Chemospecificity in arylations of δ- and γ-ketocarboxylic acids with P2O5-MsOH, TfOH, and related acidic media

Article abstract of DOI:10.1081/SCC-120013730

Remarkable contrast between chemospecificities in acid-mediated arylation of δ- and γ-ketocarboxylic acids was revealed: in the presence of P₂O₅-MsOH, TfOH, PPA, and MsOH, arylation of δ-ketocarboxylic acid 1A with arenes takes place

Full text of DOI:10.1081/SCC-120013730

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CHEMOSPECIFICITY IN ARYLATIONS OF δ- AND γ-
KETOCARBOXYLIC ACIDS WITH P2O5–MsOH, TfOH, AND
RELATED ACIDIC MEDIA
Noriyuki Yonezawa a , Masayuki Koike a , Asami Kameda a , Shin Naito b , Tetsuo Hino c ,
Katsuya Maeyama a & Tomiki Ikeda c
a Department of Organic and Polymer Materials Chemistry , Tokyo University of Agriculture
and Technology , Koganei, Tokyo, 184-8588, Japan
b Department of Chemistry , Gunma University , Kiryu, Gunma, 376-8515, Japan
c Research Laboratory of Resources Utilization , Tokyo Institute of Technology , Nagatsuda,
Midori-ku, Yokohama, 226-8503, Japan
Published online: 16 Aug 2006.
To cite this article: Noriyuki Yonezawa , Masayuki Koike , Asami Kameda , Shin Naito , Tetsuo Hino , Katsuya Maeyama &
Tomiki Ikeda (2002) CHEMOSPECIFICITY IN ARYLATIONS OF δ- AND γ-KETOCARBOXYLIC ACIDS WITH P2O5–MsOH, TfOH, AND
RELATED ACIDIC MEDIA, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 32:20, 3169-3180, DOI: 10.1081/SCC-120013730
To link to this article: http://dx.doi.org/10.1081/SCC-120013730
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 20, pp. 3169–3180, 2002
CHEMOSPECIFICITY IN ARYLATIONS
OF d- AND g-KETOCARBOXYLIC ACIDS
WITH P2O5–MsOH, TfOH, AND RELATED
ACIDIC MEDIA
Noriyuki Yonezawa,1, Masayuki Koike,1
*
Asami Kameda,1 Shin Naito,2 Tetsuo Hino,3
Katsuya Maeyama,1 and Tomiki Ikeda3
1Department of Organic and Polymer Materials
Chemistry, Tokyo University of Agriculture and
Technology, Koganei, Tokyo, 184-8588, Japan
2Department of Chemistry, Gunma University,
Kiryu, Gunma 376-8515, Japan
3Research Laboratory of Resources Utilization,
Tokyo Institute of Technology, Nagatsuda,
Midori-ku, Yokohama 226-8503, Japan
ABSTRACT
Remarkable contrast between chemospecificities in acid-
mediated arylation of d- and g-ketocarboxylic acids was
revealed: in the presence of P2O5–MsOH, TfOH, PPA, and
MsOH, arylation of d-ketocarboxylic acid 1A with arenes
takes place at the carboxycarbonyl carbon, while that of
g-ketocarboxylic acid 1B takes place at the ketone carbonyl
carbon, specifically.
*Corresponding author. E-mail: yonezawa@cc.tuat.ac.jp
3169
DOI: 10.1081/SCC-120013730
Copyright & 2002 by Marcel Dekker, Inc.
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3170
YONEZAWA ET AL.
Electrophilic aromatic substitution of free carboxylic acids[1] using
acidic medium such as PPA (polyphosphoric acid),[2] P2O5–MsOH
(phosphorus pentoxide–methanesulfonic acid mixture),[3] MsOH,[4] and
TfOH (triflic acid)[5] has attracted wide interest. In particular, TfOH-
mediated aromatic substitution reactions have been widely investigated.[6]
However, acid-promoted arylation of keto acids has been little known.
Recently, we have revealed specific and chemoselective multi-a-arylation
of a-alkoxy-[7a] and a-keto carboxylic acids.[7b]
In the course of this study, we happened to find the clear discrimi-
nation between regiospecificities in arylations of 5-ketohexanoic acid (d-keto
acid 1A) and 4-ketopentanoic acid (g-keto acid 1B). There is no more than
one carbon length difference between the two carboxylic acid substrates.
