Mild Palladium-Catalyzed Cyanation of Unprotected 2-Iodoglycals in Aqueous Media as Versatile Tool to Access Diverse C2-Glycoanalogues

Article abstract of DOI:10.1002/adsc.201901583

Access to unprotected 2-cyano-glycals via a mild palladium-catalyzed cyanation of protecting groups-free 2-iodoglycals in aqueous media has been developed. Diverse glycal substrates including disaccharide-type were successfully obtained in good to excellent yields. These unprotected 2-cyano-glycal scaffolds were successfully derivatized to different C2-glycoanalogues. (Figure presented.).

Full text of DOI:10.1002/adsc.201901583

Title: Mild Palladium-Catalyzed Cyanation of Unprotected 2-Iodoglycals
in Aqueous Media as Versatile Tool to Access Diverse C2-
Glycoanalogues.
Authors: Maciej Malinowski, Thanh Van Tran, Morgane de Robichon,
Nadège Lubin-Germain, and Angélique FERRY
This manuscript has been accepted after peer review and appears as an
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201901583
Link to VoR: http://dx.doi.org/10.1002/adsc.201901583

10.1002/adsc.201901583
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201
Mild Palladium-Catalyzed Cyanation of Unprotected 2-
Iodoglycals in Aqueous Media as Versatile Tool to Access
Diverse C2-Glycoanalogues.
Maciej Malinowski,a,b Thanh Van Tran,a Morgane de Robichon,a Nadège Lubin-
Germain*a and Angélique Ferry*a
a
Laboratoire de Chimie Biologique (LCB), Universitꢀ de Cergy-Pontoise, EA 4505, 5 Mail Gay-Lussac, 95031 Cergy-
Pontoise cedex, France. E-mail: angelique.ferry@u-cergy.fr ; nadege.lubin-germain@u-cergy.fr
Faculty of Chemistry, Warsaw University of Technology, ul. Noakowskiego 3, 00‐ 664 Warsaw, Poland
b
Received:
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract. Access to unprotected 2-cyano-glycals via a mild Keywords: unprotected glycosides; palladium catalysis;
palladium-catalyzed cyanation of protecting groups-free 2- cyanation; aqueous media; 2-iodoglycals
iodoglycals in aqueous media has been developed. Diverse
glycal substrates including disaccharide-type were
successfully obtained in good to excellent yields. These
unprotected 2-cyano-glycal scaffolds were successfully
derivatized to different C2-glycoanalogues.
Introduction
deal with the deprotection of the obtained C2-glycals.
However, deprotection may become challenging
depending on the sensitivity of the introduced
function. Indeed, per-acetylated sugars are usually
deprotected in basic conditions,[5] which are
incompatible with many functionalities. Similarly,
hydrogenolysis, commonly used to remove benzyl
protecting groups,[3i] could be deleterious in the
presence of unsaturated functions. These limitations
can constitute a dead end if the functional group
introduced on the sugar reacts both with base and in
the presence of hydrogen. One of the best example is
certainly the nitrile group. However, nitrile is a
particularly interesting functionality, which can be
derivatized in many functions such as amide,
carbonyl, tetrazole, amine, etc. Thus, C2-
cyanoglycals appear to be potential versatile
structures to access diverse glycoside derivatives. The
first and only description of a procedure to synthesize
such compounds in a protected version was by Hall et
al. in 1973 using chlorosulfonyl isocyanate as
cyanating reagent. This method was applied only on
few examples in poor to modest yields.[6] Our
strategy to reach these analogues was the opposite of
the described literature on 2-iodoglycals. We decided
to explore a new concept, to set the deprotection step
before the introduction of the sensitive function
(nitrile in our case). In consequence, this strategy
required the development of both cyanation and
subsequent derivatization steps on unprotected polar
glycals (Scheme 1). Herein, we describe an access to
diverse protecting groups-free C2-glycoanalogues via
a key mild palladium-catalyzed cyanation reaction in
aqueous media on unprotected 2-iodoglycals.
