Palladium-catalyzed cross-coupling reactions of arylboronic acids and 2-I-p-carborane

Article abstract of DOI:10.1016/S0022-328X(02)01431-6

p-Carborane has been arylated on the 2-B-atom in high yields, using the Suzuki-Miyaura reaction. Thus the reaction between 2-I-p-carborane and various arylboronic acids [1-naphthyl-, phenyl-, 4-MeO-C₆H₄-, 3-CH₃CONH-C₆

Full text of DOI:10.1016/S0022-328X(02)01431-6

Journal of Organometallic Chemistry 657 (2002) 267ꢀ272
/
www.elsevier.com/locate/jorganchem
Palladium-catalyzed cross-coupling reactions of arylboronic acids
and 2-I-p-carborane
Ludvig Eriksson a,b, Irina P. Beletskaya b,*, Vladimir I. Bregadze c,*, Igor B. Sivaev a,c,
Stefan Sjoberg a,*
¨
a Department of Organic Chemistry, Institute of Chemistry, Uppsala University, P.O. Box 531, S-751 21 Uppsala, Sweden
b Department of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory, GSP-3, 119899 Moscow, Russia
c A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov Str. 28, 119991 Moscow, Russia
Received 6 December 2001; accepted 2 April 2002
Abstract
p-Carborane has been arylated on the 2-B-atom in high yields, using the Suzukiꢀ
I-p-carborane and various arylboronic acids [1-naphthyl-, phenyl-, 4-MeOÃC6H4Ã, 3-CH3CONHÃ
C6H4Ã], gave the corresponding 2-aryl-p-carboranes in DME solution when reacted in the presence of cesium fluoride and the
catalytic Pd2(dba)3ꢀdppb system. # 2002 Elsevier Science B.V. All rights reserved.
/Miyaura reaction. Thus the reaction between 2-
/
/
/
C6H4Ã, 4-NCÃC6H4Ã, 3-NO2Ã
/
/
/
/
/
/
Keywords: p-Carborane; Arylboronic acids; SuzukiꢀMiayara reactions; Cross-coupling; Palladium
/
1. Introduction
hydrophobic pharmacophores has recently been intensi-
fied [7ꢀ9], in particular by Endo [10ꢀ13].
/
/
The carboranes C2B10H12 exhibit remarkable chemi-
cal stability and are generally biologically inactive [1].
The use of carboranes in boron neutron capture therapy
(BNCT) for cancer has attracted much interest in recent
years. For this purpose, numerous carborane-containing
Another field of potential application of carborane
derivatives is material science. High chemical and
thermal stability in combination with the rigid structure
of the carborane cage and the possibility of attachment
of different types of substituents make them good
candidates for synthesis of new interesting materials
derivatives of biomolecules have been synthesized [2ꢀ5].
/
Besides for BNCT application, until recently, only a few
cases have been described where use has been made of
the carborane cages as hydrophobic pharmacophores in
biologically active molecules. One of the most explored
compounds in this respect is o-carboranylalanine, the o-
carboranyl analogue of phenylalanine, which has been
used to replace phenylalanine and tyrosine in biological
active peptides, such as [4-carboranyl-alanine, 5-leu-
cine]-enkephalin, angiotensins, bradykinins and sub-
stance-P octapeptides. This work has recently been
reviewed [6]. Research on the use of carboranes as
[14ꢀ18].
/
We are working on the synthesis of aryl- and
heteroaryl derivatives of carboranes containing different
functional groups, which we link directly to a boron
atom.
The C-arylation of p-carborane via its C-copper
derivatives has been widely studied during the last
decade [11ꢀ
/
13,16,19ꢀ21] and was there achieved, under
/
the action of aryl- and pyridyl-halides on Li(Mg)-
derivatives of carboranes under the catalysis of copper
salts.
The B-arylation of p-carborane is much less studied.
