Cationic Iron(III) porphyrin catalyzed dehydrative friedel-crafts reaction of alcohols with arenes

Article abstract of DOI:10.1055/s-0033-1339640

Alcohols react with arenes in the presence of cationic iron(III) porphyrin catalyst. The reaction involves the formation of the C-C bond via dehydration, which is formal Lewis acid catalyzed Friedel-Crafts reaction. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0033-1339640

2148▌
LETTER
lCettaertionic Iron(III) Porphyrin Catalyzed Dehydrative Friedel–Crafts Reaction
of Alcohols with Arenes
Dehydrative Friedel–Crafts Reaction
Satoru Teranishi,a Takuya Kurahashi,*a,b Seijiro Matsubara*a,b
a
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan
Fax +81(75)3832438; E-mail: kurahashi.takuya.2c@kyoto-u.ac.jp; E-mail: matsubara.seijiro.2e@kyoto-u.ac.jp
b
JST, ACT-C, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
Received: 04.07.2013; Accepted after revision: 18.07.2013
cationic intermediate with a cation–π interaction; the in-
Abstract: Alcohols react with arenes in the presence of cationic
teraction would promote the formation of the cationic in-
iron(III) porphyrin catalyst. The reaction involves the formation of
termediate which is generally the rate-determining step
the C–C bond via dehydration, which is formal Lewis acid cata-
lyzed Friedel–Crafts reaction.
(Figure 1).4–6 To test our hypothesis and explore a poten-
tial catalytic ability of metaloporphyrin complex as Lewis
acid, we set up an experiment investigating the reaction of
Key words: alcohols, arenes, coupling, iron, porphyrins
alcohol 1a with arene 2a in the presence of [Fe(TPP)]BF4
(5 mol%) in 1,2-dichloroethane. Indeed, the reaction at 80
Dehydrative Friedel–Crafts reaction of alcohols and
°C within five hours afforded 3aa in 40% yield (Table 1,
arenes are a particularly attractive way of constructing the
entry 1). Thus, we next examined counteranions, such as
C–C bond in view of green chemistry.1 While the initial
Cl, TfO, PF6, and SbF6, for an axial ligand, which would
studies were limited to the reaction with stoichiometric
influence the Lewis acidic nature of Fe3+ (Table 1, entries
Lewis acids,2 a catalytic variant has been developed.3 The
2–5). And we found, when [Fe(TPP)]SbF6 was used as a
reaction is considered to be triggered by activation of the
catalyst, 3aa was obtained in 72% yield (Table 1, entry 5).
alcohol moiety through coordination to the Lewis acid to
The use of other Lewis acid catalysts such as FeCl3, AlCl3,
give the key electrophilic intermediate, that is, the cationic
or the use of FeCl3/AgSbF6 in place of the cationic iron
species, which reacts with the nucleophilic arene (Scheme
porphyrin complex afforded 3aa in lower yields (Table 1,
1).
entries 6–8). It was found that the reaction in benzene pro-
In this context, we speculated that a cationic iron porphy-
rin complex would be an ideal catalyst because a large
π-conjugated planar aromatic structure may stabilize the
vided the desired product in 65% yield (Table 1, entry 9),
while trace or lower amounts of 3aa were obtained in the
cases of using polar solvents such as 1,4-dioxane and THF
OMe
2a
OH
–OH
H2O
OMe
1a
3aa
Lewis acid
Lewis acid
Lewis acid
Scheme 1 Lewis acid catalyzed dehydrative Friedel–Crafts reaction of alcohol with arene
δ+
δ–
O
Lewis acid
H
18π system
cation–π interaction
Ph
N
Ph
N
N
Ph
Ph
N
Fe
Fe
N
N
Ph
Ph
N
N
Ph
Ph
Figure 1 Cationic iron(III) porphyrin complex as a Lewis acid catalyst for dehydrative Friedel–Crafts reaction of alcohol 1a with arene 2a
SYNLETT 2013, 24, 2148–2152
Advanced online publication: 28.08.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1339640; Art ID: ST-2013-U0620-L
© Georg Thieme Verlag Stuttgart · New York

