Novel Carbazole-Based N-Heterocyclic Carbene Ligands to Access Synthetically Relevant Stilbenes in Pd-Catalyzed Coupling Processes

Article abstract of DOI:10.1002/asia.201900419

A series of new carbazole-based N-heterocyclic carbene (NHC) ligands have been synthesized in a simple and facile synthetic route and subsequently used in a Pd/carbazole-based NHC catalytic system, which was found to be effective in catalyzing Heck reactions to provide substituted stilbene derivatives in good yields. Several bioactive stilbenes, including pterostilbene, pinosylvin, trimethoxy resveratrol, and resveratrol, were synthesized in good yields, and a 10 mmol scale-up was also performed for trimethoxy resveratrol. The synthetic application was also extended by performing a double-tandem chemoselective Heck reaction followed by Miyaura borylation in a one-pot procedure to give single-step access to synthetically useful stilbenyl boronate esters. Similarly, a unique triple-tandem protocol of a chemoselective Heck reaction/Miyaura borylation/Suzuki–Miyaura coupling reaction sequence was performed for the one-pot modification of biologically relevant molecules.

Full text of DOI:10.1002/asia.201900419

CHEMISTRY
AN ASIAN JOURNAL
www.chemasianj.org
Accepted Article
Title: Novel Carbazole-based N-Heterocyclic Carbene Ligands for
Accessing Synthetically Relevant Stilbenes via Pd-Catalyzed
Coupling Processes
Authors: anant kapdi and Tejpal Ramsingh Girase
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10.1002/asia.201900419
Chemistry - An Asian Journal
FULL PAPER
Novel Carbazole-based N-Heterocyclic Carbene Ligands for
Accessing Synthetically Relevant Stilbenes via Pd-Catalyzed
Coupling Processes
Tejpalsingh Ramsingh Girase,[a] and Anant R. Kapdi*[a]
Abstract: A series of new carbazole-based N-heterocyclic
carbene ligands have been synthesized via a simple and facile
synthetic route. Subsequent employment of the Pd/carbazole-
based NHC catalytic system was found to be effective in
efficiently catalyzing Heck reaction providing substituted stilbene
derivatives in good yields. Several bioactive stilbenes such as
pterostilbene, pinosylvin, trimethoxy resveratrol and resveratrol
were synthesized in good yields with a 10 mmol scale-up also
performed for trimethoxy resveratrol. The synthetic application
considerable synthetic potential4. In recent years, synthesis of
organoboron compounds has been accomplished by the
employment of transition-metal-catalyzed5 reactions to
overcome the barrier of the traditional synthetic methods such
as lithiation,6 reaction with Grignard reagent7.
was also extended by performing
a
double tandem
chemoselective Heck reaction followed by Miyaura borylation in
a one-pot procedure to provide a single step access to the
synthetically useful stilbenyl boronate esters. Similarly, a unique
triple tandem protocol involving chemoselective Heck
reaction/Miyaura borylation/Suzuki-Miyaura coupling reaction
sequence was performed for the one-pot modification of
biologically relevant molecules.
Figure 1: Examples of naturally occurring bioactive stilbenes.
Introduction
Amongst the transition metals, palladium has its own pivotal role
in organic synthesis from a past few decades with exceptional
(remarkable) functional group tolerance, milder reaction
conditions and its ability to activate a wide variety of bonds such
as C─X (Cl. Br, I, OTs), C─H, C─B, C─Sn.8 The potential of
palladium towards catalyzing most difficult organic synthetic
reactions immensely increases in combination with electron-rich
ligand such as phosphine, N-heterocyclic carbenes, which have
better ability to co-ordinate to metal. This property increases the
electron density at palladium center so as it can activate the
toughest bond9. From this perspective synthesis and
development of electron-rich ligands is of tremendous interest to
researchers due to their activating property. This fulfillment of
ligand has been accomplished by the phosphines and NHC’s
ligand, due to which researchers are attracted towards the
synthesis of new ligand system based on phosphine and NHCs.
