Metal-Free Oxidative B?N Coupling of nido-Carborane with N-Heterocycles

Article abstract of DOI:10.1002/anie.201904940

A general method for the oxidative substitution of nido-carborane (7,8-C₂B₉H₁₂^?) with N-heterocycles has been developed by using 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) as an oxidant. This metal-free B?N coupling strategy, in both inter- and intramolecular fashions, gave rise to a wide array of charge-compensated, boron-substituted nido-carboranes in high yields (up to 97 %) with excellent functional-group tolerance under mild reaction conditions. The reaction mechanism was investigated by density-functional theory (DFT) calculations. A successive single-electron transfer (SET), B?H hydrogen-atom transfer (HAT), and nucleophilic attack pathway is proposed. This method provides a new approach to nitrogen-containing carboranes with potential applications in medicine and materials.

Full text of DOI:10.1002/anie.201904940

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
International Edition Chemie
www.angewandte.org
Accepted Article
Title: Metal-Free Oxidative B−N Coupling of nido-Carborane with N-
Heterocycles
Authors: Zhongming Yang, Weijia Zhao, Wei Liu, Xing Wei, Meng
Chen, Xiao Zhang, Xiaolei Zhang, Yong Liang, Changsheng
Lu, and Hong Yan
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201904940
Angew. Chem. 10.1002/ange.201904940
Link to VoR: http://dx.doi.org/10.1002/anie.201904940
http://dx.doi.org/10.1002/ange.201904940

Angewandte Chemie International Edition
10.1002/anie.201904940
RESEARCH ARTICLE
Metal-Free Oxidative B−N Coupling of nido-Carborane with N-
Heterocycles
Zhongming Yang, Weijia Zhao, Wei Liu, Xing Wei, Meng Chen, Xiao Zhang, Xiaolei Zhang*, Yong
Liang*, Changsheng Lu*, and Hong Yan*
2 9
challenge is that the negatively charged (7,8-C B H
12−) causes
Abstract: A general method for the oxidative substitution of nido-
−
carborane (7,8-C
2
B
9
H12 ) with N-Heterocycles has been developed by
the B−H bond reluctant to nucleophilic substitution. closo Borane
or monocarbaborane anions could undergo selective reactions
with a number of nucleophiles to form B−N, B−O, or B−S bonds
after converted into aryliodonium zwitterions.[11] So we envision
that the nucleophilic attack toward the B−H bond of nido-
carborane cage could be achieved if the electric charge could be
tuned to neutral after single-electron oxidation, thus furnishing an
oxidative B−H substitution process. It is noteworthy that the
irreversible oxidation nature of nido-carborane cage has already
been observed in electrochemistry with the oxidation potential of
+0.3−+0.4 V vs Fc/Fc+,[12] but this phenomenon is scarcely
employed in synthetic chemistry. Using this as an approximate
guide for the reaction design, one can screen a number of
potential oxidants to target the nido-carboranes for reactivity
explorations.
using 2,3-dicyano-5,6-dichlorobenzoquinone (DDQ) as an oxidant.
This metal-free B−N coupling strategy, in both inter- and intra-
molecular fashions, gave rise to a wide array of charge-compensated,
boron-substituted nido-carboranes in high yields (up to 97%) with
excellent functional group tolerance under mild conditions. The
reaction mechanism was investigated by density functional theory
(DFT) calculations. A successive single electron transfer (SET), B−H
hydrogen atom transfer (HAT) and nucleophilic attack pathway is
proposed. This method provides a new approach to the nitrogen-
containing carboranes with potential applications in medicines and
materials.
Introduction
Functionalization of inert B−H bond is an efficient tool for the direct
derivatization of carboranes[1] with step and atomic economies.
Conventional methods for cage B−H functionalization of
carborane require strong oxidants or electrophiles,[3] which
exhibit low site-selectivity and limited substrate scope. To this end,
transition metal-mediated selective cage B−H functionalization[4]
has been developed, but in most cases, requires preinstalling a
directing group to realize reactivity and selectivity. Recently,
nucleophilic B−H substitution of o-carboranes has been
[2]
[5]
developed, by Xie and coworkers, which represents a new
protocol to the controlled functionalization of B−H bond. Basically,
the B(3)/B(6) vertex is the most electron-deficient since it is
bonded to two cage carbon atoms and readily undergoes
−
−
nucleophilic attacks by strong nucleophiles such as F and MeO
to afford nido-carborane anions (7,8-C
12−).[6] nido-
Carboranes, as open-cage analogous of closo-carboranes, are
important building blocks for the synthesis of
2
9
B H
Scheme 1. B−N coupling of carboranes.
metallacarboranes,[7] biologically useful molecules[8] and
luminescent materials.[9] However, functionalization of the B−H
bonds of nido-carborane still remains in its infancy.[10] One major
On the other hand, nitrogen-containing carboranes have received
much attention owing to their potential applications in drug
discovery[13] as well as in catalysis.[14] Transition metal-catalyzed
B−N bond formation from B−X (X = Br or I) or B−H bond has been
reported, delivering cage boron-aminated-carboranes (Scheme
1a).[ In addition, B−N coupled metallacarboranes has been
documented by Teixidor and coworkers as electron accumulative
[*]
Z. Yang, W. Zhao, W. Liu, X. Wei, M. Chen, X. Zhang, Dr. X. Zhang,
Prof. Dr. Y. Liang, Prof. Dr. C. Lu, Prof. Dr. H. Yan
State Key Laboratory of Coordination Chemistry, Jiangsu Key
Laboratory of Advanced Organic Materials, School of Chemistry and
Chemical Engineering, Nanjing University
Nanjing 210023 (China)
15]
o
molecules, by reacting a B−I precursor with pyridines at 200 C
E-mail: zhangxiaolei@yahoo.com
(
Scheme 1b).[16] Despite these advances, straightforward and
yongliang@nju.edu.cn
luchsh@nju.edu.cn
hyan1965@nju.edu.cn
general methods for B−N coupling of nido-carborane are rather
limited. Hawthorne and coworkers reported a B−N coupling of
nido-carborane with pyridine by using FeCl
3
as an oxidant
Supporting information for this article is given via a link at the end of
the document.
