Synthesis of quadruped-shaped polyfunctionalized o-carborane synthons

Article abstract of DOI:10.1039/c0cc05151a

o-Carborane derivatives with precisely defined patterns of substitution have been prepared from 8,9,10,12-I₄-1,2-closo-C₂B ₁₀H₈ by replacing the iodine atoms, bonded to four adjacent boron vertices in the cluste

Full text of DOI:10.1039/c0cc05151a

View Article Online / Journal Homepage / Table of Contents for this issue
Dynamic Article Links
ChemComm
Cite this: Chem. Commun., 2011, 47, 2252–2254
www.rsc.org/chemcomm
COMMUNICATION
Synthesis of quadruped-shaped polyfunctionalized o-carborane synthonsw
a
a
b
c
a
¨ ¨ ¨
˜
Alberto V. Puga, Francesc Teixidor, Reijo Sillanpaa, Raikko Kivekas and Clara Vinas*
Received 24th November 2010, Accepted 7th January 2011
DOI: 10.1039/c0cc05151a
o-Carborane derivatives with precisely defined patterns of
substitution have been prepared from 8,9,10,12-I4-1,2-closo-
C2B10H8 by replacing the iodine atoms, bonded to four adjacent
boron vertices in the cluster, with allyl, and subsequently
3-hydroxypropyl groups. The resulting structures, comprising
four pendant arms and two reactive vertices located on opposite
sides of a central o-carborane core, can be envisaged as versatile
precursors for dendritic growth.
degree and regioselectivity of substitution, while maintaining
the integrity of the underlying geometry.
A useful and general method for the functionalization of
o-carboranes through their boron atoms is electrophilic
iodination followed by Kumada cross-coupling reaction that
allows the introduction of organic moieties. This has led to
mono- and disubstituted compounds, starting from 9-I-1,2-
closo-C2B10H11, 9,12-I2-1,2-closo-C2B10H10, 3-I-1,2-closo-
C2B10H11 or 3,6-I2-1,2-closo-C2B10H10,9 but, as we are aware,
never to a higher degree of substitution. Recently, we reported
on the regioselective synthesis of 8,9,10,12-I4-1,2-closo-
C2B10H8 (2),10 where the four B–I vertices reside at the
compacted adjacent positions antipodal to the two carbon
atoms. By substitution of iodine with the appropriate organic
groups, the o-carborane cluster can be envisaged as a robust
dendritic core for multiple and diverse types of ramifications,
as illustrated in Fig. 1. Four arms may be densely appended to
the cluster through four boron vertices located at a compact
area of the cluster, whilst the two C–H vertices occupying the
two positions furthest away from them remain ready for
further functionalization or complexation. These prospects
prompted us to study the reactivity of 2 in order to create
polyfunctionalized quadruped-shaped synthons. Here, we
report on the synthesis of such structures, which may offer a
unique platform for the construction of large molecules with
full control over the position of the substituents.
Carboranes are molecules with unique structural features due
to their rigid geometry and rich derivative chemistry, which
make them of great interest as building blocks for macro-
molecular or supramolecular entities.1 Of particular interest is
the generation of dendrimers of high boron content, given
their potential use in boron neutron capture therapy (BNCT).2
This has been usually achieved by tethering boron cluster units
to the periphery of dendritic compounds or precursors.3 In
addition, globular dendrimers with twelve identical branches
appending from a central icosahedral closo-borane cluster
(closomers) have been produced.4 Nevertheless, much less
attention has been paid to carboranes as cores or focal points
for dendrimer growth, despite their possibilities for multiple
and versatile functionalisation. In this regard, we have recently
reported the synthesis of dendrons where o-carborane cluster
carbon atoms are located at the focal points.5 Subsequently,
we became interested in exploring similar molecular construction
from the boron vertices of the cluster.
