Old Key Opens the Lock in Carborane: The in Situ NHC-Palladium Catalytic System for Selective Arylation of B(3,6)-H Bonds of o-Carboranes via B-H Activation

Article abstract of DOI:10.1021/acs.orglett.9b03790

An efficient in situ Pd-NHC catalytic system for regioselective arylation of B(3,6)-H bonds of o-carborane has been developed for the first time. A series of symmetric and unsymmetric 3,6-diaryl-o-carboranes anchored with active groups have been synthesiz

Full text of DOI:10.1021/acs.orglett.9b03790

Letter
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Old Key Opens the Lock in Carborane: The in Situ NHC-Palladium
Catalytic System for Selective Arylation of B(3,6)−H Bonds of
o‑Carboranes via B−H Activation
Tao-Tao Xu, Ke Cao,* Cai-Yan Zhang, Ji Wu, Li-Fang Ding, and Junxiao Yang
State Key Laboratory of Environment-friendly Energy Materials & School of Material Science and Engineering, Southwest University
of Science and Technology, 59 Qinglong Road, Mianyang, Sichuan 0086-621010, P.R. China
*
S Supporting Information
ABSTRACT: An efficient in situ Pd-NHC catalytic system for regioselective arylation of B(3,6)−H bonds of o-carborane has
been developed for the first time. A series of symmetric and unsymmetric 3,6-diaryl-o-carboranes anchored with active groups
have been synthesized with moderate to good yields under mild conditions. This work offers an efficient protocol for selective
activation of B(3,6)−H bonds and has important value in design coupling reactions for selective functionalization of o-
carboranes.
cosahedral carboranes sharing three-dimensional aromaticity
activation; however, only one example was reported with 40%
GC yield (Scheme 1b). Until Qiu and co-workers developed
the selective borylation of B(3,6)−H of o-carboranes via
10a
I
analogues to benzene are a class of carbon−boron molecular
clusters that have important applications in functional
1
2
materials, boron neutron capture therapy, organometallics,
3
as well as coordination chemistry. Therefore, the regioselective
Scheme 1. Strategies for Functionalization of B(3,6)−H
Bonds of o-Carboranes
functionalization of carboranes has been an important project
and attracted growing interest from chemists.
For o-carboranes, according to the weak acidity of cage C−H
bonds, the methodologies for cage carbon functionalization have
been well-established by nucleophilic substitution or transition-
4
metal-mediated/catalyzed cycloaddition of carboryne. On the
other hand, the selective boron functionalization is still an
intricate subject as the 10 B−H bonds are not fully equal and the
electrophilic reactivity is reduced in the following order: B(9,12)
5
>
B(8,10) > B(4,5,7,11) > B(3,6). In recent years, the
transition-metal-catalyzed B−H activation has emerged as a
powerful tool for regioselective boron functionalization of o-
6
carboranes. According to the difference in electron density of
the 10 B−H bonds, the selective functionalization of B-
7
8
(
8,9,10,12)−H and B(4,5)−H bonds was well-developed by
electrophilic B−H activation and directing-group-guided B−H
activation, respectively. In contrast, the selective activation/
functionalization of electron-deficient B(3,6)−H bonds is still
an intractable project to be addressed.
Although the transition-metal-mediated selective B(3)−H
activation of o-carboranes has been found in transition metal
9
complexes, utilizing transition-metal-catalyzed B−H activation
for selective functionalization of B(3,6)−H bonds has been
1
0
rarely reported. In 1988, Sneddon and co-workers disclosed
Received: October 24, 2019
the first example for hydroboration of propyne via B(3)−H
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b03790
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
1
0b
iridium-catalyzed B−H activation (Scheme 1c), the multistep
deboration capping/deboration capping reaction is still the
dominating route for synthesis of B(3,6)-substituted o-
Table 1. Optimized Conditions for Regioselective Arylation
of B(3,6)−H of o-Carborane
a
11
carboranes (Scheme 1a). However, the transformation of
the borylated o-carborane to 3,6-Ar -o-carborane displayed
2
moderate efficiency even with 20 mol % of PdCl (cod) and 40
2
1
0e
mol % of PCy at high temperature (Scheme 1c). Recently, an
3
organomagnesium-mediated nucleophilic substitution protocol
for selective functionalization of B(3,6)−H bonds was also
b
entry
oxidant
ligand
solvent
T (°C) yield of 2a/3a (%)
1
2
disclosed.
1
2
3
4
5
6
7
8
9
Ag CO3
2
L1
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
L5
L1
L1
DCE
toluene
MeCN
THF
THF
THF
THF
THF
THF
THF
THF
THF
80
110
80
80
80
80
25
25
25
25
25
25
25
25
18/1
20/4
trace
33/5
16/1
N-Heterocyclic carbenes (NHCs) are important ligands with
strong σ-donating ability and high tunability and have extensive
applications in organometallic chemistry as well as synthetic
Ag CO3
2
Ag CO3
2
13
Ag CO
2 3
organic chemistry. Interestingly, pioneering works demon-
AgOAc
AgOTf
strated that the NHCs could generate zwitterionic salts of nido-
14
carborane via deboronation and deprotonation of o-carborane.
