Indium-catalyzed Friedel-crafts Alkylation of monosubstituted benzenes by 1-bromoadamantane

Article abstract of DOI:10.1055/s-0032-1316909

Indium salts such as InCl₃ and InBr₃ (ca. 1-5 mol%) efficiently catalyzed the Friedel-Crafts reaction of 1-bromoadamantane with benzene and monosubstituted benzenes to give 1-adamantyl benzenes. Indium bromide enabled faster reaction

Full text of DOI:10.1055/s-0032-1316909

1142▌
LETTER
lIenttedr ium-Catalyzed Friedel–Crafts Alkylation of Monosubstituted Benzenes by
1-Bromoadamantane
Indium-Catalyzed Aromatic Adamantylation
Paul Mosset,* René Grée
Université de Rennes 1, Institut des Sciences Chimiques de Rennes, CNRS UMR 6226, Avenue du Général Leclerc, 35042 Rennes Cedex,
France
Fax +33(2)23236978; E-mail: paul.mosset.1@univ-rennes1.fr
Received: 12.02.2013; Accepted after revision: 19.03.2013
The reaction of 1-bromoadamantane with benzene and
Abstract: Indium salts such as InCl3 and InBr3 (ca. 1–5 mol%)
toluene has been reported with a few catalysts. Initially,
efficiently catalyzed the Friedel–Crafts reaction of 1-bromo-
catalysis by AlCl3 was investigated by Newman,14 but
mixtures of mono, di, and triphenyladamantanes were
adamantane with benzene and monosubstituted benzenes to give 1-
adamantyl benzenes. Indium bromide enabled faster reactions than
indium chloride but the latter was more suitable in the case of halo- formed, suggesting that the reaction conditions were rath-
benzenes.
er harsh. Subsequently, FeCl3 in large excess at ca. 100 °C
was reported for the successful monoadamantylation of
monosubstituted benzenes with formation of only the
para isomer.15,16 Subsequently, a more systematic study
of the reaction was described by Olah et al. using boron
tris(triflate) as a very efficient, although unselective, cat-
alyst.17 Olah, Török et al. subsequently showed that sub-
stituted benzenes could be adamantylated with high
regioselectivity for the para isomer by using various sup-
ported acid catalysts at 111 °C.18 The reaction was further
studied using weaker acids, which appeared to favor ki-
netic control with a high selectivity for formation of the
para isomer, whereas strong acids initiated a secondary
isomerization reaction resulting in a thermodynamic mix-
ture of meta and para isomers.19 In the course of our pro-
gram on the design of new asymmetric catalysts, we were
interested in introducing adamantyl substituents in aro-
matic systems.
Key words: adamantanes, alkylation, catalysis, indium, Lewis
acids
Although the first steps in Friedel–Crafts (FC) chemistry
were taken more than a century ago,1 the topic still re-
ceives much attention and is a frequently studied area for
catalytic C–C bond formation.2 In recent years, due to the
high demand for environmentally benign (‘green’) pro-
cesses, the use of conventional, effective but harmful and
corrosive catalysts and promoters (AlCl3, BF3, H2SO4,
etc.) is being discouraged for large-scale industrial appli-
cations. Furthermore, although great strides have been
made in catalytic FC reactions, there remain several chal-
lenges, such as utilizing electron-deficient arenes and
avoiding side-reactions such as polyalkylation and isom-
erization. In recent years, indium(III) salts have emerged
as excellent catalysts with a Lewis acid character for
many reactions.3 They have received a great deal of inter-
est due to their relatively low toxicity, stability in air and
water, and recyclability. However, reports of their use for
FC reactions are scant, being limited to reaction of allylic4
and benzylic5 halides as well as to some acylation
reactions5b,6 and in fluorine chemistry.7 An interesting
variant was the InCl3-catalyzed reductive FC reaction us-
ing ketones and chlorodimethylsilane both as a hydride
source and as a cocatalyst.8
We first investigated the reaction of 1-bromoadamantane
with benzene in the presence of group IIIA and IIIB metal-
lic salts with Lewis acid character (Table 1).