Phosphines are electron-rich ligands providing an opportunity to
fine tune the steric and electronic properties promoted its
dominance over the other ligand system, but their sensitivity
towards the moisture and oxygen, storage and handling
Functionalized stilbene derivatives are an important class of
compounds with
a
wide variety of biological and
pharmacological activity1. These are naturally occurring
compounds mainly found in plants (phytoalexins), for instance
pinosylvin, resveratrol (commercial drug molecule), trimethoxy-
resveratrol (3M-Res), piceatannol, pterostilbene having
extensive biological activity ranging from anticancer, anti-
oxidants, neuroprotective, anti-diabetic, antifungal, anti-
inflammatory, anti-cardiac, antibacterial to antimalarial activity1,2
(fig 1). Besides these applications, stilbenoids with borane
functionalized derivatives also have exhibited enormous
applications in synthesis such as coupling reactions, OLEDs,
chemo-sensing, material science and are of pharmacological
importance3. It is therefore mandatory to investigate the
possibility of developing a synthetically elegant protocol for the
synthesis of these molecules. Brown, Matteson, Suzuki, and
Miyaura have made revolutionary contributions towards new
types of organoboron compounds, and have developed ways to
synthesize them and such an exploration has found
difficulties restricted their applicability in catalytic processes9,10
.
However, NHCs overcome the problems associated with
phosphines ligand, while their strong sigma electron donating
ability permits the efficient activation of an inert bond.11 NHCs
have provided greater modular flexibility over steric, electronic
properties and ease of synthesis. Because of these qualities
NHCs have been extensively exploited by many research
groups such as Kuhn, Hermann, Nolan, Organ8-10 etc.
[a]
T. R. Girase, Dr. A. R. Kapdi
Department of Chemistry,
Institute of Chemical Technology
Nathalal Parekh Marg Road, Matunga, Mumbai (400019).
Email id : ar.kapdi@ictmumbai.edu.in*
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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One of the areas where NHCs could play an important role
would be towards the synthesis of stilbene-based boronate
esters that have exhibited promising biological activity. In recent
years, these substrates have been prepared by using the
traditional and multistep method, for instance, Bhaskar et al. and
Ronald et al. synthesized the boronate ester by transition-metal-
catalyzed reaction followed by Wittig reaction12. But yield
obtained in most of these processes was moderate and involved
harsh reaction conditions, tedious work-up procedures while the
multistep synthetic protocol led to a large amount of homo-
coupling and deborylation. Therefore in continuation with our
endevour of providing sustainable catalytic solutions13 we report
herein the synthesis and application of a series of N-substituted
carbazole based N-heterocyclic carbene ligands, that can be
exploited towards the synthesis of stilbene based boronate ester.
For overcoming the multistep aspects and drawbacks of Wittig
reaction, the synthetic protocol reported in this manuscript is
synthetically elegant providing boronate esters via in-situ
palladium-carbazole based NHC ligand-catalyzed one-pot
sequential Heck reaction followed by Miyaura borylation towards
the aspects of sustainable chemistry i.e., step & atom economy
(scheme 1). A unique triple tandem protocol has also been
accomplished providing highly functionalized nucleoside-based
compounds via a one-pot sequential Heck reaction/Miyaura
borylation/Suzuki-Miyaura coupling of 5-iodo-2'-deoxyuridine.
75% yield.14 In the second step, carbazole was deprotonated by
potassium hydroxide with the resultant anion allowed to react
with epichlorohydrin thus yielding the epoxide derivatized motif
A and B in 75-78 % (Scheme 2)15. These derivatized motifs of
carbazole A & B were further reacted with imidazole and
benzaimidazole to furnish the corresponding products C-F
respectively, in 70-74 % yields (scheme 2). Further, molecules
C-F were condensed with benzyl bromide in acetone under
refluxing condition for 12 h resulting into the formation of
imidazolium salts L1-L4, respectively.
Scheme 1: a) Previous reports b) This work
Results and Discussion
At the outset of our studies, the synthesis of novel carbazole-
based series of N-heterocyclic carbene precursors L1, L2,L3, L4,
L5, L6, L7, and L8 was carried out in 3 to 4 steps providing
moderate to high yields of the NHC salts. The first step of
synthesis of the ligands involved the chlorination of carbazole
particularly in the case of ligands L3, L4, L6, and L7. In common
cases, the chlorination of carbazole with N-chlorosuccinimide
(NCS) suffers from selectivity issues giving multiple spots on
related to the formation of mono, di and traces of tri chlorinated
products that are difficult to separate by column chromatography
technique. However, when sulfuryl chloride was used for the
chlorination of carbazole by following the reported procedure by
Jurczak and co-workers afforded 3,6-dichlorocarbazole in 72-
Scheme 2 : Synthesis of novel carbazole-based NHC ligands.
