Phosphine oxide-directed palladium-catalyzed B(3)–H arylation of o-carboranes

Article abstract of DOI:10.1016/j.tetlet.2020.152625

The selective functionalization of carboranes has received increasing research interests due to their wild applications in chemistry, life, and material sciences. Among various structurally diverse carboranes, the development of selective functionalization of the commercially available o-carborane (1,2-C₂B₁₀H₁₂) has largely focused on the two acidic C[sbnd]H bonds. By contrast, research on the activation of the other ten hydridic cage B–H vertices is relatively less explored. Of particularly challenging, the most electron-deficient nature of B(3,6)-H bonds render very few synthetic methods available for their functionalization. Herein, we develop a phosphine oxide-directed palladium-catalyzed highly B(3)–H selective arylation of o-carboranes under very mild reaction conditions in short reaction time.

Full text of DOI:10.1016/j.tetlet.2020.152625

Journal Pre-proofs
Phosphine Oxide-Directed Palladium-Catalyzed B(3)–H Arylation of o-Car‐
boranes
Lingxiang Lian, Caixiang Lin, Yi Yu, Yaofeng Yuan, Ke-Yin Ye
PII:
S0040-4039(20)31130-8
DOI:
Reference:
https://doi.org/10.1016/j.tetlet.2020.152625
TETL 152625
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Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
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25 October 2020
31 October 2020
Please cite this article as: Lian, L., Lin, C., Yu, Y., Yuan, Y., Ye, K-Y., Phosphine Oxide-Directed Palladium-
Catalyzed B(3)–H Arylation of o-Carboranes, Tetrahedron Letters (2020), doi: https://doi.org/10.1016/j.tetlet.
2020.152625
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Graphical Abstract
Phosphine Oxide-Directed Palladium-
Leave this area blank for abstract info.
Catalyzed B(3)–H Arylation of o-Carboranes
Lingxiang Lian, Caixiang Lin*, Yi Yu, Yaofeng Yuan and Ke-Yin Ye*
A highly selective, robust and efficient phosphine oxide-directed palladium-catalyzed B(3)–H arylation of o-carborane with
a variety of arylboronic aicds was developed.
O
O
PPh2
B(OH)2
Ar2
Ar1
PPh2
Ar1
Pd
Ar2
B(3)-selectivity
robust (under air)
fast reaction (< 1 h)

1
Tetrahedron Letters
journal homepage: www.elsevier.com
Phosphine Oxide-Directed Palladium-Catalyzed B(3)–H Arylation of o-Carboranes
Lingxiang Liana, Caixiang Lina,, Yi Yua, Yaofeng Yuana and Ke-Yin Ye a,
a Key Laboratory of Molecule Synthesis and Function Discovery (Fujian Province University), College of Chemistry, Fuzhou University, Fuzhou 350108, China
———
ARTICLE INFO
ABSTRACT
 Corresponding authors, e-mail: lincaixia_fzu@fzu.edu.cn (C. Lin); kyye@fzu.edu.cn (K. Ye).
Article history:
Received
Received in revised form
Accepted
The selective functionalization of carboranes has received increasing research interests due to
their wild applications in chemistry, life, and material sciences. Among various structurally
diverse carboranes, the development of selective functionalization of the commercially available
o-carborane (1,2-C2B10H12) has largely focused on the two acidic C–H bonds. By contrast,
research on the activation of the other ten hydridic cage B–H vertices is relatively less explored.
Of particularly challenging, the most electron-deficient nature of B(3,6)-H bonds render very
few synthetic methods available for their functionalization. Herein, we develop a phosphine
oxide-directed palladium-catalyzed highly B(3)–H selective arylation of o-carboranes under
very mild reaction conditions in short reaction time.
Available online
Keywords:
