LIGAND, METHOD FOR PRODUCING THE SAME, AND CATALYST USING THE LIGAND
Technical Field
The present invention relates to a novel ligand and. a method for producing the ligand, and a catalyst using the ligand.
Background Art
The present inventors, or some of the present inventors, or inventors partly including the present inventors have developed a variety of asymmetric ligands having a glucose as a mother nucleus and catalysts therewith (see Patent Document 1 and the like) , and have found that the catalysts can promote a variety of catalytically asymmetric reactions such as a catalytically asymmetric cyanation to ketone or ketoimine, a catalytically asymmetric conjugate addition reaction of a cyano group to a,p-unsaturated carboxylic acid derivatives and a catalytically asymmetric ring opening reaction due to a cyano group of aziridine. Patent Document 1: Japanese Patent No. 3671209
Disclosure of Invention
Problem to be solved by the Invention
However, since many steps are necessary to synthesize an asymmetric ligand having a glucose as a mother nucleus (hereinafter, in some cases, simply referred to as 1glucose-derived ligand1) , the ligand was disadvantageous from

a standpoint of cost.
Further, it still has a need for catalysts having higher catalytic activity and higher enantioselectivity as well.
An object of the present invention is to provide a novel asymmetric ligand that is synthesized by a short production process at low cost and a producing method thereof, and a catalyst using the novel ligand.
Further, other than or in addition to the above-described objects, an object of the present invention is to provide a novel asymmetric ligand that is capable of developing the catalyst activity and enantioselectivity higher than that of a conventional glucose-derived ligand and a producing method thereof, and a catalyst using the novel ligand.
In particular, an object of the present invention is to provide, in a catalytically asymmetric ring opening reaction in a cyano group of aziridine, which is useful for synthesizing an optically active p-amino acid, a novel asymmetric ligand that is capable of developing functions such as catalyst activity and enantioselectivity excellent more than that of a conventional glucose-derived ligand and a producing method thereof, and a catalyst using the novel ligand.
Means for Solving Problem
The present inventors have found that the following inventions can solve the above-described problems:
<1> A ligand represented by following general formula I:


wherein each of R1d and Rd independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1 to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trifluoroacetyl group, a trif luoromethyl group, an alkoxy group represented by-ORd (Rd represents a linear or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NRdbRd (each of Rd and Rbd independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed of A2 and A3.


wherein each of R111 and Rd independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1 to Ad independently represents a hydrogen atom, a fluorine atom/ a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trif luoroacetyl group, a trif luoromethyl group, an alkoxy group represented by-ORd (Rd represents a linear or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NRdbRbd (each of RBB and Rbd independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed of A2 and A3.

wherein each of R1d and Rd independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1 to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trif luoroacetyl group, a trif luoromethyl

group, an alkoxy group represented by-ORd (Rd represents a linear or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NRdbRbd (each of R*d and Rbd independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed of A2 and A3.
<4> In any one of the above items <1> to <3>, n may be an integer of 0 or 1, and preferably 0.
<5> In any one of the above items <1> to <4>, m may be an integer of 2 to 4, and preferably 2 or 3.
<6> In any one of the above items <1> to <5>, two of the A1 to A4 may be hydrogen atoms and the other two thereof may be fluorine atoms, preferably A1 and A4 may be hydrogen atoms and A2 and A3 may be fluorine atoms.
<1> A method of producing a ligand represented by following general formula I from a compound represented by

wherein each of R-1- and Rd independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an

integer of 0 to 7; n represents an integer of 0 to 3; and each of A1 to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trifluoroacetyl group, a trifluoromethyl group, an alkoxy group represented by-ORd {Rd represents a linear or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NRBDRBD (each of R*d and Rbd independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed

wherein Rd represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms, a benzyl group, a pararaethoxy benzyl group or a silyl group; m has the same definition as described above; and each of A1 to A4 independently has the same definition as described above,
the method comprising the steps of:
a) reacting the compound representedby the general formula
II with a metal salt of diphenylphosphine, diarylphosphine or
diarylamine;
b) thereafter, processing with ammonium chloride and

hydrogen peroxide; and
b' ) when X is As or N and R^ is one other than a hydrogen atom, allowing palladium-carbon to react with hydrogen, lithium chloride, dichlorodicyanobenzoquinone, ceriumammoniumnitrate or a fluorine anion to make the R^ a hydrogen atom, to obtain the ligand represented by the general formula I.
<8> In the above item <7>, the compound represented by the general formula II may be obtained by c) reacting a compound represented by following general formula III, wherein m has the same definition as described above, in the presence of diethylazodicarboxylate or diisopropylazodicarboxylate and triphenylphosphine or tributylphosphine, with a compound represented by following general formula IV, wherein R^ and A1

<9> In the above item <8>, the compound represented by the general formula III may be obtained by d) reacting a compound represented by following general formula V, wherein m has the same definition as described above, in the presence of a phosphoric acid buffer, with a peracid:


<10> A method of producing a ligand represented by following general formula la from a compound represented by

wherein each of R-1 and R^ independently represents 0 to 5 substituent groups; X represents P, As or M; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1 to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trifluoroacetyl group, a trif luoromethyl group, an alkoxy group represented by-OR^ (R^ represents a linear or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NR'^R'^ (each of R*^ and R'^ independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed


wherein R^ represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms, a benzyl group, a paramethoxy benzyl group or a silyl group; m has the same definition as described above; and each of A1 to A4 independently has the same definition as described above,
the method comprising the steps of:
a) reacting the compound represented by the general formula
Ila with a metal salt of diphenylphosphine, diarylphosphine or
diarylamine;
b) thereafter, processing with ammonium chloride and
hydrogen peroxide; and
b' ) when X is As or N and R^ is one other than a hydrogen atom, allowing palladium-carbon to react with hydrogen, lithium chloride, dichlorodicyanobenzoquinone, ceriumammoniumnitrate or a fluorine anion to make the R^ a hydrogen atom, to obtain the ligand represented by the general formula la.
<11> In the above item <10>, the compound represented by the general formula Ilamaybe obtained by c) reacting a compound represented by following general formula Ilia, wherein m has the same definition as described above, in the presence of diethylazodicarboxylate or diisopropylazodicarboxylate and triphenylphosphine or tributylphosphine, with a compound represented by following general formula IV, wherein R^ and A1 to A4 have the same definitions as described above:



<12> In the above item <11>, the compound represented by the general formula Ilia may be obtained by d) reacting a compound represented by following general formula Va, wherein m has the same definition as described above, in the presence
wherein each of Rd and Rd independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1 to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trif luoroacetyl group, a trif luoromethyl group, an alkoxy group represented by-ORd [Rd represents a linear

or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NRBDRBD (each of RBB and R*d independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed
wherein Rbb represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms, a benzyl group, a paramethoxy benzyl group or a silyl group; m has the same definition as described above; and each of A1 to A4 independently has the same definition as described above,
the method comprising the steps of:
a) reacting the compound represented by the general formula
lib with a metal salt of diphenylphosphine, diarylphosphine or
diarylamine;
b) thereafter, processing with ammonium chloride and
hydrogen peroxide; and
bb ) when X is As or N and Rd is one other than a hydrogen atom, allowing palladium-carbon to react with hydrogen, lithium chloride, dichlorodicyanobenzoquinone, ceriumammoniumnitrate or a fluorine anion to make the R-d a hydrogen atom, to obtain the ligand represented by the general formula lb.

<14> In the above item <13>, the compound represented by the general formula Ilbmaybe obtained by c) reacting a compound represented by following general formula Illb, wherein m has the same definition as described above, in the presence of diethylazodicarboxylate or diisopropylazodicarboxylate and triphenylphosphine or tributylphosphine, with a compound represented by following general formula IV, wherein R-d and A1 to A4 have the same definitions as described above:

<15> In the above item <14>, the compound represented by the general formula Illb may be obtained by d) reacting a compound represented by following general formula Vb, wherein m has the same definition as described above, in the presence