In the present study, the boron tetraiodinated o-carborane
(2) has been chosen as the platform to prepare multiple
regioselective derivatives with different patterns of substitution
(Scheme 1). It was our main target to elucidate if the four
highly crowded iodine atoms in a compact region of the boron
cluster could be replaced. To achieve so, the cross-coupling
reaction on 2 with Grignard reagents in the presence of Pd(II)
Derivatization reactions on the o-carborane cluster (1,2-
closo-C2B10H12, 1) can be executed on either carbon or boron
vertices.6 In most of the occasions these transformations are
carried out through the carbon atoms, whereas the chemistry
of boron-substituted o-carboranes is relatively underdeveloped.
This is somewhat surprising, because B–H vertices in
o-carboranes exhibit electrophilic substitution chemistry in
many ways reminiscent of arenes.7 Furthermore, boron
vertices react at different rates depending on their position in
the cluster,8 which may enable an accurate control of the
a
`
Institut de Ciencia de Materials de Barcelona (CSIC),
Campus de la U.A.B., E-08193 Bellaterra, Spain.
E-mail: clara@icmab.es; Fax: +34 93 5805729
b Department of Chemistry, University of Jyvaskyla, FIN-40014,
Finland
¨
¨
c Department of Chemistry, University of Helsinki, FIN-00014,
Finland
w Electronic supplementary information (ESI) available: Synthesis
and characterization of 3–5 and crystallographic data of 4 and 5.
See DOI: 10.1039/c0cc05151a
Fig. 1 Vertex numbering in o-carborane and schematic representation
of its functionalization on boron (four-fold) and carbon (two-fold)
resulting in quadruped-shaped clusters. The arrows represent possible
directions for dendritic growth.
c
2252 Chem. Commun., 2011, 47, 2252–2254
This journal is The Royal Society of Chemistry 2011

View Article Online
Scheme 1 Derivatization reactions on 2. i and ii: RMgCl, cis-[Pd(PPh3)2Cl2] (cat.), CuI (cat.), THF, reflux (R = CH2QCHCH2 and C6H5 for
i and ii, respectively); iii: (1) BH3ÁTHF, (2) H2O2, NaOH (aq.).
and Cu(I) catalysts was studied. Two types of Grignard
reagents were used, phenylmagnesium and allylmagnesium
chlorides. The first would produce a highly congested region
in the o-carborane whereas the second would produce a more
relaxed space and, in addition it could provide ‘‘free’’ ends for
further reactions. Reaction of 2 with allylmagnesium chloride
proceeded completely after several hours to give 8,9,10,12-
CH2QCHCH2)4-1,2-closo-C2B10H8 (3) as a colourless oil in
high yields (see Scheme 1). The four-fold allylation of the
o-carborane cluster in 3 was confirmed by multinuclear NMR
and FT-IR spectroscopic techniques, mass spectrometry and
elemental analysis. In contrast, when 2 was reacted with
phenylmagnesium chloride, two iodine atoms were readily
exchanged, but the coupling of a third phenyl ring into the
cage was extremely slow, as observed by 11B NMR monitoring.
The resulting diiodo-diphenyl- mixed substituted o-carborane
could be isolated and characterized by spectroscopy, although
the positions of the iodine and phenyl substituents remained
unclear. Crystals suitable for X-ray diffraction were grown
from a chloroform/acetone solution.11 Solution and refine-
ment of the crystal structure unambiguously proved that the
compound obtained was 8,10-Ph2-9,12-I2-1,2-closo-C2B10H8
(4) (Fig. 2). The reason for the substitution being restricted
to B(8,10) could be a steric one, since these B–I vertices are the
furthest removed from each other in 2, whereas the iodine
atoms at B(9,12) lie at crowded positions. A similar observation
was reported for the B-arylation of the [1-Ph-6,7,8,9,10-I5-
closo-1-CB9H4]À anion.12 An interesting packing is
observed in the crystal lattice of 4, driven by Ccluster–HÁ Á Áp
interactions, established between the Ccluster–H vertices and
the centres of the phenyl ring planes (Fig. 3). Directed by such
interactions, the molecules of 4 pack into infinite layers
parallel to the crystallographic ab plane.