The ubiquitous involvements of carbohydrate
derivatives in biological responses has motivated the
chemist community to develop synthetic tools to
reach natural and unnatural analogues.[1] Design of
unnatural mimics was largely explored in order to
circumvent drawbacks of natural sugars. The main
issue encountered by these biomolecules is related to
their poor stability due to the sensitivity of natural C-
O and C-N bonds. Enzymatically and chemically
stable C-branched glycosides possessing an unnatural
C-C bond were thus highly investigated.[2] Among the
current synthetic routes to form C-C bonds on sugars,
metal-catalyzed cross-couplings emerged as new
powerful tools. In particular, during this last decade,
2-iodoglycal substrates attracted attention, due to
their suitable reactivity in palladium-catalyzed
processes. By this way, diverse C2-glycoanalogues
were reached via classical Suzuki, Sonogashira, Heck,
etc. cross-couplings. More recently, carbonylative
reactions applied to 2-iodoglycals emerged (Scheme
1).[3] All these methodologies were carried out almost
exclusively on O-protected iodoglycals (mostly
acetylated or benzylated) except a single example of
thiolation described by Messaoudi et al. on
unprotected 2-iodo-D-glucal in organic media leading
to moderate yield.[3h] Indeed, the use of unprotected
carbohydrates as starting substrates raises many
solubility and purification challenges as well as side
reactivities due to the presence of numerous free
hydroxyl groups.[4] Nevertheless, access to
unprotected glycoanalogues in an acceptable scale is
crucial for biological applications. Most of the
current literature involving 2-iodoglycals does not
1
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10.1002/adsc.201901583
Advanced Synthesis & Catalysis
stoichiometric amount of base and K4[Fe(CN)6] in a
mixture (1:1) of 1,4-dioxane/water at 100°C under
argon atmosphere.[9] These conditions led to the
formation of traces of the desired product 2a (Table 1,
entry 1). The use of tBuOH as organic co-solvent
instead of 1,4-dioxane led to a good 62% yield in 2a
(Table 1, entry 2). Moreover, the solvent ratio of
(1:1) appears to be crucial for the reactivity (Table 1,
entries 3 and 4). Indeed, it was shown that cyanation
reactions using K4[Fe(CN)6] are optimal when
cyanide anions are slowly delivered avoiding
poisoning of the palladium complex.[8a] A decrease of
the temperature to 75°C yielded 2a in a good 72%
(Table 1, entry 5). Unreactive argon atmosphere was
also a crucial parameter since only 11% of 2a were
obtained under air atmosphere (Table 1, entry 6).
Satisfyingly, we could halve both the amounts of
precatalyst and ligand without significant loss of
yield (Table 1, entry 7). On the other hand, only a
slight excess of base compared to precatalyst amount
is needed and furnished the best result yielding 2a in
an excellent 90% yield (85% isolated) (Table 1, entry
8). Indeed, the role of the base is assumed to be only
the precatalyst activator. However, when the amounts
of precatalyst, ligand and base were halved again, a
modest yield of 44% was observed (Table 1, entry 9).
The use of other couples of precatalysts/ligands was
tested without any improvement (Table 1, entries 10-
12). With the best conditions in hand (Table 1, entry
8), various unprotected 2-iodoglycals were engaged
Scheme 1: Different strategies for palladium-catalyzed
cross-couplings on 2-iodoglycals
Results and Discussion
The introduction of a nitrile group on aromatic
substrates via palladium-catalyzed cross-coupling
was largely explored in organic media[7] and was
studied, to a lesser extent, in aqueous media at
temperatures generally higher than 100°C.[8] In terms
of cyanating reagent, our choice turned to a non-toxic,
inexpensive cyanide source namely potassium
ferrocyanide (K4[Fe(CN)6]). This reagent attracted
more and more attention thanks to its non-hazardous
properties and was already successfully used in many
cyanation reactions.[7a] We started our methodology
investigation on 2-iodo-D-glucal 1a, obtained in two
steps from the commercially available peracetylated
D-glucal (Table 1, for detailed study see SI).[3g]
Inspired by Buchwald cyanation conditions applied to
aromatic compounds, 1a was reacted in the presence
of a palladium precatalyst, a ligand, a sub-
(Table
2).