<16> In any one of the above items <7> to <15>, n may be an integer of 0 or 1, and preferably 0.
<17> In any one of the above items <7> to <16>, m may be an integer of 2 to 4, and preferably 2 or 3.
<18> In any one of the above items <7> to <17>, two of the A1 to A4 may be hydrogen atoms and the other two thereof

may be fluorine atoms, preferably A1 and A4 may be hydrogen atoms and A2 and A3 may be fluorine atoms.
<19> In any one of the above items <7> to <18>, R1b may be a methyl group.
<20> A producing method of a ligand represented by following general formula I from a compound represented by

wherein each of R-1 and Rd independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1 to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trif luoroacetyl group, a trif luoromethyl group, an alkoxy group represented by-ORd (Rd represents a linear or branched alkyl group having I to 4 carbon atoms), an amino group represented by -NRBDRBD (each of Rd and Rbd independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed of A2 and A3, and


wherein Rd represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms, a benzyl group, a paramethoxy benzyl group or a silyl group; m has the same definition as described above; and each of A\ to A4 independently has the same definition as described above,
the method comprising the steps of:
g) reacting the compound represented by the general formula II with diethylaluminuin cyanide, followed by reacting with concentrated hydrochloric acid, to obtain a compound represented by following general formula VII, wherein m, Rd and A1 to A4 have the same definitions as described above;
h) reacting the compound representedby the general formula
VII with a BH3 tetrahydrofuran complex, a BH3 dimethylsulfide
complex or LiAlH4, to obtain a compound represented by following
general formula VIII, wherein m, Rd and A1 to A4 have the same
definitions as described above;
j ) reacting the compoundrepresentedby the general formula
VIII with p-toluenesulfonyl chloride, to obtain a compound
represented by following general formula IX, wherein Ts
represents a p-toluenesulfonyl group; and m, Rd and A1 to A4 have
the same definitions as described above;

k) reacting the compound represented by the general formula
IX with potassium diphenyl phosphide, followed by reacting with
hydrogen peroxide, to obtain a compound represented by following
general formula X, wherein m, Rd and A1 to A4 have the same
definitions as described above; and
1) reacting the compound represented by the general formula
X with lithium iodide, to obtain the ligand represented by the


following general formula la from a compound represented by

wherein each of Rd and Rd independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1 to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trif luoroacetyl group, a trif luoromethyl group, an alkoxy group represented by-ORd (Rd represents a linear or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NRdR*d (each of R** and R*d independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed


alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms, a benzyl group, a paramethoxy benzyl group or a silyl group; m has the same definition as described above; and each of A1 to A4 independently has the same definition as described above,
the method comprising the steps of:
g) reacting a compound represented by the general formula Ila with diethylaluminum cyanide, followed by reacting with concentrated hydrochloric acid, to obtain a compound represented by following general formula Vila, wherein m, Rd and A1 to A4 have the same definitions as described above;
h) reacting the compound represented by the general formula Vila with a BH3 tetrahydrofuran complex, a BH3 dimethylsulfide complex or LiAlH4, to obtain a compound represented by following general formula Villa, wherein m, Rbd and A1 to A4 have the same definitions as described above;
j ) reacting the compound represented by the general formula Villa with p-toluenesulfonyl chloride, to obtain a compound represented by following general formula IXa, wherein Ts represents a p-toluenesulfonyl group, and m, R1d and A1 to A4 have the same definitions as described above;
k) reacting the compoundrepresentedby the general formula IXa with potassium diphenyl phosphide, followed by reacting with hydrogen peroxide, to obtain a compound represented by following general formula Xa, wherein m, R1b and A1 to A4 have the same definitions as described above; and
1) reacting the compoundrepresentedby the general formula

Xa with lithium iodide, to obtain the ligand represented by the

<22> A method of producing a ligand represented by following general formula lb from a compound represented by following general formula lib:


wherein each of R1*1 and Rd independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1 to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trif luoroacetyl group, a trif luoromethyl group, an alkoxy group represented by-OR® (R® represents a linear or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NRBDRBD (each of RBD and Rbd independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed

wherein R-d represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms, a benzyl group, a

paramethoxy benzyl group or a silyl group; m has the same definition as described above; and each of A1 to A4 independently has the same definition as described above,
the method comprising the steps of:
g) reacting a compound represented by the general formula lib with diethylaluminum cyanide, followed by reacting with concentrated hydrochloric acid, to obtain a compound represented by following general formula Vllb, wherein m, R1d and A1 to A9 have the same definitions as described above;
h) reacting the compound represented by the general formula Vllb with a BH3 tetrahydrofuran complex, a BH3 dimethylsulfide complex or LiAlH4, to obtain a compound represented by following general formula Vlllb, wherein m, Rd and A1 to A4 have the same definitions as described above;
j ) reacting the compound represented by the general formula Vlllb with p-toluenesulfonyl chloride, to obtain a compound represented by following general formula IXb, wherein Ts represents a p-toluenesulfonyl group, and m, Rd and A1 to A4 have the same definitions as described above;
k) reacting the compound represented by the general formula IXb with potassium diphenyl phosphide, followed by reacting with hydrogen peroxide, to obtain a compound represented by following general formula Xb, wherein m, Rd and A1 to A4 have the same definitions as described above; and
1) reacting the compound represented by the general formula Xb with lithium iodide, to obtain the ligand represented by the general formula lb:


<23> In any one of the above items <20> to <22>, n may¬be an integer of 0 or 1, and preferably 0.
<24> In any one of the above items <20> to <23>, m may be an integer of 2 to 4, and preferably 2 or 3.
<25> In any one of the above items <20> to <24>, two of the A1 to A4 may be hydrogen atoms and the other two thereof may be fluorine atoms, preferably A1 and A4 may be hydrogen atoms and A2 and A3 may be fluorine atoms.

<26> In any one of the above items <20> to <25>, dd may¬be a methyl group.
<27> A catalyst being formed of:
fl) a metal alkoxide or a metal amide represented by Md (ORbd) y or MKb(NRd)yb, wherein M is a metal selected from the group consisting of titanium, zirconium, aluminum, gallium, barium and rare earth elements; each of Rbb and Rd independently represents a substituted or non-substituted, linear or branched or cyclic alkyl group having 2 to 6 carbon atoms, a substituted or non-substituted, linear or branched or cyclic alkenyl group, a substituted or non-substituted aromatic group or a trialkylsilyl group, and x and y and xb and yb are integers stoichiometrically determined by the metal M; and
B) a ligand represented by following general formula I, wherein each of Rd and Rd independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1 to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trif luoroacetyl group, a trif luoromethyl group, an alkoxy group represented by-ORd (Rd represents a linear or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NRdRbd (each of R11 and Rbb independently represents a hydrogen atom, or a linear or branched alkyl group having 1 to 4 carbon atoms}, a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed of A2 and A3:

<31> In any one of the above items <27> to <30>, the rare earth metal may be ytterbium, yttrium, lanthanum, cerium, praseodymium, samarium, europium, gadolinium, dysprosium, holmium or erbium.
<32> In any one of the above items <27> to <31>, an alkyl group of the trialkylsilyl group may be a linear or branched alkyl having 1 to 4 carbon atoms.
<33> In any one of the above items <27> to <32>, the A) metal alkoxide or metal amide may be gadolinium triisopropoxide, yttrium triisopropoxide,
tris-[N,N-bis(trimethylsilyl)amide]gadolinium (III), tris-[N,N-bis(trimethylsilyl)amide]yttrium (III) or barium diisopropoxide.
<34> In any one of the above items <27> to <33>, n may be an integer of 0 or 1, and preferably 0.
<35> In any one of the above items <27> to <34>, m may be an integer of 2 to 4, and preferably 2 or 3.
<36> In any one of the above items <27> to <35>, two of the A1 to A1 may be hydrogen atoms and the other two thereof may be fluorine atoms, preferably A1 and A4 may be hydrogen atoms and A2 and A3 may be fluorine atoms.
A ligand represented by the above-described general formula la, wherein each of Rd and Rd independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1 to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group.

an acetyl group, or a ring formed of A2 and A3.
In the above item , n may be an integer of 0 or 1, and preferably 0.
In the above item or , m may be an integer of 2 to 4, and preferably 2 or 3.
In any one of the above items to , two of the A1 to A4 may be hydrogen atoms and the other two thereof may be fluorine atoms, preferably A1 and A4 may be hydrogen atoms and A2 and A3 may be fluorine atoms.
A method of producing a ligand represented by the above-described general formula la (wherein each of R-1- and Rd independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1 to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, or a ring formed of A2 and A3) from a compound represented by the above-described general formula Ila (wherein Rd represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms, a benzyl group, a paramethoxy benzyl group or a silyl group; m has the same definition as described above; and each of A1 to A4 independently has the same definition as described above);
the method comprising the steps of:
a) reacting the compound represented by the general formula Ila with a metal salt of diphenylphosphine, diarylphosphine or diarylarnine;

b) thereafter, processing with arnmonium chloride and hydrogen peroxide; and
bb) when X is As or N1 and Rbd is one other than a hydcogen atom, allowing palladium-carbon to react with hydrogen, lithium chloride, dichlorodicyanobenzoquinone, ceriumammoniumnitrate or a fluorine anion (for example, a fluorine anion derived from tetrabutylammonium fluoride) to make the Rd a hydrogen atom, to obtain the ligand represented by the general formula la.
In the above item , the compound represented by the general formula I la may be obtained by c) reacting a compound represented by the above-described general formula Ilia, wherein m has the same definition as described above, in the presence of diethylazodicarboxylate or diisopropylazodicarboxylate and triphenylphosphine or tributylphosphine, with a compound represented by the above-described general formula IV, wherein Rd and A1 to A4 have the same definitions as described above.
In the above item , the compound represented by the general formula Ilia may be obtained by d) reacting a compound represented by the above-described general formula Va, wherein m has the same definition as described above, in the presence of a phosphoric acid buffer, with a peracid (such as 3-chioroperbenzoic acid, perbenzoic acid, peracetic acid or hydrogen peroxide, in particular, 3-chloroperbenzoic acidbeing preferred).
In any one of the above items to , n may be an integer of 0 or 1, and preferably 0.
In any one of the above items to , m may