Yttrium chloride and ytterbium triflate proved to be inef-
fective at 50 °C (Table 1, entries 1 and 2). This result may
appear surprising because of the good Lewis character of
YCl3 and Yb(OTf)3, but it may be explained by the insol-
ubility of these salts in the reaction medium. As indium
salts are known to be mild Lewis acids, which efficiently
catalyze miscellaneous reactions,3 we tested them for this
reaction. We were pleased to find that both indium chlo-
ride and bromide efficiently catalyzed the formation of 1-
phenyladamantane (3a) at room temperature. InBr3 was
found to give faster reactions and by using 0.05 equiv cat-
alyst, InCl3 and InBr3 both afforded excellent yields of 3a
in respectively 40 and 2.5 hours (entries 5 and 6). Using
more InCl3 was not beneficial because p-di(1-adaman-
tyl)benzene (3j) was formed as a by-product (entry 4) ex-
cept when the reaction temperature was lowered (entry 3).
InBr3 could even be used in a very low amount (less than
0.01 equiv, entry 7) albeit at the expense of yield and in-
creased reaction time as well as formation of 3j.20 The use
of indium triflate gave a very slow reaction at room tem-
perature due to insufficient solubility. At 55 °C, a 65%
Whereas the FC reaction with short-chain alkyl halides
has been well studied, this is not the case for adamantyl-
ation of aromatics, in spite of the potential importance of
such chemistry. The adamantyl group increases lipophi-
licity and has therefore been incorporated into biological-
ly active molecules.9 Due to its steric bulk, it has also been
incorporated into some catalysts10,11 including asymmet-
ric compounds.12 The adamantane framework has also
been used as a scaffold.13
SYNLETT 2013, 24, 1142–1146
Advanced online publication: 12.04.2013
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9
3
6
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5
2
1
4
1
4
3
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2
0
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DOI: 10.1055/s-0032-1316909; Art ID: ST-2013-D0140-L
© Georg Thieme Verlag Stuttgart · New York

LETTER
Indium-Catalyzed Aromatic Adamantylation
1143
cess. As expected, substitution of the benzene nucleus
with an alkyl group enhanced the reactivity for the forma-
tion of 3b–d but this effect diminished when the size of
the alkyl group increased (from methyl to isopropyl; Ta-
ble 2, entries 2–4). The reaction was highly selective since
the para isomer was mainly formed with only 5–7% meta
isomer.
Table 1 Influence of the Catalyst on the Adamantylation of Benzene
Br
Ph
catalyst
+
+ HBr
conditions
2a
3a
1
Entry Catalyst
Equiv
Temp (°C) Time (h) Yield (%)a
Not surprisingly, halogenated benzenes were found to be
less reactive (Table 2, entries 5–7). The yield was still rea-
sonable for fluorobenzene (65%) but dropped to 33% for
chlorobenzene and bromobenzene. For these less reactive
substrates, more polar inseparable 1-bromo-3-arylada-
mantane 4f–h and 1,3-diaryladamantane 5f–h were also
formed in minor amounts (11–18%). However, the reac-
tion was found to be completely para-selective because
no trace of the meta isomer was detected for 3f–h, 4f–h or
5f–h.
1
2
YCl3
0.106
0.08
0.15
0.08
0.05
0.05
0.0083
0.02
0.08
0.10
0.10
50
50
8
47
31
15
40
40
nr
Yb(OTf)3
InCl3
nr
3
95
75b
94
93
57c
65d
nr
4
InCl3
25
25
23
35
55
50
20
50
5
InCl3
6
InBr3
2.5
7
InBr3
166
7
Table 2 InCl3-Catalyzed Adamantylation of Benzene(s)a
8
In(OTf)3
In(OMs)3
In(OTs)3
In(OTs)3
Entry
R
Temp Time Products: isolated
para/meta
for 3
(°C)
(h)
yield (%)b
9
22
24
20
10
11
nr
1
2
3
4
5
6
7
H
25
30
30
30
45
30
35
40
15
96
43
64
30
24
3a: 94
–
76e
Me
Et
3b: 90; 4,5b: nd
3c: 92; 4,5c: nd
3d: 53; 4,5d: nd
3f: 65; 4f+5f: 12
3g: 33; 4g+5g: 19
3h: 33; 4h+5h: 12
93:7
94:6
95:5
100:0
100:0
100:0
a nr: no reaction.
