Magnesium-assisted intramolecular demethylation utilizing carborane C-H geometry

Article abstract of DOI:10.1016/j.jorganchem.2008.11.044

A novel type of demethylation reaction was designed in the Pd-catalyzed coupling reaction of iodocarboranes with several Grignard reagents, CH₃OPhMgBr. 3-Iodo-o-carborane 1 reacted with 2-CH₃OPhMgBr to afford the corresponding phenol

Full text of DOI:10.1016/j.jorganchem.2008.11.044

Journal of Organometallic Chemistry 694 (2009) 1646–1651
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Magnesium-assisted intramolecular demethylation utilizing
carborane C–H geometry
*
Kiminori Ohta, Hiroto Yamazaki, Yasuyuki Endo
Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 October 2008
Received in revised form 19 November 2008
Accepted 19 November 2008
Available online 30 November 2008
A novel type of demethylation reaction was designed in the Pd-catalyzed coupling reaction of iodocarbor-
anes with several Grignard reagents, CH3OPhMgBr. 3-Iodo-o-carborane 1 reacted with 2-CH3OPhMgBr to
afford the corresponding phenol compound 4b in 78% yield. However, when compound 1 was reacted
with the other Grignard reagents, the corresponding methoxyl compounds 5a and 6a were obtained in
excellent yields. 2-Iodo-p-carborane 3 reacted with 2-CH3OPhMgBr to afford the corresponding phenol
8b in 50% yield and the methoxyl compound 8a in 41% yield. The carborane C–H geometry, which can
form an intramolecular C–HÁ Á ÁO hydrogen bonding, seems to be an important factor in the demethylation
process. To examine the mechanism of the demethylation, compounds 1 and 4a were treated with
CH3MgBr and quenched with D2O. While the two C–Hs of compound 1 were completely deuterated, com-
pound 4a showed a replacement of one C–H with C–D. Therefore, we propose a mechanism involving
intramolecular C–MgÁ Á ÁO interaction instead of intramolecular C–HÁ Á ÁO interaction, via the generation
of 3-iodo-o-carboranyl(MgBr)2, 11. Since it is also possible to replace the C–Hs with various metals other
than Mg, new applications of carboranes in coordination and metal catalyst chemistry can be expected.
Ó 2008 Elsevier B.V. All rights reserved.
Keywords:
Carborane
Hydrogen bond
Demethylation
Grignard reagent
1. Introduction
solution states [8]. We have also reported a proton-driven molec-
ular switch based on C–HÁ Á ÁO interaction of p-carborane in solu-
Applications of dicarba-closo-dodecaborane (carborane) as a
building block for bioactive compounds, supramolecular assem-
blies, metal complexes, and macrocyclic molecules have recently
been addressed by many researchers [1]. Carborane is an icosahe-
dral structure and each vertex bears a hydrogen atom. It has high
hydrophobicity, which is similar to that of hydrocarbons, and
shows strong hydrophobic interactions with various molecules
[2]. Furthermore, the C–H hydrogens (C–Hs) of carborane are
highly acidic because of the electron-deficient nature of the carbo-
rane cage: the pKa values reported for ortho-, meta- and para-car-
borane are 22.0, 25.6 and 26.8, respectively [3]. Therefore, the C–Hs
have the potential for hydrogen bond (H-bond) formation. These
contrasting features, i.e., high hydrophobicity and H-bonding abil-
ity, both favor strong intramolecular and intermolecular interac-
tions. Thus, supramolecular assemblies utilizing carborane are
expected to be generated through hydrophobic interaction and
H-bonding via the acidic C–H vertices. The C–Hs interact with var-
tion (Chart 1) [9]. In view of the coordinating ability of the C–H
to oxygen, we focused on 3-substituted o-carborane, because o-
carborane C–H is the most acidic among the carborane isomers
and there are two acidic C–Hs. 3-Iodo-o-carborane (1) [10] reacts
with a variety of Grignard reagents in the presence of Pd catalyst
to afford 3-substituted o-carborane in high yield [11].
Vast numbers of natural products contain a phenolic hydroxyl
(OH) group(s). In developing a synthesis of any phenol-containing
product, protection is often mandatory to prevent reaction with
oxidizing agents and electrophiles, or reaction of the nucleophilic
phenoxide ion with even mild alkylating and acylating agents.