However, the carbonyl carbons attacked by arenes were clearly
distinguished. In this paper we report the striking contrast of chemospecific
reaction behaviors in the acid-mediated arylations of d-keto acid 1A and
g-keto acid 1B.
When acids 1A–B were allowed to react with arenes in the presence of
PPA, MsOH, P2O5–MsOH, and TfOH, d-keto acid 1A gave two types of
products and g-keto acid 1B gave three types, respectively. That is, d-keto
acid 1A yielded a,b-unsaturated cyclic ketones (cyclohexenones 3A) and/or
1,5-diketones 4A, while g-keto acid 1B yielded a,b-unsaturated cyclic
ketones (cyclopentenones 3B), g-arylated phenones 5–7B, and/or g-lactones
8B (Table 1). Among the products for the reactions of two keto acid
substrates, only a,b-unsaturated cyclic ketones 3 (3A or 3B) were observed
in common.
In addition to the different reaction behaviors between the two keto
acids, it was found that the product distributions varied drastically
depending on the acidic medium used.
The P2O5–MsOH mediated arylation of d-keto acid 1A yielded
cyclohexenones 3A exclusively. On the other hand, the TfOH-mediated
arylation of d-keto acid 1A gave 1,5-diketones 4A solely. Still more, the
arylation of d-keto acid 1A with PPA gave a mixture of compounds 3A
and 4A, whereas that with MsOH yielded only cyclohexenones 3A in a
low yield.
The P2O5–MsOH mediated arylation of g-keto acid 1B efficiently
produced cyclopentenones 3B. At the same time, g-arylated phenones
5–7Ba were also obtained in the reaction with anisole (2a) and lactones 8
were produced in the reaction with bromoanisole (2c). On the contrary, the
TfOH-mediated arylation of g-keto acid 1B yielded g-lactones 8B solely
except for the reaction with toluene (2b). The arylation of g-keto acid 1B
with PPA or MsOH gave a mixture of products 3B, 5–7B, and 8B, depend-
ing on the kind of the arenes used.

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d- AND g-KETOCARBOXYLIC ACIDS
3171
Table 1. Reactions of d- and g-Keto Acid 1A–B with Arenes 2a–e in Several Acidic
Mediaa
Product and Isolated Yield (%)b
Substrate
ArH
2
1A
1B
5/6/7
3
4
5/6/7
8
3
4
8
[P2O5-MsOH]
2a
2ad
2b
2c
75
–
10
69f
48
0
–
0
0
0
0/0/0
–/–/–
0/0/0
0/0/0
0/0/0
0
–
0
0
0
28c
49e
51
0
0
0
0
0
14/trace/trace
11/11/23
0/0/0
0/0/0
0/0/0
0
0
0
51g
86
29h
0
2d
[TfOH]
2a
2b
2c
2d
0
0
0
0
77
81
68j
55
0/0/0
0/0/0
0/0/0
0/0/0
0
0
0
0
0
0
0
0
0
0
0
0
0/0/0
0/0/0
0/0/0
0/0/0
81
i
–
84k
46
[Polyphosphoric acid (PPA)]
2a
2b
23
3
25
4
0/0/0
0/0/0
0
0
23
3
0
0
50/0/0
0/0/0
0
11
[MsOH]
2a
2b
23
trace
0
0
0/0/0
0/0/0
0
0
0
0
0
0
34/17/17
0/0/0
0
28l
aReaction conditions: keto acid 1 mmol, acidic medium 2 mL, arene 1 mmol, r.t., 8 h;
bYield based on the keto acid; cThe yields of cyclopentenones 3Ba and disubstituted
arene 30Ba were 11 and 17%, respectively; r.t., 24 h; The yields of cyclopentenone
3Ba and 30Ba were 36% and 13%, respectively; fp-Substituted product against meth-
oxy group/o-substituted product against methoxy group ¼ 42/24; gp-Substituted
product against methoxy group/o-substituted product against methoxy
group ¼ 17/34; hp-Substituted product against methoxy group/o-substituted product
against methoxy group ¼ 13/16; iUnidentified products were obtained; jp-Substituted
product against methoxy group/o-substituted product against methoxy
group ¼ 23/45; kThe yields of lactones 8Bc and disubstituted arene 80Bc were 42%
( p-substituted lactone against methoxy group/o-substituted lactone against methoxy
d
e
l
group ¼ 19/23) and 42%, respectively; The yields of lactones 8Bc and disubstitued
arene 80Bc were 7 and 21%, respectively.