b p-Di(1-adamantyl)benzene (3j; 7%) was also formed.
c Unreacted 1 (3%) remained and 3j (9%) was also formed.
d Compound 3j (3%), 1,3-diphenyladamantane (4%) and adamantane
(3%) were also formed; almost no reaction was observed at r.t.
e 1,3-Diphenyladamantane (9%) was also formed.
i-Pr
F
Clc
Brd
yield was obtained (entry 8). Indium mesylate21 did not
catalyze any reaction at 50 °C, probably also due to its in-
solubility in the reaction medium (entry 9). On the other
hand, indium tosylate21 catalyzed the reaction at 50 °C
(entry 11) but not at room temperature (entry 10).
a Reaction conditions: InCl3 (ca. 5 mol%) and 2.5 mL aromatic/mmol
of 1 were used except when otherwise stated.
b nd: not detected.
c Chlorobenzene (4 equiv) was used.
d InCl3 (4.5 mol%) and bromobenzene (6.5 equiv) were used.
A study of the reaction of 1-bromoadamantane (1) with a
range of monosubstituted benzenes 2b–h under InCl3-ca-
talysis was then initiated (Scheme 1, X = Cl; Table 2).22
As in the case of benzene, it was initially observed that
InBr3 was a more efficient catalyst than InCl3; the reaction
of 1 with monosubstituted benzenes 2b–h was also stud-
ied in the presence of 5 mol% InBr3 (Scheme 1, X = Br;
Table 3). Monoalkylated benzenes reacted fairly well and
gave good yields of 3b–e (77–91%). However, increasing
the size of the alkyl group decreased the reactivity.
Whereas the para-selectivity was good for toluene, ethyl-
benzene and cumene (92–94%, entries 2–5), it dropped
sharply to 65% (entry 6) with isobutylbenzene. In the case
of halogenated benzenes, InBr3 proved to be a less suit-
able catalyst than InCl3 (entries 7–9). Fluorobenzene (en-
try 7) afforded a good yield of 3f (75%) but the product
contained a small amount of the meta-isomer (1.5%), and
5f (17%) was also formed. Chlorobenzene (entry 8) af-
forded a complex mixture, and bromobenzene (entry 9)
afforded the expected product 3h but in a low yield (14%),
accompanied by 10% of the meta isomer as well as 4h and
inseparable impurities.
R
Y
R
Br
InX3
(5 mol%)
+
+ HBr
+
R
1
2a–h
3a–h
4a–h + 5a–h
(0–19%)
R = H, alkyl, halo
X = Cl, Br
4a–h: Y = Br
5a–h: Y =
R
Scheme 1 InCl3- and InBr3-catalyzed adamantylation of benzene(s)
The catalyst loading was reduced to 5 mol%, an amount
that proved to be sufficient for all studied substrates. The
aromatic component was used as both substrate and sol-
vent for the reaction and was therefore used in large ex-
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1142–1146

1144
P. Mosset, R. Grée
LETTER
Table 3 InBr3-Catalyzed Adamantylation of Benzene(s)a
mild conditions. InBr3 was found to be more efficient for
alkylbenzenes, while InCl3 was better suited for haloben-
zenes. In(OTf)3 also showed some efficiency. Dichloro-
methane was an excellent solvent that enabled the reaction
to be performed with a limited amount of aromatic sub-
strate, selectively for the para isomer.
