Novel approach to aminocarboranes by mild amidation of selected iodo-carboranes

Article abstract of DOI:10.1021/ic101620h

A mild protocol for the palladium-catalyzed Buchwald-Hartwig amidation of icosahedral carboranes is described. Employing 2-dicyclohexylphosphino-2′- (N,N-dimethylamino)biphenyl (1) as a ligand and K₃PO₄as a base, benzamide, trifluoro

Full text of DOI:10.1021/ic101620h

Inorg. Chem. 2010, 49, 10627–10634 10627
DOI: 10.1021/ic101620h
Novel Approach to Aminocarboranes by Mild Amidation of Selected
Iodo-carboranes
Yulia Sevryugina, Richard L. Julius, and M. Frederick Hawthorne*
International Institute of Nano and Molecular Medicine, School of Medicine, University of Missouri,
1514 Research Park Drive, Columbia, Missouri 65211-3450, United States
Received August 10, 2010
A mild protocol for the palladium-catalyzed Buchwald-Hartwig amidation of icosahedral carboranes is described. Employing
2-dicyclohexylphosphino-20-(N,N-dimethylamino)biphenyl (1) as a ligand and K3PO4 as a base, benzamide, trifluoroaceta-
mide, acetamide, and formamide were coupled to a series of mono- and di-iodo carboranes furnishing the respective
carborane derivatives in good to excellent yields. Subsequent base-mediated saponification of the trifluoroacetamide
derivatives was shown to provide the free aminocarboranes. The structures of N-(1,7-dicarba-closo-dodecaboran-9-yl)-
benzamide (8a), N-(1,7-dicarba-closo-dodecaboran-9-yl)trifluoroacetamide (8b), N-(1,12-dicarba-closo-dodecaboran-2-yl)-
benzamide (10a), N-(1,2-dicarba-closo-dodecaboran-9-yl)benzamide (12a), N-(1,2-dicarba-closo-dodecaboran-9-yl)aceta-
mide (12c), N-(1,2-dicarba-closo-dodecaboran-9-yl)formamide (12d), N-(1,2-dicarba-closo-dodecaboran-3-yl)benzamide
(13a), N,N0-(1,7-dicarba-closo-dodecaboran-9,10-diyl)dibenzamide (15a), and N,N0-(1,7-dicarba-closo-dodecaboran-
9,10-diyl)bis(trifluoroacetamide) (15b) have been established through X-ray single-crystal diffraction studies.
Introduction
applications.5 Key to this variety of applications is the unique
properties of carboranes, such as resistance to catabolism,
kinetic inertness to reagents, rigidity, and strong hydrophobicity.
Critical for exploiting these properties is the facile and well-
defined derivative chemistry of carborane compounds. Substi-
tution at the C-H vertices is easily accomplished through
deprotonation by a strong base (alkyllithium reagents, Grignard
reagents, etc.) affording a strong nucleophilic carboranyl anion
capable of reaction with a wide range of electrophiles including
alkyl halides, carbonyl derivatives, and chlorosilanes, to mention
only a few examples.6 Conversely, the B-H vertices permit
derivatization by reactive electrophiles, leading, for example, to
B-iodo derivatives. The latter, in combination with Pd-catalyzed
cross-coupling reactions, facilitate synthesis of a diverse range of
B-derivatives.7
The most prominent of Pd-catalyzed aryl/alkenyl-hetero-
atom coupling reactions is the Buchwald-Hartwig coupling.
The first coupling reaction between an aryl halide and amino
stannane was reported by Migita et al. in 1983 but stayed un-
referenced for a decade.8 Hartwig and Buchwald further
expanded the reaction scope by independently demonstrating
the use of milder bases (K3PO4, Cs2CO3, KOH, etc.) to depro-
tonate the amine after complexation to the palladium center.9
The icosahedral carboranes, closo-1,2-C2B10H12 (o-carbo-
rane), closo-1,7-C2B10H12 (m-carborane), and closo-1,12-C2B10-
H12 (p-carborane), have been the subject of investigation in
areas as diverse as host-guest chemistry,1 catalysis,2 ion
sensing,3 and materials science4 as well as medicinal chemistry
*To whom correspondence should be addressed. E-mail: hawthornem@
missouri.edu.
(1) (a) Yang, X.; Knobler, C. B.; Hawthorne, M. F. J. Am. Chem. Soc. 1992,
114, 380–382. (b) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001, 40, 486–516.
(c) Wedge, T. J.; Hawthorne, M. F. Coord. Chem. Rev. 2003, 240, 111–128. (d) Bayer,
M. J.; Jalisatgi, S. S.; Smart, B.; Herzog, A.; Knobler, C. B.; Hawthorne, M. F. Angew.
Chem., Int. Ed. 2004, 43, 1854–1857. (e) Bae, Y.-S.; Farha, O. K.; Spokoyny, A. M.;
Mirkin, C. A.; Hupp, J. T.; Snurr, R. Q. Chem. Commun. 2008, 35, 4135–4137.
(2) (a) Lee, H.; Diaz, M.; Hawthorne, M. F. Tetrahedron Lett. 1999, 40,
7651–7655. (b) Lyubimov, S. E.; Tyutyunov, A. A.; Vologzhanin, P. A.; Safronov,
A. S.; Petrovskii, P. V.; Kalinin, V. N.; Gavrilov, K. N.; Davankov, V. A. J.
Organomet. Chem. 2008, 693, 3321–3323. (c) Douvris, C.; Ozerov, O. V.
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Foxman, B. M.; Ozerov, O. V. J. Am. Chem. Soc. 2010, 132, 4946–4953.
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Chem. 1999, 71, 1371–1377. (b) Johnson, R. D.; Badr, I. H. A.; Diaz, M.; Wedge,
T. J.; Hawthorne, M. F.; Bachas, L. G. Electroanal. 2003, 15, 1244–1250.
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Mirkin, C. A.; Hupp, J. T. J. Am. Chem. Soc. 2007, 129, 12680–12681. (b) Hao, E.;
Fabre, B.; Fronczek, F. R.; Vicente, M. G. H. Chem. Commun. 2007, 4387–4389. (c)
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r
2010 American Chemical Society
Published on Web 10/21/2010
pubs.acs.org/IC

10628 Inorganic Chemistry, Vol. 49, No. 22, 2010
Scheme 1. Amination of o-Carborane in the 3-Positiona
Sevryugina et al.
Numerous examples of B-C bond-forming palladium-cat-
alyzed coupling exist in iodo-carborane chemistry.16 However,
many of these reactions suffer from the need for strong
nucleophilic reaction partners as well as long reaction times
at elevated temperatures. One significant contributing factor
necessitating such forcing conditions, in all probability, is the
sluggish reactivity of the B-I bond toward oxidative addi-
tion to a palladium center, presumably the first step in any
Pd-catalyzed coupling reaction.17 However, previous studies
had shown that judicious choice of ligand, base, and palladium
source exert significant influence on the kinetics of coupling
reactions.18 We wish to leverage the recent advances in coupling
reaction design to extend the B-coupling of carboranes to
include nitrogen nucleophiles with a minimum of both harsh
reaction conditions and extended reaction times.
a In all icosahedral cage structures solid sphere represents CH; hollow
sphere represents BH; bolded hollow sphere represents B.