Synthesis of phenyl- and p-fluorophenyl-derivatives of
p-carborane by the palladium-catalyzed cross-coupling
reaction of 2-iodo-p-carborane with Grignard reagents
were reported [22,23]. However, the application of
Grignard reagents limits the introduction of substituents
* Corresponding authors. Tel.:
512524.
E-mail addresses: beletska@org.chem.msu.ru (I.P. Beletskaya),
bre@ineos.ac.ru (V.I. Bregadze), ssj@kemi.uu (S. Sjoberg).
ꢁ
/
46-18-513563; fax:
ꢁ
/
46-18-
¨
0022-328X/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 3 2 8 X ( 0 2 ) 0 1 4 3 1 - 6

268
L. Eriksson et al. / Journal of Organometallic Chemistry 657 (2002) 267ꢀ272
/
containing functional groups. Besides, it is known, that
using less active arylhalides in the reaction with orga-
nomagnesium compounds often yields a larger amount
homocoupling products. To overcome this problem, we
have developed a mild method of the B-arylation using
entry 6; dppe, entry 7; and dppp, entry 9) resulted in
lower reaction rates and lower yield of 2-phenyl-p-
carborane (3), together with the formation of by-
products. It should be noted that changing the base to
K2CO3 gave no reaction with dppe as the ligand (entry
8).
However, when we used dppb as the ligand (entry 10),
the reaction gave the desired product (3) in nearly
quantitative yield without any detectable (11B-NMR)
boronated side products, when the reaction was run in
the presence of only 2 mol% of the catalyst precursor
(corresponding to 4 mol% of active catalyst).
These favorable reaction conditions were then applied
to the reactions with various commercial arylboronic
acids, containing both electron-donating and electron-
withdrawing substituents. The reaction conditions and
the isolated yields of the 2-aryl-p-carboranes are given in
Table 2. The reaction with 1-naphthylboronic acid
(entry 2) proceeds in the same smooth way as the
reaction with phenylboronic acid (entry 1). A similar
yield was obtained for p-methoxyphenyl boronic acid
(entry 3). The introduction of the electron-withdrawing
nitro group in the meta position (entry 6) did not
decrease the yield of the desired product. In the case of
o-nitrophenyl boronic acid (entry 7), however, we found
no reaction.
As expected, the introduction of an electron-with-
drawing group in the para position sharply decreases the
reaction rate. Indeed, in the case of p-cyano-phenyl-
boronic acid (entry 5) a yield of 76% was obtained after
48 h only, whereas for other arylboronic acids besides p-
acetamido-phenylboronic acid (entry 4), the reactions
the Suzukiꢀ
ylboronic acids and 2-I-p-carborane.
An attempt to use the SuzukiꢀMiyaura cross-cou-
/Miyaura cross-coupling reaction with ar-
/
pling reaction for B-phenylation of o- and m-carborane
was undertaken by Zakharkin et al. [24], but the yield of
phenylcarborane derivatives in the case of 9-I-m-carbor-
ane was very low and 9-I-o-carborane did not produce
any expected cross-coupling product. In both cases,
biphenyl and the unsubstituted carboranes were formed.
2. Results and discussion
In the palladium catalyzed cross-coupling reactions of
2-I-p-carborane (1) with arylboronic acids, we have used
CsF in DME, utilizing the facts that the fluoride ion is a
good activating nucleophile and a mild base. The use of
the fluoride ions in these reactions was supported by our
preliminary exploratory coupling experiments of B-I-
carboranes and phenylboronic acid with a variety of
bases. Indeed, using K2CO3 in DMF as the base with
PdCl2(PPh3)2 as catalyst in the coupling of phenylboro-
nic acid (2) and 2-I-p-carborane (1) was ineffective (the
reaction stopped after 4 h), although the desired product
was obtained in a yield of 30%.
Phenylboronic acid was used as a model boronic acid
in the search for a good catalytic system for the cross-
coupling reactions between arylboronic acids and 2-I-p-
carborane. The results of these experiments are sum-
marized in Table 1. Among boron containing side
were completed over 10ꢀ12 h.