Entry
R
Temp
(°C)
Time Products: isolated para/meta
(h)
yield (%)b
for 3
1
2
3
4
5
6
7
8
9
H
23
30
30
30
30
45
45
30
20
2.5
3a: 93; 5a: trace
3b: 91; 4,5b: nd
3c: 77; 4,5c: nd
3d: 60; 4,5d: nd
3d: 77; 4,5d: nd
3e: 77; 5e: 15
3f: 75; 5f: 17
3g: –c
–
Me
Et
17
22
17
41
17
27
23
40
92:8
94:6
92:8
94:6
65:35
98.5:1.5
–
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnuIpofoiprmntgirStanoIuifpog
r
t
iornat
i-Pr
i-Pr
i-Bu
F
References and Notes
(1) (a) Friedel, C.; Crafts, J.-M. Compt. Rend. 1877, 84, 1392.
(b) Friedel, C.; Crafts, J.-M. Compt. Rend. 1877, 84, 1450.
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G. A., Ed.; Wiley-Interscience: New York, 1964. (b) Olah,
G. A. In Friedel–Crafts Chemistry; Wiley-Interscience:
New York, 1973. (c) Roberts, R. M.; Khalaf, A. A. In
Friedel–Crafts Alkylation Chemistry: A Century of
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Alkylations in Comprehensive Organic Synthesis; Trost, B.
M.; Fleming, I., Eds.; Pergamon Press: Oxford, 1991.
(e) Bandini, M.; Melloni, A.; Umani-Ronchi, A. Angew.
Chem. Int. Ed. 2004, 43, 550. (f) Rueping, M.; Nachtsheim,
B. J. Beilstein J. Org. Chem. 2010, 6, doi: 10.3762/bjoc.6.6.
(g) Sartori, G.; Maggi, R. In Advances in Friedel–Crafts
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(3) For reviews for indium Lewis acids, see: (a) Frost, C. G.;
Chauhan, K. K. J. Chem. Soc., Perkin Trans. 1 2000, 3015.
(b) Fringuelli, F.; Piermatti, O.; Pizzo, F.; Vaccaro, L. Curr.
Org. Chem. 2003, 7, 1661. (c) Frost, C. G.; Hartley, J. P.
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Hammond, G. B. Chem. Eur. J. 2008, 14, 10029.
(4) Hayashi, R.; Cook, G. R. Org. Lett. 2007, 9, 1311; and
references cited within.
Cl
Br
3h: 14; 4h: 8
90:10
a Reaction conditions: InCl3 (ca. 5 mol%) and 2 or 2.5 mL aromat-
ic/mmol of 1 were used except 5 equiv for isobutylbenzene and 3
equiv for bromobenzene.
b nd: not detected
c A complex mixture was obtained.
Although, in the foregoing work, the aromatic substrate
was used in large excess, as in all previously described
studies of the adamantylation of aromatics, that is not con-
venient when the aromatic substrate is expensive or diffi-
cult to separate from product(s), or a solid. Therefore, we
focused on using a limited amount of aromatic substrate
with an additional solvent. Among several solvents tried,
dichloromethane proved to be the best choice.23 For four
type-2 aromatics,24 a satisfactory yield of monoadaman-
tylated compound 3 was obtained (Table 4).25 For the
three less reactive substrates, a minor amount of a more
polar mixture of 4 and 5 was also formed. The para iso-
mer of 3 was formed as the major product (in the case of
ethylbenzene and isobutylbenzene, respectively, 12 and
5% meta isomer) or the exclusive product when R was
bulky (in the case of tert-butylbenzene and 1-phenylada-
mantane).
(5) (a) Kaneko, M.; Hayashi, R.; Cook, G. R. Tetrahedron Lett.
2007, 48, 7085. (b) Choudhary, V. R.; Jana, S. K.; Patil, N.
S.; Bhargava, S. K. Microporous and Mesoporous Materials
2003, 57, 21. (c) Bachari, K.; Cherifi, O. J. Porous Mater.
2008, 15, 325.