Fig. 3 A perspective of the molecular assembly through periodical
C
cluster–HÁ Á Áp interactions in the crystal structure of 4. White = H,
pink = B, grey = C, purple = I. Contacts shorter than the sum of
Van der Waals radii minus 0.1 A are depicted as dashed blue lines.
Thus, the crystal structure of 4 clearly reflects the ability of
C
cluster–H vertices in o-carboranes to participate in hydrogen
bonding with aromatic p systems. As previously reported,
these Ccluster–HÁ Á Áp interactions may serve as useful vectors
in crystal engineering and supramolecular recognition.1c,d,g,13
The terminal olefinic groups in 3 are free to perform further
reactions on them. As a first approach to the development of
these molecules, a hydroboration/oxidation reaction has been
carried out to transform the four terminal double bonds to
hydroxyl groups. BH3ÁTHF was used as the hydroborating
agent. Subsequent oxidation was performed by treatment with
H2O2 in a basic aqueous solution. After work up, a crystalline
solid was obtained. Its spectroscopic characterisation
revealed that the reaction had proceeded through specific
anti-Markovnikov additions, yielding pure 8,9,10,12-
(HOCH2CH2CH2)4-1,2-closo-C2B10H8 (5), i.e. with all four
hydroxyl groups at terminal positions (see Scheme 1).
Fig. 2 Ortep drawing of 4 having crystallographic mm symmetry.
Fig. 4 Ortep drawing of 5. Thermal displacement parameters are
Thermal displacement parameters are drawn at 30% level. Selected
bond distances: C(1)–C(1i)
drawn at 30% level. Hydrogen atoms, except the hydroxyl
=
1.640(14), I(1)–B(5)
1
=
2.177(8),
1
hydrogens are omitted. Selected bond distances: C(1)–C(2) =
B(4)–C(6) = 1.667(11) A. Symmetry operations: i = À x, À y, z;
1.632(4), C(13)–B(8) = 1.593(4), C(16)–B(9) = 1.588(4),C(19)–B(10) =
1.584(4) and C(22)–B(12) = 1.591(4) A.
2
2
1
2
1
2
ii = À y, À x, z; iii = y, x, z.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 2252–2254 2253

View Article Online
No hindered hydroboranes were thus needed for the control
of the regioselectivity. In addition, the crystal structure of 5
was determined by X-ray diffraction from samples grown by
K. J. Guenther, A. S. King, P. Morel, P. Schaffer, O. O. Sogbein
and K. A. Stephenson, Coord. Chem. Rev., 2002, 232, 173;
(e) R. F. Barth, J. A. Coderre, M. G. H. Vicente and T. E. Blue,
Clin. Cancer Res., 2005, 11, 3987; (f) V. I. Bregadze and
I. B. Sivaev, Eur. J. Inorg. Chem., 2009, 1433 and references
therein.
slow evaporation from an ethanol/water solution (Fig. 4).14
A
three-dimensional hydrogen bonded network involving all
O–H and Ccluster–H units dominates the crystal lattice. In
addition, the quadruped-like molecular structure displayed
by 5 illustrates the unique four-fold armed array on the
cluster. This anticipates a versatile chemistry for dendritic
growth, given the availability of the four terminal hydroxyl
groups for further elongation of the chains. Moreover,
the Ccluster–H vertices on the rigid head remain ready for
derivatization or supramolecular assembly. Work is underway
to attain larger polyfunctionalized molecules from 5.
