Dendritic bis- and tetrakis-iminodiacetic acid-boronate complexes in one-pot cross-coupling reactions

Article abstract of DOI:10.1016/j.jorganchem.2016.06.030

Iminodiacetic acids are versatile metal chelating ligands. We herein undertook a study of dendritic bis- and tetrakis-iminodiacetic acids functionalized at the peripheries of branched core moieties. The dendritic iminodiacetic acids are synthesized by O- and N-alkylations of chosen alcohol and amine reactive sites emanating from a branched core. In order to identify the reactivities of such dendritic iminodiacetic acids, chelation with arylboronates is conducted. An assessment of the hydrolysis under aq. basic condition shows that dendritic boronates hydrolyze to boronic acid significantly slower than monomeric boronates. Slower hydrolysis of dendritic boronates is taken advantage, in order to conduct competitive [Formula presented] bond-forming Suzuki-Miyaura cross-coupling reactions. Teraryl synthesis is performed using monomeric and dendritic boronates. The iterative, multiple aryl-aryl bond formation is conducted subsequently, so as to prepare tetraaryls, through consecutive reactions of chosen boronic acid, monomeric boronate, dendritic boronate and aryl bromide, in one-pot. The study shows that slower hydrolysis of dendritic boronate is valuable in order to conduct multiple consecutive aryl-aryl bond formation.

Full text of DOI:10.1016/j.jorganchem.2016.06.030

Journal of Organometallic Chemistry 819 (2016) 138e146
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Dendritic bis- and tetrakis-iminodiacetic acid-boronate complexes in
one-pot cross-coupling reactions
Anindra Sharma, Prabhat Kumar, Rita Pal, Narayanaswamy Jayaraman*
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Iminodiacetic acids are versatile metal chelating ligands. We herein undertook a study of dendritic bis-
and tetrakis-iminodiacetic acids functionalized at the peripheries of branched core moieties. The den-
dritic iminodiacetic acids are synthesized by O- and N-alkylations of chosen alcohol and amine reactive
sites emanating from a branched core. In order to identify the reactivities of such dendritic iminodiacetic
acids, chelation with arylboronates is conducted. An assessment of the hydrolysis under aq. basic con-
dition shows that dendritic boronates hydrolyze to boronic acid significantly slower than monomeric
boronates. Slower hydrolysis of dendritic boronates is taken advantage, in order to conduct competitive
CeC bond-forming Suzuki-Miyaura cross-coupling reactions. Teraryl synthesis is performed using
monomeric and dendritic boronates. The iterative, multiple aryl-aryl bond formation is conducted
subsequently, so as to prepare tetraaryls, through consecutive reactions of chosen boronic acid, mono-
meric boronate, dendritic boronate and aryl bromide, in one-pot. The study shows that slower hydrolysis
of dendritic boronate is valuable in order to conduct multiple consecutive aryl-aryl bond formation.
© 2016 Elsevier B.V. All rights reserved.
Received 9 March 2016
Received in revised form
20 May 2016
Accepted 24 June 2016
Available online 25 June 2016
Keywords:
Boronates
Cross-coupling reactions
Dendrimers
Hydrolysis
Iminodiacetic acid
Suzuki-Miyaura reaction
1. Introduction
poly(propylene imine) series by Meijer [11] and phosphorus den-
drimer series by Caminade and Majoral [12] established a new di-
Iminodiacetic acid is a versatile chelating ligand for metal ions,
aided by additional coordination of the imine moiety of the ligand
with the metal ions [1e4]. Ethylenediamine tetraacetic acid is a
prime example of the versatility of this ligand to metal ion coor-
dination [5]. Iminodiacetic acid is a valuable ligand for organome-
tallic reactions, for example, the value of this ligand in boronate
complex formation and subsequent slow release to boronic acid
from the complex in Suzuki-Miyaura cross-coupling reactions has
been exploited elegantly by Burke and co-workers [6], as a strategy
to mitigate a major undesired homocoupling of boronic acids in the
cross-coupling reactions. With innumerable occasions in which
iminodiacetic acid ligands are involved, we undertook a study in
which this ligand is installed multiply in a dendritic fashion. Den-
dritic structures are characterized by the presence of building
blocks arranged symmetrically around a core atom or moiety.
Seminal early reports on the synthesis of cascade molecules by
rection to the synthesis and studies of highly branched molecules.
Ever since these reports, interest in highly branched and mono-
dispersed macromolecules is established thoroughly in multiple
directions of studies [13e16], including stabilization of metal cat-
alysts by dendritic ligands [17,18]. With the advancements in den-
dritic structures, we undertook an effort to study the iminodiacetic
acid ligand when arranged in a branched fashion. Dendritic imi-
nodiacetic acids were synthesized, following which, the benefits of
the newly formed dendritic iminodiacetic acids were assessed
through formation of boronate ester complexes. The dendritic
boronates were utilized subsequently in Suzuki-Miyaura iterative
cross-coupling reaction, so as to form ter- and tetraaryls in one-pot.
Synthesis and studies of new dendritic iminodiacetic acids and
their boronate complexes in the cross-coupling reactions are re-
ported herein.
€
Vogtle [7], poly(amidoamine) series by Tomalia [8], arborals by
2. Results and discussion
ꢀ
Newkome [9], poly(benzyl ether) series by Frechet [10],
2.1. Synthesis bis- and tetrakis-iminodiacetic acids
Molecular structures of the target bis- (1) and tetrakis-imino-
diacetic acids (2) containing branched dendritic structures are
* Corresponding author.
E-mail address: jayaraman@orgchem.iisc.ernet.in (N. Jayaraman).
http://dx.doi.org/10.1016/j.jorganchem.2016.06.030
0022-328X/© 2016 Elsevier B.V. All rights reserved.

A. Sharma et al. / Journal of Organometallic Chemistry 819 (2016) 138e146
139
shown in Fig. 1. These dendritic iminodiacetic acids were synthe-
sized, from commercially available monomer building blocks,
namely, bromoethyl acetate and bromoacetonitrile.
spectrometry in each case. Fig. 2 provides overlay spectra of the
conversion of tetrakis-ester 4 to octakis-ester 8, involving tetrakis-
alcohol 5 and tetrakis-nitrile 6 intermediates.
Synthesis of zero generation 1 and first generation 2 dendrimers
was initiated using 2,20-diaminoethyl ether (3) as the core, by as
divergent assembly method. Thus, iterative reactions of O- and N-
alkylations and functional group reductions, in a multistep syn-
thetic sequence, were utilized to prepare 1 and 2 (Scheme 1). The
diamine derivative 3, in turn, was prepared by subjecting dieth-
ylene glycol to bis-O-tosylation, reaction of the resulting bis-O-
tosylate with NaN3 and reduction of the resulting bis-azide to bis-
amine 3. Reaction of 3 with ethyl bromoacetate afforded tetrakis-
ester 4, in 90% yield. Tetrakis-ester derivative 4 was subjected to
reduction in the presence of LiAlH4 in THF to the corresponding
tetrakis-alcohol 5, in a nearly quantitative yield (Scheme 1).