(6) Duquenne, C.; Gillet, J.-P.; Kervennal, J.; Ruppin, C.;
Vaultier, M. WO Patent 067490, 2004; Chem. Abstr. 2004,
141, 140181
Table 4 InBr3-Catalyzed Adamantylation of Aromatics 2 by 1 in
a
CH2Cl2
R
Equiv InBr3
Temp Time Products: isolated para/meta
(7) J. Ichikawa, presented in part at the 2012 Dasan Conference:
Fluorine Chemistry to Environment and Health Aspects
(FCEHA), The City7 Pullman Ambassador Hotel,
Changwon, South Korea, November 14–16, 2012; Invited
Lecture-03: Electrophilic Activation and Cyclization of
Fluoro Alkenes Directed toward PAH Synthesis, page 51 of
abstract book: 2012-Dasan Conference-Program Book-
DSSHIN.pdf.
in 2
of 2
(equiv) (°C) (h) yield (%) for 3
Et
3
0.049 20
96 3c: 65; 4c+5c: 9 88:12
64 3e:61; 4e+5e: 6 95:5
121 3i: 68; 4i+5i: 6 100:0
16 3j: 84 100:0
i-Bu
t-Bu
1.55
1.74
0.049 25
0.038 25
1-Adb 0.833 0.05
16
(8) (a) Miyai, T.; Onishi, Y.; Baba, A. Tetrahedron Lett. 1998,
39, 6291. (b) Miyai, T.; Onishi, Y.; Baba, A. Tetrahedron
1999, 55, 1017.
a 1 mL CH2Cl2/mmol of 1.
b 1-Ad: 1-adamantyl; 0.67 mL CH2Cl2/mmol 1 was used.
(9) (a) For a recent review, see: Liu, J.; Obando, D.; Liao, V.;
Lifa, T.; Codd, R. Eur. J. Med. Chem. 2011, 46, 1949.
(b) Battilocchio, C.; Baxendale, I. R.; Biava, M.; Kitching,
M. O.; Ley, S. V. Org. Process Res. Dev. 2012, 16, 798; and
references cited therein.
In summary, InCl3 and InBr3 efficiently catalyze FC-type
alkylation of benzenes by 1-bromoadamantane under
Synlett 2013, 24, 1142–1146
© Georg Thieme Verlag Stuttgart · New York

LETTER
Indium-Catalyzed Aromatic Adamantylation
1145
(10) Adamantylphosphines: (a) Zapf, A.; Ehrentraut, A.; Beller,
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(14) Newman, H. Synthesis 1972, 692.
respectively 2 and 20 h, followed by removal of water under
vacuum at 70 °C. Remarkably, in contrast to indium
mesylate and halides, indium tosylate did not exhibit
appreciable hygroscopicity, a fact that made it far more
convenient to handle.
(22) Representative Procedure: InBr3 (7.1 mg, 0.02 mmol) was
introduced in an oven- or flame-dried 10 mL round-
bottomed flask followed by an olive-shaped magnetic
stirring bar. The apparatus was dried by heating for 1–2 min
with a heat gun under vacuum. 1-Bromoadamantane (1; 86
mg, 0.4 mmol) and the monosubstituted benzene 2a–h (or
benzene itself, 1 mL) were added. The flask was flushed
under nitrogen and well stoppered.26 The reaction was left
under gentle stirring in a water or oil bath at the specified
temperature (see Tables) with protection against light by
aluminum foil. After reaction for the specified time (see
Tables), abundant evolution of hydrogen bromide (white
smoke, caution!) occurred on opening. The reaction mixture
was taken up with pentane and washed with water until
neutral. After drying (Na2SO4) and concentration,
chromatography on silica gel (ca. 3 g), eluting with pentane,
afforded monoadamantylated benzene 3a–h followed in
some cases by more polar 1-bromo-3-aryladamantane (4)
and 1,3-diaryladamantane (5).
1-Phenyladamantane (3a): Mp 82 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.37 (dm, J ~ 8 Hz, 2 H), 7.31 (ddm, J = 8.2,
6.8 Hz, 2 H), 7.17 (ddt, J = 7.6, 6.7, 1.4 Hz, 1 H), 2.12–2.07
(m, 3 H), 1.92 (d, J = 2.8 Hz, 6 H), 1.83–1.72 (m, 6 H). 13
C
NMR (100 MHz, CDCl3): δ = 151.34 (1Cq), 128.10 (2CH),
125.50 (1CH), 124.84 (2CH), 43.23 (3CH2), 36.88 (3CH2),
36.22 (1Cq), 29.04 (3CH).