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3172
YONEZAWA ET AL.
By comparing the structure of keto acids 1A–B with products 4 and 8,
it is obvious that diketones 4 were formed through arylation at the carboxy
carbon of d-keto acid 1A and that lactones 8 were produced through
arylation at the g-keto carbonyl carbon of acid 1B. However, in case that
a,b-unsaturated cyclic ketones 3A–B and g-arylated phenones 5–7 were
obtained, whether the initial arylation occurred at the carboxy carbon or
at the keto carbonyl carbon was still ambiguous.
On the basis of the reaction behavior, 1,5-diketones 4A are considered
to be the intermediates for the formation of cyclohexenones 3A from d-keto
acid 1A. The reasons are as follows: (1) diketones 4A were obtained when
d-keto acid 1A and arenes 2 were treated with TfOH or PPA, (2) d-lactones
8A were not isolated from any of the reaction mixtures of d-keto acid 1A,
and 3) diketones 4A were quantitatively converted into cyclohexenones 3A
when they were allowed to react in P2O5–MsOH or MsOH.
Accordingly, cyclohexenones 3A are proved to be formed via Friedel–
Crafts type acylation of d-keto acid 1A to arenes 2 followed by intramole-
cular aldol condensation of the resulting diketones (4A) (4A!9!3A).
On the other hand, g-lactones 8B or the ring-opened equivalents of
g-lactones 8B are ascertained to be the intermediates for the formation of
both cyclopentenones 3B and g-arylated phenones 5–7B from g-keto acid
1B, on the basis of the following results: (1) every homologue of lactone 8B
corresponding to each arene used was isolated, (2) 1,4-diketones 4B were not
isolated from any of the reaction mixture of g-keto acid 1B, (3) lactones 8B
were quantitatively converted into cyclopentenones 3B when lactones 8B
were allowed to react in P2O5–MsOH, and (4) when lactone 8Ba was
allowed to react with anisole (2a) in P2O5–MsOH, g-arylated phenones
5–7Ba were produced.
In consequence, cyclopentenones 3B are ascertained to be produced
via g-arylated of acid 1B to give intermediates 11 or lactones 8B followed
by conversion to olefins 12 and intramolecular acylation of olefins 12.
g-Arylated intermediate 11 or lactone 8b also yielded g-arylated phenones
5–7B via intermolecular Friedel–Crafts type acylation. g-Arylated inter-
mediate 11 would be converted to lactone 8 through cyclization during
work-up process.
The results described above show that the initial arylations of d- and
g-keto acids 1A–B occur at the different carbonyl groups chemospecifically
(Sch. 1). The arylation of d-keto acid 1A progress at the carboxy carbon,
whereas the initial arylation of g-keto acid 1B proceeds at the keto carbonyl
carbon, respectively.
The specificity in the arylation of d- and g-keto acids 1A–B is
rationally explained by the existence of different types of stable intermedi-
ates at the early stages (Sch. 2). The initial stable intermediate in the

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d- AND g-KETOCARBOXYLIC ACIDS
3173
Scheme 1. Plausible reaction mechanism in these reactions.
reaction of d-keto acid 1A is assumed to be an open-chain acylium ion
equivalent (1A0), whereas that in the reaction g-keto acid 1B is suspected
to be a cyclic oxonium ion equivalent (1B0).[8,9]
In this relation, acidic medium dependence in the reactions is
interpreted as follows: formation of a,b-unsaturated cyclic ketones 3A
depends on the tendency for the intermediate, 1,5-diketones 4A, toward

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3174
YONEZAWA ET AL.
Scheme 2. Difference between d-keto acid 1A and g-keto acid 1B in this reaction.
cyclizaiton. For the acid-mediated cyclization, enolization of diketones 4A
to intermediate 9 is needed. The exclusive formation of diketones 4A in
TfOH is supposed to be due to the predominant stability of the doubly
protonated ketones (10) in such ‘super acidic’ circumstances.[6,10]
Consequently, the repulsion of dication intermediates 10 should prevent
further intramolecular reactions such as cyclization to give ketones 3A
in TfOH.
