TECHNICAL FIELD
[0001] The present invention relates to a method for producing an optically
active, fluorine-containing, carbonyl-ene product, which is an important
intermediate of medicines and agricultural chemicals.
BACKGROUND OF THE INVENTION
[0002] An optically active, fluorine-containing, carbonyl-ene product, which
is the target of the present invention, is an important intermediate of
medicines and agricultural chemicals. As publicly known techniques
relating to the present invention, there are disclosed methods of reacting
ethyl trifluoropyruvate with various alkenos in the presence of a transition
metal complex having an optically active ligand (Non-patent Publications
1-4).
Non-patent Publication l: Tetrahedron Letters (UK), 2004, Vol. 45, p.
183-185.
Non-patent Publication 2- Tetrahedron Asymmetry (UK), 2004, Vol. 15, p.
3885-3889
Non-patent Publication 3: Angew. Chem. Int. Ed. (Germany), 2005, Vol. 44, p.
7257-7260
Non-patent Publication 4: J. Org. Ch-mi. (US) 2006, browsable on the
Internet (Simon Doherty, Julian G. Knight et al., Asymmetric Platinum
Group Metal-Catalyzed Carbonyl-Ene Reactions^ Carbon-Carbon Bond
Formation versus Isomerization)
SUMMARY OF THE INVENTION
[0003] It is an object of the present invention to provide a low-cost
production process of an optically active, fluorine-containing, carbonyl-ene
product, which is an important intermediate of medicines and agricultural

chemicals. In the methods of Non-patent Publications 1-4, it has been
necessary to use high-price asymmetric catalysts by about 5mol% in order to
achieve high catalytic activity [satisfactory asymmetric induction and yield
(conversion)]. How the amount of a high-price asymmetric catalyst used
can be reduced is the key to produce an optically active, fluorine-containing,
carbonyl-ene product with low cost. It has been necessary to find out a
reaction condition that can maintain high catalytic activity even if the
amount of asymmetric catalyst used is reduced. In Non-patent Publications
1-4, studies for finding out such reaction condition have almost not been
conducted. Therefore, it has not been possible to produce an optically active,
fluorine-containing, carbonyl-ene product with low cost.
[0004] As a result of an eager study to solve the above-mentioned task, the
present inventors have found out that activity of asymmetric catalyst is
greatly influenced by the type and the usage of the reaction solvent to be
used. With this, we have reached the present invention. The invention of
the present application includes the following three modes.
[0005] [Mode 1- a mode of reacting in the absence of reaction solvent]
The inventors have found out useful findings that, when a
fluorine-containing orketoester represented by formula [l] is reacted with an
alkene represented by formula [2] to synthesize an optically active,
fluorine-containing, carbonyl-ene product represented by formula [3], it is
possible to conduct the reaction with high optical purity and good yield in the
presence of a transition metal complex having an optically native ligand and
in the absence of reaction solvent (e.g., Examples 2 and 7-20). We have also
found out that, even if the amount of a high-price asymmetric catalyst used
is greatly reduced, the optically active, fluorine-containing, carbonyl-ene
product can be obtained with high optical purity and good yield (e.g.,
Examples 10 and 14-15).
[0006] [Mode 2: a mode of reacting in a solvent that is low in relative
dielectric constant]

The inventors have found out that the optically active,
fluorine-containing, carbonyl-ene product can be obtained with high optical
purity and good yield, under a condition that the amount of a high-price
asymmetric catalyst used has greatly been reduced, by using a reaction
solvent that is relatively weak in coordination ability to metal complex and
that is 5.0 or less in relative dielectric constant sr, particularly a hydrocarbon
series reaction solvent, too (e.g., a comparison between Examples 1, 3, and
21-28 and Comparative Examples 1-13). Although toluene is cited as an
unfavorable reaction solvent in Non-patent Publication 4, it has been found
out to be a particularly preferable reaction solvent in a reaction between
ethyl trifluoropyruvate and isobutene, which is a preferable example of the
present invention.
[0007] [Mode 3: a mode of reacting in a halogenated hydrocarbon-series
solvent]
The inventors have found out that the reaction can preferably be
conducted, even if it is a halogenated hydrocarbon-series reaction solvent,
which is relatively strong in coordination ability, by limiting its usage and by
conducting the reaction under a high concentration condition (e.g., a
comparison between Examples 4-6 and Comparative Examples 1-3 and 9).
We have also found out that, even if the amount of a high-price asymmetric
catalyst used is greatly reduced, the optically active, fluorine-containing,
carbonyl-ene product can be obtained with high optical purity and good yield.
[0008] That is, the present invention includes the following first to eighth
methods and provides a method for producing an optically active,
fluorine-containing, carbonyl-ene product with low cost that is suitable for
large-scale production. The following first to third methods, the fourth to
seventh methods, and the eighth method respectively correspond to the
above-mentioned Mode 1, Mode 2, and Mode 3.
[0009] According to the present invention, there is provided a method (first
method) for producing an optically active, fluorine-containing, carbonyl-ene
product represented by formula [3]

[Chemical Formula 3]

[in the formula, Rf represents a perfluoroalkyl group, R represents an alkyl
group, each of R1, R2, R:!, R1 and R5 independently represents a hydrogen
atom, alkyl group, substituted alkyl group, aromatic ring group, or
substituted aromatic ring group, * represents an asymmetric carbon (it is,
however, not an asymmetric carbon in case that R! and Rr> are the same
substituents), and wave line represents an E configuration or Z configuration
in geometrical configuration of the double bond] by reacting a
fluorine-containing orketoester represented by formula [l]
[Chemical Formula l]

[in the formula, Rf and R respectively represent the same substituents as
above] with an alkene represented by formula [2]
[Chemical Formula 2]

[in the formula, each of R1, R2, R'5, R' and R5 independently represents the
same substituent as above] in the presence of a transition metal complex
having an optically active ligand and in the absence of reaction solvent.
[0010] The first method may be a method (second method) for producing
optically active, trifluorocarbonyl-ene product represented by formula [6]

[Chemical Formula 6]

