One-Pot Dual C?C Coupling Reaction via Site Selective Cascade Formation by PdII-Cryptate of an Amino-Ether Heteroditopic Macrobicycle

Article abstract of DOI:10.1002/chem.202005397

Selectivity of aryl iodo over ethynyl iodo toward the Suzuki cross coupling reaction is explored by utilizing a palladium complex of amino-ether heteroditopic macrobicycle. Subsequently, unreacted ethynyl iodide undergoes homocoupling reaction in the same catalytic atmosphere, thereby representing a cascade dual C?C coupling reaction. Furthermore, this approach is extended for novel one-pot synthesis of unsymmetrical 1,3-diynes.

Full text of DOI:10.1002/chem.202005397

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&
Synthetic Methods
One-Pot Dual CÀC Coupling Reaction via Site Selective Cascade
Formation by PdII-Cryptate of an Amino-Ether Heteroditopic
Macrobicycle
Sayan Sarkar, Piyali Sarkar, Sandip Munshi, and Pradyut Ghosh*[a]
Abstract: Selectivity of aryl iodo over ethynyl iodo toward
the Suzuki cross coupling reaction is explored by utilizing a
palladium complex of amino-ether heteroditopic macrobicy-
cle. Subsequently, unreacted ethynyl iodide undergoes ho-
mocoupling reaction in the same catalytic atmosphere,
thereby representing a cascade dual CÀC coupling reaction.
Furthermore, this approach is extended for novel one-pot
synthesis of unsymmetrical 1,3-diynes.
Introduction
structure and profuse reactivity. These diynes exemplifies as
the important skeleton for the synthesis of natural products,[9]
supramolecular architectures,[10] organic conductors,[11] elec-
tron-rich materials,[12] and so on. Among various synthetic tech-
niques, alkynyl halide substrates may couple to form 1,3-
diynes in certain reaction medium with considerable yields.[13]
However, formation of biaryl substituted 1,3-diynes from alkyn-
yl halides in presence of organoborons has not been investi-
gated, as both homocoupling and Suzuki coupling of alkynyl
halide might occur in a competitive manner, thus, it is hard to
control the synthesis of regioselective product.[14] Single sub-
strate having both aryl iodo and alkynyl iodo groups in Suzuki
coupling conditions generally produces scramble of products
due to the possibility of different types of reactions. Selective
protection of a particular group may effectively channelize the
reaction pathway in such a way that not only the Suzuki cou-
pling occurs at the aryl iodo centre, but also homocoupling
predominates at alkynyl iodo centre to produce the desired
product selectively.
The Suzuki coupling reaction is recognized to be one of the
most effective reactions for the construction of a carbon-
carbon bond between organoboron and organic halides.[1] Re-
cently, the scope of this coupling reaction has been extended
its path from C(sp2)ÀC(sp2) bond formation to C(sp2)ÀC(sp3)
bond,[2] C(sp3)ÀC(sp3) bond[3] and C(sp2)ÀC(sp) bond[4] forma-
tion reactions, but selective Suzuki coupling among various
C(sp/sp2/sp3)ÀX groups is itself a challenging task. Moreover,
homocoupling reaction of C(sp)ÀX (X=halogens) substrates[5]
can be in competition with its Suzuki coupling,[6] as both re-
quire nearly same catalytic conditions (Scheme 1a). On the
other hand, 1,3-diynes are important building blocks in materi-
al science[7] and organic synthesis[8] due to their unique linear
Herein, we have studied one-pot dual coupling of ethynyl
iodo based aryl iodo substrates through site selective Suzuki
coupling of aryl iodo center without hampering ethynyl iodo
group, followed by consecutive homocoupling of C(sp) atoms
(Scheme 1b). This site selectivity has been achieved upon ex-
ploring an oxyether-amine based heteroditopic macrobicy-
cle,[15] L1 (Figure 1) as an additive in PdII catalytic environment.
To the best of our knowledge, driving a substrate for a one-
pot transformation through selective Suzuki coupling on
Scheme 1. (a) Different competitive CÀC coupling reactions. (b) This report.
[a] S. Sarkar, Dr. P. Sarkar, S. Munshi, Prof. P. Ghosh
School of Chemical Sciences
Indian Association for the Cultivation of Science (IACS)
2A and 2B Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal
(India)
E-mail: icpg@iacs.res.in
Supporting information and the ORCID identification number(s) for the
author(s) of this article can be found under:
https://doi.org/10.1002/chem.202005397.
This manuscript is part of an Indo-German special collection.
Figure 1. Chemical representations of L1, L’ and L2.
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C(sp2)ÀX group without attacking C(sp)ÀX group by organo-
borons and successive homo coupling of C(sp) atom has not
been investigated till date.
