Palladium catalyzed selective mono-arylation of o-carboranes via B-H activation

Article abstract of DOI:10.1039/c5cc01331c

Palladium catalyzed selective mono-arylation of o-carboranes with aryl iodides has been developed, and a series of B(8)/B(9)-Ar-o-carboranes anchored with active groups have been synthesized with moderate to good yield as well as good selectivity. The mechanism involving Pd^II catalyzed electrophilic B-H activation was also proposed. This journal is

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Palladium catalyzed selective mono-arylation of
o-carboranes via B-H activation
Cite this: DOI: 10.1039/x0xx00000x
Ke Cao*, Yawen Huang, Junxiao Yang and Ji Wu
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
A
palladium catalyzed selective mono-arylation of
carboranes with aryl iodides has been developed, and a series has been rarely reported.
of B(8)/B(9)-Ar- -carboranes anchored with active groups For o-carboranes, molecular orbital calculation indicates the B(8, 9,
have been synthesized with moderate to good yield as well as 10,12) owned higher negative charge density than other boron atoms,
o
-
synthesis of boron functionalized o-carboranes with regioselectivity
8
, 5b
o
II
9
good selectivity. The mechanism involving a Pd catalyzed which led them favour to take electrophilic reaction. However, the
electrophilic B-H activation was also proposed.
four boron atoms of B(8, 9, 10,12) are not full equally, among them,
B(9) and B(12), B(8) and B(10) are equivalence, respectively.
Additionally, B(9,12) possess slight higher negative charge density
than that of B(8,10), hence, the electrophilic reaction of B(9,12)
Carboranes are a class of boron hydride cluster with three-
dimensional aromaticity, which have extensive applications in boron
1
2
1
0
neutron capture therapy (BNCT), supramolecular chemistry and
showed prior to that of B(8,10). Based on the three-dimensional
aromaticity of o-carboranes and transition metal catalyzed direct C-H
functionalization of arenes, we envisioned that if o-carboranes would
display similar chemical reactivity to that of arenes to coupling with
organic partners via B-H activation, and if we can distinguish the slight
difference in reactivity of B(9,12) and B(8,10) to achieve their selective
mono-functionalization. With this idea in mind and our recent
3
coordination chemistry. Thus, regioselective synthesis of carbon and
boron functionalized carboranes has been an attractive subject as
their importance in diverse applications. In the past decades, the
carbon functionalization of carboranes including transition metal
4
mediated/catalyzed method has been well developed. On the
contrary, the boron functionalization of carboranes with
regioselectivity is more challenge because of the slight difference in
reactivity among the 10 B-H bonds, thus led the boron
1
1
research interest in boron cluster chemistry, we found that the
selective mono-arylation of B(8) and B(9) could be realized by
palladium catalyzed direct functionalization of B-H bond with aryl
5
functionalization more complicated than that of carbon. The typical
1
2
method for regioselective synthesis of boron-substituted carboranes
developed by Jones Jr. and Hawthorne is based on boron-halogenated
iodides. Herein, we are pleased to present our results.
To initial of our research, o-carborane (1a) and iodobenzene were
selected to screening conditions and the results were summarized in
Table 1. Extensive investigation indicated palladium salts were
suitable for the coupling reaction. Pioneering work has demonstrated
the capture of iodide by silver salt is crucial in palladium catalyzed
6
carboranes. Due to low activity of the boron-halogen bonds, the
subsequent coupling with Grignard reagent proceeds sluggishly and
has limited application values in synthetic chemistry. Therefore, the
development of new approach, especially with selective mode, for the
boron functionalization of carboranes is eagerly desired but still a
challenging subject.
