Highly selective trifluoroacetic ester/ketone metathesis: An efficient approach to trifluoromethyl ketones and esters

Article abstract of DOI:10.1016/j.tet.2014.05.017

A highly selective and atom efficient 'trifluoroacetic ester/ketone metathesis' has been sincerely witnessed. Enolizable alkyl (at least two non-hydrogen atoms) aryl ketones were found to react readily with ethyl trifluoroacetate under the promotion of NaH to afford trifluoroacetic ester/ketone exchange products, trifluoromethyl ketones (TFMKs), and aromatic acid esters, which were quite different from the general Claisen condensation products, 1,3-diketones. The outcome of the reaction between ketone and ethyl trifluoroacetate is strongly related to the structures of substrates, the steric congestion caused by alkyl group is in favor of the C-C bond cleavage. DFT investigation further disclosed that the metathesis reaction was a kinetically favored pathway. Using only a slight excess of cheap trifluoromethylation reagent, simple operation and mild conditions make it a practical method for preparation of TFMKs on large scale, as well as a new choice of converting aryl alkyl ketones to aromatic acid esters.

Full text of DOI:10.1016/j.tet.2014.05.017

Accepted Manuscript
Highly selective trifluoroacetic ester/ketone metathesis: an efficient approach to
trifluoromethyl ketones and esters
Yuhan Zhou , Dongmei Yang , Gen Luo , Yilong Zhao , Yi Luo , Na Xue , Jingping Qu
PII:
S0040-4020(14)00677-2
10.1016/j.tet.2014.05.017
TET 25566
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 12 March 2014
Revised Date: 25 April 2014
Accepted Date: 5 May 2014
Please cite this article as: Zhou Y, Yang D, Luo G, Zhao Y, Luo Y, Xue N, Qu J, Highly selective
trifluoroacetic ester/ketone metathesis: an efficient approach to trifluoromethyl ketones and esters,
Tetrahedron (2014), doi: 10.1016/j.tet.2014.05.017.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Highly selective trifluoroacetic ester/ketone
metathesis: an efficient approach to
trifluoromethyl ketones and esters
Leave this area blank for abstract info.
Yuhan Zhou, Dongmei Yang, Gen Luo, Yilong Zhao, Yi Luo, Na Xue, Jingping Qu
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University
of Technology, Dalian 116024, P.R. China

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Highly selective trifluoroacetic ester/ketone metathesis: an efficient approach to
trifluoromethyl ketones and esters
Yuhan Zhou,∗ Dongmei Yang, Gen Luo, Yilong Zhao, Yi Luo,* Na Xue, Jingping Qu
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian 116024, P.R. China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A highly selective and atom efficient “trifluoroacetic ester/ketone metathesis” has been sincerely
witnessed. Enolizable alkyl (at least two non-hydrogen atoms) aryl ketones were found to react
readily with ethyl trifluoroacetate under the promotion of NaH to afford trifluoroacetic
ester/ketone exchange products, trifluoromethyl ketones (TFMKs) and aromatic acid esters,
which were quite different from the general Claisen condensation products, 1,3-diketones. The
outcome of the reaction between ketone and ethyl trifluoroacetate is strongly related to the
structures of substrates, the steric congestion caused by alkyl group is in favor of the C-C bond
cleavage. DFT investigation further disclosed that the metathesis reaction was a kinetically
favored pathway. Using only a slight excess of cheap trifluoromethylation reagent, simple
operation and mild conditions make it a practical method for preparation of TFMKs on large
scale, as well as a new choice of converting aryl alkyl ketones to aromatic acid esters.
Available online
Keywords:
Metathesis
Trifluoromethyl ketones
Esters
DFT
2
009 Elsevier Ltd. All rights reserved.
1
. Introduction
from the general Claisen condensation giving 1,3-dicarbonyl
products. Although the formation of TFMK and benzoate as
byproducts in the synthesis of 1,3-diketones containing
perfluoroalkyl groups in the presence of MeONa had been
Formation and cleavage of C-C bond are among the
fundamental issues in organic chemistry. As a tool of molecular
skeleton construction, classic C-C bond formation reactions, for
example Friedel–Crafts reaction, Diels–Alder reaction, Claisen
condensation, aldol reaction, Henry reaction, Suzuki coupling,
Negishi coupling and Heck reaction etc., are of crucial
importance in organic synthesis. On the other hand, C-C bond
cleavage has received increasing attention as a useful method for
skeleton diversification in recent years. Both stoichiometric and
catalytic reactions can perform C-C bond cleavage, and
compared to most heavy metal catalyzed procedures, metal-free
processes are less poisonous and more environmentally friendly.
13
mentioned in 1953, only few cases with poor to medium yield
were given and no further information of this reaction was
disclosed, let alone its application in organic synthesis. In
contrast, replacing MeONa with NaH in our protocol increased
the reactivity and selectivity dramatically, resulting in TFMKs
and benzoates as exclusive products. We are aware that it is a
highly selective “trifluoroacetic ester/ketone metathesis”, which
will supply us an efficient method to prepare trifluoromethyl
ketones and aromatic esters.
1
2
3
Some success has been achieved in transformation with strategies
4
5
of retro-reactions, including retro-alkylations, retro-arylations,
6
7
8
retro-alkynylation, retro-aldol reactions, deallylation, retro-
Claisen condensation and so on. Furthermore, the procedure
9
involving both C-C bond formation and cleavage that is
10
represented by Olefin metathesis has become one of the most
11
powerful tools for the synthesis of complex products. Despite
countless achievements, the highly effective green methodology
for C-C bond formation and cleavage is always desired.
14
TFMKs are valuable species as potential drugs and synthons
1
5
for the synthesis of other trifluoromethyl-containing materials.
Thus, synthesis of TFMKs is an important task in current organic
fluorine chemistry. Among numerous approaches to TFMKs,
the treatment of trifluoroacetic acid derivatives with
Recently, we reported an efficient method for the preparation
of trifluoromethyl ketones (TFMKs) via the reaction between
1
6-25
12
alkyl aryl ketones and ethyl trifluoroacetate. The reaction
afforded TFMKs and ethyl benzoate, which was quite different
—
——
∗
+
Corresponding author. Tel.: +86-411-84986186; fax: +86-411-84986186; e-mail: zhouyh@dl.cn (Y. Zhou); Tel.: +86-411-84986192; fax:
86-411-84986192; e-mail: luoyi@dlut.edu.cn (Y. Luo)

2
Tetrahedron
16
organometallic reagent like Grignard reagent
A
or
C
al
C
ky
E
l l
P
ith
T
iu
E
m,
D
MAprac
N
U
tica
S
l
C
s
R
yn
I
thesis of TFMKs with high yield from cheap
P
T
reactions of carboxylic acid chlorides with pyridine and
trifluoroacetic anhydride and oxidation of trifluoromethyl
carbinols are widely used. The recent development included
nucleophilic trifluoromethylation of Weinreb amides with
TMSCF3, oxidation of trifluoromethyl carbinols with Oxone
reagents is highly desirable.