Ethers are among the most widely used protective groups for phe-
nol in organic synthesis. Methyl ether is the simplest and most ro-
bust, and can be formed and removed under a wide variety of
conditions [12]. In the mechanism of demethylation, the most
important step is the activation of the oxygen atom in the ether
bond by strong interaction with a Lewis or Brønsted acid [13]. It
is also possible to conduct demethylation with Grignard reagent,
CH3MgI [14]. Since the mechanism involves activation of oxygen
atom by coordination of magnesium and nucleophilic attack on
the carbon atom of the methyl group by IÀ as a soft base, the reac-
tion hardly progresses with Grignard reagents such as CH3MgBr,
unless there is additional activation of the oxygen atom [15].
Based upon the carborane C–H geometry, we designed a novel
type of demethylation utilizing the Pd-catalyzed coupling reaction
ious substituents [4], such as halogens [5], p-rich systems [6] and
H-bond acceptors [7] in the solid state. On the other hand, we are
interested in the interactions of the C–Hs in solution and recently
reported that C–H of o-carborane forms an intramolecular H-bond
with the oxygen atom of a methoxyl (OCH3) group in the solid and
* Corresponding author. Tel.: +81 22 727 0142; fax: +81 22 275 2013.
E-mail address: yendo@tohoku-pharm.ac.jp (Y. Endo).
0022-328X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2008.11.044

K. Ohta et al. / Journal of Organometallic Chemistry 694 (2009) 1646–1651
1647
4b among these products can have an intramolecular C–HÁ Á ÁO
interaction between C–H and the OCH3 or OH group.
CH
H
3
O
H
O
H
O
H
H
Next, the reactions of 2-iodo-p-carborane (3) with isomers of
CH3OPhMgBr were performed to further evaluate the relation-
ship between intramolecular C–HÁ Á ÁO interaction and demethyl-
ation. The reaction of 3 with 2-CH3OPhMgBr gave a mixture of
methyl ether (8a) and demethylated product (8b) in 41% and
50% yields, respectively (entry 7). The demethylation rate of 8a
was clearly slow as compared with that of 3-(2-methoxy-
phenyl)-o-carborane (4a). When the amount of Grignard reagent
was decreased from 8.5 equiv. to 3.1 equiv. in the reaction of 3
with 2-CH3OPhMgBr, the methyl ether product 8a was afforded
in 94% yield and none of the phenol 8b was obtained (entry
8). Compound 3 was also reacted with 3-CH3OPhMgBr or 4-
CH3OPhMgBr to give the corresponding methyl ether products
9a and 10a in 82% or 90% yields, respectively (entries 9 and
10). The phenol was not formed, because H-bond formation
can not occur between 3 and these Grignard reagents. It seems
that phenol formation depends on the number of C–Hs available
to interact intramolecularly with the oxygen atom of the OCH3
group.
H
acid
H
H
An intramolecular
H-bonding formation
based on o-carborane
Proton-driven conformational switching
based on -carborane
p
Chart 1. Intramolecular C–HÁ Á ÁO interactions based on o-carborane and p-carbo-
rane C–Hs in solution.
of 3-iodo-o-carborane (1) with 2-methoxyphenylmagnesium bro-
mide (2-CH3OPhMgBr), anticipating that strong coordination of
the C–Hs with oxygen atom of the OCH3 group of the correspond-
ing methoxyphenyl compound 4a would assist the demethylation
during the coupling reaction to afford the corresponding com-
pound 4b (Scheme 1). In this paper, we describe Pd-catalyzed cou-
pling reactions of 3-iodo-o-carboranes (1), 9-iodo-o-carborane (2)
[16] and 2-iodo-p-carborane (3) [17] with isomers of CH3OPhMgBr
(Scheme 2). We expected that intramolecular C–HÁ Á ÁO interaction
would play an important role in the reaction mechanism of this no-
vel type of demethylation.
2.2. Deuteration of the C–Hs in the presence of Grignard reagent and a
possible reaction mechanism
2. Results and discussion
The C–Hs were easily deprotonated with various Grignard re-
agents to generate carborane C–magnesium (C–Mg) halide species.
Thus, the demethylation in this system would be facilitated by C–
MgÁ Á ÁO interaction as well as by C–HÁ Á ÁO interaction. There are
three possible mechanisms for the demethylation of 4a with Grig-
nard reagent (Scheme 3).
