic drugs.[4] The lack of stereo-directing
group at C2 position makes it more arduous task to control the
desired stereochemical outcome at the anomeric center.
Nevertheless, there are several well documented synthetic
methods available in the literature for making 2-
deoxyglycosides.[5] However, the lack of a unified strategy for
stereoselective assembly of 2-deoxyglycosides in complex
carbohydrate system has remained a major concern for the
glycochemists. Literature survey disclosed two approaches
have mainly been adopted for stereochemical syntheses of 2-
deoxyglycosides. First, indirect approach- where temporary
Scheme 1. Different synthetic approaches towards the synthesis of 2-
deoxyglycosides
Various elegant glycosyl donors such as glycosyl imidates,[11]
glycosyl phosphites,[12] (2′-carboxy)benzyl-4,6-O-benzylidene-2-
deoxyglucoside,[13] thioglycosides,[14] and glycals[15] were
employed for the synthesis of 2-deoxyglycosides. In the recent
time, several research groups have introduced the bifunctional
moiety at the anomeric position to act as leaving groups such as
S-but-3-ynyl-thioglycoside,[16] ortho-alkynylbenzoate,[17] and 3-
benzoylpropionates,[18] which could be activated by remote
participation of catalyst under mild conditions (Scheme 1a-b).
The major constraint with these direct approaches are (a)
involvement of multi-steps for the preparation of glycosyl donors,
(b) requirement of expensive additives, (c) formation of a
stoichiometric amount of lipophilic byproducts, and (d) mostly
afford the mixture of anomers. Therefore, in the recent past,
direct activation of glycals, which are also known as enol-ethers,
are considered the most suitable and efficient precursor to
access the 2-deoxyglycosides. Moreover, this approach often
competes with Ferrier-type products and hampered their broad
applications (Scheme 1c). Indeed, Bennett and co-workers have
reported an efficient synthetic method to obtain the more
challenging -deoxyglycosides from glycosyl hemiacetals via in
situ generated -glycosyl tosylates under basic conditions
(Scheme 1d).[19]
participating/non-participating functionality such as ‒Br,[6] ‒I,[7]
‒
SR,[8] ‒SePh,[9] –OAc[10] is introduced at C2-position to control
the stereochemical outcome at the anomeric position. The major
roadblocks of these approaches are the requirements of
additional synthetic steps: installation followed uninstallation of
the temporary group after the desired operation, which
eventually decreases the overall efficacy of the reactions.
Second, direct approaches majorly rely on the nature of
activated electrophilic glycosyl donors. The reactivity and
Mukta Shaw, Amit Kumar
Department of Chemistry, Indian Institute of Technology Patna, Bihta
801106, Bihar, India
E-mail: amitkt@iitp.ac.in
Results and Discussion
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Very recently, we have introduced phenylpropiolate glycosides
(PPGs) as glycosyl donors for making O-glycosidic bonds.[20]
With these understanding and continuation of our own research
interest on the development of a sustainable approach for the
product 3a was also obtained in 74% yield with poor anomeric
selectivity and reaction took a long time for completion (entry 11).
After screening with several catalysts (entry 1-11), we concluded
that AuCl3 is the best catalyst for this reaction (yield 91%, α:β
4.5:1, entry 3). Furthermore, by lowering the catalyst loading to
3 mol % gave the improved anomeric selectivity (α:β 7.5:1) of
resulted glycoside 3a (entry 16). After identifying the best
catalyst, the model glycosylation reactions were also checked in
stereoselective glycoside bond formation,[21]
we applied
phenylpropiolate glycosides for the direct and stereoselective
synthesis of 2-deoxyglycopyranosides under the mild and
additive-free catalytic system and ultimately regenerate the
leaving group (Scheme 1d). Indeed, we believe that this
approach will minimize the need for laborious column purification
process. Hence, we have synthesized a range of deoxy-
phenylpropiolates (1a-g) by coupling of deoxy hemiacetals with
phenylpropiolic acid under our previously established conditions
in good to high yields (61-84%) (Scheme 2). All the synthesized
D-PPG donors (1a-g) were characterized by 1D (1H, 13C) and 2D
(COSY, HSQC)-NMR and their anomeric ratios (α:β) were
determined by 1H NMR.