Several
pyranoside
glycal
monosaccharides such as 2-iodo-D-galactal, 2-iodo-
D-xylal as well as 2-iodo-L-rhamnal could be
converted into their cyanated analogues in excellent
yields
(Table
2,
2b,
2c,
2d).
Table 1. Optimization of the cyanation reaction on 1aa
Entry T (°C)
Solvent (ratio)
1,4-dioxane/H2O
(1/1)
Precatalyst (eq)
Ligand (eq)
KOAc (eq) Yield (%)b
100
Pd-XPhos-G3 (0.08)
XPhos (0.16)
0.3
Traces
1
100
100
100
75
t-BuOH/H2O (1/1)
t-BuOH/H2O (5/1)
t-BuOH/H2O (1/5)
t-BuOH/H2O (1/1)
t-BuOH/H2O (1/1)
t-BuOH/H2O (1/1)
t-BuOH/H2O (1/1)
t-BuOH/H2O (1/1)
t-BuOH/H2O (1/1)
t-BuOH/H2O (1/1)
t-BuOH/H2O (1/1)
Pd-XPhos-G3 (0.08)
Pd-XPhos-G3 (0.08)
Pd-XPhos-G3 (0.08)
Pd-XPhos-G3 (0.08)
Pd-XPhos-G3 (0.08)
Pd-XPhos-G3 (0.04)
Pd-XPhos-G3 (0.04)
Pd-XPhos-G3 (0.02)
Pd-tBuXPhos-G3 (0.04)
Pd-BrettPhos-G3 (0.04)
Pd-XantPhos-G3 (0.04)
XPhos (0.16)
XPhos (0.16)
XPhos (0.16)
XPhos (0.16)
XPhos (0.16)
XPhos (0.08)
XPhos (0.08)
XPhos (0.04)
tBuXPhos (0.08)
BrettPhos (0.08)
XantPhos (0.08)
0.3
0.3
62c
36
9
2
3
0.3
4
0.3
72
11d
69
90e
44
35
55
45
5
75
0.3
6
75
0.3
7
8
75
0.05
0.025
0.05
0.05
0.05
75
9
75
10
11
12
75
75
a
Conditions: 1 (0.165 mmol), K4[Fe(CN)6] (0.4 equiv.), “Pd” (X equiv.), ligand (X equiv.), KOAc (X equiv.),
organic solvent/H2O (0.760 mL), under Ar, T°C, 16h. b Determined by H NMR using DMF as internal reference
1
(see SI). c Corresponds to 56% isolated yield. d Under air atmosphere. e Corresponds to 85% isolated yield.
2
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10.1002/adsc.201901583
elimination with simultaneous reformation of Pd(0)
species (A).
Advanced Synthesis & Catalysis
Table 2: Glycal scopea
2b 92%
2e 83%b
2c 90%
2d 100%
2f 76%
2g 51%c
(91%)b
(65%)b
Scheme 2: Proposed cyanation mechanism.
2h 44%c
2i 0%
2j 71%d
This methodology is thus an easy access to protecting
groups-free 2-cyano-glycals. These scaffolds are
interesting frameworks, which might be derivatized
to many C2-glycoside derivatives (Table 3). Under
hydrogen atmosphere in the presence of supported
palladium catalyst, 2a was converted into 3a where
both nitrile and glycal double bond were reduced
(Table 3, conditions A). Only one isomer was
a
Conditions: 2 (1 equiv.), K4[Fe(CN)6] (0.4 equiv.),
Pd-XPhos-G3 (4 mol%), XPhos (8 mol%), KOAc (5
mol%), t-BuOH/H2O (1:1), under Ar, 75°C, 16h.
mol% of [Pd], 16 mol% of XPhos and 10 mol% of
b
8
c
KOAc were used.
Reactions were performed at
130°C. d Reaction was performed at 90°C.