Table 1. Optimization of the reaction conditions.[a]
Results and Discussion
Selection of macrobicyclic cage and substrates
Entry
Catalyst
Solvent
Base
T
[8C]
t
[h]
Yield
[%][b]
It is worth mentioning that a 3D cage moiety having well-de-
fined functional groups can frame a guest with efficient bind-
ing capability.[16] On the other hand, different functionalities
may provide site selective protective binding towards a specif-
ic group in presence of different labile groups of a guest mole-
cule.[17] The macrobicycle L1 having N4 cavity (Figure 1) can
form four/five coordinated complex with PdII.[18] Thus, it would
be interesting to explore the selectivity of the PdII complex of
L1 towards CÀC coupling reactions. Importantly, the ethynyl
iodo group is found to be an efficient halogen-bond donor,
having significant s-hole potential towards lone pair rich halo-
gen bond acceptors.[19] Whereas, oxygen is a well-established
acceptor for the halogen bonding interaction due to its easy
availability of lone pair of electrons.[20] Thus, L1, having a dis-
tinct 3D oxy-ether pocket, might favour a selective interaction
with the ethynyl iodide. Therefore, the Suzuki coupling is sur-
veyed of a substrate 1- iodoethynyl-4-iodobenzene, 1a, having
two different labile CÀI bonds (aryl iodo and ethynyl iodo
groups). A suitable oxy-ether pocket as well as three well-or-
ganized benzene in the framework of L1 might induce p–p
stacking interaction effectively to bind aryl iodo end of 1a to
PdII center selectively.
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd2dba3
Pd(NO3)2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
CH3OH
CH3OH
CH3OH
CH3OH
DMSO
DMF
CH3CN
C2H5OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
DMSO
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
Cs2CO3
NEt3
60
60
60
60
60
80
80
60
60
60
60
50
60
100
24
24
12
5
5
8
35
28
31
68
67
27
20
25
52
48
21
57
67
66
8
10
12
12
12
12
24
24
9
10
11
12
13
14
PdCl2
PdCl2
PdCl2
PdCl2
K2CO3
K2CO3
K2CO3
[a] The reaction was performed using 1a (1.0 mmol), phenylboronic acid
2a (1.3 mmol), catalyst (10 mol%), base (2.0 mmol) and L1 (10 mol%) in
2 mL solvent under argon atmosphere. [b] Isolated yields.
shown greater capability towards efficient product formation.
To determine the amount of PdII-L1 mixture required for the
reaction of 1a and 2a, various amounts of 1:1 mixture of PdII
and L1 are attempted (Figure 2). A linear increase in the yield
upto 10 mol% is observed for the effective percentage of the
mixture.
Consequently, the aryl iodo part of 1a can go through the
site selective Suzuki coupling with arylboronic acid keeping
ethynyl iodo part intact from organoborons. To find out the
effect of three dimensional macrobicyclic cavity of L1, its acy-
clic analog,[15] L’ (Figure 1) has also been explored. Further-
more, to verify the effect of dimension of the macrobicycle
cage, an analogous macrobicycle of L1 having smaller cavity
size, L2 (Figure 1, Scheme 1S, Supporting Information) has also
been synthesized.
Optimization of the reaction conditions
To investigate the effect of L1 toward the PdII catalysed cou-
pling reaction, 1a and phenylboronic acid 2a have been
chosen as model substrates. Since only one PdII binding site is
present in L1, equimolar mixture of PdII catalyst and L1 (1:1) is
used for the above studies. Firstly, the reaction conditions have
been optimized toward the effective production of 1,3-diyne
3a in high yield. The catalytic activity of various PdII salts such
as Pd(OAc)2, Pd(NO3)2 and PdCl2 have been screened upon
varying time as well as temperature (Table 1). Among different
solvent systems (Table 1, entries 4–8) CH3OH and DMSO have
been resulted the higher yields (67–68%) where CH3OH has
been preferred for its greater sustainability. Remarkably, ethyn-
yl iodo part does not react with the organoboron (2a), even at
higher temperature and with longer reaction time (Table 1, en-
tries 13,14). When different bases are explored, K2CO3 has
Figure 2. Survey of yield (%) vs. catalyst-cryptand mixture loading (mol%).
In this regard, use of Pd0 salt as catalyst is found to be inef-
fective towards the desired regioselective product formation
(Table 1, entry 2), which could be due to poor/non-complexing
ability of Pd0 with L1.
To understand the effect of cage structure of L1 in the cou-
pling reaction, acyclic analog of L1 that is, L’ is explored. In op-
timized condition, 3a has only been produced as the minor
product over dual Suzuki coupling product, 4a (Table 2,
entry 1) when L1 is replaced by L’. This could be due to the
flexibility of tripodal arms of L’, which is unable to protect the
ethynyl iodo group from 2a. Furthermore, to check the effect
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Table 2. Comparative reaction study using different additives.[a]
Entry
Additive
Yield of 3a
[%][b]
Yield of 4a
[%][b]
1
2
3
4
5
L’
L2
DB18C6
–
L1
11
12
8
8
68
40
35
41
43
6
[a] The reaction was performed using 1a (1.0 mmol), 2a (1.3 mmol), cata-
lyst (10 mol%), base (2.0 mmol) and additive (10 mol%) in 2 mL solvent
under argon atmosphere. [b] Isolated yields.
of cage dimension, a cryptand with smaller cavity, L2, is further
explored as an additive under optimized reaction conditions.