2.2. Studies of boronate complexes of 1 and 2
Following synthesis of bis- (1) and tetrakis-iminodiacetic acids
(2), their complexation with boronic acid and subsequent reactions
of boronates were investigated. Iminodiacetic acid forms the cor-
responding boronate upon reaction with a boronic acid. Additional
coordination of imine moiety to boron centre in the boronate
complex provides stability to the complex, and thus, iminodiacetic
acid boronate complexes are considered orthogonal to the reac-
tivity of boronic acids. Facile hydrolysis of iminodiacetic acid-
boronate complex releases the reactive boronic acid. Such a sta-
bility of a boronate and its lability under hydrolytic condition to
form boronic acid is exploited elegantly in the particular class of
boronic acid mediated reactions, namely, the Suzuki-Miyaura
cross-coupling reactions [19e21]. The boronate mediated Suzuki-
Miyaura cross-coupling reactions are developed immensely in or-
der to overcome pertinent difficulties of protodeboronation,
oxidation and homocoupling competing reactions [22], as
demonstrated by Lloyd-Jones and co-workers. Important to sus-
tained developments in Suzuki-Miyaura CeC bond forming re-
actions are: (i) the discovery of ‘slow-release’ methodology, in
which the reactive boronic acid is generated in situ through
controlled basic hydrolysis of a boronate ester, developed by Burke
and co-workers [23e26]; (ii) the development of 1,8-
diaminonaphthalene as the protecting group of boronic acids, the
deprotection to the reactive boronic acid implemented through an
acid treatment, reported by Suginome and co-workers [27,28] and
(iii) the development of organotrifluoroborate as a robust surrogate
of boronic acid, which hydrolyzes in protic media to generate the
boronic acid [29e32]. We followed these developments in order to
identify the reactivities of dendritic bis- and tetrakis-iminodiacetic
acids.
The progress of reduction of ester functionalities in 4 was
monitored by the disappearance of stretching frequency at
1741 cmꢀ1 in the IR spectrum. Upon completion of the reaction,
tetrakis-alcohol 5 was isolated from inorganic salts through differ-
ential solubilisation in MeOH and in CHCl3. Tetrakis-alcohol 5 was
reacted subsequently with bromoacetonitrile in THF:DMF (1:1), in
the presence of NaH, under reflux. The resulting reaction mixture
was purified (SiO2) to afford tetrakis-nitrile 6, in 56% yield. Tetrakis-
nitrile 6 was reduced to tetrakis-amine 7, using Raney-Co catalyst
and H2 (50 atm), in a nearly quantitative yield. The progress of the
nitrile reduction in 6 to amine was monitored by the disappearance
stretching frequency at ~2209 cmꢀ1 in the IR spectrum. The itera-
tive reaction of N-alkylation of tetrakis-amine 7 with ethyl bro-
moacetate and purification of the reaction mixture (SiO2, CH2Cl2/
MeOH linear gradient) afforded octakis-ester 8, in 48% yield
(Scheme 1). The newly-formed tetrakis- (4) and octakis- (8) esters
were hydrolysed under aq. alkaline conditions to afford the corre-
sponding tetrakis- and octakis-acids 1 and 2, respectively, in
quantitative yields. The structural homogeneities of the bis- (1) and
tetrakis- (2) iminodiacetic acids were verified by physical methods.
Changes in the chemical shifts of the eCH2- group adjacent to the
peripheral functionality were observed periodically. Thus, disap-
pearance of the singlet at ~3.59 ppm of eCH2CO2Et group and
appearance of resonances at ~2.56 and ~3.64 ppm, corresponding
to eCH2CH2OH, were observed, consistent with the presence of
these functional groups. Similarly, disappearance of the signal at
4.29 ppm of eCH2CN and appearance of resonances at ~3.45 and
~2.74 ppm of eCH2CH2NH2 were observed for the nitrile to amine
reaction. Functional group changes at the peripheries were also
confirmed by 13C NMR spectroscopy. Disappearance of eCN reso-
nance at ~116 ppm and the appearance of carbonyl group resonance
of the ester functionality at ~171 ppm confirmed complete con-
version of nitrile to amine. Similarly, reduction of ester to alcohol
led to the appearance of a signal at ~62 ppm (eCH2OH). The con-
stitutions of the dendrimers were confirmed further by mass
Syntheses of bis- and tetrakis-boronates 9 and 10 were con-
ducted upon reaction of arylboronic acids with dendritic iminodi-
acetic acids 1 and 2 in DMF or DMSO-PhMe (1:5) for ~24e48 h, with
azeotropic removal of water from the reaction mixture (Scheme 2)
[33].
The formation of the phenyl bis-boronate ester (9a) was ascer-
tained from 1H NMR spectrum, following the early report of imi-
nodiacetic acid-boronate complexes studied by Wrackmeyer and
co-workers [34]. The diastereotopic methylene protons of imino-
diacetate portion in dendritic phenyl bis-boronates appeared as a
well-resolved pair of doublets at
coupling constant of 17.1 Hz. Aromatic protons appeared as a set of
multiplets between 7.49 and 7.35 ppm. Internal methylene pro-
tons adjacent to ether and tertiary nitrogen moieties resonated as
triplets at
3.89 and 3.07 ppm, respectively. In 13C NMR spectrum,
the diastereotopic methylene carbon resonated at 59.2 ppm,
whereas carbons adjacent to tertiary nitrogen and ether moieties
appeared at 57.8 and 66.3 ppm, respectively. Carbonyl carbon of
the ester moiety appeared at
168.5 ppm. 11B NMR spectrum of
dendritic phenyl bis-boronate showed chemical shift at 11.9, as
compared to phenyl boronic acid value 29.5. Composition of the
d 4.39 and 4.22, with a geminal
d
d
d
d
d
d
d
phenyl bis-boronate (9a) was also confirmed by mass spectrometry,
which showed molecular ion peak at m/z 531.1716, corresponding
to the sodium adduct. Tetrakis-boronates (10) followed a similar
trend as that of bis-boronates. In 1H NMR spectrum of 10a, the
diastereotopic methylene protons appeared as a pair of doublets at
d
4.45 and 4.26, with geminal coupling constant of 17.2 Hz, whereas
the aromatic protons resonated as two multiplets between 7.53
and 7.36 ppm. The methylene protons of ether moiety of the
d
Fig. 1. Molecular structures of the dendritic iminodiacetic acids.

140
A. Sharma et al. / Journal of Organometallic Chemistry 819 (2016) 138e146
Scheme 1. Synthesis of bis- (1) and tetrakis- (2) dendritic iminodiacetic acids.
