JP2003231691A - Method for producing diphosphine compound and intermediate for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an excellent method for producing a phosphinobinaphthyl compound. <P>SOLUTION: The method for producing the compound represented by formula (3) (R<SP>1a</SP>, R<SP>1b</SP>, R<SP>1c</SP>, R<SP>1d</SP>, R<SP>1e</SP>, R<SP>1f</SP>, R<SP>2a</SP>, R<SP>2b</SP>, R<SP>2c</SP>, R<SP>2d</SP>, R<SP>2e</SP>, R<SP>2f</SP>, R<SP>3</SP>, R<SP>4</SP>, R<SP>5</SP>, R<SP>6</SP>, R<SP>7</SP>, R<SP>8</SP>, R<SP>9</SP>and R<SP>10</SP>are each identical or different and denote each H, or the like) or its salt is characterized by reacting a compound represented by formula (1) (X is a releasing group) or its salt with a phosphine-borane complex represented by formula (2) or its salt in the presence of an amine and a nickel complex is a solvent. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a diphosphine compound. More specifically, it relates to a method for producing phosphinobinaphthyl, which is useful as a ligand of a transition metal catalyst for asymmetric synthesis reaction, using a phosphine borane complex.

[0002]

2. Description of the Related Art 2,2 '-(Bis (diphenylphosphino) -1,1 is used as an optically active phosphine in asymmetric reduction, asymmetric isomerization, etc. using a catalyst in which an optically active phosphine is coordinated to a transition metal. Although'-binaphthyl (hereinafter sometimes abbreviated as BINAP) is widely used, various optically active phosphines are not suitable because of the insufficient reactivity, stereoselectivity, catalytic efficiency, etc. depending on the type of substrate. Manufactured and reported (see, for example, Non-Patent Document 1), for example, in Patent Document 1, 2,2′-bis (di (p-toluyl) phosphino)-
A ruthenium complex with 1,1'-binaphthyl as a ligand is carbon-
It is described that the compound is useful in asymmetric reduction of a carbon double bond, and Patent Document 2 discloses 2,2′-bis (di (3,5-dialkylphenyl) phosphino) -1,1′-binaphthyl. It is described that a ruthenium complex as a ligand is useful in asymmetric reduction of β-ketoester. And BINAP
And as a method for producing a BINAP analog: 1) Patent Document 2,

[Chemical 19] The following reaction formula is described as a method for producing a compound represented by the formula [wherein R represents a lower alkyl group] (hereinafter, abbreviated as 3,5-DABIN).

[Chemical 20] Regarding the above optical resolution, the racemic compound (IX) is heated and dissolved in carbon tetrachloride, and an ether solution of (-)-benzoyl tartaric acid is added and stirred to precipitate crystals, and the precipitated crystals are recrystallized, The same operation is repeated until the optical rotation of the crystal substance shows a constant value. It is described that the purified crystals are then suspended in methylene chloride and 2N sodium hydroxide is added to obtain free phosphine oxide (-)-(IX) in the (-) form. 2) In Patent Document 3 or Patent Document 4, the formula

[Chemical 21] BINA in which a compound represented by the formula: wherein R represents triflate, mesylate or tosylate is reacted with diphenylphosphine in the presence of an amine base and a nickel catalyst.
The manufacturing method of P is described. 3) Patent Document 5 discloses that optically active 2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl has the formula A ₂ P (O) H [in the presence of a transition metal-phosphine complex. In the formula,
A represents a phenyl group, a substituted phenyl group, a naphthyl group which may be substituted with a lower alkyl group or a lower alkoxy group], and an optically active diphosphine compound and / or an optically active diphosphine monooxide A mixture containing a compound is synthesized, and a mixture containing an optically active diphosphine compound and / or an optically active diphosphine monooxide compound is reacted with a reducing agent to obtain a compound represented by the formula:

[Chemical formula 22] A method for producing an optically active diphosphine represented by the formula [wherein A has the same meaning as defined above] is described. 4) Non-Patent Document 2 discloses that (S) -2,2′-bis (trifluoromethanesulfonyloxy) -1,1′-binaphthyl and diphenylphosphine chloride are added to NiCl ₂ · [1,2-bis (diphenyl) [Phosphino) ethane] and zinc in the presence of zinc to give (S) -BINAP. 5) Patent Document 6 discloses that in the presence of hydrogen, an amine, a hydrogenation catalyst and a transition metal catalyst,

[Chemical formula 23] [In the formula, R ¹ represents an alkyl group, a perfluoroalkyl group,
An aryl group or a perfluoroaryl group], which is represented by the formula: optically active 2,2′-dihydroxy-1,1′-binaphthyl sulfonate ester and formula

[Chemical formula 24] [In the formula, R ² and R ³ may be the same or different,
An optically active 2,2'-bis (disubstituted phosphino) -1,1 'characterized by reacting a chlorodi-substituted phosphine represented by [each represents an aryl group or a cycloalkyl group]
-A method for producing binaphthyl is described. 6) Patent Document 7 discloses that in the presence of an amine and a transition metal the formula

[Chemical 25] [Wherein, R ¹ and R ² each represent an optionally substituted alkylsulfonyl group or an optionally substituted arylsulfonyl group] and react with a diphenylphosphine having a substituent An expression characterized by

[Chemical formula 26] [In the formula, ring A, ring B, ring C and ring D each represent a benzene ring having a substituent]. In addition, as a phosphine-borane complex, 7) Non-Patent Document 3 describes a production method for obtaining a monophosphine compound by reacting an aryl triflate or aryl nonaflate with a diphenylphosphine-borane complex in the presence of a transition metal and a base. Have been described. 8) In Non-Patent Document 4, 2,2'-dimethoxy-7,7'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl is reacted with a diphenylphosphine-borane complex in the presence of a transition metal. It has been described that the synthesis of diphosphine compounds was unsuccessful. 9) Diphenylphosphine having a substituent on the phenyl group
Regarding the -borane complex, bis (p-methylphenyl) phosphine-borane complex, bis (p-biphenylyl) phosphine-borane complex and bis (2-naphthyl) phosphine-borane complex are described in Non-Patent Document 5 in Patent Document 8. Screw (4
-Methoxy-2-methylphenyl) phosphine-borane complex is described.