Table 1. Optimization of reaction conditionsa
entry
catalyst (mol %)
solvent
time
yield (%)b
α:β ratioc
1
2
Au(PPh3)Cl
AuBr3
CH2Cl2
CH2Cl2
24 h
15 min
-
33
-
1.3:1
3
AuCl3
Sc(OTf)3
Bi(OTf)3
Yb(OTf)3
Cu(OTf)2
Sn(OTf)2
FeCl3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
(CHCl2)2
THF
5 min
30 min
30 min
30 min
6 h
91
83
4.5:1
3.6:1
2:1
4
5
45
6
72
1.5:1
-
7
trace
74
8
1 h
5:1
9
6 h
80
3:1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
BF3·OEt2
TfOH
30 min
5 h
76
4.5:1
1.2:1
1.1:1
2:1
74
AuCl3
5 min
15 min
1 h
60
AuCl3
70
AuCl3
trace
trace
93 (91)
81
-
Scheme 2. Synthesis of 2-deoxy-phenylpropiolate glycosyl donors. [a]
Reaction conditions: A (1.0 equiv), phenylpropiolic acid B (1.5 equiv), DCC
(1.0 equiv), and DMAP (0.2 equiv). [b] Yield of the isolated product. [c]
Anomeric ratio was determined by 1H NMR spectroscopy.
AuCl3
toluene
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
1 h
-
d,e
AuCl3
5 min
5 min
2 h
7.5:1
2:1
f
AuCl3
At the outset, we have started optimizing the glycosylation
reaction conditions using 3,4,6-tri-O-benzyl-2-deoxy-α/β-D-
glucopyranosyl phenylpropiolate 1a as model glycosyl donor,
isopropanol 2a as model acceptor and soft electrophilic gold salt
as a choice of catalyst at room temperature using dry CH2Cl2
solvent. Initial reaction with Au(PPh3)Cl as a catalyst, did not
afford any desired 2-deoxyglycoside 3a and starting materials
was remained intact as revealed by TLC analysis (Table 1, entry
1). Interestingly, switching from gold(I) to gold(III) salt the
desired product 3a was obtained in 33% yield with poor
anomeric selectivity (entry 2). After that, several reaction
parameters were screened to obtain the desired 2-
deoxyglycoside in good yield with excellent anomeric selectivity.
HClg
-
-
HAuCl4
1 h
73h
1:1
i
AuCl3
4 h
73
7.5:1
3.5:1
1.8:1
3:1
j
AuCl3
5 min
1 h
92
k
AuCl3
72
l
AuCl3
1 h
76
[a] Reaction conditions: 1a (0.1 mmol), isopropanol 2a (0.11 mmol), catalyst
(10 mol %) and solvent (2.0 mL) at room temperature under nitrogen
atmosphere. [b] Yield of the isolated product. [c] Anomeric ratio was
determined by 1H NMR spectroscopy. [d] 3 mol % of catalyst was used. [e]
Reaction was performed on 1.0 mmol scale; the value within the parenthesis
indicates the isolated yield. [f] Inverse reaction condition was employed. [g] 10
mol % of HCl in dioxane was used. [h] Hydrolyzed product was also formed. [i]
Reaction was performed at -10 ºC. [j] Reaction was performed at 45 ºC. [k] 2-
deoxy-glycosyl-1-O-acetate 1h was used as a glycosyl donor. [l] 2-deoxy-
glycosyl-1-O-benzoate 1i was used as a glycosyl donor.