palladium
carborane
B–H activation
cross-coupling
regioselectivity
2009 Elsevier Ltd. All rights reserved.
Introduction
developed an elegant iridium-catalyzed selective cage B(3,6)-
functionalization including the monoborylation/diborylation,[13]
Carboranes, featured as a class of σ-aromatic boron hydride
clusters mixed with one or more CH unit(s), have received much
attention of chemists[1] due to their wild applications in
coordination chemistry,[2] material sciences,[3] and arguably
most prominent in medicinal chemistry as boron neutron capture
therapy agents or pharmacophores.[4] The functionalization of
carboranes, therefore, is a very significant research topic to
construct novel carborane-containing scaffolds for diverse
applications.[5] Among them, the functionalization of the
commercially available, most extensively investigated o-
carborane (1,2-C2B10H12) has largely focused on the weakly
acidic C—H bonds.[6] By contrast, the selective functionalization
of the other ten similar B—H bonds of o-carboranes are very
challenging and thus much less developed.[7,8]
and monoalkenylation/dialkenylation of o-carboranes.[14] Unlike
iridium, the rhodium-catalyzed highly selective B(3,6)-
functionalization only proceeded in the presence of an
appropriate directing group. While o-carboranes tethered a
pyridine has been demonstrated by Yan and co-workers to
undergo a facile B(3)-acyloxylation,[15] Che, Yu and their co-
worker employed the monophosphino-o-carboranes in their
B(3,6)-diarylation and dialkylation reactions (Scheme 1B).[16]
Moreover, the directed[17] and undirected[18] palladium
catalyzed B(3)-functionalization of o-carboranes have also been
reported recently (Scheme 1C). Despite these impressive
advances, the development of a highly selective, catalytic B(3)-
functionalization under mild reaction conditions is still
challenging yet demanding.
Typically, the reactivity of ten hydridic cage B—H vertices of
o-carborane towards electrophilic substitution are mainly limited
by their relative electron density, therefore, the B(3,6)—H bonds
are not prone to such an electrophilic transformation as they fall
into the most electron-deficient subunits (Scheme 1).[9]
Therefore, the indirect methods via capitation reaction of
dicarbollides with boron halides are historically dominant in the
preparation of the B(3)–functionalized o-carboranes.[10] Along
with the development of stoichiometric protocols,[11] transition-
metal catalyzed cage B(3,6)—H derivatization have been
developed recently. However, these methods generally suffered
from harsh reaction conditions including high temperature and/or
long reaction time. For instance, iridium has been shown to be
capable to catalyze the B(3)-propenylation by Sneddon at 100 oC
for 48 h (Scheme 1A). [12] Notably, Xie and co-workers have
Phosphine oxides are easy to prepare, air and moisture stable
moieties, which have been demonstrated to be very competent
directing groups in the diverse transition-metal-catalyzed C—H
activation.[19] Herein, we demonstrate the phosphine oxide
could be introduced as a readily available and efficient directing
group in the palladium-catalyzed highly selective B(3)—H
arylation of o-carboranes with arylboronic acids under very mild
reaction conditions (Scheme 1D). Using hydrogen peroxide
(H2O2) as the oxidant, a wild array of the B(3)-arylated o-
carboranes could be readily obtained in short reaction time. The
robustness of this protocol was further substantiated by the high
reaction efficiency even when reactions were run under air.

2
Tetrahedron Letters
alkenyl
BPin
H
H
H
Ir
H
or
or
(A)
alkenyl
BPin
other BH
C
B
R
numbering system
Rh
N
PAr2
3
4
R1
OCOR2
(B)
(C)
H
R
1
8
B(3)-H
2
5
7
9
12
6
activation
11
10
Ar
DG
DG
= PAr2
= CONR'2
H
Pd
R1
electron density:
B(8, 9, 10, 12) > B(4, 5, 7, 11) >> B(3, 6)
H
= 2-OHC6H4
FG
Ar
O
PPh2
Ar1
high B(3)-selectivity
robust (under air)
fast reaction (< 1 h)
Pd
(D)
Ar2
This work
Scheme 1 Transition-metal-catalyzed B(3)-functionalization of o-carboranes.
Results and Discussion
With the diphenylphosphine oxide o-carboranes in hand, we
then began to evaluate the palladium-catalyzed direct B—H
arylation reaction (Table 1). Initial trial of the phosphine oxide-
directed palladium-catalyzed cross-coupling reaction between 4a
and p-tolylboronic acid 5 [reaction conditions: 30 mol% of
Pd(OAc)2 as catalyst, 2 equiv. of Cu(OAc)2 as oxidant, 1 equiv.