Glycal disaccharide (2-iodo-D-lactal) presenting six
free hydroxyl groups required the use of 8 mol% of
Pd-XPhos-G3, 16 mol% of ligand XPhos and 10
mol% of KOAc to obtain 2e in an excellent 83%
yield (32% in standard conditions). Furanoside 2-
iodo-D-ribal led successfully to the desired product 2f
in good yield (76% in standard way, 91% when the
amount of catalytic system is doubled). Protected 2-
iodo-D-glucals (perbenzylated or persilylated) were
also successfully engaged despite lower yields and
required a higher reaction temperature (Table 2, 2g
and 2h). These results can be explained by a lower
solubility of protected glycals in the media but also
by stereoelectronic effects. In case of peracetylated 2-
iodo-D-glucal, only starting material or degradation
was observed at temperatures between 75-130°C
(Table 2, 2i). This absence of reactivity could be
correlated with the disarming effect of a fully ester
protected sugar postulated in glycosylation reactions,
which could reduce considerably the electron density
of the double bond.[10] This hypothesis is supported
by the fact that the presence of only one ester group
on the primary hydroxyl group led to improved
reactivity (Table 2, 2j). The mechanism of the
reaction is expected to proceed via a classical
Pd(0)/Pd(II)-catalytic cycle (Scheme 2). At first, the
active Pd(0)-XPhos species (A) is generated.
Secondly, an oxidative addition of Pd(0) (step 1) to
the glycal C-I bond occurs to form Pd(II) complex B.
Slow dissociation of K4Fe(CN)6 produces cyanide
anion, which forms complex C by ligand exchange.
Finally, product 2 is obtained after reductive
1
observed in H- and 13C-NMR and was isolated in
75% yield (Table 3, 3a). The C2-manno-
configuration of 3a arising from an attack of H2 by
the less hindered face of the sugar, was assigned
1
regarding both H-coupling constants and NOESY
correlations (see SI). These conditions were applied
successfully to 2d furnishing 3b in an excellent 83%
yield as a single isomer with an axial CH2-NH2 group
(Table 3, 3b). The selective reduction of the nitrile
group without affecting the double bond was
achieved by using NaBH4 reagent in the presence of a
cobalt salt in aqueous media (Table 3, conditions
B).[11] Both 2a and 2c could be transformed by this
method into the corresponding amino-glycal 4 in
moderate to good yields (Table 3, 4a and 4b).
Compounds 3 and 4 are interesting platforms bearing
a nucleophilic amine which can be used in peptide
synthesis to reach original glycopeptide analogues.
Nitriles 2a and 2f were then converted into their
corresponding amide analogues 5a and 5b in good
yields (Table 3, conditions C).[12] Heterocycles such
as tetrazoles are also accessible from nitriles 2 by a
cycloaddition reaction with sodium azide in good
yields (Table 3, conditions D, 6a and 6b).[13] Finally,
access to ketone derivatives from the 2-cyanoglycals
2 was possible by reaction with Grignard reagents,[14]
exemplified on compounds 2a and 2d in very good
yields (Table 3, 7a and 7b, conditions E). This
method is complementary to our previous work
dealing with carbonylative Suzuki-Miyaura cross-
coupling on 2-iodoglycals which was applicable only
for the synthesis of aryl and alkenylketones.[3l]
3
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10.1002/adsc.201901583
excellent yields. The reactivity of the nitrile group
allowed the possibility to reach five protecting
groups-free C2-glycoanalogue families possessing
amine, amide, tetrazole or ketone functionalities. The
development of a strategy setting the deprotection
step at an early stage of a synthesis provides
Advanced Synthesis & Catalysis
Nevertheless, in this last work we faced to
deprotection issues due to the sensitivity of the
ketone function.
Table 3: Access to diverse C2-glycoanalogues from 2a
unprotected glycosides bearing
functionality in an easier way.
a
sensitive
Experimental Section
General experimental methods
All chemical operations were carried out using standard
sealed tubes. Acetonitrile was purified before use by
distillation under an argon atmosphere. Tetrahydrofuran
(THF) was distilled over Na/benzophenone under Ar.
Other solvents were used without further purification.