19
21
Esters are ubiquitous important species in organic chemistry.
Although esters can be prepared via condensation of alcohols and
carboxylic acids, acyl halides, or acid anhydrides, acid catalyzed
addition reaction of carboxylic acids with alkenes, etc., new
methods to obtain esters are always welcomed by researchers.
Formation of esters through a C-C bond cleavage reaction
provides a new method to convert ketones to esters, and has
17b
21b
21c
or recyclable oxoammonium salt,
carboxylic acids to
trifluoroacetylation/decarboxylation, and ring opening of alkyl
-siloxycyclopropanecarboxylates by triethylamine
conversion of enolizable
26
TFMKs
via
enediolate
24
2
27
25
aroused much interest nowadays.
trihydrofluoride. Although synthetic methods of TFMKs have
been widely developed, the preparation of TFMKs is still
hindered by using of a large excess (3 - 6 equiv) of
trifluoromethyl agents or expensive reagents. Therefore, a
In this context, we describe our further study on the highly
selective “trifluoroacetic ester/ketone metathesis”, including
substrate scope, mechanism and its application in synthesis of
TFMKs and esters.
Table 1
a
Reactions of different ketones and esters
b
Product
Entry
Ketone
1
Ester
2
Time/h
3
Yield/%
4
Yield/%
1
2
CF
3
COOEt 2a
3
1
PhCOOEt
4a 98
1
aa
3a 96
2a
4a 97
c
1
ab
3b 89
O
3
4
Ph
2a
2a
5
2
Ph
1bc
4b 94
3
c 95
1
ad
5a 98
5b 98
5c 95
O
O
5
6
7
2a
2a
2a
2
2
CF3
1
b
1
c
2
1
d
5d 97
8
9
2a
2a
10
nr
1
ae
O
10
24
nr
nr
Ph
Ph
1af
1
1
0
1
1ab
1ab
CCl
3
COOEt
2b
d
0.5
2c
5
e
93
1
1
2
3
1aa
1aa
3
4
4a 94
2
d
3ad 99
3ae 98
4a 93
2
e
a
b
c
d
Reaction conditions: 1 (5.0 mmol), 2 (6.0 mmol), NaH (6.0 mmol), THF (10 mL), reflux under argon.
Isolated yield.
19
The yield of 3b was determined by F NMR with trifluoromethyl benzene as internal standard.
Room temperature.
trifluoroacetic esters is well known and widely used in the
synthesis of trifluoromethyl containing 1,3-diketones. Yet some
aryl alkyl ketones tended to give exchange products with
trifluoroacetic esters under the similar basic conditions as our
previous study. It indicated that the reaction was strongly related
2
. Results and Discussion
2
.1. Substrate scope of the reaction
Claisen condensation of aryl methyl ketones and

3
to the substrates. To better understand the rel
A
ati
C
on
C
sh
E
ip
P
b
T
etw
E
e
D
en MAsu
N
bs
U
tra
S
te
C
s a
R
ndIP
the reaction pathway, DFT calculations were
T
the reaction and substrates, under the optimized conditions of this
performed.
12
reaction established in our lab, the reactions of different ketones
and perfluorocarboxylates in the presence of NaH were explored
The enolization of ketone by NaH has been generally accepted
and no calculation was therefore carried out for this step. Starting
with the enol salt B, the reaction pathway for ester/ketone
metathesis has been calculated (Figure 1). In optimized B, the Na
(
Table 1).
Enolizable long chain alkyl (at least two non-hydrogen atoms)
3
aryl ketones reacted smoothly with ethyl trifluoroacetate, via
trifluoroacetic ester/ketone metathesis” pathway (Table 1, entry
and 2) giving TFMKs and benzoates as exclusive products,
while acetophenone (Table 1, entry 4) and some cycloketones
Table 1, entry 5-7) did not experience C-C bond cleavage and
atom adopts a η -coordination manner to interact with the O and
“
1
C atoms of carbonyl group and the α–C atom. 2a could interact
with B to form an adduct C in which the Na atom coordinates to
the carbonyl oxygen atoms. Then, the complex C goes through a
C−C bond formation transition state (TSCD) with an energy
barrier of 13.3 kcal/mol to yield complex D. From the complex
D, there are two possible reaction pathways, viz., OEt group
transfer via TSDE or H transfer via TS . In the former case, the
OEt group transfers from C (CF ) atom to C (Ph) atom leading
to an intermediate E. Subsequently, the E easily undergoes a
C−C bond breaking TS, TS , yielding the complex F composed
of PhCOOEt (4a) and 3g-Na. The further hydrolysis of F should
give the experimentally observed product. The transformation of
D to F is feasible because of its significantly exergonic feature
and moderate energy barrier (14.9 kcal/mol). In the latter case, a
hydrogen transfer event occurs via TSDH with an energy barrier
of 19.6 kcal/mol to give complex H with EtOH and enolate of
1,3-diketones moieties. However, such a hydrogen transfer
process is kinetically less favorable (19.6 kca/mol) than the OEt
group transfer (an energy barrier of 14.9 kcal/mol). In view of
this situation and the thermodynamic stability of H, the F could
be a kinetically controlled product. These results should add
better understanding to the experimental observation that the
reaction of 1ag with 2a yields trifluoromethyl ketone rather than
(
gave common Claisen condensation products (1,3-diketones).
Benzyl cinnamon ketone can also undergo “trifluoroacetic
ester/ketone metathesis” (Table 1, entry 3). Not surprisingly,
unenolizable ketones, like diphenyl ketone and 1,3-diphenyl-1-
propen-3-one (Table 1, entry 8 and 9), did not show any reaction
under such conditions. Ethyl trichloroacetate did not react with 1-
phenyl propan-1-one even under the condition of reflux for 24 h
DH
sp3
sp2
3
EF
(
Table 1, entry 10). 2,2,2-Trifluoroethyl trifluoroacetate reacted
with 1-phenylpropan-1-one and gave Claisen condensation
product (1,3-diketone) after stirring at room temperature for 0.5 h
(
Table 1, entry 11). The results are consistent with the previous
28
report of Danheiser. Finally, the reaction was successfully
extended to perfluorocarboxylic esters, and thus perfluoroalkyl
ketones could be prepared in high yield (Table 1, entry 12 and
1
3).
2
.2. Mechanism study
Our above study indicated that the outcome of the reaction
between aryl alkyl ketone and ethyl trifluoroacetate was strongly
related to the substrate. To access the whole conversion process
and understand the relationship between the structures of
1
,3-diketone.
Figure 1. Computed energy profile (energies in kcal/mol) for the reaction of 2a with enolate sodium B derived from 1ag and NaH. The free energies and
enthalpies (in parentheses) in solution are given. The energy shown is the relative energy including that of all species involved in the corresponding reaction.
