Synthesis of 3-trifluoromethyl- and 3-perfluoroalkyl-substituted 3-aryloxy-and 3-heteroaryloxypropenoic acids and of the cyclization products, 2-trifluoromethyl- and 2-perfluoroalkyl-4H-chromen-4-ones

Article abstract of DOI:10.1055/s-2007-990861

We describe a novel and simple method for the regiospecific synthesis of functionalized trifluoromethyland perfluoroalkyl-containing 4H-chromen-4-ones via the cyclization of substituted 3-aryloxy-3-perfluoroalkylpropenoic acids. The procedures give the fi

Full text of DOI:10.1055/s-2007-990861

3542
PAPER
Synthesis of 3-Trifluoromethyl- and 3-Perfluoroalkyl-Substituted 3-Aryloxy-
and 3-Heteroaryloxypropenoic Acids and of the Cyclization Products,
2-Trifluoromethyl- and 2-Perfluoroalkyl-4H-chromen-4-ones
Synthesis of
3
a
-Perfluoroa
l
lkyl-3-
e
m
enoic
A
cids
a
nd 2-Perflu
E
H
-ch
l
romen-4-onesKharrat, Rouba El Kharrat, Philippe Laurent,* Hubert Blancou
UMR-CNRS 5247 Matériaux Fluorés Synthèses et Applications, Université Montpellier, 2 c.c.1706, Place Eugène Bataillon,
34095 Montpellier Cedex 5, France
Fax +33(4)67631046; E-mail: philippe.laurent@univ-montp2.fr
Received 4 June 2007; revised 27 July 2007
a key step.19 More recently, the synthesis of chromone
Abstract: We describe a novel and simple method for the regio-
derivatives has been accomplished by the palladium-cata-
specific synthesis of functionalized trifluoromethyl- and perfluoro-
lyzed, regiospecific carbonylative annulation of o-io-
alkyl-containing 4H-chromen-4-ones via the cyclization of
dophenyl acetate and acetylenes,20 by an iodine
substituted 3-aryloxy-3-perfluoroalkylpropenoic acids. The proce-
dures give the final products in high yields, without any need for monochloride induced intramolecular cyclization of het-
erosubstituted alkynones,21 and by intramolecular ester
chromatographic purification, and no side products.
carbonyl olefination.22 However, few approaches for the
Key words: aldehydes, oxidations, carboxylic acids, regioselectiv-
ity, heterocycles
synthesis of perfluoroalkylated chromones have been de-
veloped.23 For example, polyfluoroalkylchromones were
prepared by the condensation of ethyl trifluoroacetate
with o-hydroxyacetophenone derivatives using lithium
hydride as a base.24 Most of these methods suffer from
harsh reaction conditions and achieve relatively low
yields.
The development of new and efficient methods for the
synthesis of perfluoroalkyl- and trifluoromethyl-substitut-
ed aromatic and heteroaromatic compounds is of consid-
erable interest,1,2 especially in agrochemical and
pharmaceutical fields.3,4 The introduction of a fluorine
atom or a perfluoroalkyl group onto an organic molecule
confers significant changes in its chemical and physical
properties.1 Moreover, fluorine is often introduced into
biologically active compounds to improve their activity
by enhancing their lipophilicity and changing both their
steric and electronic properties.1,2
Among the various methods, the building-block strategy
is the most attractive.25,26 Several non-regiospecific ap-
proaches to trifluoromethyl-substituted heterocycles are
known; however, high-yielding regiospecific methods for
the synthesis of trifluoromethyl-containing heteroaromat-
ic compounds are still quite limited. In a previous work,27
we reported the synthesis of b-aryloxypropenals 1 bearing
a perfluoroalkyl group. These fluorinated b-phenoxypro-
penals 1 are synthesized in high yields in a two-step reac-
tion that involves the formation of a perfluoroalkylated
gem-iodoacetoxy compound,27 which was previously de-
veloped in our group for the perfluoroalkylation reactions
of organic compounds.28,29 We described the reactivity of
compounds 1 and their application in regiospecific substi-
tution and cyclization reactions.27 Enals 1 appeared to be
a very important synthon for the synthesis of perfluoro-
alkylated compounds. A major advantage of b-phenoxy-
propenals 1 is that they are useful for the preparation of a
broad variety of six- and five-membered heterocyclic
compounds, regiospecifically perfluoroalkylated at the a-
position relative to the heteroatom.27,30
Chromones (chromenones) are a group of naturally occur-
ring compounds that are ubiquitous in nature, especially
in plants.5 Many natural and synthetic chromone deriva-
tives have unique biological and pharmacological activi-
ties,6 acting as protein kinase inhibitors,7 and as cytotoxic
(cancer treatment),8 neuroprotective,9 anti-HIV,10 anti-
allergic,11 anti-inflammatory,12 and antifungal agents,13 as
well being active at lipoxygenase and cyclooxygenase
enzymes.14 Many of these biological actions are attributed
to the ability of chromone analogues to chelate metal
catalysts,15 activate antioxidant enzymes, and inhibit
oxidases.16
There are a number of methods available for preparing
chromones and their analogues.5,17 Chromones have been
prepared on a large scale by the Allan–Robinson synthe-
sis, i.e. by the conversion of o-hydroxyaryl ketones in the
presence of benzoic anhydride and sodium benzoate.18
The most common method, however, involves the Baker–
Venkataraman synthesis; in this case, an internal Claisen
condensation of 1-acetyl-2-aryloxyarenes is employed as
Here, we report a convenient and reliable procedure for
the synthesis of substituted 3-perfluoroalkyl-3-phenoxy-
propenoic acids 2, which by an intramolecular cyclization
reaction give 2-trifluoromethyl- and 2-perfluoroalkyl-4H-
chromen-4-ones in high yields.
The oxidation of enals 1 was accomplished with near total
conversion using the inexpensive reagents sodium chlo-
rite (NaClO2) and hydrogen peroxide (H2O2) under mild
conditions to give corresponding acids 2 (Scheme 1).
SYNTHESIS 2007, No. 22, pp 3542–3552
x
x.
x
x
.