Commercially available chemicals were used as received
unless otherwise stated. Pd-XantPhos-G3 was purchased
from Sigma Aldrich, Pd-XPhos-G3, Pd-tBuXPhos-G3, Pd-
BrettPhos- were synthesized from palladium dimer
according to described procedure.[15] Reactions were
monitored by thin-layer chromatography on silica gel
plates (60 F254 aluminium sheets) which were rendered
visible by ultraviolet and/or spraying with vanillin (15%) +
3a, 75%
3b, 83%
4a, 75%
(from 2a cond. A) (from 2d cond. A) (from 2a cond. B)
1
sulfuric acid (2,5%) in EtOH followed by heating. H
NMR (400 MHz), 13C NMR (100.5 MHz) were recorded at
298 K unless otherwise stated. Chemical shifts are given in
ppm (δ) and are referenced to the internal solvent signal or
to TMS used as an internal standard. Multiplicities are
declared as follows: s (singlet), bs (broad singlet), d
(doublet), t (triplet), q (quadruplet), dd (doublet of doublet),
ddd (doublet of doublet of doublet), dt (doublet of triplet),
m (multiplet). Coupling constants J are given in Hz.
Infrared spectra (IR) were recorded on a FT-IR system
using diamond window Dura SamplIR II, and the data are
reported in reciprocal centimeters (cm−1) in the range
4000−600 cm−1. Optical rotations were measured on a
polarimeter at 589 nm. [α] is expressed in deg•cm3•
g−1•dm−1, and c is expressed in g/100 cm3. HRMS were
determined on a TOF mass analyzer coupled with
electrospray ionization (ESI) or atmospheric pressure
chemical ionization (APCI).
4b, 51%
5a, 79%
5b, 71%
(from 2c cond. B) (from 2a cond. C) (from 2f cond. C)
6a, 53%
6b, 47%
7a, 83%
(from 2a cond. D) (from 2f cond. D) (from 2a cond. E)
7b, 81%
(from 2d cond. E)
a Conditions: A: 2 (1 equiv.), H2 (4 bar), Pd(OH)2/C (20
mol%), HCl 1M, i-PrOH, r.t., 18-72h. B: 2 (1 equiv.),
NaBH4 (4.1 equiv.) CoCl2.6H2O (cat.), THF/H2O (2:1),
0°C to r.t., 2-6h. C: 2 (1 equiv.), CuI (2 equiv.), DBU (2
equiv.), Cs2CO3 (0.5 equiv.), CH3NO2/H2O (1:10),
100°C, 90 min. D: 2 (1 equiv.), NaN3 (1.1 equiv.), CuI
(0.2 equiv.), DMF, 100 °C, 18h. E: 1) 2 (1 equiv.),
MeMgBr (6 equiv.), THF, 65°C, 18h; 2) HCl 1M, 65°C,
30 min.
General experimental procedures
General procedure for iodination: To a stirred solution of
peracetylated glycal in dry MeCN (3 mL per 1 mmol of 2-
iodoglycal) at 80°C under argon were added NIS (1.2 eq)
and AgNO3 (0.2 eq) successively and stirred for 2 h. After
consumption of starting material (TLC monitoring), the
reaction mixture was filtrated on Celite®, washed with
EtOAc and concentrated to give a crude product which was
purified by silica gel column chromatography using
indicated system.
Conclusion
General procedure for deacetylation: Peracetylated 2-
iodoglycal was dissolved in methanol (6 mL per 1 mmol of
2-iodoglycal), then K2CO3 was added (0.1 eq). The
resulting mixture was stirred at room temperature for 2
hours. After that time solvent was removed under vacuum.
The crude was purified by flash chromatography using
indicated system.
In summary, nitrile group was successfully
introduced on unprotected 2-iodoglycals via a
palladium-catalyzed process in aqueous media under
mild conditions. D- or L-pyranoside-, D-furanoside-,
and disaccharide- type iodoglycals could be
converted into their cyanated derivatives in good to
4
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10.1002/adsc.201901583
Advanced Synthesis & Catalysis
General procedure for cyanation with product isolation
(C1): 2-Iodoglycal, K4Fe(CN)6*3H2O (0.4 eq), Pd-XPhos-
G3 (0.04 eq), XPhos (0.08 eq), CH3COOK (0.05 eq) were
added to a sealed tube. Then tBuOH (230 µL per 0.1 mmol
of glycal iodide) and H2O (230 µL per 0.1 mmol of 2-
iodoglycal) were added under argon. The resulting mixture
was stirred at 75°C for 18 hours. After completion of the
reaction, solvent was removed under vacuum, the crude
was purified by flash chromatography using indicated
system.