In the reaction g-keto acid 1B, lactone equivalents 11 are formed at the
early stage owing to the equilibrium shown in Sch. 2. The selectivity is
interpreted based on the relative susceptibilities of activated species
formed from lactones 8 or their equivalents 11. Then, these active intermedi-
ates cause further two types of reactions: one is the Friedel–Crafts type
acylation (formation of compounds 5–7B), and the other is olefin formation
(olefin 12), when arenes 2 have enough reactivities for ketone formation,
diarylated compounds 5–7B are formed. When reaction media have
sufficient capability for formation of olefin 12, simultaneous ring-closure
reaction propagates (12!3B). On the other hand, g-lactones 8B are
supposed to be stable enough to suppress further transformation in
TfOH. Thus, the intermediates in TfOH are considered to exist as dication
forms such as intermediates 13.[6] Consequently, cyclization of dications 13
to lactones 8B is supposed to be suppressed till aqueous work-up process.[11]
In conclusion, we examined the various reactions of d- and g-keto
acids with several arenes in some acidic media such as P2O5–MsOH, PPA,
MsOH, and TfOH. When d-keto acid 1A was treated with arenes,
compounds 3A and 4A were mainly obtained. On the other hand, when
g-keto acid 1B was treated with arenes, compounds 3B, 5–7B, and 8 were

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d- AND g-KETOCARBOXYLIC ACIDS
3175
mainly obtained. Investigation on by-products distribution, it was cleared
that arylation to d- and g-keto acids occurs at the different carbonyl
carbons, carboxy carbon or ketone carbon, respectively. The observed
discrimination in the reaction of these keto acids suggests a hitherto
unclarified intramolecular effect in oxonium ion intermediate generated by
strong to super acidic media.
EXPERIMENTAL
1
General: H and 13C NMR spectra were recorded on a JEOL JNM-
A500 (1H; 500 MHz, 13C; 125 MHz) spectrometer or a JEOL FX-200 (1H;
200 MHz) spectrometer using Me4Si (1H, d 0.00) and CDCl2 (13C, d 77.0) as
internal standards. IR spectra were recorded on a JASCO FTIR-5300 spec-
trometer. P2O5-MeOH was prepared by stirring a 1/10 (w/w) mixture of
P2O5 and MsOH at r.t. according to the method in literature.[3]
Preparative TLC was performed using WAKO Wakogel B-5F. Column
chromatography was performed using Merck silica gel 60-5B (particle size
0.063–0.200 mm).
Typical reaction procedure for reaction of d-and g-keto acids 1A-B in
acidic media: Reaction of d-keto acid 1A with anisole (2a) in P2O5–MsOH:
P2O5–MsOH (2 mL) was added to an ice-cooled mixture of acid 1A (130 mg,
1.0 mmol) with anisole (2a, 108 mg, 1.0 mmol) under vigorous stirring. The
mixture was stirred at the prescribed temperature and for the prescribed
time interval. Then the mixture was poured into ice water. The aqueous
solution was extracted with chloroform (50 mL Â 2). The combined organic
layer was washed with saturated aqueous NaCl solution, dried over MgSO4
overnight, and concentrated under reduced pressure. The residue was pur-
ified by preparative TLC to give 3-(4-methoxyphenyl)-2-cyclohexenone
(3Aa).
3-(4-Methoxyphenyl)-2-cyclohexenone (3Aa):[12] 1H NMR (CDCl3) ꢀ
2.08–2.20 (2H, m), 2.48 (2H, t, J ¼ 6 Hz), 2.70–2.80 (2H, m), 3.85 (3H, s),
6.43 (1H, t, J ¼ 2 Hz), 6.95 (2H, pseudo dd of AA0BB0 pattern, J ¼ 8, 2 Hz),
7.54 (2H, pseudo dd of AA0BB0 pattern, J ¼ 8, 2 Hz); 13C NMR (CDCl3)
ꢀ 22.6, 27.7, 37.0, 55.3, 114.2, 124.8, 127.7, 130.9, 159.3, 161.4, 200.0 ppm;
IR (KBr) 1647 cmꢀ1
.