1-(4-Methylphenyl)adamantane (3b): Mp 97–98 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.26 (half of an A2X2 system,
2 H), 7.13 (half of an A2X2 system coupled with CH3, Jwith Me
= 0.7 Hz, 2 H), 2.32 (t, J = 0.7 Hz, 3 H, CH3), 2.12–2.05 (m,
3 H), 1.90 (broad d, J = 2.8 Hz, 6 H), 1.82–1.71 (m, 6 H). 13
C
NMR (100 MHz, CDCl3): δ = 148.48 (1Cq), 134.90 (1Cq),
128.81 (2CH), 124.72 (2CH), 43.30 (3CH2), 36.87 (3CH2),
35.85 (1Cq), 29.03 (3CH), 20.87 (1CH3).
1-(4-Ethylphenyl)adamantane (3c): Mp 58 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.28 (half of an A2X2 system, 2 H),
(15) Perkins, R.; Bennett, S.; Bowering, E.; Burke, J.; Reid, K.;
Wall, D. Chem. Ind. 1980, 790.
7.15 (half of an A2X2 system coupled with CH2, Jwith CH2 =
0.6 Hz, 2 H), 2.62 (q, J = 7.6 Hz, 2 H, CH2CH3), 2.12–2.05
(m, 3 H), 1.91 (broad d, J = 2.8 Hz, 6 H), 1.82–1.71 (m,
6 H), 1.23 (t, J = 7.6 Hz, 3 H, CH2CH3). 13C NMR (100
MHz, CDCl3): δ = 148.68 (1Cq), 141.23 (1Cq), 127.55
(2CH), 124.75 (2CH), 43.29 (3CH2), 36.87 (3CH2), 35.88
(1Cq), 29.03 (3CH), 28.29 (1CH2), 15.45 (1CH3).
(16) Shortly before the report of the FeCl3-catalyzed reaction, the
reaction of 1-fluoroadamantane (very expensive, in contrast
to 1, which is inexpensive) with benzene, toluene and
bromobenzene under catalysis by PhPF4 was reported, see:
Weiß, J.-V.; Wray, V.; Schmutzler, R. Z. Naturforsch. 1979,
34b, 1286.Furthermore, benzene was not reported to give 3a
under these conditions but instead gave p-di(1-
adamantyl)benzene. Toluene gave a mixture of meta and
para isomers of mono(1-adamantyl)toluene.
(17) Olah, G. A.; Farooq, O.; Farnia, S. M. F.; Wu, A.-h. J. Org.
Chem. 1990, 55, 1516.
1-(4-Isopropylphenyl)adamantane (3d): Mp 87 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.28 (half of an A2X2 system,
2 H), 7.18 (half of an A2X2 system coupled with CH, Jwith CH
= 0.6 Hz, 2 H), 2.88 [qq, J = 6.9, 6.9 Hz, 1 H, CH(CH3)2],
2.12–2.05 (m, 3 H), 1.91 (broad d, J = 2.8 Hz, 6 H), 1.82–
1.70 (m, 6 H), 1.24 [d, J = 6.9 Hz, 6 H, CH(CH3)2]. 13
C
(18) Olah, G. A.; Török, B.; Shamma, T.; Török, M.; Surya
Prakash, G. K. Catal. Lett. 1996, 42, 5.
NMR (100 MHz, CDCl3): δ = 148.74 (1Cq), 145.81 (1Cq),
126.09 (2CH), 124.69 (2CH), 43.29 (3CH2), 36.88 (3CH2),
35.87 (1Cq), 33.55 (1CH), 29.03 (3CH), 24.02 (2CH3).
