Regioselective Nucleophilic Alkylation/Arylation of B-H Bonds in o-Carboranes: An Alternative Method for Selective Cage Boron Functionalization

Article abstract of DOI:10.1021/jacs.8b10270

A new protocol for regioselective nucleophilic cage B-H substitution in o-carboranes has been proposed that is complementary to the strategies of transition metal catalysis and electrophilic substitution. Magnesium-mediated site-selective nucleophilic cage B(3,6)-H and B(9)-H substitution reactions of o-carboranes give a series of B(3,6)-dialkylated and B(9)-alkylated/arylated o-carboranes in high yields. Both steric and electronic factors of cage C substituents play crucial roles in controlling the site selectivity.

Full text of DOI:10.1021/jacs.8b10270

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Communication
Regioselective Nucleophilic Alkylation/Arylation of B-H Bonds in o-
Carboranes: An Alternative Method for Selective Cage Boron Functionalization
Cen Tang, Jiji Zhang, Jie Zhang, and Zuowei Xie
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.8b10270 • Publication Date (Web): 15 Nov 2018
Downloaded from http://pubs.acs.org on November 16, 2018
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Journal of the American Chemical Society
Regioselective Nucleophilic Alkylation/Arylation of B-H Bonds in o-
Carboranes: An Alternative Method for Selective Cage Boron Func-
tionalization
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Cen Tang, Jiji Zhang, Jie Zhang, and Zuowei Xie*
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Department of Chemistry and State Key Laboratory of Synthetic Chemistry, The Chinese University of Hong Kong,
Shatin, New Territories, Hong Kong, China
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Supporting Information Placeholder
vital to decrease the electron density on B(4)-H vertex and to
prevent the most electron-deficient B(3)-H one from being at-
ABSTRACT: A new protocol for regioselective nucleophilic
cage B-H substitution in o-carboranes has been proposed,
tacked by the nucleophiles. These results indicate the huge
impact of cage C-substituents on nucleophilic cage B-H sub-
stitution reactions, suggesting that selective nucleophilic cage
B-H substitution among ten B-H vertices may be achieved by
tuning electronic/steric properties of two cage C-substituents.
In this Communication, we report organomagnesium-medi-
ated regioselective nucleophilic alkylation/arylation of o-car-
boranes at the most electron deficient B(3,6) positions or at
the most electron-rich B(9,12) sites (Scheme 1c).
which is complementary to the strategies of transition metal
catalysis and electrophilic substitution. Magnesium-mediated
site-selective nucleophilic cage B(3,6)-H and B(9)-H substitu-
tion reactions of o-carboranes give a series of B(3,6)-dialkyl-
ated and B(9)-alkylated/arylated o-carboranes in high yields.
Both steric and electronic factors of cage C-substituents play
crucial roles in controlling the site-selectivity.
Scheme 1. Cage B-H Substitution Reactions
Carboranes are carbon-boron molecular clusters with 3-D
aromaticity (σ-aromaticity),1 which are often viewed as ana-
logs to 2-D benzenes (π-aromaticity).2 They share some com-
mon features of aromatic molecules such as thermal stability
and ability to undergo electrophilic substitution reactions.