3-(4-Methylphenyl)-2-cyclohexenone (3Ab):[13] 1H NMR (CDCl3) ꢀ
2.09–2.20 (2H, m), 2.39 (3H, s), 2.49 (2H, t, J ¼ 6 Hz), 2.70–2.80 (2H, m),
6.41 (1H, t, J ¼ 2 Hz), 7.22 (2H, pseudo dd of AA0BB0 pattern, J ¼ 8, 2 Hz),
7.46 (2H, pseudo dd of AA0BB0 pattern, J ¼ 8, 2 Hz); 13C NMR (CDCl3)
ꢀ 18.2, 21.5, 29.8, 37.2, 42.5, 128.0, 129.2, 143.7, 158.7, 199.2, 208.3 ppm;
IR (KBr) 1711, 1672 cmꢀ1
.

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3176
YONEZAWA ET AL.
3-(2-Bromo-4-methoxyphenyl)-2-cyclohexenone and 3-(4-bromo-2-methoxy-
phenyl)-2-cyclohexenone (3Ac): These compounds were obtained as an inse-
parable mixture of regioisomers; IR (KBr) 1647, 1670 cmꢀ1
signals are shown below.
.
1H-NMR
3-(4-Bromo-2-methoxyphenyl)-2-cyclohexenone: 1H NMR (CDCl3) ꢀ
2.01–2.20 (2H, m), 2.43–2.51 (2H, m), 2.60–2.70 (2H, m), 3.81 (3H, s),
6.18 (1H, s), 6.84 (1H, d, J ¼ 2 Hz), 7.01–7.20 (2H, m) ppm.
3-(2-Bromo-4-methoxyphenyl)-2-cyclohexenone: 1H NMR (CDCl3) ꢀ
2.01–2.20 (2H, m), 2.43–2.51 (2H, m), 2.60–2.70 (2H, m), 3.83 (3H, s),
6.00 (1H, s), 6.90 (1H, d, J ¼ 2 Hz), 7.01–7.20 (2H, m) ppm.
3-(3-Bromo-4-methoxyphenyl)-2-cyclohexenone
(3Ad):
1H NMR
(CDCl3) ꢀ 2.02–2.24 (2H, m), 2.50 (2H, t, J ¼ 6 Hz), 2.65–2.79 (2H, m),
3.93 (3H, s), 6.35–6.39 (1H, m), 6.93 (1H, d, J ¼ 9 Hz), 7.50 (1H, dd,
J ¼ 2, 9 Hz), 7.75 (1H, d, J ¼ 2 Hz); 13C NMR (CDCl3) ꢀ 22.6, 27.8, 37.1,
56.3, 111.7, 112.1, 124.5, 126.5, 131.2, 132.2, 157.2, 157.6, 199.6 ppm;
IR (KBr) 1653 cmꢀ1
.
3-(4-Methoxyphenyl)-2-cyclopentenone (3Ba):[14] 1H NMR (CDCl3) ꢀ
2.54–2.61 (2H, m), 2.98–3.06 (2H, m), 3.89 (3H, s), 6.49 (1H, t, J ¼ 2 Hz),
6.95 (2H, pseudo dd of AA0BB0 pattern, J ¼ 8, 2 Hz), 7.63 (2H, pseudo
dd of AA0BB0 pattern, J ¼ 8, 2 Hz); 13C NMR (CDCl3) ꢀ 28.4, 35.0,
55.0, 114.0, 125.1, 126.5, 128.3, 161.9, 173.6, 209.1 ppm; IR (KBr)
1672 cmꢀ1
.
1
3-(4-Methylphenyl)-2-cyclopentenone (3Bb): H NMR (CDCl3) ꢀ 2.39
(3H, s), 2.52–2.57 (2H, m), 2.96–3.02 (2H, m), 6.51 (1H, t, J ¼ 2 Hz), 7.23
(2H, pseudo d of AA0BB0 pattern, J ¼ 8 Hz), 7.53 (2H, pseudo d of AA0BB0
pattern, J ¼ 8 Hz); 13C NMR (CDCl3) ꢀ 20.4, 28.5, 35.1, 126.3, 126.8, 129.5,
131.1, 142.9, 174.0, 209.1 ppm; IR (KBr) 1674 cmꢀ1
.