Recently, two reports appeared which describe the catalytic
coupling of amines with 2-iodo-p-carborane19 and amides with
both 9-iodo-m-carborane and 2-iodo-p-carborane.20 In the first
instance,19 a variety of aliphatic and aromatic amines are
reacted with 2-iodo-p-carborane using a 5% BINAP/Pd(dba)2
catalytic system (BINAP=2,20-bis(diphenylphosphino)-1,10-bi-
naphthyl, dba=dibenzylideneacetone) and employing tBuONa
as a base. The resulting aminocarboranes are formed in moderate
to good yields with the major side-products being either
p-carborane or the 2-hydroxy-p-carborane compound. While
this method furnishes the desired coupling products, it is
significantly limited by the use of tBuONa as a base. Though
tBuONa is both economical and easily obtained, use of a strong
base precludes the use of many functional groups and signifi-
cantly restricts the scope of the reaction. Additionally, tBuONa
is capable of deboronating both o- and m-carboranes to the
corresponding nido-species, ruling out its use in the majority of
carborane applications.
Further investigations of carborane-based Buchwald-
Hartwig coupling describe the coupling of amides to both
9-iodo-m-carborane and 2-iodo-p-carborane in moderate to
good isolated yields.20 The key step in this reaction is the
formation of metalloamide nucleophile through deprotonation
with NaH in dioxane. Once again, the use of a strong base
(NaH) precludes the use of a wide variety of functional groups
in this reaction. The continuing studies we report here describe
the development of a facile, inexpensive, and mild protocol for
the Pd-catalyzed coupling of a variety of nitrogen-nucleophiles
with ortho-, meta-, and para-carboranes.
While Buchwald-Hartwig coupling has facilitated the synthesis
of a great diversity of compounds, introduction of an amino
functionality at the boron atom of a carborane cage remains
challenging.
Reduction of o-carborane with sodium in liquid ammonia
leads to the 3-amino-o-carborane dianion derivative that
may then be oxidized to the neutral species with potassium
permanganate,10 as shown in Scheme 1. In a similar
fashion the N-piperidyl derivative of o-carborane has been
obtained.11 However, this reaction has proven to be difficult
because of the potential for fire and/or explosion, particularly
during the oxidation step.12 Additionally, only the 3-amino-
o-carborane isomer may be synthesized through this method
because of isomerization of both m- and p-carboranes under
these reaction conditions.11
Amino derivatives of m-carboranes may be produced
through insertion of diphenylaminodichloroborane into dicar-
bollide ion [m-C2B9H11]2- 13 or by the reaction of 2-carboxy-m-
carborane, C2B10H11(2-COOH), with HN3 in H2SO4,14 the
latter method also furnishing the p-carborane derivative, 2-amino-
p-carborane.15 However, given the ease of the high-yield,
regioselective synthesis of a large variety of iodo-carborane
derivatives and the ubiquity of the Buchwald-Hartwig cou-
pling reaction in organic synthesis, Pd-catalyzed coupling
reactions would seem an ideal route to the previously uncom-
mon B-N carborane derivatives.
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Gedymin, V. V. Russ. J. Gen. Chem. 1973, 43, 1974–1979.
General Procedures. All coupling reactions were carried out
under argon using Schlenk techniques. Toluene was freshly distilled
from CaH2 prior to use, and tetrahydrofuran (THF) was dried by
distillation over sodium metal. All other solvents were used as
purchased from commercial sources. Benzamide, 2,2,2-trifluoroa-
cetamide, 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphe-
nyl (DavePhos) (1), (2-biphenyl)dicylclohexylphosphine (2),
(15) Zakharkin, L. I.; Kalinin, V. N.; Kobel’kova, N. I. Russ. J. Gen.
Chem. 1980, 50, 919–922.
(16) (a) Zakharkin, L. I.; Kovredov, A. I.; Ol’shevskaya, V. A. Izv. Akad.
Nauk SSSR, Ser. Khim. 1985, 4, 888–892. (b) Kovredov, A. I.; Shaugumbe-
kova, Z. S.; Petrovskii, P. V.; Zakharkin, L. I. Zh. Obshch. Khim. 1989, 59, 607–
611. (c) Li, J.; Logan, C. F.; Jones, M., Jr. Inorg. Chem. 1991, 30, 4866–4868.
(d) Bregadze, V. I. Chem. Rev. 1992, 92, 209–223. (e) Zheng, Z.; Jiang, W.; Zinn,
A. A.; Knobler, C. B.; Hawthorne, M. F. Inorg. Chem. 1995, 34, 2095–2100. (f )
Jiang, W.; Knobler, C. B.; Curtis, C. E.; Mortimer, M. D.; Hawthorne, M. F. Inorg.
Chem. 1995, 34, 3491–3498. (g) Jiang, W.; Harwell, D. E.; Mortimer, M. D.;
Knobler, C. B.; Hawthorne, M. F. Inorg. Chem. 1996, 35, 4355–4359. (h)
Zakharkin, L. I.; Balagurova, E. V.; Lebedev, V. N. Russ. J. Gen. Chem. 1998, 68,
922–924. (i) Zakharkin, L. I.; Ol'shevskaya, V. A.; Zhigareva, G. G. Russ. J. Gen.
Chem. 1998, 68, 925–927. (j) Eriksson, L.; Winberg, K. J.; Rodrigo, T. C.;
(17) (a) Marshall, W. J.; Young, R. J., Jr.; Grushin, V. V. Organometallics
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2001, 20, 523–533. (b) Vinas, C.; Barbera, G.; Oliva, J. M.; Teixidor, F.; Welch,
A. J.; Rosair, G. M. Inorg. Chem. 2001, 40, 6555–6562.
(18) Molander, G. A. Catalyst Components for Coupling Reactions; John
Wiley & Sons: Hoboken, 2008.
(19) Beletskaya, I. P.; Bregadze, V. I.; Kabytaev, K. Z.; Zhigareva, G. G.;
Petrovskii, P. V.; Glukhov, I. V.; Starikova, Z. A. Organometallics 2007, 26,
2340–2347.
(20) Mukhin, S. N.; Kabytaev, K. Z.; Zhigareva, G. G.; Glukhov, I. V.;
Starikova, Z. A.; Bregadze, V. I.; Beletskaya, I. P. Organometallics 2008, 27,
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€
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Article
Inorganic Chemistry, Vol. 49, No. 22, 2010 10629
(2-biphenyl)di-tert-butylphosphine (3), ethylenebis(diphenyl-
phosphine) (4), 2-dicyclohexylphosphino-2,6-dimethoxybiphenyl
(5), 2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl (6), 2-di-
tert-butylphosphino-2,4,6-triisopropylbiphenyl (7), sodium hydro-
xide, and tris(dibenzylideneacetone)dipalladium were used as pur-
chased (Sigma-Aldrich, St.-Louis, MO). 9-Iodo-o-carborane21 and
3-iodo-o-carborane22 were prepared according to the procedures
described by Jones et al. 2-Iodo-p-carborane and 9-iodo-m-carbor-
ane were prepared analogous to earlier report.23 All iodo-carbor-
anes as well as formamide were azeotropically dried with benzene to
remove any trace of water. Tribasic potassium phosphate was
ground to a fine powder and then dried thoroughly by heating
under vacuum at 105 °C. All solids (with the exception of sodium
hydroxide) were stored in an argon-filled glovebox. Silica gel was
used as purchased (63-200 μm, Sorbent Technologies, Inc.).
