Decarbonylative diarylation of α-methoxyacetic acid yielding diarylmethanes mediated by Lewis acid and trifluoroacetic anhydride

Article abstract of DOI:10.1246/cl.2005.860

Reaction of α-methoxyacetic acid with aromatic compounds in the presence of trifluoroacetic anhydride and Lewis acid has been found to give diarylmethanes. Some of the intermediates in this transformation have been identified via direct observation by ¹H and ¹³CNMR spectroscopy. The reaction route has been clarified as follows: a mixed acid anhydride is formed from α-methoxyacetic acid and trifluoroacetic anhydride, which gives a hemiacylal type intermediate via decarbonylation followed by successive double electrophilic aromatic substitutions yielding diarylmethanes. Copyright

Full text of DOI:10.1246/cl.2005.860

8
60
Chemistry Letters Vol.34, No.6 (2005)
Decarbonylative Diarylation of ꢀ-Methoxyacetic Acid Yielding Diarylmethanes
Mediated by Lewis Acid and Trifluoroacetic Anhydride
y
yy
ꢀ
Takashi Jobashi, Tetsuo Hino, Katsuya Maeyama, Hiroyuki Ozaki, Kenji Ogino, and Noriyuki Yonezawa
Department of Organic and Polymer Materials Chemistry,
Tokyo University of Agriculture & Technology, Koganei, Tokyo 184-8588
Graduate Program of Human Sensing and Functional Sensor Engineering, Graduate School of Engineering,
Yamagata University, Yonezawa 992-8510
Graduate School of Bio-applications and System Engineering, Tokyo University of Agriculture & Technology,
Koganei, Tokyo 184-8588
y
yy
(Received April 5, 2005; CL-050453)
Reaction of ꢀ-methoxyacetic acid with aromatic com-
aromatic compounds 2 in the presence of trifluoroacetic anhy-
dride ((CF3CO)2O) (3) and Lewis acids are shown in Table 1.
In the reaction of ꢀ-methoxyacetic acid (1) with two equimolar
amounts of anisole (2a) against acid 1, diarylmethane 5 was
obtained in a 55% yield with evolution of carbon monoxide
(4) (Entry 1). The evolution of carbon monoxide (4) was con-
firmed by the aid of a gas indicator, Gas Indicator Tube No.
1H, GASTEC Corporation. On the other hand, neither carbon
monoxide (4), diarylmethane 5, nor ꢀ-methoxyacetophenone
derivatives 6 were formed when the operation was carried out
in the absence of (CF3CO)2O (3) or Lewis acid (Entries 2 and
pounds in the presence of trifluoroacetic anhydride and Lewis
acid has been found to give diarylmethanes. Some of the inter-
mediates in this transformation have been identified via direct
1
13
observation by H and C NMR spectroscopy. The reaction
route has been clarified as follows: a mixed acid anhydride is
formed from ꢀ-methoxyacetic acid and trifluoroacetic anhy-
dride, which gives a hemiacylal type intermediate via decarbon-
ylation followed by successive double electrophilic aromatic
substitutions yielding diarylmethanes.
3
). Therefore, combination of (CF3CO)2O (3) and Lewis acids
Electrophilic aromatic substitution of free carboxylic acid
1
has been proved to promote this decarbonylative diarylation in
the same manner as phosphoric acid anhydride type reagents.
On the other hand, when an equimolar amount of anisole (2a)
against acid 1 was allowed to react, diarylmethane 5 was also
produced in a rather lower yield (38%, Entry 4). In contrast,
when a large amount of anisole (2a) was treated, formation of
mediated by PPA (polyphosphoric acid), the Eaton reagent
(
P2O5–MsOH; mixture of phosphorus pentoxide and methane-
2
3
4
sulfonic acid), triflic acid, and methanesulfonic acid has been
widely investigated. However, electrophilic aromatic substitu-
tion of ꢀ-keto- and ꢀ-alkoxycarboxylic acids has been scarcely
reported.