be an integer of 2 to 4, and preferably 2 or 3.
In any one of the above items to , two of the A1 to A4 may be hydrogen atoms and the other two thereof may be fluorine atoms, preferably A1 and A4 may be hydrogen atoms and A2 and A3 may be fluorine atoms.
In any one of the above items to , Rd may be a methyl group.
A method of producing a ligand represented by the above-described general formula la (wherein each of Rd and Rd independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1 to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, or a ring formed of A2 and A3) from a compound represented by the above-described general formula Ha (wherein Rd represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms, a benzyl group, a paramethoxy benzyl group or a silyi group; m has the same definition as described above; and each of Ax to A4 independently has the same definition as described above);
the method comprising the steps of:
g) reacting a compound represented by the general fotmula Ila with diethylaluminum cyanide, followed by reacting with concentrated hydrochloric acid, to obtain a compound represented by the above-described general formula Vila, wherein m, Rd and A1 to A4 have the same definitions as described above;

h) reacting the compound representedby the general formula Vila with BH3, to obtain a compound represented by the above-described general formula Villa, wherein m, Rd and A1 to A4 have the same definitions as described above;
j ) reacting the compound represented by the general formula Villa with p-toluenesulfonyl chloride, to obtain a compound represented by following general formula IXa, wherein Ts represents a p-toluenesulfonyl group, and m, Rd and A1 to A4 have the same definitions as described above;
k) reacting the compound representedby the general formula IXa with potassium diphenyl phosphide, followed by reacting with hydrogen peroxide, to obtain a compound represented by the above-described general formula Xa, wherein m, Rd and A1 to A4 have the same definitions as described above; and
1) reacting the compound represented by the general formula Xa with lithium iodide, to obtain the ligand represented by the general formula la.
In the above item , n may be an integer of 0 or 1, and preferably 0.
In the above item or , mmay be an integer of 2 to 4, and preferably 2 or 3.
In any one of the above items to , two of the A1 to Ad may be hydrogen atoms and the other two thereof may be fluorine atoms, preferably A1 and A4 may be hydrogen atoms and A2 and A3 may be fluorine atoms.
In any one of the above items to , Rd may be a methyl group.

A catalyst being formed of:
A) a metal alkoxide or a metal amide represented by Mx (ORd) y or MKb{NRd)yb, wherein M is a metal selected from the group consisting of titanium, zirconium, aluminum, gallium and rare earth elements; each of Rd and Rd independently represents a substituted or non-substituted, linear or branched or cyclic alkyl group having 2 to 6 carbon atoms, a substituted or non-substituted, linear or branched or cyclic alkenyl group, a substituted or non-substituted aromatic group or a trialkylsilyl group, and x and y and sb and yb are integers stoichiometrically determined by the metal M; and
B) a ligand represented by the above-described general formula la, wherein each of R111 and Rd independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1 to Ad independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group or a ring formed of A2 and A3.
In the above item , the A) metal alkoxide or metal amide and B) ligand may be 1:1 to 1:4 by molar ratio of A:B.
In the above item or , the rare earth metalmay be ytterbium, yttrium, lanthanum, cerium, praseodymium, samarium, europium, gadoliniuin, dysprosium, holmium or erbium.
In any one of the above items to , an alkyl group of the trialkylsilyl group may be a linear or branched alkyl having 1 to 4 carbon atoms.

In any one of the above items to , the A) metal alkoxide or metal amide may be gadolinium triisopropoxide, yttrium triisopropoxide, tris-[N,N-bis(trimethylsilyl)amide]gadolinium (III), or tris-[N,N-bis(trimethylsilyl)amide]yttrium (III) .
In any one of the above items to , n may be an integer of 0 or 1, and preferably 0.
In any one of the above items to , m may be an integer of 2 to 4, and preferably 2 or 3.
In any one of the above items to , two of the A1 to A1 may be hydrogen atoms and the other two thereof may be fluorine atoms, preferably A1 and A4 may be hydrogen atoms and A2 and A3 may be fluorine atoms.
Effects of the invention
The present invention can provide a novel asymmetricligand that is synthesized by a short production process at low cost and a producing method thereof, and a catalyst using the novel ligand.
Further, other than or in addition to the above-described effects, the present invention can provide a novel asymmetric ligand that is capable of developing the catalyst activity and enantioselectivity higher than that of a conventional glucose-derived ligand and a producing method thereof, and a catalyst using the novel ligand.
In particular, the present invention can provide, in a catalytically asymmetric ring opening reaction in a cyano group

of aziridine, which is useful for synthesizing an optically active [J-amino acid, a novel asymmetric ligand that is capable of developing functions such as catalyst activity and enantioselectivity excellent more than that of a conventional glucose-derived ligand and a producing method thereof, and a catalyst using the novel ligand.
Best mode for carrying out the present invention
The present invention will be described in detail hereinafter.
The present invention provides a novel asymmetric ligand.
A ligand according to the present invention may be represented by a formula I or la or lb shown below (hereinafter, in some cases, formulas I, la and lb are abbreviated as 1formula I or the like1) . In the formulas, each of Rbb1 and Rd independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1 to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, a nitro group, a trifluoroacetyl group, a trifluoromethyl group, an alkoxy group represented by -ORd (Rd represents a linear or branched alkyl group having 1 to 4 carbon atoms) , an amino group represented by -NRdbRd (each of R1D and Rbd independently represents a hydrogen atom or a linear or branched alkyl group having 1 to -4 carhon atoms) , a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl

group or a ring formed of A2 and A3.
As can be seen from the formula I or the like, the ligand according to the present invention is different from a conventional ligand of which mother nucleus is derived from glucose (such as Japanese Patent No. 3671209). The ligand according to the present inventiond which is different in a structure from that of a conventional ligand, has a function such as described below. For instance, according to the ligand of the present invention, a catalyst using the ligand has high


In the formulas, n may be an integer of 0 or 1, preferably 0; m may be an integer of 2 to 4 and preferably 2 or 3; and X may be P or N, preferably P.
Among A1 to Ad, preferably two may be hydrogen atoms, and the other two may be fluorine atoms, and more preferably A1 and A4 may be hydrogen atoms and A2 and A3 may be fluorine atoms.
An asymmetric ligand according to the present invention may be prepared:
From a compound represented by the formulas II or the like (the phrase 1the formula II or the like1 used herein means a formula II, Ila or lib, and, hereinafter, in some cases, simply abbreviated as 1formula II or the like1), a ligand represented by the formula I or the likemay be prepared. The method comprises the step of:
a) reacting a compound represented by the formula II or the like with a metal salt of diphenylphosphine, a metal salt of diarylphosphine or a metal salt of diarylaraine;
b) thereafter processing with ammonium chloride and hydrogen peroxide; and
bb } when X is As or N and Rd is other than a hydrogen atom, allowing palladium-carbon to react with hydrogen, lithium chloride, dichlorodicyanobenzoquinone, ceriumammoniumnitrate or a fluorine anion (such as fluorine anion derived from tetrabutylammonium fluoride) to make Rd a hydrogen atom.
Herein, in the formula II or the like, Rd represents a hydrogen atom, a linear or branched alkyl group having 1 to 8

carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms, a benzyl group, a paramethoxybenzyl group or a silyl group. Rbb preferably represents a methyl group or a benzyl group and more preferably a methyl group. In the formula II or the like, m and A1 to A4 have same definitions as described above.
The step a) , depending on compounds used, may be carried out by use of a solvent such as tetrahydrofuran (hereinafter, abbreviated as 1THF1), ethers or dioxane under conditions of -78 to 50°C.
Further, the step b), depending on compounds used, may be carried out by use of a solvent such as THF, ethers or dioxane under conditions of -20 to 20°C.
More, the step bb)/ depending on compounds used, may be carried out by use of a solvent such as THF, ethers, dioxane, methylene chloride, dimethyl formamide, or dimethyl sulfoxide under conditions of -78 to 50°C.
The producing method that has the steps a) and b) {and step bb ) ) is preferred when one where n is zero in the formula I is obtained and in less steps.
Further, a compound represented by the formula II or the like is prepared as follows:
c) Keating a compound represented by the formula III or the like (Herein, 1the formula III or the like1 means formula III, Ilia or Illb. Hereinafter, in some cases, these are simply abbreviated to as 1formula III or the like1) , under the presence of diethylazodicarboxylate or diisopropylazodicarboxylate and

triphenyl phosphine or tributyl phosphine, preferably under the presence of diisopropylazodicarboxylate, with a compound represented by the formula IV can obtain a compound represented by the formula II or the like. In the formula III or the like and IV, m, Rd and A1 to A4 have the same definitions as described above.
The step c) , depending on compounds used, may be carried out by use of a solvent such as THF, ethers, or dioxane under conditions of 0 to 50°C.
Further, a compound represented by the formula III or the like is prepared as follows:
d) Reacting a compound represented by the formula V or the like (Herein, 1the formula V or the like1 means formulas V, Va or Vb. Hereinafter, in some cases, these are simply abbreviated as 1formula V or the like1), under the presence of a phosphoric acid buffer, with a peracid (such as 3-chloroperbenzoic acid, perbenzoic acid, peracetic acid or hydrogen peroxide, 3-chloroperbenzoic acid being particularly preferred) can obtain a compound represented by the formula III or the like . In the f ormula Vor the like, m has the same definition as described above.
The step d) , depending on compounds used, may be carried out by use of a solvent such as methylene chloride, chloroform, ethers or dioxane under conditions of -20 to 20°C.
More, a ligand according to the present invention may be produced from a compound represented by the formula II or the like through a route different from the above-mentioned ones.