LETTER
Dehydrative Friedel–Crafts Reaction
2149
(Table 1, entries 10 and 11). Thus, among various reaction ry alcohol 1t with 2a gave 3ta in low yield (Table 2, entry
solvents examined, 1,2-dichloroethane gave the best yield 20).
of 3aa (Table 1, entry 5).
Table 2 Dehydrative Friedel–Crafts Reaction of Alcohol 1 with
Anisole 2a with Cationic Iron(III) Porphyrin Catalyst7
Table 1 Optimization of Porphyrin Catalyst for the Dehydrative
Friedel–Crafts Reaction of Alcohol 1a with Arene 2a to give 3aa
Entry Alcohol 1
Product 3
Yield
(%)a,b
Entry
Catalyst
Solvent
Yield (%)a
1
2
[Fe(TPP)]BF4
[Fe(TPP)]Cl
[Fe(TPP)]OTf
[Fe(TPP)]PF6
[Fe(TPP)]SbF6
FeCl3
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
benzene
1,4-dioxane
THF
40
<1
2
OH
OH
OH
OH
72
(7:1)
1
OMe
OMe
OMe
OMe
3
1a
3aa
3ba
3ca
3da
4
<1
72
44
18
48
65
33
<1
85
(10:1)
5
2
6
1b
7
AlCl3
8
FeCl3/AgSbF6
[Fe(TPP)]SbF6
[Fe(TPP)]SbF6
[Fe(TPP)]SbF6
52
(10:1)
3
9
1c
10
11
71
(8:1)
a Isolated as a mixture of para/ortho regioisomers.
4
1d
With the optimized reaction conditions in our hands, we
first investigated the [Fe(TPP)]SbF6-catalyzed dehydra-
tive Friedel–Crafts of various alcohols 1 with 2a, and the
results are summarized in Table 2. The reaction of 1b with
2a gave 3aa in 85% yield (Table 2, entry 2). (E)-3-Phen-
ylbut-2-en-1-ol (1c) and (E)-3-methyl-4-phenylbut-3-en-
2-ol (1d) also participated in the reaction with 2a to give
correspondingly substituted products 3ca and 3da in 52%
and 71% yields, respectively (Table 2, entries 3 and 4).
Secondary allyl alcohols such as 1e, 1f, and 1g also react-
ed with 2a to give the coupling product in good to moder-
ate yields (Table 2, entries 5–7). In the presence of iron
catalyst, 1-phenylethan-1-ol (1h) reacted with 2a to give
diarylmethane 3ha in 89% yield (Table 2, entry 8). It was
found that steric repulsion between substrates and catalyst
does not show great effect on the yields of product; the re-
action of 1-tolylethanols 1i, 1j, and 1k with 2a afforded
the coupling product 3 in high yield irrelevant to their sub-
stitution pattern (Table 2, entries 9–11). 1-(4-Methoxy-
phenyl)ethan-1-ol (1l) reacted with 2a to give 3la as a sole
product in 73% yield (Table 2, entry 12), while the reac-
tion with bromo-substituted alcohol 1m gave 3ma in
45% yield (Table 2, entry 13). Furthermore, dehydrative
Friedel–Crafts reaction of a variety of alcohols with 2a af-
forded coupling products in good to moderate yields (Ta-
ble 2, entries 14–18). The reaction of propargyl alcohol 1s
with 2a furnished the desired product 3sa in 50% yield
(Table 2, entry 19). It was found that the reaction of tertia-
85
(10:1)
5
OH
OMe
1e
3ea
50
(1:1)
6
OH
OMe
1f
3fa
3ga
3ha
3ia
64
(10:1)
OH
OH
7
8
9
OMe
1g
89
(4:1)
OMe
OMe
1h
1i
OH
92
(11:1)
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 2148–2152