[in the formula, * represents an asymmetric carbon] by reacting ethyl
trifluoropyruvate represented by formula [4]
[Chemical Formula 4]

with isobutene represented by formula [5]
[Chemical Formula 5]

in the presence of 0.0005 moles or less of a bivalent cationic transition metal
complex having an optically active ligand relative to 1 mole of the ethyl
trifluoropyruvate represented by formula [4] and in the absence of reaction
solvent.
[0011] The second method may be a method (third method) for producing
(E)-trifluorocarbonyl-ene product represented by formula [7]
[Chemical Formula 9]

by reacting ethyl trifluoropyruvate represented by formula [4]
[Chemical Formula 7]


with isobutene represented by formula [5]
[Chemical Formula 8]

in the presence of 0.0003 moles or less of a bivalent cationic palladium
complex having an optically active ligand relative to 1 mole of the ethyl
trifluoropyruvate represented by formula [4] and in the absence of reaction
solvent.
[0012] According to the present invention, there is provided a method
(fourth method) for producing an optically active, fluorine-containing,
carbonyl-ene product represented by formula [3]
[Chemical Formula 12]

[in the formula, Rf represents a perfluoroalkyl group, R represents an alkyl
group, each of R'. R2, R:!, R1 and R5 independently represents a hydrogen
atom, alkyl group, substituted alkyl group, aromatic ring group, or
substituted aromatic ring group, * represents an asymmetric carbon (it is,
however, not an asymmetric carbon in case that R1 and R5 are the same
substituents), and wave line represents an E configuration or Z configuration
in geometrical configuration of the double bond] by reacting a
fluorine-containing orketoester represented by formula [l].
[Chemical Formula 10]


[in the formula, Rf and R respectively represent the same substituents as
above] with an alkene represented by formula [2]
[Chemical Formula 11]

[in the formula, each of R1, R2, R3, R1 and R5 independently represents the
same substituent as above] in the presence of 0.001 moles or less of a
transition metal complex having an optically active ligand relative to 1 mole
of the fluorine-containing crketoester represented by formula [l] and in the
presence of a reaction solvent that is 5.0 or less in relative dielectric constant
iW.
[0013] The fourth method may be a method (fifth method) for producing an
optically active, fluorine-containing, carbonyhene product represented by
formula [3]
[Chemical Formula 15]

[in the formula, Rf represents a perfluoroalkyl group, R represents an alkyl
group, each of R1, R2, R:i, R1 and R5 independently represents a hydrogen
atom, alkyl group, substituted alkyl group, aromatic ring group, or
substituted aromatic ring group, * represents an asymmetric carbon (it is,
however, not an asymmetric carbon in case that R"1 and R5 are the same

substituents), and wave line represents an E configuration or Z configuration
in geometrical configuration of the double bond] by reacting a
fluorine-containing orketoester represented by formula [l].
[Chemical Formula 13]

[in the formula, Rf and R respectively represent the same substituents as
above] with an alkene represented by formula [2]
[Chemical Formula 14]

[in the formula, each of R1, R2, R3, R4 and R5 independently represents the
same substituent as above] in the presence of 0.001 moles or less of a
transition metal complex having an optically active ligand relative to 1 mole
of the fluorine-containing orketoester represented by formula [l] and in the
presence of a hydrocarbon-series reaction solvent.
[0014] The fifth method may be a method (sixth method) for producing
optically active, trifluorocarbonyl-ene product represented by formula [6]
[Chemical Formula 18]

[in the formula, * represents an asymmetric carbon] by reacting ethyl
trifluoropyruvate represented by formula [4]
[Chemical Formula 16]


with isobutene represented by formula [5]
[Chemical Formula 17]

in the presence of 0.0005 moles or less of a bivalent cationic transition metal
complex having an optically active ligand relative to 1 mole of the ethyl
trifluoropyruvate represented by formula [4] and in the presence of an
aromatic hydrocarbon-series reaction solvent.
[0015] The sixth method may be a method (seventh method) for producing
(R)-trifl.uorocarbonyl-ene product represented by formula [7]
[Chemical Formula 21]

by reacting ethyl trifluoropyruvate represented by formula [4]
[Chemical Formula 19]

with isobutene represented by formula [5]
[Chemical Formula 20]


in the presence of 0.0003 moles or less of a bivalent cationic palladium
complex having an optically active ligand relative to 1 mole of the ethyl
trifluoropyruvate represented by formula [4] and in the presence of toluene
as reaction solvent.
[0016] According to the present invention, there is provided a method
(eighth method) for producing an optically active, fluorine-containing,
carbonyl-ene product represented by formula [3]
[Chemical Formula 24]

[in the formula, Rf, R, R1, R2, R3, R4 and R5 represent the same substituents
as above, * represents an asymmetric carbon (it is, however, not an
asymmetric carbon in case that R4 and R5 are the same substituents), and
wave line represents an E configuration or Z configuration in geometrical
configuration of the double bond] by reacting a fluorine-containing
orketoester represented by formula [l]
[Chemical Formula 22]

[in the formula, Rf represents a perfluoroalkyl group, and R represents an
alkyl group] with an alkene represented by formula [2]
[Chemical Formula 23]


[in the formula, each of R1, R2, R3, R4 and R5 independently represents a
hydrogen atom, alkyl group, substituted alkyl group, aromatic ring group, or
substituted aromatic ring group] in the presence of a transition metal
complex having an optically active ligand and in the presence of less than
1.0L (liter) of a halogenated hydrocarbon-series reaction solvent relative to 1
mole of the fluorine-containing crketoester represented by formula [l].
DETAILED DESCRIPTION
[0017] In the production method of the present invention, it is possible to
not only solve the problem (high production cost due to the use of a
high-price asymmetric catalyst in large amount) of Non-patent Publications
1-4, but also reduce the usage of methylene chloride, which is limited in
industrial use as a reaction solvent, (a reaction solvent frequently used in
Non-patent Publications 1-4). Alternatively, the reaction can also be
conducted without using it at all. Even under such condition, it is possible
to produce the target product with high yield and high asymmetric yield, and
there occurs no production of impurities that are difficult of separation.
Particularly in the case of using no reaction solvent, it is possible to
remarkably improve productivity of the reaction and operability of the
post-treatment.
[0018] A method of the present invention for producing an optically active,
fluorine-containing, carbonyl-ene product is explained in detail. Firstly,
matters common to Mode 1 to Mode 3 are explained.
[0019] As perfluoroalkyl group of fluorine-containing crketoester
represented by formula [l], it is possible to cite one having a carbon atom
number of 1-6. One having a carbon atom number of 3 or greater can take a
straight-chain or branch. As alkyl group of fluorine-containing crketoester
represented by formula [l], it is possible to cite one having a carbon atom
number of 1-6. One having a carbon atom number of 3 or greater can take a
straight-chain or branch.
[0020] Of the fluorine-containing crketoester, one is preferable, in which Rf
is a trifluoromethyl group, and R is a methyl group or ethyl group, and which

