124
Published on the web January 16, 2010
AlCl3-mediated Defluorinative Diarylhydroxylation Transformation of CF3:
Chemoselective Arylation of CF3 and Chlorocarbonyl Groups Attached to Aromatic Rings
Akiko Okamoto, Kazuhiro Kumeda, and Noriyuki Yonezawa*
Department of Organic and Polymer Materials Chemistry, Tokyo University of Agriculture and Technology,
2-24-16, Naka-machi, Koganei, Tokyo 184-8588
(Received November 10, 2009; CL-090992; E-mail: yonezawa@cc.tuat.ac.jp)
O
The CF3 group in 4-trifluoromethylbenzoyl chloride is effi-
TfOH
F3C
C
F
F
ciently diarylated and converted into a diarylhydroxymethyl group
by treatment with AlCl3 in the presence of an excess amount of
halobenzene (C6H5X; X = F, Cl, and Br). The diarylation is fol-
lowed by arylation of the chlorocarbonyl group to afford triarylated
products, diarylhydroxymethylated benzophenones. The employ-
ment of TfOH in place of AlCl3 promotes the exclusive arylation of
the chlorocarbonyl group leaving the CF3 group unchanged to
afford selectively 4-trifluoromethylbenzophenones, which then
undergo diarylhydroxymethylation with the aid of AlCl3.
O
C
reflux, 144 h
98%
+ C6H5F
Cl
3a
4a
F3C
OH
O
C
AlCl3
2a
1
F
C
rt, 24 h
75%
2
Scheme 1.
Table 1. AlCl3-mediated reaction of substrate 1/5 with halobenzene 2a
C6H5X 2
O
C
OH
4: R2
AlCl3
=
X
F3C
R1
X
C
R2
2 = COOH
2 = H
6: R
7: R
a: X = F; b: X = Cl;
c: X = Br; d: X = I
2
1: R1 = COCl; 5: R1 = H
Fluorinated organic molecules are of great interest due to
their biological, optical, electrical, and mechanical properties.
Along with such aspects of practical uses, controlled activation
of C-F bonds has received much attention in organic chem-
istry.1-7 For example, regioselective defluorination by organo-
metallic complexes successfully yields difluorinated organic
molecules.2 Furthermore, Ozerov’s group and Kambe’s group
have recently reported ready conversion of CF3 to CR3 by
treatment with AlR3.3 On the other hand, in acid-mediated
reactions such as Friedel-Crafts reactions, perfluoroalkyl (RF)-
bearing aromatic compounds show rather troublesome behavior.
Not only do RF-bearing aromatic carboxylic acid derivatives act
as labile highly electrophilic acyl-donor species, RF-bearing
aromatic compounds behave as poor acyl-acceptors. So electro-
philic aromatic substitution where an RF group is involved as a
substituent in either substrate generally suffers from low yield
and/or poor selectivity.8 As a natural consequence, a smart
solution for acid-mediated transformation of RF groups implies
further possibilities for RF-bearing compounds in a wide range
of organic chemistry.6,7
Halobenzene
(X)
Product Yield
(X)
b
Run 1/5
AlCl3
Temp
Time
/%c
1
2
3
4
5
6
7d
8
9
1
1
1
1
1
1
1
1
1
1
1
1
5
2a (F)
2a (F)
2a (F)
2a (F)
2b (Cl)
2b (Cl)
2c (Br)
2c (Br)
2d (I)
2d (I)
2d (I)
2a (F)
2a (F)
3 equiv rt
24 h
24 h
24 h
24 h
24 h
4a (F)
4a (F)
4a (F)
4a (F)
4b (Cl)
4b (Cl)
4c (Br)
4c (Br)
4d (I)
75
82
0
86
52
32
52
21
0
3 equiv reflux
1 equiv reflux
6 equiv reflux
3 equiv rt
3 equiv 100 °C 24 h
3 equiv rt 24 h
3 equiv 100 °C 24 h
3 equiv rt 24 h
3 equiv 100 °C 24 h
10
4d (I)
0
11
12
13
6 equiv rt
3 equiv rt
3 equiv rt
24 h
4d (I)
0
5 min 6a (F)
24 h 7a (F)
trace
87
aAll of the reactions were carried out under N2 atmosphere using 15
equiv of halobenzene 2 against substrate 1/5. Against 4-trifluorome-
thylbenzoyl chloride (1). Isolated yield. 6c was isolated (12%).
b
c
d
Recently, we have reported a versatile synthetic protocol for
CF3-bearing aromatic ketones by electrophilic aromatic aroyla-
tion with 4-trifluoromethylbenzoyl chloride (1).9 In this trans-
formation, trifluoromethanesulfonic acid (TfOH) has been
proven to promote excellent selectivity and high conversion in
the formation of CF3-bearing benzophenone 3. On the other
hand, employment of AlCl3 in place of TfOH for reaction of 1
and fluorobenzene (2a) resulted in formation of an unexpected
product, carbinol-ketone 4a,10 in a high conversion instead of
the expected aromatic ketone (3a; Scheme 1).
the same time, however, coloration was also observed (Run 2).
About 3 equimolar amounts of AlCl3 were required against 1 for
smooth arylations (Runs 2 vs. 3). An excess amount of AlCl3
provided a small acceleration of the reaction (Runs 4 vs. 2).
Furthermore, reaction of 2b and 2c as halobenzenes giving the
corresponding ketones also proceeded in moderate yields (Runs
5 and 7). Contrarily, 2d did not give the corresponding carbinol-
ketone (4d; Run 9). Neither elevation of temperature nor
employment of a large amount of AlCl3 yielded the carbinol-
1
ketone (Runs 10 and 11). The H NMR spectrum of the product
In this paper, we introduce and discuss the reaction behavior
and scope of this anomalous transformation of a CF3 group into
a diarylhydroxymethyl unit.
suggests the formation of carbinol-ketone structures devoid of
iodo groups at least partially but structural determination and
identification by isolation have not been achieved.
The results of the AlCl3-mediated reaction of 1 and a related
compound with halobenzene 2 are summarized in Table 1. The
reaction of 1 with 2a in the presence of AlCl3 to give 4a
proceeded at room temperature with a good conversion (Run 1).
At elevated temperature, the yield became slightly higher and at
When 1 was allowed to react with 2a for a short interval, a
trace amount of carbinol-carboxylic acid 6a was isolated from
the reaction mixture, whereas 3a was not obtained (Run 12). In a
similar manner, 6c was also obtained in the reaction of 1 with 2c
(Run 7). Yield of diarylhydroxymethylbenzene 7a from trifluo-
Chem. Lett. 2010, 39, 124-125
© 2010 The Chemical Society of Japan
Okamoto, Akiko