Strong electrophile E+ attacks preferentially B-H vertices most
distant from the cage carbon atoms in icosahedral framework,
leading to the formation of new B-E bond(s) and releasing of
H+ (Scheme 1a).1a,3 Such reaction proceeds stepwise in the or-
der B(9,12)-H > B(8,10)-H > B(4,5,7,11)-H >> B(3,6)-H, which
corresponds to the charge distribution of the cage (see
Scheme 1 for numbering system).4 It is noted that the degree
of substitution in the aforementioned electrophilic reactions
has hardly been controlled owing to electronic effects.1a,3 How-
ever, in the case of transition metal electrophiles, selective
cage B-H metalation has been achieved via tuning the bulki-
ness of the coordinating ligands and/or directing group strat-
egy, which has led to the development of catalytic selective
functionalization of cage B-H vertices.5,6
On the other hand, similar to nucleophilic benzene C-H
substitution,7 nucleophilic B-H substitution in o-carboranes
was unknown till our recent publication (Scheme 1b).8 Gener-
ally, strong nucleophiles such as MeO- and F- first attack the
most electron-deficient cage B(3) that is bonded to both cage
carbon atoms, followed by an attack of the second equivalent
of the nucleophile on the same boron atom to remove one B-
H vertex from o-carborane framework, leading to the for-
mation of dicarbollide ion [nido-C2B9H112-],9 the most popular
inorganic π ligand.10 We thought that nucleophilic cage B-H
substitution could be achieved if the second attack of the nu-
cleophile could be blocked and the departure of H- from the
cage boron could be promoted by a hydride abstractor. Our
recent proof-of-concept study shows that the replacement of
two C-H vertices with two C-Ph ones in o-carborane enables
regioselective nucleophilic B(4)-H substitution with Grignard
reagents RMgX for the first time (Scheme 1b).8
Our investigation began with the functionalization at the
most electron-deficient B(3,6) sites. Though B(3,6)-H bonds
are the most susceptible to nucleophilic attack by hard nucle-
ophiles such as MeO- and F-, they do not react with soft nu-
cleophiles such as Grignard reagents and organolithium com-
pounds. Previous work indicates that aryls on cage carbons
can sterically block B(3,6) positions. Thus, electron-withdraw-
ing yet sterically less bulky cage C-substituents are desired. In
this regard, acetylene is an appropriate moiety. Unfortunately,
many attempts to prepare 1,2-(C≡CR)2-o-carborane failed. We
then prepared 1-methyl-2-phenylethynyl-o-carborane (1a) as
the model substrate. Reaction of 1a with 1 equiv of isopropyl
magnesium chloride at room temperature in toluene for 18 h
gave 1-methyl-2-phenylethynyl-3,6-diisopropyl-o-carborane
(2a) in 21% GC yield (entry 1, Table S1 in the SI). If the amount
In such a nucleophilic cage B(4)-H substitution reaction,
the presence of two aryl groups on two cage carbon atoms is
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i
of PrMgCl was increased to 2.1 equiv, 2a was generated in
quantitative GC yield (73% isolated yield; entry 3, Table S1).
With the optimal reaction conditions in hand, we explored
the substrate scope and the results were summarized in Table
1. Both primary and secondary alkyl magnesium chlorides un-
derwent smoothly such nucleophilic substitution reaction to
give 1-methyl-2-phenylethynyl-3,6-dialkyl-o-carboranes (2) in
we chose 1,2-(TMS)2-o-carborane (TMS = Me3Si) as the model
substrate since (1) these groups can be easily removed after the
reactions, releasing the two cage carbons for further function-
alization, and (2) space-filling model indicates that
B(3,4,5,6,7,11) vertices can be sterically protected by two TMS
groups on cage carbons (vide infra).
We initially examined the reaction of 1,2-(TMS)2-o-
carborane with 1.2 equiv of iPrMgCl in Et2O at 60 oC for 24 h,
followed by desilylation in acetone via the addition of 10 equiv
of K2CO3, which gave 9-iPr-o-carborane (4a) in 75% GC yield.
We noted that the partial desilylation product was observed
by GC before adding K2CO3, indicating that the C(cage)-SiMe3
bonds were not so stable under the basic conditions. It has
been documented that the stability of C-SiR3 bond is closely
related to steric hindrance of R substituents.12 Thus, the effects
of silyls on the nucleophilic substitution reactions were eval-
uated and the results were compiled in Table S2 in the SI.
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good to high yields. No reaction with BuMgCl was observed,
probably due to steric reasons. It is noteworthy that these 3,6-
dialkylated o-carboranes may only be prepared using de-
boronation-capitation-deboronation-capitation method.1a,11
Transition metal catalyzed cross-coupling methodology is not
feasible for the synthesis of cage B-alkylated o-carboranes ow-
ing to facile β-hydrogen elimination reactions. Electrophilic B-
H substitution does not proceed at B(3,6)-H vertices.1a,3 Thus,
nucleophilic B-H substitution provides a complementary
method for convenient synthesis of 3,6-dialkyl-o-carboranes.