Fig. 2. Overlay of 1H NMR spectra of the conversion of tetrakis-ester 4 to octakis-ester 8.
dendrimer resonated as triplets at
d
3.82 and 3.63 ppm (J ¼ 4.3 Hz),
Hydrolytic stabilities of bis- and tetrakis-boronoates 9a and 10a
were assessed subsequently. In order to compare the rate of hy-
drolysis, monomeric boronate phenyl N-methyliminodiacetic acid
boronate I was used. The hydrolysis of boronates (5 mM) was
performed using aq. K3PO4 (50 mM, pH 7.8) in CD3CN at 40 ꢁC, and
1H NMR spectra were recorded at periodic time intervals until the
hydrolysis reached a plateau. The analysis was aided through
integration of two sets of diasterotopic methylene protons, as
compared to methoxy proton of p-bromoanisole, used as the in-
ternal standard. The progress of hydrolysis was plotted as a func-
tion of time and fitted to an exponential decay curve, from which
the rate constants were calculated (Table 1).
whereas tertiary nitrogen attached methylene protons of dendritic
backbone appeared as triplets at 2.98 and 2.89 ppm. In 13C NMR
spectrum of 10a, carbonyl carbon resonated at
whereas diastereotopic methylene carbon at 60.9 ppm. Carbons
adjacent to tertiary nitrogen and ether moieties appeared at 59.3
and 78.2 ppm, respectively. 11B NMR spectrum showed resonance
at
d 168.8 ppm,
d
d
d
11.8 ppm. The structure of 10a (R ¼ H) was confirmed by mass
spectrometry, which showed a signal, corresponding to the [M þ
Na]þ adduct. Aryl bis- (9b) and tetrakis- (10b) boronates were
characterized similarly through 1H, 13C and 11B NMR spectros-
copies. Mass spectrometric analysis could not be secured for these
aryl tetrakis-boronates.
As shown in Table 1, the tetrakis-boronate 10a was ~20 times

A. Sharma et al. / Journal of Organometallic Chemistry 819 (2016) 138e146
141
Scheme 2. Synthesis of dendritic bis- and tetrakis-boronates.
Table 1
and boronate I afford >80% biphenyl within 1 h, dendritic bis- (9a)
and tetrakis- (10a) boronates afford much reduced yields. After 1 h,
tetrakis-boronate 10a afforded only 49% of biphenyl product and
completion of the reaction took several hours, as a result of
significantly reduced hydrolysis to the corresponding reactive
boronic acid. In these reactions, it is noted that the biphenyl for-
mation may have occurred well as a result of a competitive
homocoupling of boronates as a source reaction, which warranted
us to conduct the reaction with differing aryl boronates. Further
reactions were thus conducted using substituted aryl-boronates
and boronic acids.
A monomeric boronate IV/VII, bis- or tetrakis-phenyl boronate
and 1-bromonaphthalene were thus subjected to the cross-
coupling reaction. The reactions were conducted in one pot in a
mixture of IV/VII, 9b/10b and aryl bromide, in DMF/water (3:1) at
40 ꢁC, in the presence of K2CO3 (3 mol equivalents) and Pd(PPh3)4
catalyst (10 mol%) (Scheme 4).
First order rate constants (k) of I, 9a and 10a, at 40 ꢁC in CD3CN.
Compound k (10ꢀ4 sꢀ1
4.5
)
Compound k (10ꢀ4 sꢀ1
9a 3.8
)
Compound k (10ꢀ4 sꢀ1
10a 0.21
)
I
slower in hydrolysis, in comparison to monomeric boronate I. Bis-
boronate also hydrolysed relatively slower than monomer boro-
nates. Hydrolysis would be initiated by the attack of the base at the
susceptible carbonyl carbon of the boronate, leading to a tetrahe-
dral oxyanion adduct. We premise that either the formation or
break-down of this adduct might account for the observed differ-
ences in the rates of hydrolysis. Presence of non-covalent in-
teractions between hydroxyl group of the tetrahedral adduct and
the dendritic scaffold might stabilize the intermediate and such a
stability in the case of tetrakis-boronate would be absent for the
monomeric or the bis-boronate complexes studied herein. From 11
B
The bis- and tetrakis-boronates were normalized and thus, for a
molar equivalent of bis-boronate and tetrakis-boronate, 2 and 4
equivalents of monomeric boronate and 1-bromonathphthalene,
respectively, were used. The progress of the reaction was followed
through GC-MS analysis. After 8 h of reaction duration, the reaction
mixture was analysed and formation of V, VI and 11 were identified.
The products formed in this reaction are given in Table 2.
From the above reactions, we infer that terphenyl product forms
in higher yields with dendritic boronates, as a result of slower
hydrolysis of dendritic boronates and faster hydrolysis of mono-
meric boronate IV/VII. This observation prompted us to continue
the one-pot cross-coupling reaction with bifunctional monomeric
and dendritic boronates.
An effort was thus undertaken to access tetraphenyl, involving
three different types of boronates and an aryl bromide. The cross-
coupling reaction was initiated by the reaction of m-tolylboronic
acid with bifunctional monomer boronate IX in DMF, in the pres-
ence of Pd(PPh3)4 (cat.) and K2CO3 at 80 ꢁC, in DMF under anhy-
drous conditions. The design of the experiment is shown in Scheme
NMR monitoring, neither evolution of a new peak nor shifting of
peak in the first few hours of the hydrolytic conditions occurred
with tetrakis-system, suggesting that the N/B coordination was
intact during this period. Thus, although we are unable to precisely
account the significantly enhanced hydrolytic stability of the tet-
rakis-system, possible origin of the effect might be accounted as
given above.
The slower hydrolysis of dendritic boronates was assessed
subsequently in competitive Suzuki-Miyaura cross-coupling re-
actions involving aryl boronates and aryl bromides. Initial reactions
were conducted using bis- and tetrakis-boronates with bromo-
benzene, and the reactivity profiles were compared with phenyl-
boronic acid and I. The reactions were performed in the presence of
base and catalyst (10 mol%) in aq. DMF, at 80 ꢁC (Scheme 3). For-
mation of biphenyl was monitored through GC-MS analysis of the
reaction mixture. Fig. 3 shows a plot of the biphenyl formation
mediated by phenylboronic acid and various phenyl boronates.
The above experiments show that whereas phenylboronic acid

142
A. Sharma et al. / Journal of Organometallic Chemistry 819 (2016) 138e146
Scheme 3. Suzuki-Miyaura cross-coupling reaction mediated by boronic acid or boronates.
5. After 6 h of reaction, H2O was added to the reaction mixture and
stirred for 1 h, so as to hydrolyze the monomer boronate. The re-
action was then continued by the addition of required molar
equivalent of tetrakis-boronate to the reaction mixture. Further
amounts of the catalyst and the base were added as that of the
initial step. The reaction was continued for 8 h, followed by further
addition of H2O to the reaction mixture. In the subsequent step, the
p-bromoanisole was added to the reaction mixture, along with
addition of the catalyst and the base. After 8 h, the reaction mixture
was worked up and the crude product was analysed by GC-MS
technique. The analysis showed formation of tetraaryl derivative,
in addition to teraryl and biaryl derivatives as shown in Scheme 5.
Formation of the tetraaryl derivative 11 in 26% yield, resulting from
three consecutive CeC bond formation reactions of boronates, was
observed. Apart from this product, a considerable amount of teraryl
derivatives VII e IX formed, along with a small amount of biaryl
derivative X. These products put together accounted for ~97% of
Fig. 3. A plot of the formation of biphenyl vs time involving different boron reagents I,
II, 9a and 10a.