According to the DFT calculations, the transformation of E to
F should be very easy for the small relative energy barrier of 2.3
kcal/mol (Figure 1). This suggested that the C-C bond cleavage
occurred shortly after the ethoxy anion transferred in basic
condition. This result was also supported by the following
experiment. In the reaction of 2-phenylacetophenone with ethyl
was also involved in the Reeves’s procedure. In that procedure,
the decarboxylation occurs on neutralization course during work
up.
trifluoroacetate, upon the consumption of the substrate, MeSO Cl
2
was added instead of acid, a trifluoromethyl substituted enol ester
6
1
was isolated in 90% yield as colorless needle crystal (Scheme
). This is different from the procedure of converting enolizable
Scheme 1. Formation of enol ester 6
24
To rationalize the proposed mechanism shown in Figure 1, the
reaction of acetophenone (1ad) with 2a has been also computed,
carboxylic acids to TFMKs reported by Reeves. A C-C bond
cleavage step, decarboxylation with release of carbon dioxide,

4
Tetrahedron
and the result is shown in Figure 2. As expec
A
ted
C
, t
C
he
E
c
P
om
T
p
E
ut
D
ed MAas
NU
a
p
S
ro
C
du
R
ct
I
.
P
The current mechanism also suggests that the
T
energy profile for the 1ad case (Figure 2) is similar to that shown
in Figure 1, except for the relative energy barrier of OEt group
transfer and H transfer. In the 1ad case, the H atom transfer is
kinetically favorable than that of OEt group transfer (10.1 vs.
intermediate D plays an important role in the reaction. For
validity, we extend the analysis of the important steps, viz., OEt
group transfer and H transfer steps, to other substrates (27
examples). As shown in Table 1S in SI, all of the cases are
consistent with the experimental observations.
1
5.7 kcal/mol). This is in good agreement with the experiment
results that the reaction of 1ad with 2a provided the 1,3-diketone
O
Na
O
O
CF3
O
NaH
H2
ONa
B
(
)
O
O
CF3
HCl
F3C OEt
Ph
Na
Ph
Ph
Ph
O
NaCl
EtOH
Na
OEt O
O
Na
O
Na
O
O
OEt
O
sol ( sol)
kcal/mol
EtO
Ph
H
CF3
O
Ph
EtO
H H
Ph
CF3
CF3
CF3
H
H
H
Ph
H
H
16.3
(2.6)
14.0
(2.1)
1
0.7
1
0.9
8.7
(
-1.0)
(-1.1)
6
.1
(
-3.5)
Na
(
-4.6)
0.6
-12.2)
15.7 (14.8)
0
.0
O
O
1
0.1 (11.2)
(
(
0.0)
Na
Ph OEt
CF3
H H
O
O
Na
O
EtO
Ph
-6.6
Na
H
O
Na
EtO O
O
EtO CF3
H
H
CF3
(-16.6)
EtOH
Na
H H
Ph
Ph
O
-27.6
(-36.1)
H
CF3
O
O
Ph
H
H
Ph
CF3
H
Figure 2. Computed energy profile (energies in kcal/mol) for the reaction of 2a with enolate sodium B derived from 1ad and NaH. The free energies and
enthalpies (in parentheses) in solution are given. The energy shown is the relative energy including that of all species involved in the corresponding reaction.
The formation of trifluoroacetic ester/ketone exchange
products, trifluoromethyl ketones and aromatic acid esters, was
postulated to be a tandem Claisen condensation and retro-Claisen
C-C bond cleavage reaction in our previous report. However,
through all the experiments, no 1,3-dicarbonyl intermediate was
found either by GC or TLC in the process of the metathesis
reaction of alkyl aryl ketone and ethyl trifluoroacetate mediated
by NaH. Thus, according to the results of DFT study and
experimental facts, we propose that the mechanism of this
2.3. Applications in synthesis
The reaction was successfully applied to the synthesis of
various TFMKs. Enolizable ketones with different functional
groups were explored successfully. In our previous report, we
have confirmed that the functional groups such as phenyl, chloro,
alkoxy, aryoxy, ester, and heterocycles are tolerant well in the
12
12
reaction. Herein, we further disclose that the substrates with
cyano, arylthio and aliphatic acid ester can also give the desired
products in good yield (Scheme 3). 3i was got as its carbonyl
“
trifluoroacetic ester/ketone metathesis” is more likely as
hydrate (3i-H O) after aqueous workup.
2
follows. The enolized aryl alky ketone attacks the carbonyl group
in ethyl trifluoroacetate to give addition intermediate, which is
the same as traditional Claisen condensation. Then, the ethoxy
anion transfers from the carbon atom connecting with
trifluoromethyl group to the carbonyl group which connected
with aryl group, results in the subsequent C-C bond cleavage and
gives benzoate and TFMK immediately (Scheme 2). That means
no 1,3-dicarbonyl intermediate nor its enolate was formed in the
process of the metathesis reaction. The second part distinguishes
this “trifluoroacetic ester/ketone metathesis” from the Claisen
condensation, which undergoes a H transfer and EtOH releasing
pathway to give 1,3-dicarbonyl product. In other words, the
reaction between alky aryl ketone and ethyl trifluoroacetate have
two possible pathways, traditional Claisen condensation or
Scheme 3. Synthesis of TFMKs via “trifluoroacetic ester/ketone metathesis”.
Reaction conditions: 1 (5.0 mmol), ethyl trifluoroacetate (6.0 mmol), NaH
(6.0 mmol, power), THF (10 mL), reflux under argon. Isolated yield after
column chromatography.
In addition, the conversion of aryl alkyl ketones to aromatic
acid esters via “trifluoroacetic ester/ketone metathesis” was
explored. 1-Aryl-1-pentanones was chosen as the substrates, and
for one of the products, 1,1,1-trifluorohexan-2-one (3g), is
volatile and can be easily removed in vacuum, with aromatic acid
esters left as the single product without further purification.
Functional groups such as halogen, alkyl, alkoxy, ester, amine,
cyano, and heterocycles are all tolerated, and the products were
isolated in 85-98% yield (Scheme 4).
“
trifluoroacetic ester/ketone metathesis”. The outcome is strongly
related to the structures of substrates, the steric congestion caused
by the alkyl group is in favor of the metathesis pathway.
Scheme 2. Proposed mechanism for the metathesis reaction.

5
O
O
1. NaH
. H+
O
O
ACCEPTED MATh
N
e
U
tw
S
o
C
va
R
lu
I
able products, TFMKs and aromatic acid esters,
P
T
+
+
Ar
F3C OR
F3C
O
Ar OR
2
were both isolated by distillation (Table 2). That proved the high
atom economy of the reaction. And most products were isolated
with good yield in decagram scale, which indicates the procedure
is viable for industry requirements.
O
O
O
OEt
Cl
, reflux, 3 h, 94%
O
OMe
F
Br
OEt
OEt
I
, rt, 3 h, 95%
,
rt, 3 h, 96%
,
rt, 3 h, 97%
3. Conclusion
O
O
O
OEt
OEt
Me
EtO
OEt
In conclusion, highly selective “trifluoroacetic ester/ketone
metathesis” was studied. Enolizable aryl alkyl (at least two non-
hydrogen atoms) ketones react smoothly with ethyl
trifluoroacetate, giving TFMKs and aromatic acid esters as the
exclusive products. The outcome of the reaction between aryl
alkyl ketone and ethyl trifluoroacetate is strongly related to the
structures of substrates, the steric congestion caused by the alkyl
group is in favor of the C-C bond cleavage. DFT investigation
further disclosed that the C-C bond cleavage was a kinetically
favored pathway for alkyl aryl ketones. The reaction affords a
highly efficient, operationally simple approach to trifluoromethyl
ketones and a new choice of converting alkyl aryl ketones to
aromatic acid esters.