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Table 1. Synthesis of 3,6-Dialkylated o-Carboranesa
Table 2. Synthesis of 9-(R/Ar)-o-carboranesa
aIsolated yields.
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Compounds 2 were characterized by H, 13C, and B NMR
spectroscopy as well as high-resolution mass spectrometry.
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Their B NMR spectra exhibited a similar pattern of 2:1:1:3:3
spanning the range of -16 to 1 ppm with the substituted cage
boron being observed at ca. 1 ppm as indicated by 1H coupled
11B NMR spectra. Single-crystal X-ray analyses of 2a unambig-
uously confirm cage B(3,6) selectivity.
aIsolated yield. b60 oC in toluene
It was found that 1,2-(DMPS)2-o-carborane (3a; DMPS = di-
methylphenylsilyl) afforded 4a in 80% GC yield (entries 1-3,
Table S2). Screening the amount of Grignard reagent indi-
cated that 1.3 equiv offered the best result (entries 4-7, Table
S2). Higher loadings led to the formation of disubstituted spe-
cies (entries 6-7 Table S2). In view of the yield and selectivity
of 4a, the reaction conditions established in entry 5 in Table
S2 were chosen as the optimal conditions.
Having achieved nucleophilic B-H substitution at B(3,6)
and B(4,5,7,11) sites,8 we wondered if the nucleophilic B-H sub-
stitution could be realized at distal positions. This seems very
challenging since (1) the electron density at B(8,9,10,12) posi-
tions is much higher than that of B(3,6) and B(4,5,7,11) vertices,
and (2) the electronic properties of cage C-substituents have
little impact on the distal B(8,9,10,12) sites in such σ-system.
These analyses suggest that relatively electron-deficient
B(3,4,5,6,7,11) vertices must be protected in order to achieve
nucleophilic substitution at distal positions. With this in mind,
Under the above optimized reaction conditions, the sub-
strate scope was examined, and the results were summarized
in Table 2. It showed that both alkyl and aryl Grignard reagents
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were compatible with the reaction, giving cage B(9)-substi-
To understand the site-selectivity at B(9), density functional
theory (DFT) calculations were performed at the B3LYP/6-
311++G(d,p) level of theory15 for 1,2-C2B10H12，1-Me-2-(C≡CPh)-
1,2-C2B10H10 (1a), 1,2-Ph2-1,2-C2B10H10, 1,2-(DMPS)2-1,2-C2B10H10
(3a), and 1,2-(TMS)2-1,2-C2B10H10 (3c). The space-filling models
of the optimized structures of both 3a and 3c clearly show that
B(3,4,5,6,7,11)-H vertices are sterically blocked by two silyl
groups and only B(8,9,10,12)-H ones are accessible by nucleo-
philes (see Figure S7 in the SI).
On the other hand, NBO (natural bond orbital) analyses
show that (1) the impact of electronic effects of cage C-substit-
uents on the vertex charge follows the order: C(1,2) > B(3,6) >
B(4,5,7,11) > B(8,9,10,12) (see Table S3 in the SI) , and (2) the
calculated charge of the B(9/12)-H vertex (ca. -0.06) in all com-
pounds aforementioned regardless of cage C-substituents is
less negative than that of B(8/10)-H one (ca. -0.08), indicating
that B(9/12)-H vertex is more susceptible to nucleophilic attack
than B(8,10)-H one.
On the basis of above analyses, it is rational to suggest that
the B(9)-selectivity in the current organomagnesium-medi-
ated nucleophilic substitution reaction is controlled by both
steric and electronic factors of the cage C-substituents. The
NBO analyses also indicate that the vertex charge of B(3,6)-H
in 1-Me-2-(C≡CPh)-1,2-C2B10H10 (1a) is calculated to be +0.241,
which is more electron-deficient than that of B(3,6)-H one
(+0.214) in o-carborane (see Table S3 in the SI). This offers an
explanation on why 1a reacts well with Grignard reagents
whereas o-carborane does not.