For example, with AuCl3 as
a catalyst, afforded the 2-
deoxyglycoside 3a in excellent yield (91%) and with optimum -
anomer selectivity (α:β 4.5:1, entry 3). By changing the gold(III)
salt with other metal salts such as Sc(OTf)3, Bi(OTf)3, Yb(OTf)3,
Cu(OTf)2, Sn(OTf)2, and FeCl3 afforded the corresponding
product 3a, albeit in compromised yield and selectivity (entry 4-
9) except with Cu(OTf)2 (entry 7). The glycosylation reaction
worked well with BF3·OEt2 and resulted in the glycoside in
moderate yield (76%, entry 10). Indeed, when the reaction was
performed using Brønsted acid such as TfOH, the glycosylated
other solvent systems such as CH3CN, (CHCl2)2, THF, and
toluene (entries 12-15). The reaction proceeded well in CH3CN,
(CHCl2)2 and gave the desired product in optimum yield (up to
70%), while THF and toluene have a detrimental effect on the
reaction outcome. Further, the glycosylation reaction was carried
out under inverse addition conditions, which eventually
decreased the yield and selectivity of the desired transformation
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Scheme 3. Acceptor scope for Au(III)-catalyzed glycosidation with donor 1a. [a] Reaction conditions: 1a (0.1 mmol), glycosyl acceptor 2 (0.11 mmol), catalyst (3
mol %) and solvent (2.0 mL) at room temperature under nitrogen atmosphere. [b] Yield of the isolated product. [c] Anomeric ratios were determined by 1H NMR of
purified product.
(entry 17). Similarly, we also checked the role of HCl in the
glycosylation reaction (entry 18). No desired product was formed
under this condition and finally illustrate that AuCl3 is the real
catalyst for this glycosylation reaction. Furthermore, the impact
of temperature on the outcome of stereoselectivity was also
evaluated (entry 20-21). For instance, when the reaction was
carried out at -10 ºC under optimized conditions afforded the
desired product without further improvement of the anomeric
selectivity (entry 20). Similarly, when the reaction was performed
at a higher temperature (45 ºC), the anomeric selectivity of
deoxyglycoside 3a was dropped to 3.5:1 (entry 21). On the other
hand, to gauge the exact role of alkyne bond in the D-PPG
donor 1, the glycosylation reaction was carried out with other
ester-based glycosyl donors, such as 2-deoxyglycosyl-1-O-
acetate 1h and 2-deoxyglycosyl-1-O-benzoate 1i under similar
reaction conditions. The desired product 3a was formed in
moderate yields, 72%, and 76% respectively, with poor
anomeric selectivity and reaction took a longer time for the
completion (entry 22, 23). Based on these control experiments,
we can conclude that the presence of a triple bond is essential
for the desired transformation. Furthermore, the stereochemistry
at the anomeric position of desired 2-deoxyglycoside 3a was
confirmed by detailed NMR analysis (1D and 2D NMR), which is
in agreement with literature data.[22] Off note, when the
glycosylation reaction was carried out at 1 mmol scale, the
desired product 3a was isolated in 91% yield with good
anomeric selectivity and the hydrophilic phenylpropiolic acid was
also recovered in 89% yield (entry 16). Indeed, the regenerated
phenylpropiolic acid was further coupled with glucosyl
hemiacetal to produce the corresponding 2-deoxyglycosyl
phenylpropiolate donor 1a in 80% yield (for details, see
Supporting Information). This outcome clearly exemplified the
scalability and reusability of the designed glycosyl donor. After
careful optimization of the reaction parameters, the conditions
described in entry 16, has been chosen as an optimal reaction
condition for the further glycosylation reactions.
Next, the AuCl3-catalyzed 2-deoxyglycosylation approach was
briefly examined with a series of alcohols (carbohydrates and
non-carbohydrates), and results are shown in Scheme 3.