3 (a) B. P. Dash, R. Satapathy, E. R. Gaillard, J. A. Maguire and
N. S. Hosmane, J. Am. Chem. Soc., 2010, 132, 6578; (b) R. Nu
A. Gonza
Org. Lett., 2005, 7, 231; (c) A. Gonza
Perez, C. Vinas, B. Boury, R. Sillanpaa, R. Kivekas and R. Nu
´ nez,
´
lez, C. Vinas, F. Teixidor, R. Sillanpaa and R. Kivekas,
¨
¨
¨
rez-
´
lez- Campo, E. J. Jua
´
´
´
nez,
¨
¨
¨
Macromolecules, 2008, 41, 8458; (d) A. Mollard and I. Zharov,
Inorg. Chem., 2006, 45, 10172; (e) G. Wu, R. F. Barth, W. L. Yang,
M. Chatterjee, W. Tjarks, M. J. Ciesielski and R. A. Fenstermaker,
Bioconjugate Chem., 2004, 15, 185; (f) D. Armspach, M. Cattalini,
E. C. Constable, C. E. Housecroft and D. Phillips, Chem.
Commun., 1996, 1823; (g) E. Hao, E. Friso, G. Miotto,
G. Jori, M. Soncin, C. Fabris, M. Sibrian-Vazquez and
M. G. H. Vicente, Org. Biomol. Chem., 2008, 6, 3732;
(h) H. J. Yao, R. N. Grimes, M. Corsini and P. Zanello, Organo-
metallics, 2003, 22, 4381.
The o-carborane cluster then provides a unique platform for
the construction of highly dense multibranched molecules with
a wide range of possibilities for derivatization. Derivatives of
o-carborane with precise patterns of substitution can be
prepared by judicious choice of the synthetic procedure. We
have coupled four hydroxyl terminated arms onto a specific,
compact area of the cluster occupied by four adjacent boron
vertices, ultimately leading to a quadruped-shaped structure
which might serve as a versatile dendritic precursor. The
system also offers the possibility for uneven substitution,
e.g., 8,10-aryl2-9,12-I2-1,2-closo-C2B10H8 in which the two
iodine atoms are ready for substitution with less crowded
substituents. Moreover, the Ccluster–H vertices on the rigid
o-carborane head are available as further linking points for
organic moieties, hydrogen bond acceptors, transition metals,
nanoparticles or surfaces. The generation of diverse macro-
molecules and supramolecular assemblies constitutes a main
focus for our current research and related advances will be
reported in the near future.
4 (a) L. Ma, J. Hamdi, F. Wong and M. F. Hawthorne, Inorg.
Chem., 2006, 45, 278; (b) T. J. Li, S. S. Jalisatgi, M. J. Bayer,
A. Maderna, S. I. Khanm and M. F. Hawthorne, J. Am. Chem.
Soc., 2005, 127, 17832.
5 R. Nu´ nez, A. Gonzalez-Campo, A. Laromaine, F. Teixidor,
´
R. Sillanpaa, R. Kivekas and C. Vinas, Org. Lett., 2006, 8,
4549.
¨
¨
¨
6 (a) F. Teixidor and C. Vinas, in Science of Synthesis., ed.
D. E. Kaufmann and D. S. Matteson, Georg Thieme Verlag,
Stuttgart, 2005; (b) V. I. Bregadze, Chem. Rev., 1992, 92, 209;
(c) R. N. Grimes, Carboranes, Academic Press, New York, 1970.
7 H. D. Smith, T. A. Knowles and H. Schroeder, Inorg. Chem., 1965,
4, 107.
8 J. A. Potenza, W. N. Lipscomb, G. D. Vickers and H. Schroeder,
J. Am. Chem. Soc., 1966, 88, 628.
9 (a) L. I. Zakharkin, A. I. Kovredov, V. A. Olshevskaya and
Z. S. Shaugumbekova, J. Organomet. Chem., 1982, 226, 217;
(b) J. Li, C. F. Logan and M. Jones, Inorg. Chem., 1991, 30,
4866; (c) Z. P. Zheng, W. Jiang, A. A. Zinn, C. B. Knobler and
M. F. Hawthorne, Inorg. Chem., 1995, 34, 2095; (d) G. Barbera,
A. Vaca, F. Teixidor, R. Sillanpaa, R. Kivekas and C. Vinas,
¨
¨
¨
Inorg. Chem., 2008, 47, 7309 and references therein.