Scheme 4. One-pot two step iterative Suzuki-Miyaura cross-coupling reactions.
Table 2
Percentage yields of products formed in one-step iterative Suzuki-Miyaura cross-coupling reaction, given in Scheme 4.
Monomer boronate
Dendritic boronate
V
VI
11
Monomer boronate
Dendritic boronate
VIII
VI
12
IV
9b
10b
20
2
13
4
47
88
VII
9b
10b
3
10
29
20
44
70
Scheme 5. One-pot iterative Suzuki-Miyaura cross-coupling reactions.

A. Sharma et al. / Journal of Organometallic Chemistry 819 (2016) 138e146
143
products of the reaction. The product formation was varying, with
terphenyls accounting for ~68% of the total yield. Formation of
terphenyls and biphenyl products suggested a protodeboronation,
during the catalytic cycle. Identity of the tetraphenyl derivative 11
was further confirmed by isolation through column chromatog-
raphy (SiO2) and characterization. Formation of tetraphenyl was
conducted further with two more variations in the phenyl boronic
acid and aryl bromide, following a similar sequence of the reaction
as in Scheme 5. The sequence of iterative, one-pot reaction led to
formation of tetraphenyl derivatives XI and XII (Fig. 4), in 29 and
13% yields, respectively.
Hertz (Hz). GC-MS analyses were performed using the gas chro-
matograph fitted with a flame ionization detector (He carrier gas,
1.2 L minꢀ1, detector temperature 250 ꢁC, detector voltage 0.1 kV)
and a fused silica column (30 m, 0.25 mm) and spectra were ac-
quired in the EI mode. The retention times and peak integrations
were obtained through chromatogram and mass spectral analysis.
4.1.1. 4-Cascade:1-aza-4-oxahexylidine[2]:ethanoic acid ethyl ester
(4) [35]
A mixture of bis-amine (3) (7.0 g, 67.2 mmol), Et3N (82.8 mL,
591.6 mmol) and ethyl bromoacetate (16.4 mL, 148.3 mmol) in DMF
(50 mL) was stirred at 80 ꢁC for 24 h. The reaction mixture was then
filtered and filtrate concentrated in vacuo. The crude reaction
mixture was dissolved in CHCl3, washed with water, dried over
Na2SO4, solvent removed in vacuo and the resulting residue was
purified by column chromatography tꢀo1afford 4, as a yellow liquid;
Major products in the reactions involving above boronates and
aryl bromides were terphenyl (35e55%) and biphenyl derivatives
(~30%), that result from the competitive protodeboronation.
3. Conclusion
yield: 27.1 g, (90%); FT-IR (neat) (cm
)
n
: 2937, 2905, 1741, 1447,
¼ 4.15 (q,
1371, 1193, 1115, 1030; 1H NMR (400 MHz, CDCl3):
d
The work illustrates the facile formation of dendritic bis- and
tetrakis-boronates from the corresponding dendritic iminodiacetic
acids. The dendritic boronates are hydrolytically more stable than
monomeric boronates and this hydrolytic stability was taken
advantage to conduct Suzuki-Miyaura cross-coupling reactions, in
conjunction with chosen monomeric boronates, boronic acids and
aryl bromides. In a one-pot sequential reaction, formation of ter-
phenyls and tetraphenyls are achieved, using bifunctional bis- and
tetrakis-boronates as key reactants. Boronates that hydrolyze to
boronic acid slower than monomeric boronate hydrolysis is hither-
to unknown. The present work illustrates that dendritic boronates,
especially tetrakis-boronate hydrolyzes ~20 times slower than
monomeric boronates. Such hydrolytically more stable boronates
are valuable to conduct one-pot, iterative, multiple CeC bond
forming reactions to ter- and tetraaryls along with chosen boronic
acids and aryl bromides.
J ¼ 7.1 Hz, 8 H, OCH2CH3), 3.59 (s, 8 H, COCH2N), 3.55 (t, J ¼ 5.6 Hz,
4 H, CH2OCH2), 2.92 (t, J ¼ 5.6 Hz, 4 H, NCH2) 1.26 (t, J ¼ 7.1 Hz, 12 H,
OCH2CH3); 13C NMR (100 MHz, CDCl3)
55.81, 53.54, 14.14; HR-MS: m/z
d
¼ 171.29, 70.10, 60.33,
¼
471.2318, calcd. for
C
C
20H36N2O9Na: 471.2319 [MþNa]þ. Elemental analysis: calcd. for
20H36N2O9: C, 53.56; H, 8.09; N, 6.25; found: C, 53.77; H, 7.78; N,
6.21.
4.1.2. 4-Cascade:1-aza-4-oxahexylidine[2]:ethanol (5)
A solution of the ester functionalized dendrimer in THF (27.0 g,
60.2 mmol) was added drop-wise to a suspension of LiAlH4 (11.3 g,
289.7 mmol) in THF at 0 ꢁC and stirred for 3 h at room temperature.
The reaction mixture was cooled, quenched with ice, filtered and
the filtrate concentrated in vacuo. The inorganic salt was precipi-
tated using MeOH, filtered, and the filtrate concentrated. The
resulting residue was re-dissolved in CHCl3, filtered and filtrate
concentrated in vacuo to afford 5, as a viscous liquid; yield: 16.4 g;
4. Experimental
(97%). FT-IR (neat) (cmꢀ1
) n: 3357, 2877,1654,1438,1114,1075,1041,
870; 1H NMR (400 MHz, CDCl3)
d
¼ 3.65e3.58 (m, 12 H, CH2OCH2),
4.1. General methods
2.62 (t, J ¼ 4.8 Hz, 4 H, NCH2), 2.56 (t, J ¼ 4.6 Hz, 8 H, NCH2); 13C
NMR (100 MHz, CDCl3)
d 67.2, 62.11, 58.24, 57.64, 52.79; HRMS: m/
Chemicals were purchased from commercial sources and were
used without further purification. Solvents were dried and distilled
according to literature procedures. Monomer N-methyliminodi-
acetic acid boronates were obtained following the literature pro-
cedure. Analytical TLC was performed on commercial Merck plates
coated with alumina GF254 (0.25 mm) or silica gel 60 F254. Neutral
alumina or silica gel (100e200 mesh) was used for column chro-
matography. Compounds were visualized by exposure to UV light
or iodine vapour. Microanalyses were performed on an automated
C, H, and N analyser. IR spectra were recorded as thin films of neat
sample. Mass spectral analysis was performed on an electrospray
ionization mass spectrometer. 1H, 13C and 11B NMR spectra were
recorded on an instrument operating at 400, 100 and 128 MHz,
respectively. Chemical shift values are reported in ppm relative to
TMS and the following abbreviations are used to explain the mul-
tiplicities: s, singlet; d, doublet; dd, double doublet; t, triplet; q,
quartet; m, multiplet; br, broad. Coupling constants (J) are given in
z ¼ 303.1896, calcd. for C12H28N2O5Na [MþNa]þ: 303.1896.