3-(2-Bromo-4-methoxyphenyl)-2-cyclopentenone and 3-(4-Bromo-2-
methoxyphenyl)-2-cyclopentenone (3Bc): These compounds were obtained
1
as an inseparable mixture of regioisomers; IR (KBr) 1672 cmꢀ1. H-NMR
signals are shown below.
3-(2-Bromo-4-methoxyphenyl)-2-cyclopentenone: 1H NMR (CDCl3) ꢀ
2.54–2.64 (2H, m), 2.95–3.05 (2H, m), 3.96 (3H, s), 6.49 (1H, t,
J ¼ 2 Hz), 6.96 (1H, d, J ¼ 8 Hz), 7.62 (1H, dd, J ¼ 8, 2 Hz), 7.86 (1H, d,
J ¼ 2 Hz) ppm.
3-(4-Bromo-2-methoxyphenyl)-2-cyclopentenone: 1H NMR (CDCl3) ꢀ
2.42–2.53 (2H, m), 3.00–3.08 (2H, m), 3.93 (3H, s), 6.87 (1H, t,
J ¼ 2 Hz), 7.12 (1H, d, J ¼ 8 Hz), 7.16 (1H, dd, J ¼ 8, 2 Hz), 7.37 (1H, d,
J ¼ 8 Hz) ppm.
3-(3-Bromo-4-methoxyphenyl)-2-cyclopentenone
(3Bd):
1H NMR
(CDCl3) d 2.54–2.64 (2H, m), 2.95–3.05 (2H, m), 3.96 (3H, s), 6.49
(1H, t, J ¼ 2 Hz), 6.96 (1H, d, J ¼ 8 Hz), 7.62 (1H, dd, J ¼ 8, 2 Hz), 7.86

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d- AND g-KETOCARBOXYLIC ACIDS
3177
(1H, d, J ¼ 2 Hz); 13C NMR (CDCl3) ꢀ 28.6, 35.2, 56.4, 111.7, 112.3, 126.5,
127.5, 128.1, 131.9, 158.1, 171.9, 208.8 ppm; IR (KBr) 1674 cmꢀ1
.
2,4-Bis(3-oxo-1-cyclopentenyl)anisole (30Ba): 1H NMR (CDCl3)
ꢀ
2.44–2.63 (4H, m), 3.00–3.18 (4H, m), 3.95 (3H, s), 6.51 (1H, s), 6.89 (1H,
s), 7.08 (1H, d, J ¼ 8 Hz), 7.75 (1H, d, J ¼ 8 Hz), 7.80 (1H, s); 13C NMR
(CDCl3) ꢀ 28.5, 30.0, 34.0, 35.0, 55.5, 111.2, 123.3, 126.0, 126.5, 123.0, 130.1,
132.0, 160.3, 168.3, 172.0, 208.5, 210.0 ppm; IR (KBr) 1684 cmꢀ1
.
1-(4-Methoxyphenyl)-1,5-hexanedione (4Aa): 1H NMR (CDCl3) ꢀ
1.90–2.09 (2H, m), 2.16 (3H, s), 2.58 (2H, t, J ¼ 7 Hz), 2.97 (2H, t,
J ¼ 7 Hz), 3.88 (3H, s), 6.94 (2H, pseudo dd of AA0BB0 pattern, J ¼ 8,
2 Hz), 7.96 (2H, pseudo dd of AA0BB0 pattern, J ¼ 8, 2 Hz); 13C NMR
(CDCl3) ꢀ 18.3, 29.8, 36.9, 42.5, 55.3, 113.6, 129.8, 130.0, 163.3, 198.1,
208.3 ppm; IR (KBr) 1709, 1669 cmꢀ1
1-(4-Methylphenyl)-1,5-hexanedione (4Ab): 1H NMR (CDCl3)
.
ꢀ
1.90–2.09 (2H, m), 2.16 (3H, s), 2.40 (3H, s), 2.57 (2H, t, J ¼ 7 Hz), 2.99
(2H, t, J ¼ 7 Hz), 7.26 (2H, pseudo dd of AA0BB0 pattern, J ¼ 8, 2 Hz), 7.87
(2H, pseudo dd of AA0BB0 pattern, J ¼ 8, 2 Hz); 13C NMR (CDCl3) ꢀ 21.2,
22.7, 27.9, 37.2, 124.6, 125.9, 129.4, 135.7, 140.3, 159.4, 199.8 ppm; IR (KBr)
1661 cmꢀ1
1-(2-Bromo-4-methoxyphenyl)-1,5-hexanedione
.