2
0
0
7
Advanced online publication: 29.10.2007
DOI: 10.1055/s-2007-990861; Art ID: Z14207SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
3-Perfluoroalkyl-Substituted 3-Aryloxypropenoic Acids and 2-Perfluoroalkyl-4H-chromen-4-ones
3543
O
In an initial attempt to prepare acids 2, the reactions were
carried out by the addition of 1.0 M aqueous NaClO2 (1.4
equiv) to a solution of aldehyde 1 and 35% H2O2 (1.0
equiv) in aqueous acetonitrile at room temperature, buff-
ered with NaH2PO4 at pH 4.3 (conditions already reported
by Dalcanale and Montanari).32 Because of the very low
solubility of the starting materials in the reported solvent
conditions, we tried adding very small amounts of water
by adding the corresponding amount of NaClO2 dropwise
directly into the reaction mixture (procedure A). Under
these conditions, high yields were obtained (Scheme 1,
Table 1). However, for the reactions using compounds 1c,
1e–h, and 1j–p, the mixture of acetonitrile and water gave
very low yields of the pure desired compounds 2 (<20%)
and large amounts of the starting product were recovered.
To enhance the yields from those oxidation reactions re-
quiring a minimum amount of water, an excess of NaClO2
and H2O2 was needed. Thus, the preferred reaction condi-
tions involved adding the required amounts of NaClO2
and NaH2PO4 to the acetonitrile solution of the corre-
sponding aldehyde and aqueous H2O2 (procedure B). The
desired compounds 2c, 2e–h, and 2j–p were isolated in
very high yields (Scheme 1 and Table 1, entries 3, 5–8,
and 10–16, respectively).
O
NaClO2, H2O2
NaH2PO4, H2O,
MeCN, r.t., 4–8h
R3
R2
X
R3
R2
X
H
OH
O
RF
O
RF
85–98%
R1
R1
1
2a–p
X = C or N
Scheme 1 Synthesis of 3-aryloxy- and 3-heteroaryloxy-3-perfluo-
roalkylpropenoic acids 2a–p
One of the most striking features of this reaction is that the
products are obtained in very high yields. Numerous reac-
tions with various other oxidizing agents were attempted.
However, none of them seemed to be completely satisfac-
tory, the major drawbacks being the high cost of the re-
agents and the low selectivity of the reaction yielding a
complex mixture of products. We decided to proceed with
the use of inexpensive NaClO2 and H2O2 in aqueous ace-
tonitrile at room temperature, buffered with sodium dihy-
drogen phosphate (NaH2PO4).31 The chosen method
allows the facile preparation of a large variety of substitut-
ed 3-aryloxy- and 3-heteroaryloxy-3-perfluoroalkylpro-
penoic acids 2 without the need for any chromatographic
purification (Table 1).
Table 1 Reaction Conditions and Conversions for the Preparation of Acids 2a–p
Entry
Starting
compound
Product
RF
R1
R2
R3
X
Procedure Time
(h)
Conversiona
(%)
1
2
1a
1b
1c
1d
1e
1f
2a
2b
2c
2d
2e
2f
C5F11
C5F11
CF3
H
H
H
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
A
A
B
A
B
B
B
B
A
B
B
B
6
6
4
4
6
6
6
8
4
6
6
8
>98
>98
>98
>98
>98
>98
>98
>95
>98
>98
>98
95
H
H
OMe
OMe
H
3
H
H
4
CF3
H
OMe
H
5
C3F7
C5F11
C3F7
C5F11
C5F11
C5F11
CF3
OMe
H
H
6
H
Me
H
7
1g
1h
1i
2g
2h
2i
H
Me
H
8
H
Cl
9
H
H
NO2
CN
OMe
10
11
12
1j
2j
H
H
1k
1l
2k
2l
Cl
H
H
C5F11
13
14
1m
1n
2m
2n
CF3
CF3
H
H
CH
CH
B
B
8
8
98
95
N
15
16
1o
1p
2o
2p
C3F7
CF3
H
H
H
H
H
H
N
N
B
B
6
6
92
95
a Determined by 19F NMR spectroscopic analysis of the reaction mixture; NMR spectroscopic yields were based on consumed 1 and formed 2.
Synthesis 2007, No. 22, 3542–3552 © Thieme Stuttgart · New York

3544
S. El Kharrat et al.
PAPER
The reaction is quite general and proceeds smoothly to alkyl-containing, trisubstituted olefinic derivatives 1 and
give the corresponding (E)- and (Z)-3-aryloxy- and 3-het- revealed that the 4JCF coupling constant observed between
eroaryloxypropenoic acids 2a–p in synthetically useful the aldehyde carbon atom and the fluorine atom of the CF3
yields and with total regiospecificity. Table 1 summarizes or CF2 group was crucial for determining their configura-
several examples of the application of this method. In tion and conformation in solution. We found that in all
4
most cases, excellent yields are obtained (see also cases the JCF coupling constant was about 8.3 to 9.0 Hz
Table 4, vide infra).
for the E-isomer, and that no coupling was observed for
the Z-isomer.27a The observed 4JCF coupling constant con-
firmed that the more spatially proximate carbon and fluo-
rine atoms assume coupling. Therefore, the 4JCF coupling
constant could be used as a criterion in the determination
of the configurational and conformational isomerism of
fluoroalkyl unsaturated carbonyl compounds.
The structures of the final products 2, obtained as a mix-
ture of the E- and Z-isomers, were established by 1H, 13C,
and 19F NMR spectroscopy and confirmed by high-reso-
lution mass spectrometry (HRMS) and microanalysis (see
Tables 4 and 5). The following general results can be ob-
served in the 1H NMR spectra: The signals for the aromat-
ic protons appeared between 6.4 and 9 ppm for the In the case of 3-trifluoromethyl- or 3-perfluoroalkylpro-
carbocyclic derivatives and between 7.2 and 8.9 ppm for penoic acids 2, the quaternary acidic carbons did not show
the heterocyclic compounds; in addition, the vinylic pro- any defined 4JCF coupling constant, even though the spa-
tons appeared between 5.0 and 6.7 ppm. Broad signals be- tial distance between the carbon and fluorine atoms are
tween 7.7 and 11.3 ppm were observed for the carboxylic supposed to be the same for compounds 1 and 2. These re-
protons. Finally, the infrared spectra showed a large band sults confirm published results33 and could be ascribed to
around 3300 cm–1, characteristic of the O–H stretching the lack of an intermediate proton for the quaternary car-
mode.