In summary, a new protocol for regioselective nucleophilic
cage B-H substitution in o-carboranes has been proposed and
validated: (1) for B(3,6)-H nucleophilic substitution, less bulky
electron-withdrawing substituents on cage carbons is neces-
sary, (2) for B(4,5,7,11)-H nucleophilic substitution, an appro-
priate size of electron-withdrawing substituents (such as aryls)
on both cage carbons are required,8 and (3) for B(9,12)-H nu-
cleophilic substitution, very sterically hindered groups (such
as silyls) on both cage carbons are needed to block
B(3,4,5,6,7,11)-H vertices. This transition-metal-free strategy is
complementary to those of transition metal-catalyzed regiose-
lective functionalization of o-carboranes,5 and electrophilic
substitution reactions,1a,3 enabling the facile synthesis of cage
B-alkylated/arylated carboranes in a regioselective and con-
trolled manner. This work opens a new window to the con-
trolled functionalization of boron clusters.
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tuted o-carboranes. Generally, alkyl Grignard reagents offered
higher yields of 4 than those of aryl Grignard reagents. Het-
eroatom-containing Grignard reagents reacted slower and re-
o
quired higher temperature (60 C) yet gave lower yields of 4
(4k, 4l and 4n), due probably to some interactions between
these heteroatoms and Mg2+. Sterically bulky tertiary carbon
nucleophiles such as tBuMgCl offered a relatively lower yield of
4b, whereas o-tolyl magnesium chloride failed to afford any
product 4q. On the other hand, CH3MgBr generated an insep-
arable mixture of isomeric species.
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Compounds 4 were characterized by H, 13C, and B NMR
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spectroscopy as well as high-resolution mass spectrometry.
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Their B NMR spectra exhibited a similar pattern of 1:1:2:4:2
spanning the range of -16 to 11 ppm with the substituted cage
boron being observed at ca. 11 ppm as indicated by 1H coupled
11B NMR spectra. The molecular structures of 4g and 4h were
further confirmed by single-crystal X-ray analyses.
To eliminate any ambiguities of site-selectivity, compound
4b was converted to 5b using Ni-catalyzed cage C-arylation
method (Scheme 2).13 Single-crystal X-ray analyses of 5b un-
ambiguously confirmed the cage B(9) selectivity.
Scheme 2. Synthesis of 5b
Scheme 3. Kinetic Isotope Effect
ASSOCIATED CONTENT
Supporting Information
To gain some insight into the reaction pathway, several con-
trol experiments were carried out. Treatment of 3a with 1.3
equiv of iPrMgCl in the presence of 1,1-diphenylethylene gave
4a in 75% yield under standard reaction conditions.14 No
change was observed if the reaction ran in dark. These results
suggested that the above B(9)-functionalization reaction may
not involve a radical pathway. On the other hand, the for-
mation of H2 at 4.5 ppm was observed in the 1H NMR spectrum
of the hydrolysis product from the reaction of 3a with iPrMgCl
(see Figure S5 in the SI), which was further confirmed by GC-
TCD analysis. Such H2 was considered to originate from the
hydrolysis of the resultant MgHCl.7 Furthermore, parallel re-
actions of 3a and [D4]3a under the standard reaction condi-
tions (Scheme 3) gave a KIE value of 1.0 by comparison of their
reaction rates. This result suggested that the B-H bond-break-
ing may not be involved in the rate-determining step (see Fig-
ure S6).
The Supporting Information is available free of charge on the
ACS Publications website.
Experimental procedures, characterization of the products
(PDF), and crystal structures (CIF)
AUTHOR INFORMATION
Corresponding Author
zxie@cuhk.edu.hk
Notes
The authors declare no competing financial interests.
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(i) Lyu, H.; Quan, Y.; Xie, Z. Rhodium-catalyzed regioselective hydrox-
ACKNOWLEDGMENT
ylation of cage B-H bonds of o-carboranes with O2 or air. Angew. Chem.
