SnBr4-promoted Friedel-Crafts type dehydrative alkylation reaction of diarylmethanols with 2-naphthol derivatives

Article abstract of DOI:10.1016/j.tetlet.2016.02.064

Tin(IV) bromide was found to act as an efficient Lewis acid catalyst for the Friedel-Crafts type dehydrative alkylation reaction of diarylmethanols with 2-naphthol derivatives under mild conditions. The effects of the substituents on the substrates were systematically evaluated, and the reaction could be applied to a variety of substrates by tuning the conditions depending on the electronic properties of the starting materials.

Full text of DOI:10.1016/j.tetlet.2016.02.064

Tetrahedron Letters 57 (2016) 1456–1459
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
SnBr -promoted Friedel–Crafts type dehydrative alkylation reaction
4
of diarylmethanols with 2-naphthol derivatives
⇑
Nobuharu Suzuki, Shiori Tsuchihashi, Kenya Nakata
Interdisciplinary Graduate School of Science and Engineering, Shimane University, 1060 Nishikawatsu, Matsue, Shimane 690-8504, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Tin(IV) bromide was found to act as an efficient Lewis acid catalyst for the Friedel–Crafts type dehydra-
tive alkylation reaction of diarylmethanols with 2-naphthol derivatives under mild conditions. The
effects of the substituents on the substrates were systematically evaluated, and the reaction could be
applied to a variety of substrates by tuning the conditions depending on the electronic properties of
the starting materials.
Received 26 December 2015
Revised 12 February 2016
Accepted 16 February 2016
Available online 16 February 2016
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Friedel–Crafts alkylation
Diarylmethylation
Carbocations
Synthetic methods
Tin(IV) bromide
The alkylation of arenes with alkyl halides, promoted by a Lewis
acid like AlCl , is commonly known as a Friedel–Crafts alkylation
been successfully extended to asymmetric catalysis, we became
interested in the Friedel–Crafts type dehydrative alkylation reac-
tions of diarylmethanols with substituted 2-naphthols to produce
a variety of diarylmethylated 2-naphthol derivatives. Although
several methods have already been reported using various cata-
3
1
reaction and is one of the most important methods for the forma-
tion of alkyl-substituted aromatic compounds. In the classical Frie-
del–Crafts reaction, the Lewis acid is used in stoichiometric
amount with coproduction of a hydrogen halide, and significant
amounts of salt residues are removed after workup. With the
increasing concern for environmental issues, the development of
more atom-economical and environmentally friendly protocols is
highly desirable. Nevertheless, in recent years, the Friedel–Crafts
type dehydrative alkylation reaction of alcohols has attracted
much attention from synthetic chemists because of the difficult
catalytic activation of the hydroxyl group due to its poor leaving
ability. Moreover, improved protocols are of great interest because
of their green chemistry nature: in fact, these reactions would ide-
ally produce water as the sole byproduct. In 1986, Uemura and co-
9
lysts, such as metal triflates (e.g., La, Yb, Sc, and Hf triflate),
1
0
11
12
13
H
2
SO
4
,
NbCl
15, pentafluorophenylboronic acid, and NaHSO
substrate scope has not been thoroughly investigated in previous
5
,
I
2
,
surfactant-type Brønsted acid, amberlyst-
1
4
15
16
4
/SiO
2
,
the
1
7
studies.
Because the reaction proceeds through carbocation
intermediates, it should be influenced by the electronic effects of
the substituents. Thus, a systematic investigation of substituents
on the substrates is highly desirable in order to evaluate their elec-
tronic and steric effects. Notably, tin(IV) bromide is known to serve
as an efficient Lewis acid for the activation of carbonyl groups; for
example, the Prins cyclization reaction of
a-acetoxy ethers was
workers first reported the TeCl
of alcohols with arenes. The other two pioneering investigations
of the catalytic Friedel–Crafts alkylation of free alcohols by Fuku-
4
-catalyzed Friedel–Crafts alkylation
successfully employed for the construction of a tetrahydropyran
ring skeleton using a stoichiometric amount of tin(IV) bromide.
2
18,19
Thus, it was hypothesized that treatment of diarylmethanols with
tin(IV) bromide would generate the corresponding carbocation
intermediates, which by reaction with 2-naphthols would provide
the target molecules. Herein, we report an efficient method for the
Friedel–Crafts type dehydrative alkylation reaction of diaryl-
methanols with various 2-naphthols using a catalytic amount of
3
4
zawa et al. and by Shimizu et al. use Sc(OTf)
3
6
and Mo(CO) ,
respectively, as catalyst. Since then, significant efforts have been
directed towards the development of new synthetic methods for
the direct substitution of alcohols using a catalytic amount of
Brønsted or Lewis acids, and many useful methods have been
5
,6
described to date. Because the use of 2-naphthol derivatives such
4
SnBr , and we systematically evaluate the effect of substituents
on this transformation.
0
0
7
8
as 2,2 -dihydroxy-1,1 -binaphthyl (BINOL) and Betti base has
In order to optimize the reaction conditions, at first, the solvent
effect was examined by carrying out the Friedel–Crafts alkylation
reaction of benzhydrol (1a) with 2-naphthol in the presence of
⇑
Corresponding author. Tel.: +81 852 32 6424; fax: +81 852 32 6429.
E-mail address: nakata@riko.shimane-u.ac.jp (K. Nakata).
http://dx.doi.org/10.1016/j.tetlet.2016.02.064
040-4039/Ó 2016 Elsevier Ltd. All rights reserved.
0

