C-carboranylation of a quasi-aromatic iron(II) cage complex and its organic aromatic analog by the metal-catalyzed (promoted) cross-coupling reactions

Article abstract of DOI:10.1016/j.inoche.2014.02.020

One-pot reaction a quasi-aromatic diiodoclathrochelate precursor with the carboranylating agent, generated in situ from equimolar amounts of lithium 1-ortho-carboranyl and trimethoxyborate, in the presence of a palladium catalyst afforded a ribbed-functionalized iron(II) mono-ortho-carboranoclathrochelate. Such a formation of C(carborane)C(clathrochelate) bond is accompanied by hydrodeiodination in a vicinal position and a monomethinemonocarborane macrobicyclic complex was isolated and characterized by the single crystal X-ray diffraction. The geometry of its FeN₆-coordination polyhedron is intermediate between a trigonal prism and a trigonal antiprism with the distortion angle φ of 24.9 and the height h of this polyhedron is equal to 2.32 A?; FeN distances vary from 1.889(2) to 1.921(2) A? and the average bite angle α is approximately 39.1. The model reaction of this carboranylating agent with 4-iodobiphenyl, giving the corresponding aryl carborane, proceeds only in vigorous reaction conditions with a palladium catalyst and copper(I) iodide as a promotor. The compounds obtained were characterized using elemental analysis, ESI and EI mass spectrometry, IR, Raman, UV-vis, ¹H, ¹¹B, ¹⁹F and ¹³C{ ¹H} NMR spectroscopy. Thus, palladium-catalyzed Suzuki-Miyaura (copper-promoted in the case of an aryl iodide) cross-coupling reactions of a generated in situ derivative of carboranylboronic ester have been successfully used, for the first time, for one-pot synthesis of a quasi-aromatic hybrid carboranoclathrochelate with an inherent polyhedral ribbed substituent and its aromatic analog 4-(1-ortho-carboranyl)biphenyl. The developed strategy has been then found useful in the organic chemistry as a versatile approach towards carborane-based organic compounds.