Analytical thin-layer chromatography (TLC) for carborane identi-
fication was performed by using precoated silica-gel XHL plates
(Sorbent Technologies, Inc.) and visualized by dipping into an
acidified (hydrochloric acid) solution of PdCl2 followed by heating.
11B, 13C, and 1H NMR spectra were obtained using Bruker DRX
500, DRX 300, Bruker Avance 400 and Avance 500 spectrometers.
19F NMR spectra were acquired on Bruker Avance 400 (376.5
MHz). 11B and 19F NMR spectra were externally referenced to
the product in yields given below. Further purification may be
accomplished by passing through active carbon column or by
recrystallization from hexane or mixtures of diethyl ether/hexane
and dichloromethane/hexane. The alternative synthetic routes using
THF as a solvent generally lead to lower yields and are provided in
the Supporting Information.
N-(1,7-Dicarba-closo-dodecaboran-9-yl)benzamide (8a). Ac-
cording to the general procedure, 449 mg (92%) of compound
8a were obtained as a white solid: mp 155.7-157.6 °C. 1H NMR
(300 MHz): δ 7.90 (m, 2H, Carom-H ), 7.41 (m, 3H, Carom-H ),
5.97 (s, 1H, NH ), 2.90 (s, 2H, Ccarborane-H ), 3.8-1.2 (m, 9H,
BH ). 13C NMR (75 MHz): δ 169.5 (CdO), 135.4, 131.3, 128.4,
127.2 (Carom), 52.0 (Ccarborane). 11B NMR (160.4 MHz): δ -0.6
(1B, s), -7.1 (2B, d, J 162), -11.2 (1B, d, J 151), -14.1 (2B, d,
J 170), -15.6 (2B, d, J 168), -18.8 (1B, d, J 180), -22.1 (1B, d,
J 162). HRMS (ESIMS) m/z for C9H16NOB10 [M-H]- calcd
262.2239, found 262.1726.
N-(1,7-Dicarba-closo-dodecaboran-9-yl)trifluoroacetamide (8b).
According to the general procedure, 394 mg (89%) of compound
8b were obtained as a slightly off-white solid. 1HNMR(400MHz):
δ 5.77 (s, 1H, NH), 2.80 (s, 2H, Ccarborane-H), 3.4-1.4 (m, 9H,
BH). 13C NMR (125.8 MHz): δ 159.4 (q, JF 36.4, CdO), 115.8 (q,
JF 292.5, CF3), 52.5 (Ccarborane). 19F NMR: δ -75.7 (CF3). 11B
NMR (128.4 MHz): δ -1.6 (1B, s), -6.8 (2B, d, J 164), -10.4 (1B,
d, J 152), -13.7 (2B, d, J 154), -14.8 (2B, d, J 161), -18.2 (1B, d,
J 182), -20.9 (1B, d, J 182). HRMS (APCI) m/z for C4H12-
NOB10F3 [M] calcd 255.1876, found 255.1667.
BF3 Et2O (δ = 0 ppm for 11B NMR and -153.0 ppm for 19F
3
NMR). 1H NMR and 13C NMR spectra were internally referenced
to residual solvent signals (CDCl3, δ = 7.24 ppm for 1H NMR and
77.0 ppm for 13C NMR). All NMR spectra were recorded from
CDCl3 solutions. All here reported coupling constants J are in hertz
(Hz). Mass spectra were obtained on an ABI QSTAR and Mariner
Biospectrometry Workstation by PerSeptive Biosystems. Melting
points were obtained using an automated melting point system
OptiMelt (Stanford research system).
N-(1,12-Dicarba-closo-dodecaboran-2-yl)benzamide (10a).
According to the general procedure, 407 mg (83%) of com-
pound 10a were obtained as a white solid: mp 141.6-143.6 °C.
1H NMR (500 MHz): δ 7.82 (m, 2H, Carom-H ), 7.53 (m, 1H,
Carom-H ), 7.45 (m, 2H, Carom-H ), 6.18 (s, 1H, NH ), 3.84 (s,
1H, Ccarborane-H ), 2.77 (s, 1H, Ccarborane-H ), 3.2-1.4 (m, 9H,
BH ). 13C NMR (125.8 MHz): δ 169.88 (CdO), 134.8, 131.7,
128.5, 127.1 (Carom), 65.2, 60.6 (Ccarborane). 11B NMR (160.4
MHz): δ -5.4 (1B, s), -14.2 (2B, d, J 172), -15.7 (4B, d, J 164),
-16.6 (2B, d, J 159), -19.8 (1B, d, J 178). HRMS (ESIMS) m/z
for C9H16NOB10 [M-H]- calcd 262.2239, found 262.1666.
N-(1,12-Dicarba-closo-dodecaboran-2-yl)trifluoroacetamide (10b).
According to the general procedure, 363 mg (82%) of compound
10b were obtained as a slightly off-white solid: mp 79.6-81.9 °C. 1H
NMR (500 MHz): δ 6.36 (s, 1H, NH), 3.61 (s, 1H, Ccarborane-H),
2.82 (s, 1H, Ccarborane-H), 3.2-1.6 (m, 9H, BH). 13C NMR (125.8
MHz): δ159.8 (q, JF 37.5, CdO),116.2(q,JF 296.0, CF3), 64.9, 61.6
(Ccarborane). 11B NMR (160.4 MHz): δ -6.7 (1B, s), -14.4 (2B, d,
J 176), -15.5 (4B, d, J 152), -16.3 (2B, d, J 144), -19.0 (1B, d,
J 167). HRMS (APCI) m/z for C4H11NOB10F3 [M-H]- calcd
254.1798, found 254.1197.
Test Reactions. In a glovebox, dry test tubes were charged
with 50 mg (0.18 mmol) of 9-iodo-m-carborane, 3 equiv (118 mg,
0.54 mmol) of K3PO4, 5 equiv (112 mg, 0.90 mmol) of benzamide,
2.5 mol % (4 mg, 0.005 mmol) of Pd2(dba)3, and 5 mol % of the
respective ligand 1-7. The tubes were then sealed with a latex cap,
approximately 2 mL of dry toluene was added via syringe, and the
tubes were then suspended in a 100 °C oil bath. The reaction was
monitored via thin layer chromatography (TLC).