N. Suzuki et al. / Tetrahedron Letters 57 (2016) 1456–1459
1457
5
mol % SnBr
4
, used as model system, in various organic solvents at
Table 2
Friedel–Crafts alkylation reaction of diarylmethanols with 2-naphthol
room temperature for 24 h (Table 1). The reaction was not influ-
enced by the polarity of the solvent and low or no reactivity was
observed in oxygen-containing solvents, such as Et
and DMF (entries 3, 4, 7, and 9), probably because the oxygen atom
coordinated to SnBr , thus reducing its catalytic activity. On the
contrary, other solvents such as hexane, toluene, CH Cl , (CH Cl)
2
O, THF, EtOAc,
4
2
2
2
2
,
and MeCN, not containing oxygen atoms, were all effective in pro-
ducing the desired product 2a in good yields (entries 1, 2, 5, 6, and
8
). Although the alkylation proceeded preferentially at the C-1
1
position rather than at the oxygen atom of 2-naphthol, the
H
Entry
Ar
n (mol %)
Yielda (%)
NMR spectrum of the crude reaction mixture showed a small
amount of O-alkylated product 3a and/or bis(diphenylmethyl)
ether (4a), except when CH Cl was used as the solvent. Upon
2 2
increasing the catalyst loading to 30 mol %, the reaction was com-
1
2
3
4
5
o-MeC
o-MeC
m-MeC
p-MeC
6
H
H
H
6 4
4
4
(1b)
(1b)
(1c)
(1d)
5
30
5
5
5
5
5
5
5
110
5
30
110
5
5
5
5
5
87 (2b)
96 (2b)
89 (2c)
92 (2d)
40 (2e)
69 (2e)
94 (2f)
87 (2g)
3 (2h)
6
6
H
4
plete within 4 h to give 2a in 95% yield (entry 10). We next exam-
o-MeOC H4 (1e)
6
b
ined other tin salts, such as SnCl
Interestingly, an appreciable amount of O-alkylated ether 3a was
obtained in the reaction using SnCl and SnCl , although starting
2
, SnCl
4
and SnBr
2
, in CH
2
Cl
2
.
6
o-MeOC
m-MeOC
p-MeOC
o-ClC
o-ClC
m-ClC
m-ClC
m-ClC
6
H
4
(1e)
(1f)
(1g)
7
8
9
6
H
4
6
H
4
2
4
6
H
H
4
4
(1h)
(1h)
(1i)
(1i)
(1i)
(1j)
material 1a was completely consumed and 2a was obtained in
good and moderate yields, respectively, (entries 11 and 12). In
10
6
79 (2h)
1 (2i)
11
6
6
6
H
4
H
4
H
4
12
13
14
15
41 (2i)
83 (2i)
86 (2j)
94 (2k)
89 (2l)
90 (2m)
the case of SnBr
the reaction with SnBr
a small amount of 3a and 4a and 1a was recovered in 10% yield
2
, the reactivity was reduced as compared with
4
: 2a was afforded in 81% yield along with
p-ClC
-Np (1k)
b-Np (1l)
p-Me NC
6
H
4
a
(
entry 13).
16
17
After identifying the optimal solvent and catalyst, we surveyed
2
6
H
4
(1m)
(1n)
(1n)
(1n)
c
18
19
20
21
p-EtO
p-EtO
p-EtO
p-NCC
p-NCC
2
2
2
CC
CC
CC
6
6
6
H
H
H
4
4
4
NR (2n)
the reaction of a series of diarylmethanols 1b–o with 2-naphthol,
to systematically explore the electronic and steric effects of the
substituents on the aromatic rings of the substrates (Table 2).
We examined the reactions of 1b–d bearing methyl substituents
at the ortho, meta, and para positions of the aromatic rings (entries
110
330
5
61 (2n)
89 (2n)
c
6
H
H
4
(1o)
(1o)
NR (2o)
c
22
6
4
330
NR (2o)
a
b
c
Isolated yield.
The reaction temperature was 0 °C.
No reaction.
1