10 A. Vaca, F. Teixidor, R. Kivekas, R. Sillanpaa and C. Vinas,
Dalton Trans., 2006, 4884.
This work was supported by Generalitat de Catalunya
¨
¨
¨
209/SGR/00279 and Spanish Ministerio de Ciencia
Innovacion by CTQ2010-16237.
e
´
11 Crystal data for 4. C14H18B10I2, Mr = 548.18, tetragonal, space
group P42/n c m (no. 138), a = b = 9.7507(3), c = 21.3372(8) A,
a = b = g = 901, V = 2028.66(12) A3, T = 173(2) K, Z = 4,
m(Mo-Ka) = 3.095 mmÀ1, 10 054 reflections collected, 1080 unique
reflections (Rint = 0.054) which were used in calculations. The final
wR(F2) was 0.0765 (all data) and R[F2 > 2s(F2)] = 0.0359.
12 A. Franken, C. A. Kilner, M. Thornton-Pett and J. D. Kennedy,
Chem. Commun., 2002, 2048.
Notes and references
1 (a) R. N. Grimes, Angew. Chem., Int. Ed. Engl., 1993, 32, 1289;
(b) T. J. Wedge and M. F. Hawthorne, Coord. Chem. Rev., 2003,
240, 111; (c) M. A. Fox and A. K. Hughes, Coord. Chem. Rev.,
2004, 248, 457; (d) P. C. Andrews, M. J. Hardie and C. L. Raston,
Coord. Chem. Rev., 1999, 189, 169; (e) B. H. Northrop, H. B. Yang
and P. J. Stang, Chem. Commun., 2008, 5896; (f) A. V. Puga,
13 (a) H. Lee, C. B. Knobler and M. F. Hawthorne, Chem. Commun.,
2000, 2485; (b) M. J. Hardie and C. L. Raston, Eur. J. Inorg.
Chem., 1999, 195.
F. Teixidor, R. Sillanpaa, R. Kivekas, M. Arca, G. Barbera and
¨
¨
¨
C. Vinas, Chem.–Eur. J., 2009, 15, 9755; (g) A. V. Puga,
F. Teixidor, R. Sillanpaa, R. Kivekas, M. Arca, G. Barbera and
C. Vinas, Chem.–Eur. J., 2009, 15, 9764.
14 Crystal data for 5. C14H36B10O4, Mr = 376.53, monoclinic, space
group P21/n (no. 14), a = 12.1257(5), b = 14.7447(6), c = 13.6855(5)
A, a = 90, b = 113.738(2), g = 901, V = 2239.82(15) A3, T = 173(2)
K, Z = 4, m(Mo-Ka) = 0.068 mmÀ1, 8518 reflections collected,
4395 unique reflections (Rint = 0.050) which were used in calcula-
tions. The final wR(F2) was 0.1835 (all data) and R[F2 > 2s(F2)] =
0.0746.
¨
¨
¨
2 (a) M. F. Hawthorne, Angew. Chem., Int. Ed. Engl., 1993, 32, 950;
(b) A. H. Soloway, W. Tjarks, B. A. Barnum, F. G. Rong,
R. F. Barth, I. M. Codogni and J. G. Wilson, Chem. Rev., 1998,
98, 1515; (c) V. I. Bregadze, I. B. Sivaev, D. Gabel and D. Wohrle,
¨
J. Porphyrins Phthalocyanines, 2001, 5, 767; (d) J. F. Valliant,
c
2254 Chem. Commun., 2011, 47, 2252–2254
This journal is The Royal Society of Chemistry 2011