Table 1. Reaction of ꢀ-methoxyacetic acid (1) with aromatic
compounds 2 in the presence of (CF3CO)2O (3) and Lewis acidsa
Recently, we have found that decarbonylative ꢀ,ꢀ-diaryla-
tion reaction of ꢀ-alkoxycarboxylic acid proceeds instead of
the Friedel–Crafts type acylation in the presence of phosphoric
(
CF CO) O 3 CO 4
O
O
3
2
5
+
OH
Lewisacid
CH Cl
+
MeO
acid anhydride type mediators such as PPA or P2O5–MsOH.
Ar-H
2
MeO
Ar
Ar
2
2
Ar
5
6
About this arylation reaction, the scope and the limitation, the
structural requirements, and the reaction mechanism have been
elucidated. The plausible reaction pathway of this transforma-
tion is proposed to have following three stages: 1) formation
of a reactive intermediate from an ꢀ-alkoxycarboxylic acid
and phosphoric acid like mixed acid anhydride, 2) decarbonyla-
tive electrophilic attack of the intermediate to arenes yielding
monoarylated intermediates, 3) electrophilic aromatic substitu-
tion of the monoarylated intermediates yielding decarbonyla-
tively diarylated products.
During the course of the investigation on decarbonylative
diarylation reaction, we have discriminated the two governing
factors for the first and the second stages of this reaction. One
is the forming ability for mixed acid anhydride type intermediate
and the other is acidic mediation for decarbonylative diarylation.
In this consequence, we have found that combination of other re-
agents taking the place of these two roles also induces decarbon-
ylative diarylation. In this communication, we wish to discuss
the reaction behavior, the governing factors, and the intermedi-
ates and the reaction pathway of the decarbonylative diarylation
reaction of ꢀ-alkoxycarboxylic acid mediated by acid anhydride
and Lewis acid.
1
rt, 24 h
2a:Ar = 4-MeOC6H4
b: Ar = 2,4-Me2C6H3
2c: Ar = 4-MeC6H4
2d:Ar = Ph
2
3/1
Yield/%
2
/1
Entry
1
2
Lewis acid
(
mol/mol)
5
6
(
mol/mol)
2a
2
2
AlCl3
—
1
1
0
1
1
1
0
1
1
1
1
1
1
55
0
0
2b 2a
3b 2a
0
0
2
AlCl3
0
4
5
6
2a
2a
2a
1
AlCl3
38
47
38
49
31
10
69
80
56
25
0
10
2
AlCl3
12
0
c
AlCl3
7d 2a
40
2
P2O5–MsOH
SnCl4
0
8
9
0
2a
2a
2a
2b
2c
2d
0
2
ZnCl2
0
.
1
2
BF3 OEt2
0
.
11
12
13
2
BF3 OEt2
0
.
2
BF3 OEt2
0
.
2
BF3 OEt2
0
a
Reaction conditions: ꢀ-methoxyacetic acid (1), 1 mmol; Lewis
acid, 5 mmol; CH2Cl2, 5 mL. Evolution of CO (4) was not con-
2
firmed. Reflux, 4 h. P O –MsOH (1 mL) was employed instead
b
c
d
5
The results of the reaction of ꢀ-methoxyacetic acid (1) with
of Lewis acid and CH2Cl2.
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.6 (2005)
-methoxyacetophenone derivative 6 (12%) along with diaryl-
methane 5 (47%) was observed (Entry 5). By this reaction sys-
tem, ꢀ-methoxyacetic acid (1) and arene 2 are transformed into
diarylmethane 5 more effectively in comparison to P2O5–MsOH
mediated one (Entry 7).
861
ꢀ
anhydride 7 formed in situ is smoothly decarbonylated to gener-
ate hemiacylal intermediate 8.