General Procedure for Coupling of Compounds 8, 10, 12, 13,
15. Into an argon-filled glovebox was brought a dry 25 mL
Schlenk flask, where was added 500 mg (1.85 mmol) of the appro-
priate iodo-carborane, 3 equiv (5.54 mmol) of the appropriate
nitrogen nucleophile, 5 equiv (1.96 g, 9.23 mmol) of K3PO4,
5 mol % (36 mg, 0.09 mmol) of 1, 2.5 mol % (42 mg, 0.046 mmol)
of Pd2(dba)3, and a Teflon-coated magnetic stir bar. The flask was
then capped with a stopper, removed from the glovebox, and
approximately 8 mL of dry toluene was added by syringe. The
amount of toluene should be minimal, just enough to cover the base
so that reaction mixture looks as a thick slurry. The flask was then
placed in a 100 °C oil bath for 2 h during which the color changed
from purple to orange. After 2 h, the flask was removed from the oil
bath and reaction mixture filtered. The filtrate was evaporated to
leave orange-to-red oily residue. The residue was then dissolved in
dichloromethane and evaporated with about 3 mL of SiO2 (63-200
μm) and then twice coevaporated with a small amount of hexane.
The solid was added directly to the top of a silica column and eluted
beginning with 0:100 dichloromethane/hexane mixture and con-
tinuously increasing the concentration of dichloromethane. It is
important to move quickly from reaction to column. This is
especially needed for the ortho-carborane and trifluoroacetamide
derivatives reactions. Once the compound was isolated from a
column, the volatiles were removed by rotary evaporator to provide
N-(1,2-Dicarba-closo-dodecaboran-9-yl)benzamide (12a). Accor-
ding to the general procedure, 440 mg (90%) of compound 12a were
obtained as a slightly off-white solid: mp 181.9-182.5 °C. 1H NMR
(400 MHz): δ 7.76 (m, 1H, Carom-H), 7.74 (m, 1H, Carom-H),
7.41 (m, 3H, Carom-H), 5.73 (s, 1H, NH), 3.54 (s, 1H,
Ccarborane-H), 3.49 (s, 1H, Ccarborane-H), 3.4-1.4 (m, 9H, BH).
13C NMR (125.8 MHz): δ 168.9 (CdO), 135.6, 131.2, 128.4, 127.1
(Carom), 51.2, 45.6 (Ccarborane). 11B NMR (160.4 MHz): δ5.9 (1B, s),
-3.5 (1B, d, J 148), -9.7 (2B, d, J 149), -14.5 (2B, d, J 175), -16.1
(2B, d, J 159), -16.7 (2B, d, J 130). HRMS (APCI) m/z for
C9H16NOB10 [M-H]- calcd 262.2239, found 262.1984.
N-(1,2-Dicarba-closo-dodecaboran-9-yl)trifluoroacetamide (12b).
According to the general procedure, 423 mg (90%) of compound
12b were obtained as a pale yellow solid, which was further recrys-
tallized from hexane to yield 197 mg of off-white crystals (yield
42%): mp 96.1-96.6 °C. 1H NMR (400 MHz): δ 5.63 (s, 1H, NH),
3.57 (s, 1H, Ccarborane-H), 3.55 (s, 1H, Ccarborane-H), 3.2-1.4 (m,
9H, BH). 13C NMR (125.8 MHz): δ 158.7 (q, JF 36.3, CdO), 115.8
(q, JF 300.0, CF3), 51.9, 47.2 (Ccarborane). 19F NMR: δ -76.2 (CF3).
11B NMR (128.4 MHz): δ 4.4 (1B, s), -3.4 (1B, d, J 150), -9.8 (2B,
d, J 152), -14.7 (2B, d, J 150), -15.7 (2B, d, J 140), -16.6 (2B, d,
(21) Andrews, J. S.; Zayas, J.; Jones, M., Jr. Inorg. Chem. 1985, 24, 3715–
3716.
(22) Li, J.; Logan, C. F.; Jones, M., Jr. Inorg. Chem. 1991, 30, 4866–4868.
(23) Jiang, W.; Knobler, C. B.; Curtis, C. E.; Mortimer, M. D.;
Hawthorne, M. F. Inorg. Chem. 1995, 34, 3491–3498.

10630 Inorganic Chemistry, Vol. 49, No. 22, 2010
Sevryugina et al.
J 181). HRMS (APCI) m/z for C4H12NOB10F3 [MþH]þ calcd
the glovebox, and approximately 8 mL of dry toluene was added
by syringe. The flask was then placed in a 100 °C oil bath for 12 h
during which the color changed from purple to orange. After 12
h, the flask was removed from the oil bath and approximately 2 g
of silica gel was added to the reaction mixture. The volatiles were
then removed, and the remaining solid was added directly to the
top of a silica column. The product was then eluted beginning with a
0:100 diethyl ether/hexane mixture and finishing in a 100:0 diethyl
ether/hexane mixture while increasing diethyl ether concentration
10% at a time stepwise. The volatiles were then removed under
reduced pressure by rotary evaporator to provide 848 mg (88%)
255.1876, found 255.1176.
N-(1,2-Dicarba-closo-dodecaboran-9-yl)acetamide (12c). To a
mixture of 9-iodo-o-carborane (1.90 g, 7.04 mmol), acetamide
(1.25 g, 21.2 mmol), Pd2(dba)3 (0.161 g, 0.176 mmol), 1 (0.138 g,
0.352 mmol) and K3PO4 (7.47 g, 35.2 mmol) was added freshly
distilled THF (20 mL), and the reaction mixture was stirred at
room temperature for 48 h. After this time starting material was
still present in the reaction mixture, so it was heated to 40 °C for
another 24 h. The reaction mixture was filtered and coevapo-
rated with 30 mL of SiO2 (63-200 μm), which was put on the top
of the chromatography column (120 mL, 63-200 μm). It was
chromatographed using ethyl acetate gradient in hexanes (0 to
55%) to give after evaporation 0.780 g (55%) of white crystalline
solid: mp 155.8-157.0 °C. 1H NMR (500 MHz): δ 5.21 (br s, 1H,
NH ), 3.55 (s, 1H, Ccarborane-H ), 3.51 (s, 1H, Ccarborane-H ),
2.8-1.6 (m, 9H, BH ), 1.97 (s, 3H, CH3). 13C NMR (125.8
MHz): δ 172.8 (CdO), 51.4, 45.8 (Ccarborane), 25.1 (CH3). 11B
NMR (160.4 MHz): δ 5.5 (1B, s), -3.5 (1B, d, J 147), -9.7 (2B,
d, J 151), -14.5 (2B, d, J 163), -15.9 (2B, d, J 131), -16.6 (2B, d,
J 179). HRMS (APCI) m/z for C4H17NOB10 [Mþ2H] calcd
203.2315, found 203.1816; m/z for C4H14NOB10 [M-H]- calcd
200.2080, found 200.2106.
1
of product 15a as a white solid: mp 225.6-228.1 °C. H NMR
(500 MHz): δ 7.91 (4H, m, Carom-H), 7.46 (6H, m, Carom-H),
7.05 (2H, s, NH),2.88(2H,s,Ccarborane-H),3.5-1.5(8H,m,BH).
13C NMR (100.6 MHz): δ 171.3 (CdO), 135.0, 131.4, 128.4, 127.3
(Carom), 48.2 (Ccarborane). 11B NMR (160.4 MHz): δ -1.8 (2B, s),
-7.6 (2B, d, J 140), -15.8 (4B, d, J 140), -23.7 (2B, d, J 152).