bon: the proton plays an important role in the transmission
of the spin information.33 The assignment of the Z and E
configurations of compounds 2 was based on the differ-
ence in the 19F NMR spectroscopic chemical shifts of
CF3(a) or CF2(a) (CF3 or CF2 groups a to the vinylic pro-
ton, =CH) for the two isomers.34,35 The downfield signals
The stereochemistry of acids 2 was confirmed by looking
at the H and 19F NMR spectroscopic coupling constants
1
and chemical shifts of the olefinic protons. In a previous
work,27 we studied the stereochemistry of the perfluoro-
Table 2 Chemical Shifts for the Configurational Assignments of Acids 2a–p
Entry
Compound Ratioa (E/Z) of
starting compound 1
Ratioa (E/Z) of 2 1H NMR d =CH (ppm)b
19F NMR d CF2(a) or CF3(a) (ppm)b
E
Z
E
Z
1
2
2a
64:36
63:37
38:62
48:52
39:61
53:47
12:88
61:39
36.5:63.5
100:0
37:63
63:37
100:0
45:55
40:60
60:40
34:66
5.5
5.4
5.1
5.2
5.2
5.8
5.5
5.4
5.6
5.4
5.0
5.4
5.8
5.0
6.1
5.8
6.3
6.2
6.0
6.1
5.9
6.1
6.3
6.2
–
–112.6
–113.2
–66.7
–66.6
–113.1
–112.5
–113.3
–112.6
–113.0
–112.7
–66.5
–112.5
–66.5
–66.5
–113.8
–68.5
–115.8
–116.1
–70.0
–70.8
–116.7
–115.6
–116.6
–115.7
–
2b
92:8
59:41
65:35
46:54
20:80
58:42
92:8
3
2c
4
2d
5
2e
6
2f
7
2g
8
2h
9
(E)-2i
2j
100:0
60:40
39.5:60.5
100:0
65:35
38:62
88:12
43:57
10
11
12
13
14
15
16
6.2
6.0
–
–115.8
–70.5
–
2k
(E)-2l
2m
2n
6.7
6.4
6.7
6.6
–70.2
–71.3
–116.4
–70.7
2o
2p
a Determined by 19F NMR spectroscopy.
b Spectra performed in CDCl3 for 2a–n and in DMSO-d6 for 2o and 2p.
Synthesis 2007, No. 22, 3542–3552 © Thieme Stuttgart · New York

PAPER
3-Perfluoroalkyl-Substituted 3-Aryloxypropenoic Acids and 2-Perfluoroalkyl-4H-chromen-4-ones
3545
were assigned to the E-isomer, in which CF3(a) or CF2(a) noxypropenoic acids 2. In an initial attempt to prepare 4H-
experiences a great steric interaction with the vicinal car- chromen-4-ones 3, the heating (150 °C) of b-phenoxypro-
boxylic group (Table 2). Further, the signals of the olefin- penoic acids 2 was unsuccessful; none of the desired com-
ic proton when the carboxyl group is in the trans-position pounds were obtained and largely unconverted starting
relative to CF3(a) or CF2(a) were present downfield to material was recovered. However, extension of the reac-
those obtained when the carboxyl group was in the cis-po- tion time resulted in the total decomposition of 2.
sition.34
We then studied the preparation of compounds 3 via a cat-
Most of the reactions gave a mixture of stereoisomers alyzed cyclization: acids 2 were treated with a Lewis acid
(Table 2). However, those reactions starting from stereo- (anhyd AlCl3) in reaction conditions similar to those we
isomers (E)-1 were completely stereoselective and the had previously reported.30 The target products were ob-
products, i.e. 2i and 2l (entries 9 and 12, respectively), tained in poor yields. Finally, we attempted the reaction
were obtained as the single E-isomer. This could be ex- using the dehydrating agent poly(phosphoric acid) (PPA)
plained by the fact that the presence of a highly electron- at high temperatures. After some modifications of the re-
withdrawing group (e.g., NO2 in 2i) or a bulky substituent ported procedures,39 the desired 4H-chromen-4-ones 3
(e.g., naphthyl in 2l) inhibits the isomerization of these were obtained in predominantly very high yields
push–pull derivatives. Previous works report that the (Scheme 2).
push–pull effect has a decisive influence on both the dy-
O
namic behavior and chemical reactivity of this class of
O
PPA
80–180 °C
4–48 h
compounds.27a,36 These olefins are often in an isomeric
equilibrium that can be driven by heat,37 light,37 medium
polarity,37,38 or concentration38 and that is greatly influ-
enced by steric factors and the electronic effects of sub-
stituents.36,38
R3
R2
X
R3
R2
X
OH
– H2O
42–95%
O
RF
O
RF
R1
R1
2
3a–r
Scheme 2 Synthesis of functionalized 2-trifluoromethyl- and 2-per-
fluoroalkyl-4H-chromen-4-ones 3a–r
In the second stage of our investigation, we looked at fa-
vorable conditions for the synthesis of trifluoromethyl- or
perfluoroalkyl-substituted 4H-chromen-4-ones 3 by in-
tramolecular cyclization of the previously obtained b-phe-
Table 3 Reaction Conditions and Conversions for the Preparation of the Cyclization Products 3a–r
Entry
Starting compound Product
Structure
Temp (°C)
Time (h)
4
Conversiona (%)
>98
O
1
2a
2b
2c
3a
3b
3c
3d
3e
80
O
C5F11
O
MeO
MeO
2
3
4
80
80
80
4
4
4
>98
>98
>98
O
O
C5F11
O
O
CF3
2db
MeO
O
CF3
MeO
O
O
O
CF3
5
2e
3f
80
6
96
O
C3F7
OMe
Synthesis 2007, No. 22, 3542–3552 © Thieme Stuttgart · New York

3546
S. El Kharrat et al.
PAPER
Table 3 Reaction Conditions and Conversions for the Preparation of the Cyclization Products 3a–r (continued)
Entry
6
Starting compound Product
Structure
Temp (°C)
80
Time (h)
4
Conversiona (%)
>98
O
Me
2f
3g
3h
3i
O
O
C5F11
7
2gc
80
4
95
Me
O
C3F7
Me
O
O
C3F7
O
Cl
8
9
2h
2i
3j
120
180
180
6
36
36
45
0
O
C5F11
O
O2N
NC
3k
O
C5F11
O
10
2j
3l
0
O
C5F11
O
MeO
11
2k
3m
100
6
88
O
O
CF3
Cl
12
13
14
2l
3n
3o
3p
120
120
150
8
8
75
76
55
O
O
C5F11
2m
2n
O
O
CF3
N
12
O
CF3
15
16
2o
2p
3q
3r
–
–
180
180
48
48
0
0
a Determined by 19F NMR spectroscopic analysis of the reaction mixtures; NMR spectroscopic yields were based on consumed 2 and formed 3.
b The products were formed in a ratio of (3d/3e) 74:26.
c The products were formed in a ratio of (3h/3i) 72:28.