–4). In entry 1, the desired 2b was obtained in 87% yield along
with 7% of O-alkylated ether 3b; however, increasing the catalyst
loading to 30 mol %, the yield of 2b was improved to 96% (entry
2
). On the contrary, the other two reactions proceeded smoothly
to afford the desired 2c and 2d in good yields (entries 3 and 4).
In addition, the reactions of 1e–g, bearing methoxy substituents,
were performed (entries 5–8). Substrate 1e afforded the corre-
sponding product in moderate yields, although the starting mate-
rial was completely consumed (entry 5). The side products were
not identified; however, because of the high reactivity of the
diarylmethyl cation intermediate, several substitution reactions
on the naphthol ring possibly occurred. The production of byprod-
ucts was relatively suppressed by decreasing the reaction temper-
ature, to afford 2e in 69% yield (entry 6). The reactions of 1f and 1g
with substituents at the meta and para positions, respectively,
afforded high yields of the desired products (entries 7 and 8).
Table 1
Optimization of reaction conditions
2
0
The reactivity of 1h–j containing electron-withdrawing groups
showed a tendency similar to that of substrates bearing methyl
substituents (entries 9–14). Almost no product was detected in
Entry
SnX
Solvent
Yield of 2aa (%)
(3a; 4a)b (%)
4
the reactions of 1h and 1i using 5 mol % of SnBr (entries 9 and
c
1
2
3
4
5
6
7
8
9
SnBr
SnBr
SnBr
SnBr
SnBr
SnBr
SnBr
SnBr
SnBr
SnBr
4
4
4
4
4
4
4
4
4
4
Hexane
Toluene
94
89
36
NR
96
90
NR
91
NR
95
82
66
81
(ND ; trace)
1
1); however, the reactivity was improved by increasing the cata-
(2; 4)
c
lyst loading to 110 mol % (entries 10, 12, and 13). On the contrary,
the reaction of 1j bearing para substituents was not affected and
the corresponding product 2j was afforded in good yields (entry
Et
THF
CH Cl
(CH Cl)
2
O
(ND ; trace)
d
(—; —)
c
c
2
2
(ND ; ND )
(1; 4)
2
2
1
1
4). The reaction of 1k and 1l with naphthyl substituents and of
m with strong electron-donating groups proceeded smoothly to
d
EtOAc
MeCN
DMF
(—; —)
(trace; 5)
(—; —)
20
d
generate 2k–m in good yields (entries 15–17). Substrate 1n con-
0e
1
CH
2
CH
2
CH
2
CH
2
Cl
2
Cl
2
Cl
2
Cl
2
(ND ; ND )
(5; 8)
c
c
1
1
1
1
taining an ethyl ester showed low reactivity; however, the yield of
SnCl
SnCl
2
2
n was improved by increasing the catalyst loading from 5 to
2
3
4
(10; 13)
(2; 2)
3
30 mol % (entries 18–20). Unfortunately, regardless of the catalyst
SnBr
2
2
0
loading, the reaction of 1o did not proceed at all and the starting
material was recovered unchanged (entries 21 and 22). Presum-
ably, because of the strong electron-withdrawing nature of the
cyano group, the corresponding diarylmethyl cation intermediate
could not be generated. It is noteworthy, however, that a variety
a
b
c
Isolated yield.
Determined by 1H NMR.
Not detected.
d
e
No reaction.
4
The reaction was carried out by using 30 mol % of SnBr for 4 h.