2.1. Pd-catalyzed coupling reaction of iodocarboranes with isomers of
CH3OPhMgBr
Pd-catalyzed coupling reactions were performed as follows: A
solution of iodocarborane, Grignard reagent (8.5 equiv.) generated
from Mg and bromoanisole in THF, Pd(PPh3)2Cl2 (10 mol%) and CuI
(10 mol%) in THF was refluxed for 34 h (Scheme 2) [11]. Yields of
products are shown in Table 1. Interestingly, the reaction of 3-
iodo-o-carborane (1) with 2-CH3OPhMgBr afforded 4b as a major
product in 78% yield and C-methylated phenol (4c) as a minor
product in 10% yield (Chart 2); none of 4a was obtained (entry
1). When the amount of Grignard reagent was reduced (4.0 equiv.),
the yield of 4b markedly decreased, and 4a was isolated as a major
product in 56% yield (entry 2). After quenching for 24 h, com-
pounds 4a and 4b were isolated in 34% and 25% yields, respectively
(entry 3). On the other hand, 3-CH3OPhMgBr and 4-CH3OPhMgBr
reacted with 1 to afford only the corresponding methyl ether prod-
ucts 5a and 6a in excellent yields (entries 4 and 5).
To investigate whether the demethylation is caused by 2-
CH3OPhMgBr, the reaction of 9-iodo-o-carborane (2), which has
an iodine atom apart from the C–Hs, with 2-CH3OPhMgBr was per-
formed, and afforded the corresponding methyl ether product (7a)
in 95% yield (entry 6). This result shows that the demethylation is
not caused by an effect of 2-CH3OPhMgBr, but involves a synergis-
tic effect between 1 and 2-CH3OPhMgBr. Thus, we speculated that
the demethylation process was related to an intramolecular C–
HÁ Á ÁO interaction in the products, because only compounds 4a or
First, the demethylation of 4a with methylmagnesium bromide
(CH3MgBr) was examined under the same conditions as used for
the coupling reaction; [4a] = 0.15 M in THF, CH3MgBr (8.5 equiv.),
reflux for 34 h (Method A; Scheme 4). Although the corresponding
phenol 4b was obtained in 20% yield, 4a was recovered in 48%
yield. In addition, C-methylated compounds 4c and 4d were iso-
lated in 13% and 15% yield, respectively. Next, we examined the
participation of Pd and Cu catalysts in the demethylation process.
When 10 mol% of PdCl2(PPh3)2 and 10 mol% of CuI were added to
the reaction mixture, or 2-CH3OPhMgBr was used instead of
CH3MgBr, there were no significant change in the yields of the
products: compounds 4a–4d were isolated in 49%, 22%, 11% and
15% yields, respectively (Method B; Scheme 4). Pd and Cu catalysts
had no influence on the demethylation, and efficient demethyla-
tion of 4a was not obtained under these conditions compared to
those of entry 1 in Table 1. Why was the demethylation efficiently
accelerated by the Pd-catalyzed coupling reaction of 1 with Grig-
nard reagent?
To answer this question, we deuterated the C–Hs by quenching
with cold deuterated water (D2O) after the treatment of 4a with
CH3MgBr (8.5 equiv.) under reflux for 2.5 h. Interestingly, only
one C–H of 4a was found to have been converted to C–D when
the replacement efficiency was evaluated by means of integration
of the C–H signals in the NMR spectrum (Fig. 1). This result indi-
cates that one of the two C–Hs was deprotonated with CH3MgBr
and converted to C–MgBr.
ArMgBr
On the other hand, when compound 1 was treated with
CH3MgBr (8.5 equiv.) under the same conditions, both C–Hs were
completely converted to C–Ds. The C–Hs of 1 disappeared without
any change of the carborane B–H peaks in the NMR spectra (Fig. 2).
This result means that both C–Hs were converted to C–MgBr.
From the results of demethylation with CH3MgBr and the deu-
teration studies, it seems that the number of C–Hs replaced with
C–MgBr is correlated with the yield of phenols. In addition, the
reaction of 3 with 2-CH3OPhMgBr to afford a mixture of 8a and
I
Pd-catalyzed
coupling reaction
H
CH
3
+
H
O
H
O
H
H
H
H
H
1
4a
4b
Scheme 1. Pd-catalyzed coupling reaction of 3-iodo-o-carborane with 2-CH3OPh-
MgBr and consecutive demethylation assisted by intramolecular C–HÁ Á ÁO
interaction.

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K. Ohta et al. / Journal of Organometallic Chemistry 694 (2009) 1646–1651
OCH
OCH
H
3
3
OCH
H
3
H
H
H
H
ortho: 8a
meta: 9a
para: 10a
PdCl (PPh ) (10 mol%)
ortho: 4a
meta: 5a
para: 6a
2
3 2
7a
I
I
I
CuI (10 mol%)
H
H
H
CH OPhMgBr (8.5 eq)
3
OH
OH
THF
reflux, 34 h
H
H
H
1
3
OH
H
2
H
H
H
H
H
ortho: 8b
meta: 9b
para: 10b
ortho: 4b
meta: 5b
para: 6b
7b
Scheme 2. Pd-catalyzed coupling reactions of iodocarboranes with CH3OPhMgBr.