However, it fails to produce 3a substantially and only a minor
amount (12%) is obtained (Table 2, entry 2).
Scheme 2. List of synthesized symmetrical 1,3-diynes. Reactions were carried
out using 1a (1.0 mmol), arylboronic acids (1.3 mmol), catalyst (10 mol%),
base (2.0 mmol) and L1 (10 mol%) in 2 mL CH3OH under argon atmosphere.
Isolated yields.
When Dibenzo-18-crown-6 (DB18C6) is used as additive, 3a
is found to be the minor product (Table 2, entry 3). Most im-
portantly, when a simple PdII salt (PdCl2) is used as catalyst for
this reaction (Table 2, entry 4), insignificant amount of 3a (8%)
has been isolated. Thus, effect of rigidity (macrobicyclic versus
acyclic tripodal), cavity dimensions of different macrobicycles
and simple PdII salt versus PdII-cryptate as catalyst typically
prove that suitable 3D cavity of L1 and its PdII complex are
very crucial for the protection of ethynyl iodo to produce 3a
as the main product (Table 2, entry 5).
Thus, the above reaction method can be generalized as a
cascade CÀC coupling process involving site selective Suzuki
coupling of aryl iodide followed by the tandem homocoupling
of ethynyl iodo part as an inevitable effect of the reaction
medium.
Figure 3. ORTEP plot of (a) compound 3c and (b) compound 3i [50% Proba-
bility].
Substrate scope
At the optimized reaction condition, various aromatic boronic
acids have been reacted with 1a to produce nine dual cou-
pling products (3a–i, Scheme 2). All the products have been
thoroughly characterized by NMR (Figure S2–S19, Supporting
Information), IR and HRMS. Scheme 2 clearly demonstrates that
the reaction of different arylboronic acids and 1a has a gener-
alized impact towards the dual coupling product 1,3-diynes
formation. Electron donating aryl boronic acids reacts more
prominently with C(sp2) atom of 1a to form finally the 1,3
diyne products with better yields (3b–g).
However, electron withdrawing boronic acids have produced
relatively poor yields of 1,3-diyne products (3h–i) because of
its greater self-coupling tendency by performing efficient de-
borylation. Importantly, we have been successful to crystalize
two of the products 3c and 3i, where both the single-crystal
X-ray diffraction structural analyses have confirmed the forma-
tion of 1,3-diynes (Figure 3).
Scope in dual heterocoupling
We have extended the viability of this reaction procedure by
adding different ethynyl iodo derivatives 5a–d (Scheme 3) to
the reaction mixture after 30 min of initialization to observe
the one pot site selective dual CÀC bond forming heterocou-
pling reactions. Remarkably, unsymmetrical 1,3-diynes have
been formed in considerable yields (Figures S22–S29, Support-
ing Information). Thus, this event creates an opportunity for
the one-pot cross C(sp2)ÀC(sp2) coupling plus cross C(sp)ÀC(sp)
coupling under optimized reaction conditions.
Insight into the cascade dual CÀC coupling
It can be emphasized that for the effective formation of 1,3-
diyne products, PdII catalyzed reaction of 1a and arylboronic
acids in presence of macrobicycle L1 must prefer a particular
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When the species I is further reacted with 1a, 2a and K2CO3
for 30 min in reflux condition, the ESI-MS of the crude reaction
mixture shows a peak at m/Z 1205.21 (Figure S35, Supporting
Information), which corresponds to [L1-Pd(C6H4CꢀC-I)(Cl)]+
(Species III, Scheme S2, Supporting Information). The formation
of species III in the above reaction condition could be ex-
plained by simultaneous reduction of PdII center (Species I) to
Pd0 (Species II) and oxidative addition of 1a to Pd0 preferably
via breaking of the Ar-I bond. Further, the encapsulation of 1a
through cascade complexation in the cavity of PdII-L1 cryptate
1
has been confirmed by a comparative H NMR studies of L1,
Scheme 3. List of synthesized unsymmetrical 1,3-diynes.Reactions were car-
ried out using 1a (1.0 mmol), 2a (1.0 mmol), 5a–5d (1.0 mmol), catalyst
(10 mol%), base (2.0 mmol) and L1 (10 mol%) in 2 mL CH3OH under argon
conditions. Isolated yields.
L1-PdCl2 (1:1 mixture at 608C) and L1-PdCl2-1a (1:1:1 basic
mixture at 608C) (Figures S39–S44, Supporting Information).