Glycosylation
of
perbenzylated-2-deoxyglucosyl
phenylpropiolate 1a with primary alcohols such as d4-methanol
2b, allyl alcohol 2c proceeded well and gave the desired
products 3b and 3c respectively, in good yields with exclusive α-
anomeric selectivity. Bulky secondary acceptors such as
cholesterol 2d and N-hydroxyphthalimide 2e also provided good
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Scheme 4. Substrate scope for Au(III)-catalyzed synthesis of 2-deoxyglycosides. [a] Reaction conditions: Glycosyl donor 1b-1e (0.1 mmol), glycosyl acceptor 2
(0.11 mmol), catalyst (3 mol %) and solvent (2.0 mL) at room temperature under nitrogen atmosphere. [b] In case of disarmed donors 1b, 1e, 5 mol % of AuCl3
was used. [c] Yield of the isolated product. [d] The ratio indicates α:β anomeric ratio and determined by 1H NMR of isolated product.
procured the 2-deoxy-O-glycosylated products 3i and 3j in good
yields of 2-deoxyglycosides 3d (71%) and 3e (69%) respectively,
yields (84% and 73%, respectively), with exclusive α-selectivity.
with complete control of anomeric stereochemistry. N-glycosides
are the important structural motif of glycoproteins and several
Similarly, thioglycosides containing primary -OH 2k also afforded
the product 3k in 69% yield without self-dimerization, which was
medicinal compounds.[23] Therefore, we became interested in
exploring the designed D-PPG 1a for the synthesis of 2-deoxy-
a
major concern. The reaction of 1a with diacetone-D-
galactoside 2l and benzylidine protected 3-OH 2m sugars under
the optimal conditions furnished 2-deoxy-α-glycosides 3l and 3m
in good yields. The 1,1´-linked sugar (trehalose) in general
present in the cell wall of mycobacteria and showed anti-
tuberculosis activity.[24] Hence, the reaction was carried out with
N-glycosides. Reaction with TsNH2 2g and TMSN3 2h afforded
N-glycosylated products (3f-3h) in excellent yields (up to 92%)
with optimum anomeric selectivity (up to α:β 5:1). Furthermore,
sterically hindered and less reactive sugar based acceptors 2i,
and 2j also reacted well under the given conditions and
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glucose-hemiacetal 2n as an acceptor with 1a to access the
heterodimeric 1,1´-linked trehalose-type sugar 3n.
product 11 in 86% yield (Scheme 6c). These control
experiments clearly revealed the orthogonal character of
phenylpropiolate group over the other functional groups.
To further evaluate the scope of the optimized reaction
conditions, armed and disarmed deoxy-PPG donors (1b-1e)
were treated with various glycosyl acceptors (Scheme 4). To our
delight, the glycosylation reactions with the disarmed donor,
peracetylated-2-deoxyglucosyl phenylpropiolate 1b reacted well
with several bulky acceptors with a catalyst loading of 5 mol %
and furnished the desired α-selective 2-deoxyglycosides 4a-4f in
good to excellent yields (77-88%). After successful synthesis of
peracetylated-2-deoxy glycosides 4a-4f, the scope of another
disarmed donor, perbenzoylated-2-deoxy phenylpropiolate 1c
was also checked.
Remarkably, the glycosylation of 1c with non-sugar acceptors
(isopropanol, (+)-menthol, cholesterol) and glucose and
mannose derived primary sugar acceptors (2i and 2s) under the
established reaction conditions also furnished the corresponding
2-deoxyglycosides (5a-5e) in good to excellent yields (up to
89%) and exclusive α-selectivity. Subsequently, differentially
protected 2-deoxy-PPGs armed (1d) and disarmed (1e) donors
were subjected under similar reaction conditions. Pleasingly, the
desired perbenzylated (6a-f) and peracetylated (7a-d) 2-
deoxygalactosides were isolated in good to excellent yields with
complete control of anomeric selectivity.