Our phosphine oxide-tethered o-carboranes could be
conveniently prepared following the reported synthetic
procedures (Scheme 2). The dehydrogenative alkyne-insertion
products 3 of decarborane were easily synthesized according to
Sneddon’s protocol using biphasic ionic-liquid/toluene
mixtures.[20] The sequential lithiation-phosphinylation-oxidation
then delivered the anticipated functionalized o-carboranes 4
tethered with a desired phosphine oxide directing group.[21]
o
of HOAc as additive in toluene at 40 C, 24 h] afforded the
desired B(3)-arylated o-carborane 6 in 15% yield (entry 1). X-ray
diffraction analysis of the arylated product 6 (CCDC number:
1924703) unambiguously confirmed the B(3)—H bond being site-
selectively functionalized (Figure 1). We then found the
replacement of HOAc by TFA as the additive afforded a slightly
higher yield (entry 2). Screening of various inorganic oxidants
(entries 3-5) revealed that the aqueous hydrogen peroxide (H2O2)
turned out to be the optimal oxidant giving the arylated product 6
in 50% yield. Notably, the adoption of 4 equiv. of both the p-
tolylboronic acid 5 and hydrogen peroxide could promote the
reaction yield to 84% in less than 1 h (entry 6). The robustness of
this reaction further allowed the decreasing the catalyst loading
as low as to 10 mol% and running under air without affecting the
reaction efficiency (entries 7, 8).
nBu
N
Cl
O
1) nBuLi, THF, -78 oC, 2 h
N
H
PPh2
Ar
2) ClPPh2, -78 oC to RT
3) H2O2, 4-6 h
(BMIMCL)
Me
Ar
B
10H14
2
(
H
)
Ar
1
toluene, reflux, 0.5 h
3
4
Scheme 2 Synthetic route towards the phosphine oxide-tethered
o-carboranes.
Table 1. Reaction condition optimization.a
O
Pd(OAc)2 (30 mol%)
B(OH)2
O
PPh2
oxidant (x equiv.)
PPh2
Ph
Ph
additive (1 equiv.)
toluene, 40 oC, N2
Me
Me
4a
5
6
entry
1
oxidant
Cu(OAc)2
Cu(OAc)2
AgOAc
K2S2O8
H2O2
X (equiv.)
additive
time (h)
24
yieldb (%)
2
2
2
2
2
4
4
4
HOAc
TFA
TFA
TFA
TFA
TFA
TFA
TFA
15
2
24
25
3
24
5
4
24
40
5
24
50
6c
H2O2
24
84
7 c,d
8 c,d,e
H2O2
0.5
0.5
83
H2O2
85 (78)f
a 0.05 mmol of 4a, 0.1 mmol of 5, 30 mol% of Pd(OAc)2, 1 equiv. of additive, 2 equiv. of oxidant, and 1 mL of solvent for 24 h under an argon atmosphere.
b 31P NMR yield.
c 4 equiv. of 5 and 4 equiv. of H2O2.
d 10 mol% of Pd(OAc)2.
e Reaction under air.
f Isolated yield.

3
electron-withdrawing groups (4-F, 4-CF3, 3-F, 3-Cl, 3-CF3) still
proceeded smoothly albeit with slightly lower yields (10-14, 42-
59%). It is noteworthy the trifluoromethoxy substituted
arylboronic acids were also well survived (15 and 16). Other
fused aromatic moieties including 1-naphthalene (17), 2-
naphthalene (18), and 1-phenanthrene (19) could also be
efficiently incorporated into the o-carborane scaffold by using
their corresponding boronic acids. Following the preparative
procedure shown in Scheme 2, a diverse array of phosphine
oxide-tethered o-carboranes could be potentially assembled from
readily available starting materials. To demonstrate such a
modularity, we synthesized p-tolyl substituted phosphine oxide-
tethered o-carboranes, which could also be well applied in
current B(3)-arylation protocol even in preparative scale (20-26).
However, boronic acids bearing potentially competing
coordination site versus phosphine oxide such as pyridine, indole,
tetrahydrothiophene etc. were not reactive under current reaction
setting (see Supplementary Material for more details).
Figure 1. X-ray diffraction analysis of B(3)-arylated o-carborane 6.
Table 2 Substrate scope of the palladium-catalyzed B(3)-
It is important to note that all the reactions were run under
very mild reaction conditions. For instance, the robustness nature
of current protocol even allowed the reaction proceeding
smoothly when open to air. Additionally, the high reaction
efficiency of this arylation reaction further rendered most of the
reactions to complete within 1 hour. On the contrary to the
generally requisite harsh conditions of methods developed in
literature, i.e., high temperature (> 100 oC) and long reaction time
(>24 h), our method should find broad applications in the diverse
functionalization of o-carboranes.
a
arylation of o-carboranes.