4.1.3. 4-Cascade:1-aza-4-oxahexylidine[2]:3-oxo-1-
pentylidinenitrile (6)
NaH (0.26 g, 10.8 mmol) was added in portions to a solution of 5
(0.5 g, 1.78 mmol) in THF:DMF (1:1) and stirred at 60 ꢁC for 2 h,
followed by the addition of bromoacetonitrile (0.6 mL, 8.6 mmol) in
THF. The reaction mixture stirred at 60 ꢁC for 6 h cooled, filtered
through celite and filtrate concentrated in vacuo. The crude reaction
mixture was dissolved in CHCl3, washed with water (3 ꢂ 15 mL),
dried over Na2SO4, concentrated in vacuo and the resulting crude
reaction mixture was purified (SiO2), to afford 6, as a viscous liquid;
yield: 0.44 g (56%); FT-IR (neat) (cmꢀ1
2209, 1706, 1342, 1107; 1H NMR (400 MHz, CDCl3)
) n: 3618, 2921, 2861, 2355,
d
¼ 4.29 (s, 8 H,
OCH2CN), 3.64 (t, J ¼ 5.4 Hz, 8 H, OCH2), 3.50 (t, J ¼ 5.7 Hz, 4 H,
OCH2), 2.82 (t, J ¼ 5.4 Hz, 8 H, NCH2), 2.76 (t, J ¼ 5.7 Hz, 4 H, NCH2);
13C NMR (100 MHz, CDCl3)
d 116.1, 69.9, 69.5, 56.4, 54.4, 54.3;
HRMS: m/z ¼ 437.2516, calcd. for C20H32N6O5H [MþH]þ: 437.2512.
Elemental analysis: calcd. for C20H32N6O5: C, 55.03; H, 7.39; N,
19.25; found: C, 55.25; H, 7.32; N, 18.97.
4.1.4. 4-Cascade:1-aza-4-oxahexylidine[2]:3-oxo-1-
pentylidineamine (7)
6 (1.0 g, 2.30 mmol) was transferred to a hydrogenation reactor
vessel, mixed with Raney-Co in H2O (1.0 g, 500 mL), hydrogenated
(H2, 50 atm.) at 70 ꢁC for 5 h, cooled, filtered and the filtrate
Fig. 4. Tetraphenyls XI and XII prepared through iterative, one-pot cross-coupling
reactions involving the sequence of m-tolylboronic acid þ 4-bromophenyl monomer
boronate þ 10b þ bromobenzene (in the case of XI) and m-tolylboronic acid þ 4-
bromo-3-anisyl monomer boronate
þ
9b
þ
2-fluoro-4-bromobenzonitrile (in the
case of XII), in the presence of the catalyst and base.

144
A. Sharma et al. / Journal of Organometallic Chemistry 819 (2016) 138e146
concentrated in vacuo to afford 7, as a viscous liquid; yield ¼ 1.01 g;
(98%); FT-IR (neat) (cmꢀ1 : 3397, 2973, 1627, 1489, 1123, 1028; 1H
NMR (400 MHz, D2O)
¼ 3.53 (m, 12 H, OCH2), 3.45 (t, J ¼ 5.0 Hz,
8 H, OCH2), 2.74 (bs, 8 H, NCH2), 2.69 (bs, 12 H, NCH2); 13C NMR
(100 MHz, D2O)
¼ 70.8, 67.8, 53.0, 39.6.
z ¼ 531.1716, calcd. for C24H26B2N2O9Na [MþNa]þ: 531.1717.
)
n
d
4.1.9. 4-Bromophenyl bis-boronate (9b)
4-Bromophenyl boronic acid (0.33 g, 1.64 mmol) was added to a
solution of 1 (0.25 g, 0.74 mmol) in DMF (25 mL), stirred at 120 ꢁC
under an inert atmosphere for 24 h. The reaction mixture was then
worked up as described in the case of preparation of 9a, to afford
d
4.1.5. 8-Cascade:4-oxabutylidine [2]:(1-aza-4-
oxahexylidine):ethanoic acid ethyl ester (8)
Ethyl bromoacetate (1.1 mL, 9.9 mmol) was added drop wise to a
solution of 7 (0.5 g, 1.1 mmol) and Et3N (2.7 mL, 19.3 mmol) in DMF
(5 mL), stirred at 80 ꢁC for 48 h. The reaction mixture was then
worked up as described in the general procedure to afford 8, as a
9b, as a white solid; yield: 0.45 g (90%); FT-IR (neat) (cmꢀ1
)
n
: 3348,
3018, 2962, 1746, 1584, 1288, 1221, 1037, 983, 858, 807; 1H NMR
(400 MHz, CD3CN)
d
¼ 7.58 (d, J ¼ 7.76 Hz, 4 H, ArH), 7.43 (d,
J ¼ 7.88 Hz, 4 H, ArH), 4.13 (d, J ¼ 17.24 Hz, 4 H, NCHCO), 3.98 (d,
J ¼ 17.2 Hz, 4 H, NCHCO), 3.56 (t, J ¼ 4.16 Hz, 4 H, CH2OCH2), 2.81 (t,
liquid; yield: 0.6 g (48%); FT-IR (neat) (cmꢀ1
)
n
: 2980, 2936, 1745,
J ¼ 4.16 Hz, 4 H, CH2NCH2); 13C NMR (100 MHz, CD3CN)
d
¼ 168.6,
1370, 1193, 1116, 1031, 970; 1H NMR (400 MHz, CDCl3)
d
¼ 4.15 (q,
135.8, 134.6, 130.9, 65.9, 59.2, 57.7; 11B NMR (100 MHz, CD3CN)
J ¼ 7.0 Hz, 16 H, OCH2CH3), 3.60 (s, 16 H, COCH2N), 3.54 (t, J ¼ 5.7 Hz,
8 H, OCH2), 3.46 (t, J ¼ 5.7 Hz, 12 H, OCH2), 2.94 (t, J ¼ 5.4 Hz, 8 H,
NCH2), 2.72 (t, J ¼ 5.7 Hz, 12 H, NCH2) 1.26 (t, J ¼ 7.1 Hz, 24 H,
d
¼ 11.7.
4.1.10. Phenyl tetrakis-boronate (10a)
OCH2CH3); 13C NMR (100 MHz, CDCl3)
55.7, 54.4, 55.3, 14.1; HRMS: m/z
d
¼ 171.2, 70.1, 69.4, 60.29,
Phenylboronic acid (0.058 g, 0.48 mmol) was added to a solution
of 2 (0.100 g, 0.11 mmol) in DMSO-PhMe (1:4) (15 mL), stirred at
120 ꢁC under an inert atmosphere for 36 h. The reaction mixture
was then worked up as described in the case of preparation of 9a, to
afford phenyl tetrakis-boronate (10a), as a white solid; yield:
¼
1163.6527, calcd. for
C
C
52H96N6O21Na [MþNa]þ: 1163.6526; Elemental analysis: calcd for
52H96N6O21: C, 54.72; H, 8.48; N, 7.36; found: C, 54.94; H, 8.32; N,
7.14.