Table 1
Pd-catalyzed coupling reaction of iodocarborane with Grignard reagent.
Entry
Starting material
Grignard reagent
Yield of product (%)b
Methoxyl (CH2OPh)
Hydroxyl (HOPh)
1
2
3
4
5
6
7
8
9
3-Iodo-o-carborane
1
1
1
1
1
2
3
3
3
3
2-CH3OPhMgBr
2-CH3OPhMgBr
2-CH3OPhMgBr
3-CH3OPhMgBr
4-CH3OPhMgBr
2-CH3OPhMgBr
2-CH3OPhMgBr
2-CH3OPhMgBr
3-CH3OPhMgBr
4-CH3OPhMgBr
0(4a)
78 (4b)c
6 (4b)d
25 (4b)e
0 (5b)
0 (6b)
0 (7b)
50 (8b)
0 (8b)f
0 (9b)
56 (4a)
34 (4a)
99 (5a)
98 (6a)
95 (7a)
41 (8a)
94 (8a)
82 (9a)
90 (10a)
9-Iodo-o-carborane
2-Iodo-p-carborane
10
0 (10b)
Reactions condition: [substrate] = 0.15 M in THF, Grignard reagent (8.5 equiv.), Pd(PPh3)2Cl2 (10 mol%), CuI (10 mol%), reflux for 34 h.
b
Yield of isolated product.
C-methyl compound (4c) was isolated in 10% yield.
Grignard reagent (4.0 equiv.).
Reaction time: 24 h.
c
d
e
f
Reaction conditions: 2-CH3OPhMgBr (3.1 equiv.), 9 h.
H
O
CH3
H
4c
Chart 2. The structure of 4c.
8b can be explained by the replacement of one C–H of 3 with C–
MgBr (entry 7; Table 1). It seems likely that C–MgBr interacts with
OCH3 through a C–MgÁ Á ÁO interaction. Therefore, we concluded
that the demethylation was mainly caused by C–MgÁ Á ÁO interac-
tion and depended upon the number of C–MgÁ Á ÁO interactions.
A plausible mechanism for the demethylation process is illus-
trated in Scheme 5. Compound 1 reacts with an excess of 2-
CH3OPhMgBr to generate o-carboranyl(MgBr)2 (11), followed by
Pd-catalyzed coupling to afford 3-(2-CH3OPh)-o-carbora-
nyl(MgBr)2 (12), in which intramolecular C–MgÁ Á ÁO interactions
might activate the oxygen atom of the methoxyl group. Bromide
anion (BrÀ) attacks at the backside of the carbon atom of the meth-
oxyl group in compound 12 to afford intermediate 13 with elimi-
nation of CH3Br. Finally, compound 13 is quenched with H3O+ to
afford the demethylated compound 4b and with CH3Br generated
within the system to afford compound 4c as a by-product.
The dual activation process of the OCH3 with two C–Mg is the
key to efficient demethylation. The spherical structure of the car-
borane cage plays an important role in the demethylation, as well
as intramolecular C–HÁ Á ÁO and C–MgÁ Á ÁO interactions. That is, the
three-dimensionally fixed geometry of carborane C–Hs, which
can form intramolecular H-bonds, makes it possible for the
demethylation to accompany the Pd-catalyzed coupling reaction.
This reaction appears to have great potential, because the carbo-
rane C–Hs can be replaced with various metals, thereby opening
up new fields in metal coordination chemistry.

K. Ohta et al. / Journal of Organometallic Chemistry 694 (2009) 1646–1651
1649
RMgBr
CH
CH
3
O
H
H
H
CH
H
O
3
3
O
O
H
H
H
H
Mg
Br
4a
4b
CH
3
O
Br
Mg
Mg
Br
Scheme 3. Possible demethylation mechanisms involving C–MgÁ Á ÁO or C–HÁ Á ÁO
interaction.
3. Conclusion
Fig. 1. NMR spectra of 4a and the deuteration product. Spectra (a) and (b) are those
of the deuterated product and compound 4a in CDCl3 at 25 °C, respectively.
