Nickel-catalyzed cross-coupling reactions of o-carboranyl with aryl iodides: Facile synthesis of 1-aryl-o-carboranes and 1,2-diaryl-o-carboranes

Article abstract of DOI:10.1002/anie.201502502

A nickel-catalyzed arylation at the carbon center of o-carborane cages has been developed, thus leading to the preparation of a series of 1-aryl-o-carboranes and 1,2-diaryl-o-carboranes in high yields upon isolation. This method represents the first examp

Full text of DOI:10.1002/anie.201502502

.
Angewandte
Communications
International Edition: DOI: 10.1002/anie.201502502
German Edition: DOI: 10.1002/ange.201502502
Carboranes
Nickel-Catalyzed Cross-Coupling Reactions of o-Carboranyl with Aryl
Iodides: Facile Synthesis of 1-Aryl-o-Carboranes and 1,2-Diaryl-o-
Carboranes**
Cen Tang and Zuowei Xie*
Abstract: A nickel-catalyzed arylation at the carbon center of
o-carborane cages has been developed, thus leading to the
preparation of a series of 1-aryl-o-carboranes and 1,2-diaryl-o-
carboranes in high yields upon isolation. This method
represents the first example of transition metal catalyzed
C,C’-diarylation by cross-coupling reactions of o-carboranyl
with aryl iodides.
the efficient and high-yielding synthesis of a variety of 1-aryl-
o-carboranes and 1,2-diaryl-o-carboranes.
We commenced our studies by screening for a suitable
temperature for the cross-coupling reaction of 1-MgCl-1,2-
C2B10H11 with phenyl iodide in THF under nickel catalysis. 1-
MgCl-1,2-C2B10H11 was conveniently prepared in situ from an
equimolar reaction of o-carborane (1) with iPrMgCl in THF.
Selected results are compiled in Table 1 (see the Supporting
Information for a complete list). Of the factors examined,
I
cosahedral carboranes (closo-C2B10H12) have received
increasing interest in medicine as boron neutron capture
therapy agents,[1] in supramolecular design/nanomaterials as
building blocks,[2] and in coordination/organometallic chemis-
try as ligands.[3] Recently, the discovery of very interesting
photophysical properties of aryl-o-carboranes implies the
existence of a unique role of o-carborane cages on the
electronic systems.[4] However, the cage structure makes its
derivatization difficult, thus resulting in a limited application
scope. In general, 1-aryl-o-carboranes and 1,2-diaryl-o-car-
boranes are prepared from the condensation reaction of the
corresponding aryl or diaryl acetylenes with decaborane,[4,5]
and the yields of the desired products are variable. The
hypertoxicity of decaborane also complicates this method.
Table 1: Optimization of nickel-catalyzed cross-coupling reaction.[a]
Entry
PhI [equiv]
T [8C]
Solvent
NiCl2 (mol%)
Yield [%][b]
1
2
3
4
5
6
7
8
1.0
1.0
1.0
1.0
1.0
1.0
1.1
1.2
1.2
1.2
1.2
1.2
RT
40
70
THF
THF
THF
THF
THF
THF
THF
THF
Et2O
DME
toluene
toluene
10
10
10
10
5
2
2
2
2
n.r.
5
67
88
86
86
88
91
n.r.
100
100
100
100
100
60
100
100
100
À
Obviously, a direct Ccage Csp2 bond formation by cross-
coupling of an o-carboranyl and aryl is an attractive strategy
for the synthesis of 1,2-(aryl)n-o-carboranes (n = 1, 2).
Unfortunately, direct nucleophilic substitution reaction of
lithiocarboranes with aryl iodides does not proceed. In
contrast, the reaction of 1-Cu-o-C2B10H11 or 1,2-Cu2-o-
C2B10H10 with aryl iodides affords 1-aryl-o-carboranes in
moderate yields[6] and no 1,2-diaryl-o-carboranes are pro-
duced,[6,7] probably a result of steric reasons and the
formation of the homocoupling product bis(carborane).[8]
Inspired by the transition metal catalyzed cross-coupling
reaction of aryls,[9] we initiated a study to develop a transition
metal catalyzed arylation of o-carboranes. Herein we report
a nickel-catalyzed cross-coupling of carboranyls with aryls for
9
[c]
10
11
12
2
2
0
–
96
n.r.