The action of PPA on propenoic acids 2 allowed the prep- any side reactions (Table 3). We optimized the reaction
aration of the corresponding 4H-chromen-4-ones 3, which conditions accordingly: an excess of 85% PPA was added
were the only products formed. The 19F NMR spectra of to 2 and the mixture was heated to the temperature indi-
the crude reaction mixtures indicated that the reaction pre- cated in Table 3. The corresponding 2-trifluoromethyl-
dominantly proceeded in near total conversion without and 2-perfluoroalkyl-4H-chromen-4-ones 3 were isolated
Synthesis 2007, No. 22, 3542–3552 © Thieme Stuttgart · New York

PAPER
3-Perfluoroalkyl-Substituted 3-Aryloxypropenoic Acids and 2-Perfluoroalkyl-4H-chromen-4-ones
3547
in moderate to high yields without any need for chromato- bonyl carbon signal was at 175.5 ppm and that of the
graphic purification (Scheme 2, Table 3; see also Table 4, vinylic carbon a to the trifluoromethyl group was at 150.9
vide infra).
ppm with a coupling constant of 2JCF = 39.2 Hz. The 19F
NMR spectra showed the presence of the CF3 group at
–71.4 ppm.
The reaction proved to be very sensitive to the electronic
features of the starting acids 2. For example, using similar
conditions, the electron-donating substituents (i.e, OMe, In conclusion, we have synthesized a series of new func-
Me, Table 3, entries 2–7) of acids 2b–g promote the reac- tionalized 3-aryloxy- and 3-heteroaryloxy-3-perfluoro-
tion and the substrates cyclize to give the corresponding alkylpropenoic acids 2a–p using a one-step synthesis.
4H-chromen-4-ones 3b–i in high yields. Decreased yields These derivatives could be easily converted into 2-trifluo-
were observed for compounds containing moderately romethyl- and 2-perfluoroalkyl-4H-chromen-4-ones 3a–j
electron-withdrawing groups (e.g., Cl, entry 8). Unfortu- and 3m–p possessing a variety of functionalities.
nately, our attempts to perform the reaction of b-phenoxy-
From a practical synthetic standpoint, our method is very
convenient for the regiospecific synthesis of 4H-
chromen-4-ones bearing a trifluoromethyl or perfluoro-
propenoic acids substituted on the benzene ring by strong
electron-withdrawing groups, such as nitro and cyano
groups (entries 9 and 10, respectively), failed to give the
alkyl group. The reactions have the advantage of requiring
desired 4H-chromen-4-ones. In these cases, using the re-
only short reaction times to obtain the products in very
action conditions with a higher temperature of 180 °C re-
high yields and with no need for chromatographic purifi-
sulted in the decomposition of the starting substrates. For
cation.
the reactions of the acids substituted with a pyridyl ring
(i.e, 2o and 2p, entries 15 and 16, respectively), no cy-
All solvents were distilled before use. The reactions were per-
clization products were obtained; this could be explained
formed in oven-dried glassware, and their progress was monitored
by the low reactivity of pyridine toward electrophilic aro-
1
by TLC using silica gel plates and by 19F NMR spectroscopy. H,
matic substitution.40
13C, and 19F NMR spectra were recorded in CDCl3 or DMSO-d6 on
a 300 MHz Bruker AC300 spectrometer using TMS as an internal
The reaction was also sensitive to the structural features of
2. Moderate yields were obtained in the cases of 3n–p that
could be explained by the steric hindrance of the naphthyl
1
standard for the H and 13C NMR spectra, and CFCl3 for the 19F
NMR spectra. Mass spectrometry and HRMS were carried out on a
Jeol SX102 instrument and were recorded using FAB technique. All
and quinolinyl groups (Table 3, entries 12–14). More-
reagents were of commercial purity; 35% H2O2 soln was supplied
over, 19F NMR spectroscopy of each of the reaction mix-
by Prolabo, NaH2PO4 was obtained from J. T. Baker, and NaClO2
tures showed only one sharp singlet, which was assigned
to the perfluoroalkyl group of the corresponding
chromone (vide infra). The NMR coupling patterns of 3n–
p showed unambiguously that cyclization occurs only at
the 1-position of the naphthyl group of acids 2l and 2m,
and at the 5-position of the quinolinyl group of acid 2n,
yielding 3-perfluoroalkylated 1H-benzo[f]chromen-1-
ones 3n and 3o and 3-trifluoromethyl-1H-pyrano[3,2-
f]quinolin-1-one (3p), respectively.
was supplied by Fluka Chemika.
(E)- and (Z)-3-Aryloxy-3-perfluoroalkylpropenoic Acids 2a, 2b,
2d, and 2i (Procedure A); General Procedure
To a mixture of b-phenoxypropenal 1 in MeCN (5 mL per 1 g of 1)
and 35% aq H2O2 (1.0 equiv) was cautiously added 0.66 M aq
NaH2PO4 (ca. 0.5 mL per 1 g of 1) dropwise to limit the precipita-
tion of the starting product 1. The resulting mixture was stirred for
a few min in a water bath. Then, NaClO2 (1.2 equiv) was added. Ox-
ygen evolved from the solution and a deep yellow mixture was ob-
tained. After ca. 10 min, the mixture changed very slowly to a clear
yellow. Stirring was continued for 2 h. The reaction was monitored
by TLC and 19F NMR spectroscopy. The CF3 or CF2 signals of com-
pound 1 faded as the reaction evolved, and new peaks appeared cor-
responding to the CF3 or CF2 signals of product 2. If TLC revealed
that small amounts of the starting enal 1 were still present, excess
NaClO2 (1 equiv) and H2O2 were added, and the mixture was stirred
for a further 2 h. Under these conditions, complete consumption of
the starting product 1 was observed, and the 3-aryloxy-3-perfluoro-
alkylpropenoic acid 2 was the only product formed in the crude
mixture. On completion of the reaction, the mixture was diluted,
acidified with 10% aq HCl, and extracted with Et2O (5 ×). The or-
ganic layers were washed with H2O and dried (Na2SO4). The ob-
tained pure compound 2 was isolated by direct crystallization on
Previous reports on the electrophilic aromatic substitu-
tions (alkylation or acylation)41,42 of naphthalene or quin-
oline derivatives describe the reactions occurring at the 5-
position of quinoline for the latter, and that generally the
1-acylated or 1-alkylated naphthalenes are the major
products of the former.42
The meta-substituted phenoxypropenoic acids 2d and 2g
(m-OMe and m-Me, Table 3, entries 4 and 7, respectively)
both reacted to afford two regioisomers. The ratio of these
isomers was deduced from the 19F NMR spectra of each of
the reaction mixtures.