[0003]

[Patent Document 1] JP-A-63-63690

[Patent Document 2] Japanese Unexamined Patent Publication No. 3-255090

[Patent Document 3] Japanese Patent Publication No. 10-501234

[Patent Document 4] International Publication No. WO 95/32934 Pamphlet

[Patent Document 5] Japanese Patent Laid-Open No. 9-124669

[Patent Document 6] Japanese Patent Laid-Open No. 2000-7688

[Patent Document 7] Japanese Patent Laid-Open No. 2000-136194

[Patent Document 8] US Pat. No. 2,926,194

[Non-Patent Document 1] Handbook of Enantioselective Catal
ysis with Transition Metal Compounds, Published by VCH Publisher, 1993

[Non-Patent Document 2] Chemical Communications (Ch
emical Communications), pp. 2359-2360, 1997

[Non-Patent Document 3] Tetrahedrons Letters
on Letters), No. 40, pp. 201-204, 1999

[Non-patent document 4] Tetrahedron asymmetry (Tet
rahedron Asymmetry), Issue 5, pp. 325-328, 1994

[Non-Patent Document 5] Tetrahedron, 51
Issue, pages 7655-7666, 1995

[0004]

Problems to be Solved by the Invention 2), 4), 5)
In 6 and 6), a trivalent organophosphorus compound that is easily oxidized and unstable is used as a reaction reagent, and in 1) and 3) above, trichlorosilane is used as a reducing agent.
Although it is not an industrially advantageous method of implementation, establishment of a production method of BINAP and a BINAP analog suitable for industrial mass production is desired. On the other hand, in 7) and 8) above, it has been attempted to react a stable and easily handled diphenylphosphine-borane complex with an aryl triflate, but in 7), a monophosphine compound alone has been successfully synthesized. On the other hand, as described in 8), the synthesis of the diphosphine compound necessary for the production method of BINAP has not been successful. Moreover, in order to synthesize various BINAP analogs from diphenylphosphine-borane complex, diphenylphosphine-borane complex having a substituent on the phenyl group is required. Only synthetic examples are given.

[0005]

[Means for Solving the Problems] The present inventors investigated various methods for producing a BINAP analog suitable for industrial mass production,

[Chemical 27] (In the formula, R ^1a , R ^1b , R ^1c , R ^1d , R ^1e , R ^1f , R ^2a , R ^2b , R
^2c , R ^2d , R ^2e and R ^2f are the same or different and each is a hydrogen atom, a fluorine atom, a chlorine atom, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, or an optionally substituted An aryl group, an optionally substituted hydroxy group, an optionally substituted amino group,
An optionally substituted alkylcarbonyl group, an optionally substituted alkoxycarbonyl group, a carboxyl group or an optionally substituted carbamoyl group, wherein X represents a leaving group] (II) may be abbreviated] or its salt and formula

[Chemical 28] [In the formula, R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ and R ¹⁰ are the same or different and each is a hydrogen atom, a fluorine atom, a chlorine atom, or an optionally substituted hydrocarbon. Represents a group, an optionally substituted hydroxy group or an optionally substituted amino group, and R ³ and R ⁴ and R ⁷ and R ⁸ together form a 5- to 8-membered homolog with an adjacent carbon atom. A ring or a heterocycle may be formed] in a solvent in the presence of an amine and a nickel catalyst with a phosphine-borane complex [hereinafter, sometimes abbreviated as compound (III)] When I reacted for the first time, the formula

[Chemical 29] [Wherein the symbols have the same meaning as described above] [hereinafter, sometimes abbreviated as compound (I)] or a salt thereof can be efficiently obtained in a short step without causing isomerization. The
It was found that the production method is industrially excellent in terms of simplicity, economy, and easiness of operation based on the stability of raw materials, and based on these, the present invention has been completed.

That is, the present invention is based on the formula [1]

[Chemical 30] (In the formula, R ^1a , R ^1b , R ^1c , R ^1d , R ^1e , R ^1f , R ^2a , R ^2b , R
^2c , R ^2d , R ^2e and R ^2f are the same or different and each is a hydrogen atom, a fluorine atom, a chlorine atom, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, or an optionally substituted An aryl group, an optionally substituted hydroxy group, an optionally substituted amino group,
An optionally substituted alkylcarbonyl group, an optionally substituted alkoxycarbonyl group, a carboxyl group or an optionally substituted carbamoyl group, X is a leaving group] or a salt thereof. formula

[Chemical 31] [In the formula, R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ and R ¹⁰ are the same or different and each is a hydrogen atom, a fluorine atom, a chlorine atom, or an optionally substituted hydrocarbon. Represents a group, an optionally substituted hydroxy group or an optionally substituted amino group, and R ³ and R ⁴ and R ⁷ and R ⁸ together form a 5- to 8-membered homolog with an adjacent carbon atom. Or a heterocycle may be formed] represented by the formula: phosphine-borane complex or a salt thereof is reacted in the presence of an amine and a nickel catalyst in a solvent.

[Chemical 32] [Wherein the symbols have the same meanings as defined above] or a salt thereof, [2] X is an optionally substituted alkylsulfonyloxy group or an optionally substituted arylsulfonyloxy group. [3] R ^1a , R ^1b , R ^1c , R ^1d , R ^1e , R ^1f ,
R ^2a , R ^2b , R ^2c , R ^2d , R ^2e and R ^2f are the same or different and each is a hydrogen atom, a fluorine atom, a chlorine atom, an optionally substituted alkyl group, or an optionally substituted cycloalkyl group. A hydroxy group which may be substituted, an amino group which may be substituted, an alkylcarbonyl group which may be substituted, an alkoxycarbonyl group which may be substituted, a carboxyl group or a carbamoyl group which may be substituted. , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ are the same or different and each is a hydrogen atom, a fluorine atom, a chlorine atom, an optionally substituted hydrocarbon group, or an optionally substituted hydroxy group. A group or an optionally substituted amino group, both R ⁹ and R ¹⁰ are hydrogen atoms, and X is an optionally substituted alkylsulfonyloxy group or an optionally substituted aryl. [4] R ^1a and R ^2a , R ^1b and R ^2b , R ^1c , which is a sulfonylsulfonyl group.
And R ^2c , R ^1d and R ^2d , R ^1e and R ^2e and R ^1f The production method according to the above [3], wherein R ^2f are the same group, [5] R ^1a , R
[1] to [3], wherein ^1f , R ^2a and R ^2f are hydrogen atoms, [6] R ^1a , R ^1b , R ^1c , R ^1d ,
^{R 1e, R 1f, R 2a} , R 2b, R 2c, R 2d, wherein R ^2e and R ^2f is a hydrogen atom [3] The process according, (7) R ^3, R ^5, R ⁶
And R ⁸ are lower alkyl groups, and R ⁴ and R ⁷ are hydrogen atoms or lower alkoxy groups, [8] R ³ , R ⁵ , R ⁶ and R ⁸ are hydrogen atoms Wherein R ⁴ and R ⁷ are a lower alkyl group or a lower alkoxy group, [3]