[a] Reactions were conducted on 1.0 mmol scale of 1 in 5 mL of solvent
in a closed flask for 12 h. [b] Determined by GC. [c] Complicated reaction
mixture. DME=dimethoxyethane, n.r.=no reaction, THF=tetrahydro-
furan.
reaction temperature and solvent played the most important
role. High temperatures facilitated the cross-coupling reac-
tion. No obvious change in the yields of 2a was observed
when the catalyst loading was changed from 10 to 2 mol%.
Accordingly, the reaction conditions of entry 11 (Table 1)
were identified as the optimal reaction conditions. Under such
reaction conditions, PhI offered the best yield of 2a among all
the PhX tested (X = I, Br, Cl; see Table S1 in the Supporting
Information).
[*] C. Tang, Prof. Dr. Z. Xie
Department of Chemistry and State Key Laboratory of Synthetic
Chemistry, The Chinese University of Hong Kong
Shatin, N.T., Hong Kong (China)
E-mail: zxie@cuhk.edu.hk
Subsequently, the scope of this cross-coupling reaction
was examined and the results were summarized in Table 2. In
general, such a cross-coupling reaction was very efficient, thus
giving 1-aryl-o-carboranes in high to excellent yields. It was
tolerant of functional groups such as Cl, F, CF3, OCH3, and N-
aryl carbazole. In addition, iodonaphthalene and iodophen-
anthrene were compatible with the reaction conditions, thus
[**] The work described herein was supported by grants from the
Research Grants Council of the Hong Kong Special Administration
Region (Project No. CUHK7/CRF/12G and 14306114) and the
National Basic Research Program of China (973 Program, Grant No.
2012CB821600).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201502502.
7662
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 7662 –7665

Angewandte
Chemie
Table 2: Synthesis of 1-aryl-o-carboranes.[a,b]
Table 3: Synthesis of 1,2-diaryl-o-carboranes.[a,b]
[a] Yield of isolated products. [b] Reactions were conducted at 1.0 mmol
scale in 5 mL of toluene in a closed flask at 1008C for 6 h. [c] Used
3 equiv of p-IC6H4Cl. [d] Reaction time was 8 h. [e] Reaction was
performed at 1408C (bath temperature).
species 2n (Table2). For an aryl iodide with a strong electron-
withdrawing group, such as CF3, the diarylation product 3d
was obtained in a considerably reduced yield of 56%
(Table3).
1
The compounds 2 and 3 were fully characterized by H,
13C, and 11B NMR spectroscopy as well as high-resolution
mass spectrometry. The molecular structures of 2b, 2d, 2 f, 2g,
2j, 2l, 2r and 3a, 3b, 3c, 3e, 3 f, 3g were further confirmed by
single-crystal X-ray analyses. Figure 1 shows the representa-
tive structures of 2l and 3g.
[a] Yield of isolated products. [b] Reactions were conducted at 1.0 mmol
scale in 5 mL of toluene in a closed flask at 1008C for 12 h. [c] Heated at
1408C. [d] Used 0.6 equiv of either 1,4-diiodobenzene or 4,4’-diiodobi-
phenyl or 1,3-diiobenzene.
affording 2k (81%) and 2l (67%), respectively. For diiodo-
benzene and diiodobiphenyl, dicarboranylation proceeded to
generate 2o, 2p, and 2q in 68–78% yields upon isolation. 1-
Methyl-o-carborane also worked well to give 2r in 88% yield.
For substrates with ortho substituents, a higher bath temper-
ature (1408C) was required to afford the desired products 2h
and 2n in more than 75% yield.
In contrast, during the isolation of 2a, a trace amount of
1,2-diphenyl-o-carborane was detected by GC-MS, thus
indicating that diarylation on both cage carbon atoms was
possible. We then screened the reaction conditions and
identified the optimal conditions as shown in Table 3 (see
Table S2 for details). This reaction was compatible with
a variety of aryl iodides, thus giving 1,2-diaryl-o-carboranes in
56–86% yields, except for 1,2-dinaphthyl-o-carborane (3k).
The low yield of 3k was probably a result of poor reactivity of
iodonaphthalene and steric reasons. A higher bath temper-
ature (1408C) was required for 1-iodo-2-methylphenyl to
afford 3h in 73% yield. The more sterically demanding 1-
iodo-2-isopropylphenyl produced only the monoarylated cage
Figure 1. Molecular structures of 2l (left) and 3g (right).