can easily be produced and can industrially be used. It is preferable for
producing the optically active, fluorine-containing, carbonyl-ene product.
[0021] As alkyl groups of alkene represented by formula [2], it is possible to
cite those having a carbon atom number of 1-6. Those having a carbon atom
number of 3 or greater can take a straight-chain or branch. Two alkyl
groups can also form by a covalent bond a cyclopentane ring, cyclohexane
ring, cycloheptane ring, cyclopentene ring, cyclohexene ring, cycloheptene
ring, or the like.
[0022] As substituted alkyl group of alkene represented by formula [2], a
hydroxyl-group's protector or the like can substitute in the alkyl group. As
the protecting group of the hydroxyl group, it is possible to suitably use those
mentioned in Protective Groups in Organic Synthesis, Third Edition, 1999,
John Wiley & Sons, Inc. Of those, benzyl group and t-butyldiphenylsilyl
group are preferable.
[0023] As aromatic ring group of alkene represented by formula [2], it is
possible to cite aromatic hydrocarbon groups, such as phenyl group, and the
like.
[0024] As substituted aromatic ring group of alkene represented by formula
[2], a halogen atom, such as fluorine atom or chlorine atom, a lower alkyl
group, such as methyl group, or the like can substitute in the aromatic ring
group. The aromatic ring group and the alkyl group can also form a
covalent bond.
[0025] Of the alkene, 1,1'disubstituted olefin, which is high in reactivity, is
preferable. Isobutene is preferable, in view of importance of the obtained
product as a medicine intermediate. We have made it clear that the
production method of the present invention is a single-step, very excellent
method, in view of that a method for industrially producing optically active,
trifluorocarbonyl-ene product represented by formula [6], particularly
(R)-trifluorocarbonyl-ene product represented by formula [7], has been
limited in conventional techniques to a two-step method of synthesizing the
corresponding racemate and conducting optical resolution.

[0026] The usage of alkene represented by formula [2] is not particularly-
limited. Normally, the use of 0.7moles or greater is enough, the use of
0.8-10moles is preferable, and particularly the use of 0.9-7moles is more
preferable, relative to lmole of fluorine-containing orketoester represented
by formula [l].
[0027] As the transition metal complex having an optically active ligand, it
is possible to cite a bivalent cationic complex represented by formula [8]
[Chemical Formula 25]

[in the formula, X-*-X represents the following optically active SEGPHOS
derivative (chemical formula 26), optically active BINAP derivative
(chemical formula 27), optically active BIPHEP derivative (chemical formula
28), optically active P-Phos derivative (chemical formula 29), optically active
PhanePhos derivative (chemical formula 30), optically active
l,4-Et2-cyclo-C6H8-NUPHOS (chemical formula 31) or optically active BOX
derivative (chemical formula 32), or the like, Y represents Ni, Pd, Pt or Cu,
and Z represents SbF6, C104, BF4, OTf (T£ CF3SO2), AsF6, PF6, or
B(3,5-(CF3)2C6H3)4]
[Chemical Formula 26]

[Chemical Formula 27]

[in the formula, R represents a hydrogen atom, chlorine atom, bromine atom,
iodine atom or trifluoromethyl group, and Me represents a methyl group] or
the like. Of these, the bivalent cationic complex is preferable, and
particularly the bivalent cationic palladium complex is more preferable (As
the optically active ligand, representative ones are cited, and it is possible to
suitably use those mentioned in CATALYTIC ASYMMETRIC SYNTHESIS,
Second Edition, 2000, Wiley-VCH, Inc. As Z, SbF6) BF4, OTf, and '!

B(3,5-(CF3)2C6H3)4 are preferable. Particularly, SbF6, OTf, and
B(3,5-(CF3)2C6H3)4 are more preferable).
[0028] These complexes can be prepared by pxiblicly known methods (for
example, Non-patent Publications 1-4, J. Am. Chem. Soc. (US), 1999, Vol.
121, p. 686-699, nature (UK), 1997, Vol. 385, p. 613-615, etc.), and, besides
an isolated complex (e.g., Reference Examples 1-2; isolated), the use without
isolation following a previous preparation in the reaction system is also
possible (e.g., Methods C to D-2 and F of Examples; in situ). As these
complexes, it is also possible to use ones to which water or an organic solvent
such as acetonitrile is coordinated (solvation) [since the usage of asymmetric
catalyst is extremely small, the solvent coordinated to the complex can be
neglected, and it is not treated (not converted) as reaction solvent]. As in
situ complex, a bivalent cationic complex having a fluorine-containing
orketoester as a ligand is preferable, which is represented by formula [10]
[0029] [Chemical Formula 34]

[in the formula, X-*-X, Y and Z represent the same ones as those of formula
[8], Rf and R represent the same ones as those of formula [l]], which can
easily be prepared by novel Method D, D-2 or F with no necessity of using

reaction solvent at all, and which is extremely high in activity of asymmetric
catalyst.
[0030] Furthermore, it is possible in some cases to use a cationic binuclear
complex, too, which is represented by formula [ll]
[Chemical Formula 35]

[in the formula, X-*-X, Y and Z represent the same ones as those of formula
[8]], similar to the bivalent cationic complex represented by formula [8].
[0031] It is possible to suitably use stereochemistry [(R), (S), (R,R), (S,S),
etc.] of the optically active ligand in accordance with stereochemistry of the
target optically active, fluorine-containing, carbonyl-ene product. In view of
importance of the obtained product as a medicine intermediate,
stereochemistry of the optically active ligand that gives a
(R)-fluorine-containing carbonyl-ene product is preferable. It suffices to
suitably set optical purity of the optically active ligand in accordance with
the target optical purity of the optically active, fluorine-containing
carbonyl-ene product. Normally, it suffices to use 95%ee (enantiomeric
excess) or greater, the use of 97%ee or greater is preferable, and particularly
the use of 99%ee or greater is more preferable.
[0032] Of these optically active ligands, BINAP derivatives are preferable,
since both enantiomers can be obtained with the lowest price, and since
activity upon converted into an asymmetric catalyst is also extremely high.
BINAP and Tol-BINAP are preferable, and particularly BINAP is more
preferable.
[0033] As the usage of the transition metal complex having an optically
active ligand, it suffices to use 0.001 moles or less, the use of 0.0005 moles or