/
It is difficult to explain the decrease of the reaction
rate in the case of p-acetamido-phenylboronic acid. The
reaction proceeds selectively and gives the desired
product in 28% yield after 24 h.
products, p-carborane could be detected by GCꢀ
/MS
analysis and 11B-NMR.
Using the conventional PdCl2(PPh3)2 catalyst, a
rather good yield of 2-phenyl-p-carborane (3) (73%, 2
h) was obtained in the presence of a sufficiently large
amount of the catalyst (Table 1, entry 2). Using the same
amount of the catalyst (as in entry 2) but adding extra
ligand (PPh3) resulted in a sharp decrease of the reaction
rate, a lower yield of the desired coupling product, and
an increased yield of by-products (entry 3).
A change from PdCl2(PPh3)2 to Pd(PPh3)4 as the
catalyst did not significantly increase the desired pro-
duct yield (entry 4). Changing CsF to Bu4NF resulted in
a fast and complete consumption of 2-iodo-p-carborane,
but sharply increased the yield of by-products (entry 5).
To achieve an increase in the rate of the oxidative
addition step and an increase of the stability of the
palladium intermediate formed in this step, the mono-
dentate ligand (PPh3) was then changed to bidentate
ligands. Using CsF as the base and Pd2(dba)3 as the
catalyst precursor, the three bidentate ligands (BINAP,
The large effect of the nature of the arylboronic acid
on the reaction rate indicates that trans-metallation is
the rate-determining step of the reaction. Concerning
the first step, oxidative addition, it should be noted that
no formation of a palladium(II) intermediate (corre-
sponding to A in the Scheme 1) was observed in the 11B-
NMR spectrum of a mixture of one equivalent of Pd(0),
two equivalent of Ph3P, and one equivalent of 2-iodo-p-
carborane (1) in CDCl3. This spectrum contains only
signals from 1. This observation is in accordance with
observations reported by Marshall et al. [25], at the time
when our study was in a final stage. These authors
studied the reactivity of 9-I-m-carborane towards Pd(0)
complexes and were unable to observe the presence of a
L2I Pd-B-m-carboranyl Pd-complex as judged from the
31P-NMR spectrum of a mixture of (Ph3P)4Pd and 9-I-
m-carborane in toluene-d8.
Our data regarding the oxidative addition step could
be explained in a similar way as Marshall et al. [25]

L. Eriksson et al. / Journal of Organometallic Chemistry 657 (2002) 267ꢀ
/272
269
Table 1
Reaction of 2-I-p-carborane with phenonylboronic acid in the presence of CsF
a
b
Ratio of boronated products (3/1/side products)
Entry
Catalyst (mol%)
Time (h)
1
2
3
4
PdCl2(PPh3)2 (5)
PdCl2(PPh3)2 (10)
4
2
48/41/11
73/23/4
51/13/36
78/12/10
45/0/55
28/0/72
33/52/15
0/100/0
26/72/2
93/7/0
PdCl2(PPh3)2/PPh3 (10/20)
Pd(PPh3)4 (10)
PdCl2(PPh3)2 (10)
10
4
c
5
4
6
7
Pd2(dba)3/BINAP (2/5)
Pd2(dba)3/dppe (2/5)
Pd2(dba)3/dppe (2/5)
Pd2(dba)3/dppp (2/5)
Pd2(dba)3/dppb (2/4)
16
18
8
d
8
9
10
10
10
a
General conditions: 1 equivalent of 2-iodo-p-carborane (1), 1.5 equivalents of phenylboronic acid (2) and 3 equivalents of CsF in DME (2 ml/
mmol 1).
b
The ratios was determined by 11B-NMR.
c
Bu4NF.