[9] R³, R^Four, R^Five, R⁶, R⁷Oh
And R⁸[1] is a hydrogen atom, [1]
0] X is trifluoromethanesulfonyloxy, methane
With sulfonyloxy or p-toluenesulfonyloxy
The production method according to [1], wherein the nickel catalyst is [11]
NiCl₂・ Bis (diphenyl) phosphino C_1-4Alkane, N
iBr₂, NiCl₂, NiCl₂・ Bis (diphenyl) phosphinyl
Ferrocene, NiCl₂・ Bis (triphenylphosphine
), Ni ・ Tetrakistriphenylphosphine, Ni ・ Te
Trakistriphenylphosphite or Ni-dicarb
[1] which is nilbis (triphenyl) phosphine
To [3], the nickel catalyst is Ni.
Cl₂・ Bis (diphenyl) phosphino C_1-4In the alkane
[13] The manufacturing method according to the above [1] to [3],
Kell catalyst is NiCl₂・ Bis (diphenyl) phosphinoeta
[1] to [3] above, which is a
4] The above [1] to [3], wherein the amine is a tertiary amine
[15] amine is 1,4-diazabicyclo
[2.2.2] The above [1] to [3] described as octane
[16] The solvent is N, N-dimethylformamide,
N, N-dimethylacetamide, 1-methyl-2-pyrrolidone
Is one selected from 1,3-dimethyl-2-imidazolidinone.
Or a mixed solvent of two or more of the above [1] to [3]
Manufacturing method described in [17] R^1a, R^1b, R^1c, R^1f, R^2a,
R^2b, R^2cAnd R^2fIs a hydrogen atom, R^1dAnd R ^2dIs hydrogen
Child or C_6-10Aryl group, R^1eAnd R^2eIs a hydrogen atom
Or C_1-6Alkoxy group, R³Is a hydrogen atom or C_1-6Archi
Lu group, R^FourIs hydrogen atom, fluorine atom, chlorine atom, C_1-6Al
Kill group, C_6-10Aryl group, C_1-6Alkoxy group or di-C
_1-6Alkylamino group or R³And R^FourAdjacent carbon
Form benzene ring or 1,3-dioxolane ring with atom
Then R^FiveIs a hydrogen atom or C_1-6Alkyl group, R⁶Is a hydrogen atom
Or C_1-6Alkyl group, R⁷Is hydrogen atom, fluorine atom, salt
Elementary atom, C_1-6Alkyl group, C_6-10Aryl group, C_1-6Al
Coxy group or di-C_1-6Alkylamino group or R⁶When
R⁷Benzene ring or 1,3-dio with adjacent carbon atoms
Forms a xoxolane ring, R⁸Is a hydrogen atom or C_1-6Alkyl
Base, R⁹Is a hydrogen atom or C_1-6Alkyl group, R^TenIs hydrogen
Child or C_1-6Alkyl group, X is trifluoromethanesulfur
Honyloxy, nickel catalyst is NiCl₂・ Bis (Dipheni
Le) phosphinoethane, wherein the production method according to [1] above,
[18] Expression

[Chemical 33] [Wherein each symbol has the same meaning as described in [1] above] and a compound represented by the formula

[Chemical 34] [Wherein each symbol has the same meaning as described in [1] above], both of the axial asymmetry parts of the compound are (R) isomers, [19] racemization The reaction without the reaction, [18]
[20] Expression

[Chemical 35] [Wherein each symbol has the same meaning as described in [1] above] and a compound represented by the formula

[Chemical 36] [Wherein each symbol has the same meaning as described in [1] above], and both of the axial asymmetry parts of the compound are (S) isomers, [21] racemization A method of reacting without the reaction, [20].
[22] Expression

[Chemical 37] [Wherein each symbol has the same meaning as described in [1] above] and a compound represented by the formula

[Chemical 38] [Wherein each symbol has the same meaning as described in the above [1]], the production method according to the above [1], wherein both axial asymmetric parts of the compound are racemic, [23] 2,2 ′ -Bis [bis (3,5-di-
tert-Butyl-4-methoxyphenyl) phosphino] -1,1′-binaphthyl or a salt thereof, [24] formula

[Chemical Formula 39] [In the formula, R ^{3 ′} , R ^{5 ′} , R ^{6 ′} and R ^{8 ′} are a hydrogen atom, a lower alkyl group or a lower alkoxy group respectively, and R ^{4 ′} and R ^{7 ′} are a hydrogen atom, a fluorine atom and a chlorine atom, respectively. ,
C _2-6 alkyl group, lower alkoxy group, mono-lower alkylamino group or di-lower alkylamino group (R ^{3 '} and
R ^{4 '} and R ^{7 '} and R ^{8 '} may form a lower alkylenedioxy group (provided that R ^{3 '} , R ^{4 '} , R ^{5 '} , R ^{6 '} , R ^{7 '}
And R ^{8 ′} are all hydrogen atoms)]] or a salt thereof, [25] R ^3
' , R ^{5 '} , R ^{6 '} and R ^{8 '} are each a hydrogen atom or a lower alkyl group, and R ^{4 '} and R ^{7 '} are a hydrogen atom, a fluorine atom, a chlorine atom, a lower alkoxy group, a mono-lower alkylamino group or [26] The phosphine-borane complex according to the above [24], which is a di-lower alkylamino group.
R ^{3 '} , R ^{5 '} , R ^{6 '} and R ^{8 '} are hydrogen atoms, and R ^{4 '} and R ^{7 '} are fluorine atoms, chlorine atoms, lower alkoxy groups or di-lower alkylamino groups [25] [27] The phosphine-borane complex according to [25], wherein [27] R ^{3 ′} , R ^{5 ′} , R ^{6 ′} and R ^{8 ′} are lower alkyl groups, and R ^{4 ′} and R ^{7 ′} are hydrogen atoms. Phosphine-borane complex, [28] The phosphine according to the above [25], wherein R ^{3 ′} , R ^{5 ′} , R ^{6 ′} and R ^{8 ′} are lower alkyl groups, and R ^{4 ′} and R ^{7 ′} are lower alkoxy groups. -Borane complex, [29] R
^{5 'and} R ^8' is a hydrogen atom, ^{'R 4 and'} R ³ and R ^7
' And R ^{8 '} form a methylenedioxy group [24]
Phosphine according - borane complex, [30] ^{R 3 ', R 5',} R
^{6 'and} R ^8' is a hydrogen atom, R ^{4 'and} R ^7' is C
The phosphine-borane complex according to the above [24], which is a _2-6 alkyl group, wherein [31] R ^{4 ′} , R ^{5 ′} , R ^{7 ′} and R ^{8 ′} are hydrogen atoms, and R ^{3 ′} and R ^{6 ′} are The phosphine-borane complex according to the above [24], which is a lower alkyl group, [32] formula

[Chemical 40] [In the formula, R ^{9 '} and R ^{10 '} each represent a lower alkyl group], [33] formula

[Chemical 41] [In the formula, R ^{3 ′} , R ^{5 ′} , R ^{6 ′} and R ^{8 ′} are a hydrogen atom, a lower alkyl group or a lower alkoxy group respectively, and R ^{4 ′} and R ^{7 ′} are a hydrogen atom, a fluorine atom and a chlorine atom, respectively. ,
A C _2-6 alkyl group, a lower alkoxy group, a mono-lower alkylamino group or a di-lower alkylamino group, R ^{9 '} and
R ^{10 '} represents a hydrogen atom or a lower alkyl group (R ^{3 '} and R ^{4 '} and R ^{7 '} and R ^{8 '} may form a lower alkylenedioxy group) (provided that R ^{3 '} , R ^{4 '} , R ^{5 '} , R ^{6
', R 7', R 8} ', R 9' compound represented by and except when R ^{10 'are} all hydrogen atoms)] or a salt thereof in the presence of cerium chloride and sodium borohydride, hydrogen Formula characterized by reduction with lithium aluminum iodide