less is preferable, and particularly the use of 0.0003 moles or less is more
preferable, relative to 1 mole of fluorine-containing crketoester represented
by formula [l], to gain the maximum of the effect of the present invention (to
have a production with a cost as low as possible). Of course, it is also
possible to conduct it with a usage of more than 0.001 moles in no
consideration of the production cost. In Mode 2 in the present invention,
however, 0.001 moles or less of the asymmetric catalyst (transition metal
complex) is used relative to 1 mole of fluorine-containing crketoester
represented by formula [l].
[0034] The reaction temperature is not particularly limited. Normally, it
suffices to conduct it in a range of-60 to +60°C. It is preferable to conduct
it in a range of-50 to +50°C. Particularly, it is more preferable to conduct it
in a range of-40 to +40°C. Furthermore, in the reaction between ethyl
trifluoropyruvate and isobutene, which is a preferable example of the
present invention, sometimes the reaction proceeds, even if asymmetric
catalyst does not exist, and there exists a reaction pathway to give a
racemate (lowering optical purity of the target optically active
trifiuorocarbonyl-ene product), and sometimes isobutene remaining in the
reaction-terminated liquid generates side reactions (lowering chemical
purity of the target optically active trifiuorocarbonyl-ene product).
Therefore, in the present reaction, normally it suffices to conduct it in a
range of-60 to +30°C. It is preferable to conduct it in a range of-50 to
+20°C. Particularly, it is more preferable to conduct it in a range of-40 to
+10°C.
[0035] The order of adding the raw material substrates, asymmetric
catalyst, and the reaction solvent is not limited to [Method A] to [Method F]
mentioned in Examples. In the case of adding alkene at last that is one of
the raw material substrates, it is possible to obtain an optically active
fluorine-containing carbonyl-ene product with high optical purity by
gradually adding it while controlling it to the above reaction temperature or
lower.

[0036] The reaction time is not particularly limited. Normally, it suffices
to conduct it within 24 hours. It depends on the raw material substrates,
asymmetric catalyst, the reaction conditions, etc. Therefore, it is preferable
to monitor the condition of the reaction progress by analytical means such as
gas chromatography, thin-layer chromatography, liquid chromatography, or
nuclear magnetic resonance (NMR) and judge the time when the raw
material substrates have almost disappeared as being the end point.
[0037] Next, an explanation is conducted on each matter of Mode 1 to Mode
3 of the present invention.
[0038] Firstly, Mode 1 is explained. Mode 1 of the present invention is a
method of conducting the target reaction in the absence of reaction solvent.
[0039] Herein, to conduct the reaction in the absence of reaction solvent
means that the reaction solvent does substantially not exist in the reaction
system (neat condition). Specifically, it refers to a condition of the reaction
solvent being less than 0.10L, relative to lmol of fluorine-containing
orketoester represented by formula [l]. A condition of less than 0.05L is
preferable, and particularly a condition of less than 0.01L is more preferable.
More typically, it suffices to conduct the reaction without adding liquid
compound from the outside of the system on one's own initiative, besides the
reaction substrates and the transition metal complex. It is the most
preferable mode of Mode 1.
[0040] Due to that the reaction solvent does substantially not exist in the
reaction system, not only productivity of the reaction improves remarkably,
but also waste liquid derived from the reaction solvent is not discharged in
the post-treatment. Therefore, it is extremely advantageous from the
viewpoint of reducing burden on the environment, too. Thus, it is one of
important findings of the present invention that the target reaction proceeds
with high yield and high optical purity even in the absence of reaction
solvent.
[0041] Furthermore, the inventors have found out that the reaction
proceeds well by the existence of an asymmetric catalyst in an extremely

small amount under such no solvent condition. By these findings, it has
become possible to conduct the target reaction of the present invention
economically remarkably advantageously as compared with the past.
[0042] In Mode 1, a method for producing optically active,
trifluorocarbonyhene product represented by formula [6] by reacting ethyl
trifluoropyruvate represented by formula [4] with isobutene represented by
formula [5] in the presence'of 0.0005 moles or less of a bivalent cationic
transition metal complex having an optically active ligand relative to lmole
of ethyl trifluoropyruvate represented by formula [4] and in the absence of
reaction solvent is particularly preferable in terms of usefulness of the
product, the raw material availability, that the reaction can preferably be
conducted, etc.
[0043] In Mode 1, a method for producing (R)-trifluorocarbonyl-ene product
represented by formula [7] by reacting ethyl trifluoropyruvate represented
by formula [4] with isobutene represented by formula [5] in the presence of
0.0003 moles or less of a bivalent cationic palladium complex having an
optically active ligand relative to lmole of ethyl trifluoropyruvate
represented bj^ formula [4] and in the absence of reaction solvent is still more
preferable due to that the reaction can be conducted still more economically
advantageously, etc.
[0044] Next, Mode 2 is explained. Mode 2 of the present invention is one
in which the target reaction is conducted in the presence of a reaction solvent
that is 5.0 or less in relative dielectric constant sr.
[0045] Herein, as a reaction solvent that is 5.0 or less in relative dielectric
constant E,-, it is possible to cite aliphatic hydrocarbon series such as
irpentane, n-hexane, cyclohexane, and n-heptane; aromatic hydrocarbon
series such as benzene, toluene, xylene, and mesitylene," ethers such as
diethyl ether, t-butyl methyl ether, and 1,4-dioxane (however,
tetrahydrofuran is excluded); etc [in the present invention, it refers to the
value of relative dielectric constant er of the reaction solvent at around 20°C
(20-25°C)]. Of these, hydrocarbon series is preferable, particularly aromatic

hydrocarbon series is more preferable, and furthermore toluene is extremely
preferable. These reaction solvents that are 5.0 or less in relative dielectric
constant sr can be used alone or in combination.
[0046] The usage of the reaction solvent that is 5.0 or less in relative
dielectric constant sr is not particularly limited. Normally, it suffices to use
3.0L or less, the use of 2.0L or less is preferable, and particularly the use of
1.0L or less is more preferable, relative to 1 mole of fluorine-containing
crketoester represented by formula [l].
[0047] To conduct the reaction in the presence of a reaction solvent
(reaction solvent that is 5.0 or less in relative dielectric constant sr) refers to
a condition in which 0.10L or greater is used relative to 1 mole of
fluorine-containing crketoester represented by formula [l].
[0048] In Mode 2, it is also possible to use a mixed solvent prepared by
combining a reaction solvent that is greater than 5.0 in relative dielectric
constant sr and a reaction solvent that is 5.0 or less in relative dielectric
constant sr. In this case, substantially the same effect can be expected as
that of the reacting in the presence of a reaction solvent that is 5.0 or less in
relative dielectric constant sr, due to that coordination ability to metal
complex, which is originally owned by a reaction solvent that is greater than
5.0 in relative dielectric constant sr, is weakened. For example, in case that
a hydrocarbon-series reaction solvent is used in the same volume or more as
that of a halogenated hydrocarbon-series reaction solvent, it is possible to
obtain the target product with high optical purity and good yield by a small
amount of asymmetric catalyst, even if the usage of the halogenated
hydrocarbon-series reaction solvent is in 1.0L or more relative to 1 mole of
fluorine-containing crketoester represented by formula [l]. Therefore, in
the case of mentioning a reaction solvent that is 5.0 or less in relative
dielectric constant sr in the present invention, there is also included a mixed
solvent of a reaction solvent that is 5.0 or less in relative dielectric constant
sr and a reaction solvent that is greater than 5.0 in relative dielectric