(Scheme 1c).[17] However, this reaction suffers from the limitation
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201904940
RESEARCH ARTICLE
Figure 1. Mechanistic studies.
on substrate scope and the in situ generated nido-carborane
dianion could react with metal ions to generate metallacarboranes
as side reactions. In this sense, a metal-free protocol for the cage
B−H oxidative substitution would be highly desirable considering
the functional group tolerance, environmental sustainability as
well as the avoidance of metal-removal process in the late-stage
synthesis of carborane derivatives. Herein, we report the DDQ-
mediated site-selective B−N coupling of nido-carborane with N-
Table 1. Reaction development.[a]
heterocycles, affording
a vast class of nitrogen-containing
carboranes in a metal-free manner. Both experiments and
theoretical calculations indicate that this oxidative substitution
reaction with DDQ represents a new reaction mode for the B−H
functionalization of nido-carboranes.
o
Yield [%][b]
Entry
Oxdiant
Solvent
T [ C]
o
1
2
3
4
5
6
PhI(OAc)
2
CH
CH
CH
CH
CH
3
3
3
3
3
CN
CN
CN
CN
CN
80 C
31%
29%
26%
47%
trace
96%
24%
94%
Results and Discussion
o
K
2
S
O
2 8
80 C
o
BQ
80 C
As a proof-of-principle experiment, we studied the intermolecular
B−N coupling of (NMe
4
)(7,8-Ph
2
-nido-C
2
B
9
H10) (1a) with 4-
o
DDQ
AgNO
DDQ
DDQ
DDQ
80 C
phenylpyridine with a major focus on the oxidants (Table 1, entry
o
3
80 C
1-5). The use of 2.0 equiv of DDQ resulted in a promising yield of
2
a (47 %) when the reaction was conducted in anhydrous CH
3
CN
o
DME
DME
DME
80 C
o
at 80 C for 10 hours (Table 1, entry 4). Further solvent screening
7[c]
80 C
o
(
Table S1) indicated that anhydrous DME was the best reaction
medium of choice, leading to the nearly quantitative conversion of
a to 2a in 96 % isolated yield (Table 1, entry 6). Reducing the
8[d]
R.T.
1
[
a] 1a (0.1 mmol), 4-phenylpyridine (1.2 equiv), oxidant (2.0 equiv),
solvent (2.0 mL), 10 h, Ar atmosphere. [b] Isolated yield. [c] DDQ
1.0 equiv). [d] 4-phenylpyridine (3.0 equiv) and 2 h. (BQ:
oxidant load to 1.0 equiv led to a significant loss of yield (Table 1,
entry 7).
(
benzoquinone, DDQ: 2,3-dicyano-5,6-dichlorobenzo-quinone,
DME: 1,2-dimethoxyethane. See more conditions in Table S1.)
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201904940
RESEARCH ARTICLE
Table 2. Reaction scope for the intermolecular B−N of nido-carborane with N-heterocycles.[a]
[
a] nido-Carboranes (0.1 mmol), 4-phenylpyridine (3.0 equiv), DDQ (2.0 equiv), DME (2.0 mL), 2-5 h, Ar atmosphere. Isolated yield. [b]
4-Chloropyridine hydrochloride was used. [c] nido-Carborane (0.3 mmol), 1,2-di(pyridin-4-yl)ethene (0.1 mmol). [d] Combined yield of
two isomers.
To gain insight into the reaction mechanism, both control
experiments and theoretical calculations (M06-2X with solvation)
were carried out. The activation of bridging hydrogen atom
intrinsic reaction coordinate (IRC) plots of key B−N coupling
transition state. Along with the red line, the N atom of pyridine
2 3
gradually moves to the B atom in the C B plane with the B−N
(
B−H−B) on the C
2
B
3
plane was validated by deuterium-labeled
distance decreased from 3.07 to 1.96 Å. The corresponding B−H
experiment in which bridging deuterium (B−D−B) was fully
distance is kept around 1.19 Å during this process. Starting from
grabbed by DDQ after standard B−N coupling process (Figure 1a). the blue line, accompanied by the further shortening of the
−
distance between B and N atom, the H shifts twice along the C
2
B
3
Theoretical calculations were conducted to gain a whole picture
of the reaction pathway (Figures 1b and 1c). Firstly, the nido-
carborane anion is oxidized by DDQ via single electron transfer
face spontaneously (no barrier) to form the B-H-B in the final
product. The formation of B−N coupling product is exergonic by
55.8 kcal/mol. The overall activation free energy was found to be
26.7 kcal/mol (black double-headed arrow, 1.0 equiv of pyridine,
Figure 1c) which is comparable with the experimental conditions
(80 oC). Inspired by the computed reaction pathway, we
speculated that the overall barrier would be decreased to 15.8
kcal/mol (red double-headed arrow, Figure 1c) with additional free
pyridine. In other words, the experimental temperature might be
lowered to room temperature with more pyridine. To our delight,
experimental data confirmed our prediction: when increasing the
loading of 4-phenylpyridine to 3.0 equiv, the reaction runs
smoothly at room temperature with an excellent isolated yield of
94 % in 2 hours (Table 1, entry 8). With the optimal conditions in
hand (Table 1, entry 8), a variety of N-heterocycles coupling
partners were examined (Table 2). We were pleased to find that
(
SET) to form int-I which is slightly endergonic by 0.3 kcal/mol.