We found a novel type of demethylation reaction that accompa-
nies the Pd-catalyzed coupling reaction of 1 and 3 with 2-CH3OPh-
MgBr. Compounds 1 and 3 reacted with 2-CH3OPhMgBr to afford
the corresponding phenol compounds 4b and 8b in 78% and 50%
yield, respectively. We propose a mechanism involving intramolec-
ular C–MgÁ Á ÁO interaction instead of intramolecular C–HÁ Á ÁO inter-
action, based on the results of deuteration studies with compounds
1 and 4a. Since it is possible to replace the C–Hs with various met-
als, novel intermolecular interactions in solution may become
available in coordination chemistry.
4.2. Materials
Unless otherwise noted, the reagents and solvents were pur-
chased from Aldrich Chemical Co., Kanto Chemicals, Tokyo Kasei,
or Wako Chemicals, Inc. and were used as received. Carboranes
were purchased from Katchem s.r.o. (Prague, Czech Republic). 3-
Iodo-o-carborane (1), 9-iodo-o-carborane (2) and 2-iodo-p-carbo-
rane (3) were synthesized according to the literature [10,16,17].
4. Experimental
4.3. Pd-catalyzed coupling of iodocarboranes with Grignard reagent
4.1. General
A solution of 1.70 M Grignard reagent (10 mL, 17.0 mmol),
which was freshly prepared from magnesium turnings and a tiny
quantity of I2 with the corresponding bromoanisole in dry THF,
was added dropwise to a stirred dry THF solution (3.0 mL) of iod-
ocarborane (540 mg, 2.0 mmol), Pd(PPh3)2Cl2 (140 mg, 0.2 mmol)
and CuI (38 mg, 0.2 mmol) under an Ar atmosphere. The mixture
was refluxed, and then excess Grignard reagent was quenched by
the slow addition of a dilute HCl solution. The mixture was ex-
tracted with AcOEt and the organic phase was washed with water,
dried over MgSO4, and concentrated. The residue was purified by
silica gel column chromatography. Yields are shown in Table 1.
Compound 4a: Colorless needles (n-hexane-CH2Cl2). M.p. 105.0–
106.0 °C. 1H NMR (396 MHz, CDCl3) d (ppm) 1.3–3.2 (brm, 9H, car-
borane B–H), 3.79 (s, 3H, OCH3), 4.23 (brs, 2H, carborane C–H), 6.84
(d, J = 8.2 Hz, 1H, Ar), 7.04 (dt, J = 1.0 Hz, 7.2 Hz, 1H, Ar), 7.38 (ddd,
Melting points were determined with a Yanaco micro melting
point apparatus and were not corrected. 1H NMR, 13C NMR and
10B NMR spectra were recorded with JEOL JNM-EX-270, JNM-LA-
400 and JNM-LA-600 spectrometers. Chemical shifts for 1H NMR
spectra were referenced to tetramethylsilane (0.0 ppm) as an inter-
nal standard. Chemical shifts for 13C NMR spectra were referenced
to residual 13C present in deuterated solvents. Chemical shift val-
ues for 11B spectra were referenced to external BF3 Á OEt2
(0.0 ppm with negative values upfield). The splitting patterns are
designated as follows: s (singlet), d (doublet), t (triplet), and m
(multiplet). Mass spectra were recorded on a JEOL JMS-DX-303
spectrometer. Elemental analyses were performed with a Perkin–
Elmer 2400 CHN analyzer.
CH3
O
H
H
CH3
H
CH3
H
O
H
O
H
O
H
O
H
H
CH3
Method A or Method B
CH3
H
4d
4a
4a
4b
4c
Method A
Method B
48%
49%
20%
22%
13%
11%
15%
15%
product yields
Scheme 4. Demethylation of 4a with CH3MgBr. Conditions: Method A: [substrate] = 0.15 M in THF, CH3MgBr (8.5 equiv.), reflux for 34 h; Method B: [substrate] = 0.15 M in
THF, CH3MgBr (8.5 equiv.), Pd(PPh3)2Cl2 (10 mol%), CuI (10 mol%), reflux for 34 h.

1650
K. Ohta et al. / Journal of Organometallic Chemistry 694 (2009) 1646–1651
Compound 6a: Colorless needles (n-hexane-CH2Cl2). 94.0–
94.5 °C. 1H NMR (396 MHz, CDCl3) d (ppm) 1.7–3.1 (brm, 9H, car-
borane B–H), 3.67 (brs, 2H, carborane C–H), 3.82 (s, 3H, OCH3),
6.90 (d, J = 8.7 Hz, 2H, Ar), 7.52 (d, J = 8.7 Hz, 2H, Ar). 13C NMR
(99 MHz, CDCl3) d (ppm) 55.20 (OCH3), 56.69 (carborane), 113.90
(Ar), 134.50 (Ar), 160.99 (Ar). MS (EI) m/z 250 (M+, 100%). HRMS
Calcd. for C9H18B10O: 250.2365. Found: 250.2356.