To gain some insight into the reaction mechanism, the
following control experiments were carried out. No reaction
proceeded in the absence of NiCl2, thus suggesting that the
nickel catalyst was essential for such cross-coupling reactions.
In addition, the yield of 2a remained unchanged after
Angew. Chem. Int. Ed. 2015, 54, 7662 –7665
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
7663

.
Angewandte
Communications
J. A. Maguire, N. S. Hosmane, J. Am. Chem. Soc. 2010, 132,
6578 – 6587; e) P. Bauduin, S. Prevost, P. Farràs, F. Teixidor, O.
Diat, T. Zemb, Angew. Chem. Int. Ed. 2011, 50, 5298 – 5300;
Angew. Chem. 2011, 123, 5410 – 5412; f) A. M. Cioran, A. D.
addition of 1 equivalent of the radical trapping agent 1,1-
diphenylethylene[10] to the reaction system, and thus ruled out
the radical pathway. Under the similar reaction conditions, 3a
was obtained in 80% yield when using 2a as the starting
material. In contrast, an equimolar reaction of trans-(p-
methoxyphenyl)iodobis(triethylphosphine)nickel(II)[11] with
1-MgCl-1,2-C2B10H11 in 1,2-xylene at 1508C for 12 hours
afforded 2g in 46% yield upon isolation. These experimental
data suggested that the aforementioned cross-coupling is
a Kumada-type reaction.[12] Accordingly, a reaction mecha-
nism is proposed as follows. The catalysis is initiated by a Ni0
species which is generated in situ from the reaction of NiCl2
with the Grignard reagent. Oxidative addition of ArI on Ni0
results in the formation of [ArNiI(solvent)2]. Transmetalation
between [ArNiI(solvent)2] and 1-MgCl-1,2-C2B10H11 affords
[ArNi(o-carboranyl)(solvent)2]. Reductive elimination gives
1-aryl-o-carboranes and regenerates the catalyst Ni0. Repeat
of this catalytic cycle using 1-MgCl-2-aryl-1,2-C2B10H10 as
a starting material produces 1,2-diaryl-o-carboranes.
ˇ
´
Musteti, F. Teixidor, Z. Krpetic, I. A. Prior, Q. He, C. J. Kiely, M.
Brust, C. ViÇas, J. Am. Chem. Soc. 2012, 134, 212 – 221; g) D.
Brusselle, P. Bauduin, L. Girard, A. Zaulet, C. ViÇas, F. Teixidor,
I. Ly, O. Diat, Angew. Chem. Int. Ed. 2013, 52, 12114 – 12118;
Angew. Chem. 2013, 125, 12336 – 12340; h) R. N. Grimes, Dalton
Trans. 2015, 44, 5939 – 5956.
[3] For selected reviews, see: a) N. S. Hosmane, J. A. Maguire in
Comprehensive Organometallic Chemistry III, Vol. 3 (Eds.:
R. H. Crabtree, D. M. P. Mingos), Elsevier, Oxford, 2007,
chap. 5; b) Z. Xie, Coord. Chem. Rev. 2002, 231, 23 – 46; c) Z.
Xie, Acc. Chem. Res. 2003, 36, 1 – 9; d) L. Deng, Z. Xie, Coord.
Chem. Rev. 2007, 251, 2452 – 2476; e) Z.-J. Yao, G.-X. Jin, Coord.
Chem. Rev. 2013, 257, 2522 – 2535; f) R. N. Grimes, Carboranes,
2nd ed., Elsevier, Oxford, 2011; g) N. S. Hosmane, Boron
Science: New Technologies and Applications, Taylor & Francis
Books/CRC, Boca Raton, FL, 2011; h) Z. Xie, Sci. China Chem.
2014, 57, 1061 – 1063.
[4] a) K. R. Wee, W. S. Han, D. W. Cho, S. Kwon, C. Pac, S. O. Kang,
Angew. Chem. Int. Ed. 2012, 51, 2677 – 2680; Angew. Chem.
2012, 124, 2731 – 2734; b) K. R. Wee, Y. J. Cho, S. Jeong, S.
Kwon, J. D. Lee, I. H. Suh, S. O. Kang, J. Am. Chem. Soc. 2012,
134, 17982 – 17990; c) A. Ferrer-Ugalde, E. J. Juµrez-PØrez, F.