Subsequently, another electron is oxidized by the second DDQ
coupling with a deprotonation process forming a cage-open
carborane intermediate int-II. The formal H atom transfer process
is exergonic by 21.9 kcal/mol. Besides, DFT calculations indicate
that the non-covalent hydrogen bond (H-bond) between pyridine,
·
as a Brønsted base, and the proton in [HDDQ] would further pull
down the energy by 10.9 kcal/mol (−32.5 vs. −21.6 kcal/mol).
Furthermore, since the carbon-linked B(9/11) sites are more
electron-positive, the free pyridine undergoes a nucleophilic
attack toward the B(9/11)−H site of cage-open carborane
−
intermediate with the departure of H , which could be abstracted
2 3
by the C B face as the B−H−B hydrogen. Figure 1d shows the
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201904940
RESEARCH ARTICLE
a vast class of pyridines and quinolines could react smoothly with
nido-carboranes to provide efficient access to B−N coupling
products with good to excellent yields. For pyridines, electron-
donating groups on the pyridine ring give rise to higher yields than
electron-withdrawing substituents (2a-2e vs 2h-2l). Sterically
hindered 2-methylpyridine forms the product (2f) in only 15 %
yield. Notably, methoxyl, carboxyl methylester, amino, and vinyl
substituents are well-tolerated, affording the desired products
the cage B(9/11) selectivity (Table S2). The stability of such B−N
coupling compounds has been further investigated. The solution
of compound 2a (0.4 mL CD
3
CN), for instance, was treated with
0.1 mL D O, DCl or NaOD, respectively. The 2-day NMR tracking
2
experiments demonstrate that 2a has excellent stability in a
neutral or an acidic environment, however, it is completely
destroyed in an alkaline environment after 6 hours (Figures S24-
S26).
(
2b-2c, 2l-2m, 2o-2r, and 3e-3i) in synthetically satisfying yields.
The Boc-protected amino group furnished the desired products
2o, 2p and 3f-3g) in excellent yields (80 % to 93 %). The free
The versatility of intermolecular B−N coupling with N-heterocycles
led us to investigate the intramolecular B−N annulations. Using
compound 6a as the substrate, the nucleophilic nitrogen atom
reacted with the B(9/11)−H vertex of nido-carboranyl in the
presence of 2.0 equiv of DDQ at room temperature, affording the
products 7a (Table 3) with a BN-fused six-membered ring. Note
that although B−N fused benzenes or cyclohexenes have been
developed,[19] rare examples contain a polyhedron carboranyl unit
with BN-fusion.[20] Sterically hindered substituents (methyl, n-/s-
butyl, and phenyl-) at the 2-quinolyl position afforded slightly
decreased yield (7b-7e), whereas tert-butyl substitution totally
blocked the conversion (7f). 2-tetrahydrofuryl and 1,4-dioxan-2-yl
substituents at the 2-quinolyl position were also tolerated,
affording two conformational isomers in 80 % and 83 % combined
yields, respectively. Either changing the substituents at the cage-
carbon site or replacing the quinolyl with pyridyl moiety afforded
comparable outcomes (7i-7k). Compounds 7a-7k were fully
characterized by H, 13C, and 11B NMR spectroscopy and HRMS.
The molecular structures of 7c, 7g (7g-1 and 7g-2), 7h, 7i, 7j, and
7k were unambiguously identified by single-crystal X-ray analysis
(Table S2).
(
amino group could also be tolerated under the mild oxidative
conditions, though the amine-substituted products (2q, 2r, 3h,
and 3i) were isolated in relatively lower yields. This metal-free
protocol was compatible with halogenated (F, Cl, Br and I)
substituents (2h-2k, and 3j-3n), which can be utilized for further
modifications. By using
a
ratio of 1:3 between 4,4’-
vinylenedipyridine and 1a, the product 2s containing two nido-
carboranyl units was isolated in 60% yield (Table 2a), which was
further confirmed by X-ray analysis (Table S2).
To further probe the scope of B−N bond formation, we evaluated
other N-heterocyclic substrates with comparable nucleophilicity to
pyridines (Nu value = 11.5 in MeCN from Mayr’s database[18]). To
our delight, the B−N coupling of 1a proceeds well with imidazole,
oxazole, thiazole, pyrimidine, and azaindole, affording the
corresponding B−N compounds in good to excellent yields (4a-4i,
1
63 to 90 %). No reaction with triazole was observed, probably
owing to much lower nucleophilicity (Nu value = 7.7). To our
knowledge, very few reports documented the incorporation of N-
heterocycles into carboranes via boron linkage. One example for
the imidazole-substituted m-carborane was prepared by using
palladium-catalyzed cross-coupling reaction and bromo- or iodo-
carborane precursors.[15a] Thus, oxidative B−N coupling provides
a new route to the convenient and versatile synthesis of N-
heterocycle-substituted carboranes.