Int. Ed. 2016, 55, 11840–11844. (j) Lyu, H.; Quan, Y.; Xie, Z. Transition
metal catalyzed direct amination of the cage B(4)–H bond in o-car-
boranes: synthesis of tertiary, secondary, and primary o-carboranyl
Amines. J. Am. Chem. Soc. 2016, 138, 12727–12738. (k) Hoel, E. L.; Tale-
binasab-Savari, M.; Hawthorne, M. F. Deuterium exchange at terminal
boron-hydrogen bonds catalyzed by certain transition metal com-
plexes. A qualitative study of selectivity and mechanism. J. Am. Chem.
Soc. 1977, 99, 4356–4367. (l) Mirabelli, M. G. L.; Sneddon, L. G. Transi-
tion-metal-promoted reactions of boron hydrides. 9. Cp*Ir-catalyzed
reactions of polyhedral boranes and acetylenes. J. Am. Chem. Soc. 1988,
110, 449–453. (m) Cao, K.; Huang, Y.; Yang, J.; Wu, J. Palladium cata-
lyzed selective mono-arylation of o-carboranes via B–H activation.
Chem. Commun. 2015, 51, 7257–7260. (n) Wu, J.; Cao, K.; Xu, T.-T.;
Zhang, X.-J.; Jiang, L.; Yang, J.; Huang, Y. Palladium catalyzed regiose-
lective mono-alkenylation of o-carboranes via Heck type coupling re-
action of a cage B–H bond. RSC Adv. 2015, 5, 91683–91685. (o) Zhang,
Y.; Sun, Y.; Lin, F.; Liu, J.; Duttwyler, S. Rhodium(III)-catalyzed alkenyl-
ation-annulation of closo-dodecaborate anions through double B-H
activation at room temperature. Angew. Chem. Int. Ed. 2016, 55, 15609–
15614. (p) Cao, K.; Xu, T.; Wu, Ji.; Jiang, L.; Yang, J. Palladium cata-
lyzed/silver tuned selective mono-/tetra-acetoxylation of o-carboranes
via B–H activation. Chem. Commun. 2016, 52, 11446–11449. (q) Cheng,
R.; Qiu, Z.; Xie, Z. Iridium-catalysed regioselective borylation of car-
boranes via direct B–H activation. Nat. Commun. 2017, 8, 14827–14833.
(r) Quan, Y.; Lyu, H.; Xie, Z. Dehydrogenative cross-coupling of o-car-
borane with thiophenes via Ir-catalyzed regioselective cage B–H and
C(sp2)–H activation. Chem. Commun. 2017, 53, 4818–4821. (s) Lyu, H.;
Quan, Y.; Xie, Z. Transition metal catalyzed, regioselective B(4)-halo-
genation and B(4,5)-diiodination of cage B-H bonds in o-carboranes.
Chem. Eur. J. 2017, 23, 14866–4871. (t) Zhang, X.; Zheng, H.; Li, J.; Xu,
F.; Zhao, J.; Yan, H. Selective catalytic B–H arylation of o-carboranyl
aldehydes by a transient directing strategy. J. Am. Chem. Soc. 2017, 139,
14511−14517. (u) Zhang, X.; Yan, H. Transition metal-induced B–H func-
tionalization of o-carborane. Coord. Chem. Rev. 2017,
https://doi.org/10.1016/j.ccr.2017.11.006. (v) Zhang, X. L.; Yan, H.
Pd(II)-catalyzed synthesis of bifunctionalized carboranes via cage B–
H activation of 1-CH2NH2-o-carboranes. Chem. Sci. 2018, 9, 3964-3969.
(w) Eleazer, B. J. Smith, M. D.; Popov, A. A.; Peryshkov, D. V. Rapid
reversible borane to boryl hydride exchange by metal shuttling on the
carborane cluster surface. Chem. Sci. 2017, 8, 5399-5407.
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This work was supported by grants from the Research Grants
Council of The Hong Kong Special Administration Region
(Project No. 14305918), and Incentive Grant from Faculty of
Science, CUHK.
REFERENCES
(1) (a) Carboranes, 3rd ed.; Grimes, R. N., Ed.; Elsevier: Oxford,
UK,2016. (b) Boron Science: New Technologies and Applications;
Hosmane,N. S., Ed.; Taylor & Francis Books/CRC: Boca Raton, FL, 2011.