(4Ac):
1H NMR
(CDCl3) ꢀ 1.91–2.08 (2H, m), 2.17 (3H, s), 2.55 (2H, t, J ¼ 7 Hz), 2.98
(2H, t, J ¼ 7 Hz), 3.97 (3H, s), 6.86 (1H, dd, J ¼ 3, 9 Hz), 7.13 (1H, d,
J ¼ 3 Hz), 7.49 (1H, d, J ¼ 9 Hz); 13C NMR (CDCl3) ꢀ 18.4, 29.9, 40.8,
42.4, 55.7, 113.1, 119.5, 120.8, 130.8, 132.6, 161.6, 201.5, 208.5 ppm; IR
(KBr) 1713, 1682 cmꢀ1
1-(4-Bromo-2-methoxyphenyl)-1,5-hexanedione
.
(4Ac0):
1H NMR
(CDCl3) ꢀ 1.87–2.04 (2H, m), 2.16 (3H, s), 2.53 (2H, t, J ¼ 7 Hz), 2.98
(2H, t, J ¼ 7 Hz), 3.90 (3H, s), 7.09–7.20 (2H, m), 7.58 (1H, d, J ¼ 8 Hz);
13C NMR (CDCl3) ꢀ 18.2, 29.9, 42.5, 42.7, 55.8, 115.1, 123.9, 126.8, 127.6,
131.5, 158.9, 200.7, 208.6 ppm; IR (KBr) 1713, 1670 cmꢀ1
.
(4Ad):
1-(3-Bromo-4-methoxyphenyl)-1,5-hexanedione
1H NMR
(CDCl3) ꢀ 1.87–2.07 (2H, m), 2.16 (3H, s), 2.57 (2H, t, J ¼ 7 Hz), 2.95
(2H, t, J ¼ 7 Hz), 3.96 (3H, s), 6.95 (1H, d, J ¼ 9 Hz), 7.91 (1H, dd, J ¼ 2,
9 Hz), 8.16 (1H, d, J ¼ 2 Hz); 13C NMR (CDCl3) ꢀ 18.0, 29.7, 42.3, 56.2,
56.3, 110.9, 111.7, 129.0, 130.6, 133.2, 159.3, 197.0, 208.2 ppm; IR (KBr)
1715, 1672 cmꢀ1
.
4-Hydroxy-1,4-bis(4-methoxyphenyl)pentanal (5Ba): 1H NMR (CDCl3)
ꢀ 1.60 (3H, s), 2.20–2.30 (2H, m), 2.82–2.97 (2H, m), 3.80 (3H, s), 3.85
(3H, s), 6.88 (4H, dd, J ¼ 8, 2 Hz), 7.33–7.46 (2H, m), 7.87 (2H, dd,
J ¼ 8, 2 Hz); 13C NMR (CDCl3) ꢀ 31.5, 33.7, 38.2, 55.4, 55.7, 74.0, 113.7,
113.8, 126.3, 130.1, 130.6, 139.8, 158.4, 163.7, 200.0 ppm; IR (KBr)
1674 cmꢀ1
.

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YONEZAWA ET AL.
1,4-Bis(4-methoxyphenyl)-4-penten-1-one (6Ba) and 1,4-bis(4-methoxy-
phenyl)-3-penten-1-one (7Ba): These compounds were obtained as an
inseparable mixture of isomers; IR (KBr) 1676, 1672 cmꢀ1. 1H NMR signals
are shown below.
1,4-Bis(4-methoxyphenyl)-4-penten-1-one (6Ba): 1H NMR (CDCl3) ꢀ
2.83–3.16 (4H, m), 3.81 (3H, s), 3.85 (3H, s), 5.04 (1H, s), 5.25 (1H, s),
6.78–7.02 (4H, m), 7.38 (2H, dd, J ¼ 8, 2 Hz), 7.90 (2H, dd, J ¼ 8, 2 Hz)
ppm.