2,6-dideoxypyranosides are an important structural component
present in the variety of bioactive natural molecules and play an
important role in controlling many biological processes.[11a,25]
Encouraged by the above results, we became interested in
utilizing our 2-deoxy-phenylpropiolate system for the
stereoselective synthesis of 2,6-dideoxyglycosides (Scheme 5).
Gratifyingly, the reaction of 2-deoxyrhamnosyl phenylpropiolate
1f with (+)-menthol 2p and primary OH of glucose 2i, galactose
2r, and mannose 2s acceptors gave their corresponding 2,6-
dideoxyrhamnosides 8a-d in exclusive α-selectivity and good
yields (75-80%).
Scheme 6. Demonstration of the orthogonal character of phenylpropiolate
To understand the stereochemical outcome of the produced 2-
deoxyglycosides, preliminary DFT calculations were carried out
at the B3LYP/6-31+G(d) level.[26,27] In general, six-membered
oxocarbenium ions are present in two possible half-chair
4
conformations H3 and 3H4 (Figure 1). DFT calculations showed
that out of these two conformations (4H3 and 3H4), the conformer
(4H3) is energetically more stable than the conformer (3H4, 4.58
kJmol-1). Therefore, the attack of the acceptor (MeOH)
4
preferentially occurs on conformer H3. Further, there are two
possible sites (-and - faces) of nucleophilic attack on
conformer 4H3. Attack of nucleophile from the above face (β-
face) leads to β-glycoside via an energetically less favored twist-
boat-like transition state, whereas attack of the nucleophile
(MeOH) from the bottom side (α-face) lead to α-glycoside via
energetically more favorable a chair-like transition state (TS).
The energy difference between the chair and twist-boat-like
transition state is 29.63 kJmol-1 (G), which could be the driving
force for -selectivity.
Scheme 5. Au(III)-catalyzed synthesis of 2,6-dideoxyglycosides
The orthogonal protection-deprotection strategy is an important
aspect for carbohydrate chemistry, in particular to
oligosaccharides synthesis. Therefore, we became interested to
illustrate the orthogonal character of phenylpropiolate ester over
the other ester groups. Fortunately, treatment of peracetylated-
2-deoxyglucosyl-phenylpropiolate 1b under Zemplén conditions
(NaOMe/MeOH) resulted in the formation of corresponding
peracetylated-2-deoxyglucopyranose 9 in 72% yield without
affecting other ester groups (Scheme 6a). On the other hand,
when peracetylated-2-deoxyglucosyl-1-O-acetate was treated
under similar conditions (NaOMe/MeOH), a complex reaction
mixture was observed through TLC analysis (Scheme 6b).
Similarly, the reaction of 3,4-di-O-benzyl-6-O-phenylpropioloyl-2-
deoxy-α/β-D-glucopyranosyl phenylpropiolate 1g with 6-OH
Figure 1. Schematic representation of possible half-chair conformations of
oxocarbenium ion and preferred nucleophilic attack
On the basis of previous literature reports,[13,18] and DFT
calculations, an anticipated mechanism for the stereoselective
synthesis of 2-deoxyglycosides have been depicted in Scheme 7.
At first, the alkynophilic and mild Lewis acidic AuCl3
simultaneously coordinates with triple bond and carbonyl oxygen
of glycosyl phenylpropiolate 1 to facilitate the expulsion of
phenylpropiolate leaving group with the involvement of endo-
cyclic oxygen atom via the intermediate A and lead to the
formation of oxocarbenium ion intermediate B. In situ generated
phenylpropiolate anion further increases the nucleophilicity of
alcohol by abstracting the proton and allowing them for
preferentially attack from bottom face to the intermediate B to
form the desired C‒O bond and eventually afford the
sugar acceptor 2i
under given conditions gave the
corresponding disaccharide 10 in 65% yield and with excellent
α-selectivity without affecting the 6-phenylpropiolate group.
Furthermore, 6-phenylpropiolate glycoside 10 was selectively
deprotected under Zemplén conditions to afford the desired
deoxyglycoside
3 in a stereoselective manner with the
regeneration of phenylpropiolic acid and Au(III)salt.