OEt
MeO
O
rt, 3 h, 96%
, rt, 3 h, 98%
, rt, 4 h, 95%
, rt, 4 h, 97%
O
S
O
O
O
OEt
OEt
OEt
N
,
reflux, 2 h, 94%
, reflux, 2 h, 90%
, reflux, 2.5 h, 92%
O
O
O
OEt
OEt
Fe OEt
NC
Me N
2
,
reflux, 5 h, 92%
, reflux, 6 h, 85%
, rt, 3 h, 91%
Scheme 4. Synthesis of esters via “trifluoroacetic ester/ketone metathesis”.
Reaction conditions: 1 (5.0 mmol), 2 (6.0 mmol), NaH (6.0 mmol, power),
THF (10 mL) under argon. Isolated yield. Methyl trifluoroacetate was used
for the preparation of 4f, for others, ethyl trifluoroacetate were used.
Furthermore, this “trifluoroacetic ester/ketone metathesis” is
powerful for large scale preparation of TFMKs and aromatic acid
esters. To confirm this, the reaction was done in decagram scale.
Table 2
a
Separation of trifluoroacetic ester/ketone exchange products by distillation
Entry
Substrate
3
Yield (%)
4 Yield (%)
O
b
1
4a 94
4k 81
Ph
1ag
3
g 78
2
3
4
5
1
kk
3k 73
3l 82
4l 79
4m 75
4e 77
1
ll
3
m 74
1
mm
1
en
3n 87
a
Reaction conditions: 1 (50 mmol), ethyl trifluoroacetate (60 mmol), NaH (60 mmol, power), THF (100 mL) under argon.
b
In 30 g scale.
acetophenone and aldehydes, reduced by H /Pd-C according the
literature.
4
. Experimental Section
2
29
4
.1. General
4
.2. General procedure for “trifluoroacetic ester/ketone
Unless otherwise noted, all reactions were performed under
metathesis” and the preparation of TFMKs
argon atmosphere in oven-dried glassware with magnetic stirring.
Anhydrous solvents were freshly distilled from sodium and
benzophenone or calcium hydride. Column chromatograph was
performed on silica gel (100~200 mesh) using petroleum
ether/EtOAc (100:0 - 70:30) as an eluant. NMR spectra were
Under Ar atmosphere in a dry Schlenk tube, a mixture of NaH
6.0 mmol) and trifluoroacetate (6.0 mmol) was stirred in THF (5
(
mL) at room temperature for 10 min. To this mixture enolizable
o
ketones (5.0 mmol) in THF (5 mL) was added dropwise at 0 C
6
1
under Ar atmosphere. After stirring for 2 - 6 h at reaction
recorded in CDCl , d -DMSO or CD OD at 400 MHz ( H), 100
3
3
o
13
19
temperature, the reaction solution was cooled to 0 C again and
MHz ( C), and 376 MHz ( F) with Bruker Avance III-400 or
Varian VA400 spectrometers. Chemical shift (δ) are reported in
parts per million (ppm) relative to the residual solvent signal.
High-resolution mass spectra (HRMS) were performed on a GCT
mass spectrometer (EI) or a Q-TOF mass spectrometer in
quenched with five drops of 1 mol/L HCl. After stirring for
additional 15 min, the mixture was neutralized with saturated
NaHCO solution. After usual workup, the residue was purified
3
by chromatography on silica gel to afford the trifluoromethyl
alkyl ketone products.
+
positive electrospray ionization (ESI ) mode (Micromass Corp.,
3
0
UK). GC-MS spectra were performed on HP6890/GC5973 MSD
analyzer. Melting points were taken on a Micro melting point
apparatus (X-6, Beijing Tech Instrument Co. Ltd) and were
uncorrected. Enolizable ketones were purchased from
commercial sources or prepared from corresponding
4
1
7
2
.2.1 1,1,1-Trifluoro-3-(4-methylphenylthio)propan-2-one (3h).
1
0.5 g, 90% yield; colorless oil; H NMR (400 MHz, CDCl ): δ =
3
.29 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 3.79 (s, 2H),
13
.89 (s, 3H); C NMR (100 MHz, CDCl ): δ = 185.1 (q, J = 34.4
3
Hz), 139.0, 132.8, 129.9, 128.6, 115.6 (q, J = 290.8 Hz), 39.8,

6
Tetrahedron
19
2
1.0; F NMR (376 MHz, CDCl ): δ = -76.5
A
; H
C
R
C
M
E
S
P
(E
T
I)
E
m
D
/z MAfo
N
r R
U
O
S
C
C
S,
R
S
I
EM. We also thank Prof. Baomin Wang and Dr.
P
T
3
calcd. for C H F OS: 234.0326, found: 234.0327.
Yuming Song for valuable discussions.
10
9 3
4
.2.2 1,1,1-Trifluoro-3-(4-cyanophenoxy) propan-2,2-diol (3i-
o 1
References and notes
H O). 1.07 g, 87% yield; white solid, m.p.: 83-84 C; H NMR
2
(
400 MHz, CD OD): δ = 7.65 (d, J = 8.8 Hz, 2H), 7.10 (d, J = 8.8
3
13
1. (a) Jun, C.-H. Chem. Soc. Rev. 2004, 33, 610; (b) Ruhland, K. Eur.
J. Org. Chem. 2012, 2683; (c) Korotvicka, A.; Necas, D.; Kotora,
M. Curr. Org. Chem. 2012, 16, 1170; (d) Liu, H.; Jiang, X. Synlett
2013, 24, 1311.
Hz, 2H), 4.24 (AB q, J = 11.2 Hz, 2H); C NMR (100 MHz,
CDCl ): δ = 163.0, 135.2, 124.3 (q, J = 287.0 Hz), 119.9, 116.7,
1
δ = -83.07; HRMS (EI) m/z: calcd. for C H F NO : 247.0456,
found: 247.0459.
3
19
05.5, 95.7 (q, J = 30.5 Hz), 67.9; F NMR (376 MHz, CDCl3):
2
.
(a) Joanna, W.; Frank, G. Nature Chem. 2013, 369; (b) Egami, H.;
Shimizu, R.; Kawamura, S.; Sodeoka, M. Angew. Chem. Int. Ed.