Compound 7a: Colorless prisms (n-hexane-CH2Cl2). 135.0–
136.0 °C. 1H NMR (396 MHz, CDCl3) d (ppm) 1.6–3.2 (brm, 9H, car-
borane B–H), 3.52 (brs, 1H, carborane C–H), 3.56 (brs, 1H, carbo-
rane C–H), 3.75 (s, 3H, OCH3), 6.77 (d, J = 8.7 Hz, 1H, Ar), 6.86 (dt,
J = 1.0 Hz, 7.2 Hz, 1H, Ar), 7.20 (dt, J = 1.9 Hz, 7.7 Hz, 1H, Ar), 7.36
(d, J = 6.8 Hz, 1H, Ar). 13C NMR (99 MHz, CDCl3) d (ppm) 49.95
(OCH3), 52.91 (carborane), 55.05 (carborane), 110.43 (Ar), 120.18
(Ar), 128.96 (Ar), 135.94 (Ar), 161.53 (Ar). MS (EI) m/z 250 (M+,
100%). HRMS Calcd. for C9H18B10O: 250.2365. Found: 250.2360.
Compound 8a: Colorless prisms (n-hexane). M.p. 84.5–85.0 °C.
1H NMR (396 MHz, CDCl3) d (ppm) 1.2–3.4 (brm, 9H, carborane
B–H), 2.79 (brs, 1H, carborane C–H), 3.69 (brs, 1H, carborane C–
H), 3.72 (s, 3H, OCH3), 6.81 (d, J = 8.2 Hz, 1H, Ar), 6.97 (dt,
J = 1.0 Hz, 7.5 Hz, 1H, Ar), 7.30 (ddd, J = 1.9 Hz, 7.4 Hz, 8.3 Hz, 1H,
Ar), 7.67 (d, J = 6.8 Hz, 1H, Ar). 13C NMR (68 MHz, CDCl3) d (ppm)
55.0 (OCH3), 61.7 (carborane), 65.4 (carborane), 110.2 (Ar), 120.6
(Ar), 129.7 (Ar), 136.0 (Ar), 161.8 (Ar). MS (EI) m/z 250 (M+, 100%).
Anal. Calc. for C9H18B10: C, 43.18; H, 7.25. Found: C, 43.04; H, 7.16%.
Compound 8b: Colorless leafs (n-hexane-CH2Cl2). M.p. 112.0–
113.0 °C. 1H NMR (396 MHz, CDCl3) d (ppm) 1.5–3.3 (brm, 9H, car-
borane B–H), 2.84 (brs, 1H, carborane C–H), 3.66 (brs, 1H, carbo-
rane C–H), 4.91 (brs, 1H, OH), 6.68 (dd, J = 1.0 Hz, 8.2 Hz, 1H, Ar),
6.93 (dt, J = 1.0 Hz, 7.2 Hz, 1H, Ar), 7.20 (dt, J = 1.5 Hz, 7.2 Hz, 1H,
Ar), 7.57 (d, J = 7.6 Hz, 1H, Ar). 13C NMR (68 MHz, CDCl3) d (ppm)
62.2 (carborane), 65.7 (carborane), 115.3 (Ar), 120.7 (Ar), 129.8
(Ar), 136.1 (Ar), 158.1 (Ar). MS (EI) m/z 236 (M+, 100%). Anal. Calc.
for C8H16B10: C, 40.66; H, 6.82. Found: C, 40.90; H, 6.97%.
Fig. 2. NMR spectra of 1 and the deuteration product. Spectra (a) and (b) are those
of the deuterated product and compound 1 in CDCl3 at 25 °C, respectively.
J = 1.8 Hz, 7.4 Hz, 8.3 Hz, 1H, Ar), 7.88 (dd, J = 1.0 Hz, 7.2 Hz, 1H,
Ar). 13C NMR (99 MHz, CDCl3) d (ppm) 55.16 (OCH3), 55.76 (carbo-
rane), 109.91 (Ar), 121.34 (Ar), 131.06 (Ar), 138.44 (Ar), 161.12
(Ar). MS (EI) m/z 250 (M+, 100%). HRMS Calcd. for C9H18B10O:
