42
Chemistry Letters Vol.38, No.1 (2009)
Simple and Efficient Metal-free Hydroarylation and Hydroalkylation
Using Strongly Acidic Ion-exchange Resin1
Biswanath Das,Ã Martha Krishnaiah, Keetha Laxminarayana, Kongara Damodar, and D. Nandan Kumar
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500007, India
(Received September 19, 2008; CL-080900)
O
O
Higly efficient hydroarylation and hydroalkylation of sty-
O
O
Ar
R3
renes with various arenes and 1,3-dicarbonyl compounds respec-
tively have been developed using Amberlyst-15 as a hetero-
geneous catalyst. The excellent yields, short reaction times,
and high selectivity are the advantages of this method. The
C–H functionalization has been achieved here under metal-free
conditions.
R2
Ar-H
R3
R
R2
1
1
R
1
R
Amberlyst-15
Amberlyst-15
DCE, 80 °C
DCE, 80 °C
20-55 min
R
R
R
15-40 min
74-95%
82-95%
Scheme 1.
Table 1. Hydroarylation of styrenes using Amberlyst-15a
Styrene
1
Arene
2
Product
3
Time
/min
Yield
/%b
Selec-
tivityc
Entry
a
The functionalization of aromatic compounds is highly use-
ful for the synthesis of pharmaceuticals and agrochemicals.
Classically this conversion is carried out by Friedel–Craft reac-
tions with alkyl or acyl halides using Lewis acids as catalysts.
However, the drastic reaction conditions, formation of by-prod-
ucts and low selectivity are drawbacks of these reactions. Re-
cently several transition metals and organometallics have been
applied as catalysts for C–H transformation of aromatic com-
pounds.2 The hydroarylation of styrenes using a metal catalyst
or a Lewis acid has also emerged as an important method for this
purpose.3 The resulting diarylalkane motif has been found in
various bioactive molecules.4
In continuation of our work5 on the development of useful
synthetic methodologies we have observed that hydroarylation
of styrenes with aromatic compounds and hydroalkylation with
1,3-dicarbonyl compounds can easily and efficiently be carried
out in the presence of Amberlyst-15 as a heterogeneous catalyst
(Scheme 1).
20
40
25
30
98
95
93
96
92:8
94:6
89:11
91:9
OH
OH
b
c
d
OH
OH
Br
Br
Cl
OH
Cl
OH
OH
e
f
20
45
98
83
92:8
93:7
OH
OH
g
35
92
88:12
Br
Br
Various styrenes were treated with different aromatic com-
pounds following the above method to prepare a series of diaryl-
alkanes (Table 1). The reaction was conducted in DCE at 80 ꢀC.
Initially different other solvents such as CH2Cl2, CHCl3, MeCN,
and MeNO2 were employed to carry out this reaction but con-
sidering the yields and reaction times DCE was preferred. The
products were formed in excellent yields and the conversion
was complete within 20–55 min.
The selectivity of the reaction is intresting. In the case of
phenols the ortho-substituted products were major while in other
cases the para-substituted products were major (Table 1). With
3-methoxyphenols the substitution took place mainly at C-2
position (Entries p and q) while with 3-methylphenol at the C-
6 position (Entries k, l, and m).
h
i
50
45
83
90
86:14
94:6
OH
OH
OH
j
k
l
20
15
20
96
93
95
88:12
82:18
84:16
OH
CH3
OH
OH
OH
m
n
20
55
40
93
87
93
91:9
The ethers were not formed in the present reaction of phe-
nols and styrenes. The lone pairs of oxygen of the phenolic hy-
droxyl groups are engaged in resonance and so their availability
is low to form the ethers (O-addition products).
The present method has successfully been extended to the
hydroalkylation of styrenes with 1,3-dicarbonyl compounds.
Typically the alkylation of 1,3-dicarbonyl compounds is carried
out using stoichiometric amount of base and alkyl halides but the
reaction has an overall low atom economy6 and generates a large
amount of salt by-products. Recently the addition of 1,3-dicar-
Br
OH
Br
OMe
OMe
87:13
OMe
o
91:9
Cl
Cl
continued
Copyright Ó 2009 The Chemical Society of Japan