[Chemical 42] [Wherein each symbol has the same meaning as defined above], a process for producing a phosphine-borane complex or a salt thereof, [34] formula

[Chemical 43] (In the formula, R ^1a , R ^1b , R ^1c , R ^1d , R ^1e , R ^1f , R ^2a , R ^2b , R
^2c , R ^2d , R ^2e and R ^2f are the same or different and each is a hydrogen atom, a fluorine atom, a chlorine atom, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, or an optionally substituted An aryl group, an optionally substituted hydroxy group, an optionally substituted amino group,
An optionally substituted alkylcarbonyl group, an optionally substituted alkoxycarbonyl group, a carboxyl group or an optionally substituted carbamoyl group, X represents a leaving group] or an optically active compound thereof Salt and formula

[Chemical 44] [In the formula, R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ and R ¹⁰ are the same or different and each is a hydrogen atom, a fluorine atom, a chlorine atom, or an optionally substituted hydrocarbon. Represents a group, an optionally substituted hydroxy group or an optionally substituted amino group, and R ³ and R ⁴ and R ⁷ and R ⁸ together form a 5- to 8-membered homolog with an adjacent carbon atom. A ring or a heterocycle may be formed], a compound obtained by reacting a phosphine-borane complex represented by the following formula or a salt thereof in a solvent in the presence of an amine and a nickel catalyst.

[Chemical formula 45] [Wherein the symbols have the same meanings as defined above] or the salt thereof is reduced to reduce the compound to be reduced,
5] Formula for producing an optically active compound by asymmetric reduction

[Chemical formula 46] [In the formula, R ^{3 ′} , R ^{5 ′} , R ^{6 ′} and R ^{8 ′} are a hydrogen atom, a lower alkyl group or a lower alkoxy group respectively, and R ^{4 ′} and R ^{7 ′} are a hydrogen atom, a fluorine atom and a chlorine atom, respectively. ,
C _2-6 alkyl group, lower alkoxy group, mono-lower alkylamino group or di-lower alkylamino group (R ^{3 '} and
R ^{4 '} and R ^{7 '} and R ^{8 '} may form a lower alkylenedioxy group (provided that R ^{3 '} , R ^{4 '} , R ^{5 '} , R ^{6 '} , R ^{7 '}
And R ^{8 '} is all hydrogen atoms)]] represented by phosphine-borane complex or formula

[Chemical 47] [Wherein R ^{9 ′} and R ^{10 ′} each represent a lower alkyl group] or a salt thereof, [36] for producing an optically active compound by asymmetric reduction S) -2,2'-bis [bis (3,5-di-tert-butyl-4-methoxyphenyl) phosphino] -1,1'-binaphthyl or (R) -2,2'-bis [bis ( It relates to the use of 3,5-di-tert-butyl-4-methoxyphenyl) phosphino] -1,1′-binaphthyl or salts thereof and the like.

Compound (I) and compound (II) are (R) form,
The (S) form and the mixture of the (R) form and the (S) form (both ratios are not limited) are shown.

In the above formula, R ^1a , R ^1b , R ^1c , R ^1d , R ^1e ,
"Alkyl group" of "optionally substituted alkyl group" represented by R ^1f , R ^2a , R ^2b , R ^2c , R ^2d , R ^2e or R ^2f
Is, for example, a lower alkyl group (methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,
tert-butyl, pentyl, hexyl and other C _1-6 alkyl groups) and the like. As the substituent of the “alkyl group”,
Nitro, nitroso, cyano, hydroxy, lower alkoxy groups (eg methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy,
C such as tert-butoxy, pentoxy, hexyloxy
_1-6 alkoxy group), formyl, lower alkylcarbonyl group (eg, C _1-6 alkyl-carbonyl group such as acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl), lower alkoxycarbonyl group (eg, methoxycarbonyl) , Ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl,
sec-butoxycarbonyl, tert-butoxycarbonyl,
C _1-6 alkoxy-carbonyl groups such as pentoxycarbonyl, hexyloxycarbonyl), carboxyl, N-
Mono-lower alkylcarbamoyl group (for example, N-monoC such as N-methylcarbamoyl, N-ethylcarbamoyl, N-propylcarbamoyl, N-isopropylcarbamoyl, N-butylcarbamoyl, N-isobutylcarbamoyl, N-tert-butylcarbamoyl) _1-6 alkyl-carbamoyl group), N, N-di-lower alkylcarbamoyl group (eg, N,
N-dimethylcarbamoyl, N, N-diethylcarbamoyl,
N, N- such as N, N-dipropylcarbamoyl, N, N-diisopropylcarbamoyl, N-ethyl-N-methylcarbamoyl
Di C _1-6 alkyl-carbamoyl group) and the like.
It may have 1 to 3 selected from these substituents at substitutable positions.

In the above formula, R^1a, R^1b, R^1c, R^1d, R^1e,
R^1f, R^2a, R^2b, R^2c, R^2d, R^2eOr R^2fRepresented by
The “cycloalkyl” of “optionally substituted cycloalkyl group”
The "alkyl group" means, for example, cyclopropyl, cyclobutyl.
C such as le, cyclopentyl, cyclohexyl_3-6Cyclo
An alkyl group and the like are shown. Substitution of the "cycloalkyl group"
As a group, R^1a, R^1b, R^1c, R^1d, R^1e, R^1f, R ^2a,
R^2b, R^2c, R^2d, R^2eOr R^2fRepresented by "replaced
The same as the substituent that the “optionally substituted alkyl group” may have.
The number and similar substituents can be mentioned.

In the above formula, R ^1a , R ^1b , R ^1c , R ^1d , R ^1e ,
"Aryl group" of "optionally substituted aryl group" represented by R ^1f , R ^2a , R ^2b , R ^2c , R ^2d , R ^2e or R ^2f
Is, for example, phenyl, 1-naphthyl, 2-naphthyl, etc.
A C _6-10 aryl group and the like are shown. The substituent of the "aryl group" includes R ^1a , R ^1b , R ^1c , R ^1d , R ^1e , R ^1f , R ^2a ,
The same number and the same number of substituents as the “optionally substituted alkyl group” represented by R ^{2 b} , R ^2c , R ^2d , R ^2e or R ^2f may have.