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S. Teranishi et al.
LETTER
Table 2 Dehydrative Friedel–Crafts Reaction of Alcohol 1 with
Anisole 2a with Cationic Iron(III) Porphyrin Catalyst7 (continued)
Table 2 Dehydrative Friedel–Crafts Reaction of Alcohol 1 with
Anisole 2a with Cationic Iron(III) Porphyrin Catalyst7 (continued)
Entry Alcohol 1
Product 3
Yield
(%)a,b
Entry Alcohol 1
Product 3
Yield
(%)a,b
OH
OH
90
(4:1)
50
10
19
(2:1)
OMe
OMe
1j
3ja
1s
3sa
3ta
OH
OH
28
(10:1)
95
(11:1)
20
11
OMe
OMe
1t
1k
3ka
a Isolated yields are given.
b Ratio of regioisomers (para/ortho).
OH
73
12
(10:1)
MeO
OMe
MeO
We next explored the scope of the dehydrative Friedel–
Crafts reaction using various arenes 2 with alcohol 1a, and
the results are summarized in Table 3. The reaction of 1,4-
or 1,3-dimethoxy-substituted benzene with 1a afforded
correspondingly substituted products in high yields (Ta-
ble 3, entries 1 and 2). Furthermore, 1,3,5-trimethoxy-
substituted benzene and 1,3,5-mesitylene also participat-
ed in the reaction with 1h to give 3hd and 3he in excellent
yields (Table 3, entries 3 and 4). Heterocyclic arenes, such
as benzothiophene and benzofuran, also reacted with 1h
in the presence of cationic iron(III) porphyrin catalyst to
give the coupling product in 94% and 61% yields, respec-
tively (Table 3, entries 5 and 6). Phenol (2h) and its deriv-
atives 2i reacted with 1h to furnish diarylmethans 3hh and
3hi.
1l
3la
OH
45
(4:1)
13
Br
OMe
Br
1m
3ma
OH
91
(8:1)
14
t-Bu
t-Bu
OMe
1n
3na
OH
93
(8:1)
15
OMe
We performed the dehydrative Friedel–Crafts reaction of
chiral alcohol with arene to gain insight into the reaction
mechanism catalyzed with the cationic iron(III) porphyrin
complex; the reaction of (R)-1-phenylethan-1-ol (1h) with
anisole (2a) in the presence of iron porphyrin catalyst
gave coupling product 3ha as a racemic mixture. These
results suggested that the catalytic process includes the
formation of a cationic intermediate, which leads to race-
mization of the products.
1o
3oa
3pa
OH
67
(6:1)
16
OMe
1p
In conclusion, we have developed a novel catalyst for the
dehydrative Friedel–Crafts reaction of alcohols and
arenes. The readily available metalloporphyrin complex,
which consists of a Lewis acidic cationic iron center and
a large π-conjugated planar aromatic structure, effectively
catalyzed the reaction with high functional-group toler-
ance and robustness. Further efforts for detailed studies to
elucidate the mechanism underlying the unique reactivity
of cationic iron(III) porphyrin are under way.
98
(8:1)
17
OH
OMe
1q
3qa
99
(5:1)
18
OH
OMe
Acknowledgment
1r
3ra
This work was supported by JST, ACT-C, and Grants-in-Aid from
the Ministry of Education, Culture, Sports, Science, and Technolo-
gy, Japan. T.K. also acknowledges the Asahi Glass Foundation, the
Synlett 2013, 24, 2148–2152
© Georg Thieme Verlag Stuttgart · New York