Table 3. Reaction scope for the intramolecular B−N annulation.[a]
The scope of nido-carborane with different carbon substituent
effects was next explored using 4-phenylpyridine as the coupling
partner. Both aryl and alkyl substituents were well-tolerated,
furnishing the corresponding products (5a-5h) in 73 to 95 % yields.
In the case of unsymmetric carbon substitutions, the addition
2 3
favors the sterically less hindered site on the C B plane, affording
an inseparable mixture of 5i-1 and 5i-2 (ratio = 3:2) for methyl
substitution and 5j-1 and 5j-2 (ratio = 5:1) for tert-butyl substitution.
The configuration of the isomers was identified by 2D-NOESY
(
Figure S10) and further supported by DFT calculations (Figures
S21 and S22).
The B−N coupled products (2-5) are neutral and can be
recognized as the zwitterionic compounds. They are fully
characterized by 1H, 11B, 13C, and 19F NMR spectroscopy and
high-resolution mass spectrometry (HRMS). Their 11B{ H} NMR
spectra span the range of −36 to 5 ppm, with the N-substituted
cage boron observed at ca. 5 ppm. The single-crystal X-ray
analysis of 2a, 2g, 2l, 2r, 3a, and 4c unambiguously confirmed
1
[a] 6 (0.1 mmol), DDQ (2.0 equiv), DCM (2.0 mL), R.T., Ar
atmosphere and 0.5-1 h. Isolated yield. [b] Isolated as two
isomers.
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201904940
RESEARCH ARTICLE
The conventional method of introducing a nido-carboranyl unit
into a functional molecule was based on deboronation of parent
closo-carboranes in an alkaline environment, which is not suitable
for the basic sensitive molecules. However, this oxidative B−N
coupling protocol could be applied to the direct incorporation of a
nido-carboranyl unit into pharmaceutical drugs. For example,
antifungal drugs such as clotrimazole and miconazole reacted
with 1a to give the nido-carboranyl-containing products 8 and 9
Different from traditional methods for carborane transformations,
this metal-free strategy complements the toolbox of direct B−H
functionalization of carboranes, enabling the incorporation of a
wide array of N-heterocycles into the nido-carboranyl units via
B−N coupling both intermolecularly and intramolecularly. Given
the experimental and theoretical indications on the successive
oxidation and hydrogen atom transfer of nido-carborane anion,
the redox behavior of nido-carborane may be utilized in the future
electro-redox or photo-redox synthesis. The facile synthesis has
application potentials for materials and pharmaceuticals.
(
Figure 2a). In another hand, closo-carborane-based luminescent
materials molecules have been extensively studied,[21] but few
examples were involved in the nido-carborane derivatives.[9] Here
we find that product 2n exhibits a significant AIE effect in a
THF/H
2
O
mixed solution (Figures 2c and 2e). When the Experimental Section
vol%) reached to 80%, a light yellow
volumetric ratio of water (f
w
nido-Carboranes (0.1 mmol) and corresponding N-heterocycles (0.3 mmol,
emission started to appear at 525 nm, indicative of the AIE-
behavior. In the case of product 3i, a positive solvatochromism
phenomenon was observed as the emission peak exhibits a red
shift from 492 nm (n-hexane) to 547 nm (DMSO), and the
quantum yield reaches a maximum value (Ф = 80%) in THF
3.0 equiv) were added to a flame-dried Schlenk tube with a magnetic stir
bar under argon atmosphere. Then anhydrous DME (2.0 mL) was added
via a syringe, followed by addition of DDQ (45.4 mg, 0.2 mmol) under
argon atmosphere. The mixture was stirred at room temperature for 2-5
hours, then filtered and concentrated under vacuo. The crude product was
purified on preparative TLC using PE/DCM as an eluent to afford the
intermolecular B−N coupling products 2-5.
(
Figures 2d and 2f). These results demonstrate the potential
applications of the N-heterocycle-containing nido-carborane
compounds in pharmaceuticals, luminescent materials,
bioimaging, biosensing, etc.
Compounds 6 (0.1 mmol) and anhydrous DCM (2.0 mL) were added to a
flame-dried 10 mL Schlenk tube with a magnetic stir bar under argon
atmosphere. Then DDQ (45.4 mg, 0.2 mmol) was added and the mixture
was stirred at room temperature for 0.5-1 hour. The reaction mixture was
then filtered through a celite plug, and concentrated under vacuo. The
crude product was purified on preparative TLC using PE/DCM as an eluent
to afford the intramolecular products 7.
Acknowledgements
The authors gratefully acknowledge the financial support from
NSFC (21820102004, 21531004, and 21803030), the National
Thousand Young Talents Program, the Jiangsu Specially-
Appointed Professor Plan, and the NSF of Jiangsu Province
(
BK20170631) in China. We are grateful to Prof. Zhuangzhi Shi
for his helpful suggestions and the High Performance Computing
Center (HPCC) of Nanjing University for doing the numerical
calculations in this paper on its blade cluster system.
Keywords: B−N cross-coupling • mechanistic study • metal-free
•
nido-carborane • oxidative substitution
[
1]
a) N. S. Hosmane in Boron Science: New Technologies and Applications,
CRC Press: Boca Raton, FL, 2011; b) M. Scholz, E. Hey-Hawkins, Chem.