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minutes), monitored by TLC. After completion of the reaction, the mixture
was diluted with CH2Cl2 and washed thrice with a cold saturated aqueous
solution of NaHCO3. The combined organic phase was washed with brine
solution, dried over anhydrous Na2SO4, evaporated in vacuo, and purified
by column chromatography using the different gradient of ethyl acetate
and hexanes to afford the desired product.
Acknowledgments
A.K. acknowledges DST-SERB, New Delhi, SB/FT/CS-069/2014
and IIT Patna for providing financial support. M.S. thanks IIT
Patna for providing institute research fellowship. We express
sincere thanks to Jagannath Pal and Dr. Ranga Subramanian,
Dept. of Chemistry, IIT Patna for their support in DFT
calculations.
Scheme 7. Anticipated mechanism for Au(III)-catalyzed 2-deoxyglycosides
Conflict of interest
Conclusions
In conclusion, we have successfully developed
a novel
The authors declare no conflict of interest.
methodology for the α-stereoselective synthesis of 2-deoxy and
2,6-deoxyglycosides using gold(III)-catalytic system under
additive-free conditions. The advantages of developed protocol
are: (i) the deoxy-PPG donors are shelf-stable and easily
synthesizable, (ii) remote activation could be achieved with low
catalyst loading (3-5 mol %) and in a very short time (5-30
minutes), (iii) the regeneration of hydrophilic phenylpropiolic acid,
which could be easily removed from the reaction mixture during
the workup and can be reused, (iv) broad substrate tolerance
with good to excellent yields and selectivity, and (v) additive-free
catalytic system. The optimized methodology further enables the
synthesis of N-glycosides and unsymmetrical 1,1´-linked
disaccharide. Experimental results indicated the orthogonal
character of phenylpropiolate based donor. High -anomeric
selectivity could be rationalized by the preferential attack of
nucleophiles to the more stable half-chair-oxocarbenium ions.
We expect that this class of donor will find large application in
the glycosylation reaction for the complex molecules.
Keywords:
deoxy-phenylpropiolate
•
stereoselective
glycosylation • bifunctional donor • reusable and recyclable
leaving group
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Experimental Section
General procedure for the synthesis of glycosyl donor (GP1): An oven-
dried round-bottom flask was charged with 2-deoxy glycosyl hemiacetal
(1.0 mmol) and phenylpropiolic acid (1.5 mmol) in dry CH2Cl2 (10.0 mL),
and the mixture was stirred at 0 °C for 10 minutes. A solution containing
the mixture of DCC (1.5 mmol) and DMAP (0.2 mmol) in dry CH2Cl2 (10.0
mL) was added to the reaction solution at 0 °C, and the reaction mixture
was allowed to stir at 0 °C for 15-30 minutes. The completion of the
reaction was monitored by TLC, and upon completion, the reaction
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(ethyl acetate-hexanes gradient elution) to afford the corresponding
glycosyl donors (1a-g).
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DFT calculations were performed at the B3LYP/6-31+G(d) level. The
calculations are carried out both in the gas phase and CH2Cl2 phase.
All the calculations were carried out with Gaussian 16. Computed
structures are visualized using GaussView0.5 (for details see
Supporting Information).
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Mukta Shaw, Amit Kumar*
Page No. – Page No.
Additive Free Gold(III)-Catalyzed
Stereoselective Synthesis of 2-
Deoxyglycosides Using
Phenylpropiolate Glycosides as
Donors
Gold(III)-catalyzed stereoselective synthesis of deoxyglycosides has been achieved
from easily synthesizable and benchtop stable deoxy phenylpropiolate glycosides.
Broad ranges of deoxyglycoides were synthesized with armed and disarmed donors
in high to excellent yields and exclusive α-anomeric selectivity and regenerate
easily separable and reusable phenylpropiolic acid.
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