HRMS (APCI) m/z for C16H21N2O2B10 [M-H]- calcd 381.2614,
found 381.1670.
N,N0-(1,7-dicarba-closo-dodecaboran-9,10-diyl)bis(trifluoroaceta-
mide) (15b). Following the synthetic procedure for 15a but using
1.14 g (10.08 mmol) of trifluoroacetamide, 775 mg (84%) of
compound 15b were obtained as an off-white solid: mp 165.1-
167.2 °C. 1H NMR (500 MHz): δ 6.63 (2H, s, NH ), 2.98 (2H, s,
Ccarborane-H ), 3.5-1.7 (8H, m, BH ). 13C NMR (100.6 MHz): δ
160.3 (CdO), 117.3, 114.4 (CF3), 49.2 (Ccarborane). 19F NMR: δ
-76.1 (CF3). 11B NMR (160.4 MHz): δ -3.0 (2B, s), -7.8 (2B, d,
J 164), -15.4 (4B, d, J 152), -22.7 (2B, d, J 197). HRMS (APCI)
m/z for C6H11N2O2B10F6 [M-H]- calcd 365.1731, found
365.0845.
N-(1,2-Dicarba-closo-dodecaboran-9-yl)formamide (12d). A
250 mL Schlenk flask was charged with 9-iodo-o-carborane
(7.5 g, 27.6 mmol), Pd2(dba)3 (0.632 g, 0.69 mmol), 1 (0.543 g,
1.38 mmol), K3PO4 (29.3 g, 138 mmol), formamide (3.73 g, 82.8
mmol), and 35 mL of THF. The reaction mixture was heated at
60 °C for 3 h under argon atmosphere. After cooling to room
temperature, the solvent was dried under vacuum, redissolved in
dichloromethane, and run onto a small silica plug, washed, and
dried under vacuum. The product was isolated by silica gel
column chromatography as a white solid: 2.61 g (50%). 1H
NMR (500 MHz): δ 7.96 (d, 1H, CH ), 5.55 (s, 1H, NH ), 3.52 (s,
1H, Ccarborane-H ), 3.43 (s, 1H, Ccarborane-H ), 3.0-0.7 (m, 9H,
BH ). 13C NMR (125.8 MHz): δ 166.1 (CdO), 51.3, 44.9
(Ccarborane). 11B NMR (160.4 MHz): δ 5.9 (1B, s), -4.1 (1B, d,
J 149), -10.4 (2B, d, J 151), -15.6 (2B, d, J 162), -16.0 (2B, d,
J 162), -17.1 (2B, d, J 184). HRMS (TOF MS) m/z for
C3H12NOB10 [M-H]- calcd 186.1923, found 186.1937.
N-(1,2-Dicarba-closo-dodecaboran-3-yl)benzamide (13a). Ac-
cording to the general procedure, 440 mg (90%) of compound
General Procedure for the Hydrolysis of Compounds 8b, 10b,
and 13b (Compounds 9b, 11b, 14b). In a round-bottom flask
equipped with a magnetic stir bar was added 300 mg (1.18 mmol)
of the appropriate trifluoroacetamide derivative (8b, 10b, or
13b) along with 1.5 g of NaOH, 10 mL of distilled water, 3 mL of
THF, 3 mL of MeOH, and 3 mL of iPrOH. The mixture was then
allowed to stir at room temperature. Reaction was completed
after 3 days for 9b, 7 days for 11b, and 6 days for 14b. It is
recommended to monitor the reaction progress by TLC. For 11b
an additional 1 g of NaOH dissolved in 5 mL of water was
introduced after 3 days from the reaction start, and the stirring
was resumed. Upon completion, to the reaction mixture was
added approximately 15 mL of distilled water. The solution was
then extracted with dichloromethane (3 ꢀ 15 mL), the organic
fractions were combined, dried over Na2SO4, and all volatiles
were removed by rotary evaporator. For 11b even after 7 days of
stirring at room temperature some of starting material was still
present in the reaction mixture. Therefore, the product was
further purified by silica-gel column chromatography. Com-
pounds 9b, 11b, 14b were obtained as white powders.
1
13a were obtained as a slightly off-white solid. H NMR (500
MHz): δ 7.82 (m, 2H, Carom-H ), 7.59 (m, 1H, Carom-H ), 7.51
(m, 2H, Carom-H ), 6.39 (s, 1H, NH ), 4.62 (s, 2H, Ccarborane-H
), 3.1-1.5 (m, 9H, BH ). 13C NMR (125.8 MHz): δ 171.3 (CdO),
133.6, 132.5, 128.8, 127.1 (Carom), 54.8 (Ccarborane). 11B NMR
(160.4 MHz): δ -4.5 (2B, d, J 149), -6.7 (1B, s), -11.0 (1B, d,
J 151), -12.7 (2B, d, J 167), -14.4 (2B, d, J 132), -15.1 (2B, d,
J 146). HRMS (ESIMS) m/z for C9H17NOB10 [M] calcd
263.2317, found 263.1584.
9-Amino-1,7-dicarba-closo-dodecaborane (9b). According to
the general procedure, 166 mg (89%) of compound 9b were
N-(1,2-Dicarba-closo-dodecaboran-3-yl)trifluoroacetamide (13b).
According to the general procedure, 240 mg (51%) of compound
13b were obtained as an off-white crystalline solid: mp 80.3-
1
obtained as a white solid: mp 165.0-166.7 °C. H NMR (400
MHz): δ 2.71 (s, 2H, Ccarborane-H ), 0.71 (s, 2H, NH2), 3.2-1.1
(m, 9H, BH ). 13C NMR (100.6 MHz): δ 50.8 (Ccarborane). 11B
NMR (128.4 MHz): δ 5.1 (1B, s), -7.5 (2B, d, J 161), -10.7 (1B,
d, J 149), -14.2 (2B, d, J 163), -16.0 (2B, d, J 166), -19.5 (1B, d,
J 180), -25.5 (1B, d, J 181). HRMS (APCI) m/z for C2H14NB10
[MþH]þ calcd 160.2130, found 160.2390.
1
81.3 °C. H NMR (500 MHz): δ 6.46 (s, 1H, NH), 4.41 (s, 2H,
Ccarborane-H), 3.1-1.6 (m, 9H, BH). 13C NMR (125.8 MHz): δ
160.5 (q, JF 37.5, CdO), 115.2 (q, JF 286.3, CF3), 54.7 (Ccarborane).
11B NMR (160.4 MHz): δ -3.8 (2B, d, J 151), -8.2 (1B, s), -10.7
(1B, d, J 151), -13.1 (3B, d, J 175), -14.6 (3B, d, J 181). HRMS
(APCI) m/z for C4H12NOB10F3 [MþH]þ calcd 255.1876, found
255.1189.