Rev.2011, 111, 7035; c) R. N. Grimes, Dalton Trans. 2015, 44, 5939-
Figure 2. a) nido-carborane modified drug molecules. b) The normalized UV/Vis
absorption of 2n and 3i. c) Emission spectra of 2n, upon increasing water from
5
956. d) R. N. Grimes in Carboranes, 3rd ed., Elsevier: Oxford, U.K.,
2
4
0% to 99% (λex = 373 nm). d) Emission spectra of 3i in different solvents (λex
30 nm). e) Photographs of 2n in THF/H O solution with various fractions of
) taken under UV light (365 nm). f) Photographs of 3i in different
=
2
2016;
water (f
w
[2]
For selected examples, see: a) T. Peymann, A. Herzog, C. B. Knobler,
M. F. Hawthorne, Angew. Chem. 1999, 111, 1130-1132; Angew. Chem.
Int. Ed. 1999,38, 1061-1064; b) S. Kongpricha, H. Schroeder, Inorg.
Chem. 1969, 8, 2449-2452.
solvents taken under UV light (365 nm).
[
3]
For selected examples, see: a) J. Li, C. F. Logan, M. Jones, Inorg. Chem.
Conclusion
1991, 30, 4866-4868; b) J. A. Potenza, W. N. Lipscomb, G. D. Vickers,
H. Schroeder, J. Am. Chem. Soc. 1966, 88, 628-629; c) A. Herzog, A.
Maderna, G. N. Harakas, C. B. Knobler, M. F. Hawthorne, Chem. - Eur.
J. 1999, 5, 1212-1217.
In summary, a new reaction mode for the oxidative cage B−N
coupling of nido-carboranes has been proposed and validated.
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201904940
RESEARCH ARTICLE
[
4]
a) M. G. L. Mirabelli, L. G. Sneddon, J. Am. Chem. Soc. 1988, 110, 449-
53; b) R. Zhang, L. Zhu, G, Liu, H. Dai, Z. Lu, J. Zhao, H. Yan, J. Am.
2013, 125, 13676-13680; Angew. Chem. Int. Ed. 2013, 52, 13434-13438;
c) R. Visbal, I. Ospino, J. M. López-de-Luzuriaga, A. Laguna, J. Am.
Chem. Soc. 2013, 135, 4712-4715; d) B. Wang, D. P. Shelar, X. Z. Han,
T. T. Li, X. Guan, W. Lu, K. Liu, Y. Chen, W. F. Fu, C. M. Che, Chem. -
Eur. J. 2015, 21, 1184-1190; e) J. C. Axtell, K. O. Kirilikovali, P. I.
Djurovich, D. Jung, V. T. Nguyen, B. Munekiyo, A. T. Royappa, A. L.
Rheigold, A. M. Spokoyny, J. Am. Chem. Soc. 2016, 138, 15758-15765;
f) K. Nishino, Y. Morisaki, K. Tanaka, Y. Chujo, New J. Chem. 2017, 41,
10550-10554; g) N. Van Nghia, S. Jana, S. Sujith, J. Y. Ryu, J. Lee, S.
U. Lee, M. H. Lee, Angew. Chem. 2018, 130, 12663-12668; Angew.
Chem. Int. Ed. 2018, 57, 12483-12488.
4
Chem. Soc. 2012, 134, 10341-10344; c) Z. Wang, H, Ye, Y. Li, Z. Li, H.
Yan, J. Am. Chem. Soc. 2013, 135, 11289-11298; d) Z. Qiu, Y. Quan, Z,
Xie, J. Am. Chem. Soc. 2013, 135, 12192-12195; e) Y. Quan, Z, Xie, J.
Am. Chem. Soc. 2014, 136, 15513-15516; f) H. Lyu, Y. Quan, Z. Xie,
Angew. Chem .2015, 127, 10769-10772; Angew. Chem. Int. Ed. 2015,
54, 10623-10616; g) K. Cao, Y. Huang, J. Yang, J. Wu, Chem. Commun.
2015, 51, 7257-7260; h) Y. Quan, Z. Xie, Angew. Chem. 2016, 128,
1317-1320; Angew. Chem. Int. Ed. 2016, 55, 1295-1298; i) Y. Quan, C.
Tang, Z. Xie, Chem. Sci. 2016, 7, 5838-5845; j) H. Lyu, Y. Quan, Z. Xie,
Angew. Chem. 2016, 128, 12019-12023; Angew. Chem. Int. Ed. 2016,
[10] a) L. I. Zakharkin, V. N. Kalinin, G. G. Zhigareva, Russ. Chem. Bull., 1979,
28, 2198-2199; b) V. I. Meshcheryakov, P. S. Kitaev, K. A. Lyssenko, Z.
A. Starikova, P. V. Petrovskii, Z. Janoušek, M. Corsini, F. Laschi, P.
Zanello, A. R. Kudinov, J. Organomet. Chem. 2005, 690, 4745-4754; c)
M. Y. Stogniy, E. N. Abramova, I. A. Lobanova, I. B. Sivaev, V. I. Bragin,
P. V. Petrovskii, V. N. Tsupreva, O. V. Sorokina, V. I. Bregadze, Collect.
Czech. Chem. Commun. 2007, 72, 1676-1688; d) R. Frank, T. Grell, M.
Hiller ,E. Hey-Hawkins, Dalton Trans. 2012, 41, 6155-6161; e) R. Frank,
H. Auer, E. Hey-Hawkins, J. Organomet. Chem. 2013, 747, 217-224; f)
R. Frank, A. K. Adhikari, H. Auer, E. Hey-Hawkins, Chem. Eur. J. 2014,
20, 1440-1446; g) S. V. Timofeev, O. B. Zhidkova, E. A. Prikaznova, I. B.