250.2365. Found: 250.2360.
Compound 4b: Colorless needles (n-hexane-CH2Cl2). M.p. 160.0–
162.0 °C. 1H NMR (396 MHz, CDCl3) d (ppm) 1.2–3.2 (brm, 9H, car-
borane B–H), 4.29 (brs, 2H, carborane C–H), 4.98 (s, 1H, OH), 6.67
(dd, J = 1.0 Hz, 7.2 Hz, 1H, Ar), 7.02 (dt, J = 1.0 Hz, 7.7 Hz, 1H, Ar),
7.27 (dt, J = 1.9 Hz, 7.7 Hz, 1H, Ar), 7.83 (d, J = 6.8 Hz, 1H, Ar). 13C
NMR (99 MHz, CDCl3) d (ppm) 55.94 (carborane), 114.91 (Ar),
121.57 (Ar), 130.96 (Ar), 138.29 (Ar), 157.19 (Ar). MS (EI) m/z
236 (M+, 100%). HRMS Calcd. for C8H16B10O: 236.2208. Found:
236.2209.
Compound 4c: Colorless needles (CH3OH-H2O). M.p. 110.0–
113.0 °C. 1H NMR (396 MHz, CDCl3) d (ppm) 1.5–3.2 (brm, 9H, car-
borane B–H), 1.81 (s, 3H, CH3), 4.71 (brs, 1H, carborane C–H), 4.98
(s, 1H, OH), 6.70 (d, J = 8.2 Hz, 1H, Ar), 7.04 (dt, J = 1.0 Hz, 7.2 Hz,
1H, Ar), 7.29 (dt, J = 1.9 Hz, 7.7 Hz, 1H, Ar), 7.76 (d, J = 7.2 Hz, 1H,
Ar). 13C NMR (99 MHz, CDCl3) d (ppm) 23.60 (CH3), 62.11 (carbo-
rane), 70.75 (carborane), 115.23 (Ar), 121.50 (Ar), 131.10 (Ar),
139.18 (Ar), 157.87 (Ar). MS (EI) m/z 250 (M+, 100%). HRMS Calcd.
for C9H18B10O: 250.2365. Found: 250.2360.
Compound 5a: Colorless leafs (n-hexane-CH2Cl2). 76.0–77.0 °C.
1H NMR (396 MHz, CDCl3) d (ppm) 1.5–3.2 (brm, 9H, carborane
B–H), 3.70 (brs, 2H, carborane C–H), 3.83 (s, 3H, OCH3), 6.95 (dd,
J = 2.2 Hz, 8.8 Hz, 1H, Ar), 7.13–7.15 (m, 2H, Ar), 7.29 (t,
J = 7.7 Hz, 1H, Ar). 13C NMR (99 MHz, CDCl3) d (ppm) 55.24
(OCH3), 56.64 (carborane), 114.83 (Ar), 119.15 (Ar), 125.12 (Ar),
129.50 (Ar), 159.28 (Ar). MS (EI) m/z 250 (M+, 100%). HRMS Calcd.
for C9H18B10O: 250.2365. Found: 250.2349.
Compound 9a: Colorless oil. 1H NMR (396 MHz, CDCl3) d (ppm)
1.2–2.8 (brm, 9H, carborane B–H), 2.89 (brs, 1H, carborane C–H),
3.07 (brs, 1H, carborane C–H), 3.82 (s, 3H, OCH3), 6.87 (ddd,
J = 1.0 Hz, 2.4 Hz, 8.2 Hz, 1H, Ar), 7.09 (s, 1H, Ar), 7.11 (d,
J = 7.2 Hz, 1H, Ar), 7.23 (t, J = 7.7 Hz, 1H, Ar). 13C NMR (99 MHz,
CDCl3) d (ppm) 55.10 (OCH3), 63.52 (carborane), 65.40 (carborane),
113.48 (Ar), 119.15 (Ar), 125.62 (Ar), 128.96 (Ar), 158.95 (Ar). MS
(EI) m/z 250 (M+, 100%). HRMS Calcd. for C9H18B10O: 250.2365.
Found: 250.2352.
Compound 10a: Colorless leafs (n-hexane-CH2Cl2). M.p. 101.0–
101.5 °C. 1H NMR (396 MHz, CDCl3) d (ppm) 1.3–3.2 (brm, 9H, car-
borane B–H), 2.89 (brs, 1H, carborane C–H), 3.03 (brs, 1H, carbo-
rane C–H), 3.81 (s, 3H, OCH3), 6.86 (d, J = 8.7 Hz, 2H, Ar), 7.47 (d,
J = 8.2 Hz, 2H, Ar). 13C NMR (99 MHz, CDCl3) d (ppm) 55.10
(OCH3), 63.66 (carborane), 65.77 (carborane), 113.46 (Ar), 134.69
H
O
H
H3O+
H
Br
Mg
I
I
Br
Pd-catalyzed
coupling reaction
CH
Mg
H
3
H
O
O
Mg
Br
Br
4b
Mg
Mg
Mg
Br
CH3Br
11
1
CH3Br
13
12
OCH
BrMg
OCH
3
3
HO
CH
3
H
4c
Scheme 5. A plausible demethylation mechanism in the Pd-catalyzed coupling reaction of 1 with 2-CH3OPhMgBr.