10
8
3
3
2
013, 52, 4000; (c) Xi, S.; Yang, L.; Hu, L.; Kang, C.; Zhi, Q.;
31
Zhang, J. Chem. Eur. J. 2012, 18, 16214; (d) Park, Y.; Park, J.;
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4
.2.3 Methyl 7,7,7-trifluoro-6-oxo-Heptanoate (3j). 1.05 g, 90%
1
yield; colorless oil; H NMR (400 MHz, CDCl ): δ = 3.68 (s,
3
3
H), 2.78 (t, J = 6.8 Hz, 2H), 2.36 (t, J = 7.2 Hz, 2H), 1.68 - 1.71
13
(m, 4H); C NMR (100 MHz, CDCl ): δ = 191.1 (q, J = 34.6
3
Hz), 173.5, 115.5 (q, J = 290.1 Hz), 51.4, 35.9, 33.4, 23.8, 21.7;
19
F NMR (376 MHz, CDCl ): δ = -80.2; MS (EI) m/z 181, 153,
3
1
43, 125, 115, 112, 101, 74.
3
4
.
.
Characterization data of other TFMKs and aromatic acid
esters are provided in the Supporting Information, available
online.
4
.3. Synthesis of 3,3,3-trifluoro-1-phenylprop-1-en-2-yl
(a) Kuninobu, Y.; Kawata, A.; Takai, K. J. Am. Chem. Soc. 2006,
methanesulfonate (6)
1
28, 11368; (b) Kuninobu, Y.; Kawata, A.; Nishi, M.; Yudha, S.
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10222.
Under argon atmosphere in a dry Schlenk tube, a mixture of
NaH (6.0 mmol) and trifluoroacetate (6.0 mmol) was stirred in
THF (5 mL) at room temperature for 10 min. To this mixture 1,2-
diphenylacetone (5.0 mmol) in THF (5 mL) was added dropwise
5
.
o
at 0 C under Ar atmosphere. After reflux for 3 h, the reaction
o
6. (a) Grenning, A. J.; Tunge, J. A. J. Am. Chem. Soc. 2011, 133,
4785; (b) Yamamoto, E.; Gokuden, D.; Nagai, A.; Kamachi, T.
mixture was cooled to 0 C again and MeSO Cl (6.0 mmol) was
2
1
added dropwise. After stirring for additional 15 min, the mixture
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was neutralized with saturated NaHCO solution. After usual
3
7
.
workup, the residue was purified by chromatography on silica gel
to afford the trifluoromethyl substituted enol ester 6 as colorless
o
1
needle crystal (1.19 g, 90%). m.p. 90 - 91 C; H NMR (400 MHz,
(c) Pan, B.; Wang, C.; Wang, D.; Wu, F.; Wan, B. Chem.
CDCl ): δ = 7.95 - 7.97 (m, 2H), 7.70 - 7.72 (m, 3H), 7.26 (s,
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3
13
1
3
H), 3.41 (s, 3H); C NMR (100 MHz, CDCl ): δ = 132.9 (q, J =
3
0.5 Hz), 130.6, 130.1, 130.0, 129.0, 126.5, 120.2 (q, J = 271.5
19
Hz), 39.99; F NMR (376 MHz, CDCl ): δ = -69.0; HRMS (EI)
3
m/z: calcd. for C H F O S: 266.0224, found: 266.0229.
10
9
3
3
8
9
.
.
4
.4. Computational Details
32
Gaussian 09 program was used to fully optimize all the
33
structures reported in this paper at the B3LYP level theory
together with the basis set 6-31G(d) for all atoms. Each
optimized structure was analyzed by harmonic vibrational
frequencies obtained at the same level and characterized as a
minimum (NImag= 0) or a transition state (NImag= 1). To obtain
more reliable relative energies, a larger basis set and solvation
effect were considered. The single-point energies in THF
solution (used in experiment) were calculated on the basis of gas-
phase optimized geometry by using the SMD implicit solvation
4
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model (with UFF atomic radii ) at the B3LYP/6-311+G(d,p)
level. The energies in solution include corresponding energy
corrections obtained from gas-phase calculations. In this paper,
the free energies in solvation are used to analyze the reaction
mechanism.
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The authors gratefully acknowledge the financial support of
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ACCEPTED MANUSCRIPT
Highly selective trifluoroacetic ester/ketone metathesis: an efficient
approach to trifluoromethyl ketones and esters
Yuhan Zhou*, Dongmei Yang, Gen Luo, Yilong Zhao, Yi Luo*, Na Xue, Jingping Qu
(
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology,
Dalian University of Technology, Dalian 116024, P.R. China)
*
E-mail: zhouyh@dl.cn (Y. Zhou); luoyi@dlut.edu.cn (Y. Luo).
Supporting Information
Contents
1
2
3
4
5
. The calculated energy barrier of the substances
. Characterization data for TFMKs
. Characterization data for aromatic acid esters
. References
S2
S2
S5
S7
S9
1
13
19
. H, C and F NMR spectra of the products
S1

ACCEPTED MANUSCRIPT
1
. The calculated energy barriers of the substances
To understand the relationship between the reaction outcome and the substances, the
energy barriers of the important steps, viz., OEt group transfer via TSDE and H transfer via
TS , were calculated for other substrates (Table S1). All of the cases are consistent with the
DH
experimental observations.
Table S1 The calculated energy barriers for OEt group transfer (TSDE) and H transfer (TSDH
)
O
O
O
O
O
O
1
. NaH
+
R
+
R
Ar
CF3
2. H+
F3C
Cl
Ar OEt
Ar
F3C OEt
R
1
2a
3
4
5
O
O
O
O
O
O
R
Ph
O
Ph
Ph
Ar
Ph
Ph
1
Me
Cl
TSDE 14.9 (13.8)
TSDH 19.5 (20.4)
TSDE 13.7 (12.6)
TSDH 15.6 (16.3)
TSDE 13.9 (13.2)
TSDH 20.6 (21.1)
TSDE G ( H)
TSDH G ( H)
TSDE 15.8 (14.9)
TSDH 20.6 (21.0)
TSDE 15.8 (14.4)
TSDH 21.4 (22.1)
O
O
O
OMe
O
O
O
S
OPh
Ph
Ph
Ph
Ph
Ph
Ph
OMe
TSDE 15.6 (13.9)
TSDE 16.1 (15.0)
TSDH 20.5 (21.5)
TSDE 16.5 (16.7)
TSDH 22.0 (23.9)
TSDE 15.2 (13.6)
TS
TSDH
TSDE 15.6 (14.4)
TSDH 19.6 (20.2)
DE 14.0 (13.2)
TSDH 23.2 (23.2) TSDH 21.4 (21.5)
20.7 (21.2)
O
O
O
O
O
S
O
Ph
Ph
Ph
Ph
TS
Me
TSDE 14.9 (13.3)
TSDH 22.4 (23.2)
COOMe
15.7 (14.8)
TSDE 17.3 (18.6) TSDE 14.8 (15.7)
TSDH 8.3 (9.9)
DE
TSDE 14.8 (13.5)
TSDH 19.9 (20.1)
TSDE 15.8 (14.4)
TSDH 21.9 (22.2)
TSDH 10.1 (11.2)
TSDH 9.2 (10.2)
O
O
O
S
O
O
O
O
EtO
MeO
Cl
Me
O
TSDE 16.5 (15.4)
TSDH 20.8 (21.3)
TSDE 13.6 (12.6)
TSDH 19.8 (20.4)
TSDE 10.7 (10.2)
TSDH 12.3 (13.6)
TSDE 15.9 (14.5)
TSDH 20.8 (20.7)
TSDE 18.3 (17.7)
TSDH 22.6 (22.4)
TSDE 17.2 (15.8)
TSDH 23.3 (22.7)
O
O
O
O
F
NC
Br
N
TSDE 12.7 (11.6)
TSDE 14.6 (13.5)
TSDH 20.3 (20.8)
TSDE 14.2 (13.0)
TSDH 20.4 (20.7)
TSDE 13.5 (12.4)
TSDH 19.9 (20.4)
TSDH 20.1 (20.4)
2
. Characterization data for other TFMKs
1
1
,1,1-Trifluoro-4-phenylbutan-2-one (3a)
1
13
Colorless oil; H NMR (400 MHz, CDCl ): δ = 7.11 - 7.25 (m, 5H), 2.7 - 3.1 (m, 4H); C
3
3
NMR (100 MHz, CDCl ): δ = 197.3 (q, J = 35.0 Hz), 139.5, 128.6, 128.3, 126.7, 115.7 (q, J =
19
2
91.0 Hz), 38.0, 28.3; F NMR (376 MHz, CDCl ): δ = -79.8; HRMS (EI) m/z calcd. for
3
C
10
H
9
F
3
O: 202.0605, found: 202.0606.