2-Amino-1,12-dicarba-closo-dodecaborane (11b). Product 11b
was purified by column chromatography eluted beginning with
dichloromethane and then slowly increasing concentration of 5%
Et2NH/MeOH solution in dichloromethane to 7%. First was eluted
the starting material 10b still present in the reaction mixture (42 mg,
14% of the initial load). Product 11b was isolated as a white powder
(142 mg, 76% yield). The product (11b) has a strong and distinct
odor as well as high volatility, which results in the here reported yield
being lower than the actual one. The compound sublimes before
melting at atmospheric pressure: Tsubl is 163.4-166.4 °C. 1H NMR
N,N0-(1,7-dicarba-closo-dodecaboran-9,10-diyl)dibenzamide
(15a). Into an argon-filled glovebox was brought a dry 25 mL
round-bottom flask into which was added 1.00 g (2.52 mmol) of
9,10-diiodo-m-carborane. To this was added 4 equiv (1.22 g,
10.08 mmol) of benzamide, 5 equiv (2.67 g, 12.6 mmol) of
K3PO4, 5 mol % (50 mg, 0.13 mmol) of 1, 2.5 mol % (58 mg,
0.06 mmol) of Pd2(dba)3, and a Teflon-coated magnetic stir bar.
The flask was then capped with a latex stopper, removed from

Article
Inorganic Chemistry, Vol. 49, No. 22, 2010 10631
(400 MHz): δ 2.95 (s, 1H, Ccarborane-H), 2.77 (s, 1H, Ccarborane
-
Scheme 2. Deboronation of o-Carborane to 7,8-Dicarba-nido-unde-
caborate
H), 1.07 (s, 2H, NH2), 3.3-0.9 (m, 9H, BH). 13C NMR (100.6
MHz): δ 68.5, 62.7 (Ccarborane). 11B NMR (128.4 MHz): δ -0.8
(1B, s), -14.7 (2B, d, J 158), -15.9 (4B, d, J 164), -17.9 (2B, d, J
167), -23.2 (1B, d, J 166). HRMS (APCI) m/z for C2H14NB10
[MþH]þ calcd 160.2130, found 160.2323.
3-Amino-1,2-dicarba-closo-dodecaborane (14b). According to
the general procedure, 185 mg (99%) of compound 14b was
obtained as a white solid. 1H NMR (400 MHz): δ 3.52 (2H, s,
Ccarborane-H ), 1.38 (2H, s, NH2), 3.2-0.7 (9H, BH ). 13C NMR
(100.6 MHz): δ 58.0 (Ccarborane). 11B NMR (128.4 MHz): δ 0.3
(1B, s), -4.4 (2B, d, J 148), -9.7 (1B, d, J 149), -14.1 (1B, d,
J 182), -14.8 (2B, d, J 155), -15.4 (2B, d, J 163), -18.6 (1B, d,
J 152). HRMS (APCI) m/z for C2H14NB10 [MþH]þ calcd
160.2130, found 160.2039; for C2H12NB10 [M-H]- calcd
158.1974, found 158.1949.
Scheme 3. Phosphine Ligands Screening Test Reactions
X-ray Diffraction Studies. The X-ray quality crystals were
obtained upon slow evaporation of diethyl ether/hexane mix-
tures, except for crystals of 15bO, which were grown from
dichloromethane/hexane. Data collection for the studied crys-
tals was carried out at -100 °C on a Bruker SMART 1000 CCD
area detector system using the ω scan technique with Mo KR
˚
radiation (λ = 0.71073 A) from a graphite monochromator.
Data reduction and integration were performed with the soft-
ware package SAINT.24 Data were corrected for absorption
using SADABS.25 The crystal structures were solved with the
direct methods program SHELXS-97 and were refined by full
matrix least-squares techniques with the SHELXTL26 suite of
programs. All non-hydrogen atoms were refined with anisotro-
pic thermal parameters, except for the three disordered CF3-
groups in crystal structures of 8b, four in 15bM and one in 15bO,
for which disorder was modeled over three rotational orienta-
tions. The hydrogen atoms were located in difference Fourier
maps and refined individually. For 8a and 12c, some hydrogens
were included at geometrically idealized positions and refine-
ment was mixed. Crystallographic data and details of data
collection and structure refinements of 8a,b, 10a, 12a,c,d, 13a,
15a,b are provided in Supporting Information, Table S2.
to the carbon vertices are susceptible to attack by nucleo-
philic bases leading to loss of a BH vertex from the
cage and formation of the nido-C2B9H12 structure
-
(Scheme 2).29
Tribasic potassium phosphate, commonly employed in
Buchwald-Hartwig coupling, was selected to circumvent
this undesired side reaction. Many Buchwald-type biaryl
phosphine ligands are commercially available and possess
excellent substrate tolerance and versatility. A selection
of ligands 1-7 was chosen to be screened in test reactions
involving the coupling of benzamide to 9-iodo-m-carbor-
ane (Scheme 3). As 9-iodo-m-carborane was shown to be
less reactive in cross-coupling reactions than 2-iodo-p-
carborane30 and its deboronation to occur under more
drastic conditions comparing to o-carborane, it was
chosen as a test-substrate. Reactions were carried out at
the 50 mg scale (0.18 mmol of iodo-carborane) and
monitored by TLC.
After 2 h, the reaction using catalyst ligand 1 showed
complete consumption of starting 9-iodo-m-carborane
and presence of substituted 9-amido-m-carborane, while
other reaction mixtures exhibited substantial amounts of
unreacted starting material, particularly the tert-butyl
substituted phosphines.
Results and Discussion
Test Reactions. Key to successful Buchwald-Hartwig
coupling reactions is careful selection of both ligand and
base.27 Carboranes exhibit a nonuniform electrondensity
pointing toward the boron atoms furthest away from the
carbons,28 which is most pronounced in ortho-carborane.
In the latter, the most electron poor boron atoms nearest
(24) SAINT, v 7.68A; Bruker AXS Inc.: Madison, WI, 2009.
(25) Sheldrick, G. M. SADABS 2008/1; Univerity of Gottingen: Gottingen,
Germany, 2008.
(26) Sheldrick, G. M. SHELXTL, version 6.14; Bruker AXS, Inc.: Madison,
WI, 2001.
(27) (a) Lober, O.; Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2001,
123, 4366–4367. (b) Pawlas, J.; Nakao, Y.; Kawatsura, M.; Hartwig, J. F. J. Am.
Chem. Soc. 2002, 124, 3669–3679. (c) Stauffer, S. R.; Hartwig, J. F. J. Am.
Chem. Soc. 2003, 125, 6977–6985. (d) Frisch, A. C.; Zapf, A.; Briel, O.; Kayser,
B.; Shaikh, N.; Beller, M. J. Mol. Catal. A: Chem. 2004, 214, 231–239. (e) Li,
J. J.; Corey, E. J. Name Reactions of Functional Group Transformations; John
Wiley & Sons: Hoboken, 2007.
(28) Maruca, R.; Schroeder, H.; Laubengayer, A. W. Inorg. Chem. 1967,
6, 572–574.