In the above formula, R ^1a , R ^1b , R ^1c , R ^1d , R ^1e ,
As the substituent of the “optionally substituted hydroxy group” represented by R ^1f , R ^2a , R ^2b , R ^2c , R ^2d , R ^2e or R ^2f , an optionally substituted lower alkyl group ( For example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, C _1-6 alkyl group such as hexyl), an optionally substituted lower alkylcarbonyl group (eg, acetyl, C _1-6 alkyl-carbonyl group such as propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl) and the like. As the substituent of the "optionally substituted hydroxy group", the "optionally substituted lower alkyl group" and the "optionally substituted lower alkylcarbonyl group" may have. As R
^{1a, R 1b, R 1c,} R 1d, R 1e, R 1f, R 2 a, R 2b, R 2c, R 2d,
The same number and the same number of substituents as the “optionally substituted alkyl group” represented by R ^2e or R ^2f may have.

In the above formula, R^1a, R^1b, R^1c, R^1d, R^1e,
R^1f, R^2a, R^2b, R^2c, R^2d, R^2eOr R^2fRepresented by
The substituent of the “optionally substituted amino group” is
An optionally substituted lower alkyl group (eg, methyl
Ru, ethyl, propyl, isopropyl, butyl, isobu
Chill, sec-butyl, tert-butyl, pentyl, hexyl
Such as C_1-6Alkyl group), optionally substituted lower group
Rukylcarbonyl group (eg acetyl, propioni
Le, butyryl, isobutyryl, valeryl, isovaleri
C such as le, pivaloyl_1-6Alkyl-carbonyl group)
And mono- or di-substitution with these substituents.
It may have been done. The “optionally substituted amino
A "optionally substituted lower group" as a substituent of "group"
"Alkyl group" and "optionally substituted lower alkyl"
The substituent which the “carbonyl group” may have is R
^1a, R^1b, R^1c, R^1d, R^1e, R^1f, R^2a, R ^2b, R^2c, R^2d,
R^2eOr R^2fRepresented by "the optionally substituted alkyl
The same number and the same number of substituents that the “group” may have.
Groups.

In the above formula, R^1a, R^1b, R^1c, R^1d, R^1e,
R^1f, R^2a, R^2b, R^2c, R^2d, R^2eOr R^2fRepresented by
“Alkylcarbonyl group which may be substituted”
As the “alkylcarbonyl group”, for example, a lower alkyl group
Rubonyl groups (eg acetyl, propionyl, butyryl)
, Isobutyryl, valeryl, isovaleryl, pivaloy
C such as le_1-6Alkyl-carbonyl group)
It The "optionally substituted alkylcarbonyl group"
The substituent of R is^1a, R ^1b, R^1c, R^1d, R^1e, R^1f, R
^2a, R^2b, R^2c, R^2d, R^2eOr R^2f"Replaced
Substituents that the “optionally substituted alkyl group” may have
The same number and the same substituents as are mentioned.

In the above formula, R ^1a , R ^1b , R ^1c , R ^1d , R ^1e ,
Examples of the “alkoxycarbonyl group” of the “optionally substituted alkoxycarbonyl group” represented by R ^1f , R ^2a , R ^2b , R ^2c , R ^2d , R ^2e or R ^2f include a lower alkoxycarbonyl group ( (For example, a C _1-6 alkoxy-carbonyl group such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, pentoxycarbonyl, hexyloxycarbonyl) And so on. Examples of the substituent of the "optionally substituted alkoxycarbonyl group" include R ^1a , R ^1b , R ^1c , R ^1d ,
R ^1e , R ^1f , R ^2a , R ^2b , R ^2c , R ^2d , R ^2e or R ^2f has the same number of substituents that an “optionally substituted alkyl group” may have, Similar substituents can be mentioned.

In the above formula, R^1a, R^1b, R^1c, R^1d, R^1e,
R^1f, R^2a, R^2b, R^2c, R^2d, R^2eOr R^2fRepresented by
As a substituent of “optionally substituted carbamoyl group”
Are, for example, an optionally substituted lower alkyl group (eg,
For example, methyl, ethyl, propyl, isopropyl, buty
Ru, isobutyl, sec-butyl, tert-butyl, pliers
C such as le, hexyl_1-6Alkyl group), substituted
A lower alkylcarbonyl group (eg, acetyl,
Propionyl, butyryl, isobutyryl, valeryl, a
C such as buckwheat ril and pivaloyl_1-6Alkyl-carboni
Group, etc., and mono-substitution with these substituents
May be di-substituted. The "may be substituted
“Substituted as a substituent of“ carbamoyl group ”
Optionally lower alkyl group "and" optionally substituted "
As a substituent of the "lower alkylcarbonyl group", R is^1a, R
^1b, R^1c, R^1d, R^1e, R^1f, R^2a, R^2b, R^2c, R ^2d, R^2eWell
Or R^2f“Alkyl which may be substituted
The same number of substituents that the “group” may have, the same substituents
Is mentioned.

In the above formula, the leaving group represented by X is
Examples thereof include a bromine atom, an iodine atom, an optionally substituted alkylsulfonyloxy group, and an optionally substituted arylsulfonyloxy group. Examples of the “optionally substituted alkylsulfonyloxy group” as the leaving group represented by X include, for example, a halogen atom (eg, fluorine, chlorine, bromine, iodine, etc.), and an optionally halogenated C A substituent selected from a _1-6 alkyl group and a C _1-6 alkoxy group (eg, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, etc.)
1 to 13 C _1-6 alkylsulfonyloxy groups (eg, methanesulfonyloxy, ethanesulfonyloxy, etc.) and the like may be included. Examples of the above-mentioned “optionally halogenated C _1-6 alkyl group” include 1
To 13, preferably 1 to 9 halogen atoms (eg, fluorine, chlorine, bromine, iodine, etc.) C _1-6 alkyl group optionally having (eg, methyl, ethyl, propyl,
Isopropyl, butyl, isobutyl, sec-butyl, ter
t-butyl, pentyl, hexyl, etc.) and the like. Specific examples of the “optionally substituted alkylsulfonyloxy group” as the leaving group represented by X include methanesulfonyloxy, ethanesulfonyloxy, trifluoromethanesulfonyloxy, chloromethanesulfonyloxy, trichloromethanesulfonyloxy. , Nonafluorobutanesulfonyloxy and the like. Of these, methanesulfonyloxy, trifluoromethanesulfonyloxy and the like are preferable.

Examples of the “optionally substituted arylsulfonyloxy group” as the leaving group represented by X include a halogen atom (eg, fluorine, chlorine, bromine, iodine etc.), C _1-6 alkyl Groups (eg, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,
tert-butyl, pentyl, hexyl, etc.), C _1-6 alkoxy group (eg, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, etc.), 1 to 5 substituents selected from nitro and cyano May
C _6-10 arylsulfonyloxy group (eg, benzenesulfonyloxy, 1-naphthalenesulfonyloxy, 2-naphthalenesulfonyloxy, etc.) and the like can be mentioned. Specific examples include benzenesulfonyloxy, p-toluenesulfonyloxy, 1-naphthalenesulfonyloxy, 2-naphthalenesulfonyloxy, p-nitrobenzenesulfonyloxy, m-nitrobenzenesulfonyloxy, m-toluenesulfonyloxy, o-toluenesulfonyloxy. ,Four-
Examples include chlorobenzenesulfonyloxy, 3-chlorobenzenesulfonyloxy, 4-methoxybenzenesulfonyloxy and the like. Of these, p-toluenesulfonyloxy and the like are preferable. As X, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy and the like are preferable, and trifluoromethanesulfonyloxy is particularly preferable.