The method may comprise the steps of:
g) reacting the compound represented by the general formula II or the like with diethylaluminum cyanide, followed by reacting with concentrated hydrochloric acid, to obtain a compound represented by the formula VII or the like (the term 1the formula VII or the like1 used herein means a formula VII, Vila or Vllb. Hereinafter, in some cases, these are simply abbreviated as 1the formula VII or the like1);
h) reacting the compound represented by the general formula
VII or the like with a BH3 tetrahydrofuran complex, a BH3
dimethylsulfide complex or LiAlH4, to obtain a compound
represented by the formula VIII or the like (the term 1the formula
VIII or the like1 used herein means a formula VIII, Villa or
Vlllb. Hereinafter, in some cases, these are simply abbreviated
as 1the formula VIII or the like1);
j) reacting the compound represented by the formula VIII or the like withp-toluenesulf onyl chloride, to obtain a compound represented by the formula IX or the like (the term 1the formula
IX or the like1 used herein means a formula IX, IX a or IX b.
Hereinafter, in some cases, these are simply abbreviated as 1the
formula IX or the like1);
k) reacting the compound represented by the formula IX or the like with1potassium diphenyl phosphide, followed by reacting with hydrogen peroxide, to obtain a compound represented by the formula X or the like (the term 1the formula X or the like1 used herein means a formula X, X a or X b. Hereinafter, in some cases, these are simply abbreviated as 1the formula X

or the like1); and
1) reacting the compound represented by the general formula X with lithium iodide, to obtain the ligand represented by the formula I or the like.
In the formulae VII or the like, VIII or the like, IX or the like and X or the like, m, R1d andA1 to A4 have the same definitions as described above. Further, in the formula IX or the like, Ts represents p-toluenesulfonyl group.
The step g) , depending on compounds used, may be carried out by use of a solvent such as THF, ethers, dioxane or toluene under conditions of -20 to lOOdC.
The step h) , depending on compounds used, may be carried out by use of a solvent such as THF, ethers, dioxane or toluene under conditions of -20 to 20°C.
The step j ) , depending on compounds used, may be carried out by use of a solvent such as methylene chloride or pyridine under conditions of -78 to 50°C.
The step k) , depending on compounds used, may be carried out by use of a solvent such as THF, ethers, dioxane or toluene under conditions of -78 to 50°C.
The step 1), depending on compounds used, may be carried out by use of a solvent such as dimethyl formamide or dimethyl sulfoxide under conditions of -78 to 200°C.
The present invention provides a catalyst using the above-described asymmetric ligand.
A catalyst according to the present invention is formed

of a metal alkoxide or a metal amide represented by A) Mx{ORd)y or Mxb(NRd)yb; and B) a ligand represented by the formula I.
Herein, M is a metal selected from a group of titanium, zirconium, aluminum, gallium, barium and rare earth elements. Each of Rbb and Rd independently represents a substituted or non-substituted linear or branched or cyclic alkyl group having 2 to 6 carbon atoms, a substituted or non-substituted linear or branched or cyclic alkenyl group, a substituted or non-substituted aromatic group or a trialkylsilyl group, wherein xandyandxb and yb are integers determined stoichiometrically by the metal M. An alkyl group of the trialkylsilyl group may be a linear or branched alkyl having 1 to 4 carbon atoms.
Among the M, preferable examples of the rare earth metals may include ytterbium, yttrium, lanthanum, cerium, praseodymium, samarium, europium, gadolinium, dysprosium, holmium and erbium. The M is particularly preferably gadolinium or yttrium.
Preferable examples of A) metal alkoxides or metal amides may include gadolinium triisopropoxide, yttrium triisopropoxide,
tris-[N,N-bis(trimethylsilyl)amide]gadolinium (III) and tris-[N,N-bis(trimethylsilyl)amide]yttrium (III) . Furthermore, A) metal alkoxide or metal amide is preferably barium diisopropoxide.
Herein, 1being formed of1 means a state including all of i) a case where both of the A component and B component work as a catalyst, ii) a case where ORbd or ORd of the A component ispartially or entirely substituted by a ligand of the B component

to work as a catalyst, and i±i) a case where both states of the i) and ii) are present and work as a catalyst.
In the A) metal alkoxide or metal amide and B) ligand, a mole ratio of A: B is 1:1 to 1:4 and preferably 1:1 to 1:2.
Such a catalyst may be prepared as shown below: Mixing the A component and B component in THF or propionitrile such that the mixture is in the above-described mole ratio, followed by reacting the mixture at a temperature from room temperature to 80°C can obtain the catalyst.
The present invention will be illustrated in more detail by way of, but is not limited to the following examples. Furthermore, Fig. 1 shows a scheme surveying following examples.

Optically active allylalcohol (see Lussem, B.J.; Gals, H.-J. J. Am. Chem. Soc. 2003, 125, 6066, 100 mg, 0.968 mmol) was dissolved in methylene chloride (10 mL> and a phosphoric acid buffer (2 mL), followed by, under ice-cooling, adding 3-chloroperbenzoic acid (0.34g, 0.968 mmol) . After stirring for 1 hr, sodium sulfate was added and a reaction solution was purified directly by means of alumina column chromatography (eluting solvent =methylene chloride -> ethyl acetate) to obtain

a target subject, epoxy alcohol (0.34 g, yield: 91%). NMR {CDCL3) 5 1.21-1.31 (IH, m) , 1.41-1.49 (IH, m> , 1.51-1.60 (2H, m) , 1.75-1.81 (IH, m} , 1.84-1.90 (IH, m) , 1.98 (IH, brs) , 3.31 (IH, t, J= 3.7 Hz) , 3.34 (IH, t, J= 3.7 Hz) , 4.00 (IH, brs) .

To a solution of triphenyl phosphine (1.12 g, 4.27 mmol) and monomethylfluorocatecol (584 mg, 4.27 mmol) in tetrahydrofuran (hereinafter, simply abbreviated as 1THF1)(5 rtiL) , a solution (1 mL) of diisopropylazodicarboxylate (DIAD)
(840 mL, 4.27 mmol) and epoxy alcohol (325 mg, 2.85 mmol) in THF was added under ice-cooling. After reacting the mixture at room temperature for 18 hr, the mixture was diluted with ethyl acetate, followed by washing an organic layer with water and a saturated saline solution. The organic layer was dried over sodium sulfate, filtered and concentrated. A resulting crude product was purified by use of silica gel column chromatography
(ethyl acetate: hexane = l: 5) , thereby toobtaina target product,
epoxy ether (649 mg, yield: 89%).
NMR (CDCL3) 5 1.24-1.33 (IH, m), 1.40-1.48 {IH, m), 1.51-1.57
{IH, m), 1.78-1.85 (IH, m), 1.89-1.95 (IH, m) , 2.04-2.10 (IH, m), 3.22 (IH, d, J=3.5 Hz), 3.26-3.28 (IH, m), 4.36 (IH, dd.


Epoxy ether (1.50 g, 5.85 mmol) was dissolved in THF (20 mL) , followed by adding diphenyl phosphine {3 mL, 17.6 irunol) and BuLi (1.6 M in hexane, 10 mL, 17.6 ramol) at -78°C to react the mixture for 20 min. Thereafter, after stirring at room temperature for 15 hr, a saturated ammonium chloride aqueous solution was added. The resulting solution was ice-cooled, followed by adding hydrogen peroxide water (5 mL) and stirring for 30 min, further followed by adding a saturated sodium thiosulfate aqueous solution. A resulting product was extracted with ethyl acetate, followed by washing an organic layer with a saturated saline solution. The organic layer was dried over sodium sulfate, followed by filtering and concentrating. A resulting product was subjected to silica gel column chromatography (ethyl acetate: hexane =1:1-^2:1) to obtain a target subject, phosphine oxide (2.29 g, yield: 68%) . The resulting crystal was recrystallized from isopropyl alcohol to obtain an asymmetric ligand having 100% optical purity. The optical purity of the ligand was confirmed by use of the optically

active HPLC (trade name: CHIRALCEL-ODH, produced by Daicel, isopropyl alcohol ;hexane = 1:9, flow rate: 1. 0 inL/min, tR = 6.8 min (minor: not observed), 9.5 min (major)).
NMR (CDCL3) 5 1.0-1.1 (IH, m) , 1.30-1.38 (IH, m) , 1.40-1.50 (IH, m) , 1.68-1.8 3 (2H, m) , 2.15-2.22 (IH, m) , 2.66 (IH, m) , 3.58-3.63 (IH, m), 3.98-4.04 (IH, m) , 3.58-3.64 (IH, m), 3.98-4.04 (IH, m), 6.73-6.79 (2H, m), 6.88 (IH, brs), 7.50-7.57 (4H, m) , 7.58-7.66 (2H, m), 7.71-7.78 (4H, m) .