constant sr, the mixed solvent being such that the former has been used in
the same volume or more as that of the latter.
[0049] In Mode 2, a method for producing optically active
fluorine-containing carbonyl-ene product represented by formula [3] by
reacting fluorine-containing crketoester represented by formula [l] with
alkene represented by formula [2] in the presence of 0.001 moles or less of a
transition metal complex having an optically active ligand relative to 1 mole
of fluorine-containing crketoester represented by formula [l] and in the
presence of a hydrocarbon-series reaction solvent is preferable, since
reactivity is good.
[0050] In Mode 2, a method for producing optically active
trifluorocarbonyl-ene product represented by formula [6] by reacting ethyl
trifluoropyruvate represented by formula [4] with isobutene represented by
formula [5] in the presence of 0.0005 moles or less of a bivalent cationic
transition metal complex having an optically active ligand relative to 1 mole
of ethyl trifluoropyruvate represented by formula [4] and in the presence of
an aromatic hydrocarbon-series reaction solvent is particularly preferable,
due to usefulness of the product, the raw material availability, that
reactivity is good, etc.
[0051] In Mode 2, a method for producing (R)-trifluorocarbonyl-ene product
represented by formula [7] by reacting ethyl trifluoropyruvate represented
by formula [4] with isobutene represented by formula [5] in the presence of
0.0003 moles or less of a bivalent cationic palladium complex having £.-.i
optically active ligand relative to 1 mole of ethyl trifluoropyruvate
represented by formula [4] and in the presence of toluene as reaction solvent
is still more preferable, due to usefulness of the product, the raw material
availability, that reactivity is still better, etc.
[0052] Next, Mode 3 is explained. Mode 3 is one in which the reaction is
conducted in the presence of less than 1.0L of a halogenated
hydrocarbon-series reaction solvent relative to 1 mole of fluorine-containing
crketoester represented by formula [l].

[0053] Herein, as a halogenated hydrocarbon-series reaction solvent, it is
possible to cite methylene chloride, chloroform, 1,2-dichloroethane, etc. Of
these, methylene chloride and 1,2-dichloroethane are preferable, and
particularly methylene chloride is more preferable. These halogenated
hydrocarbon-series reaction solvents can be used alone or in combination. Of
course, they can also be used in combination with a reaction solvent that is 5.0
or less in relative dielectric constant sr.
[0054] As the usage of a halogenated hydrocarbon-series reaction solvent,
less than 1.0L is used, the use of less than 0.7L is preferable, and particularly
the use of less than 0.5L is more preferable, relative to 1 mole of
fluorine-containing orketoester represented by formula [l].
[0055] In the present invention, the reacting in the presence of a halogenated
hydrocarbon-series reaction solvent refers to a condition in which the
halogenated hydrocarbon-series reaction solvent is used in 0.10L or more
relative to 1 mole of fluorine-containing orketoester represented by formula [l].
[0056] Next, the post-treatment step common to Mode 1 to Mode 3 is
explained.
[0057] As the post-treatment, there is no particular limitation. It is possible
to obtain the target optically active fluorine-containing carbonyl-ene product
represented by formula [3] by conducting normal operations on the
reaction-terminated liquid. According to need, the crude product can be
purified to high purity by an operation such as activated carbon treatment,
distillation, recrystallization, or column chromatography. In a reaction
between ethyl trifluoropyruvate and isobutene, which is a preferable example
of the present invention, it is extremely important to control side reactions by
removing under low temperature isobutene remaining in the
reaction-terminated liquid to the outside of the system. Therefore, in the
present post-treatment, normally conducting in a range of-60 to +30°C is
enough, conducting in a range of-50 to +20°C is preferable, and particularly
conducting in a range of-40 to +10°C is more preferable. As the manner for
removal to

the outside of the system, there is no particular limitation. There is
preferable a method of removing it to the outside of the system by blowing
inert gas such as nitrogen, argon or the like and accompanying it or a
method of directly removing it from the reaction-terminated liquid under
reduced pressure. Furthermore, in the present post-treatment, after
isobutene is removed from the reaction-terminated liquid by the above
method to a make condition where no side reaction occurs, it is possible to
continuously recover (reaction solvent can also be recovered in the case of
using reaction solvent) the target product by fractional distillation (according
to need, it can be conducted under reduced pressure). Therefore, it is
possible to remarkably improve operability of the post-treatment (an
example of preferable post-treatments). Furthermore, as a method of
controlling side reactions of isobutene remaining in the reaction-terminated
liquid, there is also effective a method of adding to the reaction-terminated
liquid a reaction solvent that is greater than 5.0 in relative dielectric
constant sr, such as dimethylsulfoxide, N,N-dime thy lformamide, acetonitrile,
propionitrile, acetone, methylene chloride, tetrahydrofuran, ethyl acetate or
the like, a phosphine ligand such as triphenylphosphine,
l,2-bis(diphenylphosphino)ethane or the like, etc.
[0058] In the present invention, recovery and reuse of asymmetric catalyst
are possible, and method of recovery and reuse is not particularly limited.
There is preferable a method where, in the above-mentioned preferable
examples of the post-treatment, asymmetric analyst is recovered as a
distillation residue, and then it is reused by adding again ethyl
trifluoropyruvate and isobutene, or a method where asymmetric catalyst
[according to need, which has been allowed to stand under cooling or to
which a poor solvent (e.g., aliphatic hydrocarbon-series solvent or the like)
has been added] precipitated from the reaction-terminated liquid is
recovered by decantation, filtration or the like, and then it is reused similar
to the above. Particularly, the latter is more preferable, since it can be
applied to the recovery of an asymmetric catalyst that is thermally unstable.