Sivaev, A. Semioshkin, I. A. Godovikov, Z. A. Starikova, V. I. Bregadze,
J. Organomet. Chem. 2014, 757, 21-27; h) M. V. Zakharova, I. B. Sivaev,
S. A. Anufriev, S. V. Timofeev, K. Yu. Suponitsky, I. A. Godovikov , V. I.
Bregadze, Dalton Trans. 2014, 43, 5044–5053; i) S. A. Anufriev, I. B.
Sivaev, K. Yu. Suponitsky, I. A. Godovikov, V. I. Bregadze, Eur. J. Inorg.
Chem. 2017, 4436-4443; j) S. A. Anufriev, M. V. Zakharova, I. B. Sivaev,
V. I. Bregadze, Russ. Chem. Bull. 2017, 66, 1643-1649; k) S. A. Erokhina,
M. Yu. Stogniy, K. Yu. Suponitsky, I. D. Kosenko, I. B. Sivaev, V. I.
Bregadze, Polyhedron, 2018, 153, 145-151; l) M. Yu. Stogniy, S. A.
Erokhina, K. Yu. Suponitsky, A. A. Anisimov, I. B. Sivaev , V. I. Bregadze,
New J. Chem. 2018, 42, 17958-17967.
5
5, 11840-11844; J. Am. Chem. Soc. 2016, 138, 12727-12730; k) K.
Cao, T. Xu, J. Wu, L, Jiang, J, Yang, Chem. Commun. 2016, 52, 11446-
11449; l) Y. Zhang, Y. Sun, F. Lin, J. Lin, S. Duttwyler, Angew. Chem.
2016, 128, 15838-15843; Angew. Chem. Int. Ed. 2016, 55, 15609-15614;
m) R. M. Dziedzic, J. L. Martin, J. C. Axtell, L. M. A. Saleh, T.-C. Ong,
Y.-F. Yang, M. S. Messina, A. L. Rheingold, K. N. Houk, A. M. Spokoyny,
J. Am. Chem. Soc. 2017, 139, 7729-7732; n) X. Zhang, H. Zheng, J. Li,
F. Xu, J. Zhao, H. Yan, J. Am. Chem. Soc .2017, 139, 14511-14517; o)
R. Cheng, Z, Qiu, X, Xie, Nat. Commun. 2017, 8, 14827; p) C.-X. Li, H.-
Y. Zhang, T.-Y. Wong, H.-J. Cao, H. Yan, C-S. Lu, Org. Lett. 2017, 19,
5
178-5181; q) Y. Quan, Z. Qiu, X. Xie, Chem. -Eur. J. 2018, 24, 2795-
805; r) X. Zhang, H. Yan, Chem. Sci. 2018, 9, 3964-3969; s) F. Lin, J.-
2
L. Yu, Y. Shen, S.-Q. Zhang, B. Spingler, J. Liu, X. Hong, S. Duttwyler,
J. Am. Chem. Soc. 2018, 140, 13798-13807; t) F. Lin, Y. Shen, Y. Zhang,
Y. Sun, J, Liu, S. Duttwyler, Chem. -Eur. J. 2018, 24, 551-555; u) H, Lyu,
J. Zhang, Y. Quan, X. Xie, J. Am. Chem. Soc. 2019, 141, 4219-4224; v)
X. Zhang, H. Yan, Coord. Chem.Rev. 2019, 378, 466-482.
[
5]
a) C. Tang, J. Zhang, Z. Xie, Angew. Chem. 2017, 56, 8642-; Angew.
Chem. Int. Ed. 2017, 129, 8768-8772; b) C. Tang, J. Zhang, J. Zhang, Z.
Xie, J. Am. Chem. Soc. 2018, 140, 16423-16427.
[
[
6]
7]
a)M. F. Hawthorne, D. C. Young, J. Am. Chem. Soc. 1965, 87, 1818-
1819; b) J. Yoo, J.-W. Hwang, Y. Do, Inorg. Chem. 2001, 40, 568-570.
[11] a) P. Tokarz, P. Kaszyński, S. Domagala, K. Wozniak, J.
Organomet.Chem. 2015, 798, 70-79; b) J. Pecyna, P. Kaszyński, B.
Ringstrand, D. Pociecha, S. Pakhomov, A. G. Douglass, V. G. Young, Jr,
Inorg. Chem. 2016, 55, 4016-4025; c) A. N. Hajhussein, L. S. Abyzahra,
A. Pietrzak, M. F. Sadek, M. O. Ali, J. Wojciechowski, A. C. Friedli, P.
Kaszyński, Arkivoc, 2018, part vii, 225-235; d) R. Zurawiński, R.
Jakubowski, S. Domagala, P. Kaszyński, K. Wozniak, Inorg. Chem. 2018,
57, 10442-10456; e). M. O. Ali, J. C. Lasseter, R. Zurawiński, A. Pietrzak,
J. Pecyna, J. Wojciechowski, A. C. Friedli, D. Pociecha, P. Kaszyński,
Chem. Eur. -J. 2019, 25, 2616-2630.
For selected examples, see: a) Z. Xie, Acc. Chem. Res. 2003, 36,1-9; b)
N. S. Hosmane, J. A. Maguire in Comprehensive Organometallic
Chemistry III, Vol 3, (Eds.: R. H. Crabtree, D. M. P. Mingos), Elsevier:
Oxford, U.K., 2007, Chapter 5; c) Z. J. Yao, G.-X. Jin, Coord. Chem. Rev.
2013, 257, 2522-2535; d) D. Olid, R. Núñez, C. Viñas, F. Teixidor, Chem.