Teixidor, C. ViÇas, R. Sillanpää, E. PØrez-Inestrosa, R. NfflÇez,
Chem. Eur. J. 2012, 18, 544 – 553; d) K. R. Wee, Y. J. Cho, J. K.
Song, S. O. Kang, Angew. Chem. Int. Ed. 2013, 52, 9682 – 9685;
Angew. Chem. 2013, 125, 9864 – 9867; e) C. Shi, H. Sun, X. Tang,
H. Lv, H. Yan, Q. Zhao, J. Wang. W. Huang, Angew. Chem. Int.
Ed. 2013, 52, 13434 – 13438; Angew. Chem. 2013, 125, 13676 –
13680; f) C. Shi, H. Sun, Q. Jiang, Q. Zhao, J. Wang, W. Huang,
H. Yan, Chem. Commun. 2013, 49, 4746 – 4748; g) H. J. Bae, J.
Chung, H. Kim, J. Park, K. M. Lee, T.-W. Koh, Y. S. Lee, S. Yoo,
Y. Do, M. H. Lee, Inorg. Chem. 2014, 53, 128 – 138; h) H. Naito,
Y. Morisaki, Y. Chujo, Angew. Chem. Int. Ed. 2015, 54, 5084 –
5087; Angew. Chem. 2015, 127, 5173 – 5176; i) A. Ferrer-Ugalde,
A. Gonzµlez-Campo, C. ViÇas, J. Rodríguez-Romero, R. Santil-
lan, N. Farfµn, R. Sillanpää, A. Sousa-Pedrares, R. NfflÇez, F.
Teixidor, Chem. Eur. J. 2014, 20, 9940 – 9951.
[5] a) T. L. Heying, J. W. Ager. , Jr., S. L. Clark, D. J. Mangold, H. L.
Goldstein, M. Hillman, R. J. Polak, J. W. Szymanski, Inorg.
Chem. 1963, 2, 1089 – 1092; b) U. Kusari, Y. Li, M. G. Bradley,
L. G. Sneddon, J. Am. Chem. Soc. 2004, 126, 8662 – 8663; c) Y.
Li, P. J. Carroll, L. G. Sneddon, Inorg. Chem. 2008, 47, 9193 –
9202; d) D. Olid, R. NfflÇez, C. ViÇas, F. Teixidor, Chem. Soc.
Rev. 2013, 42, 3318 – 3336; e) M. E. El-Zaria, K. Keskar, A. R.
Genady, J. A. Ioppolo, J. McNulty, J. F. Valliant, Angew. Chem.
Int. Ed. 2014, 53, 5156 – 5160; Angew. Chem. 2014, 126, 5256 –
5260; f) Z. Qiu, Tetrahedron Lett. 2015, 56, 963 – 971.
À
In summary, a nickel-catalyzed Ccage Csp2 bond-forming
reaction by the cross-coupling reaction of o-carboranyl with
aryls has been developed for efficient and high-yield synthesis
of 1-aryl-o-carboranes and 1,2-diaryl-o-carboranes. This
method is general for the C-arylation of o-carboranes and
represents the first transition metal catalyzed cage C,C’-
diarylation of o-carboranes, as well as offers a facile and direct
route for the incorporation of o-carborane unit into con-
jugated p systems.
Experimental Section
Typical procedure for the preparation of 1-aryl-o-carboranes (2):
iPrMgCl (2.0m in THF, 0.6 mL, 1.2 mmol) was slowly added to a THF
solution (5 mL) of o-carborane (144 mg, 1.0 mmol) at 08C, and the
mixture was stirred at 08C for 1 h. After replacement of THF with
toluene (5 mL), and addition of aryl iodide (1.2 mmol) and NiCl2
(2.6 mg, 0.02 mmol), the reaction mixture was heated at 1008C under
stirring for 12 h in a closed flask. Then, the reaction was quenched
with water (10 mL) and extracted with diethyl ether (20 mL ” 3). The
ether solutions were combined and concentrated to dryness in vacuo.
The residue was subjected to flash column chromatography on silica
gel (230–400 mesh) using n-hexane as eluent to give 1-aryl-o-
carboranes (2).
À
Keywords: arylation · C C formation · cross-coupling ·
homogeneous catalysis · nickel
[6] R. Coult, M. A. Fox, W. R. Gill, P. L. Herbertson, K. Wade, J.
Organomet. Chem. 1993, 462, 19 – 29.