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Similarly, when molecules C-F were condensed with 9-
(chloromethyl) anthracene in toluene at 125 oC for 24 h provided
the NHC salts L5-L7 in moderate to excellent yields. For the
assessment of the effect of change in anionic counterpart on the
properties and catalytic activity of the synthesized ligands, a
simple anion exchange reaction was performed on the NHC
salts. The reaction was performed with ligands L1 using sodium
tetraflouroborate in methanol at room temperature resulting in
the formation of a crystalline salt of NHC-tetrafluoroborate L8 in
excellent yield (Scheme 2)16. These imidazolium salts (L1-L8)
were further characterized by standard spectroscopic techniques.
The formation of imidazolium salts was confirmed from the 1H
and 13C NMR spectras providing the characteristics peaks for N-
CH-N as shown in Table 1. The influence of the substituent at
3,6 position of carbazole and nitrogen centre of imidazolium
showed remarkable variation in 1H and 13C δ values. Benzyl
substituent based imidazolium salts exhibit higher δ value
compared to those obtained from 9-(chloromethyl) anthracene-
based salts.
salts L6, led to the desired product in 82-83% in isolated yield at
1.0 mol% catalyst loading in 24 h (Table 2, entries no. 3, 4 & 5).
Since the in situ generated catalytic system provided good
reactivity in the Heck cross-coupling reaction, using Pd(OAc)2 as
the precursor, further optimization of the remaining NHC salts
was carried out.
Table 2. Optimization of the reaction conditions for Heck
reactiona
Sr.No.
Catalyst
(mol %)
Ligand
(mol %)
Base
(2 eq.)
Yieldb
(%)
Pd precursor screening
1
2
3
PdCl2
Pd(OAc)2
PdCl2
-
-
L6
L6
L6
L6
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
<5c
<5c
82
83
82
83
4
5
6d
Pd(OAc)2
Pd2(dba)3
Pd(OAc)2
Table 1: NMR comparison for N-CH-N Chemical shift for NHC
Ligand
Benzyl based NHC-
ligand
1H-δ value for N-CH-N
L1
L2
9.92
143.1
L5
L3
9.30
139.5
L6
L4
9.86
143.6
L7
L8a
9.27
Ligand screening
7d
L1
L2
L3
L4
L5
L6
L7
L8
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
82
80
82
80
82
83
81
83
59
73
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
9.26
140.5
8d
9d
13C- δ value for N-CH-N
140.5
10d
11d
12d
13d
14d
15d
16d
9-methylanthracene
based NHC-ligand
1H-δ value for N-CH-N
9.00
8.99
8.91
13C-δ value for N-CH-N
141.8
139.5
140.7
IMes.HCl
IPr.HCl
Based on the study reported by Hunuyh and co-workers17 for the
13C NMR spectroscopic determination of donor strength of NHC
ligands, increase in the chemical shift observed in 13C NMR for
different ligands the donor capacity of the respective ligands was
predicted to increase and a similar trend could be observed in
the case of the carbazole-derived NHC salts L1 to L7. Largest
shift could be observed for ligands L2 and L4 suggesting better
donor possibility from these ligands. Accordingly, donor strength
for various ligands could be written in the following increasing
order as L4 > L2 > L5 > L7 > L1~L8 > L3~L6. Although,
analysis of the catalytic activity would determine whether the
donation capacity of ligands has any rate enhancing effect.
Base screening
17d
18d
19d
20d
Et3N
CH3COOK
K3PO4
83
25
80
62
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
L6
L6
L6
L6
K2CO3
Catalyst loading studies
Pd(OAc)2 (1.0)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.1)
Pd(OAc)2 (0.1)
Pd(OAc)2 (0.1)
Pd(OAc)2 (0.1)
L6
L6
L6
L6
L6
L6
21
22
23
24e
25f
26g
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
83
83
60
71
78
84
aReaction condition: aryl iodide (0.5 mmol), styrene (1 mmol), Pd
Application of in-situ generated Palladium-NHC complexes
towards Heck-Borylation reaction.