0.062 g; (45%); FT-IR (neat) (cmꢀ1
1021, 856, 758; 1H NMR (400 MHz, CD3CN)
)
n
: 3423, 1766, 1436, 1295, 1226,
¼ 7.53 (m, 8H, ArH),
4.1.6. 4-Cascade:1-aza-4-oxahexylidine[2]:ethanoic acid (1)
d
NaOH (0.54 g, 13.4 mmol) was added to a solution of 4 (1.0 g,
2.23 mmol) in THF:water (1:1) and stirred at rt for 20 h. The re-
action mixture was neutralized by Amberlite IR-120H resin and
filtered through sintered funnel. The resin was washed 2e3 times
with MeOH (25 mL) and the filtrate concentrated in vacuo and the
resulting residue was triturated with hexane, ethyl acetate and
CH2Cl2 several times to afford tetra-acid 1, as a white solid; yield:
7.36 (m, 12H, ArH), 4.45 (d, J ¼ 17.2 Hz, 8H, NCHCO), 4.26 (d,
J ¼ 17.2 Hz, 8H, NCHCO), 3.82 (t, J ¼ 4.3 Hz, 8H, CH2OCH2), 3.63 (m,
12H, CH2OCH2), 2.98 (t, J ¼ 4.3 Hz, 8H, CH2NCH2), 2.89 (m, 12H,
CH2NCH2); 13C NMR (100 MHz, acetone-d6)
d
¼ 168.8, 132.4, 128.9,
127.7, 78.2, 60.9, 59.3; 11B NMR (128 MHz, acetone-d6)
d
¼ 11.8;
HRMS: m/z ¼ 1283.5359, calcd. for C60H76 B4N6O21Na [MþNa]þ:
1283.5328.
0.72 g (98%); FT-IR (neat) (cmꢀ1
1398, 1248, 1129, 903, 699; 1H NMR (400 MHz, D2O)
NCH2CO), 3.71 (t, J ¼ 3.8 Hz, 4 H, CH2OCH2), 3.43 (t, J ¼ 3.8 Hz, 4 H,
)
n
: 3448, 3016, 2518, 1731, 1635,
¼ 3.80 (s, 8 H,
d
4.1.11. 4-Bromophenyl tetrakis-boronate (10b)
4-Bromophenylboronic acid (0.107 g, 0.53 mmol) was added to a
solution of 2 (0.11 g, 0.12 mmol) in DMSO-PhMe (1:4) (15 mL),
stirred at 120 ꢁC under an inert atmosphere for 36 h and worked up
as described in the case of preparation of 9a, to afford 4-
bromophenyl tetrakis-boronate (10b), as a white solid; yield:
CH2NCH2); 13C NMR (100 MHz, D2O)
d
¼ 169.2, 64.8, 56.8, 55.4;
HRMS: m/z 359.1067, calcd. for C12H20N2O9Na [MþNa]þ: 359.1067.
4.1.7. 8-Cascade:4-oxabutylidine [2]:(1-aza-4-
oxahexylidine):ethanoic acid (2)
NaOH (0.21 g, 5.3 mmol) was added to a solution of 8 (0.5 g,
0.44 mmol) in THF:water (1:1) and stirred at rt for 24 h. The re-
action mixture was worked up as described in the general proce-
0.067 g (35%); 1H NMR (400 MHz, CD3CN)
ArH), 7.48 (d, J ¼ 8 Hz, 8 H, ArH), 4.49 (d, J ¼ 17.2 Hz, 2 H, NCHCO),
4.24 (d, J ¼ 17.6 Hz, 8 H, NCHCO), 3.84 (bs, 12 H, CH2OCH2), 3.57 (bs,
8 H, CH2OCH2), 3.10e2.84 (bs, 20 H, CH2NCH2); 13C NMR (100 MHz,
d
¼ 7.54 (d, J ¼ 7.2 Hz, 8 H,
dure to afford 2, as a white solid; yield: 0.38 g (94%); FT-IR (KBr) (cm
CD3CN)
d
¼ 168.9, 135.5, 133.8, 113.2, 112.7, 68.7, 68.5, 65.6, 65.4,
ꢀ1
)
n
: 3427, 1735, 1636, 1400, 1255, 1127, 905, 694; 1H NMR
59.0, 57.5; 11B NMR (128 MHz, CD3CN)
d
¼ 11.6.
(400 MHz, D2O)
4.04 (bs, 8 H, CH2OCH2), 3.84 (bs, 8 H, CH2NCH2), 3.60 (bs, 12 H,
CH2NCH2); 13C NMR (100 MHz, D2O)
d
¼ 4.31 (s,16 H, NCH2CO), 4.09 (bs,12 H, CH2OCH2),
4.1.12. Hydrolysis of boronates
Stock solutions of boronates in acetonitrile-d3 were prepared as
follows: I (1.9 mg, 0.008 mmol), 9a (2.0 mg, 0.004 mmol) or 10a
d
¼ 169.1, 64.9, 64.4, 56.6; 55.5,
53.4, 53.2; HRMS: m/z ¼ 917.4204, calcd. for C36H64N6O21H:
917.4203.
(2.5 mg, 0.002 mmol) were dissolved in acetonitrile-d3 (500 mL).
Each boronate solution was admixed with 4-bromo anisole
(1.5 mg). The solution was transferred to an NMR tube, a solution of
4.1.8. Phenyl bis-boronate (9a)
Phenyl boronic acid (0.20 g, 1.64 mmol) was added to a solution
of 1 (0.25 g, 0.74 mmol) in DMF (25 mL), stirred at 120 ꢁC, under an
inert atmosphere for 24 h. The reaction mixture was cooled to room
temperature and concentrated in vacuo. The resulting residue was
dissolved in EtOAc (100 mL), washed with aq. NaHCO3 (2 ꢂ 10 mL),
water (2 ꢂ 10 mL), dried (Na2SO4), concentrated and dried in vacuo.
The crude product was purified (SiO2) (hexane/acetone eluent) to
K3PO4 in D2O (50 mM, 40 m
L) was added and 1H NMR spectra were
recorded at defined time intervals (0, 0.5 h,1.0 h, 2.0 h, etc.) at 40 ꢁC.