O
Pd(OAc)2 (10 mol%)
2O2 (4 equiv.)
TFA (1 equiv.)
O
R
PPh2
Ph
H
PPh2
Ar
B(OH)2
R
toluene, 40 o
air, 0.5 h or 1 h
C
O
O
O
O
PPh2
Ph
PPh2
Ph
PPh2
Ph
PPh2
Ph
Me
tBu
F
Interestingly, it was found that the steric hindrance of aryl
substituents vicinal to the phosphine oxide profoundly correlates
to the observed reactivity (Scheme 3). While substrate with a p-
tolyl underwent the cross-coupling reaction smoothly (21), the
yield of that with a m-tolyl substituent decreased to 52% (27).
Further increasing the steric influence by using a o-tolyl
substituted carborane, however, led to no desired reactivity but
only the recovery of starting material (28). Interestingly, the aryl
substitution vicinal to the phosphine oxide could also be replaced
by a hydrogen atom albeit a slightly lower yield of B(3)-coupling
product was obtained (29).
7
8
9
10
, 69%
, 73%
, 74%
, 46%
O
O
O
O
PPh2
Ph
PPh2
Ph
PPh2
Ph
PPh2
Ph
F
Cl
CF3
CF3
11
12
13
14
, 59%
, 51%
, 42%
, 53%
O
O
O
O
PPh2
Ph
PPh2
Ph
PPh2
Ph
PPh2
Ph
O
OCF3
B(OH)2
O
PPh2
R
PPh2
standanrd conditions
OCF3
R
15
16
17
18
, 56%
, 57%
, 67%
, 49%
O
Me
Me
O
O
O
O
PPh2
Ph
O
O
O
PPh2
PPh2
PPh2
PPh2
p-tol
PPh2
o-tol
PPh2
m-tol
PPh2
p-Tol
p-Tol
p-Tol
H
tBu
Me
Me
Me
Me
Me
b
b
b
19
20
21
22
, 65%
, 51%
, 61%
, 73%
21
27
28
29
, 43%
, 73%
, 52%
, <5%
O
O
O
O
PPh2
PPh2
p-Tol
PPh2
PPh2
Scheme 3 Impact of substituents vicinal to the phosphine oxide
p-Tol
p-Tol
p-Tol
on the reactivity.
Cl
Me
b
b
b
b
Based on the experimental observation and literature
precedence, a plausible mechanism is proposed (Scheme 4). A
ligand exchange event is likely to be involved before the CMD
step of the B(3)—H bond. The use of phosphine oxide as the
directing group brings the palladium catalyst (I) close to
carborane moiety and thus determines the putative site selectivity
of B—H bond cleavage (II). Followed by transmetalation of
arylboronic acid and reductive elimination (III), the desired
B(3)-arylation of o-carborane could be readily obtained. The
catalytically competent palladium species is then regenerated via
an additional oxidation of the resulting Pd(0) in the presence of
H2O2.
23
24
25
26
, 59%
, 67%
, 44%
, 42%
a 0.05 mmol of o-carborane, 0.2 mmol of boronic acid, 10 mol% of Pd(OAc)2,
1 equiv. of TFA, 4 equiv. of H2O2, and 1 mL of solvent for 0.5 h or 1 h
under air.
b 0.65 mmol scale reaction.
The scope and limitation of this highly selective B(3)-H
arylation of o-carboranes were then further evaluated (Table 2).
Specifically, phenyl and arylboronic acid derivatives bearing
electron-donating groups (4-Me, 4-tBu, 3-Me) were generally
well tolerated under current reaction conditions to afford the
desired arylation products in good yields (6-9, 69-78%). On the
contrary, the reactions with arylboronic acid derivatives bearing

4
Tetrahedron
Pd(OAc)2
RCO2H
Aznareza, F.; Jin, G.-X. Chem. Commun. 2019, 55, 210-213; (c)
Gao, Y.; Cui, P.-F.; Aznareza, F.; Jin, G.-X. Chem. Eur. J. 2018,
24, 10357-10363; (d) Guo, S.-T.; Cui, P.-F.; Gao, Y.; Lin, Y.-J.;
Jin, G.-X. Dalton Trans. 2018, 47, 13641-13646; (e) Yang, Z.;
Zhao, W.; Liu, W.; Wei, X.; Chen, M.; Zhang, X.; Zhang, X.;
Liang, Y.; Lu, C.; Yan, H. Angew. Chem. Int. Ed. 2019, 58,
11886–11892; (f) Li, C.-X.; Ning, Q.; Zhao, W.; Cao, H.-J.;
Wang, Y.-P.; Yan, H.; Lu, C.-S.; Liang, Y. Chem. Eur. J.