a) Heck alkenylation
precursor
yields
(1 mol%), base (2 eq.), solvent (1 mL), bIsolated
using column chromatography. of
c<10%
hydrodehalogenated product observed along with only <5%
With the aim of developing an efficient protocol for obtaining
stilbene-based boronate esters, we envisaged the analysis of
the synthesized NHC salts as ligands in palladium-catalyzed
Heck coupling reaction18 of aryl iodide with styrene. Initial
studies revealed, palladium precursor such as Pd(OAc)2, PdCl2
without the addition of activating ligands were found to be
ineffective in carrying out the Heck reaction under the mentioned
conditions in Table 2. Furthermore this reaction carried out with
Pd(OAc)2, PdCl2 and Pd2(dba)2 in combination with imidazolium
d
product formation and rest is starting material, 1.5 eq. styrene
f
used, eReaction carried out at 100oC, Reaction carried out at
120 oC, gReaction carried out at 0.2 mol% of ligand loading.
When the reaction was carried out using different imidazolium
salts L1 to L8 in combination with Pd(OAc)2 at 1.0 mol% loading
at 1.5 equiv. of styrene in acetonitrile as solvent, leading to the
desired product in 80-83% isolated yield. Since, the entries no.7
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to 14 suggested that there is no appreciable change in the final
output of the reaction, indicated that electronic influence of the
ligand system doesn`t play any crucial role on the outcome of
the reaction. Hence, from Table 2, Pd(OAc)2 in combination with
ligand L6 was chosen as the most effective catalytic system for
further optimization study (ease of synthesis was also one of the
factors). Commercially available NHC ligands, Imes.HCl and
Ipr.HCl were also tested under the given set of conditions.
Although, IPr.HCl furnished better yield of the product than its
Imes.HCl counterpart, in comparison to the synthesized NHC
salt L6 the catalytic activity was found to be lower. In case of
base screening studies, Et3N proved to be most effective base
over CH3COOK and K2CO3, but the reactivity of K3PO4 and Et3N
were found to be comparable, giving 80% and 83% yield of
product, respectively (entries no.15, 17 Table 2). Furthermore,
catalyst loading was also performed with 1.0 mol% (TON = 83),
0.5 mol% (TON = 415), and 0.1 mol% (TON = 6000) of
Pd(OAc)2 in combination with L6 was investigated. Although, 0.1
mol% at 80 oC provided lower yield of the product, increasing the
temperature to 120 oC resulted into competitive yield suggesting
that 0.1 mol% (TON = 8400) is effective in efficiently catalyzing
Heck reaction at such reduced Pd concentration.
catalytic activity observed (Scheme 3). Uniqueness of the
developed protocol is highlighted via the excellent
chemoselectivity observed for the activation of C─I bond in
preference to C─Br bond in examples such as 1a and 1f. Such a
strategy could prove to be potentially useful towards the
development of tandem catalytic protocols and will be discussed
in further sections.
b) Application of Heck reaction towards the Synthesis of
drug molecule.
Stilbene derivatives are an important class of compounds with
wide occurrence in natural sources having potential biological
applications such as cytotoxicity, anti-obesity, antioxidant19. The
developed Heck coupling protocol was therefore expanded
towards the synthesis of some naturally occurring and
pharmaceutically important stilbene derivatives such as
pterostilbene, pinosylvin, trimethoxy-resveratrol, and DMU
providing the respective product in yields ranging from 64% to
70% in two steps involving palladium-catalyzed Heck coupling
followed by demethylation using BBr3 in CH2Cl2 (Scheme 4).
Most of the catalytic systems described in literature suffer from
higher catalyst loadings and temperature in excess of 100 °C.18
In this regards, the Pd/NHC catalytic system presented in this
manuscript allows the synthesis of stilbene derivatives in good to
excellent yields at lower catalyst loading and at relatively lower
temperature.
We next proceeded to utilise the optimized reaction conditions
towards the synthesis of various stilbene derivatives. As
summarized in scheme 3, a variety of styrene derivatives were
employed as a coupling partner with 4-iodoanisole, furnishing
the desired products in good to excellent yields.
Scheme 4 : Synthesis of bio-active stilbene derivatives.
c) Tandem One-Pot Sequential Protocol: Synthesis of
Stilbene-boronate esters
Taking into consideration the potential applications of stilbene-
based derivatives in synthesis and medicinal chemistry, we
envisaged that the modification of stilbene derivatives would
help further enhance the synthetic utility of these molecules.