Full text of DOI:10.1016/j.inoche.2014.02.020

Inorganic Chemistry Communications 43 (2014) 142–145
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Inorganic Chemistry Communications
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C-carboranylation of a quasi-aromatic iron(II) cage complex and its organic
aromatic analog by the metal-catalyzed (promoted)
☆
cross-coupling reactions
Simyon V. Svidlov a, Oleg A. Varzatskii b, Tamara V. Potapova a, Anna V. Vologzhanina c, Sergey S. Bukalov c,
a,c
Larisa A. Leites c, Yan Z. Voloshin c, , Yurii N. Bubnov
⁎
a
Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, Moscow 119991, Russian Federation
Vernadsky Institute of General and Inorganic Chemistry of the National Academy of Sciences of Ukraine, Kyiv 03680, Ukraine
Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences, Moscow 119991, Russian Federation
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
One-pot reaction a quasi-aromatic diiodoclathrochelate precursor with the carboranylating agent, generated in
situ from equimolar amounts of lithium 1-ortho-carboranyl and trimethoxyborate, in the presence of a palladium
catalyst afforded a ribbed-functionalized iron(II) mono-ortho-carboranoclathrochelate. Such a formation of
С(carborane)\C(clathrochelate) bond is accompanied by hydrodeiodination in a vicinal position and a
monomethinemonocarborane macrobicyclic complex was isolated and characterized by the single crystal X-
ray diffraction. The geometry of its FeN6-coordination polyhedron is intermediate between a trigonal prism
and a trigonal antiprism with the distortion angle φ of 24.9° and the height h of this polyhedron is equal to
2.32 Å; Fe\N distances vary from 1.889(2) to 1.921(2) Å and the average bite angle α is approximately 39.1°.
The model reaction of this carboranylating agent with 4-iodobiphenyl, giving the corresponding aryl carborane,
proceeds only in vigorous reaction conditions with a palladium catalyst and copper(I) iodide as a promotor. The
compounds obtained were characterized using elemental analysis, ESI and EI mass spectrometry, IR, Raman,
UV–vis, 1H, 11B, 19F and 13C{1H} NMR spectroscopy. Thus, palladium-catalyzed Suzuki–Miyaura (copper-
promoted in the case of an aryl iodide) cross-coupling reactions of a generated in situ derivative of
carboranylboronic ester have been successfully used, for the first time, for one-pot synthesis of a quasi-
aromatic hybrid carboranoclathrochelate with an inherent polyhedral ribbed substituent and its aromatic
analog 4-(1-ortho-carboranyl)biphenyl. The developed strategy has been then found useful in the organic
chemistry as a versatile approach towards carborane-based organic compounds.
Received 10 December 2013
Accepted 18 February 2014
Available online 26 February 2014
Keywords:
Macrocyclic compounds
Clathrochelates
Ligand reactivity
Carboranylation
Cross-coupling reaction
© 2014 Elsevier B.V. All rights reserved.
Polyazomethine iron(II) clathrochelates have highly conjugated
three-dimensional macrobicyclic 18 electron framework [1] and this
corresponds to Hückel's rule (4n + 2). Therefore, these cage complexes
can be regarded as quasi-aromatic compounds with a reactivity similar
to those of their organic aromatic analogs. Such clathrochelates have
been shown to effectively inhibit the action of T7 RNA polymerase (T7
RNAP) in vitro, with the inhibition constant depending on the shape of
the inhibitor's molecule [2]. Their bis-clathrochelates analogs, which
contain two C\C conjugated macrobicyclic fragments, showed even
higher inhibitory activity; being in submicromolecular range [3], it
places them among the best metal-based transcription inhibitors.
Bis-polyhedral cobalt bis-carbollides [4] and their dimeric forms [5]
have been tested as efficient HIV protease inhibitors; so hybrid ditopic
carboranoclathrochelate with inherent carboranyl substituents seems to
be very prospective for the design of such type of antiviral and antitumor
drug candidates (so-called “topological drugs” [6]).
A series of carborane-containing iron(II) clathrochelates has been ear-
lier obtained in our group using Lewis acidity of ortho-carboranylboronic
acids and their derivatives [7,8]. As apical groups, the corresponding
ortho-carboranyl substituents, however, affected the electronic and spa-
tial structures of the clathrochelate framework only slightly.
On the other hand, carboranylated aromatic compounds are known
to have a wide range of properties useful for practical purposes, in-
cluding an intensive phosphorescence [9,10], catalytic [11] and
antiandrogenic [12] activities. However, only a limited number of
approaches to their synthesis have been described up to date;
those include the reaction of lithium [9] and copper [13] carboranes
with suitable aromatic precursors as well as “building” of a carborane
core by a reaction of decaborane with aryl acetylenes [14]. To the best
of our knowledge, there were no examples of the creation of a
C(carborane)\C(aryl) bond using the carboranylboronic acids and
their derivatives by the metal-promoted (catalyzed) cross-coupling
☆
A preliminary account of this work was presented at the 6th European Conferences on
Boron Chemistry, Radziejowice, Poland, 8–13th September 2013.
⁎
Corresponding author. Tel.: +7 499 1359344; fax: +7 499 1355085.
E-mail address: voloshin@ineos.ac.ru (Y.Z. Voloshin).
http://dx.doi.org/10.1016/j.inoche.2014.02.020
1387-7003/© 2014 Elsevier B.V. All rights reserved.