Soc. Rev. 2013, 42, 3318-3336; e) S. A. Anufriev, M. V. Zakharova, M.
Y. Stogniy, I. B. Sivaev, V. I. Bregadze, Pure Appl. Chem. 2018, 90, 633-
6
42; f) S. V. Timofeev, O. B. Zhidkova, I. B. Sivaev, Z. A. Starikova, K.
Y. Suponitsky, H. Yan, V. I. Bredadze, J. Organomet. Chem. 2018, 867,
42-346;
3
[12] a) R. Núñez, M. Tarrés, A. Ferrer-Ugalde, F. F. Biani, F. Teixidor, Chem.
Rev. 2016, 116, 14307-14378; b) N. Van Nghia, J. Oh, J. Jung, M. H.
Lee, Organometallics 2017, 36, 2573-2580.
[
8]
For selected examples, see: a) Y. Zhu, A. T. Peng, K. Carpenter, J. A.
Maguire, N. S. Hosmane, M. Takagaki, J. Am. Chem. Soc. 2005, 127,
9
875-9880; b) P. Cígler, M. Kožíšek, P. Řezáčová, J. Brynda, Z.
[13] For selected examples, see: a) A. H. Soloway, W. Tjarks, B. A. Barnum,
F. G. Rong, R. F. Barth, I. M. Codogni, J. G. Wilson, Chem. Rev. 1998,
98, 1515-1562; b) M. F. Hawthorne, A. Maderna, Chem. Rev. 1999, 99,
3421-3434; c) I. V. Korolkov, A. L. Kozlovskiy, Y. G. Gorin, A. V.
Kazantsev, D. I. Shlimas, M. V. Zdorovets, N. K. Ualieva, V. S. Rusakov,
J. Nanopart. Res. 2018, 20, 240; d) T. O. B. Olusanya, G. Calabrese, D.
G. Fatouros, J. Tsibouklis, J. R. Smith, Biophys. Chem. 2019, 247, 25-
33.
Otwinowski, J. Pokorná, J. Plešek, B. Grüner, L. Dolečková-Marešová,
M. Máša, J. Sedláček, J. Bodem, H.-G. Kräusslich, V. Král, J. Konvalinka,
Proc. Natl. Acad. Sci. U.S.A. 2005,102,15394-15399; c) J. Brynda, P.
Mader, V. Šícha, M. Fábry, K. Poncová, M. Bokardiev, B. Grüner, P,
Cígler, P. Řezáčová, Angew. Chem. 2013, 125, 14005-14008; Angew.
Chem. Int. Ed. 2013, 52, 13760-13763; d) M.-B. Sárosi, W. Neumann, T.
P. Lybrand, E. Hey-Hawkins, J. Chem. Inf. Model. 2017, 57, 2056-2067;
e) D. J. Worm, S. Els-Heindl, M. Kellert, R. Kuhnert, S. Saretz, J.
Koebberling, B. Riedl, E. Hey-Hawkins, A. G. Beck-Sickinger, J. Pep. Sci.
[14] a) N. S. Hosmane, J. A. Maguire, Eur. J. Inorg. Chem. 2003, 3989-3999;
b) Z. Xie, Coord. Chem. Rev. 2006, 250, 259-272; c) H. Shen, Z, Xie, J.
Am. Chem. Soc.2010, 132, 11473-11480.
2
018, 24, e3119; f) M. Couto, M. F. García, C. Alamón, M. Cabrera, P.
Cabral, A. Merlino, F. Teixidor, H. Cerecetto, C. Viñas, Chem. - Eur. J.
018, 24, 3122-3126. g) R. F. Barth, J. Neuro-Oncol. 2003, 62, 1-5; h) M.
[15] a) R. M. Dziedzic, L. M. Saleh, J. C. Axtell, J. L. Martin, S. L. Stevens, A.
T. Royappa, A. L. Rheingold, A. M. Spokoyny, J. Am. Chem. Soc. 2016,
138, 9081-9084; b) H. Lyu, Y. Quan, Z. Xie, J. Am. Chem. Soc., 2016,
138, 12727-12730. c) H. Li, F. Bai, H. Yan, C. Lu, V. I. Bregadze, Eur. J.
Org. Chem. 2017, 1343-1352; d) Y. Shen, Y. Pan, K. Zhang, X. Liang, J.
Liu, B. Spingler, S. Duttwyler, Dalton Trans. 2017, 46, 3135-3140.
[16] A. B. Buades, V. S. Arderiu, D. Olid-Britos, C. Viñas, R. Sillanpää, M.
Haukka, X. Fontrodona, M. Paradinas, C. Ocal, F. Teixidor, J. Am. Chem.
Soc. 2018, 140, 2957-2970.
2
F. Hawthorne, M. W. Lee, J. Neuro-Oncol. 2003, 62, 33-45; i) J. Cabrera-
González, E. Xochitiotzi-Flores, C Viñas, F. Teixidor, H. García-Ortega,
N. Farfán, R. Santillan, T. Parella, R. Núñez, Inorg. Chem. 2015, 54,
5021-5031.
[
9]
For selected examples, see: a) B. P. Dash, R. Satapathy, E. R. Gaillard,
J. A. Maguire, N. S. Hosmane, J. Am. Chem. Soc. 2010, 132, 6578-6587;
b) C. Shi, H. Sun, X. Tang, W. Lv, H. Yan, W. Huang, Angew. Chem.