With this is in mind, we proceeded with our investigation towards
the development of a sustainable protocol for synthesizing
stilbene-based boronate esters (also called as the analogue of
polyphenol). The chemoselective Heck coupling involving the
preferential activation of C─I bond over C─Br could now be
envisaged as an important strategy for the installation of the
Scheme 3: Substrate scope for stilbene derivative synthesis
using Heck alkenylation reaction with Pd/NHC catalytic system.
The developed protocol was found to be tolerant to the presence
of electron donating, electron withdrawing and bulkier
substituents, giving yields ranging from 64% to 84% except for
3-nitro styrene . The electronic effect of substituents present on
the aryl iodide was also evaluated by altering the substituent
such as CN, Br, and NO2 with no appreciable difference in
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boronate ester via the subsequent activation of C─Br bond
under the Miyaura borylation conditions5a. Such a procedure
could help circumvent the problems associated with multi-step
synthesis followed by Bhaskar and Ronald in a recent report.11
Tandem catalytic reactions in the recent years have emerged as
an important tool providing a sustainable solution for the
The final optimized conditions for the one-pot tandem therefore
involved the first step catalyzed by Pd(OAc)2 (0.1 mol%) in
combination with ligand L6 (0.2 mol%) and Et3N (2 equiv.) as
base in acetonitrile at 120 oC, while for the Miyaura borylation
step a catalyst combination of Pd(OAc)2 (3.0 mol%) and X-phos
o
(6.0 mol%) with K2CO3 (2 equiv.) as base at 80 C was found to
formation of multiple C─C or C─X bonds in
a
one-pot
offer the desired product in good to excellent yield. We next
explored this active catalytic system towards the synthesis of
various stilbene-based boronate esters. Performance of this
catalytic system investigated towards the substrate containing
procedure.20 Such
a
synthetic strategy provides multiple
advantages over the challenging multi-step synthesis including
low solvent usage, better yields and removal of tedious isolation
procedures. For the incorporation of the boronate ester in a
tandem catalytic procedure could therefore be made possible by
combining the chemoselective Heck coupling with Miyaura
borylation. Screening of reaction conditions for the installation of
boronate ester on the stilbene moiety using bispinacaloto boron
(1.5eq.) was performed in a tandem fashion with Heck reaction
(See supporting information for screening studies). It was
observed that for the activation of C─Br bond on the stilbene
structural motif as a part of the boronate ester installation,
catalytically more active system (combination of Pd(OAc)2 with
X-Phos and K2CO3 as the base) provided optimum results.
t
ethoxy, methoxy, butyl, chloro, methyl functional groups at para
and meta position of aromatic ring furnished the desired product
in 50% to 76% in yields (Scheme 5). The presence of a labile
acetoxy group, however was found to dissociate under the given
set of conditions, although providing the stilbene-boronate
product in decent yield (3h, Scheme 5). Several other
substituted boronate esters with different aryl and naphthyl units
were thus prepared (3i-n, Scheme 5).
Successful demonstration of the tandem one-pot procedure for
the installation of boronate ester provided us with the required
impetus to explore the possiblity of extending this methodology
towards the modification of nucleosides21. Limitations on the part
of the basic set of nucleosides in terms of poor absorbance
values and low applicability has allowed researchers to explore
the possibility of modifying nucleosides using a wide variety of
synthetic methods including transition metal-catalyzed coupling
processes.22 In recent years, tandem catalytic processes has
emerged as a promising alternative to multi-step synthesis for
obtained highly derivatized nucleosides with promising biological
activity.23 To this perspective, we envisaged the installation of
stilbene derivative on the nucleoside backbone to create a
library of modified nucleosides with improved biological and
photophyscial activities.24
Scheme 5. One-pot sequential chemoselective Heck/Miyaura
borylation tandem protocol for the synthesis of stilbene-based
boronate esters.
Scheme 6: Triple Tandem Heck/Miyaura borylation/Suzuki-
Miyuara reaction.
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An unprecedented triple tandem one-pot sequential protocol
Furthermore, to ascertain the involvement of Pd nanoparticles
the catalytic solution was directly subjected to HR-TEM (high
resolution transmission electron microscope) analysis. This was
performed by subjecting the catalytic solution or reaction mass
to HR-TEM analysis after completion of reaction between
iodoanisole and styrene (Scheme 7) by simple deposition of the
reaction mass on carbon coated Cu grid. Presence of Pd
nanoparticles were found to be present in the reaction mass with
sizes ranging from 2 nm to 5 nm.