When equimolar amount of 1a is added to the in situ L1-PdII
complex in presence of K2CO3 and upon heating at 608C, the
aromatic protons of 1a shifts to the downfield region (Dd
ꢁ0.15 and ꢁ0.08 ppm), which could be due to suitable p–p
stacking interaction between aromatic moieties of 1a and L1-
PdII cryptate upon cascade complex formation. 13C NMR peak
shift of CÀI carbon in the presence of halogen bond acceptor
atoms depicts probable halogen bonding interaction and is
well described in recent literatures.[22] Therefore, to verify the
halogen bonding interaction of ethynyl iodo group inside the
oxyether pocket of L1, we have performed comparative
13C NMR spectral studies (Figure S55, Supporting Information)
of 1a with 1:1:1 basic mixture of L1, PdII and 1a which shows
that the peak of the ethynyl carbon atom (Ca) of 1a attached
to the iodo group has been significantly shifted (Dd
ꢁ1.7 ppm). The next carbon (Cß) is also shifted to some extent
(Ddꢁ0.3 ppm). This indicates potential halogen bonding inter-
action of ethynyl iodide with the oxy-ether pocket of L1. Con-
sequently, all of these facts rules out the formation of Inter-
mediate A or Intermediate B (Scheme 4) during the course of
the reaction, as the formation of those intermediates entirely
depend on the initial breaking of the ethynyl iodo bond of 1a.
Finally, when phenylboronic acid 2a undergoes reaction
with the species III, a transmetalation reaction at the PdII
center probably taking place to form the species IV, which fur-
ther undergoes reductive elimination of C(sp2)ÀC(sp2) coupling
product V to regenerate the species II having Pd0 center
(Scheme S2, Supporting Information). Finally, ethynyl iodo in-
termediate V undergoes a C(sp)ÀC(sp) homocoupling reaction
to form 1,3-diyne 3a in considerable yields, catalyzed by spe-
cies II.
pathway among different possibilities of competitive CÀC cou-
pling reactions (Scheme 4). Thus, to get insight into the L1 as-
sisted PdII catalyzed cascade dual CÀC coupling reaction be-
tween 1a and 2a, a systematic investigation have been carried
out. Upon reacting L1 with PdCl2 in CH3OH for 10 min, a char-
acteristic peak at m/Z 941.31 is observed in the ESI-MS (Fig-
ure S34, Supporting Information), which indicates the forma-
tion of [L1-Pd(Cl)]+ (Species I, Scheme S2, Supporting Informa-
tion) in the system. Complexation of PdII with L1 is further evi-
dent from the splitting of all the aromatic protons of L1 due of
1
the change in the chemical environment. H NMR splitting pat-
tern indicates that the complex is dissymmetric in nature,
having four coordinated square planar geometry around PdII
center in the tris-amine pocket of L1.[18] Furthermore, the
DOSY-NMR spectrum (Figure S37, Supporting Information) of
the mixture shows a similar diffusion coefficient values of all
the assigned peaks. Fitting of the amplitude decay of all the
selected peaks to the mono-exponential function (Figure S38,
Supporting Information) has clearly shown comparable decay
constants along with similar residuals. These results confirmed
the existence of only one type of complex in the solution.[21]
To exactly determine the proper series of cascade reaction,
detection of the intermediate is indeed important. Thus the ex-
istence of the particular intermediate in the mechanistic path-
way has been verified by quenching the reaction mixture after
1 h. Upon purification it has been observed that the intermedi-
ate V is being produced during the course of this reaction. Fur-
thermore, as a support, we have attempted to trap the inter-
mediate V by reacting with benzyl azide and CuI for 30 min
(Scheme 5). A peak at m/z 460.04 in the ESI-MS of the crude in-
dicates the formation of 5-iodotriazole 2b (Figure S52, Sup-
porting Information). Hence, this confirms that the course of
this macrobicycle assisted cascade CÀC coupling is following
Scheme 4. Different possible cascade CÀC coupling reactions involving vari-
ous potential intermediates; Green arrows indicate the macrobicycle assisted
cascade reaction pathway.
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Scheme 5. Formation of 5-iodotriazole derivative.
the transformation from 1a to intermediate V followed by ho-
mocoupling of intermediate V to 3a (Scheme 4, green arrows).
To support the involvement of L1-PdCl2 complex in this ho-
mocoupling reaction, separate homocoupling reactions of 1-
(Iodoethynyl) benzene and intermediate V in the presence of
L1-PdCl2 in situ complex are studied which has eventually
yielded affordable CÀC coupling products (Table 3).
Figure 4. Time-dependent formation of 3a by the reaction of 1a and 2a
under optimized conditions. Inset pictures represent (a) change of absorb-
ance at 290 nm and 340 nm with time, (b) change of absorbance at 290 and
340 nm within 200 s, (c) change in absorbance at 340 nm with time.
Moreover, to rationalize the existence of PdII/Pd0 in the cata-
lytic cycle, L1-PdCl2 complex is heated in methanol for 15 min
in presence of K2CO3 and the ESI-MS (positive ion mode) of
this mixture shows a peak at 906.34 which corresponds to [L1-
Pd]+ species (Figure S36, Supporting Information). This could
be due to the presence of Pd0 species in the mixture which is
originated upon reduction of PdII species in the presence of a
base in suitable solvent.[23]
Table 3. Homocoupling study.[a]
Entry Substrate
1
Product
Yield [%][b]
81
10
3a
Figure 5. Time-dependent formation of 3a by the homocoupling of Inter-
mediate V under optimized condition.