Chem., 2019, 43, 696-699; k) A. Ahmed, N. Hussain,
M. Bhardwaj, A. K. Chhalodia, A. Kumar, D.
Mukherjee, RSC Adv., 2019, 9, 22227-22231; l) M. de
Robichon, A. Bordessa, N. Lubin-Germain, A. Ferry, J.
Org. Chem., 2019, 84, 3328-3339; m) W. Fan, Y. Chen,
Q. Lou, L. Zhuang, Y. Yang, J. Org. Chem., 2018, 83,
6171-6177; n) J. Liu, P. Han, J.-X. Liao, Y.-H. Tu, H.
Zhou, J.-S. Sun, J. Org. Chem., 2019, 84, 9344-9352;
o) A. Shamim, F. B. Souza, S. N. S. Vasconcelos, H. A.
Stefani, Tetrahedron Lett., 2017, 58, 884-888; p) A.
Shamim, C. S. Barbeiro, B. Ali, H. A. Stefani,
ChemistrySelect, 2016, 1, 5653-5659. q) H. A. Esteves,
M. P. Darbem, D. C. Pimenta, H. A. Stefani, Eur. J.
Org. Chem., 2019, 7384-7388.
Procedure for condition screening cyanation with NMR
yield determination (C2): The reaction was performed
according to the procedure C1 starting from 2-iodoglucal
(45 mg, 0.165 mmol). However, after quenching reaction,
the mixture was filtered through a pad of Celite® and
thoroughly washed several times with methanol. Volatiles
were evaporated off then internal standard (DMF) was
added (12.8 µL, 0.165 mmol) to the crude. To determine
[4] a) K. H. Shaughnessy, Molecules, 2015, 20, 9419-
9454; b) F. Zhu, M. J. Rourke, T. Yang, J. Rodriguez,
M. A. Walczak, J. Am. Chem. Soc., 2016, 138, 12049-
12052.
1
the yield analytical signals were integrated on H NMR
[5] V. Di Bussolo, M. Caselli, M. Pineschi, P. Crotti, Org.
Lett. 2003, 5, 2173-2176.
spectrum (7.99 ppm - DMF singlet set as reference which
was compared with product’s 7.29 ppm singlet signal
(proton in anomeric position on the glycal double bond)).
[6] R. H. Hall, A. Jordaan, J. Chem. Soc., Perkin Trans. 1,
1973, 1059-1062.
[7] a) A. M. Nauth, T. Opatz, Org. Biomol. Chem., 2019,
17, 11-23; b) T. Najam, S. S. A. Shah, K. Mehmood, A.
U. Din, S. Rizwan, M. Ashfaq, S. Shaheen, A. Waseem,
Inorg. Chim. Acta, 2018, 469, 408-423; c) G. Yan, Y.
Zhang, J. Wang, Adv. Synth. Catal., 2017, 359, 4068-
4101.
Acknowledgements
This work has benefited from the facilities and expertise of the
Small Molecule Mass Spectrometry platform of ICSN (Centre de
Recherche de Gif - http://www.icsn.cnrs-gif.fr). M.M. and A. F.
thank the Fondation de la Maison de la Chimie for the financial
support.
[8] a) M. Vafaeezadeh, M. Mahmoodi Hashemi, M.
Karbalaie-Reza, Inorg. Chem. Commun., 2016, 72, 86-
90; b) P. Y. Yeung, C. M. So, C. P. Lau, F. Y. Kwong,
Angew. Chem. Int. Ed., 2010, 49, 8918-8922; c) G.
Chen, J. Weng, Z. Zheng, X. Zhu, Y. Cai, J. Cai, Y.
Wan, Eur. J. Org. Chem., 2008, 3524-3528; d) S.