2
1
,1,1-Trifluoro-butan-2-one (3b)
S2

ACCEPTED MANUSCRIPT
1
Colorless oil; H NMR (400 MHz, CDCl
3
): δ = 2.77 (q, J = 7.2 Hz, 2H), 1.18 (t, J = 7.2 Hz,
1
3
3
6
H)； C NMR (100 MHz, CDCl
3
): δ = 192.3 (q, J = 35.0 Hz), 115.8 (q, J = 289.9 Hz), 30.1,
1
9
.4; F NMR (376 MHz, CDCl ): δ = -80.1; MS (EI) m/z 97, 69, 57.
3
3
1
,1,1-Trifluoro-3-phenylpropan-2-one (3c)
1
13
Colorless oil; H NMR (400 MHz, CDCl
3
): δ = 7.23 - 7.33 (m, 5H), 3.35 (s, 2H); C NMR
): δ = 188.3 (q, J = 34.8 Hz), 130.5, 129.7, 128.9, 127.9, 115.9 (q, J = 290.6
Hz), 42.9; F NMR (376 MHz, CDCl ): δ = -78.9; HRMS (EI) m/z calcd. for C H F O:
(
100 MHz, CDCl
3
1
9
3
9
7 3
1
88.0456, found: 188.0449.
4
1
,1,1,2,2-Pentafluoro-5-phenylpentan-3-one (3ad)
1
Colorless oil; H NMR (400 MHz, CDCl ): δ = 7.17 - 7.32 (m, 5H), 3.07 (t, J = 8.0 Hz, 2H),
3
1
3
2
1
.98 (t, J = 8.0 Hz, 2H); C NMR (100 MHz, CDCl
3
): δ = 193.5 (t, J = 26.0 Hz), 139.4, 128.7,
1
9
28.3, 126.7, 117.9 (qt, J = 284.0, 33.0 Hz), 107.1 (tq, J = 265.0, 38.0 Hz), 39.1, 28.4; F
NMR (376 MHz, CDCl
3
9 5
): δ = -81.9, -123.3; HRMS (EI) m/z calcd. for C11H F O: 252.0574,
found: 252.0571.
5
Perfluoroheptan-(2-phenyl)ethyl-one (3ae)
1
Colorless oil; H NMR (400 MHz, CDCl ): δ = 7.19 - 7.33 (m, 5H), 3.08 (t, J = 8.0 Hz, 2H),
3
13
2
1
1
3
.99 (t, J = 8.0 Hz, 2H); C NMR (100 MHz, CDCl ): δ = 193.0 (q, J = 26.0 Hz), 139.4,
1
9
28.4, 128.2, 126.8, 106.7 - 118.8 (m), 39.8, 28.6; F NMR (376 MHz, CDCl ): δ = -81.9, -
3
21.1 - -127.1 (m); HRMS (EI) m/z calcd. for C H F O: 502.0414, found: 502.0418.
16
9 15
6
1
,1,1-Trifluorohexan-2-one (3g)
o
1
Colorless oil; b.p. 91 - 93 C; H NMR (400 MHz, CDCl
3
): δ = 2.73 (t, J = 7.2 Hz, 2H), 1.67
1
3
(
m, 2H), 1.39 (m, 2H), 0.94 (t, J = 7.6 Hz, 3H); C NMR (100 MHz, CDCl ): δ = 191.7 (q, J
3
19
=
34.5 Hz), 116.0 (q, J = 289.9 Hz), 36.2, 24.6, 22.1, 13.5; F NMR (376 MHz, CDCl
3
): δ = -
8
0.1; MS (EI) m/z 125, 112, 85, 69, 57.
7
1
,1,1-Trifluoro-4-(4-methoxycarbonyl)phenyl)butan-2-one (3k)
O
F3C
COOMe
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Colorless oil; H NMR (400 MHz, CDCl
H), 3.91 (s, 3H), 3.03 (t, J = 8.0 Hz, 2H), 2.96 (t, J = 8.0 Hz, 2H); C NMR (100 MHz,
CDCl ): δ = 190.3 (q, J = 35.0 Hz), 166.8, 144.7, 125.3, 129.9, 128.3, 115.5 (q, J = 290.0 Hz),
3
): δ = 7.97 (d, J = 7.2 Hz, 2H), 7.28 (d, J = 7.2 Hz,
13
2
3
19
5
1.9, 37.4, 28.1; F NMR (376 MHz, CDCl ): δ = -79.9; HRMS (EI) m/z calcd. for
3
12 11 3 3
C H F O : 260.0660, found: 260.0658.
1
1
,1,1-Trifluoro-4-(4-methoxyphenyl)butan-2-one (3l)
1
Colorless oil; H NMR (400 MHz, CDCl ): δ = 7.11 (d, J = 8.4 Hz, 2H), 6.84 (d, J = 8.4 Hz,
3
13
2
H), 3.79 (s, 3H), 3.01 (t, J = 7.2 Hz, 2H), 2.93 (t, J = 7.2 Hz, 2H); C NMR (100 MHz,
CDCl ): δ = 190.6 (q, J = 35.0 Hz), 158.4, 131.3, 129.2, 120.1, 114.1 (q, J = 290.6 Hz), 54.7,
3
1
9
3
2
8.1, 27.3; F NMR (376 MHz, CDCl ): δ = -79.3; HRMS (EI) m/z: calcd. for C H F O :
3 11 11 3 2
32.0711, found: 232.0710.