The percentage of boronate remaining was calculated by comparing
the ratio of the integrated OCH3 singlet of 4-bromoanisole
(3.78 ppm, internal std) to that of the NCH2 doublets of the
boronates.
afford 9a, as a white solid; yield ¼ 0.35 g (91%); FT-IR (neat) (cmꢀ1
)
4.1.13. Suzuki-Miyaura cross-coupling reaction
n
: 3503, 1769, 1435, 1296, 1226, 1044, 854, 757, 706; 1H NMR
Pd(PPh3)4 (2.26 mg,1.96
(4.96 mg, 4.29 mol for I) (9.48 mg, 8.2
benzene (3.08 mg, 19.6 mol for 9a, 1.24 mg, 7.92
6.74 mg, 42.9 mol for II,12.87 mg, 82.0 mol for I)) were added to a
solution of 9a (5.0 mg, 9.8 mol) or 10a (2.5 mg, 1.98 mol) or I
(10.0 mg, 82.0 mol) or II (10 mg, 42.9 mol) in DMF/H2O (1:1)
m
mol for 9a) (0.9 mg, 0.78
mol for II) and bromo-
mol for 10a,
mmol for 10a)
(400 MHz, acetone-d6)
d
¼ 7.49 (m, 4 H, ArH), 7.35 (m, 6 H, ArH),
m
m
4.39 (d, J ¼ 17.1 Hz, 4 H, NCHCO), 4.22 (d, J ¼ 17.1 Hz, 4 H, NCHCO),
m
m
3.89 (t, J ¼ 4.7 Hz, 4 H, CH2OCH2), 3.07 (t, J ¼ 4.7 Hz, 4 H, CH2NCH2);
m
m
13C NMR (100 MHz, acetone-d6)
d
¼ 168.5, 132.4, 128.9, 127.7, 66.3,
m
m
59.2, 57.8; 11B NMR (128 MHz, acetone-d6)
d
¼ 11.9; HRMS: m/
m
m

A. Sharma et al. / Journal of Organometallic Chemistry 819 (2016) 138e146
145
and environmental applications, Pure Appl. Chem. 77 (2005) 1445e1495.
(4 mL), stirred at room temperature for ~5 min under nitrogen
atmosphere, followed by addition of K2CO3 (16.23 mg, 117.6 mol
for 9a) (6.6 mg, 47.5 mol for 10a) (35.5 mg, 257.4 mol for I)
(67.9 mg, 492.0 mol for II). The reaction mixture was stirred at
[3] S.E. Castillo-Blum, N. Barba-Behrens, Coordination chemistry of some bio-
logically active ligands, Coord. Chem. Rev. 196 (2000) 3e30.
[4] D. Parker, Excitement in f block: structure, dynamics and function of nine-
coordinate chiral lanthanide complexes in aqueous media, Chem. Soc. Rev.
33 (2004) 156e165.
m
m
m
m
80 ꢁC under an inert atmosphere, aliquot of the reaction mixture
was taken out at periodic time intervals and worked up in EtOAc
and H2O. The EtOAc portion was dried (Na2SO4) and concentrated
in vacuo. An MeOH solution of the resulting product was analysed
by GC-MS analysis, using fused silica column.
[5] Andris Molnar (Ed.), EDTA: Synthesis, Uses and Environmental Concerns, Nova
Science Publishers, Inc., Hauppauge, N. Y, 2014.
[6] D.M. Knapp, E.P. Gillis, M.D. Burke, A general solution for unstable boronic
acids: slow-release cross-coupling from air-stable MIDA boronates, J. Am.
Chem. Soc. 131 (2009) 6961e6963.
€
[7] E. Buhleier, W. Wehner, F. Vogtle, “Cascade”- and “nonskid-chain-like” syn-
thesis of molecular cavity topologies, Synthesis (1978) 155e158.
[8] D.A. Tomalia, H. Baker, J. Dewald, M. Hall, C. Kallos, S. Martin, J. Roeck,
4.1.14. One-pot, two-step iterative cross-coupling reaction to the
synthesis of teraryls
P. Smith,
A new class of polymers: starburst-dendritic macromolecules,
Polym. J. (Tokyo) 17 (1985) 117e132.
Pd(PPh3)4 (16.3 mg, 0.014 mmol for 9b) (2.8 mg, 0.0024 mmol
for 10b) and 1-bromo naphthalene (27.9 mg, 0.134 mmol for 9b)
(4.0 mg, 0.0193 mmol for 10b) were added to a solution of 9b
(23.5 mg, 0.035 mmol) or 10b (7.6 mg, 0.0048 mmol) and IV
(18.6 mg, 0.070 mmol for 9b) (5.1 mg, 0.0193 mmol for 10b) or VII
(17.3 mg, 0.070 mmol for 9b) (4.8 mg, 0.0193 mmol for 10b) in DMF/
H2O (3:1) (4 mL), stirred at room temperature for 5 min under
nitrogen atmosphere, followed by addition of K2CO3 (39.0 mg,
0.283 mmol for 9b) (4.0 mg, 0.028 mmol for 10b). The reaction
[9] G.R. Newkome, Z. Yao, G.R. Baker, V.K. Gupta, Cascade molecules: a new
approach to micelles. A [27]-Arborol, J. Org. Chem. 50 (1985) 2003e2004.
[10] C.J. Hawker, J.M.J. Frechet, Preparation of polymers with controlled molecular
ꢀ
architecture. A new convergent approach to dendritic macromolecules, J. Am.
Chem. Soc. 112 (1990) 7638e7647.
[11] E.M.M. de Brabander-van den Berg, E.W. Meijer, Poly(propy1ene imine)
dendrimers: large scale synthesis by hetereogeneously catalyzed hydroge-
nations, Angew. Chem. Int. Ed. Engl. 32 (1993) 1308e1311.
[12] C. Galliot, D. Prevote, A.-M. Caminade, J.-P. Majoral, Polyaminophosphine
containing dendrimers. Syntheses and characterization, J. Am. Chem. Soc. 117
(1995) 5470e5476.
[13] U. Boas, J.B. Christensen, P.M.H. Heegaard, Dendrimers: design, synthesis and
chemical properties, J. Mater. Chem. 16 (2006) 3785e3798.
[14] D. Astruc, E. Boisselier, C. Ornelas, Dendrimers designed for functions: from
physical, photophysical, and supramolecular properties to applications in
sensing, catalysis, molecular electronics, photonics, and nanomedicine, Chem.
Rev. 110 (2010) 1857e1959.
mixture stirred at 40 ꢁC under inert atmosphere for 6 h, 200
mL
aliquot was taken and worked up in EtOAc (3 mL) and H2O (10 mL).
The EtOAc layer was dried (an. Na2SO4) and concentrated and dried
in vacuo. The resulting product was diluted with 200 mL of MeOH
[15] G.R. Newkome, C. Shreiner, Dendrimers derived from 1/3 branching motifs,
Chem. Rev. 110 (2010) 6338e6442.
and analysed by GC-MS analysis, using fused silica column.
[16] G.M. Soliman, A. Sharma, D. Maysinger, A. Kakkar, Dendrimers and miktoarm
polymers based multivalent nanocarriers for efficient and targeted drug de-
livery, Chem. Commun. 47 (2011) 9572e9787.
[17] M. Keller, A. Hameau, G. Spataro, S. Ladeira, A.-M. Caminade, J.-P. Majoral,
A. Quali, An efficient and recyclable dendritic catalyst able to dramatically
decrease palladium leaching in Suzuki couplings, Green Chem. 14 (2012)
2807e2815.
[18] G. Jayamurugan, P. Umesh, N. Jayaraman, Preparation and catalytic studies of
palladium nanoparticles stabilized by dendritic phosphine ligand-
functionalized silica, J. Mol. Catal. A Chem. 307 (2009) 142e148.
[19] N. Miyaura, A. Suzuki, Palladium-catalyzed cross-coupling reactions of orga-
noboron compounds, Chem. Rev. 95 (1995) 2457e2483.
[20] A. Suzuki, Recent advances in the cross-coupling reactions of organoboron
derivatives with organic electrophiles, 1995-1998, J. Organomet. Chem. 576
(1999) 147e168.