In the above formula, "hydrocarbon group" of "optionally substituted hydrocarbon group" represented by R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ or R ^10. The "" includes an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group, an aralkyl group and the like. The "alkyl group" is a lower alkyl group (eg, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-
Butyl, pentyl, hexyl and the like C _1-6 alkyl group) and the like. The lower alkenyl group "Alkenyl group" (e.g., vinyl, allyl, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl, butadienyl, 2-methylallyl, hexatrienyl, such as 3-octenyl C _{2- 6} alkenyl group) and the like. The “alkynyl group” refers to a lower alkynyl group (eg, C _2-6 alkynyl group such as ethynyl, 2-propynyl, butynyl, 3-hexynyl) and the like. The “cycloalkyl group” is, for example, a C _3-6 cycloalkyl group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like. The “aryl group” refers to, for example, a C _6-10 aryl group such as phenyl and naphthyl. The “aralkyl group” is, for example, a C _7-10 aralkyl group such as benzyl and phenethyl. As the substituent of the “optionally substituted hydrocarbon group” represented by R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ or R ¹⁰ , R ^1a , R ^1b , R ^1c , R ^1d , R ^1e , R ^1f , R ^2a , R ^2b , R
^2c , R ^2d , R ^2e or R ^2f represents the same number of substituents that the “optionally substituted alkyl group” may have,
Similar substituents can be mentioned.

In the above formula, the “optionally substituted hydroxy group” represented by R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ or R ¹⁰ is R ^1a , R ^1b , R ^1c , R ^1d , R ^1e , R ^1f , R ^2a , R ^2b ,
The same as the "optionally substituted hydroxy group" represented by R ^2c , R ^2d , R ^2e or R ^2f can be mentioned. Of these, a lower alkoxy group (C _1-6 alkoxy group), that is, a hydroxy group substituted with a lower alkyl group (C _1-6 alkyl group) is preferable.

In the above formula, R³, R^Four, R^Five, R⁶, R⁷, R⁸, R⁹Well
Or R^Ten"Amino group which may be substituted"
And R^1a, R^1b, R^1c, R^1d, R^1e, R^1f, R^2a, R^2b,
R^2c, R^2d , R^2eOr R^2fRepresented by "even if replaced
The same as "good amino group" can be mentioned. Above all,
Di-lower alkylamino group (di-C_1-6Alkylamino group),
That is, a lower alkyl group (C_1-6Di-substitution with alkyl group)
Preferred are amino groups.

In the above formula, examples of the “5- to 8-membered homocyclic ring” which may be formed by R ³ and R ⁴ and R ⁷ and R ⁸ together with the adjacent carbon atom are, for example, cyclopentane. ,
Examples thereof include cyclohexane, cycloheptane, cyclooctane, benzene and the like. The "5- to 8-membered homocyclic ring" is
It may have a substituent, and as the substituent,
R ^1a , R ^1b , R ^1c , R ^1d , R ^1e , R ^1f , R ^2a , R ^2b , R ^2c ,
The same number and the same number of substituents as the “optionally substituted alkyl group” represented by R ^2d , R ^2e or R ^2f may have. The "5- to 8-membered homocyclic ring" is preferably a 6-membered homocyclic ring such as cyclohexane or benzene, and particularly preferably benzene.

In the above formula, “5- to 8-membered heterocycle” which may be formed by R ³ and R ⁴ and R ⁷ and R ⁸ together with the adjacent carbon atom is, for example, pyrrole or imidazole. , Pyrrolidine, pyrroline, imidazolidine, imidazoline, pyridine, pyrazine, pyrimidine, piperidine, pyrimidine, oxazole, furan, pyran, 1,3-
Examples include dioxolane and 1,4-dioxane. The "5
To 8-membered heterocycle, which may have a substituent,
As the substituent, R ^1a , R ^1b , R ^1c , R ^1d , R ^1e , R ^1f ,
R ^2a , R ^2b , R ^2c , R ^2d , R ^2e or R ^2f has the same number of substituents as the “optionally substituted alkyl group” represented by R ^2f , and similar substituents. To be The "5 to 8
As the "membered heterocycle", an oxygen-containing heterocycle is preferable, and among them, 1,3-dioxolane, 1,4-dioxane and the like are preferable,
Particularly, 1,3-dioxolane is preferable.

The compound (II) includes R ^1a and R ^2a , and R ^1b
R ^2b , R ^1c and R ^2c , R ^1d and R ^2d , R ^1e and R ^2e and R ^1f R ^2f
Are preferably the same groups, among which R
It is preferable that ^1a , R ^1f , R ^2a and R ^2f are hydrogen atoms. Further, R ^1a , R ^1b , R ^1c , R ^1f , R ^2a , R ^2b , R ^2c and R ^2f are hydrogen atoms, R ^1d and R ^2d are hydrogen atoms or C
_6-10 aryl group, R ^1e and R ^2e is preferably a hydrogen atom or a C _1-6 alkoxy group, particularly R ^1a , R ^1b ,
R ^1c , R ^1d , R ^1e , R ^1f , R ^2a , R ^2b , R ^2c , R ^2d , R ^2e and
It is preferred that all R ^2f are hydrogen atoms.

Specific examples of the compound (II) include 2,2'-bis (methanesulfonyloxy) -1,1'-binaphthyl and 2,2 '.
-Bis (trifluoromethanesulfonyloxy) -1,1'-
Binaphthyl, 2,2'-bis (p-toluenesulfonyloxy) -1,1'-binaphthyl, 6,6'-diphenyl-2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl, 7,7'-dimethoxy-2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl and the like can be mentioned. Of these, 2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl and 6,6'-diphenyl-2,2'-bis (trifluoromethanesulfonyloxy) -1,1'- are preferable. Binaphthyl, 7,7′-dimethoxy-2,2′-bis (trifluoromethanesulfonyloxy) -1,1′-binaphthyl and the like, more preferably 2,2′-bis (trifluoromethanesulfonyloxy) -1,1 ′ -Binaphtyl is an example. As the compound (II), an optically active compound (II) [(R)
Body or (S) body] is preferred. As an example of the optically active compound (II), for example, (R) -2,2′-bis (trifluoromethanesulfonyloxy) -1,1′-binaphthyl has the formula