(c) Qiu, Z. Recent advances in transition metal-mediated functionali-
zation of o-carboranes. Tetrahedron Lett. 2015, 56, 963–971. (d) Scholz,
M.; Hey-Hawkins, E. Carbaboranes as pharmacophores: properties,
synthesis, and application strategies. Chem. Rev. 2011, 111, 7035–7062.
(e) Spokoyny, A. M. New ligand platforms featuring boron-rich clus-
ters as organomimetic substituents. Pure Appl. Chem. 2013, 85, 903–
919.
(2) For selected articles, see: (a) Poater, J.; Solà, M.; Viñas, C.; Teixidor,
F. π Aromaticity and three-dimensional aromaticity: two sides of the
same coin? Angew. Chem. Int. Ed. 2014, 53, 12191–12195. (b) Chan, T.;
Xie, Z. Synthesis, structure and aromaticity of carborane-fused carbo-
and heterocycles. Chem. Sci. 2018, 9, 2284–2289. (c) Balaban, A. T.;
Oniciu, D. C.; Katritzky, A. R. Aromaticity as a cornerstone of hetero-
cyclic chemistry. Chem. Rev. 2004, 104, 2777–2812. (d) Chemical Reac-
tivity Theory: A Density Functional View; Chattaraj, P. K. Ed.; Taylor &
Francis Books/CRC: Boca Raton, FL, 2009.
(3) For selected examples, see: (a) Plešek, J.; Plzak, Z.; Stuchlik, J.; Her-
manek, S. Synthesis of β-alkyl derivatives of o-carborane by alkylation
under electrophilic conditions; Scope and limitation. Collect. Czech.
Chem. Commun. 1981, 46, 1748-1763. (b) Herzog, A.; Maderna, A.;
Harakas, G. N.; Knobler, C. B.; Hawthorne, M. F. A Camouflaged nido-
carborane anion: facile synthesis of octa-β-methyl-1,2-dicarba-closo-
dodecaborane(12) and its deboration reaction. Chem. Eur. J. 1999, 5,
1212-1217. (c) Li, J.; Logan, C. F.; Jones Jr, M. Simple syntheses and alkyl-
ation reactions of 3-iodo-o-carborane and 9,12-diiodo-o-carborane. In-
org. Chem. 1991, 30, 4866-4868. (d) Potenza, J. A.; Lipscomb, W. N.;
Vickers, G. D.; Schroeder, H. Order of electrophilic substitution in 1,2-
dicarbaclovododecaborane(12) and nuclear magnetic resonance as-
signment. J. Am. Chem. Soc. 1966, 88, 628-629.
(4) (a) Teixidor, F.; Barberà, G.; Vaca, A.; Kivekäsc, R.; Sillanpää, R.;
Oliva, O.; Viñas, C. Are methyl groups electron-donating or electron-
withdrawing in boron clusters? permethylation of o-carborane. J. Am.
Chem. Soc. 2005, 127, 10158–10159. (b) Farràs, P.; Juárez-Pérez, E.;
Lepšík, M.; Luque, R.; Núñez, R.; Teixidor, F. Metallacarboranes and
their interactions: theoretical insights and their applicability. Chem.
Soc. Rev. 2012, 41, 3445-3463.
(5) (a) Qiu, Z.; Quan, Y.; Xie, Z. Palladium-catalyzed selective fluori-
nation of o-carboranes. J. Am. Chem. Soc. 2013, 135, 12192–12195. (b)
Quan, Y.; Qiu, Z.; Xie, Z. Transition-metal-mediated three-component
cascade cyclization: selective Cage B–C(sp2) coupling of carborane
with aromatics and synthesis of carborane-fused tricyclics. J. Am.
Chem. Soc. 2014, 136, 7599–7602. (c) Quan, Y.; Xie, Z. Iridium catalyzed
regioselective cage boron alkenylation of o-carboranes via direct cage
B–H activation. J. Am. Chem. Soc. 2014, 136, 15513–15516. (d) Quan, Y.;
Xie, Z. Palladium-catalyzed regioselective intramolecular coupling of
o-carborane with aromatics via direct cage B–H activation. J. Am.