How to cite: Angew. Chem. Int. Ed. 2015, 54, 7662–7665
Angew. Chem. 2015, 127, 7772–7775
[7] Reaction of 1-phenyl-2-sodium-o-carborane with 4-nitrofluoro-
benzene gave the corresponding aromatic nucleophilic substitu-
tion product. The NO2 group is essential for this reaction. See:
a) K. Ohta, T. Goto, Y. Endo, Inorg. Chem. 2005, 44, 8569 – 8573;
b) K. Ohta, T. Goto, Y. Endo, Tetrahedron Lett. 2005, 46, 483 –
485.
[8] S. Ren, Z. Xie, Organometallics 2008, 27, 5167 – 5168.
[9] For selected reviews, see: a) I. A. I. Mkhalid, J. H. Barnard, T. B.
Marder, J. M. Murphy, J. F. Hartwig, Chem. Rev. 2010, 110, 890 –
931; b) R. Martin, S. L. Buchwald, Acc. Chem. Res. 2008, 41,
1461 – 1473; c) C.-L. Sun, B.-J. Li, Z.-J. Shi, Chem. Rev. 2011, 111,
1293 – 1314; d) D.-G. Yu, B.-J. Li, Z.-J. Shi, Acc. Chem. Res. 2010,
43, 1486 – 1495; e) S. R. Neufeldt, M. S. Sanford, Acc. Chem. Res.
2012, 45, 936 – 946; f) T. W. Lyons, M. S. Sanford, Chem. Rev.
[1] For selected reviews, see: a) M. F. Hawthorne, Angew. Chem.
Int. Ed. Engl. 1993, 32, 950 – 984; Angew. Chem. 1993, 105, 997 –
1033; < lit b > A. F. Armstrong, J. F. Valliant, Dalton Trans.
2007, 4240 – 4251; c) F. Issa, M. Kassiou, L. M. Rendina, Chem.
Rev. 2011, 111, 5701 – 5722.
[2] For selected examples, see: a) X. Yang, W. Jiang, C. B. Knobler,
M. F. Hawthorne, J. Am. Chem. Soc. 1992, 114, 9719 – 9721; b) H.
Jude, H. Disteldorf, S. Fischer, T. Wedge, A. M. Hawkridge,
A. M. Arif, M. F. Hawthorne, D. C. Muddiman, P. J. Stang, J.
Am. Chem. Soc. 2005, 127, 12131 – 12139; c) M. Koshino, T.
Tanaka, N. Solin, K. Suenaga, H. Isobe, E. Nakamura, Science
2007, 316, 853 – 853; d) B. P. Dash, R. Satapathy, E. R. Gaillard,
7664 www.angewandte.org
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 7662 –7665

Angewandte
Chemie
2010, 110, 1147 – 1169; g) X. Chen, K. M. Engle, D.-H. Wang, J.-
Q. Yu, Angew. Chem. Int. Ed. 2009, 48, 5094 – 5115; Angew.
Chem. 2009, 121, 5196 – 5217; h) K. M. Engle, T.-S. Mei, M.
Wasa, J.-Q. Yu, Acc. Chem. Res. 2012, 45, 788 – 802; i) G. Song, F.
Wang, X. Li, Chem. Soc. Rev. 2012, 41, 3651 – 3678; j) J.-Q. Yu, Z.
Shi, C-H Activation, Springer, Berlin, 2010.
Soc. 2010, 132, 16737 – 16740; b) M. Ochiai, T. Shu, T. Nagaoka,
Y. Kitagawa, J. Org. Chem. 1997, 62, 2130 – 2138.
[11] T. T. Tsou, J. K. Kochi, J. Am. Chem. Soc. 1979, 101, 6319 – 6322.
[12] a) K. Tamao, K. Sumitani, M. Kumada, J. Am. Chem. Soc. 1972,
94, 4374 – 4376; b) R. J. P. Corriu, J. P. Masse, J. Chem. Soc.
Chem. Commun. 1972, 144a – 144a.
[10] Selected examples of using 1,1-diphenylethylene as a radical
trapping reagent, see: a) W. Liu, H. Cao, H. Zhang, H. Zhang,
K. H. Chung, C. He, H. Wang, F. Y. Kwong, A. Lei, J. Am. Chem.
Received: March 17, 2015
Published online: May 8, 2015
Angew. Chem. Int. Ed. 2015, 54, 7662 –7665
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
7665