The structures of the isolated chromones 3a–j and 3m–p removal of solvent as colorless needles.
are all consistent with their 1H, 13C, and 19F NMR spectra
(E)- and (Z)-3-Aryloxy- and 3-Heteroaryloxy-3-perfluoroalkyl-
propenoic Acids 2c, 2e–h, and 2j–p (Procedure B); General Pro-
cedure
Procedure B differs from procedure A in that the only aqueous so-
lution added was the 35% H2O2 and the corresponding amounts of
NaH2PO4 were added directly to the reaction media. The final prod-
ucts were isolated by direct crystallization on removal of solvent as
colorless needles.
(see Table 6), and are in full agreement with the previous-
ly reported data.24 The HRMS and elemental analysis data
provide confirmation of the chromone structures. As an
example, characteristic features for the chromone 3c were
a singlet at 6.6 ppm for the vinylic proton in the 1H NMR
spectrum and signals between 7.2 and 7.5 ppm for the pro-
tons of the aromatic ring. In the 13C NMR spectra, the car-
Synthesis 2007, No. 22, 3542–3552 © Thieme Stuttgart · New York

3548
S. El Kharrat et al.
PAPER
Functionalized 2-Trifluoromethyl- and 2-Perfluoroalkyl-4H-
chromen-4-ones 3a–j and 3m–p
To propenoic acid 2 were added a few drops of 85% PPA (excess).
The sticky mixture was then heated to the appropriate temperature
as shown in Table 3 (between 80 and 180 °C) and stirred. The reac-
tion was monitored by TLC and 19F NMR spectroscopy. On com-
pletion of the reaction, most of the starting material 2 had
disappeared, as determined by TLC. The mixture was cooled to r.t.,
diluted cautiously with H2O, and extracted with Et2O (3 ×). The or-
ganic layers were collated, washed with H2O, and dried (anhyd
Na2SO4). Removal of solvent afforded the corresponding crude
chromones 3a–j and 3m–p in an acceptable NMR spectroscopic pu-
rity.
Table 4 Physical Data of Compounds 2a–p, 3a–j, and 3m–p
Com-
pound (%)
Yielda Molecular
MS (70eV): HRMS (70eV):
Elemental analysis
formula
m/z [M + H]+ m/z [M + H]+
Calcd
Found
Calcd
Found
2a
2b
2c
2d
2e
2f
95
95
94
92
95
95
95
94
92
95
98
88
90
88
85
86
85
95
95
68
23
88
92
65
25
42
81
70
70
53
C14H7F11O3
C15H9F11O4
C11H9F3O4
C11H9F3O4
C13H9F7O4
C15H9F11O3
C13H9F7O3
C14H6ClF11O3
C14H6F11NO5
C15H6F11NO3
C11H8ClF3O4
C18H9F11O3
C14H9F3O3
C13H8F3NO3
C11H6F7NO3
C9H6F3NO3
C14H5F11O2
C15H7F11O3
C11H7F3O3
C11H7F3O3
C11H7F3O3
C13H7F7O3
C15H7F11O2
C13H7F7O2
C13H7F7O2
C14H4ClF11O2
C11H6ClF3O3
C18H7F11O2
C14H7F3O2
C13H6F3NO2
433
463
263
263
363
447
347
466
478
458
297
483
283
284
334
234
415
445
245
245
245
345
429
329
329
448
279
465
265
266
433.0298
463.0403
263.0531
263.0531
363.0467
447.0454
347.0518
466.9908
478.0149
458.0250
297.0141
483.0454
283.0582
284.0535
334.0314
234.0378
415.0192
445.0298
245.0426
245.0426
245.0426
345.0362
429.0349
329.0413
329.0413
448.9802
279.0036
465.0349
265.0476
266.0429
433.0295
463.0406
263.0535
263.0533
363.0469
447.0457
347.0520
466.9910
478.0152
458.0258
297.0143
483.0456
283.0580
284.0537
334.0311
234.0380
415.0195
445.0211
245.0430
245.0428
245.0430
345.0365
429.0352
329.0415
329.0413
448.9800
279.0033
465.0351
265.0478
266.0428
C, 38.91; H, 1.63; O, 11.11
C, 38.98; H, 1.96; O, 13.85
C, 50.39; H, 3.46; O, 24.41
C, 50.39; H, 3.46; O, 24.41
C, 43.11; H, 2.50; O, 17.67
C, 40.38; H, 2.03; O, 10.76
C, 45.10; H, 2.62; O, 13.86
C, 36.03; H, 1.30; O, 10.29
C, 35.24; H, 1.27; O, 16.76
C, 39.41; H, 1.32; O, 10.50
C, 44.54; H, 2.72; O, 21.58
C, 44.83; H, 1.88; O, 9.95
C, 59.58; H, 3.21; O, 17.01
C, 55.13; H, 2.85; O, 16.95
C, 39.66; H, 1.82; O, 14.41
C, 46.36; H, 2.59; O, 20.59
C, 40.60; H, 1.22; O, 7.73
C, 40.56; H, 1.59; O, 10.81
C, 54.11; H, 2.89; O, 19.66
C, 54.11; H, 2.89; O, 19.66
C, 54.11; H, 2.89; O, 19.66
C, 45.37; H, 2.05; O, 13.95
C, 42.07; H, 1.65; O, 7.47
C, 47.58; H, 2.15; O, 9.75
C, 47.58; H, 2.15; O, 9.75
C, 37.48; H, 0.90; O, 7.13
C, 47.42; H, 2.17; O, 17.23
C, 46.57; H, 1.52; O, 6.89
C, 63.65; H, 2.67; O, 12.11
C, 58.88; H, 2.28; O, 12.07
C, 38.95; H, 1.63; O, 11.15
C, 38.96; H, 1.95; O, 13.80
C, 50.41; H, 3.46; O, 24.38
C, 50.40; H, 3.45; O, 24.42
C, 43.13; H, 2.51; O, 17.66
C, 40.40; H, 2.02; O, 10.72
C, 45.11; H, 2.62; O, 13.83
C, 36.05; H, 1.29; O, 10.26
C, 35.22; H, 1.27; O, 16.77
C, 39.43; H, 1.30; O, 10.50
C, 44.56; H, 2.70; O, 21.55
C, 44.85; H, 1.88; O, 9.93
C, 59.56; H, 3.22; O, 17.00
C, 55.15; H, 2.86; O, 16.93
C, 39.68; H, 1.82; O, 14.39
C, 46.38; H, 2.60; O, 20.55
C, 40.62; H, 1.22; O, 7.70
C, 40.58; H, 1.61; O, 10.80
C, 54.15; H, 2.88; O, 19.63
C, 54.12; H, 2.89; O, 19.64
C, 54.10; H, 2.88; O, 19.68
C, 45.38; H, 2.06; O, 13.98
C, 42.10; H, 1.66; O, 7.54
C, 47.60; H, 2.16; O, 9.74
C, 47.59; H, 2.16; O, 9.73
C, 37.49; H, 0.89; O, 7.11
C, 47.45; H, 2.19; O, 17.21
C, 46.59; H, 1.52; O, 6.90
C, 63.67; H, 2.67; O, 12.09
C, 58.90; H, 2.30; O, 12.04
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3m
3n
3o
3p
a Yield of the isolated compound.