(29) (a) Wiesboeck, R. A.; Hawthorne, M. F. J. Am. Chem. Soc. 1964, 86,
1642–1643. (b) Hawthorne, M. F.; Young, D. C.; Garrett, P. M.; Owen, D. A.;
Schwerin, S. G.; Tebbe, F. N.; Wegner, P. A. J. Am. Chem. Soc. 1968, 90, 862–
€
€
Coupling Reactions of 9-Iodo-m-carborane. In an effort
to fully characterize and quantify reaction products, the
reaction shown in Scheme 3 with phosphine ligand 1 was
attempted on a larger scale. After 2 h, TLC analysis
~
868. (c) Vinas, C.; Butler, W. M.; Teixidor, F.; Rudolph, R. W. Inorg. Chem. 1986,
25, 4369–4374. (d) Fox, M. A.; Gill, W. R.; Herbertson, P. L.; MacBride, J. A. H.;
Wade, K. Polyhedron 1996, 15, 565–571. (e) Crespo, O.; Gimeno, M. C.; Jones,
P. G.; Laguna, A. J. Chem. Soc., Dalton Trans. 1997, 1099–1102. (f ) Imamura,
K.; Yamamoto, Y. Bull. Chem. Soc. Jpn. 1997, 70, 3103–3110. (g) Fox, M. A.;
Wade, K. J. Organomet. Chem. 1999, 573, 279–291. (h) Yoo, J.; Hwang, J.-W.;
Do, Y. Inorg. Chem. 2001, 40, 568–570.
(30) Beletskaya, I. P.; Bregadze, V. I.; Ivushkin, V. A.; Petrovskii, P. V.;
Sivaev, I. B.; Sjoeberg, S.; Zhigareva, G. G. J. Organomet. Chem. 2004, 689,
2920–2929.

10632 Inorganic Chemistry, Vol. 49, No. 22, 2010
Sevryugina et al.
Scheme 4. Synthetic Route to 9-Amino-m-carborane (9b)a
Scheme 6. Synthetic Route to Amino-o-carboranesa
a (i) Toluene, 100 °C, 2 h, 2.5 mol % Pd2(dba)3, 5 equiv of K3PO4,
5 mol % 1; (ii) rt, 3 d, H2O, THF, MeOH, iPrOH.
Scheme 5. Synthetic Route to 2-Amino-p-carborane (11b)a
a (i) Toluene, 100 °C, 2 h, 2.5 mol % Pd2(dba)3, 5 equiv of K3PO4,
5 mol % 1; (ii) rt, 6 d, H2O, THF, MeOH, iPrOH.
a (i) Toluene, 100 °C, 2 h, 2.5 mol % Pd2(dba)3, 5 equiv of K3PO4,
5 mol % 1; (ii) rt, 7 d, H2O, THF, MeOH, iPrOH.
indicated the consumption of the starting 9-iodo-m-car-
borane. Following silica-gel chromatography, the pro-
duct, N-(1,7-dicarba-closo-dodecaboran-9-yl)benzamide
(8a) was isolated in 92% yield. The facile conjugation of
benzamide to the cage accomplished above prompted further
exploration into the coupling of other amides that would
provide the free aminocarboranes after deprotection. While
benzamide itself presents a possible route to aminocarborane
products through acid-catalyzed hydrolysis, this technique
generally involves prolonged heating, which may lead to
degradation of the cage to the nido-structure through nu-
cleophilic attack by the now deprotected amine. As a result, it
was decided to attempt the coupling of trifluoroacetamide to
the respective iodo-carborane. The resulting N-carboranyl-
trifluoroacetamide derivative could then be easily hydro-
lyzed under basic conditions at room temperature.31 Using a
protocol similar to that which furnished the N-benzamide
derivative, N-(1,7-dicarba-closo-dodecaboran-9-yl)trifluor-
oacetamide (8b) was produced in 89% yield. A subsequent
base-mediated saponification of 8b leads to the correspond-
ing 9-amino-m-carborane (9b) in 89% yield (Scheme 4).
Coupling reactions of 2-iodo-p-carborane. Using these
optimized reaction conditions, we have carried out the amida-
tion of 2-iodo-p-carborane to produce N-(1,12-dicarba-closo-
dodecaboran-2-yl)benzamide (10a) and N-(1,12-dicarba-clo-
so-dodecaboran-2-yl)trifluoroacetamide (10b) in 83% and
82% yields, respectively. A subsequent base-mediated sapo-
nification of 10b leads to the 2-amino-p-carborane (11b) in
76% yield (Scheme 5).
ortho-carborane and Lewis base, such as alkoxides, amines,
and fluoride commonly results in deboronation of the
icosahedral [C2B10]-cage affording a nido-anion [7,8-C2B9-
H12]-. However, the mild reaction conditions reported here
successfully produced closo-ortho-carborane derivatives
bearing benzamido (12a and 13a), trifluoroacetamido (12b
and 13b), acetamido (12c) and formamido (12d) groups
(Scheme 6). It is notable, that this is the first time when
amidation of ortho-carborane is achieved directly from the
parent iodo-carborane. The previously known o-carborane
derivatives, all being substituted at the B(3)-position, were
obtained from the 3-amino-o-carborane. The latter was
prepared following Zakharkin’s procedure or its successful
modification by Kasar.10-12 In fact, compounds 12a-d are
the first 9-substituted ortho-carboranylamides reported.
A subsequent base-mediated saponification of 3-trifluor-
oacetamido-o-carborane (13b) leads to the almost quantita-
tive yield (99%) of 3-amino-o-carborane (14b). Although the
o-carborane is known to be susceptible to the alcoholic base
degradation to the nido-monoanion [7,8-C2B9H12]-, we
observed no deboronation of the [C2B10]-cage when using
NaOH/MeOH/THF/iPrOH/H2O route for synthesis of 14b.
On the other hand, hydrolysis of 9-trifluoroacetamido-o-
carborane (12b) using either base or acid-mediated hydro-
lysis leads to cage deboronation and formation of a 5(6)-
ammonium-7,8-dicarba-nido-undecaborate. Moreover, the
treatment of 3-trifluoroacetamido-o-carborane (13b) in
strongly acidic medium (hydrochloric acid) also resulted in
closo-cage degradation to the nido-anion. While the mechan-
isms of deboronation upon acidic hydrolysis for both tri-
fluoroactemido-ortho-carboranes (12b and 13b) are not
emphasized in this paper, it needs to be mentioned that
similar precedents have been reported in literature. Levit
et al. described the deboronation of N-tosyl-(S)-prolyl- and
Coupling Reactions of o-Carboranes. The above reac-
tion conditions were explored for the synthesis of o-carbor-
anylbenzamides. As mentioned above,29 the reaction of
(31) Green, T. W.; Wuts, P. G. Protective Groups in Organic Synthesis;
Wiley-Interscience: New York, 2006.