2
78
[a] The reactions were carried out using substrates (0.5 mmol), PdCl2 cata-
lyst (10 mol%), L1 (10 mol%) and K2CO3 (1.0 mmol) in 2 mL CH3OH under
argon atmosphere for 5 h. [b] Isolated yields.
by the homocoupling of intermediate V in presence of L1-Pd
complex has also been observed. In this case the rate of the
reaction is found to be 4.8”10À4 mÀ1 sÀ1 (Figure 5 and Fig-
ure S46, Supporting Information).
Kinetic aspects of the cascade dual CÀC coupling
Almost comparable rates of these two reactions have clearly
pointed out that the formation of 3a from intermediate V is
the slowest step in the optimized two-step transformation of
1a to 3a. The faster rate of formation of intermediate V from
1a is probably due to the noncovalent interactions of 1a (pro-
tective halogen bonding and p–p stacking interaction) with
the cage. This interaction assists the substrate 1a in such a
way that aryl iodo group becomes closer to the metal center
which thereby facilitates faster attack of boronic acid to this
C(sp2)ÀX group. After the formation of intermediate V, it
comes out from the macrobicycle and performs slower homo-
coupling reaction of ethynyl iodo group to form 3a. Finally to
rationalize the importance of the macrobicycle L1 for this dual
coupling, some cross experiments have been incorporated via
kinetic measurements. Reaction of simple trimethylsilyl protect-
ed ethynyl-4-iodobenzene with phenylboronic acid in presence
Furthermore, the proposed mechanism has been substantiated
by the time dependent kinetic studies in optical spectroscopy.
The optimized reaction of 1a with 2a in the presence of L1-Pd
complex has been monitored by observing the appearance of
3a with time. For the initial 200 s of the reaction, the charac-
teristic absorption maxima of 3a at 340 nm does not appear.
After 200 s, the peak at 340 nm begins to form and increases
following a pseudo-first order kinetics with a rate of 3.2”
10À4 mÀ1 sÀ1 (Figure 4 and Figure S45, Supporting Information).
This observation clearly establishes that a lag phase of 200 s
exists before the formation of 3a. In this lag phase, the inter-
mediate V is possibly forming by the faster Suzuki coupling of
aryl iodo group, which initializes the homocoupling of ethynyl
iodo group towards the formation of 3a after 200 s. On the
contrary, the pseudo-first order kinetics for the formation of 3a
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1-iodoethynyl-4-iodobenzene 1a (1 mmol), arylboronic acids
(1.3 mmol) and K2CO3 (2 mmol) were then added and overall reac-
tion mixture was allowed to stir for another 5 h at 608C. Then the
crude was filtered and solvent of the filtrate was evaporated and
all the products were purified by preparative thin layer chromatog-
raphy.
of only PdCl2 salt shows a slower reaction kinetics (Figure S48,
Supporting Information) where the substrate does not reach
the equilibrium even after 10000 s. Also, the homocoupling of
1-(iodoethynyl)benzene does not even occurred in presence of
only PdCl2 catalyst (Figure S49, Supporting Information). These
reactions have clearly shown that in absence of L1, PdCl2 cata-
lyzed Suzuki coupling of aryl iodo group and homocoupling of
ethynyl iodo functionality are not substantial reactions to ach-
ieve. From all these kinetic experiments it can be anticipated
that employment of L1 thus not only imposes the selectivity
of aryl iodo group towards Suzuki coupling over ethynyl iodo
functionality, but also increases the feasibility of both the CÀC
coupling reactions.
General procedure for synthesis of unsymmetrical 1,3-
diynes (6aa–6ad)
In a 10 mL round bottom flask macrobicycle L1 (10 mol%) and
PdCl2 (10 mol%) was mixed in CH3OH and stirred for 10 min.
1-iodoethynyl-4-iodobenzene, 1a (1 mmol), phenylboronic acids
(1 mmol), and K2CO3 (2 mmol) were then added and allowed to stir
at 608C. After 30 min, ethynyl iodo derivatives 5a–5d (1 mmol)
was added to the reaction mixture. Overall reaction mixture was al-
lowed to stir for another 5 h at 608C. Then the crude was filtered
and solvent of the filtrate was evaporated and all the products
were purified by preparative thin layer chromatography.
Conclusions
In summary, we have designed a heteroditopic macrobicycle-
PdII complex catalyzed one-pot synthetic route for preparing
1,3-diynes by site selective Suzuki coupling of aryl iodo groups
with arylboronic acids and sequential homocoupling of the
ethynyl iodo functionality of a single substrate. Protection of
ethynyl iodo group from arylboronic acids has been imparted
probably due to protective halogen-bonding interaction of
ethynyl iodide with the oxy-ether pocket of macrobicycle.
Moreover, the scope of this approach has been extended by
the novel preparation of unsymmetrical 1,3-diynes with excel-
lent yields. Furthermore, kinetic aspects of this multistep reac-
tion have also been studied. Exploitation of macrobicycles for
selective CÀC coupling reactions may advance recent synthetic
methods in near future.