Velmathi, N. E. Leadbeater, Tetrahedron Lett., 2008,
49, 4693-4696; e) G.-Y. Zhang, J.-T. Yu, M.-L. Hu, J.
Cheng, J. Org. Chem., 2013, 78, 2710-2714; f) P. Y.
Yeung, C. M. So, C. P. Lau, F. Y. Kwong, Org. Lett.,
2011, 13, 648-651.
References
[1] a) P. M. Rudd, T. Elliott, P. Cresswell, I. A. Wilson, R.
A. Dwek, Science, 2001, 291, 2370-2376; b) P. H.
Seeberger, D. B. Werz, Nature, 2007, 446, 1046-1051;
c) B. Ernst, J. L. Magnani, Nat. Rev. Drug Discovery,
2009, 8, 661-677; d) H. Liao, J. Ma, H. Yao, X.-W. Liu,
Org. Biomol. Chem., 2018, 16, 1791-1806.
[2] F. Nicotra, Top. Curr. Chem., 1997, 187, 55-83.
[9] T. D. Senecal, W. Shu, S. L. Buchwald, Angew. Chem.
Int. Ed., 2013, 52, 10035-10039.
[3] a) M. A. Rodriguez, O. Boutureira, M. I. Matheu, Y.
Diaz, S. Castillon, P. H. Seeberger, J. Org. Chem.,
2007, 72, 8998-9001; b) A. Shamim, S. N. S.
Vasconcelos, B. Ali, L. S. Madureira, J. Zukerman-
Schpector, H. A. Stefani, Tetrahedron Lett., 2015, 56,
5836-5842; c) N. Hussain, M. Bhardwaj, A. Ahmed, D.
Mukherjee, Org. Lett., 2019, 21, 3034-3037. d) S. Jana,
J. D. Rainier, Org. Lett., 2013, 15, 4426-4429; e) I.
Cobo, M. I. Matheu, S. Castillon, O. Boutureira, B. G.
Davis, Org. Lett., 2012, 14, 1728-1731; f) S. R.
Chemler, U. Iserloh, S. J. Danishefsky, Org. Lett., 2001,
3, 2949-2951; g) S. Dharuman, Y. D. Vankar, Org.
Lett., 2014, 16, 1172-1175; h) R. A. A. Al-Shuaeeb, D.
Montoir, M. Alami, S. Messaoudi, J. Org. Chem.,
2017, 82, 6720-6728; i) A. Bordessa, A. Ferry, N.
Lubin-Germain, J. Org. Chem., 2016, 81, 12459-
12465; j) M. P. Darbem, K. S. Kanno, I. M. de Oliveira,
C. H. A. Esteves, D. C. Pimenta, H. A. Stefani, New J.
[10] D. R. Mootoo, P. Konradsson, U. Udodong, B. O.
Fraser-Reid, J. Am. Chem. Soc., 1988, 110, 5583-5584.
[11] A. S. Brat, J. Gervay-Hague, Org. Lett., 2001, 3,
2081-2084.
[12] J. Kuwabara, Y. Sawada, M. Yoshimatsu, Synlett.,
2018, 29, 2061-2065.
[13] S. Vorona, T. Artamonova, Y. Zevatskii, L. Myznikov,
Synthesis, 2014, 46, 781-786.
[14] N. E. S. Guisot, I. E. Obame, P. Ireddy, A. Nourry, C.
Saluzzo, G. Dujardin, D. Dubreuil, M. Pipelier, S.
Guillarme, J. Org. Chem., 2016, 81, 2364-2371.
[15] N. C. Bruno, M. T. Tudge, S. T. Buchwald, Chem. Sci,
2013, 4, 916-920
5
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10.1002/adsc.201901583
Advanced Synthesis & Catalysis
FULL PAPER
Mild Palladium-Catalyzed Cyanation of
Unprotected 2-Iodoglycals in Aqueous Media as
Versatile Tool to Access Diverse C2-
Glycoanalogues.
Adv. Synth. Catal. Year, Volume, Page – Page
Maciej Malinowski, Thanh Van Tran, Morgane de
Robichon, Nadège Lubin-Germain* and Angélique
Ferry*
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