Chem. Soc. 2015, 137, 3502–3505. (e) Lyu, H.; Quan, Y.; Xie, Z. Palla-
dium-catalyzed direct dialkenylation of cage B-H bonds in o-car-
boranes through cross-coupling reactions. Angew. Chem. Int. Ed. 2015,
54, 10623–10626. (f) Quan, Y.; Xie, Z. Palladium-catalyzed regioselec-
tive diarylation of o-carboranes by direct cage B-H activation. Angew.
Chem. Int. Ed. 2016, 55, 1295–1298. (g) Quan, Y.; Tang, C.; Xie, Z. Palla-
dium catalyzed regioselective B–C(sp) coupling via direct cage B–H ac-
tivation: synthesis of B(4)-alkynylated o-carboranes. Chem. Sci. 2016,
7, 5838–5845. (h) Liu, D.; Dang, L.; Sun, Y.; Chan, H.-S.; Lin, Z.; Xie, Z.
Hydrogen-mediated metal-carbon to metal-boron bond conversion in
metal-carboranyl complexes. J. Am. Chem. Soc. 2008, 130, 16103–16110.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(6) (a) Shen, Y.; Pan, Y.; Zhang, K.; Liang, X.; Liu, J.; Spingler, B.; Dutt-
wyler, S. B-H functionalization of the monocarba-closo-dodecaborate
anion by rhodium and iridium catalysis. Dalton Trans. 2017, 46, 3135 –
3140. (b) Shen, Y.; Pan, Y.; Liu, J.; Sattasathuchana, T.; Baldridge, K. K.;
Duttwyler, S. Synthesis and full characterization of an iridium B–H ac-
tivation intermediate of the monocarba-closo-dodecaborate anion.
Chem. Commun. 2017, 53, 176 –179. (c) Lin, F.; Shen, Y.; Zhang, Y.; Sun,
Y.; Liu, J.; Duttwyler, S. Fusing carborane carboxylic acids with alkynes:
3D analogues of isocoumarins via regioselective B−H activation. Chem.
Eur. J. 2017, 24, 551-555.
(7) Wilson, A. S. S.; Hill, M. S.; Mahon, M. F.; Dinoi, C.; Maron, L. Or-
ganocalcium-mediated nucleophilic alkylation of benzene. Science
2017, 358, 1168–1171.
(8) Tang, C.; Zhang, J. Xie, Z. Direct nucleophilic substitution reaction
of cage B-H bonds by Grignard reagents: a route to regioselective B4-
alkylation of o-carboranes. Angew. Chem. Int. Ed. 2017, 56, 8642–8646.
(9) (a) Hawthorne, M. F.; Young, D. C.; Wegner, P. A. Carbametallic
boron hydride derivatives. I. apparent analogs of ferrocene and ferri-
cinium ion. J. Am. Chem. Soc. 1965, 87, 1818−1819. (b) Yoo, J.; Hwang, J-
W.; Do. Y. Facile and mild deboronation of o-carboranes using cesium
fluoride. Inorg. Chem. 2001, 40, 3, 568-570.
(10) (a) Hosmane, N. S.; Maguire, J. A. In Comprehensive Organome-
tallic Chemistry III; Crabtree, R. H., Mingos, D. M. P., Eds.; Elsevier:
Oxford, U.K., 2007; Vol. 3, Chapter 5. (b) Xie, Z. Advances in the chem-
istry of metallacarboranes of f-block elements. Coord. Chem. Rev. 2002,
231, 23–46. (c) Xie, Z. Cyclopentadienyl−carboranyl hybrid com-
pounds:ꢀ a new class of versatile ligands for organometallic chemistry.
Acc. Chem. Res. 2003, 36 ,1–9. (d) Yao, Z.-J.; Jin, G.-X. Transition metal
complexes based on carboranyl ligands containing N, P, and S donors:
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Journal of the American Chemical Society
synthesis, reactivity and applications. Coord. Chem. Rev. 2013, 257,
carboranyl with aryl iodides:facile synthesis of 1-aryl-o-carboranes and
1,2-diaryl-o-carboranes. Angew. Chem. Int. Ed. 2015, 54, 7662–7665.