1-(4-Isobutylphenyl)adamantane (3e): Mp 34.5 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.25 (half of an A2X2 system,
2 H), 7.08 (half of an A2X2 system coupled with CH2, Jwith
CH2 = 0.6 Hz, 2 H), 2.44 (d, J = 7.2 Hz, 2 H, CH2 of i-Bu),
2.12–2.05 (m, 3 H), 1.91 (broad d, J = 2.8 Hz, 6 H), 1.85
[tqq, J = 7.2, 6.6, 6.6 Hz, 1 H, CH(CH3)2], 1.82–1.70 (m,
6 H), 0.90 (d, J = 6.6 Hz, 6 H, CH(CH3)2). 13C NMR (CDCl3,
100 MHz): δ = 148.67 (1Cq), 138.70 (1Cq), 128.80 (2CH),
124.49 (2CH), 45.00 (CH2), 43.30 (3CH2), 36.89 (3CH2),
35.88 (1Cq), 30.19 (1CH), 29.04 (3CH), 22.48 (2CH3). Anal.
(19) (a) Beregszászi, T.; Török, B.; Molnár, Á.; Olah, G. A.;
Surya Prakash, G. K. Catal. Lett. 1997, 48, 83. (b) Török, B.;
Molnár, Á. Compt. Rend. Acad. Sci. Paris, Série IIc 1998,
381. (c) Török, B.; Kiricsi, I.; Molnár, Á.; Olah, G. A. J.
Catal. 2000, 193, 132.
(20) Using more InBr3 than 0.05 equiv favored the formation of a
small amount of the more polar 1,3-diphenyladamantane.
(21) Indium mesylate and tosylate were prepared by dissolving
metallic indium powder in aqueous methanesulfonic acid
(3.2 equiv) or p-toluenesulfonic acid (3.0 equiv) at 70 °C
(respectively 0.3 and 0.8 mL H2O/mmol In was used) for
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1142–1146

1146
P. Mosset, R. Grée
LETTER
(23) For instance, no reaction was observed with 1 and
Calcd for C20H28 (268.44): C, 89.49; H, 10.51. Found: C,
89.57; H, 10.46.
isobutylbenzene at 40 °C in CCl4. In 1,2-dichloroethane and
1-chlorobutane at 35–40 °C, the reactions of 1 with
isobutylbenzene and tert-butylbenzene afforded complex
mixtures.
1-(4-tert-Butylphenyl)adamantane (3i): Mp 127.5 °C. 1H
NMR (CDCl3, 400 MHz): δ = 7.34 (half of an A2X2 system,
2 H), 7.29 (half of an A2X2 system, 2 H), 2.12–2.05 (m, 3 H),
1.91 (d, J = 2.8 Hz, 6 H), 1.83–1.70 (m, 6 H), 1.31 [s, 9 H,
C(CH3)3]. 13C NMR (CDCl3, 100 MHz): δ = 148.30 (1Cq),
148.06 (1Cq), 124.92 (2CH), 124.42 (2CH), 43.22 (3CH2),
36.85 (3CH2), 35.76 (1Cq), 34.25 (1Cq), 31.40 (3CH3), 28.99
(3CH).
(24) Halobenzenes were not studied in CH2Cl2 as solvent because
of their reduced reactivity and also due to the fact that InBr3
was not a good catalyst in their case.
(25) The same procedure as previously described was used,
except that a reduced amount of aromatic substrate was used
(see Table 3) and dichloromethane was added (its amount
was adjusted by weight after flushing with nitrogen and
stoppering).
1,4-Di-1-adamantylbenzene (3j)
1H NMR (400 MHz, CDCl3): δ = 7.31 (s, 4 H), 2.12–2.05 (m,
6 H), 1.91 (d, J = 2.8 Hz, 12 H), 1.82–1.71 (m, 12 H). 13
C
NMR (100 MHz, CDCl3): δ = 148.35 (2Cq), 124.45 (4CH),
43.21 (6CH2), 36.86 (6CH2), 35.79 (2Cq), 28.99 (6CH).
For data of other compounds, see the Supporting
Information.
(26) Based on two experiments that were performed with toluene
and ethylbenzene with HBr vented through a bubbler, no
change was observed in reaction rate or selectivity (same
para/meta ratios). Yields of 99% were obtained compared
with 90 and 92% (InCl3 as a catalyst).
Synlett 2013, 24, 1142–1146
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