LETTER
Dehydrative Friedel–Crafts Reaction
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References and Notes
Table 3 Dehydrative Friedel–Crafts Reaction of Alcohol 1h with
Arenes 2 with Cationic Iron(III) Porphyrin Catalyst
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Uemura, S. Bull. Chem. Soc. Jpn. 1986, 59, 3617.
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T.; Fukuzawa, S.-i. J. Org. Chem. 1997, 62, 6997.
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Laali, K. K. Green Chem. 2006, 8, 615. (e) Tsuchimoto, T.;
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Entry Arene 2
Product 3
Yield (%)a
OMe
OMe
1
70
OMe
OMe
OMe
2b
3hb
3hc
OMe
2
72
OMe
OMe
OMe
OMe
2c
OMe
3
83
92
94
MeO
OMe
MeO
2d
3hd
4
2e
3he
3hf
S
S
5
2f
O
O
6
61
59
2g
3hg
3hh
OH
7
OH
2h
(5) (a) Fujiwara, K.; Kurahashi, T.; Matsubara, S. J. Am. Chem.
Soc. 2012, 134, 5512. (b) Wakabayashi, R.; Kurahashi, T.;
Matsubara, S. Org. Lett. 2012, 14, 4794. (c) Ozawa, T.;
Kurahashi, T.; Matsubara, S. Org. Lett. 2012, 14, 3008.
(d) Terada, T.; Kurahashi, T.; Matsubara, S. Heterocycles
2012, 85, 2415.
OH
OH
8
87
(6) For examples of the use of metalloporphyrins in
nonoxidative bond formation, see: (a) Suda, K.; Baba, K.;
Nakajima, S.-I.; Takanami, T. Chem. Commun. 2002, 2570.
(b) Suda, K.; Kikkawa, T.; Nakajima, S.-I.; Takanami, T.
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Nakajima, S.-I.; Takanami, T. Tetrahedron Lett. 1999, 40,
7243. (d) Chen, J.; Che, C.-M. Angew. Chem. Int. Ed. 2004,
43, 4950. (e) Li, Y.; Chan, P. W. H.; Zhu, N.-Y.; Che, C.-M.;
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2i
3hi
a Isolated yields are given.
Uehara Memorial Foundation, Tokuyama Science Foundation, and
Kurata Memorial Hitachi Science and Technology Foundation.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
m
iotSrat
ungIifoop
r
t
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 2148–2152

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S. Teranishi et al.
LETTER
(7) General Procedure for the Dehydrative Friedel–Crafts
Reaction of Alcohols with Arenes
Selected Data for Compound 3aa
Yield: 72%; colorless oil. TLC: Rf = 0.62 (hexane–
toluene, 2:1). 1H NMR (500 MHz, CDCl3): δ = 7.36 (d,
J = 7.5 Hz, 2 H), 7.31–7.28 (m, 2 H), 7.22–7.16 (m, 3 H),
6.88–6.86 (m, 1 H), 6.44 (d, J = 16.0 Hz, 1 H), 6.38–6.32 (m,
1 H), 3.81 (s, 3 H), 3.50 (d, J = 6.5 Hz, 3 H). 13C NMR (125
MHz, CDCl3): δ = 158.1, 137.5, 132.2, 130.7, 129.7, 129.6,
128.5, 127.0, 126.1, 113.9, 55.3, 38.4. IR (neat): 3025, 1511,
1246, 1175, 1035, 966, 827, 729, 692 cm–1. MS: m/z (%) =
224/25 (100/17) [M+]. HRMS (APCI): m/z [M + H]+ calcd
for C16H16O: 225.1274; found: 225.1269.
To a screw-cap vial was added [Fe(TPP)][SbF6] (0.02 mmol,
18 mg), followed by the alcohol (0.4 mmol), the arene (2
mmol), and dry 1,2-DCE (1.0 mL) in a dry box. The vial was
sealed and stirred at 80 °C for 5 h. The reaction mixture was
diluted with hexane–EtOAc (10:1), passed through a short
silica gel pad and washed with hexane–EtOAc (1:1),
concentrated in vacuo. The crude product was purified by
flash column chromatography using SiO2 (hexane–EtOAc).
Synlett 2013, 24, 2148–2152
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