Synthesis 2007, No. 22, 3542–3552 © Thieme Stuttgart · New York

PAPER
3-Perfluoroalkyl-Substituted 3-Aryloxypropenoic Acids and 2-Perfluoroalkyl-4H-chromen-4-ones
3549
Table 5 1H, 13C, and 19F NMR Spectroscopic Data of Compounds 2a–pa
Productb 1H NMR d (ppm), J 13C NMR d (ppm), JCF
19F NMR d (ppm)
2a
2b
2c
2d
5.5 [s, 1 H, =CH (E)], 6.3 [s, 1 H, 104.5, 115.9, 120.6, 121.0, 123.4, 125.8, 126.7, 129.4,
=CH (Z)], 7.0–7.5 (m, 5 H), 10.5
(br s, 1 H, COOH)
–80.9 (s, 3 F), –112.6 [s, 2 F, (E)
63%], –115.8 [s, 2 F, (Z) 37%],
–120.0 (s, 2 F), –122.0 (m, 2 F),
–126.2 (s, 2 F)
129.5, 130.5, 150.7, 151.4 (t, 2JCF = 25.7 Hz, C–CF2),
152.3, 154.1 (t, 2JCF = 27.7 Hz, C–CF2), 156.4, 166.9,
168.7, 169.8
3.8 (s, 3 H, OMe), 3.9 (s, 3 H,
55.5, 55.7, 103.6, 110.3 [t, 3JCF = 5.2 Hz, =CH (Z)],
–81.0 (s, 3 F), –113.2 [s, 2 F, (E)
38%], –116.1 [s, 2 F, (Z) 62%],
OMe), 5.4 [s, 1 H, =CH (E)], 6.2 [s, 114.5, 115.4, 117.2, 121.8, 145.4, 150.2, 152.0 (t, 2JCF
=
1 H, =CH (Z)], 6.8–7.0 (m, 4 H),
24.9 Hz, C–CF2), 155.0 (t, 2JCF = 27.9 Hz, C–CF2), 155.9, –121.0 (s, 2 F), –123.0 (m, 2 F),
8.5 (br s, 1 H, COOH)
157.9, 166.9, 168.7
–127.0 (s, 2 F)
3.7 (s, 3 H, OMe), 3.8 (s, 3 H,
55.5, 55.6, 101.1, 109.4, 114.4, 114.5, 115.4, 117.4 (q,
–66.7 [s, 3 F, (E) 48%], –70.0 [s, 3
2
OMe), 5.1 [s, 1 H, =CH (E)], 6.0 [s, JCF = 30.9 Hz, C–CF3), 117.9, 121.1 (q, 2JCF = 37.7 Hz, F, (Z) 52%]
1 H, =CH (Z)], 6.6–7.0 (m, 4 H),
8.8 (br s, 1 H, COOH)
C–CF3), 121.7, 122.2, 145.5, 149.7, 156.1, 157.9, 167.6,
168.9
3.6 (s, 3 H, OMe), 3.7 (s, 3 H,
OMe), 5.2 [s, 1 H, =CH (E)], 6.1 [s, JCF = 3.77 Hz, =CH (Z)], 111.6, 112.5, 112.6, 129.8,
1 H, =CH (Z)], 6.4–6.7 (m, 3 H),
7.0–7.3 (m, 1 H), 10.2 (br s, 1 H,
COOH)
55.7, 56.1, 101.5, 102.8, 106.7, 107.6, 109.7, 110.0 [q,
–66.6 [s, 3 F, (E) 39%], –70.8 [s, 3
F, (Z) 61%]
3
130.9, 150.7 (q, 2JCF = 35.4 Hz, C–CF3), 151.6, 153.1,
156.4 (q, 2JCF = 38.4 Hz, C–CF3), 157.1, 161.3, 168.7,
170.5
2e
2f
3.7 (s, 3 H, OMe), 3.8 (s, 3 H,
56.3, 58.3, 111.7, 112.1, 114.0, 121.6, 122.3, 126.7,
–80.5 (s, 3 F), –113.1 [s, 2 F, (E)
53%], –116.7 [s, 2 F, (Z) 47%],
–125.0 [s, 2 F, (E)], –126.2 [s, 2 F,
(Z)]
OMe), 5.2 [s, 1 H, =CH (E)], 5.9 [s, 141.8, 142.8 (t, 2JCF = 27.1 Hz, C–CF2), 151.2, 170.7,
1 H, =CH (Z)], 6.7–7.2 (m, 4 H),
10.2 (br s, 1 H, COOH)
172.1
1.2 (s, 3 H, Me), 2.2 (s, 3 H, Me), 20.2, 29.6, 103.8, 111.4, 115.7, 120.2, 130.0, 130.9,
5.8 [s, 1 H, =CH (E)], 6.1 [s, 1 H, 133.5, 136.7, 150.0, 151.0, 151.8 (q, 2JCF = 24.9 Hz,
=CH (Z)], 6.7–7.1 (m, 4 H), 9.8 (br C–CF2), 154.8, 167.0, 168.9
s, 1 H, COOH)
–80.9 (s, 3 F), –112.5 [s, 2 F, (E)
12%], –115.6 [s, 2 F, (Z) 88%],
–121.9 (s, 2 F), –122.6 (m, 2 F),
–126.2 (s, 2 F)
2g
2h
2.3 (s, 3 H, Me), 2.4 (s, 3 H, Me), 20.9, 21.2, 104.2, 112.5, 116.5, 117.7, 121.3, 122.1,
–80.5 (s, 3 F), –113.3 [s, 2 F, (E)
5.5 [s, 1 H, =CH (E)], 6.3 [s, 1 H, 124.7, 124.8, 127.5, 129.1, 129.2, 139.7, 150.6, 151.3 (t, 61%], –116.6 [s, 2 F, (Z) 39%],
=CH (Z)], 6.8–7.4 (m, 4 H), 10.9
2JCF = 25.6 Hz, C–CF2), 152.2, 154.2 (t, 2JCF = 27.9 Hz, –125.0 [s, 2 F, (E)], –126.5 [s, 2 F,
(br s, 1 H, COOH)
C–CF2), 156.3, 168.7, 169.9
(Z)]
5.4 (s, 1 H, =CH (E)], 6.2 (s, 1 H, 105.0, 112.3, 116.6, 116.9, 119.2, 122.2, 122.9, 129.3,
–80.9 (s, 3 F), –112.6 [s, 2 F, (E)
=CH (Z)], 6.7–7.4 (m, 4 H), 10.0
(br s, 1 H, COOH)
130.4, 132.4, 149.0, 150.9, 151.2 (t, 2JCF = 24.8 Hz, C– 36.5%], –115.7 [s, 2 F, (Z) 63.5%],