In the case of the former, an asymmetric catalyst that is thermally unstable
can also be recovered, under a condition that a relatively high activity is
maintained, by conducting a distillation under reduced pressure by
controlling the bath temperature at 70°C or lower (preferably 60°C or lower,
and more preferably 50°C or lower).
[0059] [EXAMPLES]
Embodiments of the present invention are specifically explained by
examples, but the present invention is not limited to these examples.
Furthermore, reference examples and comparative examples are mentioned
in order to supplementarily explain examples. Regarding the concentration
indication of reaction solvent of Table 1 and Table 3, the case of using
reaction solvent in COL, 2.0L, 1.0L, 0.5L, 0.25L, 0.2L, 0.167L, or 0.125L
relative to 1 mole of fluorine-containing crketoester represented by formula
[1] is respectively represented by 0.25M, 0.5M, 1.0M, 2.0M, 4.0M, 5.0M, 6.0M,
or 8.0M.
[0060] [REFERENCE EXAMPLE l]
A reaction container was charged with 85.7mg (0.109mmol, leq) of
(S)-SEGPHOS-PdCl2 represented by the following formula
[Chemical Formula 36]

followed by replacement with argon. 5.4ml of acetone (50ml/lmmol of
(S)-SEGPHOS-PdCl2), 5.1mg (0.283mmol, 2.6eq) of water, and 82.4mg
(0.240mmol, 2.2eq) of AgSbFe were added, followed by stirring for 1 hour at
room temperature.

[0061] The preparation-terminated liquid was subjected to Celite filtration,
followed by concentration under reduced pressure, adding methylene
chloride to the concentration residue, and allowing it to stand for 1 day.
The methylene chloride solution was subjected again to Celite filtration,
followed by concentration under reduced pressure, vacuum drying, and
recrystallizing the dried residue from methylene chloride and n-hexane,
thereby obtaining 92.0mg (solid, yield 69%) of
(S)-SEGPHOS-Pd(2+)(OH2)2-2SbF6" (isolated) represented by the following
formula.
[Chemical Formula 37]

[0062] [REFERENCE EXAMPLE 2]
A reaction container was charged with 160.0mg (0.200mmol, leq) of
(R)-BINAP-PdCl2 represented by the following formula
[Chemical Formula 38]

followed by replacement with nitrogen. 10.0ml of acetone (50ml/lmmol of
(R)-BINAP-PdCl2), 9.4mg (0.520mmol, 2.6eq) of water, and 151.2mg

(0.440mmol, 2.2eq) of AgSbF6 were added, followed by stirring for 1 hour at
room temperature.
[0063] The preparation-terminated liquid was subjected to Celite filtration,
followed by concentration under reduced pressure, adding 5.0ml of
methylene chloride to the concentration residue, and allowing it to stir for all
night. The methylene chloride solution was subjected again to Celite
filtration, followed by concentration under reduced pressure, vacuum drying,
and recrystallizing (stirring for all night) the dried residue from 2.0ml of
methylene chloride and 15.0ml of n-hexane, thereby obtaining 213.2mg (a
yellow-color solid, yield 86%) of (R)-BINAP-Pd(2+)(OH2)2-2SbF6_ (isolated)
represented by the following formula.
[Chemical Formula 39]

[0064] [EXAMPLES 1-28] AND [COMPARATIVE EXAMPLES 1-13]
General production methods A to F of Examples and Comparative
Examples are shown, and these results are put together in Tables 1-3.
Furtherm jre, representative post-treatment operations are also described.
[0065] [Method A]
A reaction container was charged with
(S)-SEGPHOS-Pd(2+)(OH2)2-2SbF6~ (isolated: meaning an isolated one.
Hereinafter, the same.) represented by the following formula
[Chemical Formula 40]


followed by replacement with argon (in the case of using reaction solvent, it
was added at this stage). It was cooled down to a predetermined,
substrate-addition temperature and charged with ethyl trifluoropyruvate
represented by the following formula
[Chemical Formula 41]

and isobutene represented by the following formula
[Chemical Formula 42]

followed by stirring at a predetermined reaction temperature for a
predetermined reaction time.
[0066] The reaction-terminated liquid was subjected to post-treatment,
thereby obtaining (R)-trifluorocarbonyl-ene product represented by the
following formula.
[Chemical Formula 43]


[0067] [Method B]
A reaction container was charged with
(R)-BINAP-Pd(2+)(OH2)2-2SbF6~ (isolated) represented by the following
formula
[Chemical Formula 44]

followed by replacement with nitrogen. At room temperature, ethyl
trifluoropyruvate represented by the following formula
[Chemical Formula 45]

was added (in the case of adding reaction solvent, it was added at this stage),
followed by cooling down to a predetermined, substrate-addition
temperature, adding isobutene represented by the following formula
[Chemical Formula 46]


and stirring at a predetermined reaction temperature for a predetermined
reaction time.
[0068] The reaction-terminated liquid was subjected to post-treatment,
thereby obtaining (S)-trifluorocarbonyl-ene product represented by the
following formula.
[Chemical Formula 47]

[0069] [Method C]
A reaction container was charged with (R)-BINAP"PdCl2 (leq)
represented by the following formula
[Chemical Formula 48]

and AgSbF6 (2.2eq), followed by vacuum drying and replacement with
nitrogen. To the dried residue, acetone (200ml/lmmol of GO-BINAP-PdCk)
and water (2.6eq) were added, followed by stirring at room temperature for
lhr.
[0070] The preparation-terminated liquid was subjected to concentration
under reduced pressure and vacuum drying, thereby obtaining
(R)-BINAP-Pd(2+)(OH2)2-2SbF6" (in situ) represented by the following
formula
[Chemical Formula 49]


(a yellowcolor solid, yield was assumed to be 100%).
[0071] The reaction container was replaced with nitrogen and charged at
room temperature with ethyl trifluoropyruvate represented by the following
formula
[Chemical Formula 50]

followed by cooling down to a predetermined, substrate-addition
temperature, adding isobutene represented by the following formula
[Chemical Formula 51]

and stirring at a predetermined reaction temperature for a predetermined
reaction time.
[0072] The reaction-terminated liquid was subjected to post-treatment,
thereby obtaining (S)-trifluorocarbonyl-ene product represented by the
following formula.
[Chemical Formula 52]