Epoxy ether (lOOrtig, 0.390 mmol) was dissolved in diethyl ether (3.9mL), followed by adding diethyl aluminuin cyanide (1.0 M in toluene, 470 mL, 0.585 mmol) at 0°C to react the mixture for 3 hr, further followed by adding a saturated sodium chloride aqueous solution. Thereto, a saturated Rochelle salt aqueous solution was added, followed by stirring for 1 hr. A product was extracted with ethyl acetate and an organic layer was washed with a saturated salins solution. The organic layer was dried over sodium sulfate, followed by filtering and concentrating, further followed by subjecting a resulting product to silica gel column chromatography (ethyl acetate:hexane = 5: 2) , thereby to obtain a target object, cyanohydrin (80 mg, yield: 73%). NMR (CDCL3) 51.24-1.34 (IH, m), 1.48-1.56 (IH, m), 1.64 (IH,

m) , 1.82-1.88 (IH, m), 2.07-2.18 (2H, m) , 2.50 {IH, ddd, J= 13, 10, 3.7 Hz), 3.78-3.82 (IH, m), 3.83 {3H, s), 4.02 (IH, brs), 6.75 (IH, dd, J=12,7.6 Hz), 6.85 (IH, dd, J=12, 7.6 Hz).

Cyanohydrin (196mg, 0.691mmol) wasdissolvedindimethoxy ethane (15 mL), followed hy adding 12N hydrochloric acid (15 rtiL) and reacting the mixture at 85°C for 24 hr. A resulting product was extracted with ethyl acetate, followed by washing an organic layer with a saturated saline solution. The organic layer was dried over sodium sulfate, filtered and concentrated. A resulting product was dissolved in 3N sodium hydroxide aqueous solution (1 mL), followed by washing with diethyl ether. To a resulting product, IN hydrochloric acid was added, followed by extracting with ethyl acetate, an organic layer was dried over sodiumsulfate, filteredand concentrated, thereby to obtain a target subject, hydroxycarboxylic acid (374 mg, yield: quant). NMR (CDCLa) 6 1.28-1.37 (IH, m), 1.46-1,60 (IH, m), 1.84-1.90 (IH, m), 2.08-2,14 (IH, m), 2.15-2.21 (IH, m), 2.43 (IH, ddd, J=12.5, 10.5, 4.3H2), 3.68 (IH, ddd, J=11.3, 8.6, 4.9Hz), 3.85 (3H, s), 3.93 (IH, dd, J=10.7, 8.9 Hz), 6.76 (IH, dd, J- 11.3, 7.7 Hz), 6.89 (IH, dd, J= 10.7, 7.9 Hz).


Hydroxycarboxylic acid (295 mg, 0.976inmol) was dissolved in THF (5rnL), followed by adding borane tetrahydrofuran complex (1.17 M in THF, 3.34 mL, 3.90 mmol) to react the mixture for 2 hr. Thereafter, IN hydrochloric acid was added, followed by adding a saturated sodium hydrogen carbonate aqueous solution. A product was extracted with ethyl acetate, followed by washing an organic layer with a saturated saline solution, further followed by drying over sodium sulfate, filtering and concentrating. A resulting product was subjected to silica gel column chromatography (ethyl acetate: hexane =2: 3), thereby to obtain a target object, diol (281 mg, yield: quant). The resulting crystal was recrystallized from methylene chloride and hexane to obtain diol having 10 0% optical purity. The optical purity of the diol body was confirmed by use of the optically active HPLC {trade name: CHIRALCEL-ADH, produced by Daicel, isopropyl alcoholihexane = 1: 9, flow rate: l.OmL/min, tR=12.2 min (major), 14.9 min (minor: not observed)). NMR (CDCL3) 5 1.05 (IH, ddd, J= 26.3, 13.1, 3.7 Hz), 1.28-1.38 (IH, ra>, 1.42-1.51 (IH, m), 1.60-1.74 (2H, m), 1.77-1.82 (IH, m), 2.11-2.17 (IH, m), 3.62-3.75 (4H, m), 3.84 (3H, s), 3.91 (IH, brs), 6.74 (IH, dd, J= 11.0, 8.0 Hz).


Diol (38 mg, 0.132 mmol) was dissolved in methylene chloride (1.3 mL) , followed by adding triethyl amine (37 mL) , H.N-dimethylamino pyridine and tosylchloride to react the mixture at room temperature for 6 hr. Thereto, IN hydrochloric acid was added, followed by extracting a product with ethyl acetate, further followed by washing an organic layer with a saturated sodium hydrogen carbonate aqueous solution and a saturated saline solution. The organic layer was dried over sodium sulfate, filtered and concentrated, to obtain a target object, tosylate (58 mg, yield: quant). NMR (CDCL3) 5 0.87-0.92 (IH, m), 1.21-1.26 (IH, m), 1.41-1.48
(IH, m), 1.70-1.80 (3H, m), 2.07-2.13 (IH, m), 2.45 (3H, s), 3.40 (IH, s> , 3.50 (IH, t, J= 9.5 Hz) , 3.61-3.66 (IH, m) , 4.16
(IH, dd, J= 9.5, 6.1 Hz), 4.22 (IH, dd, J- 9.5, 3.1 Hz), 6.73
(IH, dd, J- 11.0, 7.3 Hz) , 6.84 (IH, dd, J- 11.0, 7.9 Hz) , 7.34
(2H, d, J= 7.9 Hz), 7.81 (2H, d, J= 8.3 Hz).
EXAMPLE 8:


Tosylate (86.3 mg, 0.195 mmol) was dissolved in THF (1 mL) , followed by adding potassium diphenyl phosphide (0.5 M in THF, 858mL, 0.429mmol) under ice cooling to reacting the mixture forlSmin. Thereafter, hydrogen peroxide water (5raL) was added, followed by stirring for 30 min, further followed by adding a saturated sodium thiosulfate aqueous solution. After a product was extracted with sthyl acetate, an organic layer was washed with saturated saline solution. The organic layer was dried over sodiumsulfate, filtered and concentrated, to obtain a crude product.
The resulting crude product was dissolved in DMF (1 mL) , thereto lithium iodide (157 mg, 1.17 mmol) was added, followed by reacting the mixture at 160°C for 19 hr. After adding water thereto, a product was extracted with ethyl acetate . An organic layer was washed with saturated saline solution, followed by drying over sodium sulfate, further followed by filtering and concentrating, to obtain a target object, phosphine oxide [74.1 mg, yield: 81%).
NMR (CDCL3) 5 1.10-1.19 (IH, m), 1.26-1.35 (2H, m), 1.48-1.57 (IH, m), 1.67-1.80 (2H, m), 2.13-2.18 (IH, m), 2.39-2.44 (2H, m), 3.31-3.37 (IH, m), 3.56 (IH, t, J- 9.2 Hz), 6.72 (IH, dd, J-11.6, 8.0Hz), 6.78 (IH, dd, J=10.7, 8.3Hz), 7.46-7.60 (6H, m), 7.69-7.78 (5H, m).

An asymmetric ligand obtained in Example 3 (in Tatole 1 below, represented by 141 of 1ligand1, simply represented as 1ligand1 in the formula) (13.3 mg, 0.03 mmol) was dissolved in 0.6 mL of THF, Gd[0dPr}3 (0.2 M in THF, 100 diL, 0.02 mmol) was added thereto, followed by stirring at 54°C for 1 hr. The solvent was distilled away, followed by drying a residue under reduced pressure by use of a vacuum pump for 2 hr. Thereto, aziridine 18a that is a raw material (24 6mg, 1.0 mmol) , 2, 6-dimethyl phenol (122 mg, 1.0 mmol) and THF (5 mL) were added, followed by further adding 40 (xL of TMSCN (0.30 mmol) at room temperature. After a reaction was carried out for 13 hr, water and ethyl acetate were added to stop a reaction. A product was extracted with ethyl acetate, a collected organic layer was dried over sodium sulfate, followed by filtering and distilling away the solvent, a resulting crude product was purified by use of a silica gel column (hexane:ethyl acetate = 3:1 to 3:2), thereby to obtain an aziridine ring opened body 19a at the yield of 99% (269 mg, 0.99 mmol) . From the optically active HPLC analysis [Chiralpak AD-H, 2-propanol/hexane 1/9d flow 1.0 mL/min, detection at 254 nm: tR 18 . 4 min (major) and 2 . 09 min (minor) ] , the optical purity was determined to be 98% ee. Example 9 is shown in Table 1 below