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201904940
RESEARCH ARTICLE
[
[
[
17] H. C. Kang, S. S. Lee, C. B. Knobler, M. F. Hawthorne, Inorg. Chem.
991, 30, 2024-2031.
18] The Nu values
http://www.cup.lmu.de/oc/mayr/reaktionsdatenbank).
1
were
obtained
from
Mayr’s
database
(
19] a) Y. Quan, Z. Xie, J. Am. Chem. Soc .2015, 137, 3502-3505; b) D. Zhao,
J. Zhang, Z. Xie, J. Am. Chem. Soc . 2015, 137, 13938-13942; c) T. L.
Chan, Z. Xie. Chem. Sci. 2018, 9, 2284-2289; d) R. Zhang, Y. Yuan, Z.
Qiu, Z. Xie, Chin. J. Chem. 2018, 36, 273-279; e) F. Lin, Y. Shen, Y.
Zhang, Y. Sun, J. Liu, S. Duttwyler, Chem. -Eur. J. 2018, 24, 551-555; f)
Z. X. Giustra, S. Y. Liu, J. Am. Chem. Soc. 2018, 140, 1184-1194; g) K.
Edel, J. S. A. Ishibashi, S. Y. Liu, H. F. Bettinger, Angew. Chem. 2019,
1
31, 4103-4106; Angew. Chem. Int. Ed. 2019, 58, 4061-4064; h) C.-Y.
Zhang, K. Cao, T.–T. Xu, L. Jiang, J. Yang, Chem. Commun. 2019, 55,
30-833;.
8
[
20] a) J. H. Wright, C. E. Kefalidis, F. S. Tham, L. Maron, V. Lavallo, Inorg.
Chem. 2013, 52, 6223-6229; b) M. Asay, C. E. Kefalidis, J. Estrada, D.
S. Weinberger, J. Wright, C. E. Moore, A. L. Rheingold, L. Maron, V.
Lavallo, Angew. Chem. 2013, 125, 11774-11777; Angew. Chem. Int. Ed.
2013, 52, 11560-11563; c) A L. Chan, J. Fajardo, Jr., J H. Wright, II, M.
Asay, V. Lavallo, Inorg. Chem. 2013, 52, 12308-12310; d) Y. Sun, J.
Zhang , Y. Zhang, J. Liu, S. van der Veen, S. Duttwyler, Chem. -Eur. J.
2018, 24, 10364-10371.
[
21] For selected examples, see: a) L. Zhu, S. Liu, H. Yan, Q. Zhao, W. Huang,
Chem. Commun. 2013, 49, 10638-10640; b) C. Shi, H. Sun, Q. Jiang, Q.
Zhao, J. Wang, W. Huang, Chem. Commun. 2013, 49, 4746-4748; c), Y.
Lee, J. Park, J. Lee, S. Lee, M. Lee, J. Am. Chem. Soc. 2015, 137, 8018-
8021; d) D. Tu, P. Leong, S. Guo, H. Yan, C. Lu, Q. Zhao, Angew. Chem.
2017, 129, 11528-11532;Angew. Chem. Int. Ed. 2017, 56, 11370-11374;
e) J. Li, C. Yang, X. Peng, Y. Chen, Q.Qi, X. Luo, W-Y. Lai , W. Huang,
J. Mater. Chem. C. 2018, 6, 19-28; f) R. Huang, K. Liu, H. Liu, G. Wang,
T. Liu, R. Miao, H. Peng, Y. Fang, Anal. Chem. 2018, 90, 14088-14093;
g) X. Wu, J. Guo, Y. Quan, W. Jia, D. Jia, Y. Chen, Z. Xie, J. Mater.
Chem. C. 2018, 6, 4140-4149; h) M. Z. Shafikov, A. F. Suleymanova, A.
Schinabeck, H. Yersin, J. Phys. Chem. Lett. 2018, 9, 702-709; i) S-Y.
Kim, Y-J. Cho, H-J. Son, D. W. Cho, S. O. Kang, J. Phys. Chem. A. 2018,
122, 3391-3397; j) H. Mori, K. Nishino, K. Wada, Y. Morisaki, K. Tanaka,
Y. Chujo, Mater. Chem. Front. 2018, 2, 573-579; k) A. V. Marsh, N. J.
Cheetham, M. Little, M. Dyson, A. J. P. White, P. Beavis, C. N. Warriner,
A. C. Swain, P. N. Stavrinou, M. Heeney, Angew. Chem. Int. Ed. 2018,
57, 10640-10645; l) K.Nishino, K. Uemura, K. Tanaka, Y. Chujo, New J.
Chem. 2018, 42, 4210-4214; m) Z. Peng, K. Zhang, Z. Huang, Z. Wang,
S. Duttwyler, Y. Wang, P. Luk, J. Mater. Chem. C. 2019, 7, 2430-2435.
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201904940
RESEARCH ARTICLE
Entry for the Table of Contents (Please choose one layout)
Layout 2:
RESEARCH ARTICLE
Zhongming Yang, Weijia Zhao, Wei Liu,
Xing Wei, Meng Chen, Xiao Zhang,
Xiaolei Zhang*, Yong Liang*,
Changsheng Lu*, and Hong Yan *
Page No. – Page No.
Metal-Free Oxidative B−N Coupling of
nido-Carborane with N-Heterocycles
A metal-free B−N coupling of nido-carboranes with various N-heterocycles was
studied in detail, in both inter- and intra-molecular manner at ambient temperature,
with high to excellent yield and high atom economy.
This article is protected by copyright. All rights reserved.