CF2), 151.6, 154.1 (t, 2JCF = 28.1 Hz, C–CF2), 155.6,
–121.9 (s, 2 F), –122.6 (m, 2 F),
–126.2 (s, 2 F)
168.9, 169.9
(E)-2i
5.6 [s, 1 H, =CH (E)], 7.1 (d, J = 9.1 110.6, 114.0, 120.1, 126.2, 139.2, 145.3, 149.3 (t, 2JCF
=
–80.9 (s, 3 F), –113.0 [s, 2 F, (E)
100%], –121.0 (s, 2 F), –122.8 (s, 2
F), –126.2 (s, 2 F)
Hz, 2 H, Ar), 7.7 (br s, 1 H,
28.6 Hz, C–CF2), 158.0, 167.5
COOH), 8.2 (d, J = 9.1 Hz, 2 H, Ar)
2j
5.4 [s, 1 H, =CH (E)], 6.2 [s, 1 H, 105.0, 111.8, 115.2, 116.6, 116.9, 117.7, 122.1, 122.2,
–80.9 (s, 3 F), –112.7 [s, 2 F, (E)
=CH (Z)], 6.7–7.4 (m, 4 H), 9.9 (br 127.6, 128.6, 129.1, 129.3, 129.6, 130.5, 149.1, 151.6 (t, 37%], –115.8 [s, 2 F, (Z) 63%],
s, 1 H, COOH)
2JCF = 25.1 Hz, C–CF2), 153.6, 154.1 (t, 2JCF = 28.2 Hz, –120.7 (s, 2 F), –122.6 (m, 2 F),
C–CF2), 154.9, 166.3, 168.7, 169.4 –126.1 (s, 2 F)
2k
3.6 (s, 3 H, OMe), 3.7 (s, 3 H,
55.7, 55.8, 100.7, 107.0 [q, 3JCF = 3 Hz, =CH (Z)], 113.1, –66.5 [s, 3 F, (E) 63%], –70.5 [s, 3
OMe), 5.0 [s, 1 H, =CH (E)], 6.0 [s, 113.4, 115.3, 115.6, 116.2, 116.9, 118.6, 120.5, 123.2,
1 H, =CH (Z)], 6.6–7.0 (m, 3 H),
9.8 (br s, 1 H, COOH)
F, (Z) 37%]
125.1, 126.9, 145.2, 150.9 (q, 2JCF = 35.4 Hz, C–CF3),
155.6 (q, 2JCF = 38.4 Hz, C–CF3), 156.6, 157.7, 167.3,
168.6
(E)-2l
5.4 [s, 1 H, =CH (E)], 6.6–7.9 (m, 104.7, 114.0, 118.3, 119.6, 124.3, 126.4, 127.2, 127.6,
7 H), 10.1 (br s, 1 H, COOH)
–80.7 (s, 3 F), –112.5 [s, 2 F, (E)
130.9, 131.7, 139.2, 149.7, 154.3 (t, 2JCF = 28.6 Hz, C– 100%], –120.5 (s, 2 F), –122.5 (s, 2
CF2), 167.9
F), –126.0 (s, 2 F)
2m
5.8 [s, 1 H, =CH (E)], 6.7 [s, 1 H, 107.1, 107.3, 109.4, 113.7 [q, 3JCF = 3.1 Hz, =CH (Z)],
=CH (Z)], 7.2–9.0 (m, 7 H), 9.5 (br 116.0, 117.6, 120.1, 120.7, 120.9, 121.0, 121.5, 122.0,
–66.5 [s, 3 F, (E) 45%], –70.2 [s, 3
F, (Z) 55%]
s, 1 H, COOH)
124.0, 127.0, 128.9, 129.9, 130.8, 133.4, 134.6, 134.7,
144.5, 147.1, 148.3, 148.8, 149.4, 152.8 (q, 2JCF = 34.2
Hz, C–CF3), 168.1, 176.6
Synthesis 2007, No. 22, 3542–3552 © Thieme Stuttgart · New York

3550
S. El Kharrat et al.
PAPER
Table 5 1H, 13C, and 19F NMR Spectroscopic Data of Compounds 2a–pa (continued)
Productb 1H NMR d (ppm), J 13C NMR d (ppm), JCF
19F NMR d (ppm)
2n
5.0 [s, 1 H, =CH (E)], 6.4 [s, 1 H, 110.5, 118.4, 121.5, 125.1, 128.5, 130.0, 131.7, 136.1,
=CH (Z)], 7.2–8.9 (m, 6 H), 10.1
–66.5 [s, 3 F, (E) 40%], –71.3 [s, 3
F, (Z) 60%]
136.4, 145.3, 148.2, 148.6, 149.6, 150.9 (q, 2JCF = 35.6
(br s, 1 H, COOH)
Hz, C–CF3), 154.9, 165.0, 165.8, 169.3
2o
6.1 [s, 1 H, =CH (E)], 6.7 [s, 1 H, 111.0, 117.0, 122.4, 124.2, 125.0, 127.6, 138.0, 141.8,
–80.6 (s, 3 F), –113.8 [s, 2 F, (E)
60%], –116.4 [s, 2 F, (Z) 40%],
–125.4 (s, 2 F, (E)], –126.3 (s, 2 F,
(Z)]
=CH (Z)], 7.3–7.7 (m, 2 H), 8.3–
8.6 (m, 2 H), 11.3 (br s, 1 H,
COOH)
144.5, 145.1 (t, 2JCF = 25.6 Hz, C–CF2), 145.8 (t, 2JCF
=
27.1 Hz, C–CF2), 147.0, 149.7, 152.7, 162.6, 163.7
2p
5.8 [s, 1 H, =CH (E)], 6.6 [s, 1 H, 108.2, 114.6 [q, 3JCF = 3 Hz, =CH (Z)], 117.6, 122.3,
–68.5 [s, 3 F, (E) 34%], –70.7 [s, 3
=CH (Z)], 7.2–7.8 (m, 2 H), 8.3–
8.6 (m, 2 H), 10.0 (br s, 1 H,
COOH)
124.7, 127.9, 130.4, 138.0, 138.2, 141.9, 145.0, 149.3 (q, F, (Z) 66%]
2JCF = 36.1 Hz, C–CF3), 153.1 (q, 2JCF = 39.2 Hz, C–
CF3), 162.6, 163.7, 166.2, 169.2
a At 300 MHz, in CDCl3 for 2a–n and in DMSO-d6 for 2o and 2p.
b For both the E- and Z-isomers, unless indicated.