Article
Inorganic Chemistry, Vol. 49, No. 22, 2010 10633
a
˚
Table 1. Selected Bond Lengths (A) and Bond Angles (deg) for 8a,b, 10a, 12a,c,d, 13a, 15a,b of General Formula a-C2B10-n(B(b)NHCOR)nH12-n
,
a
b
R
n
B-N
N-C
CdO
B-Cc
B-Bc
B-N-C
8ab
m
m
p
o
o
o
o
m
m
m
9
9
2
9
9
9
3
9,10
9,10
9,10
C6H5
CF3
C6H5
C6H5
CH3
H
C6H5
C6H5
CF3
1
1
1
1
1
1
1
2
2
2
1.487(5)
1.495(5)
1.475(4)
1.492(3)
1.4926(15)
1.4914(18)
1.4601(13)
1.480(3)
1.486(6)
1.494(3)
1.347(5)
1.328(4)
1.350(4)
1.349(3)
1.3437(15)
1.3216(18)
1.3633(12)
1.343(3)
1.328(5)
1.337(3)
1.235(4)
1.219(4)
1.237(3)
1.238(3)
1.2353(15)
1.2337(18)
1.2275(12)
1.235(3)
1.218(5)
1.219(3)
1.698(7)
1.704(6)
1.705(5)
1.702(4)
1.708(2)
1.705(2)
1.7144(14)
1.703(4)
1.699(7)
1.704(3)
1.767(7)
1.772(7)
1.770(5)
1.778(4)
1.7829(19)
1.780(2)
1.782(16)
1.784(3)
1.778(8)
1.781(4)
125.8(3)
125.5(3)
126.8(3)
125.95(19)
127.36(10)
126.64(13)
126.46(8)
127.41(18)
127.3(4)
8bb
10a
12ab
12c
12d
13a
15ad
15bM
b,d,e
d,e
15bO
CF3
126.50(19)
a a = o-, m-, or p-; b is a substitution position; n = 1 or 2; R = C6H5, CF3, CH3 or H. b Averaged for several crystallographically independent
molecules. c Averaged for all distances. d Averaged for both amido-groups. e Compound 15b crystallized in two different crystal forms: monoclinic, 15bM
and orthorhombic, 15bO.
,
for other carboranylamides20,35 (Supporting Information,
Table S3). Despite no significant discrepancies in the major-
ity of bond lengths and angles, the B-N bond lengths
vary with respect to the electron density at the B-atom of
the corresponding carborane: 3-o-Cb , 2-p-Cb < 9-m-Cb<
9-o-Cb.36
Scheme 7. Amidation of 9,10-Diiodo-m-carborane
Free rotation of the amide moiety with respect to the
carborane cage in solution results in dihedral angles
around the B-N bond ranging from 3.0(2) to 174.6(2)°
upon crystallization (Supporting Information, Table S4). On
the contrary, the rotation around the N-C bond is signifi-
cantly more hindered (the reported rotation barrier is 75-
84 kJ/mol)37 and the B-N-CdO angles range from 0.0(6)
to 19.2(3)°. It is only in 12d, 9-formamido-o-carborane, that
this angle is 179.74(16)°, the carborane being oriented trans-
to the formamide oxygen and 12d thus being the first carbo-
ranylamide found to crystallize as the E-isomer.
N-phthaloyl-(S)-alanyl amides of 3-amino-1-phenyl-1,2-di-
carba-closo-dodecaborane under reflux in a mixture of
glacial acetic acid and concentrated HCl.32
Aminocarboranes would be an excellent source of new
B-derivatives if they were easy to obtain. Herein, we have
successfully realized the base-mediated hydrolysis of car-
boranyl trifluoroacetamides to afford the 9-amino-m- (9b),
2-amino-p- (11b), and 3-amino-o- (14b) carboranesin89%,
76%, and 99% isolated yields, respectively.
To broaden the scope of this chemistry, the amidation
of 9,10-diiodo-m-carborane by benzamide and trifluor-
oacetamide were investigated and found to result in high
yields (88% for 15a and 84% for 15b) of disubstituted
amido-derivatives of m-carborane (Scheme 7).
Structural Characterization. Structural determinations
using X-ray diffraction of compounds 8a,b, 10a, 12a,c,d,
13a, 15a,b confirm the assignments of their structures from
spectroscopic data. Their molecular structures along with
the atom numbering schemes, are given in Supporting Infor-
mation, Figures S1-S10. Selected bond distances and angles
are given in Table 1.
Conclusions
Four monoiodo-carborane compounds, 9-iodo-m-carbor-
ane, 2-iodo-p-carborane, 9-iodo-o-carborane, and 3-iodo-o-
carborane have been successfully coupled through Pd-cata-
lyzed reactions to both benzamide and trifluoroacetamide.
Also, 9-iodo-o-carborane was coupled to acetamide and for-
mamide. In addition to mono-, bis(2,2,2-trifluoroacetamide),
and dibenzamide derivatives have been successfully synthe-
sized. Crucial to this effort was the proper choice of a highly
active phosphine ligand, 2-dicyclohexylphosphino-20-(N,N-di-
methylamino)biphenyl (1) and a mild base K3PO4, both of
which significantly expand the scope of substrates amenable to
such coupling reactions. In the course of this study we were able
to obtain single crystals of compounds 8a,b, 10a, 12a,c,d, 13a,
15a,b and confirm their molecular structures by X-ray crystal-
lography. The trifluoracetamide derivatives facilitated the
synthesis of the respective aminocarboranes through base-
mediated saponification. Aminocarboranes are important re-
active synthons, and it is encouraging that the protocol devel-
oped here allows the introduction of amino groups at various
The carborane cage displays B-B and B-C bond lengths
˚
of 1.767(7)-1.784(3) and 1.698(7)-1.7144(14) A, respec-
tively, which are within the expected values for carborane
cage.33 Similarly, the N-C and CdO bonds are within the
predicted range for their parent amides.34 All bond lengths
and angles are within the range of distances reported
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10634 Inorganic Chemistry, Vol. 49, No. 22, 2010
Sevryugina et al.
reactive positions of the carborane cage. In the future, it is
hoped to extend this protocol to include other coupling
partners, including oxygen containing nucleophiles38 and
enolates.39
9-formamido-o-carborane and crystals of 9-acetamido-o-car-
borane and 9-formamido-o-carborane. The authors thank
Dr. Satish S. Jalisatgi, Dr. Mark W. Lee, and Dr. Charles
Barnes for helpful discussions. The authors also thank
Dr. Oscar Tutusaus for in-house mass spectrum analysis
program “MS Simulator” and Dr. Ilia Guzei (UW-Madison)
for in-house crystallographic program “ModiCIFer”.
Acknowledgment. We gratefully acknowledge the Natio-
nal Science Foundation (CHE-0702774) for the financial
support of this work. We are very grateful to Dr. Alexander
Safronov for the synthesis of 9-acetamido-o-carborane
and Dr. Radha Kishan Motkuri for the synthesis of
Supporting Information Available: X-ray crystallographic
files in CIF format for compounds 8a,b, 10a, 12a,c,d, 13a, 15a,
b, the molecular structures of studied compounds, packing
diagrams, details of structures refinement, and scrupulous
analysis of hydrogen bonding. This material is available free
of charge via the Internet at http://pubs.acs.org.
(38) Mann, G.; Hartwig, J. J. Am. Chem. Soc. 1996, 118, 13109–13110.
(39) Shaughnessy, K. H.; Hamann, B. C.; Hartwig, J. F. J. Org. Chem.
1998, 63, 6546–6553.