S.V. Svidlov et al. / Inorganic Chemistry Communications 43 (2014) 142–145
143
reaction, although the latter is among the most powerful and frequently
used approaches in the modern organic chemistry [15]. In the present
paper, we describe this new synthetic pathway for the creation of
such bond, based on the metal-promoted (catalyzed) cross-coupling re-
actions of lithium (1-ortho-carboranyl)trimethoxyborate with the
iodine-containing quasi-aromatic clathrochelate and aromatic organic
precursors. We also report the synthesis and structure of the first
ribbed-functionalized quasi-aromatic cage complex with a C\C conju-
gated carboranyl substituent (a carboranoclathrochelate) and its organ-
ic analog 4-(1-ortho-carboranyl)biphenyl, trying to compare the
reactivity of their precursors under such reaction conditions.
gave no target 4-(1-ortho-carboranyl)biphenyl even after reflux of
the reaction mixture for 20 h with Pd(DPPF)Cl2 as a catalyst. This
product was obtained by Scheme 1 only in the presence of an excess
of CuI; the plausible reaction scheme includes the formation of
coppercarborane species and binding of iodide anion by a copper
ion. We also found that this copper-promoted reaction did not proceed
without a palladium complex as a probable catalyst for the formation of
a coppercarborane derivative.
The compounds obtained were characterized using elemental
analysis, ESI and EI mass spectrometry, IR, Raman, UV–vis, 1H, 11B,
19
F and 13C{1H} NMR spectroscopy, and by X-ray diffraction (the
This carboranylating agent was generated in situ from equimolar
amounts of lithium 1-ortho-carboranyl and trimethoxyborate, and
its one-pot reaction with a quasi-aromatic diiodoclathrochelate pre-
cursor FeBd2(I2Gm)(BF)2 in the presence of catalytic amounts of
Pd(DPPF)Cl2 by Scheme 1 gave a ribbed-functionalized mono-
ortho-carboranoclathrochelate FeBd2(HGm(C2B10H11))(BF)2 [16];
no formation of a dicarboranylated clathrochelate product was observed
even in the presence of an excess of this carboranylating agent (probably
due to some steric restrictions). The formation of a С(carborane)–
C(clathrochelate) bond is accompanied by hydrodeiodination in a vicinal
position, giving a monomethinemonocarborane clathrochelate product.
The plausible mechanism of this reaction, which resulted in the substitu-
tion of one of the two iodine atoms by a carboranyl group and the
other by a hydrogen atom, includes either the anion radical
hydrodeiodination of a diiodoclathrochelate with a solvent followed
by substitution of the resulting product with a carboranyl group or the
substitution of one of the two iodine atoms by a carboranyl group follow-
ed by hydrodehalogenation of the resulted monoiodomonocarborane
clathrochelate (see SM, Scheme S1). The same reaction of this
clathrochelate precursor has been earlier observed for its modification
with copper(I) cyanide [17]; such precursor also undergoes a copper-
promoted reductive homocoupling under these reaction conditions.
The model reaction in the case of organic aromatic compounds of
lithium (1-ortho-carboranyl)trimethoxyborate with 4-iodobiphenyl
iron(II) carboranoclathrochelate).
The molecular structure of the carboranoclathrochelate FeBd2-
(HGm(C2B10H11))(BF)2 is shown in Fig. 1; its main geometrical param-
eters are listed in Table S1 (see SM). The geometry of its FeN6-
coordination polyhedron is intermediate between a trigonal prism
(TP, the distortion angle φ = 0°) and a trigonal antiprism (TAP, φ =
60°) with the average φ angle of 24.9°. Fe\N distances (from 1.889(2)
to 1.921(2) Å), the average bite angle α (39.1°) and the height of this co-
ordination polyhedron h (2.32 Å) are characteristic of the X-rayed
fluoroboron-capped monoribbed-functionalized iron(II) clathrochelates
[17–19]. The φ values for the monomethinemonofunctionalized iron(II)
clathrochelates vary from 23.2 to 24.9° (this work, [17–19]) and are
higher than that of their glyoximate analog (φ = 21.6° [19]). So the
presence of such ribbed functionalized substituents (C2B10H11, CH3,
CN or 2,6-di-tert-butylphenol substituents) causes an additional ro-
tation–contraction distortion of the macrobicyclic frameworks
around their three-fold pseudo-symmetry axis B…Fe…B in compari-
son with their dimethinoclathrochelate analog. Moreover, in the case
of the bulky ortho-carboranyl substituent this distortion is the most
pronounced due to the steric hindrances in the rigid cage complex,
which may be the reason for the formation of the monocarboranylated
clathrochelate product only. Its carboranyl substituent forms six-
membered cycle O1.N1.C1.C31.C32.H32A via an intramolecular
C(carborane)\H…O interaction. Typically, C…O distances for inter-
H
C
C
P
H
Fe
DPPF =
P
1eq. n-BuLi
1.6M solution in hexane
1eq. B(OCH3)3
F
B
B(OCH3)3
H
I
C
C
(Li+)
O
N
O
N
no reaction
O
3 mol % Pd(DPPF)Cl2
or
an excess of CuI
THF–hexane, reflux, 20h
N
Fe2+
N
I
I
N
O
N
O
O
B
Pd(DPPF)Cl2
F
3 mol % Pd(DPPF)Cl2,
+
an excess of CuI
THF–hexane
reflux, 5 h
THF – hexane
I
r.t.
5 h
F
B
O
N
O
N
O
N
H
C
C
Fe2+
C
C
N
O
N
N
H
O
O
60%
B
H
F
78%
FeBd2(HGm(C2B10H11))(BF)2
Scheme 1. The synthesis of lithium (1-ortho-carboranyl)trimethoxyborate and its reactions with iron(II) diiodoclathrochelate and 4-iodobiphenyl.