[Chemical 48] The compound represented by

[Chemical 49] The compound represented by

As the compound (III), R³Is a hydrogen atom
Is C_1-6Alkyl group, R^FourIs hydrogen atom, fluorine atom, chlorine source
Child, C_1-6Alkyl group, C_6-10Aryl group, C_1-6Arcoki
Si group or di-C_1-6Alkylamino group or R³And R^FourBut
Benzene ring or 1,3-dioxo with adjacent carbon atoms
Forming a orchid ring, R^FiveIs a hydrogen atom or C_1-6An alkyl group,
R⁶Is a hydrogen atom or C_1-6Alkyl group, R⁷Is a hydrogen atom,
Fluorine atom, chlorine atom, C_1-6Alkyl group, C_6-10Aryl
Base, C_1-6Alkoxy group or di-C_1-6Alkylamino group,
R⁸Is a hydrogen atom or C_1-6Alkyl group or R⁷And R⁸But
Benzene ring or 1,3-dioxo with adjacent carbon atoms
Forming a orchid ring, R⁹Is a hydrogen atom or C_{1 -6}An alkyl group,
R^TenIs a hydrogen atom or C_1-6Those that are alkyl groups are preferred
Good Above all, R³, R^Five, R⁶And R⁸Are the same group, R^FourOh
And R⁷Are the same group, R⁹And R^TenIs a hydrogen atom
Is preferred. For example, (i) R³, R^Four, R^Five, R⁶, R⁷, R⁸, R⁹
And R^TenIs a hydrogen atom, (ii) R³, R^Five, R⁶,
R⁸, R⁹And R^TenIs a hydrogen atom and R^FourAnd R⁷But
Those that are elementary atoms or chlorine atoms, (iii) R³, R^Five, R⁶, R
⁸, R⁹And R^TenIs a hydrogen atom and R^FourAnd R⁷Is lower
Rukiru group (C_1-6An alkyl group), (iv) R³, R^Five,
R⁶, R⁸, R⁹And R^TenIs a hydrogen atom and R^FourAnd R⁷But
Lower alkoxy group (C_1-6An alkoxy group),
(v) R³, R^Five, R⁶, R⁸, R⁹And R^TenIs a hydrogen atom and R^Four
And R⁷Is a di-lower alkylamino group (di-C_1-6Alkyla
A (mino group), (vi) R³, R^Five, R⁶And R⁸Is low
Alkyl group (C_1-6Alkyl group), and R^Four, R⁷, R⁹And
And R^TenIs a hydrogen atom, (vii) R³, R^Five, R⁶And R⁸
Is a lower alkyl group (C_1-6Alkyl group), and R^Fourand
R⁷Is a lower alkoxy group (C_1-6An alkoxy group) and R⁹
And R^TenIs a hydrogen atom and (viii) R³, R^Five, R
⁶, R⁸, R⁹And R^TenIs a hydrogen atom and R^FourAnd R⁷Is C
_6-10Those that are aryl groups can be mentioned. In particular (i)
R³, R^Four, R^Five, R⁶, R⁷, R⁸, R⁹And R^TenIs a hydrogen atom
Things, (ii) R³, R^Five, R⁶, R⁸, R⁹And R^TenIs a hydrogen atom
And R^FourAnd R⁷Is a lower alkyl group (C_1-6Alkyl
Group), (iii) R³, R^Five, R⁶, R⁸, R⁹And R^TenBut
A hydrogen atom, R^FourAnd R⁷Is a lower alkoxy group (C_1-6
An alkoxy group), (iv) R³, R^Five, R⁶And R⁸But
Lower alkyl group (C_1-6Alkyl group), and R^Four, R⁷, R⁹
And R^TenIs a hydrogen atom and (v) R³, R^Five, R⁶
And R⁸Is a lower alkyl group (C_1-6Alkyl group),
R^FourAnd R⁷Is a lower alkoxy group (C_1-6Alkoxy group)
Yes, R⁹And R^TenIs preferably a hydrogen atom.
Also, (i) R³And R⁶Is a lower alkyl group (C_1-6Alkyl
Group) and R^Four, R^Five, R ⁷, R⁸, R⁹And R^TenIs a hydrogen atom
And (ii) R³And R^FourAnd R⁷And R⁸Together
Benzene ring or 1,3-dio with adjacent carbon atoms
Forming xoxolan, R^Five, R⁶, R⁹And R^TenIs a hydrogen atom
Some are also mentioned as preferable examples.

Specific examples of the compound (III) include, for example,
Diphenylphosphine-borane complex, bis (4-methylphenyl) phosphine-borane complex, bis (4-methoxyphenyl) phosphine-borane complex, bis (3,5-dimethylphenyl) phosphine-borane complex, bis (3,5- Di-tert
-Butyl-4-methoxyphenyl) phosphine-borane complex, bis (4-fluorophenyl) phosphine-borane complex, bis (4-dimethylaminophenyl) phosphine-borane complex, bis (1,3-benzodioxole-5 -Yl) phosphine-borane complex, bis (4-chlorophenyl) phosphine-borane complex, bis (3,5-dimethyl-4-methoxyphenyl) phosphine-borane complex, bis (4-tert-butylphenyl) phosphine-borane complex , Bis (3-methylphenyl) phosphine-borane complex, bis (3,5-di-tert-
Butylphenyl) phosphine-borane complex and the like.

Examples of the "amine" used in the present invention include 1,4-diazabicyclo [2.2.2] octane (abbreviation: D
ABCO), triethylamine, diisopropylethylamine, tri (n-propyl) amine, tri (n-butyl) amine, 1,8-diazabicyclo [5.4.0] -7-undecene (abbreviation: DBU), tetramethylethylenediamine, dimethylaniline , 1,4-dimethylpiperazine, 1-methylpiperidine, 1-methylpyrrolidine, 4-dimethylaminopyridine,
Examples include amines such as pyridine and diethylamine. Of these, 1,4-diazabicyclo [2.2.2] is preferable.
It is a tertiary amine such as octane, triethylamine and diisopropylethylamine. Particularly preferred is 1,4-diazabicyclo [2.2.2] octane.

The nickel catalyst used in the present invention includes
NiCl₂・ Bis (diphenyl) phosphino C_1-4Alkane, N
iBr₂, NiCl₂, NiCl₂・ Bis (diphenyl) phosphinyl
Ferrocene, NiCl₂・ Bis (triphenylphosphine
), Ni ・ Tetrakistriphenylphosphine, Ni ・ Te
Trakistriphenylphosphite, Ni-dicarbonyl
Bis (triphenyl) phosphine, NiBr₂・ Bis (bird
Phenylphosphine), Ni-bis (1,5-cyclooctadi)
Ene), Ni-bis (cyclopentadienyl), Ni-bis
(Ethylcyclopentadienyl), NiCl₂・ Dimethoxy
Ethane, Ni (BF_Four)₂Or Ni (PF₃)_FourAnd so on. Na
But, NiCl₂・ Bis (diphenyl) phosphino C_1-4A
Lucan, NiBr₂, NiCl ₂, NiCl₂・ Bis (diphenyl) pho
Sphinylferrocene, NiCl₂・ Bis (triphenylpho
Sphine), Ni / tetrakistriphenylphosphine,
Ni ・ tetrakistriphenylphosphite or Ni ・ di
Carbonylbis (triphenyl) phosphine etc. are preferred
Good Above all, NiCl₂・ Bis (diphenyl) phosphine
No C_1-4Alkanes and the like are preferred, especially NiCl₂・ Bis
Phenyl) phosphinoethane is preferred.