K2CO3.
d
explained their results, namely, that this step is rever-
sible and that the complex (in our case A) is thermo-
dynamically disfavored. Marshall et al. used this
conclusion together with the known low nucleophilicity
of arylboronic acids to explain the low yield of coupling
product between 9-I-m-carborane and phenylboronic
acid. The formation of unsubstituted carboranes (meta-
as reported by Zakharkin et al. [24] and para- in our
case) according to Marshall et al. [25] ‘may involve o-
palladation of coordinated PPh3 to give a carboranyl
Pd-hydride which produces carborane upon BÃ
/
H re-
ductive elimination’.
The success of our reaction using cesium fluoride
could be explained by assuming that a borate, formed
via coordination of ArB(OH)2 with Fꢂ, moves the
equilibrium in the initial oxidative addition step. It is not
known which borate is the reactive species but in the
Scheme we have indicated that it might be ArÃ
B(OH)2Fꢂ, although Wright et al. [26], in a paper
introducing the use of fluoride ions in SuzukiꢀMiyaura
/
/
Table 2
Reaction of 2-I-p-carborane with various arylboronic acids
a
Entry
Substrate Ar-B(OH)2
Reaction time (h)
Product (2-aryl-p-carborane)
Isolated yields (%)
1
2
3
4
5
6
7
Phenyl
1-Naphthyl
12
12
12
24
48
12
24
3
4
5
6
7
8
90
93
4-MeO-C6H4
3-CH3CONH-C6H4
4-NC-C6H4
3-NO2-C6H4
2-NO2-C6H4
90
b
28/84
76
94
No reaction
a
General conditions: 1 equivalent of 2-I-p-carborane (2), 1.5 equivalents of arylboronic acid, 3 equivalents of CsF, 2 mol% Pd2(dba)3, 4 mol %
dppb, DME (2 ml/mmol 1), reflux under argon.
b
Yield based on recovered 1.

270
L. Eriksson et al. / Journal of Organometallic Chemistry 657 (2002) 267ꢀ272
/
external standard at 0 ppm. In the 13C-NMR spectra
of the compounds 5ꢀ7, the signals for the Car-B atoms
could not be detected. GCꢀMS analyses were performed
/
/
with a non-polar column and a Thermquest GCQ mass
spectrometer. Melting points were measured in sealed
tubes using a Buchi capillary melting point apparatus.
¨
MIKRO KEMI AB, Uppsala, Sweden, performed the
elemental analyses.
4.1. 2-Iodo-p-carborane (3)
2-Iodo-p-carborane was prepared in analogy with the
procedure described by Jones et al. [28] for 9-iodo-o-
carborane and adapted to p-carborane by Hawthorne et
al. [23].
1H-NMR (ppm) d 3.21 (s, 1H, CH), 2.90 (s, 1H, CH),
1.50ꢀ
65.4. 11B-NMR (ppm) d ꢂ
13.5 (4B, d, Jꢃ190 Hz), ꢂ
16.3 (1B, d, Jꢃ168 Hz), ꢂ28.3 (1B, s).
/
3.00 (broad m, 9H, BH). 13C-NMR (ppm) d 67.9,
Scheme 1.
/
11.8 (2B, d, Jꢃ/195 Hz),
coupling reactions, suggest that ArÃ
/
BF3ꢂ is the species
ꢂ
/
/
/
14.1 (2B, d, Jꢃ/156 Hz),
ꢂ
/
/
/
that undergoes the trans-metallation step. This has
recently been questioned by Littke et al. [27], who
showed that 4-bromo-N,N-dimethylaniline did not
form any coupling product with K[o-tolyl-BF3] in the
5. General procedure for the cross-coupling reactions
presence of Pd2(dba)3ꢀP(t-Bu)3 under conditions where
/
5.1. Experiments in Table 1
the coupling reaction between 4-bromo-N,N-dimethy-
laniline and o-tolylboronic acid proceeds to completion
in the presence of 3.3 equivalent of KF.