Ag CO3
2
50/17
50/18
9/trace
Maybe for this reason, the NHC transition metal catalytic
system has not been applied in the B−H activation of o-
carboranes. One characteristic of the electron-deficient B(3,6)−
H bonds is they prefer to undergo oxidative addition to electron-
c
Ag CO3
2
Ag CO3
2
1
0
Ag CO3
2
10a,b
11
Ag CO
2 3
rich transition metal species over other B−H bonds.
In
12
13
14
Ag CO3
2
25/trace
18/50
5/89
connection with our continued interest in palladium-catalyzed
selective B−H activation of o-carborane, we envisioned
employing the NHC as a ligand to accomplish the B(3,6)−H
activation for two reasons: (1) The Pd-NHC complex could be
Ag CO3
2
Et O
2
d
Ag CO3
2
Et O
2
a
All reactions were carried out using 0.1 mmol o-carborane, 0.4 mmol
iodobenzene, 10 mol % of Pd(OAc) , 20 mol % of ligand, 0.2 mmol
oxidant, and 1 mL of solvent for 24 h under an argon atmosphere.
GC yields. Using 0.2 mmol iodobenzene, 5 mol % of Pd(OAc) , 10
mol % of L1, 0.1 mmol Ag CO . Ag CO was added twice, and the
15
2
in situ formed smoothly (Scheme 2) and thus prevent the
b
c
2
d
Scheme 2. In Situ Formed Pd-NHC
2
3
2
3
reaction was carried out with 1 equiv of Ag CO ; another 1 equiv of
2
3
Ag CO was added after 3 h.
2
3
known deboronation and deprotonation of o-carborane. (2)
The strong σ-donating ability of NHC would reduce the
electrophilicity of Pd-NHC compared to that of Pd(OAc)2;
therefore, the B(3,6)−H bonds might be activated by Pd-NHC,
and the electrophilic palladation of B(8,9,10,12)−H bonds with
activity for this transformation (entries 9−11). It is worth noting
that 2a could be afforded with 25% yield in the presence of 1,3-
bis(2,6-diisopropylphenyl)imidazol-2-ylidene (L5), and the
deboronation and deprotonation of o-carborane was not
7b
Pd(OAc) disclosed in our previous work would be inhibited.
2
Herein, we present the first and efficient in situ NHC-palladium
catalytic system for selective arylation of B(3,6)−H bonds of o-
carboranes.
To begin our research, o-carborane and iodobenzene were
selected as the model substrates to screen conditions, and the
results are summarized in Table 1. When 1,3-bis(2,6-
diisopropylphenyl)imidazolium chloride (IPrHCl, L1) was
used, we found the selective arylation of the B(3)−H bond
could be accomplished with 18% yield; meanwhile, the
diarylation product on B(3,6) was also detected by GC analysis
14
found (entry 12). This result indicates the proposed Pd-
NHC should be in situ formed first, being the catalytic active
species for B(3,6)−H activation. Fortunately, when the reaction
was conducted in ethyl ether, the yield of 3a could be enhanced
to 50% (entry 13). After many efforts, the yield of 3a was further
improved to 89% by adding Ag CO twice.
2
3
Based on the optimized conditions (Table 1, entry 14), the
scope of aryl iodides was then examined. As we can see from
Scheme 3, halogenated iodobenzenes were compatible with this
transformation and gave the expected products with moderate to
good yields (3b−3d, 3f−3i). However, when 1-fluoro-2-
iodobenzene was subjected to the standard conditions, the
desired product was only obtained with 33% yield (3e). This
result demonstrated the steric hindrance of aryl iodides has a
distinct influence on the coupling. Additionally, aryl iodides
substituted with cyano, aldehyde, and ester were also compatible
with this selective arylation and generated the corresponding
products with moderate yields (3j−3l). Meanwhile, the exact
structure of 3j was also confirmed by X-ray crystallographic
(
entry 1). Further studies indicated that THF is more favorable
for this transformation (entries 2−4), and Ag CO is superior to
2
3
other silver salts (entries 5 and 6). To our delight, when the
reaction was carried out at 25 °C, the yields of 2a and 3a could
be improved to 50 and 17%, respectively (entry 7), and the yield
as well as product ratio has no change and even when there is a
decrease of the loading amount of catalyst, oxidant, and
iodobenzene by half (entry 8). Meanwhile, the exact structures
of 2a and 3a were unambiguously confirmed by X-ray
crystallographic analysis (Supporting Information (SI), Figures
S1 and S2). Additionally, other imidazolium salts displayed poor
B
DOI: 10.1021/acs.orglett.9b03790
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 3. Regioselective Arylation of B(3,6)−H of o-
transformation provides an efficient approach for the synthesis
of triaryl-substituted o-carborane derivatives.