Table 6 1H, 13C, and 19F NMR Spectroscopic Data of Compounds 3a–j and 3m–pa
Product 1H NMR d (ppm), J
13C NMR d (ppm), JCF
19F NMR d (ppm)b
C–CF2 or C=O CF3 CF2(a) CF2(b,g) CF2(d)
R
=CH
Ar
C–CF3 (2JCF
)
3a
3b
3c
–
6.7 (s) 7.3–8.2 (m, 4 H)
112.9, 118.3, 123.9, 125.9,
126.4, 134.9, 155.8
152.7
(28.6 Hz)
176.4 –80.9 –117.9 –122.4, –126.2
–122.7
3.9 (s, 3 6.8 (s) 7.3–7.6 (m, 3 H)
H, OMe)
56.0, 104.9, 111.9, 119.8,
124.7, 125.1, 150.6, 157.8
152.3
(29.4 Hz)
176.4 –80.7 –117.6 –122.4, –126.1
–122.6
3.8 (s, 3 6.6 (s) 7.2–7.5 (m, 3 H)
H, OMe)
54.5, 103.5, 108.2, 113.9,
118.4, 123.3, 123.7, 144.3,
156.4
150.9
(39.2 Hz)
175.5 –71.4
175.0 –71.6
175.4 –71.8
–
–
–
–
–
–
–
–
3d
3e
3f
3.8 (s, 3 6.7 (s) 6.8–7.7 (m, 3 H)
H, OMe)
55.0, 99.4, 106.4, 109.0,
109.6, 115.8, 126.3, 156.5,
164.0
151.1
(38.4 Hz)
–
3.9 (s, 3 6.6 (s) 6.8–7.6 (m, 3 H)
H, OMe)
55.9, 99.5, 106.6, 109.6,
111.0, 116.8, 126.4, 156.6,
164.1
150.6
(38.6 Hz)
–
3.9 (s, 3 6.7 (s) 7.1–7.7 (m, 3 H)
H, OMe)
56.5, 112.7, 115.7, 116.3,
126.2, 127.6, 146.4, 149.1,
163.6
152.4
(29.4 Hz)
176.5 –80.4 –118.6
–126.5
3g
2.4 (s, 3 6.7 (s) 6.8–7.6 (m, 3 H)
H, Me)
30.1, 112.6, 115.2, 118.0,
120.3, 125.2, 136.8, 150.1,
154.2
152.6
(29.4 Hz)
176.9 –80.8 –117.8 –122.4, –126.2
–122.7
3h
3i
2.4 (s, 3 6.7 (s) 7.1–7.3 (m, 2 H), 8.0 21.8, 112.8, 118.0, 121.7,
152.2
(30.1 Hz)
176.4 –80.4 –118.8
172.3 –80.8 –114.1
–
–
–126.6
–125.9
H, Me)
(d, J = 8.1 Hz, 1 H)
125.7, 127.9, 146.7, 155.9
2.6 (s, 3 5.6 (s) 6.7–7.1 (m, 3 H)
H, Me)
22.3, 110.5, 113.8, 121.5,
122.4, 126.8, 141.6, 151.2
144.1
(28.3 Hz)
3j
–
5.6 (s) 6.9–8.2 (m, 3 H)
103.0, 109.0, 118.3, 120.8,
127.7, 129.4, 133.5, 159.4
151.9
(30.2 Hz)
173.5 –80.8 –117.8 –122.3, –126.0
–122.6
3m
3.8 (s, 3 6.7 (s) 6.8 (s, 1 H), 7.1
H, OMe) (s, 1 H)
55.1, 104.0, 108.1, 113.7,
119.2, 123.4, 123.7, 144.3,
157.1
160.2
(27.3 Hz)
175.3 –71.4
–
–
–
Synthesis 2007, No. 22, 3542–3552 © Thieme Stuttgart · New York

PAPER
3-Perfluoroalkyl-Substituted 3-Aryloxypropenoic Acids and 2-Perfluoroalkyl-4H-chromen-4-ones
3551
Table 6 1H, 13C, and 19F NMR Spectroscopic Data of Compounds 3a–j and 3m–pa (continued)
Product 1H NMR d (ppm), J 13C NMR d (ppm), JCF
19F NMR d (ppm)b
R
=CH
Ar
C–CF2 or C=O CF3
CF2(a) CF2(b,g) CF2(d)
C–CF3 (2JCF
)
3n
3o
3p
–
6.9 (s) 7.4–7.5 (m, 1 H), 7.6 104.5, 114.0, 118.0, 119.1,
153.6
(28.9 Hz)
175.1 –80.6 –117.6 –122.4, –126.0
–122.5
(t, J = 7.8 Hz, 1 H),
7.8 (t, J = 7.9 Hz, 1
H), 7.9 (d, J = 7.8 Hz,
1 H), 8.1 (d, J = 9.1
Hz, 1 H), 9.9 (d, J =
8.4 Hz, 1 H)
124.1, 126.4, 127.3, 131.1,
134.0, 139.3, 150.0
–
–
6.8 (s) 7.4–7.6 (m, 1 H), 7.6 104.0, 114.2, 118.1, 119.5,
153.2
(30.1 Hz)
176.0 –71.6
–
–
–
–
–
–
(t, J = 7.7 Hz, 1 H),
7.7 (t, J = 7.9 Hz, 1
H), 8 (d, J = 7.8 Hz, 1
H), 8.2 (d, J = 9 Hz, 1
H), 10 (d, J = 8.5 Hz,
1 H)
124.4, 126.3, 127.1, 132.1,
134.2, 140.1, 150.6
6.9 (s) 7.6 (dd, J = 8.7, 4.2
Hz, 1 H), 7.8 (d, J =
9.3 Hz, 1 H), 8.4 (d,
J = 9.4 Hz, 1 H), 8.9–
9.0 (m, 1 H), 10.2 (d,
J = 8.6 Hz, 1 H)
105.2, 114.0, 119.2, 119.6,
125.1, 127.0, 127.1, 133.3,
134.2, 139.6, 150.6
155.2
(29.1 Hz)
174.1 –71.1
a At 300 MHz, in CDCl3.
b Refer to, for example, CF2(a)-CF2(b)-CF2(g)-CF2(d)-CF3.
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Synthesis 2007, No. 22, 3542–3552 © Thieme Stuttgart · New York