2-I-p-Carborane (ca. 100 mg, one equivalent), aryl-
boronic acid (1.5 equivalent), base (three equivalent)
and catalyst were all weighted into a 10 ml reaction vial
containing a magnetic stirring bar and connected to a
reflux condenser. The equipment was evacuated and
back-filled with argon, solvent (2 ml) was added and the
mixture was heated to reflux. In each case, the progress
of the reaction was monitored by TLC using pentane as
the eluent. The reaction was stopped either after
precipitation of palladium-black and decolorization of
the supernatant or when all 2-I-p-caborane was con-
sumed. The resulting mixture was diluted with diethyl
ether, filtered through a pad of Celite and concentrated
under reduced pressure. The reaction mixtures were
analyzed by 11B-NMR.
3. Conclusions
In this paper, we have shown that by a proper choice
of the reaction conditions it is possible to use the
SuzukiꢀMiyaura method for preparation of a number
/
of functionalized 2-B-aryl-p-carboranes. Work on the
corresponding cross-coupling reaction using other iodo-
carboranes including 9-iodo-m-carborane, is in pro-
gress.
4. Experimental
5.2. Syntheses of the aryl-p-carboranes 3ꢀ8 (Table 2)
/
All experiments were performed under argon atmo-
sphere. DME was freshly distilled from sodium benzo-
phenone. The arylboronic acids, ligands and palladium
sources were purchased from Lancaster Synthesis Ltd.
The general procedure described above was followed,
but in these experiments 300 mg (1.11 mmol) of 2-iodo-
p-carborane, arylboronic acid (ca. 1.5 mmol), cesium
fluoride 506 mg (3.33 mmol), Pd2(dba)3 20.3 mg (0.022
mmol, corresponding to 4 mol% Pd), dppb 18.9 mg
(0.044 mmol,), and 6 ml DME were used. The crude
products were purified by flash chromatography.
Merck Silica Gel 60 (230ꢀ400 mesh) and Merck Silica
/
60 F254 were used for flash chromatography and TLC,
respectively. TLC-plates were developed with palladium
chloride in acidified (hydrochloric acid) methanol solu-
tion.
Unless otherwise stated 1H, 13C and 11B-NMR
spectra were recorded in CDCl3 with a Varian XL-400
spectrometer at 400, 100.6 and 128.3 MHz, respectively.
5.3. 2-Phenyl-p-carborane (3)
2-Phenyl-p-carborane (1) was prepared according to
the general procedure for syntheses of the aryl-p-
11B-NMR spectra were acquired with BF3×
/
Et2O as

L. Eriksson et al. / Journal of Organometallic Chemistry 657 (2002) 267ꢀ
/272
271
carboranes employing 203 mg (1.66 mmol) of phenyl-
boronic acid. The reaction mixture was heated under
reflux for 12 h. Purification of the residue by flash
chromatography with pentane as the eluent gave 221 mg
(90%) of 1 as a clear oil, which slowly crystallized when
left unattended. The NMR data were in accordance with
those reported in the literature [23].
acetamidophenylboronic acid. The reaction mixture was
heated under reflux for 24 h. Purification of the residue
by flash chromatography using first pentane as the
eluent to give 201 mg of unreacted 2-I-p-carborane.
Subsequent eluation with diethyl ether gave 85 mg (28 or
84% based on recovered 2-I-p-carborane) of 6 as a white
solid. The sample for elemental analysis was obtained by
recrystallization from chloroform.