,
a b
Carborane with Aryl Iodides
To further expand the diversity of o-carborane derivatives, we
intended to synthesize unsymmetric 3,6-diaryl-o-carboranes
from 2a via B(6)−H activation. To initiate this work, the 3-Ph-o-
carborane (2a) was synthesized according to the optimized
conditions (Table 1, entry 8) with 50% yield. We can see that the
selective arylation of B(6)−H of 2a could proceed smoothly for
aryl iodides substituted with electron-withdrawing groups and
gave the expected products with moderate to good yields
(
Scheme 5, 6a−6h). Meanwhile, the regioselective B(6)−H
Scheme 5. Synthesis of Asymmetric 3,6-Diaryl-o-carboranes
,
a b
via B(6)−H Activation
a
All reactions were carried out on 0.1 mmol scale in 1 mL of Et O for
4 h under an argon atmosphere. Isolated yields.
2
b
2
analysis (SI, Figure S3). On the other hand, aryl iodides
decorated with electron-donating groups displayed poor
efficiency for the transformation, and only 3m was afforded
with 51% yield. This phenomenon has been disclosed in
a
All reactions were carried out on 0.1 mmol scale in 1 mL of THF for
4 h under an argon atmosphere. Isolated yields.
b
2
arylation was confirmed by X-ray crystallographic analysis of 6a
SI, Figure S4). On the other hand, the aryl iodides decorated
Pd(OAc) /IPrHCl-catalyzed cross-coupling of aryl halides and
2
(
indicated that the oxidative addition of aryl iodides should be the
16
with electron-donating groups displayed slight lower activity for
this transformation, and the desired products were afforded with
moderate yields (Scheme 5, 6i−6j). This stepwise selective
arylation of the B−H bond provides an efficient approach for
construction of unsymmetric 3,6-diaryl-o-carboranes under mild
conditions. Moreover, the introduced active groups offer an
opportunity to design and synthesize various unsymmetric 3,6-
diaryl-o-carborane derivatives via further chemical transforma-
tions.
rate-determining step of the reaction.
Subsequently, the boron-functionalized o-carboranes were
then explored. As can be seen from Scheme 4, the o-carboranes
substituted with aryl or benzyl on cage B(9) were compatible
with the selective arylation of B(3,6)−H bonds and gave the
expected products with moderate yields (5a−5d). This
Scheme 4. Regioselective arylation of B(3,6)−H of 9-(R)-o-
,
a b
Carboranes with Iodobenzene
For the mechanism, deboronation and deprotonation of o-
14
carborane were not found with carbene L5 (Table 1, entry 12),
and the electrophilic activation of B(8,9,10,12)−H was
7b
completely inhibited in the presence of Pd(OAc) ; therefore,
2
the Pd-NHC would be in situ formed and be the catalytic active
species for selective B(3)−H activation. According to the rate-
determining step of oxidative addition to aryl iodides deduced
from the results in Scheme 3, the electrophilic activation of the
B(3)−H bond by Pd-NHC should take place first and give the
II
B−Pd -NHC intermediate. Then, oxidative addition of
II
iodobenzenes to B−Pd -NHC and subsequent reductive
elimination would generate B(3)-Ar-o-carborane. Finally, the
active palladium species was regenerated by cleavage of the Pd−
7b
3
I bond with Ag CO for the next catalytic cycle.
2
a
All reactions were carried out on 0.1 mmol scale in 1 mL of Et O for
4 h under an argon atmosphere. Isolated yields.
In conclusion, we have developed an efficient protocol for
regioselective arylation of o-carboranes via in situ formed Pd-
2
b
2
C
DOI: 10.1021/acs.orglett.9b03790
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
NHC-catalyzed B(3,6)−H activation for the first time. This
reaction displays broad substrate scope and excellent tolerance
of various active groups under mild conditions. A series of
symmetric and unsymmetric 3,6-diaryl-o-carboranes anchored
with active groups have been synthesized with moderate to good
yields, which offers a platform for the design and synthesis of
boron-substituted o-carboranes by further chemical trans-
formation and has important value for diverse applications in
related fields. This work offers a facile approach for selective
activation of B(3,6)−H bonds under mild conditions, which
would be useful in design coupling reactions for selective
functionalization of o-carboranes.
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AUTHOR INFORMATION
Corresponding Author
■
*
E-mail: caoke@swust.edu.cn.
ORCID
(
j) Wu, J.; Cao, K.; Zhang, C.-Y.; Xu, T.-T.; Ding, L.-F.; Li, B.; Yang, J.
Org. Lett. 2019, 21, 5986−5989.
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Ke Cao: 0000-0003-0348-2386
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7, 6388−6395. (c) Liu, D.; Dang, L.; Sun, Y.; Chan, H.-S.; Lin, Z.; Xie,
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
This work is supported by National Natural Science Foundation
of China (21602182), Longshan academic talent research
supporting program of SWUST (17LZX324, 18LZX305,
8LZXT02), and the Project of State Key Laboratory of
Environment-friendly Energy Materials, SWUST (17fksy0102,
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DOI: 10.1021/acs.orglett.9b03790
Org. Lett. XXXX, XXX, XXX−XXX