1
3
direct arylation of arenes with iodobenzene. Therefore, various silver
salts were examined. With Ag O as additive, the coupling product 2a
could be obtained in only 5% yield (entry 1, Table 1). The yield was
slightly increased with AgOAc (entry 2). To our delight, when Ag CO
was used, the yield was enhanced to 36% (entry 3), and the arylation
2
To synthesize boron-substituted carboranes, transition metal
catalyzed direct functionalization via B-H activation would be an ideal
approach, which would avoid the pre-functionalization of carboranes
and generate of versatile carborane derivatives for their diverse
applications. Although selective B-H activation of o-carboranes has
been found in transition metal complex by forming B-M (M =
2
3
1
4
was selective on B(8) and B(9) with a ratio of 1:8. Control
experiments demonstrated that Pd(OAc) and Ag CO were essential
for this coupling reaction, the reaction could not proceed at all
without Pd(OAc) or Cs CO instead (entries 4-5). When the reaction
2
2
3
7
transition metal) bonds, utilization of selective B-H activation for the
2
2
3
was conducted in dioxane and toluene, the corresponding product
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a
Table 1. Palladium catalyzed arylation of o-carborane with iodobenzene.
coupling products with moderate to good yields (2b-2e). However, 1f
was very sluggish for this coupling and only generated trace amount
of the expected product (2f). These results indicate the substituent
groups on Ccage play an important role in the reaction as well as
selectivity.
2
Table 3. Palladium catalyzed selective mono-arylation of 1, 2-Me -o-
a, b
carborane with various aryl iodides.
b
entry
1
catalyst
additive solvent
yield %
(
10 mol%)
c
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
Pd(OAc)
2
2
2
Ag
AgOAc
2
O
DCE
DCE
5
8
36
-
-
12
24
13
trace
Pd(OAc)
Pd(OAc)
-
d
Ag
Ag
2
CO
CO
3
DCE
DCE
2
3
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
2
2
Cs
2
CO
3
DCE
Ag
Ag
Ag
Ag
Ag
2
2
2
2
2
CO
CO
CO
CO
CO
3
3
3
3
3
dioxane
toluene
DCE
DCE
DCE
Pd(PPh
Pd(dppf)
Pd(OAc)
3
2
) Cl
2
2
Cl
2
e
1
0
2
82
a
All reactions were carried on 0.25 mmol 1a or 1b, 0.025 mmol catalyst,
o
0
4
.75 mmol iodobenzene, 0.50 mmol additive and 1 mL solvent at 60 C for
b
c
d
8h under argon atmosphere. Isolated yields. DCE: 1,2-dichloroethane.
e
The ratio of arylation on B(8)/B(9) was 1:8 and determined by GC-MS. The
ratio of arylation on B(8)/B(9) was 1:1.6.
was afforded in 12% and 24% yields, respectively (entries 6-7). The
palladium source was also examined, the catalytic efficiency of
Pd(PPh
Pd(OAc)
employed, the coupling product 2b was obtained with 82% yield
entry 10), and the structure of B(9)-Ph-1,2-dimethyl-o-carborane was
3
)
2
Cl
2 2 2
and Pd(dppf) Cl behaved lower activity than that of
2
(entries 8-9). When 1, 2-dimethyl-o-carborane (1b) was
a
o
All reactions were carried on 0.25 mmol scale in 1 mL DCE for 48h at 60 C
(
b
under argon atmosphere. Isolated yields，the ratio of B(8) and B(9) isomers
15
confirmed by X-ray crystallographic analysis (Figure S1, ESI). The was determined by GC-MS is given in parentheses .
similar phenomenon of prominent yield enhancement has also been
8
b,16
found in fluorination of o-carboranes.
It is worth noting that we
have not detected poly-arylated o-carboranes.
Table 2. Palladium catalyzed selective mono-arylation of o-carboranes with
a, b
iodobenzene.
a
o
All reactions were carried on 0.25 mmol scale in 1 mL DCE for 48h at 60 C
b
under argon atmosphere. Isolated yields, the ratio of B(8) and B(9) isomers
was determined by GC-MS is given in parentheses.