K. Ohta et al. / Journal of Organometallic Chemistry 694 (2009) 1646–1651
1651
(Ar), 160.07 (Ar). MS (EI) m/z 250 (M+, 100%). HRMS Calcd. for
C9H18B10O: 250.2365. Found: 250.2352.
(135 mg, 0.5 mmol) under an Ar atmosphere. The mixture was re-
fluxed for 3 h and poured into a cold D2O solution at 0 °C. The mix-
ture was extracted with AcOEt and the organic phase was washed
with water, dried over MgSO4, and concentrated. The residue was
purified by silica gel column chromatography with 10:1 n-hex-
ane:AcOEt to give 133 mg (98%) of deuterated compound: Color-
less needles (n-hexane). M.p. 77.0–78.0 °C. 1H NMR (396 MHz,
CDCl3) d (ppm) 1.2–3.3 (brm, 9H, carborane B–H). 13C NMR
(99 MHz, CDCl3) d (ppm) not detected. 11B NMR (127 MHz, CDCl3)
d (ppm) À29.54 (1B), À13.19 (1B), À12.64 (2B), À111.23 (3B), 7.30
(1B), À1.43 (2B). MS (EI) m/z 272 (M+, 100%). HRMS Calcd. for
C2H9D2B9I: 272.1035. Found: 272. 1025.
4.4. Dealkylation study of 4a with CH3MgBr
A solution of 3.0 M of CH3MgBr in ether (1.13 mL, 8.5 mmol)
was added dropwise to a stirred dry THF solution (2.7 mL) of 4a
(100 mg, 0.4 mmol) under an Ar atmosphere. The mixture was re-
fluxed for 34 h, and then the excess Grignard reagent was
quenched by the slow addition of a dilute HCl solution. The mix-
ture was extracted with AcOEt and the organic phase was washed
with water, dried over MgSO4, and concentrated. The residue was
purified by silica gel column chromatography with 8:1 to 3:1 n-
hexane:AcOEt to give 48 mg (48%) of 4a, 19 mg (20%) of 4b,
13 mg (13%) of 4c and 16 mg (15%) of 4d.
Acknowledgements
Compound 4d: Colorless needles (CH3OH-H2O). M.p. 103.0–
104.0 °C. 1H NMR (396 MHz, CDCl3) d (ppm) 1.5–3.2 (brm, 9H, car-
borane B–H), 1.75 (s, 3H, CH3), 3.82 (s, 3H, OCH3), 4.63 (brs, 1H, car-
borane C–H), 6.88 (d, J = 8.7 Hz, 1H, Ar), 7.06 (t, J = 7.2 Hz, 1H, Ar),
7.40 (dt, J = 1.4 Hz, 7.8 Hz, 1H, Ar), 7.81 (d, J = 7.2 Hz, 1H, Ar). 13C
NMR (99 MHz, CDCl3) d (ppm) 23.60 (CH3), 55.24 (OCH3), 60.29
(carborane), 70.50 (carborane), 110.39 (Ar), 121.34 (Ar), 131.22
(Ar), 139.36 (Ar), 161.80 (Ar). MS (EI) m/z 264 (M+, 100%). Anal.
Calc. for C10H20B10O: C, 45.43; H, 7.63. Found: C, 45.69; H, 7.75%.
This work was supported by Grants-in-Aid for Scientific Re-
search (B) (No. 16390032 and 20390035) and by a Grant-in-Aid
for Young Scientists (B) (No. 18790089) from the Ministry of Edu-
cation, Culture, Sports, Sciences and Technology, Japan.
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(125 mg, 0.5 mmol) under an Ar atmosphere. The mixture was re-
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H), 3.79 (s, 3H, CH3), 4.22 (brs, 1H, carborane C–H), 6.84 (d,
J = 8.2 Hz, 1H, Ar), 7.05 (dt, J = 1.0 Hz, 7.2 Hz, 1H, Ar), 7.38 (ddd,
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added dropwise to a stirred dry THF solution (1.85 mL) of 1