5
1
,1,1-Trifluoro-4-(2-thiophenyl)butan-2-one (3m)
1
Yellow oil; H NMR (400 MHz, CDCl
3
): δ = 7.15 (d, J = 4.8 Hz, 1H), 6.93 (m, 1H), 6.84 (d,
13
J = 3.6 Hz, 1H), 3.22 (t, J = 7.2 Hz, 2H), 3.11 (t, J = 7.2 Hz, 2H); C NMR (100 MHz,
CDCl ): δ = 190.3 (q, J = 35.0 Hz), 141.7, 127.2, 125.3, 124.1, 115.6 (q, J = 290.0 Hz), 38.5,
3
19
2
2
2.7. F NMR (376 MHz, CDCl
08.0170, found: 208.0175.
3
8 7 3
): δ = -79.8; HRMS (EI) m/z: calcd. for C H F OS:
1
1
,1,1-Trifluoro-4-(4-methylphenyl)butan-2-one (3n)
1
Colorless oil; H NMR (400 MHz, CDCl
3
): δ = 7.10 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.0 Hz,
13
2
H), 2.99 (t, J = 6.8 Hz, 2H), 2.92 (t, J = 6.8 Hz, 2H), 2.30 (s, 3H); C NMR (100 MHz,
CDCl ): δ = 190.1(q, J = 35.0 Hz), 136.4, 129.5, 129.2, 128.5, 115.9 (q, J = 290.3 Hz), 38.3,
3
1
9
2
2
8.0, 21.1; F NMR (376 MHz, CDCl
16.0762, found: 216.0764.
3
11 3
): δ = -79.7; HRMS (EI) m/z calcd. for C11H F O:
8
4
,4,4-Trifluoro-1-phenylbutane-1,3-dione (5a)
o
1
This product was isolated in enol-form. White needle crystal; m.p. 35 - 37 C; H NMR (400
MHz, CDCl ): δ = 15.14 (br, 1H), 7.95 (t, J = 8.4 Hz, 2H), 7.52 - 7.65 (m, 3H), 6.58 (s, 1H);
3
1
3
C NMR (100 MHz, CDCl
3
): δ = 186.3, 177.3 (q, J = 36.0 Hz), 134.2, 132.9, 129.1, 127.7,
19
1
17.4 (q, J = 281.0 Hz), 92.2; F NMR (376 MHz, CDCl ): δ = -77.0.
3
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2
-(2,2,2-Trifluoroacetyl)-3,4-dihydro-2H-naphthalen-1-one (5b)
O
O
CF3
o
1
This product was isolated in enol-form. White needle crystal; m.p. 49 - 50 C; H NMR (400
MHz, CDCl ): δ = 15.67 (s, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.50 (t, J = 8.4 Hz, 1H), 7.37 (t, J =
3
13
8
.4 Hz, 1H), 7.27 (d, J = 8.4 Hz, 1H), 2.91 (t, J = 8.4 Hz, 2H), 2.76 (t, J = 8.4 Hz, 2H); C
NMR (100 MHz, CDCl ): δ = 182.1, 175.1 (q, J = 34.2 Hz), 141.8, 133.8, 129.7, 128.0, 127.3,
3
19
1
3
26.6, 118.0 (q, J = 283.0 Hz), 104.4, 27.7, 20.7; F NMR (376 MHz, CDCl ): δ = -72.1.
1
0
2
-(2,2,2-Trifluoroacetyl)-cyclopentanone (5c)
1
This product was isolated in enol-form. Colorless oil; H NMR (400 MHz, CDCl
3
): δ = 12.79
1
3
(
br, 1H), 2.64 (m, 2H ), 2.39 (t, J = 7.6 Hz, 2H ), 1.89 (t, J = 7.6 Hz, 2H ); C NMR (100
MHz, CDCl
3
): δ = 210.0,158.3 (q, J = 37.0 Hz), 118.8 (q, J = 276.4 Hz), 110.8, 36.8, 25.1,
19
+
2
0.3; F NMR (376 MHz, CDCl ): δ = -73.4; HRMS (ESI) m/z calcd. for C H F O +H
3 7 7 3 2
+
(
[M+H] ): 181.0471, found: 181.0472.
10
2
-(2,2,2-trifluoroacetyl)-cyclohexanone (5d)
1
This product was isolated in enol-form. Colorless oil; H NMR (400 MHz, CDCl ): δ = 2.33 -
3
1
3
2
3
.36 (m, 4H), 1.56 - 1.63 (m, 4H); C NMR (100 MHz, CDCl ): δ = 189.4, 179.6 (q, J =
3
19
3
4.3 Hz), 117.4 (q, J = 285.1 Hz), 104.8, 31.7, 22.2, 21.7, 20.9; F NMR (376 MHz, CDCl ):
δ = -74.1; HRMS (EI) m/z calcd. for C H F O : 194.0555, found: 194.0558.
8
9
3
2
2
4
,4,4-trifluoro-2-methyl-1-phenyl-1,3-butanedione (5e)
1
Colorless oil; H NMR (400 MHz, CDCl ): δ = 7.91 (m, 2H), 7.56 (t, J = 7.6 Hz, 1H), 7.44 (m,
3
13
2
1
H), 4.98 (q, J = 7.2 Hz, 1H), 1.46 (d, J = 7.2 Hz, 3H); C NMR (100 MHz, CDCl ): δ =
3
95.7, 189.1 (q, J = 35.0 Hz), 134.5, 129.3, 128.9, 128.7, 115.6 (q, J = 290.4 Hz), 50.1, 13.2;
1
9
F NMR (376 MHz, CDCl
found: 230.0551.
3 9 3 2
): δ = -78.0; HRMS (EI) m/z calcd. for C11H F O : 230.0555,
3
. Characterization data for aromatic acid esters
12
Ethyl benzenecarboxylate (4a)
1
Colorless oil; H NMR (400 MHz, CDCl ): δ = 8.05 (d, J = 8.0 Hz, 2H), 7.55 (t, J = 7.2 Hz,
3
1
H), 7.44 (t, J = 8.0 Hz, 2H), 4.39 (q, J = 7.2 Hz, 2H), 1.39 (t, J = 7.2 Hz, 3H).
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Ethyl 3-phenyl-2-propenoate (4b)
1
Colorless oil; H NMR (400 MHz, CDCl ): δ = 7.70 (d, J = 16.0 Hz, 1H), 7.49 - 7.70 (m, 2H),
3
7
3
.39 - 7.49 (m, 3H), 6.45 (d, J = 16.0 Hz, 1H), 4.28 (q, J = 7.2 Hz, 2H), 1.35 (t, J = 7.2 Hz,
H).
1
2
Ethyl p-fluorobenzoate (4c)
o
1
White needle crystal; m.p. 26 - 27 C; H NMR (400 MHz, CDCl
3
): δ = 8.00 (d, J = 8.4 Hz,
2
H), 6.94 (d, J = 8.4 Hz, 2H), 4.10 (q, J = 7.2 Hz, 2H), 1.45 (t, J = 7.2 Hz, 3H).
13
Ethyl p-bromobenzoate (4d)
1
Colorless oil; H NMR (400 MHz, CDCl ): δ = 7.90 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 8.4 Hz,
3
2
H), 4.36 (q, J = 7.2 Hz, 2H), 1.39 (t, J = 7.2 Hz, 3H).