1
M.p. 193 8C. H-NMR, CD3OD, (ppm) d 1.6ꢀ
5.4. 2-(1-Naphtyl)-p-carborane (4)
/3.2
(broad m, BH, 9H), 2.15 (s, 3H), 3.40 (broad s, 1H),
The naphtylcarborane (4) was prepared according to
the general procedure for syntheses of the aryl-p-
carboranes employing 287 mg (1.65 mmol) of 1-naph-
tylboronic acid. The reaction mixture was heated under
reflux for 12 h. Purification of the residue by flash
chromatography with 2% diethyl ether in pentane as the
eluent gave 281 mg (93%) of 4 as a white solid. The
sample for elemental analysis was obtained by recrys-
3.61 (broad s, 1H), 7.24ꢀ
/
7.31 (m, 2H), 7.58 (ddd, Jꢃ
/
2.2, 2.8, 7.2 Hz, 1H), 7.62 (m, 1H). 13C-NMR, CD3OD,
(ppm) d 23.8, 65.1, 66.9, 121.2, 125.8, 129.3, 129.9,
139.4, 168.3. 11B-NMR, CD3OD, (ppm) d ꢂ
/
4.6 (ArÃ
/
B,
17.5 (1B). Anal. Calc.
1B), ꢂ
/
13.3 (2B), ꢂ
/
14.5 (6B), ꢂ
/
for C10H19B10NO (277.37); C, 43.30; H, 6.90; N, 5.05.
Found: C, 43.1; H, 6.7; N, 5.1%.
tallization from hexane.
1
M.p. 109 8C. H-NMR (ppm) d 1.6ꢀ
5.7. 2-(4-Cyanophenyl)-p-carborane (7)
/3.2 (broad m,
BH, 9H), 2.99 (broad s, 1H), 3.39 (broad s, 1H), 7.41
(dd, Jꢃ7.1, 8.1 Hz, 1H), 7.50 (ddd, Jꢃ1.2, 6.8, 8.1 Hz,
1H), 7.56 (ddd, Jꢃ1.2, 6.8, 8.4 Hz, 1H), 7.68 (d m, Jꢃ
2-(4-Cyanophenyl)-p-carborane (7) was prepared ac-
cording to the general procedure for syntheses of the
aryl-p-carboranes employing 245 mg (1.67 mmol) of 4-
cyanophenylboronic acid. The reaction mixture was
heated under reflux for 48 h. Purification of the residue
by flash chromatography with 10% EtOAc in pentane as
the eluent gave 208 mg (76%) of 7 as a white solid. The
sample for elemental analysis was obtained by recrys-
/
/
/
/
7.1 Hz, 1H), 7.84 (d m, Jꢃ
/
8.1 Hz, 1H), 7.88 (dd, Jꢃ
/
8.1, 1.2 Hz, 1H). 13C-NMR (ppm) d 63.3, 66.0, 125.0,
125.3, 126.0, 127.3, 129.1, 129.5, 133.6, 133.8, 136.2. 11B-
NMR (ppm) d ꢂ
/
5.4 (ArÃ
/
B, 1B), ꢂ
/
13.1 (2B), ꢂ15.0
/
(6B), ꢂ16.7 (1B). Anal. Calc. for C12H18B10 (272.23); C,
/
53.31; H, 6.71. Found: C, 53.6; H, 6.6%.
tallization from hexane.
1
M.p. 110 8C. H-NMR (ppm) d 1.6ꢀ
/
3.2 (broad m,
5.5. 2-(4-Methoxyphenyl)-p-carborane (5)
BH, 9H), 2.95 (broad s, 1H), 3.08 (broad s, 1H), 7.58
(XX? part of AA?XX? system, 4-cyanophenyl, 2H), 7.63
(AA? part of AA?XX? system, 4-cyanophenyl, 2H). 13C-
NMR (ppm) d 63.9, 65.2, 112.1, 118.9, 131.2, 133.7. 11B-
2-(4-Methoxyphenyl)-p-carborane (5) was prepared
according to the general procedure for syntheses of the
aryl-p-carboranes employing 253 mg (1.66 mmol) of 4-
methoxyphenylboronic acid. The reaction mixture was
heated under reflux for 12 h. Purification of the residue
by flash chromatography with 5% EtOAc in pentane as
the eluent gave 251 mg (90%) of 5 as a white solid. The
sample for elemental analysis was obtained by recrys-
NMR (ppm) d ꢂ
/
6.0 (ArÃ
/
B, 1B), ꢂ
/
13.8 (2B), ꢂ14.8
/
(6B), ꢂ17.0 (1B). Anal. Calc. for C9H15B10N (245.32);
/
C, 44.06; H, 6.16; N, 5.71. Found: C, 44.1; H, 6.1; N,
5.7%.
tallization from hexane.