1
458
N. Suzuki et al. / Tetrahedron Letters 57 (2016) 1456–1459
of diarylmethanols 1b–n were viable for the present reaction,
regardless of the nature of the functional groups on the aromatic
rings.
Next, the reaction of benzhydrol (1a) was carried out with var-
ious 2-naphthol derivatives 5a–i, in order to elucidate the scope
and limitations under the optimized reaction conditions
(Scheme 1). The reaction of compounds 5a–c with an ethyl ester
on the naphthyl ring, performed under the previously optimized
conditions, that is, in the presence of 5 mol % of catalyst at room
temperature for 24 h, generated the target molecules 6a–c in mod-
erate yields along with the formation of the bis(diphenylmethyl)
ether (4a) as a byproduct. Upon increasing the catalyst loading to
3
0 mol %, 6a–c were obtained in high yields and byproduct 4a
was not detected. On the other hand, the reaction of 6- and 7-
bromo substituted 2-naphthol derivatives 5e and 5f gave good
results using 5 mol % of SnBr ; however, surprisingly, 3-bromo
4
substituted 2-naphthol derivative 5d afforded a moderate yield
of the corresponding desired product, even upon increasing the
catalyst loading. Several other 2-naphthols 5g–i were examined
and high yields were obtained regardless of the steric and elec-
tronic effects of the substituent groups on the naphthyl rings.
In order to identify the reaction intermediates, the reaction of
1
4
a with 2-naphthol catalyzed by 5 mol % of SnBr was quenched
after 4 h, and the desired compound 2a was obtained in 85% yield
along with 2% of O-alkylated product 3a and 11% of ether 4a as
byproducts (Scheme 2, Eq. 1). Because the same transformation
conducted for 24 h afforded 2a as the sole product (Table 1, entry
Scheme 2. Examination of the reaction intermediates 3a and 4a.
to afford 2a in 96% yield (Scheme 2, Eq. 3). These results indicated
that the reaction partially proceeds via ethers 3a and 4a.
A proposed catalytic pathway is illustrated in Scheme 3. At first,
the hydroxyl oxygen of alcohol 1a is activated upon coordination
with SnBr , to generate diphenylmethyl cation Int-ii via Int-i. We
4
suggest that Int-ii and ethers 3a and 4a are partially in equilib-
rium, that is, Int-ii reacts with 2-naphthol and 1a to produce 3a
5
), we speculated that ethers 3a and 4a could be activated by SnBr
4
9,21,22
to regenerate the diphenylmethyl cation.
Thus, in order to
confirm this hypothesis, ether 3a was subjected to the above con-
ditions in the absence of 2-naphthol and 2a was produced in 91%
yield (Scheme 2, Eq. 2). Similarly, the reaction of 4a was conducted
4
and 4a, which are activated by SnBr to regenerate Int-ii. Finally,
the formed cation Int-ii reacts with 2-naphthol to afford the
desired 2a with dehydration and regeneration of the catalyst. On
the other hand, for less reactive substrates with electron-with-
drawing groups, stoichiometric amounts of catalysts are required.
In summary, we have developed an efficient Friedel–Crafts type
dehydrative alkylation reaction of diarylmethanols with 2-naph-
4
thols promoted by SnBr under mild conditions. Variously substi-
tuted substrates were applicable for this transformation by
adjusting the catalyst loading and the reaction temperature
according to the electronic nature of the substrates. Further studies
Scheme 1. Friedel–Crafts alkylation reaction of benzhydrol with substituted 2-
naphthols. a Using 30 mol % of SnBr
b
Using 110 mol % of SnBr
Scheme 3. Proposed catalytic reaction pathway.
4
.
4
.

N. Suzuki et al. / Tetrahedron Letters 57 (2016) 1456–1459
1459
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