X-ray crystallographic refinement details
X-ray quality single crystals of compound 3c and compound 3i
were obtained by slow evaporation of CHCl3 solution of the com-
pounds. Single crystal X-ray diffraction data were collected using
Bruker APEX III D8 Venture, PHOTON II detector (MoKa, l=
0.7107 Š). Data collection, data reduction, structure solution and
refinement were carried out using the software package of the cor-
responding diffractometer. All the structures were solved by direct
methods and refined in a routine manner. Hydrogen atoms were
geometrically fixed. All the non-hydrogen atoms were treated ani-
sotropically. Deposition numbers 2020012 (for 3c) and 2020013 (for
3i) contain the supplementary crystallographic data for this paper.
These data are provided free of charge by the joint Cambridge
Crystallographic Data Centre and Fachinformationszentrum Karls-
ruhe Access Structures service www.ccdc.cam.ac.uk/structures.
Experimental Section
General details
Characterization data
All the starting materials were purchased from commercial sources
such as Sigma Aldrich, Merck, Spectrochem and Alfa Aesar and are
used as received without further purification. Compound 1a was
synthesized using previously reported procedure.[24] Iodoalkynes
5a, 5b, 5c and 5d were synthesized by following the previously
reported general procedure.[25] Detailed synthetic method for the
preparation of Macrobicycle L2 has been described in Supporting
Information File. L1 and L’ were synthesized according to the pre-
vious literature report.[15] Melting points of all the compounds were
determined on a Labtronics digital auto melting/boiling point ap-
paratus. Solution electronic spectra (single and time-dependent)
were measured on an Agilent 8453 diode array spectrophotometer.
IR data was recorded on a SHIMADZU FTIR-8400S Infrared spectro-
photometer. All the NMR experiments were obtained on 300, 400
and 500 MHz Bruker DPX. For DOSY-NMR data, the fit of the ampli-
tude decay for selected peaks to the mono-exponential function
has been processed using GNAT (General NMR Analysis Toolbox)
software (https://www.nmr.chemistry.manchester.ac.uk/?q=node/
430).
1,4-bis(4-biphenyl)buta-1,3-diyne (3a): Yellowish solid (241 mg,
68%), purified by column chromatography (eluent: hexane), mp:
1
2428C; IR (KBr): n=2925, 2854, 1741, 1461, 837, 757 cmÀ1; H NMR
(400 MHz, CDCl3): d=7.37 (t, J=7.2 Hz, 2H), 7.46 (t, J=7.4 Hz, 4H),
7.57–7.62 ppm (m, 12H); 13C NMR (100 MHz, CDCl3): 74.8, 82.0,
120.8, 127.2, 127.3, 128.0, 129.1, 133.1, 140.3, 142.2; HRMS (EI) m/z:
M+ Calcd for [C28H18]: 354.1408, Found 354.1410.
1,4-bis(4’-methyl-4-biphenyl)buta-1,3-diyne (3b): White solid
(267 mg, 70%), purified by column chromatography (eluent:
hexane), mp: >2508C; IR (KBr): n=2923, 2852, 1741, 1463, 1377,
1
812 cmÀ1; H NMR (500 MHz, CDCl3): 2.40 (s, 6H), 7.27 (s, 2H), 7.49–
7.52 (m, 6H), 7.55–7.60 (m, 8H); 13C NMR (100 MHz, CDCl3): 21.3,
74.7, 82.0, 120.5, 127.0, 129.8, 133.1, 137.4, 138.0, 142.0; HRMS (EI)
m/z: M+ Calcd for [C30H22]: 382.1721, Found 382.1720.
1,4-bis(3’-methyl-4-biphenyl)buta-1,3-diyne (3c): Pale yellow
solid (256 mg, 67%), purified by column chromatography (eluent:
hexane), mp: 1828C; IR (KBr): n=2923, 2852, 2146, 1600, 1479,
1
1375, 835, 738 cmÀ1; H NMR (500 MHz, CDCl3): 2.43 (s, 6H), 7.19 (d,
J=7 Hz, 2H), 7.33–7.43 (m, 6H), 7.56–7.61 (m, 8H); 13C NMR
(100 MHz, CDCl3): 21.7, 74.8, 82.0, 120.7, 124.3, 127.3, 128.0, 128.8,
129.0, 133.0, 138.7, 140.2, 142.3; HRMS (EI) m/z: M+ Calcd for
[C30H22]: 383.1721, Found 383.1718.
General procedure for synthesis of symmetrical 1,3-diynes
(3a–3i)
In
a
10 mL round bottom flask macrobicycle L1 (10 mol%)
1,4-bis(4’-ethyl-4-biphenyl)buta-1,3-diyne (3d): White solid
and PdCl2 (10 mol%) was mixed in CH3OH and stirred for 10 min.