1
6. 2-(3-Nitrophenyl)-p-carborane (8)
M.p. 99ꢀ
/
100 8C. H-NMR (ppm) d 1.6ꢀ
/3.2 (broad
multiple, BH, 9H), 2.90 (broad s, 1H), 3.03 (broad s,
1H), 3.82 (s, 3H), 6.87 (XX? part of AA?XX? system, 4-
methoxyphenyl, 2H), 7.48 (AA? part of AA?XX? system,
4-methoxyphenyl, 2H). 13C-NMR (ppm) d 55.1, 63.7,
2-(3-Nitrophenyl)-p-carborane (8) was prepared ac-
cording to the general procedure for syntheses of the
aryl-p-carboranes employing 279 mg (1.67 mmol) of 3-
nitrophenylboronic acid. The reaction mixture was
heated under reflux for 48 h. Purification of the residue
by flash chromatography with 10% EtOAc acid in
pentane as the eluent gave 276 mg (94%) of 8 as a
slightly yellow solid. The sample for elementary analysis
65.8, 113.6, 134.7, 160.2. 11B-NMR (ppm) d ꢂ
B, 1B), ꢂ13.8 (2B), ꢂ14.8 (4B), ꢂ15.5 (2B), ꢂ
(1B). Anal. Calc. for C9H18B10O (250.34); C, 43.18; H,
/
4.7 (ArÃ
/
/
/
/
/
18.0
7.25. Found: C, 43.2; H, 7.2%.
was obtained by recrystallization from hexane.
1
5.6. 2-(3-Acetamidophenyl)-p-carborane (6)
M.p. 105 8C. H-NMR (ppm) d 1.6ꢀ
/3.2 (broad m,
BH, 9H), 2.99 (broad s, 1H), 3.15 (broad s, 1H), 7.51
(dd, Jꢃ7.5, 8.2 Hz, 1H), 7.88 (d, m, Jꢃ7.5 Hz, 1H),
8.20 (ddd, Jꢃ
8.2, 2.4, 1.2 Hz, 1H), 8.36 (m, 1H). 13C-
NMR (ppm) d 64.0, 65.4, 123.3, 127.6, 128.8, 139.3,
2-(3-Acetamidophenyl)-p-carborane (6) was prepared
according to the general procedure for syntheses of the
aryl-p-carboranes employing 298 mg (1.66 mmol) of 3-
/
/
/

272
L. Eriksson et al. / Journal of Organometallic Chemistry 657 (2002) 267ꢀ272
/
147.7. 11B-NMR (ppm) d ꢂ
(2B), 14.7 (6B), 17.1 (1B). Anal. Calc. for
C8H15B10NO2 (265.31); C, 36.22; H, 5.70; N, 5.28.
/
6.11 (ArÃ
/
B, 1B), ꢂ13.8
/
[11] Y. Endo, T. Iijima, Y. Yamakoshi, A. Kubo, A. Itai, Bioorg.
Med. Chem. Lett. 9 (1999) 3313.
ꢂ
/
ꢂ
/
[12] Y. Endo, T. Iijima, Y. Yamakoshi, M. Yamaguchi, H. Fukasawa,
K. Shudo, J. Med. Chem. 42 (1999) 1501.
Found: C, 36.1; H, 5.6; N, 5.3%.
[13] Y. Endo, T. Iijima, T. Yoshimi, Y. Yamakoshi, Bioorg. Med.
Chem. Lett. 9 (1999) 3387.
[14] W. Jiang, D.E. Harwell, M.D. Mortimer, C.B. Knobler, M.F.
Hawthorne, Inorg. Chem. 35 (1996) 4355.