4.1.15. Cross-coupling reaction to tetraaryl derivative 13
Catalyst Pd(PPh3)4 (2.3 mg), K2CO3 (6.7 mg) were added to a
solution of IX (5.5 mg) and m-tolylboronic acid (2.2 mg) in DMF
(5 mL), stirred at 80 ꢁC for 6 h, water (0.5 mL) was then added and
stirred further for 1 h at same temperature. The reaction mixture
was added with 10b (6.4 mg), catalyst (2.3 mg) and K2CO3 (6.7 mg)
and stirring continued for 8 h. Further amount of water (0.5 mL),
followed by p-bromoanisole, catalyst (2.3 mg) and K2CO3 (6.7 mg)
were added to the reaction mixture, and stirring continued for 8 h.
The reaction mixture was worked up as given before and analysed
by GC-MS analysis. The crude reaction mixture was also purified
(SiO2) (eluent: 2% EtOAc in hexane) to afford 13, as a white solid;
[21] N.E. Leadbeater, Fast, easy, clean chemistry by using water as a solvent and
microwave heating: the Suzuki coupling as an illustration, Chem. Commun.
(2005) 2881e2902.
[22] A.J.J. Lennox, G.C. Lloyd-Jones, The slow-release strategy in Suzuki-Miyaura
coupling, Isr. J. Chem. 50 (2010) 664e674;
yield: 1.8 mg (26%). 1H NMR (400 MHz, CDCl3)
d
¼ 7.60e7.56 (t,
J ¼ 8.0 Hz, 4 H, ArH), 7.47e7.43 (t, J ¼ 8.0 Hz, 3 H, ArH), 7.36e7.31
(m, 2 H, ArH), 7.20 (d, J ¼ 7.2 Hz,1 H, ArH), 7.12 (br, 2 H, ArH), 7.02 (d,
J ¼ 8.4 Hz, 2 H, ArH), 3.88 (s, 3 H, ArOCH3), 2.43 (s, 3 H, ArCH3), 2.42
(s, 3 H, ArCH3), 2.24 (s, 3 H, ArCH3); 13C NMR (100 MHz, CDCl3)
(b) A.J.J. Lennox, G.C. Lloyd-Jones, Organotrifluoroborate hydrolysis: boronic
acid release mechanism and an acid-base paradox in cross-coupling, J. Am.
Chem. Soc. 134 (2012) 7431e7441;
d
¼ 141.2, 140.8, 140.7, 137.7, 134.6, 133.7, 133.6, 131.9, 129.6, 128.6,
(c) A.J.J. Lennox, G.C. Lloyd-Jones, Transmetalation in the Suzuki-Miyaura
coupling: the fork in the trail, Angew. Chem. Int. Ed. 52 (2013) 7362e7370;
(f) A.J.J. Lennox, G.C. Lloyd-Jones, Selection of boron reagents for Suzu-
kieMiyaura coupling, Chem. Soc. Rev. 43 (2014) 412e443.
128.1, 127.9, 127.7, 126.7, 126.8, 126.0, 123.3, 114.1, 55.3, 22.2, 21.4,
19.6; GC-MS m/z calcd. for C28H26O: 378.5; found 378.0.
[23] S.J. Lee, K.C. Gray, J.S. Paek, M.D. Burke, Simple, efficient, and modular syn-
theses of polyene natural products via iterative cross-coupling, J. Am. Chem.
Soc. 130 (2008) 466e468.
Acknowledgements
[24] J.R. Struble, S.J. Lee, M.D. Burke, Ethynyl MIDA boronate: a readily accessible
and highly versatile building block for small molecule synthesis, Tetrahedron
66 (2010) 4710e4718.
[25] E.M. Woerly, J.R. Struble, N. Palyam, S.P. O’Hara, M.D. Burke, (Z)-(2-
Bromovinyl)-MIDA boronate: a readily accessible and highly versatile build-
ing block for small molecule synthesis, Tetrahedron 67 (2011) 4333e4343.
[26] J. Li, S.G. Ballmer, E.P. Gillis, S. Fujii, M.J. Schmidt, A.M.E. Palazzolo,
J.W. Lehmann, G.F. Morehouse, M.D. Burke, Synthesis of many different types
of organic small molecules using one automated process, Science 347 (2015)
1221e1226.
[27] H. Noguchi, K. Hojo, M. Suginome, Boron-masking strategy for the selective
synthesis of oligoarenes via iterative Suzuki-Miyaura coupling, J. Am. Chem.
Soc. 129 (2007) 758e759.
[28] N. Iwadate, M. Suginome, Differentially protected biboron for regioselective
diboration of alkynes: internal-selective cross-coupling of 1-alkene-1,2-
diboronic acid derivative, J. Am. Chem. Soc. 132 (2010) 2548e2549 (and
references therein).
We are grateful to Department of Science and Technology, New
Delhi, for a financial support. Council of Scientific and Industrial
Research, New Delhi, is acknowledged for a fellowship to PK.
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.jorganchem.2016.06.030.
References
[1] C. Kremer, J. Torres, S. Dominguez, Lanthanide complexes with oda, ida, and
nta: from discrete coordination compounds to supramolecular assemblies,
J. Mol. Struct. 879 (2008) 130e149.
[2] G. Anderegg, F. Arnaud-Neu, R. Delgado, J. Felcman, K. Popov, Critical evalu-
ation of stability constants of metal complexes of complexones for biomedical
[29] G.A. Molander, N. Ellis, Organotrifluoroborates: protected boronic acids that
expand the versatility of the Suzuki coupling reaction, Acc. Chem. Res. 40
(2007) 275e286.

146
A. Sharma et al. / Journal of Organometallic Chemistry 819 (2016) 138e146
[30] S. Darses, J.-P. Genet, Potassium organotrifluoroborates: New perspectives in
organic synthesis, Chem. Rev. 108 (2008) 288e325.
[33] S.G. Ballmer, E.P. Gillis, M.D. Burke, B-Protected haloboronic acids for iterative
cross-coupling, Org. Synth. 86 (2009) 344e359.
[31] G.A. Molander, B. Canturk, Organotrifluoroborates and monocoordinated
palladium complexes as catalysts-A perfect combination for SuzukieMiyaura
coupling, Angew. Chem. Int. Ed. 48 (2009) 9240e9261.
[32] J. Raushel, D.L. Sandrok, K.V. Josyula, D. Pakyz, G.A. Molander, Reinvestigation
of aminomethyltrifluoroborates and their application in Suzuki-Miyaura
cross-coupling reactions, J. Org. Chem. 76 (2011) 2762e2769.
[34] T. Mancilla, B. Contreras, B. Wrackmeyer, New bicyclic organylboronic esters
derived from iminodiacetic acids, J. Organomet. Chem. 307 (1986) 1e6.
[35] Nomenclature follows the guidelines proposed by Newkome and co-workers,
G.R. Newkome, G.R. Baker, J.K. Young, J.G. Traynham, A systematic nomen-
clature for cascade polymers, Polymer 31 (1993) 641e651.