10.1002/chem.202003634; (g) Ni, H.; Lu, Z.; Xie, Z. W. J. Am.
Chem. Soc. 2020. doi.org/10.1021/jacs.0c08652; (h) Cheng, R.;
Qiu, Z.; Xie, Z. Chin. J. Chem. 2020, 38, 1575–1578; (i) Chen, Y.;
Quan, Y.; Xie, Z. W. Chem. Commun. 2020,
doi.org/10.1039/D0CC05207H; (j) Wang, Q.; Tian, S.; Zhang, C.;
Li, J.; Wang, Z.; Du, Y.; Zhou, L.; Lu, J. Org. Lett. 2019, 21,
8018−8021.
Potenza, J. A.; Lipscomb, W. N.; Vickers, G. D. and Schroeder,
H. J. Am. Chem. Soc. 1966, 88, 628–629; (b) Koetzle, T. F. and
Lipscomb, W. N. Inorg. Chem. 1970, 9, 2743–2748.
Ph2
P
O
Ar1
H2O2
+
RCO2H
LnPd(OCOR)
I
Ph2
P
O
[Pd]0
Ar1
[Pd]II
Ph2
P
O
II
ArB(OH)2
Ph2
Ar1
P
O
Ar2
Ar1
[Pd]II
Ar2
III
Scheme 4 Proposed mechanism.
9.
In summary, we have developed a phosphine oxide-directed
highly regioselective palladium-catalyzed B(3)-arylation of o-
carboranes with a multitude of arylboronic acids. The mild
reaction conditions, short reaction time, and well functional
tolerance should render this protocol appealing in the preparation
of a diverse array of functionalized o-carboranes. The detailed
mechanistic investigation as well as the palladium-catalyzed
asymmetric functionalization of o-carboranes[22] are currently
undergoing in our lab.
10. (a) Hawthorne, M. F.; & Wegner, P. A. J. Am. Chem. Soc. 1968,
90, 896–901; (b) Roscoe, J. S.; Kongpricha, S.; & Papetti, S.
Inorg. Chem. 1970, 9, 1561–1563; (c) Viñas, C.; Barberà, G.;
Oliva, J. M.; Teixidor, F.; Welch, A. J.; Rosair, G. M. Inorg.
Chem. 2001, 40, 6555–6562; (d) Ogawa, T.; Ohta, K.; Yoshimi,
T.; Yamazaki, H.; Suzuki, T.; Ohta, S.; Endo, Y. Bioorg. Med.
Chem. Lett. 2006, 16, 3943–3946; (e) Safronov, A. V.;
Shlyakhtina, N. I.; Hawthorne, M. F. Organometallics. 2012, 31,
2764–2769.
11. (a) Hoel, E. L.; Talebinasab-Savari, M.; Hawthorne, M. F. J. Am.
Chem. Soc. 1977, 99, 4356-4367; (b) Tang, C.; Zhang, J.; Zhang,
J.; Xie, Z. J. Am. Chem. Soc. 2018, 140, 16423-16427; (c) Quan,
Y.; Tang, C.; Xie, Z. Dalton. Trans. 2019, 48, 7494-7498.
12. Mirabelli, M. G. L.; Sneddon, L. G. J. Am. Chem. Soc. 1988, 110,
449–453.
13. Cheng, R.; Qiu, Z.; Xie, Z. Nat. Commun. 2017, 8, 14827-14833.
14. Cheng, R.; Qiu, Z.; Xie, Z. Chem. Eur. J. 2020, 26, 7212-7218.
15. (a) Li, C.-X.; Zhang, H.-Y.; Wong, T.-Y.; Cao, H.-J.; Yan, H.; Lu,
C.-S. Org. Lett. 2017, 19, 5178–5181; (b) Zhang, R.; Zhu, L.; Liu,
G.; Dai, H.; Lu, Z.; Zhao, J.; Yan, H. J. Am. Chem. Soc. 2012,
134, 10341–10344; (c) Wang, Z.; Ye, H.; Li, Y.; Li, Y.; Yan, H. J.