as 1entry1 No. 111.
19a: IR (KBr): 3334, 3113, 2950, 2865, 2244, 1647, 1521, 1344, 877, 725 cm1d; dH NMR (d-DMSO) : 5 = 8.92 (d, J = 8.5 Hz, IH) , 8.35 (d, J= 9.0 Hz, 2H) , 8.06 (d, J= 9.0 Hz, 2H) , 4.12-3.97 (m, IH}, 2.86-2.75 [m, IH), 2.17-2.06 (m, IH), 1.91-1.81 (m, IH), 1.77-1.55 (m, 3H), 1.44-1.27 (m, 2H), 1.25-1.12 (m, IH); ddC NMR [d-DMSO): 5=164.0, 149,1, 139.8, 128.7, 123.7, 121.3, 49.7, 33.8, 31.7, 28.8, 23.9, 23.8; MS (ESI): m/z 2 96 [M+Na+]; Anal, calcd for C14H15N3O3: C, 61.53; H, 5.53; N, 15.38%. Found: C, 61.13; H, 5,61; N, 15.21%; [a]ddD-72.5 (c= 0,350, Acetone) (>99% ee) .
EXAMPLES 10 to 19:
Except that, in place of a ligand in the example 9, a ligand represented by 151 in Table 1 below was used and/or in place of a raw material aziridine 18a in the example 9, each of 18b to 18i was used, an aziridine ring opening reaction was carried out in a manner similar to example 9. Results thereof are shown in Table 1 below. Examples 10 to 19, respectively, are shown by 1entry1 Nos. 121, 141, 161, 181, 1101, 1111, 1131, 1151, 1171 and 1191.
(COMPARATIVE EXAMPLES 1 to 9)
By use of a conventional ligand derived from glucose (ligand represented by 111 in the table 1 below) in place of the ligand in the example 9, a raw material aziridine 18a was subjected to aringopeningreactioninamanner similar to example

9. The result thereof is shown in 1entry1 No. 131 of Table 1.
Further, except that, in the comparative example 1, in place of a raw material aziridine 18a, by use of each of 18b to 18i, an aziridine ring opening reaction was carried out in a manner similar to example 1. Results thereof are shown in Table 1 below. Comparative examples 2 to 9, respectively, are represented by 1entry1 Nos. 151, 171, 191, 1121, 1141, 1161, 1181 and 1201.
When examples and comparative examples that have the same raw materials are compared, it is found that the optical purities of examples (values represented by [ee (%) ] in Table 1) are higher than that of the comparative examples. From the foregoing results, it was found that when the ligand according to the present invention is used, in comparison with a conventional ligand derived from glucose, a product is obtained with higher optical purity.

An asymmetric ligand obtained in example 3 (in Table 1, representedby141of 1ligand1) (6.7mg, O.OlSmmol) wasdissoived in 0.3 mL of THF, Gd(0dPr)3 (0.2 M in THF, 50 |iL, 0.01 mmol) was added at room temperature, followed by stirring at 54°C for 1 hr. A solvent was distilled away and a residue was dried under reduced pressure by use of a vacuum pump for 2 hr. Thereto, 2,6-dimethyl phenol (24.4 mg, 0.2 mmol} was added, followed by adding a raw material 21a (35.4 mg, 0.2 mmol) after dissolving in 0.2 mL of THF. A reaction solution was cooled to -20°C and TMSCN (40mL, 0.30 mmol) was added thereto. After5.5hr, silica gel was added to stop the reaction, followed by loading to a silica gel column and eluting at hexane:ethyl acetate =10:1 to 4:1 to purify, thereby 22a was obtained by 40.5 mg at the yield of 99%. From the optically active HPLC analysis [Chiralcel OD-H, 2-propanol/hexane 1/20, f low 1. 0 mL/min, detection at 254 nm: tR 13,0 min (minor) and 16.7 min (major) ] , the optical purity was determined to be 93% ee. Example 20 is shown in Table 2 below as 1entry1 No. 111.
22a: IR (KBr) : 3402, 3145, 2960, 2931, 2242, 1708, 1474, 1374, 1292, 921 cm1S- dH NMR (CDCI3) : 6 = 7.27 {brs, 2H) , 6.32 (t, J = 2.3 Hz, 2H), 3.33-3.16 (m, 2H) , 3.06 (dd, J-=6.1, 16.7, IH) , 1.98-1.82 (m, IH), 1.75-1.57 (m, IH) , 1.49-1.34 (m, IH) , 1.00 (d, J = 6.4 Hz, 3H) , 0.99 (d, J - 6.7 Hz, 3H) ; ddC NMR(CDCl3) :

d= 166.5, 121.1, 118.8, 113.9, 40.8, 37.3, 26.2, 25.0, 22.9, 21.1; MS: m/z 204 [M*] ; Anal, calcd for C12H16N2O: C, 70.56; H, 7.90; N, 13.71%. Found: C, 70.48; H, 8.03; N, 13.74%; [a]dd -26.2 (c = 0.940, CHCI3) (97% ee) .
EXAMPLES 21 to 27:
Except that, in the example 20, an amount of Gd{0dPr)3 and an amount of the ligand were varied and/or, in place of the raw material 21a in the example 20, each of 21b to 21h were used, a cyano-Michael addition reaction was carried out in a manner similar to example 9. The results thereof are shown in Table 2 below. In Table 2, examples 21 to 27, respectively, are shown with 1entry1 Nos. 121, 141, 161, 181, 1101, 1121 and 1141.
(COMPARATIVE EXAMPLES 10 to 16)
By use of a conventional ligand derived from glucose
(ligand represented by 111 in the table 1 and Table 2 below) in place of the ligand in the example 20, a cyano-Michael addition reaction was carried out with a raw material 21a in a manner similar to example 20. The result thereof is shown in 1entry1 No. 131 of Table 2.
Further, except that, in the comparative example 10, in place of a raw material 21a, each of 21b to 21h was used, a cyano-Michael addition reaction was carried out in a manner similar to comparative example 10. Results thereof are shown in Table 2 below. Comparative examples 11 to 16, respectively, are shown by d-entry1 Nos. 151, 171, 191, 1111, 1131 and 1151.

When examples and comparative examples that have the same rawmaterials are compared/ it is found that the optical purities of examples (values represented by 1ee (%) 1 in Table 2) are equal to or higher than that of the comparative examples. From the foregoing results, it was found that when the ligand according to the present invention is used, in comparison with a conventional ligand derived from glucose, a product is obtained with equal or higher optical purity.

/
./ b -
/■— - I
_-- b

To a THF solution (0.44 mL) of a compound 22a (44.8 mg, 0.219 nimol) obtained in example 20, a 1 M NaOH aqueous solution (0.44 mL) was added at room temperature. After 1 hr, THF was distilled away under reducedpressure, thereto a saturated sodium hydrogen carbonate aqueous solution was added, followed by washing an aqueous layer with methylene chloride three times. The aqueous layer was controlled to pH = 1 by adding hydrochloric acid and methylene chloride was used to extract. Organic layers were combined, followed by drying over sodium sulfate, further followed by filtering and distilling away the solvent, thereby to obtain 31.8 mg (94%) of 24.
24: IR (neat): 2961, 2244, 1714, 1469, 1414, 1371, 1175, 924, 619 cm1d; IH NMR {CDCI3) : 6 = 9.29 (brs, IH) , 3.12-2.9 6 (m, IH) , 2.76 (dd, J= 7.5, 17.0 Hz, IH), 2.62 (dd, J= 6.1, 17.0 Hz, IH), 1.95-1.78 (m, IH), 1.74-1.57 (m, IH), 1.43-1.30 (m, IH), 0.98 (d, J- 6.7 Hz, 3H) , 0.96 (d, J- 6.7 Hz, 3H) ; ddC NMR(CDCl3) : □ = 175.5, 120.8, 40.6, 36.8, 26.1, 25.5, 22.8, 21.2; MS: m/z 155 [M*] ; HRMS (EI) : m/z caicd f or C8H14NO2 [M+Hd] : 156.1025. Found; 156.1026; [a]ddD-15.0 (c - 0 . 590, CHCI3) . Observed value: [ajdo -16.7 (c = 0.5, CHCI3) (J. Am. Chem. Soc. 2003, 125, 4442).
The compound 24 obtained in the example is readily converted to Pregabalin by reference to a prior literature (J. Am. Chem. Soc. 2003, 125, 4442) .
Thus, when by use of examples 20 and 28, intermediate bodies
55

are obtained at a smaller quantity of catalyst at a shorter time; accordingly, a precursor 24 of an antiepileptic agent Pregabalin is obtained efficiently more than ever.
EXAMPLE 29:
Except that, in example 2, monomethylchlorocatechol was used in place of monomethyldifluorocatechol, an asymmetric ligand where X = Ci in 1ligand 21 of the following formula was prepared in a manner similar to examples 1 to 3. dH NMR (CDCI3) : 5 = 9.2 8 (s, IH), 7.74-7.70 (m, 4H), 7.62-7.47 (m, 6H), 7.03 (s, IH), 6.98 (s, IH}, 6.84 (bs, IH), 4.00 (dd, J-=18.6, 8.5 Hz, IH) , 3.64-3.59 (m, IH) , 2.64 (ddd, J=22.9, 12.1, 3.3 Hz, IH), 2.19-2.16 {m, IH) , 1.81-1.69 (m, 2H) , 1.48-1.28

In a well-dried and argon-substituted test tube, an asymmetric ligand (0.02 mmol) prepared in example 3 was added, followed by adding THF (0.323 mmol) . Thereto, 100 mL of a THE solution of Ba(0Pr)2/ left standing for 1 hr after the solution was diluted to be 0 . 2 M, was gradually added at room temperature . Pifter stirring at 50°C for 1 hr, the solvent was distilled away, followed by drying under vacuum at room temperature for 3 hr.