1,4-Bis(4-methoxyphenyl)-3-penten-1-one (7Ba): 1H NMR (CDCl3) ꢀ
2.11 (3H, d, J ¼ 1 Hz), 3.79 (3H, s), 3.80–3.90 (5H, m), 5.95–6.09
(1H, m), 6.78–7.02 (4H, m), 7.37 (2H, dd, J ¼ 8, 2 Hz), 7.99 (2H, dd,
J ¼ 8, 2 Hz) ppm.
5-(4-Methoxyphenyl)-g-valerolactone (8Ba):[15] 1H NMR (CDCl3) ꢀ
1.68 (3H, s), 2.27–2.75 (4H, m), 3.80 (3H, s), 6.89 (2H, d, J ¼ 8 Hz), 7.28
(2H, d, J ¼ 8 Hz); 13C NMR (CDCl3) ꢀ 28.9, 29.3, 36.0, 55.1, 86.9, 113.7,
125.3, 136.2, 158.9, 176.6 ppm; IR (KBr) 1772 cmꢀ1
.
5-(4-Methylphenyl)-g-valerolactone (8Bb):[16] 1H NMR (CDCl3) ꢀ 1.70
(3H, s), 2.34 (3H, s), 2.34–2.76 (4H, m), 7.17–7.27 (4H, m) ppm; IR (KBr)
1779 cmꢀ1
.
5-(2-Bromo-4-methoxyphenyl)-g-valerolactone and 5-(4-bromo-2-methoxy-
phenyl)-g-valerolactone (8Bc): These compounds were obtained as
1
an inseparable mixture of isomers (19 : 23); IR (KBr) 1778 cmꢀ1. H NMR
signals are shown below.
5-(2-Bromo-4-methoxyphenyl)-g-valerolactone: 1H NMR (CDCl3) ꢀ
1.71 (3H, s), 2.36–2.67 (4H, m), 3.87 (3H, s), 7.05 (1H, d, J ¼ 2 Hz), 7.10
(1H, dd, J ¼ 2, 8 Hz), 7.34 (1H, d, J ¼ 8 Hz) ppm.
5-(4-Bromo-2-methoxyphenyl)-g-valerolactone: 1H NMR (CDCl3) ꢀ
1.85 (3H, s), 2.49–2.85 (4H, m), 3.79 (3H, s), 6.85 (1H, dd, J ¼ 3, 9 Hz),
7.18 (1H, d, J ¼ 3 Hz), 7.57 (1H, d, J ¼ 9 Hz) ppm.
5-(3-Bromo-4-methoxyphenyl)-g-valerolactone
(8Bd):
1H NMR
(CDCl3) ꢀ 1.71 (3H, s), 2.28–2.75 (4H, m), 3.90 (3H, s), 6.89 (1H, d,
J ¼ 8 Hz), 7.30 (1H, dd, J ¼ 2, 8 Hz), 7.55 (1H, d, J ¼ 2 Hz); 13C NMR
(CDCl3) ꢀ 28.9, 29.3, 36.0, 56.2, 86.1, 111.7, 111.7, 124.3, 129.3, 137.7,
155.2, 176.2 ppm; IR (KBr) 1765 cmꢀ1
.
5-Bromo-2,4-bis(5-methyl-2-oxo-5-tetrahydrofuranyl)anisole
(80Bc):
This compound was obtained as an inseparable mixture of
diastereomers. 1H NMR (CDCl3) ꢀ 1.75 (3H, pseudo d, J ¼ 2 Hz), 1.83
(3H, pseudo d, J ¼ 2 Hz), 2.40–2.78 (8H, m), 3.88 (3H, pseudo s), 7.15
(1H, pseudo s), 7.69 (1H, pseudo d, J ¼ 4 Hz); 13C NMR (CDCl3) ꢀ 26.7,
27.0, 28.7, 28.8, 34.0, 34.4, 55.8, 85.7, 85.8, 86.9, 87.0, 118.0, 118.1, 119.2,
123.9, 128.2, 131.5, 131.6, 134.7, 155.2, 155.3, 175.7, 176.2 ppm; IR (KBr)
1772 cmꢀ1
.

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d- AND g-KETOCARBOXYLIC ACIDS
ACKNOWLEDGMENTS
3179
The authors thank Totoku Toryo Co., Ltd. for financial support.
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Received in Japan August 8, 2001