Am. Chem. Soc. 2013, 135, 11289–11298; (d) Dai, H.; Liu, G.;
Zhang, X.; Yan, H.; Lu, C. Organometallics. 2016, 35, 1488-
1496.
16. Zhang, Z.-Y.; Zhang, X.; Yuan, J.; Yue, C.; Meng, S.; Chen, J.;
Yu, G.-A.; Che, C.-M. Chem. Eur. J. 2020, 26, 5037-5050.
17. (a) Cui, C.-X.; Zhang, J.; Qiu, Z.; Xie, Z. Dalton. Trans. 2020, 49,
1380-1383; (b) Liang, Y.-F.; Yang, L.; Jei, B.; Kuniyila, R.;
Ackermann, L. Chem. Sci. 2020, 11, 10764-10769.
Acknowledgments
Financial support from the National Natural Science
Foundation of China (No. 21772023 and 21901041) is gratefully
acknowledged.
References and notes
1.
2.
Grimes, R. N. Dalton Trans. 2015, 44, 5939-5956.
For selected reviews, see: (a) Hosmane, N. S.; Maguire, J. A. In
Comprehensive Organometallic Chemistry III; Crabtree, R. H.;
Mingos, D. M. P. Ed.; Elsevier: Oxford, 2007; vol. 3; (b) Xie, Z.
Acc. Chem. Res. 2003, 36, 1-9; (c) Yao, Z.-J.; Jin, G.-X. Coord.
Chem. Rev. 2013, 257, 2522-2535; (d) Qiu, Z.; Ren, S. and Xie, Z.
Acc. Chem. Res. 2011, 44, 299-309; (e) Xie, Z. Coord. Chem. Rev.
2002, 231, 23-46; (f) Yu, W.-B.; Cui, P.-F.; Gao, W.-X.; Jin, G.-
X. Coord. Chem. Rev. 2017, 350, 300-319; For selected recent
works, see: (g) Cui, P.-F.; Lin, Y.-J.; Li, Z.-H.; Jin, G.-X. J. Am.
Chem. Soc. 2020, 142, 8532–8538; (h) Cui, P.-F.; Gao, Y.; Guo,
S.-T. Lin, Y.-J.; Li, Z.-H.; Jin, G.-X. Angew. Chem. Int. Ed. 2019,
58, 8129-8133.
18. Xu, T.-T.; Cao, K.; Zhang, C.-Y.; Wu, J.; Ding, L.-F.; Yang, J.
Org. Lett. 2019, 21, 9276–9279.
19. (a) Ma, Y.-N.; Li, S.-X.; Yang, S.-D. Acc. Chem. Res. 2017, 50,
1480–1492; (b) Zhao, D.; Nimphius, C.; Lindale, M.; Glorius, F.
Org. Lett. 2013, 15, 4504−4507; (c) Liu, L.; Yuan, H.; Fu, T.;
Wang, T.; Gao, X.; Zeng, Z.; Zhu, J.; Zhao, Y. J. Org. Chem.
2014, 79, 80−87; (d) Du, Z.-J.; Guan, J.; Wu, G.-J.; Xu, P.; Gao,
L. -X. Han, F.-S. J. Am. Chem. Soc. 2015, 137, 632−635; (e) Hu,
X.-H.; Yang, X.-F.; Loh, T.-P. Angew. Chem. Int. Ed. 2015, 54,
15535−15539; (f) Yang, Y.; Li, R.; Zhao, Y.; Zhao, D.; Shi, Z. J.
Am. Chem. Soc. 2016, 138, 8734–8737; (g) Yang, Y.; Qiu, X.;
Zhao, Y.; Mu, Y.; Shi, Z. J. Am. Chem. Soc. 2016, 138, 495-498;
(h) Sun Y; Cramer N. Angew. Chem.; Int. Ed. 2017, 56, 364−367.
20. Li, Y.; Carroll, P. J.; Sneddon, L. G. Inorg. Chem. 2008, 47,
9193–9202.
3.
(a) Yang, X.; Jiang, W.; Knobler, C. B.; Hawthorne, M. F. J. Am.
Chem. Soc. 1992, 114, 9719-9721; (b) Jude, H.; Disteldorf, H.;
Fischer, S.; Wedge, T.; Hawkridge, A. M.; Arif, A. M.;
Hawthorne, M. F.; Muddiman, D. C.; Stang, P. J. J. Am. Chem.