Figure 1. Crystal structure of 2q-B(9) (up) and 2q-B(8) (down)
Based on the optimized conditions, the scope of o-carboranes was
then examined and the results were summarized in Table 2. As we can
see, except o-carborane 1a, Ccage-substituted o-carboranes were all
compatible with this transformation, and gave the corresponding
From the aspect of aryl iodides, further investigations demonstrated
this transformation has a broad substrate scope. Various substituent
groups were compatible with this reaction with moderate to good
yields (Table 3). Aryl iodides substituted with electron donating
2
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groups such as methoxyl, ethyoxyl and tert-butyl favored the proposed. A series of 8(9)-aryl-o-carboranes anchored with active
transformation, and the expected products were isolated in good groups have been synthesized with moderate to good yields. It offers
yields (2g
lower reactivity and gave the desired products with moderated yields applications of B-substituted-o-carboranes in related fields. This work
2l 2n 2p). Importantly, bromide, chloride and fluoride substituents represents the first example in cross-coupling of boron hydride cluster
, 2h, 2j, 2k). Halogenated iodobenzenes showed slightly an opportunity for further chemical transformation and diverse
(
,
-
were all untouched, which offered an opportunity to further with organic partner by direct B-H functionalization, which would be
derivatization the products through transition metal catalyzed cross- useful in the design of other coupling reactions of o-carboranes.
couplings. Furthermore, aryl iodides decorated with electron
withdrawing groups such as ethyl 4-iodobenzoate and 4- This work is supported by Scientific Research Fund of Sichuan
iodoacetophenone were also tested, and the corresponding products Provincial Education Department (Nos.13ZB0173, 13TD0022), Open
were obtained with 51% and 43% yields, respectively (2q, 2r). Project of State Key Laboratory Cultivation Base for Nonmetal
Meanwhile, both isomers of 2q could be separated by column Composites and Functional Materials (Nos. 11zxfk26, 13zxfk06).
chromatography, and the structures were confirmed by X-ray
15
crystallographic analysis. (Figure 1) Additionally, the steric hindrance Notes and references
State Key Laboratory Cultivation Base for Nonmetal Composite and
of aryl iodides also has a large influence on the coupling. When 2-
Functional Materials & School of Materials Science and Engineering,
Southwest University of Science and Technology, Mianyang, P. R. China
E-mail: caoke@swust.edu.cn
Iodoanisole and 1-Bromo-2-iodobenzene were subjected to the
conditions, the coupling could not proceed at all (2i, 2m).
Comparing to the documented method, in which, large excess of Electronic Supplementary Information (ESI) available: Complete
Grignard reagents are required and has poor group tolerance, for characterization data, cif files for 2b-B(9), 2d-B(9), 2q-B(9), 2q-B(8) and
synthesis of boron arylated carboranes by palladium catalyzed cross 2r-B(9). See DOI: 10.1039/b000000x/
1
0a, 17-18
coupling of Grignard regents with iodocarboranes,
this method offers an efficient and economical way for synthesis of
(9)-aryl-o-carboranes with active groups.
we can see
1
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8
,
Although the exact mechanism is not clear, based on the experiment
results, a plausible mechanism was proposed as shown in Scheme 1.
An electrophilic substitution of more nucleophilic B(9,12) and B(8,10)
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to Pd(OAc)
2
takes place first leading to intermediate
I
. Then, forming
, after
IV
Pd intermediate II by oxidation addition of iodobenzenes to
I
reductive elimination give rise to product and release III. Finally,
regenerating the active Pd(OAc) by cleavage of Pd-I bond by Ag CO
We consider the ratio of regioisomers is reasonable in view of the
2
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2
2
3
.
8
b, 19
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anchored on boron atom, the congested environment would hinder
1
7
secondary arylation by forming transition state II
.
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with aryl iodides.
6
7
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3
Conclusions
In summary, we have developed a palladium catalyzed mono-
arylation of o-carboranes selectively at B(8) and B(9) under mild
conditions, and a Pd(II) catalyzed electrophilic B-H activation was also
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2
1
1
B
6
1
5
CCDC of isomers 2b-B(9), 2d-B(9), 2q-B(9), 2q-B(8) and 2r-B(9)
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respectively.
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