To ascertain the role of NHC ligand in catalytic system and to
investigate whether it co-ordinates to Pd nanoparticle or first is
preceeded by complexation to form an in-situ Pd-NHC complex
that could later undergo degradation to form NHC-stabilized
nanoparticles, we analyzed the reaction mass (containing
Pd(OAc)2 and NHC ligand L6) on HRMS. HRMS analysis
provided further evidence of a possible formation of Pd(NHC)2 at
involving
borylation/Suzuki-Miyuara
a
chemoselective
Heck
reaction/Miyaura
sequence was
cross-coupling
investigated (Scheme 6). Keeping this in mind, we successfully
performed the triple tandem protocol albeit in poor yields.
Mechanistic studies :
The given catalytic system was found to be most effective
towards the Heck cross coupling reaction, but it is also important
to investigate the pathway of reaction i.e. whether homogeneous
or heterogeneous pathways.24 To investigate the possiblity of
either of the pathways operating under the given set of
conditions, we performed the mercury drop test and CS2
poisoningtests, which are considered as highly reliable tools for
the inspection of the type catalytic pathways26. Hg drop and CS2
tests were both found to inhibit the catalytic activity bringing
about a drastic reduction in the product yield to 5% & 9%,
respectively (Scheme 7). These results suggest the possibility
that the catalytic reaction could be following a heterogeneous
pathway with the formation of NHC-stabilized Pd-nanoparticles,
that are known to be active species in catalytic reactions27. One
of the reason for the formation of Pd nanoparticles would be the
size of the NHC ligand that would prefer to dissociate under the
catalytic conditions which would help enhance the reactivity of
the developed catalytic system.
m/z
=
1206.1676 while other peaks corresponding to
[Pd(NHC)2Na2]2+ at m/z = 1252.1699 and [Pd(NHC)2ClNa2]2+at
m/z = 1287.0914, respectively were also detected (Figure 3).
The possible formation of the nanopartcles could therefore be
taking place under the catalytic conditions and to verify this
assumption we envisaged to carry out recycling studies of the
catalytic material, which could be isolated at the end of the first
catalytic reaction.
Recycling studies were performed by the isolation of the
catalytic material at the end of the first parent cycle,
subsequently adding new batch of substrate for continuing the
studies (Scheme 8). It was observed that the recycling ability of
the isolated material was limited as possible aggregation of the
NHC-stabilized nanoparticles might be happening leading to
reduced catalytic activity even after the first recycle.
Additive
Hg test
CS2 test
-
Yield (%)
5
9
84
Scheme 7: Catalyst poisoning study for the presence of
heterogeneous or nanoparticular pathway.
Recycle
Parent cycle
<99
1st recycle
90
2nd recycle
50
%Conversion
Scheme 8: Recycling studies for Heck alkenylation reaction.
Conclusion:
In conclusion, series of novel N-substituted carbazole-based
NHC ligands were synthesized and characterized by standard
characterization technique. The investigation of the catalytic
performance of synthesized ligand in combination with Pd
precursor was successfully attempted towards the development
of chemo-selective double tandem Heck-Borylation protocol for
obtaining stilbene-based boronate esters using readily available
simple starting material, 1,4-iodobromobenzene, styrene’s,
bispinacaloto borane in good to excellent yields. Finally, the
modification of biologically important nucleosides (5-iodo-2'-
deoxyuridine) was carried out by the installation of the stilbene
derivatives at 5 positions of nucleoside via an unprecedented
one-pot chemoselective Heck/Miyaura borylation/Suzuki-
Miyuara triple tandem reaction sequence. Mechanistic studies
Figure 2: HR-TEM analysis of catalytic solution.
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were also performed to ascertain the presence of active
molecular species, which was investigated and confirmed by the
catalyst poisoning tests (Hg drop, CS2 test) along with HR-TEM
analysis of the catalytic reaction mass.
(No. EMR/2016/005439). We also thank the University
Grants Commission for BSR fellowship given to TSG
.
Keywords: Carbazole, N-Heterocyclic ligand, Tandem protocol,
Heck-Borylation reaction
Aknowledgements
ARK acknowledges ‘The Alexander von Humboldt
Foundation’ for the equipment grant to ARK. ARK also
would like to thank DST SERB for providing research grant
Figure 3: HRMS analysis of reaction mixture for the detection of Pd species in solution.
Sirerol, M. L. Rodríguez, S. Mena, M. A. Asensi, J. M. Estrela,
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