Soc. 2005, 127, 12131-12139; (c) Qian, E. A.; Wixtrom, A. I.;
Axtell, J. C.; Saebi, A.; Jung, D.; Rehak, P.; Han, Y. X.; Moully,
E. H.; Mosallaei, D.; Chow, S.; Messina, M. S.; Wang, J. Y.;
Royappa, A. T.; Rheingold, A. L.; Maynard, H. D.; Kral, P.;
Spokoyny, A. M. Nat. Chem. 2017, 9, 333-340; (d) Saha, A.;
Oleshkevich, E.; Vinas, C.; Teixidor, F. Adv. Mater. 2017, 29,
1704238-1704244.
21. Popescu, A. -R.; Laromaine, A.; Teixidor, F.; Sillanpää, R.;
Kivekäs, R.; Llambias, J. I.; Viñas, C. Chem. Eur. J. 2011, 17,
4429 – 4443.
22. Cheng, R.; Li, B.; Wu, J.; Zhang, J.; Qiu, Z.; Tang, W.; You, S.-
L.; Tang, Y.; Xie, Z. J. Am. Chem. Soc. 2018, 140, 4508-4511.
4.
(a) Hawthorne, M. F. Angew. Chem. Int. Ed. Engl. 1993, 32, 950-
984; (b) Hawthorne, M. F.; Maderna, A. Chem. Rev. 1999, 99,
3421-3434; (c) Armstrong, A. F.; Valliant, J. F. Dalton Trans.
2007, 4240-4251; (d) Issa, F.; Kassiou, M.; Rendina, L. M. Chem.
Rev. 2011, 111, 5701-5722; (e) Scholz, M.; Hey-Hawkins, E.
Chem. Rev. 2011, 111, 7035-7062.
5.
6.
For selected reviews, see: (a) Bregadze, V. I. Chem. Rev. 1992,
92, 209-223; (b) Qiu, Z. Tetrahedron Lett. 2015, 56, 963-971; (c)
Yuan, Y.; Ren, S.; Qiu, Z.; Wang, S.; Xie, Z. Sci. China Chem.
2014, 57, 1061-1063; (d) Olid, D.; Núñez, R.; Viñas, C.; Teixidor,
F. Chem. Soc. Rev. 2013, 42, 3318-3336.
For selected reviews, see: (a) Grimes, R. N. Carboranes, 3rd Ed,
Elsevier: Oxford, 2016; (b) Xie, Z.; Jin, G.-X. Dalton Trans. 2014,
43, 4924; (c) Sato, S.; Ishii, S.; Nakamura, H. Eur. J. Inorg. Chem.
2017, 4344.
For selected reviews, see: (a) Quan, Y.; Qiu, Z.; & Xie, Z. Chem.
Eur. J. 2018, 24, 2795-2805; (b) Quan, Y.; Xie, Z. Chem. Soc.
Rev. 2019, 48, 3660-3673.
For selected recent works on the catalytic B-H activation, see: (a)
Cui, P.-F.; Gao, Y.; Guo, S.-T.; Jin, G.-X. Chin. J. Chem. 2020,
38, 10.1002/cjoc.202000461; (b) Gao, Y.; Guo, S.-T.; Cui, P.-F.;
Supplementary Material
Supplementary data to this article can be found at
https://www.journals.elsevier.com/tetrahedron-letters.
Crystallographic data (excluding structure factors) for the
structure in this paper (compound 6) have been deposited with
the Cambridge Crystallographic Data Centre (CCDC number:
1924703).
7.
8.
Highlights

5
• Palladium-catalyzed highly B(3)-selective
arylation of o-carboranes.
• The reaction is insensitive to air and moisture.
• The reaction is fast, generally less than one hour.
• Phosphine oxide as the efficient site-selective
directing group.
Graphical Abstract
Phosphine Oxide-Directed Palladium-
Leave this area blank for abstract info.
Catalyzed B(3)–H Arylation of o-Carboranes
Lingxiang Lian, Caixiang Lin*, Yi Yu, Yaofeng Yuan and Ke-Yin Ye*
A highly selective, robust and efficient phosphine oxide-directed palladium-catalyzed B(3)–H arylation of o-carborane with
a variety of arylboronic aicds was developed.
O
O
PPh2
B(OH)2
Ar2
Ar1
PPh2
Ar1
Pd
Ar2
B(3)-selectivity
robust (under air)
fast reaction (< 1 h)