Furthermore, in this reaction system, electrophilic aromatic
substitution of hemiacylal 8 should readily yield ꢀ-aryl-ꢀ-
methoxymethane 9 in preference to the formation of diaryl-
methane 5. However, the existence of ꢀ-aryl-ꢀ-methoxy-
methane 9 has not been observed under the reaction conditions
examined. The transformation of the monoarylated compound
9 into diarylmethane 5 is supposed to be so fast that the
formation of the intermediate 9 could not be observed.5a In this
course of transformation, evolution of carbon monoxide (4) is
evidently the driving force for the formation of the activated
intermediate 8, which readily gives the further arylated product
From the point of dependence on the kind of Lewis acids,
.
BF3 OEt2 is found to be the most effective Lewis acid among
those we have been evaluated, as shown in Table 1 (Entries 1,
8–10). In contrast, employment of other Lewis acids for this
reaction generally gave complex mixtures containing some
unknown products (Entries 1, 8, and 9). Thus, choice of Lewis
acid is significant to achieve high efficiency of decarbonylative
diarylation of acid 1. On the other hand, this reaction is proved
to be applicable for other aromatic compounds, such as m-xylene
9
of diarylmethane 5.
(2b), toluene (2c), and benzene (2d), producing the correspond-
ing diarylmethanes 5 (Entries 11–13).
For this transformation, some of the intermediates formed in
The preference of decarbonylative diarylation yielding di-
arylmethane 5 against electrophilic aromatic acylation giving
acetophenone 6 is interpreted as follows: both of the two reaction
pathways of mixed-acid anhydride 7, decarbonylation and elec-
trophilic aromatic acylation, have possibility to proceed via con-
certed process. However, decarbonylation of mixed-acid anhy-
dride 7 proceeds far faster than concerted electrophilic aromatic
acylation. Only when excess amount of aromatic compound is
present, electrophilic aromatic acylation product 6 is generated
in a low yield (Table 1, Entry 5). Generally, under the conditions
described in this paper, electrophilic aromatic acylation scarcely
proceeds in competition with decarbonylation of mixed-acid
anhydride 7.
In conclusion, we have found that combination of
(CF3CO)2O (3) and Lewis acid functions as a promoter of decar-
bonylative diarylation of ꢀ-methoxyacetic acid (1) in place of
PPA and P2O5–MsOH. Furthermore, the intermediates in this
transformation are experimentally identified as mixed-acid an-
hydride and hemiacylal compounds. Further work on clarifica-
tion of scope and limitation of this transformation is currently
being undertaken.
1
13
situ were directly observed with the aid of H and C NMR
spectroscopy. H and 13C NMR spectra of the reaction solution
show that mixed-acid anhydride 7 and trifluoroacetic acid
1
5
c
(
TFA) are immediately formed after mixing of ꢀ-methoxyacetic
acid (1) and (CF3CO)2O (3) (Figure 1). Furthermore, when
.
BF3 OEt2 was added to the solution of mixed-acid anhydride
7
, carbon monoxide (4) was evolved. The signals of hemiacylal
1
13
equivalent to intermediate 8 is observed in the H and C NMR
spectra of the solution (Figure 1).
Based on this observation, the reaction pathway is presumed
as follows (Scheme 1): initially, ꢀ-methoxyacetic acid (1) reacts
with (CF3CO)2O (3) to form mixed-acid anhydride 7. Trifluoro-
acetic anhydride (3) is known to give mixed-acid anhydride by
6
the reaction with carboxylic acid as well as p-trifluoromethyl-
7
8
benzoic anhydride and diphenyl chlorophosphonate. The acid
(
CF3CO)2O 3
− TFA
O
O
MXn
Xn M
O
O
O
O
MeO
MeO
CF3
OH
O
CF3
1
MeO
7
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CO 4
MeO
O
Ar-H
Ar-H
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Figure 1. 1H and 13C NMR spectra of ꢀ-methoxyacetic acid (1)
in CDCl3 and the reaction mixtures obtained by addition of
.
(
CF3CO)2O (3) and BF3 OEt2 in CDCl3.
Published on the web (Advance View) May 21, 2005; DOI 10.1246/cl.2005.860