A residual was dissolved in CH2CI2 (300 mL) and cooled to -20°C. Thereto, diene (52.9 ml, 0.3mmol) and dienophile (O.5MCH2CI2 solution 200 mL, 0.1 mmol) were added, followed by stirring until the raw material disappears. After heating to room temperature, acetic acid (ca. 75 mL) and TBAF (0.1 M THF solution, 800 mL, O.Smmol) were added, followedby stirring for 5min. Asaturated sodium hydrogen carbonate aqueous solution was carefully added and an aqueous phase was extracted with ethyl acetate, followed by washing an organic phase with saturated saline solution. Sodium sulfate was used to dry, followed by filtering and distilling away a solvent, further followed by silica gel column chromatography, a target subject was obtained as a mixture of

For a alcohol: % IJMR (CDCI3, 500 MHz) d5.88 (m, 2H) , 4.49 (m, IH), 3.72 (S, 3H), 3.69 (s, 3H) , 2.99 (ddd, J=5.5, 11.3, 11.8 Hz, IH}, 2.92 (dd, J- 4.0, 11.8 Hz, IH) , 2.48 - 2. 43 (m, IH) , 2.16 - 2.10 (m, IH) ; For p alcohol: dH TdMR (CDCI3, 500 MHz) d 5.77 - 5.73 (m, IH), 5.70 - 5.67 (m, IH), 4.42 (m, IH), 3.73 (s, 3H), 3.67 (s, 3H) , 2.96 - 2.92 (m, IH) , 2.76 (dd, J= 8.9, 11.3 Hz, IH), 2.41 - 2.36 (m, IH), 2.26 - 2.20 (m, IH); For diastereomer mixture: 1C NMR (CDCI3, 125 MHz) d 175.5, 174.1, 174.0, 172.8, 129.4, 128.9, 127.1, 126.3, 68.5, 63.9, 52.2, 52.1, 52.0, 52.0, 49.8, 47.6, 40.7, 36.2, 28.7, 27.7; IR {neat, cm1d)

3460, 2953, 1736; ESI-MS m/z 237 [M + Na]d GC (CHIRASIL-DEX CB, column temperature 150 °C, injection temperature 200 °C, detection temperature 250 °C.} : tRl2.2min (endo / exo miture) , 13.3 min (endo, major), 13.8 min [endo, minor).
EXAMPLES 31 to 33:
Except that, in the example 30, X of Ligand 2 was changed to CI (asymmetric ligand of example 29) or F and/or a reaction time and/or a reaction temperature in the example 30 were changed, similarly to example 30, reactions were carried out. Results thereof are shown in Table 3 below.
(COMPARATIVE EXAMPLE 17)
Except that, in place of a ligand in the example 30, a conventional glucose-derived ligand (ligand represented by 111 in the tables 1 and 2) was used, a reaction was carried out in a manner similar to example 30. Results thereof are shown in Table 3 below.
When example 33 and comparative example 17 are compared, it is found that the optical purity of a product of example 33 is higher. Further, when examples 30 to 33 are compared, it is found that a ligand having a substituent group of chlorine or fluorine in a catechol site are higher in the endo/exo ratio and yield.

What is cIAimed is:

wherein each of R1 and R2 independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trifluoroacetyl group, a trifluoromethyl group, an alkoxy group representedby-OR2 (R2 represents a linear or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NRB2RC (each of RB and Rc independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed of A2 and A3. 2. A ligand represented by following general formuIA IA:


wherein each of R1 and R2 independently represents 0 to 5 substituent groups; X represents P, As or H; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1to A1independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trifluoroacetyl group, a trif luoromethyl group, an aikoHy group represented by-OR2 (R2 represents a linear or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NRBRC (each of RB and Rc independently represents a hydrogen atom or a linear or branched alkyl group haying 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed of A2 and A3. 3. A ligand represented by following general formuIA lb:


wherein each of R-2 and R2 independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1to A2 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trif luoroacetyi group, a trif luoromethyl group, an alkoxy group representedby-OR2 (R2 represents a linear or branched alkyl group having 1 to 4 carbon atoms) , an amino group represented by -NRBRC (each of RB and Rc independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed of A2 and A3.
4. The ligand according to any one of cIAims 1 to 3, wherein n is an integer of 0 or 1.
5. The ligand according to any one of cIAims 1 to 4, wherein m is an integer of 2 to 4.
6. The ligand according to any one of cIAims 1 to 5, wherein two of the A1to A4 are hydrogen atoms and the other two thereof are fluorine atoms.
7. A method of producing a ligand represented by following general formuIA I from a compound represented by following general formuIA II:


wherein each of R-2 and R2 independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trif luoroacetyl group, a trifluoromethyl group, an alkoxy group represented by-OR2 (R2 represents a linear or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NRbRc (each of Rb and Rc independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed

wherein R2 represents a hydrogen atom, a linear or branched alkyl group having 1 to 9 carbon atoms, a linear or branched

rf-LKenyi group naving 2 to 8 carbon atoms, a benzyl group, a paramethoxy benzyl group or a silyl group; m has the same definition as described above; and each of A1to A4 independently has the same definition as described above, the method comprising the steps of:
a) reacting the compound represented by the general formuIA
II with a metal salt of diphenylphosphine, diarylphosphine or
diaryIAmine;
b) thereafter, processing with ammonium chloride and
hydrogen peroxide; and
b ) when X is As or N and Rb is one other than a hydrogen atom, allowing palIAdium-carbon to react with hydrogen, lithium chloride, dichlorodicyanobenzoquinone, ceriumammoniumnitrate or a fluorine anion to make the R2 a hydrogen atom, to obtain the ligand represented by the general formuIA I. 8. The method according to cIAim 7, wherein the compound represented by the general formuIA II is obtained by c) reacting a compound represented by following general formuIA III, wherein m has the same definition as described above, in the presence of diethyIAzodicarboxyIAte or diisopropyIAzodicarboxyIAte and triphenylphosphine or tributylphosphine, with a compound represented by following general formuIA IV, wherein R2 and A1to A4 have the same definitions as described above:



9. The method according to cIAim 8, wherein the compound
represented by the general formuIA III is obtained by d} reacting
a compound represented by following general formuIA V, wherein
m has the same definition as described above, in the presence
of a phosphoric acid buffer, with a peracid:
10. A method of producing a ligand represented by following
general formuIA IA from a compound represented by following
general formuIA IIA:

wherein each of R2 and R2 independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A: to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trif luoroacetyl group, a trif luoromethyl group, an alkoxy group represented by-OR2 (R2 represents a linear

or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NRBRB (each of R" and R= independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed of A2 and A3, and

wherein R"2 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms, a benzyl group, a paramethoxy benzyl group or a silyl group; m has the same definition as described above; and each of A1to A4 independently has the same definition as described above,
the method comprising the steps of:
a) reacting the compound represented by the general formuIA
IIA with a metal salt of diphenylphosphine, diarylphosphine or
diaryIAmine;
b) thereafter, processing with ammonium chloride and
hydrogen peroxide; and
b ) when X is As or N and R2 is one other than a hydrogen atom, allowing palIAdium-carbon to react with hydrogen, lithium chloride, dichlorodicyanobenzoquinone, ceriumammoniumnitrate or a fluorine anion to make the R"2 a hydrogen atom, to obtain the ligand represented by the general formuIA IA.