(14) Selected examples using 1,1-diphenylethylene as the radical trap-
ping reagent, see: (a) Liu, W.; Cao, H.; Zhang, H.; Chung, K. H.; He, C.;
Wang, H.; Kwong, F. Y.; Lei, A. Organocatalysis in cross-coupling:
DMEDA-catalyzed direct C−H arylation of unactivated benzene. J. Am.
Chem. Soc. 2010, 132, 16737–16740. (b) Ochiai, M.; Shu, T.; Nagaoka, T.;
Kitagawa, Y. -Vinylation of 1,3-dicarbonyl compounds with
alkenyl(aryl)iodonium tetrafluoroborates: effects of substituents on
the aromatic ring and of radical inhibitors. J. Org. Chem. 1997, 62, 2130–
2138. (c) Ghosh, I.; Kónig, B. Chromoselective photocatalysis:con-
trolled bond activation through light-color regulation of redox poten-
tials. Angew. Chem. Int. Ed. 2016, 55, 7676–7679. (d) Pan, J.; Chen, T.;
Zhang, Z.; Li, Y.; Zhang, X.; Zhang, F. A Cu-mediated one-pot Michael
addition/a-arylation strategy using a diaryliodonium salt: a direct and
efficient approach to -aryl-β-substituted cyclic ketone scaffolds.
Chem. Commun. 2016, 52, 2382–2385.
2522–2535. (e) Qiu, Z.; Ren, S.; Xie, Z. Transition metal−carboryne
complexes: synthesis, bonding, and reactivity. Acc. Chem. Res. 2011, 44,
299–309. (f) Joost, M.; Zeineddine, A.; Estévez, L.; Mallet-Ladeira, S.;
Miqueu, K.; Amgoune, A.; Bourissou, D. Facile oxidative addition of
aryl iodides to gold(I) by ligand design: bending turns on reactivity. J.
Am. Chem. Soc. 2014, 136, 14654–14657. (g) Adams, R. D.; Kiprotich, J.;
Peryshkov, D. V.; Wong, Y. O. Cage opening of a carborane ligand by
metal cluster complexes. Chem. Eur. J. 2016, 22, 6501–6504. (h) El-Hel-
lani, A.; Lavallo, V. Fusing N-heterocyclic carbenes with carborane an-
ions. Angew. Chem. Int. Ed. 2014, 53, 4489–4493. (i) Axtell, J. C.; Kir-
likovali, K. O.; Djurovich, P. I.; Jung, D.; Nguyen, V. T.; Munekiyo, B.;
Royappa, A. T.; Rheingold, A. L.; Spokoyny, A. M. Blue phosphorescent
Zwitterionic Iridium(III) complexes featuring weakly coordinating
nido-carborane-based ligands. J. Am. Chem. Soc. 2016, 138, 15758-15765.
(j) Wong, H.; Wu, L.; Lin, Z.; Xie, Z. Synthesis, structure and reactivity
of a borylene cation [(NHSi)2B(CO)]+ stabilized by three neutral lig-
ands. J. Am. Chem. Soc. 2017, 139, 13680−13683.
1
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32
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34
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42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(15) (a) Becke, A. D. Density-functional thermochemistry. III. The role
of exact exchange. J. Chem. Phys. 1993, 98, 5648-5652. (b) Lee, C.; Yang,
W.; Parr, R. G. Development of the Colle-Salvetti correlation-energy
formula into a functional of the electron density. Phys. Rev. B. 1988, 37,
785-789.
(11) Yamazaki, H.; Ohta, K.; Endo, Y. Regioselective synthesis of trii-
odo-o-carboranes and tetraiodo-o-carborane. Tetrahedron Lett. 2005,
46, 3119–3122.
(12) Greene, T. W.; Wuts, P. G. M. In Protective Groups In Organic Syn-
thesis, 4th ed.; John Wiley & Sons: New Jersey, 2007.
(13) Tang, C.; Xie, Z. Nickel-catalyzed cross-coupling reactions of o-
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