(299 mg, 73%), purified by column chromatography (eluent:
Chem. Eur. J. 2021, 27, 7307 –7314
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Chemistry—A European Journal
hexane), mp: 2408C; IR (KBr): n=2924, 2880, 2142, 1603, 1482,
4-[4-(4-methylphenyl)buta-1,3-diyn-1-yl]biphenyl (6ab): White
solid (140 mg, 48%), purified by column chromatography (eluent:
hexane), mp: 1618C; IR (KBr): n=2920, 2360, 1598, 1485, 1020,
1
820 cmÀ1; H NMR (500 MHz, CDCl3): 1.28 (t, J=7.8 Hz, 6H), 2.70 (q,
J=7.6 Hz, 4H,), 7.29 (d, J=8.0 Hz, 4H), 7.52 (d, J=8.0 Hz, 4H),
7.56–7.60 (m, 8H). 13C NMR (100 MHz, CDCl3): 15.6, 28.7, 74.8, 82.1,
120.5, 127.1, 127.1, 128.6, 133.1, 137.6, 142.1, 144.3; HRMS (EI) m/z:
M+ Calcd for [C32H26]: 410.2035, Found 410.2040.
1
840, 761, 694 cmÀ1; H NMR (400 MHz, CDCl3): 2.37 (s, 3H), 7.15 (d,
J=8.0 Hz, 2H), 7.37 (t, J=7.2 Hz, 1H), 7.42–7.47 (m, 4H), 7.56–7.61
(m, 6H); 13C NMR (100 MHz, CDCl3): 21.8, 73.6, 74.9, 81.4, 82.4,
118.9, 121.0, 127.2, 127.3, 128.0, 129.1, 129.4, 132.6, 133.1, 139.8,
140.3, 142.0; HRMS (EI) m/z: M+ Calcd for [C23H16]: 292.1252, Found
292.1250.
1,4-bis(3’,5’-dimethyl-4-biphenyl)buta-1,3-diyne (3e): White solid
(274 mg, 67%), purified by column chromatography (eluent:
hexane), mp: >2508C; IR (KBr): n=2924, 2860, 1595, 1478, 1381,
1
832, 742 cmÀ1; H NMR (500 MHz, CDCl3): 2.31 (s, 12H), 6.98 (s, 2H),
4-[4-(3-methylphenyl)buta-1,3-diyn-1-yl]biphenyl (6ac): Pale
yellow solid (134 mg, 46%), purified by column chromatography
(eluent: hexane), mp: 1528C; IR (KBr): n=2921, 2850, 2142, 1598,
7.22–7.24 (m, 6H), 7.67–7.70 (m, 6H); 13C NMR (100 MHz, CDCl3):
21.2, 75.3, 81.4, 121.3, 129.4, 130.6, 133.2, 134.0, 137.6, 137.9, 138.1;
HRMS (EI) m/z: M+ Calcd for [C32H26]: 410.2035, Found 410.2038.
1
1481, 1006, 840, 784, 765, 686 cmÀ1; H NMR (400 MHz, CDCl3): 2.35
(s, 3H), 7.18–7.24 (m, 2H), 7.34–7.39 (m, 3H), 7.46 (t, J=7.6 Hz,
2H), 7.58–7.61 (m, 6H); 13C NMR (100 MHz, CDCl3): 21.3, 73.8, 74.8,
81.5, 82.3, 120.9, 121.8, 127.2, 127.3, 128.0, 128.5, 129.1, 129.8,
130.3, 133.1, 133.2, 138.4, 140.3, 142.1; HRMS (EI) m/z: M+ Calcd
for [C23H16]: 292.1252, Found 292.1256.
1,4-bis[4-(2-naphthyl)-phenyl]buta-1,3-diyne (3 f): Pale yellow
solid (286 mg, 63%), purified by column chromatography (eluent:
2% ethyl acetate in hexane), mp: 2088C; IR (KBr): n=2923, 2852,
1585, 1382, 800, 781 cmÀ1 1H NMR (500 MHz, CDCl3): 7.24 (d, J=
;
8.5 Hz, 1H), 7.29 (t, J=7.8 Hz, 3H), 7.40 (d, J=8.5 Hz, 2H), 7.46–
7.50 (m, 6H), 7.60 (t, J=7.5 Hz, 3H), 7.69 (d, J=8.5 Hz, 1H), 7.94–
7.96 (m, 6H); 13C NMR (125 MHz, CDCl3): 75.2, 81.4, 121.3, 125.5,
125.9, 126.1, 126.7, 128.0, 128.0, 128.3, 133.0, 133.7, 134.0, 137.9,
138.6, 139.4; HRMS (EI) m/z: M+ Calcd for [C36H22]: 454.1721, Found
454.1718.