11. The method according to cIAim 10, wherein the compound
represented by the general formuIA IIA is obtained by c) reacting
a compound represented by following general formuIA Ilia, wherein
m has the same definition as described above, in the presence
of diethyIAzodicarboxyIAte or diisopropyIAzodicarboxyIAte and
triphenylphosphine or tributylphosphine, with a compound
represented by following general formuIA IV, wherein R2 and A1to A4 have the same definitions as described above:

12. The method according to cIAim 11, wherein the compound representedby the general formuIA Ilia is obtainedby d) reacting a compound representedby following general formuIA Va, wherein m has the same definition as described above, in the presence of a phosphoric acid buffer, with a peracid:
13. A method of producing a ligand represented by following general formuIA lb from a compound represented by following general formuIA lib;


wherein each of R-2 and R independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trifluoroacetyl group, a trifluoromethyl group, an alkoxy group represented by-OR2 (R2 represents a linear or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NR2Rb (each of R and Rb independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed of A2 and A3, and

wherein P? represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyi group having 2 to 8 carbon atoms, a benzyl group, a

paramethoxy benzyl group or a silyl group; m has the same definition as described above; and each of A1to A4 independently has the same definition as described above, the method comprising the steps of:
a) reacting the compound represented by the general formuIA
lib with a metal salt of diphenylphosphine, diarylphosphine or
diaryIAmine;
b) thereafter, processing with ammonium chloride and
hydrogen peroxide; and
b ) when X is As or N and R2 is one other than a hydrogen atom, allowing palIAdium-carbon to react with hydrogen, lithium chloride, dichlorodicyanobenzoquinone, ceriumammoniumnitrate or a fluorine anion to make the R2 a hydrogen atom, to obtain the ligand represented by the general formuIA lb. 14. The method according to cIAim 5, wherein the compound represented by the general formuIA lib is obtained by c) reacting a compound representedby following general formuIA Illb, wherein m has the same definition as described above, in the presence of diethyIAzodicarboxyIAte or diisopropyIAzodicarboxyIAte and triphenylphosphine or tributylphosphine, with a compound represented by following general formuIA IV, wherein R2 and A1to A4 have the same definitions as described above:



15. The method according to cIAim 6, wherein the compound
representedbythe general formuIA Illb is obtained by d) reacting
a compound represented by following general formuIA Vb, wherein
m has the same definition as described above, in the presence
of a phosphoric acid buffer, with a peracid:

16. A producing method of a ligand represented by following
general formuIA I from a compound represented by following
general formuIA II:
wherein each of R"2 and R2 independently represents 0 to 5 sutostituent groups; X represents P, As or W; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, atrifluoroacetylgroup, atrifluoromethyl group, an alkoxy group representedby-OR2 (R2 represents a linear

or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NR2R (each of R2 and R= independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed

wherein Rb represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms, a benzyl group, a paramethoxy benzyl group or a silyl group; m has the same definition as described above; and each of A1to A4 independently has the same definition as described above,
the method comprising the steps of:
g) reacting the compound represented by the general formuIA II with diethyIAluminum cyanide, followed by reacting with concentrated hydrochloric acid, to obtain a compound represented by following general formuIA VII, wherein m, R"2 and A1to A4 have the same definitions as described above;
h) reacting the compound representedby the general formuIA VII with a BH3 tetrahydrofuran complex, a BH3 dimethylsulfide complex or LiAlH4, to obtain a compound represented by following general formuIA VIII, wherein m, R2 and A1to A4 have the same

definitions as described above;
j ) reacting the compound representedby the general formuIA
VIII with p-toluenesulfonyl chloride, to obtain a compound
represented by following general formuIA IX, wherein Ts
represents a p-toluenesulfonyl group; and m, R2 and A1to A4 have
the same definitions as described above;
k) reacting the compound represented by the general formuIA
IX with potassium diphenyl phosphide, followed by reacting with
hydrogen peroxide, to obtain a compound represented by following
general formuIA X, wherein m, P? and A1to A4 have the same
definitions as described above; and
1) reacting the compound represented by the general formuIA
X with lithium iodide, to obtain the ligand represented by the



17. A method of producing a ligand represented by following general formuIA IA from a compound represented by following

wherein each of R2 and R2 independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trifluoroacetyl group, a trif luoromethyl group, an alkoxy group represented by-OR2 (R2 represents a linear or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NRBRB (each of R*2 and Rb independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxy1 group or a ring formed


wherein R2 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms, a benzyl group, a paramethoKy benzyl group or a silyl group; m has the same definition as described above; and each of A1to A4 independently has the same definition as described above,
the method comprising the steps of:
g) reacting a compound represented by the general formuIA IIA with diethyIAluminum cyanide, followed by reacting with concentrated hydrochloric acid, to obtain a compound represented by following general formuIA ViIA, wherein m, R2 and A1to A4 have the same definitions as described above;
h) reactingthe compound represented by the general formuIA ViIA with a BH3 tetrahydrofuran complex, a BH3 dimethylsulfide complex or LiAlHi, to obtain a compound represented by following general formuIA VilIA, wherein m, R2 and A1to A4 have the same definitions as described above;
j ) reactingthe compound represented by the general formuIA VilIA with p-toluenesulfonyl chloride, to obtain a compound represented by following general formuIA IXa, wherein Ts represents a p-toluenesulfonyl group, and m, R2 and Aj to A4 have the same definitions as described above;

k) reacting the compound representedby the general formuIA IXa with potassium diphenyi phosphide, followed by reacting with hydrogen peroxide, to obtain a compound represented by following general formuIA Xa, wherein m, R"* and A1to A4 have the same definitions as described above; and
1) reacting the compound represented by the general formuIA Xa with lithium iodide, to obtain the ligand represented by the


general formuIA lb from a compound represented by following

wherein each of R"" and R2 independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1to A4 independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, a trifluoroacetyl group, a trifluoromethyl group, an alkoxy group represented by-OR2 (R2 represents a linear or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NR2R*2 {each of R*2 and Rb independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed


alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms, a benzyl group, a paramethoxy benzyl group or a silyl group; m has the same definition as described above; and each of A1to A2 independently has the same definition as described above,
the method comprising the steps of;
g) reacting a compound represented by the general formuIA lib with diethyIAluminum cyanide, followed by reacting with concentrated hydrochloric acid, to obtain a compound represented by following general formuIA Vllb, wherein m, R2 and A1to A2 have the same definitions as described above;
h) reacting the compound represent edby the general formuIA Vllb with a BH3 tetrahydrofuran complex, a BH3 dimethylsulfide complex or LiAlH4, to obtain a compound represented by following general formuIA Vlllb, wherein m, R2 and A1to A4 have the same definitions as described above;
j ) reacting the compoundrepresentedby the general formuIA Vlllb with p-toluenesulfonyl chloride, to obtain a compound represented by following general formuIA IXb, wherein Ts represents a p-toluenesulfonyl group, and m, R2 and A], to A4 have the same definitions as described above;
k) reacting the compoundrepresentedby the general formuIA IXb with potassium diphenyl phosphide, followed by reacting with hydrogen peroxide, to obtain a compound represented by following general formuIA Xb, wherein m, R2 and A1to A4 have the same definitions as described above; and
1) reacting the compound represent edby the general formuIA

Xb with lithium iodide, to obtain the ligand represented by the

A) a metal alkoxide or a metal amide represented by M2 (OR*) y or M2. (NR2)y., whe rein M is a metal selected from the group consisting of titanium, zirconium, aluminum, gallium, barium and rare earth elements; each of R2 and R2 independently represents a substituted or non-substituted, linear or branched

or cyclic alkyl group having 2 to 5 carbon atoms, a substituted or non-substituted, linear or branched or cyclic alkenyl group, a substituted or non-substituted aromatic group or a trialkylsilyl group, and x and y and x and y are integers stoichiometrically determined by the metal M; and
B) a ligand represented by following general formuIA I, wherein each of R"2 and R2 independently represents 0 to 5 substituent groups; X represents P, As or N; m represents an integer of 0 to 7; n represents an integer of 0 to 3; and each of A1to A1independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a benzoyl group, an acetyl group, anitrogroup, atrifluoroacetylgroup, atrifluoromethyl group, an alkoxy group representedby-OR2 (R2 represents a linear or branched alkyl group having 1 to 4 carbon atoms), an amino group represented by -NRBRB (each of R"2 and R2 independently represents a hydrogen atom, or a linear or branched alkyl group having 1 to 4 carbon atoms), a linear or branched alkyl group having 1 to 4 carbon atoms, a hydroxyl group or a ring formed



22. The catalyst according to anyone of cIAims 19 to 21, wherein
the A) metal alkoxide or metal amide and B) ligand are 1:1 to
1:4 by moIAr ratio of A:B.
23, The catalyst according to any one of cIAims 19 to 22, wherein
the rare earth metal is ytterbium, yttrium, IAnthanum, cerium,
praseodymium, samarium, europium, gadolinium, dysprosium,
holmium or erbium.
24 . The catalyst according to any one of cIAims 19 to 23, wherein alkyl of the trialkylsilyl group is a linear or branched alkyl having 1 to 4 carbon atoms.

25 . The catalyst according to anyone of cIAims 19 to 24, wherein
a metal alkoxide or metal amide of the A) is gadolinium
triisopropoxide, yttrium triisopropoxide,
tris-[N,N-bis(triraethylsilyl)amide]gadolinium (III),
tris-[N,N-bis(trimethylsilyl)amide]yttrium (III) or barium
diisopropoxide.
26. The catalyst according to any one of cIAims 19 to 25, wherein
the m is an integer of 2 to 4.
27 . The catalyst according to any one of cIAims 19 to 2 6, wherein
two of the Al to A4 are hydrogen atoms and the other two are
fluorine atoms.
28 . The catalyst according to anyone of cIAims 19 to 27, wherein
the n is an integer of 0 or 1.