[0073] [Method D]
A reaction container was charged with (R)-BINAP-PdCl2 (leq)
represented by the following formula
[Chemical Formula 53]

followed by replacement with nitrogen. At room temperature, ethyl
trifluoropyruvate represented by the following formula
[Chemical Formula 54]

and AgSbF6 (2.2eq) were added, and stirring was conducted at room
temperature for Ihr.
[0074] As the preparation-terminated liquid, an ethyl trifluoropyruvate
solution of (R)-BINAP-Pd(2+)-CF3COC02C2H5-2SbF6~ (in situ) represented by
the following formula
[Chemical Formula 55] ;


was obtained (a yellow-color suspension, yield was assumed to be 100%).
[0075] It was cooled down to a predetermined, substrate-addition
temperature, followed by adding isobutene represented by the following
formula
[Chemical Formula 56]

and stirring at a predetermined reaction temperature for a predetermined
reaction time.
[0076] The reaction-terminated liquid was subjected to post-treatment,
thereby obtaining (S)-trifluorocarbonyl-ene product represented by the
following formula.
[Chemical Formula 57]

[0077] [Method D-2]
In Method D, in place of (R)-BINAP-PdCl2, (S)-BINAP-PdCl2
represented by the following formula
[Chemical Formula 58]


was used to conduct it similarly, thereby obtaining (R)-tri£Luorocarbonyl-ene
product represented by the following formula.
[Chemical Formula 59]

[0078] [Method E]
A reaction container was charged with
(S)-SEGPHOS-Pd(2+)(OH2)2-2SbF6~ (isolated) represented by the following
formula
[Chemical Formula 60]

followed by replacement with argon. It was cooled down to a predetermined,
substrate-addition temperature, followed by adding ethyl trifluoropyruvate
represented by the following formula
[Chemical Formula 61]


and methylenecyclohexane represented by the following formula
[Chemical Formula 62]

and stirring at a predetermined reaction temperature for a predetermined
reaction time.
[0079] The reaction-terminated liquid was subjected to post-treatment,
thereby obtaining (R)-trifluorocarbonyl-ene product represented by the
following formula.
[Chemical Formula 63]

[0080] [Method F]
A reaction container was charged with (S)-Tol"BINAP-PdCl2 (leq)
represented by the following formula
[Chemical Formula 64]


followed by replacement with nitrogen. At room temperature, ethyJ
trifiuoropyruvate represented by the following formula
[Chemical Formula 65]

and AgSbF6 (2.2eq) were added, followed by stirring at room temperature for
1.5 hours.
[0081] As the preparation-terminated liquid, an ethyl trifiuoropyruvate
solution of (S)-Tol-BINAP-Pd(2+)-CF3COC02C2H5-2SbF6- (in situ)
represented by the following formula
[Chemical Formula 66]

was obtained (an orange-color to yellow-color suspension, yield was assumed
to be 100%).
[0082] It was cooled down to 1 predetermined, substrate-addition
temperature, followed by adding isobutene represented by the following
formula
[Chemical Formula 67]

and stirring at a predetermined reaction temperature for a predetermined
reaction time.

[0083] The reaction-terminated liquid was subjected to post-treatment,
thereby obtaining (R)-trifluorocarbonyl-ene product represented by the
following formula.
[Chemical Formula 68]

[0084] Conversion was calculated from the following formula after
measuring gas chromatography of Condition-1 and Condition-2. Relative
areal values of A, B and C were determined on the basis of areal value of C
(in the case of Condition-2, the total areal value of R configuration and S
configuration) in each measurement condition (Condition-1,* comparison
between areal value of B and areal value of C, Condition-2; comparison
between areal value of A and areal value of C).
[Numerical Formula l]
Relative areal value of C
Conversion (%) = xlOO
Relative areal value of A + Relative areal value of B + Relative areal value of C
A; ethyl trifluoropyruvate
B; ethyl trifluoropyruvate hydrate
C; optically active trifluorocarbonyl-ene product
Conversion of Comparative Example 7 was, however, calculated by the
following formula from the measurement result of Condition-1, since peaks
of propionitrile ot the reaction solvent and ethyl trifluoropyruvate
overlapped with each other in the measurement of Condition-2.
[Numerical Formula 2]
Areal value of C
Conversion of Comparative Example 7 (%) = xlOO
Areal value of B + Areal value of C
Furthermore, conversions of Examples 1, 2 and 12 and Comparative
Example 1 were determined by ^-NMR.

Optical purity was calculated by the following formula after
measuring gas chromatography of Condition-2.
[Numerical Formula 3]
~ ,. , -^ c Areal value of R configuration-Areal value of S configuration
Optical purity of = = ° x {00
R configuration (%ee) Areal value of R configuration + Areal value of S configuration
cr
[Numerical Formula 4]
„ ^. , . _ Areal value of S configuration - Areal value of R configuration
Optical purity of^ = t _ x \ 00
S configuration (%ee) Areal value of s configuration + Areal value of R configuration
Condition-1)
Column; DB-5 (I. D. 0.25mmx30m, film 0.25um), carrier gas," He, flow rate,'
163kPa (column inlet pressure), temperature condition; 50°C (5 minutes
retention) -> 10°C/min (temperature rise) -» 250°C (5 minutes
retention)/total 30 minutes, injection; 250°C, detector (FID),* 250°C, split
ratio,' 50, retention time; ethyl trifluoropyruvate hydrate for about 6 minutes,
and optically active trifluorocarbonyl-ene product (derived from isobutene)
for about 9 minutes.
Condition-2)
Column,' Cyclodex-p (I. D. 0.25mmx30m, film 0.25um), carrier gas,' He, flow
rate; 163kPa (column inlet pressure), temperature condition,' 50°C (5
minutes retention) -» 10°C/min (temperature rise) -> 150°C (10 minutes
retention)/total 25 minutes, injection,' 200°C, detector (FID); 200°C, split
ratio'. 50, retention time; ethyl trifluoropyruvate for about 2 minutes, and
optically active trifluorocarbonyl-ene product (derived from isobutene) R
configuration for 11.6 minutes and S configuration for 11.7 minutes.
[0085] Instrumental data of optically active trifluorocarbonyl-ene product
(derived from isobutene) are shown. 1H-NMR [standard substance;
(CH3)4Si, deuterated solvent; CDC13], 8ppm; 1.34(t, 7.1Hz, 3H), 1.78(s, 3H),
2.58(d, 14.0Hz, 1H), 2.75(d, 14.0Hz, 1H), 3.86(br, 1H), 4.34(m, 2H), 4.8l(s,
1H), 4.9l(s, 1H),

13ONMR [standard substance,* (CH^Si, deuterated solvent! CDCI3], 5 ppm'
13.9, 23.9, 38.7, 63.7, 78.l(q, Jc-F=28.7Hz), 116.1, 123.3(q, Jc-F=286.8Hz),
138.7, 169.5,
specific rotation [optical purity 97.9%ee(R)]; [a]23-7D=-6.8(CHCl3, c=2.47).