1
3
Ethyl o-chlorobenzoate (4e)
1
Colorless oil; H NMR (400 MHz, CDCl ): δ = 7.81 (d, J = 7.6 Hz, 1H), 7.40 - 7.45 (m, 2H),
3
7
.29 - 7.32 (m, 1H), 4.40 (q, J = 7.2 Hz, 2H), 1.40 (t, J = 7.2 Hz, 3H).
1
4
Methyl 2-iodobenzoate (4f)
1
Colorless oil; H NMR (400 MHz, CDCl
3
): δ = 7.9 -8.0 (m, 1H), 7.7 - 7.8 (m, 1H), 7.3 -7.5
(
m, 1H), 7.1 - 7.2 (m, 1H), 3.93 (s, 3H).
1
2
Ethyl p-methylbenzoate (4g)
1
Colorless oil; H NMR (400 MHz, CDCl
3
): δ = 7.93 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.0 Hz,
2
H), 4.36 (q, J = 7.2 Hz, 2H), 2.39 (s, 3H), 1.38 (t, J = 7.2 Hz, 3H).
12
Ethyl p-methoxybenzoate (4h)
1
Colorless oil; H NMR (400 MHz, CDCl
3
): δ = 8.00 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz,
2
H), 4.34 (q, J = 7.2 Hz, 2H), 3.84 (s, 3H), 1.37 (t, J = 7.2 Hz, 3H).
12
p-Diethyl phthalate (4i)
o
1
6
White solid; m.p. 44 - 45 C; H NMR (400 MHz, d -DMSO): δ = 8.07 (s, 4H), 4.34 (q, J =
7
.2 Hz, 2H), 1.35 (t, J = 7.2 Hz, 3H).
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Ethyl 1-naphthalenecarboxylate (4j)
O
OEt
1
Colorless oil; H NMR (400 MHz, CDCl ): δ = 8.95 (d, J = 8.4 Hz, 1H), 8.13 (d, J = 7.2 Hz,
3
1
2
H), 7.88 (d, J = 8 Hz, 1H), 7.77 (d, J = 8.4 Hz, 1H),7.55 (d, J = 7.2 Hz, 1H), 7.35 - 7.45 (m,
H),4.40 (q, J = 7.2 Hz, 2H), 1.37 (t, J = 7.2 Hz, 3H).
13
Ethyl 2-furylcarboxylate (4k)
O
O
OEt
1
Colorless oil; H NMR (400 MHz, CDCl ): δ = 7.60 (s, 1H), 7.13 (s, 1H), 6.52 (s, 1H), 4.36
3
(
q, J = 7.2 Hz, 2H), 1.37 (t, J = 7.2 Hz, 3H).
13
Ethyl 2-thiophenecarboxylate (4l)
O
S
OEt
1
Colorless oil; H NMR (400 MHz, CDCl ): δ = 7.80 (d, J = 3.6 Hz, 1H), 7.54 (d, J = 4.8 Hz,
3
1
H), 7.10 (dd, J = 4.8 Hz, 3.6 Hz, 1H), 4.36 (q, J = 7.2 Hz, 2H), 1.37 (t, J = 7.2 Hz, 3H).
1
2
Ethyl 3-pyridinecarboxylate (4m)
1
Colorless oil; H NMR (400 MHz, CDCl
3
): δ = 9.23 (s, 1H), 8.77 (d, J = 4.8 Hz, 1H), 8.29 (d,
J = 8.0 Hz, 1H), 7.39 (dd, J = 8.0 Hz, 4.8 Hz, 1H), 4.42 (q, J = 7.2 Hz, 2H), 1.41 (t, J = 7.2
Hz, 3H).
1
2
Ethyl p-cyanobenzoate (4n)
o
1
White needle crystal; m.p. 53 - 54 C; H NMR (400 MHz, CDCl ): δ = 8.15 (d, J = 8.4, 2H),
3
7
.75 (d, J = 8.4 Hz, 2 H), 4.43 (q, J = 7.2 Hz, 2 H), 1.42 (t, J = 7.2 Hz, 3H).
15
Ethyl p-dimethy1aminobenzoate (4o)
o
1
White needle crystal; m.p. 63 - 64 C; H NMR (400 MHz, CDCl
3
): δ = 7.91 (d, J = 8.8 Hz,
), 1.36 (t, J = 7.6
2
H), 6.63 (d, J = 8.8 Hz, 2H), 4.31 (q, J = 7.6 Hz, 2H), 3.02 (s, 6H, N(CH
3
)
2
Hz, 3H).
16
Ethyl ferrocenecarboxylate (4p)
o
1
Red needle crystal; m.p. 63 - 64 C; H NMR (400 MHz, CDCl ): δ = 4.80 (s, 2H), 4.37 (s,
3
2
H), 4.19 (s, 5H), 4.27 (q, J = 6.8 Hz, 2H), 1.34 (t, J = 6.8 Hz, 3H).
4
. References
1
Rudzinski, D. M.; Kelly, C. B.; Leadbeater, N. E. Chem. Commum. 2012, 48, 9610.
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3
4
5
6
7
Barkley, L. B.; Levine, R. J. Am. Chem. Soc. 1953, 75, 2059.
Linderman, R. J.; Graves, D. M. J. Org. Chem. 1989, 54, 661.
Kitazume, T.; Ohnogi, T.; Lin, J. T.; Yamazaki, T.; Ito, K. J. Fluorine Chem. 1989, 42, 17.
Yang, D.; Zhou, Y.; Xue, N.; Qu, J. J. Org. Chem. 2013, 78, 4171.
Dishart, K. T.; Levine, R. J. Am. Chem. Soc. 1956, 78, 2268.
Cheng, H.; Hwang, I.; Chong, Y.; Tavassoli, A.; Webb, M. E.; Zhang, Y.; Wilson, I. A.;
Benkovic, S. J.; Boger, D. L. Bioorg. Med. Chem. 2005, 13, 3593.
Joshi, A.; Verma, S.; Jain, A.; Saxena, S. Main Group Met. Chem. 2005, 28, 31.
Salman, S. R.; Farrant, R. D.; Lindon, J. C. Magn. Reson. Chem. 1990, 28, 645.
0 Ebraheem, K. A. K. Monatsh. Chem. 1991, 122, 157.
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9
1
1
1
1
1
1
2 Shang, R.; Fu, Y.; Li, J.; Zhang, S.; Guo, Q.; Liu, L. J. Am. Chem. Soc. 2009, 131, 5738.
3 Wu, X.; Darcel, C. Eur. J. Org. Chem. 2009, 1144.
4 Kulbitski, K.; Nisnevich, G.; Gandelmana, M. Adv. Synth. Catal. 2011, 353, 1438.
5 Schmidt, A.; Habeck, T.; Snovydovych, B.; Eisfeld, W. Org. Lett. 2007, 9, 3515.
6 Stoll, A. H.; Mayer, P.; Knochel, P. Organometallics 2007, 26, 6694.
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. H, C and F NMR spectra of the products
3
a
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ae
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