Acknowledgements
[15] D.M. Murphy, D.M.P. Mingos, J.M. Forward, J. Mater. Chem. 3
(1993) 139.
[16] U. Schoberl, T.E. Magnera, R.M. Harrison, F. Fleischer, J.L.
¨
The authors gratefully acknowledge the support by
INTAS (grant 99-00806), the Russian Foundation for
Basic Research (grant 99-03-33073), and the Swedish
Cancer Society (grant 3009-B00-11XBB).
Pflug, P.F.H. Schwab, X. Meng, D. Lipiak, B.C. Noll, V.S.
Allured, T. Rudalevige, S. Lee, J. Michl, J. Am. Chem. Soc. 119
(1997) 3907.
[17] P. Kaszynski, A.G. Douglas, J. Organomet.Chem. 581 (1999)
28.
[18] D.G. Allis, J.T. Spenser, J. Organomet. Chem. 614 (2000) 309.
[19] R. Coult, M.A. Fox, W.R. Gill, P.L. Herbertson, J.A.H.
MacBride, K. Wade, J. Organomet. Chem. 462 (1993) 19.
[20] M.A.H. Fox, J.A. MacBride, R.J. Peace, K. Wade, J. Chem. Soc.
Dalton Trans. (1998) 401.
References
[1] V.I. Bregadze, Chem. Rev. 92 (1992) 209.
[2] M.F. Hawthorne, Angew. Chem. Int. Ed. Engl. 32 (1993) 950.
[3] C. Morin, Tetrahedron 50 (1994) 12521.
[4] S. Sjoberg, J. Carlsson, H. Ghaneolhusseini, L. Gedda, T.
¨
[21] W.R. Gill, P.L. Herbertson, J.A.H. MacBride, K. Wade, J.
Organomet. Chem. 507 (1996) 249.
Hartman, J. Malmquist, C. Naeslund, P. Olsson, W. Tjarks, J.
Neuro-Oncol. 33 (1997) 41.
[22] L.I. Zakharkin, A.I. Kovredov, V.A. Ol’shevskaya, Z.S. Shau-
gumbekova, J. Organomet. Chem. 226 (1982) 217.
[23] W. Jiang, C.B. Knobler, C.E. Curtis, M.D. Mortimer, M.F.
Hawthorne, Inorg. Chem. 34 (1995) 3491.
[5] A.H. Soloway, W. Tjarks, B.A. Barnum, F.-G. Rong, R.F. Barth,
I.M. Codogni, J.G. Wilson, Chem. Rev. 98 (1998) 1515.
[6] I.M. Wyzlic, W. Tjarks, A.H. Soloway, A.K.M. Anisuzzaman, F.-
G. Rong, R.F. Barth, Int. J. Radiat. Oncol. Biol. Phys. 28 (1994)
1203.
[24] L.I. Zakharkin, E.V. Balagurova, V.N. Lebedev, Russ. J. Gen.
Chem. 68 (1998) 972.
[25] W.J. Marshall, R.J. Young, V.V. Grushin, Organometallics 20
(2001) 523.
[7] G. Oros, I. Ujvary, R.J. Nachman, Amino Acids 17 (1999) 357.
[8] R.J. Nachman, P.E.A. Teal, I. Ujvary, Peptides (New York) 22
(2001) 279.
[26] S.W. Wright, D.L. Hageman, L.D. McLure, J. Org. Chem. 59
(1994) 6095.
[9] I. Ujvary, R.J. Nachman, Peptides (New York) 22 (2001) 287.
[10] Y. Endo, T. Iijima, Y. Yamakoshi, H. Fukasawa, C. Miyaura, M.
Inada, A. Kubo, A. Itai, Chem. Biol. 8 (2001) 341 (and references
cited therein).
[27] A.F. Littke, C. Dai, C.F. Fu, J. Am. Chem. Soc. 122 (2000)
4020.
[28] J. Li, C.F. Logan, M. Jones, Inorg. Chem. 30 (1991) 4866.