[0086] [Post-treatment operation of Example 2]
The reaction-terminated liquid was directly subjected to column
chromatography (silica gel, n-pentane:diethyl ether = 8:1), thereby obtaining
(R)-trifluorocarbonyl-ene product (derived from isobutene) in 4.433g (a
colorless, transparent liquid, yield 98%, chemical purity 99%, optical purity
98%ee).
[0087] [Post-treatment operation of Example 7]
Isobutene remaining in the reaction-terminated liquid was
concentrated under reduced pressure at -10 to -5°C, followed by distillation
under reduced pressure (bath temperature; ~+70°C), thereby obtaining
(S)-trifluorocarbonyl-ene product (derived from isobutene) in 10.90g (a
colorless, transparent liquid, yield 96%, chemical purity 99%, optical purity
95%ee).
[0088] [Post-treatment operation of Example 14]
Isobutene remaining in the reaction-terminated liquid was
concentrated under reduced pressure at 0°C, followed by distillation under
reduced pressure (bath temperature," ~50°C), thereby obtaining
(S)-trifluorocarbonyl-ene product (derived from isobutene) in 12.89g (a
colorless, transparent liquid, yield 91%, chemical purity 99%, optical purity
96%ee).
[0089] [Post-treatment operation of Example 21]
Isobutene and diethyl ether remaining in the reaction-terminated
liquid were concentrated under reduced pressure at 0°C, foltowed by
distillation under reduced pressure (bath temperature,' ~50°C), thereby
obtaining (S)-trifluorocarbonyl-ene product (derived from isobutene) in
11.21g (a colorless, transparent liquid, yield 99%, chemical purity >99%,
optical purity 97%ee).

WE CLAIM:
1. A method for producing an optically active, fluorine-containing,
carbonyl-ene product represented by formula [3]

wherein Rf represents a trifluoromethyl group,
R represents an alkyl group,
each of R1, R2, R3, R4 and R5 independently represents a hydrogen
atom, alkyl group, substituted alkyl group, aromatic ring group, or
substituted aromatic ring group,
* represents an asymmetric carbon, but is not an asymmetric
carbon in case that R4 and R5 are the same substituents, and
wave line represents an E configuration or Z configuration in
geometrical configuration of the double bond, the method comprising
reacting a fluorine-containing crketoester represented by formula [l]

wherein Rf and R respectively represent the same substituents as
above, with an alkene represented by formula [2]

wherein each of R1, R2, R3, R4 and R5 independently represents the
same substituent as above, characterised in that the reaction is carried out

in the presence of a bivalent cationic transition metal complex having an
optically active ligand,
wherein usage of the bivalent cationic transition metal complex
having the optically active ligand is 0.001 moles or less relative to 1 mole of
the fluorine-containing a-ketoester represented by formula [1],
wherein the reaction is conducted without intentionally adding any
liquid compound from the outside of the reaction system, besides the
reaction substrates and the bivalent cationic transition metal complex.
2. A method as claimed in claim 1 for producing optically active,
trifluorocarbonyl-ene product represented by formula [6]

wherein * represents an asymmetric carbon, the method comprising
reacting ethyl trifluoropyruvate represented by formula [4]

with isobutene represented by formula [5]

in the presence of 0.0005 moles or less of a bivalent cationic transition metal
complex having an optically active ligand relative to 1 mole of the ethyl
trifluoropyruvate represented by formula [4],
wherein the reaction is conducted without intentionally adding any
liquid compound from the outside of the reaction system, besides the
reaction substrates and the bivalent cationic transition metal complex.

3. A method as claimed in claim 2 for producing
(R)_trifluorocarbonyl-ene product represented by formula [7]

the method comprising reacting ethyl trifluoropyruvate represented by
formula [4]

with isobutene represented by formula [5]

in the presence of 0.0003 moles or less of a bivalent cationic palladium
complex having an optically active ligand relative to 1 mole of the ethyl
trifluoropyruvate represented by formula [4],
wherein the reaction is conducted without intentionally adding any
liquid compound from the outside of the reaction system, besides the
reaction substrates and the bivalent cationic transition metal complex.
4. A method as claimed in claim 1 for producing optically active,
trifluorocarbonyl-ene product represented by formula [6]

wherein * represents an asymmetric carbon to give R-form or
S-form, or the following formula,


wherein * represents an asymmetric carbon to give R-form or
S-form, the method comprising reacting ethyl trifluoropyruvate represented
by formula [4]

with isobutene represented by formula [5]

or methylenecyclohexane represented by the following formula,

in the presence of 0.0003 moles or less of a bivalent cationic palladium
complex relative to 1 mole of the ethyl trifluoropyruvate represented by
formula [4],
wherein the reaction is conducted without intentionally adding any
liquid compound from the outside of the reaction system, besides the
reaction substrates and the bivalent cationic palladium complex,
wherein the bivalent cationic palladium complex is represented by
the general formula [8],


or the general formula [10],

wherein, in the general formula [10], Rf represents a
trifluoromethyl group, and R represents an ethyl group,
wherein, in the general formulas [8] and [10], Y represents Pd, Z
represents SbF6, and X-*-X represents an optically active SEGPHOS
derivative represented by the following formula,

wherein R represents a phenyl group, or an optically active BINAP
derivative represented by the following formula,


wherein R represents a phenyl group.

ABSTRACT

Title: METHOD FOR PRODUCING OPTICALLY ACTIVE
FLUORINE-CONTAINING CARBONYL-ENE PRODUCT
An optically active, fluorine-containing carbonyl-ene product is
produced by reacting a fluorine-containing orketoester with an alkene in the
presence of a transition metal complex having an optically active ligand.
There are Mode 1 of conducting this reaction in the absence of reaction
solvent. Mode 2 of conducting this reaction in a solvent that is low in relative
dielectric constant, and Mode 3 of conducting this reaction in a halogenated
hydrocarbon-series solvent. In each of these three modes, it is possible to
produce the optically active, fluorine-containing carbonyl-ene product with
low cost.