144
S.V. Svidlov et al. / Inorganic Chemistry Communications 43 (2014) 142–145
Fig. 1. General view of the carboranoclathrochelate FeBd2(HGm(C2B10H11))(BF)2. Hereafter, the non-hydrogen atoms are represented as thermal ellipsoids (p = 50%).
and intramolecular interactions C\H…O in carboranes fall in the range
of 2.65–3.55 Å [20]. In the crystal FeBd2(HGm(C2B10H11))(BF)2 C8H18
the corresponding value of 2.767(4) Å suggests rather strong bonding
in accordance with unexpectedly large value of chemical shift for
carboranyl C\H proton signal (δ1H = 5.67 ppm).
copper-promoted cross-coupling reaction with a generated in situ de-
rivative of carboranylboronic ester as a carboranylating agent. Starting
from a cage complex, it gave the first hybrid carboranoclathrochelate
with an inherent polyhedral ribbed substituent, while from the aromat-
ic precursor the corresponding aryl carborane was obtained, such C-
carboranylation reaction with a derivative of carboranylboronic ester
was used for the synthesis of such carborane-containing aromatic com-
pounds for the first time. Therefore, this synthetic approach paves the
way towards a wide range of metal complexes as well as organic
compounds.
,
IR spectra of the carboranoclathrochelate FeBd2(HGm(C2B10H11))
(BF)2 show C = N, N\O and B\O stretching vibrations characteristic
of the boron-capped tris-dioximate clathrochelates; in the Raman spec-
trum the cage breathing and stretching vibrations ν(B\H) and
ν(C\H) are observed at 770, 2590 and 3074 cm−1, respectively, being
characteristic of the ortho-carboranyl substituent. The same vibrations
of ortho-carboranyl fragment in the Raman spectrum of 4-phenyl(1-
ortho-carboranyl)benzene are observed at approximately 750, 2600
and 3070 cm−1, while its biphenyl fragment shows the intensive
Acknowledgments
The authors gratefully acknowledge the support of RFBR (grants 12-
03-00955, 12-03-90431 and 13-03-90452), the Marie Curie International
Research Staff Exchange Scheme (IRSES) of the 7th EU Framework Pro-
gram (grant 295160), RAS (programs 6 and P8) and Russian State Atomic
Energy Corporation “ROSATOM” (project D.4 f.43.90.13.1053). We also
thank Dr. A. Belov and Dr. V. Novikov for their donation of the
diiodoclathrochelate precursor and for NMR measurements. High resolu-
tion mass spectra were recorded in the Department of Structural Studies
of Zelinsky Institute of Organic Chemistry RAS.
Raman lines at 1275, 1584 and 1598 cm−1
.
UV–vis spectra of the dichloromethane solutions of the
clathrochelate precursor FeBd2(I2Gm)(BF)2 and its carboranylated
derivative FeBd2(HGm(C2B10H11))(BF)2 (see SM, Fig. S1) contain,
in the visible range, four intensive absorption bands assigned to the
metal-to-ligand charge transfer Fed → Lπ* (see SM, Table S2). Only
one of these bands is substantially (by 30 nm) longwave-shifted and
suffers from a dramatical decrease in its relative intensity. The latter
may be explained by substantial electronic changes in only one of the
three ribbed fragments of a clathrochelate framework, resulting from
its hydrodehalogenation and C\C conjugation with a strong electron-
withdrawing carboranyl substituent.
Appendix A. Supplementary material
This is the first example of the one-pot C-carboranylation of a quasi-
aromatic cage metal complex and its organic aromatic analog by the
palladium-catalyzed Suzuki–Miyaura and, in the case of aryl iodide,
The details of analytical, spectral and X-ray data collections, the cor-
responding tables and the description of the initial compounds and re-
agents are given in Supplementary material.

S.V. Svidlov et al. / Inorganic Chemistry Communications 43 (2014) 142–145
145
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[16] Syntheses. Lithium (1-ortho-carboranyl)trimethoxyborate. 1.6 M solution of
n-BuLi (0.33 ml, 0.54 mmol) in hexane was added to a solution of ortho-carborane
(0.78 g, 0.54 mmol) in THF (7 ml) at −78 °C and the reaction mixture was stirred
for 1 h at this temperature. Then trimethoxyborate (0.60 ml, 0.54 mmol) was added
and the reaction mixture was stirred for 1 h at −78 °C and for 1 h at 20 °C. The obtained
solution of lithium (1-ortho-carboranyl)trimethoxyborate in THF-hexane mixture was
used without its further purification.
CCDC 961075 contains the supplementary crystallographic data
for FeBd2(HGm(C2B10H11))(BF)2 · C8H18. These data can be obtained
free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html.
Supplementary data to this article can be found online at http://dx.
doi.org/10.1016/j.inoche.2014.02.020.
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