4-[4-(4-cyanophenyl)buta-1,3-diyn-1-yl]biphenyl (6ad): White
solid (121 mg, 40%), purified by column chromatography (eluent:
2% ethyl acetate in hexane), mp: 1888C; IR (KBr): n=2920, 2850,
2229, 2216, 1598, 1483, 1402, 1269, 1105, 837, 767, 703 cmÀ1
;
1H NMR (400 MHz, CDCl3): 7.36–7.40 (m, 1H), 7.44–7.48 (m, 2H),
7.58–7.65 (m, 10H); 13C NMR (100 MHz, CDCl3): 74.1, 78.4, 79.8,
84.1, 112.6, 118.4, 120.1, 127.1, 127.2, 127.4, 128.2, 129.1, 132.1,
132.3, 133.1, 133.2, 140.1, 142.7; HRMS (EI) m/z: M+ Calcd for
[C23H13N]: 303.1048, Found 303.1050.
1,4-bis(4’-tert-butyl-4-biphenyl)buta-1,3-diyne (3g): White solid
(354 mg, 76%), purified by column chromatography (eluent:
hexane), mp: >2508C; IR (KBr): n=2836, 2142, 1577, 1490, 1250,
820 cmÀ1 1H NMR (400 MHz, CDCl3): 1.36 (s, 18H), 7.48 (d, J=
;
Compound 10: White solid, purified by column chromatography
8.8 Hz, 4H) 7.51–7.61 (m, 12H); 13C NMR (75 MHz,CDCl3): 31.5, 34.8,
74.7, 82.0, 120.5, 126.0, 126.8, 127.1, 133.1, 137.3, 141.9; HRMS (EI)
m/z: M+ Calcd for [C36H34]: 466.2661, Found 466.2665.
1
(Eluent: hexane); H NMR (300 MHz, CDCl3): 7.31–7.40 (m, 6H), 7.54
(d, J=6.6 Hz, 4H); 13C NMR (75 MHz, CDCl3): 74.1, 81.7, 121.9, 128.6,
129.3, 132.7; HRMS (EI) m/z: M+ Calcd for [C16H10]: 202.0782, Found
202.0780.
1,4-bis(3’,5’-dichloro-4-biphenyl)buta-1,3-diyne (3h): White solid
(270 mg, 55%), purified by column chromatography (eluent:
hexane), mp: 1908C; IR (KBr): n=2958, 2852, 2198, 1238, 820,
790 cmÀ1 1H NMR (400 MHz, CDCl3): 7.36–7.37 (m, 2H), 7.46–7.46
;
Acknowledgements
(m, 4H), 7.51–7.54 (m, 4H), 7.60–7.63 (m, 4H); 13C NMR (100 MHz,
CDCl3): 75.4, 81.8, 122.1, 125.7, 127.3, 127.9, 133.3, 135.7, 139.4,
143.2; HRMS (EI) m/z: M+ Calcd for [C28H14Cl4]: 489.9824, Found
489.9819.
P.G. gratefully acknowledges the Science and Engineering Re-
search Board (SERB; CRG/2019/002236), India, for financial sup-
port. S.S. and S.M. thank Council for Scientific and Industrial
Research (CSIR, New Delhi) for their fellowship (SRF). P.S. thanks
the SERB project CRG/2019/002236 for her fellowship (RA). The
authors also thank Indian Association for the Cultivation of Sci-
ence (IACS, Kolkata) for the Instrumentation Facility.
1,4-bis(3’-chloro-4-biphenyl)buta-1,3-diyne (3i): Pale yellow solid
(245 mg, 58%), purified by column chromatography (eluent:
hexane), mp: 1858C; IR (KBr): n=3012, 2280, 1234, 1155, 822,
1
753 cmÀ1; H NMR (500 MHz, CDCl3): 7.34–7.40 (m, 4H), 7.47 (d, J=
7.5 Hz, 2H), 7.55–7.58 (m, 6H), 7.62 (d, J=8.0 Hz, 4H); 13C NMR
(125 MHz, CDCl3): 75.1, 81.9, 121.5, 125.4, 127.3, 127.4, 128.0, 130.3,
133.2, 135.0, 140.7, 142.1; HRMS (EI) m/z: M+ Calcd for [C28H16Cl2]:
422.0629, Found 422.0632.
Conflict of interest
4-(Phenylethynyl)-1,1’-biphenyl (4a): White solid, purified by
column chromatography (Eluent: hexane), mp: 1658C; IR (KBr): n=
The authors declare no conflict of interest.
1
3061, 3032, 1901, 1441, 1404, 1180, 1065 cmÀ1; H NMR (400 MHz,
CDCl3): 7.35–7.38 (m, 4H), 7.44–7.48 (m, 2H), 7.54–7.62 (m, 8H);
13C NMR (100 MHz, CDCl3): 89.5, 90.2, 122.4, 123.5, 127.2, 127.8,
128.4, 128.5, 129.0, 131.8, 132.2, 140.5, 141.1; HRMS (EI) m/z: M+
Calcd for [C20H14]: 254.1096, Found 254.1095.
Keywords: 1,3-diyne · CÀC coupling · macrobicycle
regioselectivity · supramolecular catalysis
·
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Manuscript received: December 18, 2020
Accepted manuscript online: January 13, 2021
Version of record online: March 18, 2021
Chem. Eur. J. 2021, 27, 7307 –7314
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