Specific examples of the compound (I) include 2,2'-bis
[Bis (3,5-dimethylphenyl) phosphino] -1,1'-binaphthyl, 2,2'-bis [bis (4-methoxyphenyl) phosphino] -1,1'-binaphthyl, 2,2'-bis [Bis (4-dimethylaminophenyl) phosphino] -1,1'-binaphthyl, 2,2'-
Bis [bis (4-fluorophenyl) phosphino] -1,1'-binaphthyl, 2,2'-bis [bis (3,5-di-tert-butyl-4-methoxyphenyl) phosphino] -1,1 ' -Binaphtyl, 2,2'-
Bis (diphenylphosphino) -1,1'-binaphthyl, 2,2 '
-Bis [bis (2-methylphenyl) phosphino] -1,1'-binaphthyl, 2,2'-bis [bis (3-methylphenyl) phosphino] -1,1'-binaphthyl, 2,2'-bis [Bis (4-methylphenyl) phosphino] -1,1'-binaphthyl, 2,2'-bis [bis (4-tert-butylphenyl) phosphino] -1,1'-binaphthyl, 2,2'-bis [Bis (3,5-di-tert-butylphenyl)
Phosphino] -1,1'-binaphthyl, 2,2'-bis [bis (4-methoxy-3,5-dimethylphenyl) phosphino] -1,1'-binaphthyl, 2,2'-bis [bis (4 -Chlorophenyl) phosphino] -1,1'-binaphthyl, 2,2'-bis [bis (1,3-benzodioxol-5-yl) phosphino] -1,1'-binaphthyl, 2,
2'-bis [bis (2-naphthyl) phosphino] -1,1'-binaphthyl, 2,2'-bis (diphenylphosphino) -6,6'-diphenyl-1,1'-binaphthyl, 2,2 Examples include'-bis (diphenylphosphino) -7,7'-dimethoxy-1,1'-binaphthyl. The above compounds are (R) form, (S) form and (R) form
A mixture with the (S) form (the ratio of the two is not limited) is included. As an example of the optically active compound (I), for example, (R) -2,
2'-bis (diphenylphosphino) -1,1'-binaphthyl has the formula

[Chemical 50] The compound represented by the formula (S) -2,2'-bis (diphenylphosphino) -1,1'-binaphthyl has the formula

[Chemical 51] The compound represented by

Compound (I), Compound (II) and Compound (III)
Examples of the salts include salts with inorganic acids (eg, hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, etc.) or organic acids (eg, formic acid, acetic acid, trifluoroacetic acid, fumaric acid, oxalic acid, tartaric acid) , Maleic acid, citric acid, succinic acid,
Malic acid, methanesulfonic acid, benzenesulfonic acid, p-
Toluenesulfonic acid, etc.) and the like are used. Further, when the compound (I), the compound (II) and the compound (III) have an acidic group such as a carboxyl group, an inorganic base (for example, alkali metal or alkali such as sodium, potassium, calcium, magnesium) Salts with earth metals, ammonia, etc., or salts with organic bases (eg, trimethylamine, triethylamine, pyridine, picoline, ethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, N, N'-dibenzylethylenediamine). Are used.

Further, in the compound (III),

[Chemical 52] [In the formula, R ^{3 ′} , R ^{5 ′} , R ^{6 ′} and R ^{8 ′} are a hydrogen atom, a lower alkyl group or a lower alkoxy group respectively, and R ^{4 ′} and R ^{7 ′} are a hydrogen atom, a fluorine atom and a chlorine atom, respectively. ,
C _2-6 alkyl group, lower alkoxy group, mono-lower alkylamino group or di-lower alkylamino group (R ^{3 '} and
R ^{4 '} and R ^{7 '} and R ^{8 '} may form a lower alkylenedioxy group (provided that R ^{3 '} , R ^{4 '} , R ^{5 '} , R ^{6 '} , R ^{7 '}
And R ^{8 '} excludes all hydrogen atoms)]) or a salt thereof (hereinafter sometimes abbreviated as compound (III')) and a formula

[Chemical 53] A phosphine-borane complex represented by the formula [wherein R ^{9 '} and R ^{10 '} each represent a lower alkyl group] or a salt thereof [hereinafter sometimes abbreviated as compound (III ")] is a novel compound. .

In the compound (III ′), the “lower alkyl group” represented by R ^{3 ′} , R ^{5 ′} , R ^{6 ′} or R ^{8 ′} is a C _1-6 alkyl group such as methyl, Ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-
Butyl, pentyl, hexyl and the like can be mentioned. In the compound (III ′), the “lower alkoxy group” represented by R ^{3 ′} , R ^{5 ′} , R ^{6 ′} or R ^{8 ′} is a C _1-6 alkoxy group,
For example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-
Examples include butoxy, pentoxy, and hexyloxy.

R in compound (III ')^{Four '}Or R^{7 '}Table
Will be "C_2-6“Alkyl group” means, for example, ethyl, pro
Pill, isopropyl, butyl, isobutyl, sec-butyl
, Tert-butyl, pentyl, hexyl etc.
Among them, isopropyl, isobutyl, sec-butyl,
branched C such as tert-butyl_3-6Alkyl groups are preferred.
R in compound (III ′)^{Four '}Or R^{7 '}Represented by "Lower
"Alkoxy group" means C _1-6Indicates an alkoxy group, for example
For example, methoxy, ethoxy, propoxy, isopropoxy
Ci, butoxy, isobutoxy, sec-butoxy, tert-but
Examples include toxy, pentoxy, hexyloxy and the like.

In the compound (III '), the "mono-lower alkylamino group" represented by R ^{4 '} or R ^{7 '} is a mono C _1-6 alkylamino group, such as methylamino, ethylamino, Propylamino, isopropylamino, butylamino, isobutylamino, sec-butylamino, tert-
Butylamino, pentylamino, hexylamino and the like can be mentioned. In the compound (III ′), the “di lower alkylamino group” represented by R ^{4 ′} or R ^{7 ′} is a di C _1-6 alkylamino group, and examples thereof include dimethylamino, diethylamino, dipropylamino, Examples include diisopropylamino, dibutylamino, diisobutylamino and the like.

[0035] 'In, R ³ compound ^(III)' R ⁴ and ^'and R ^7
'And R ^8' are formed in the "lower alkylenedioxy _{group", -OCH 2 O -, - OCH} 2 CH 2 O -, - OCH 2 CH 2 CH 2 O -, - OCH 2 CH 2 CH
₂ CH ₂ O- and the like. Above all, -OCH ₂ O-, -OCH ₂ CH ₂ O
-Is preferred.

Compounds preferable as the compound (III ')
And then (i) R^{3 '}, R^{Five '}, R^{6 '}And R^{8 '}Is lower alkyl
Group (C_1-6Alkyl group), and R ^{Four '}And R^{7 '}Is hydrogen
A compound that is a child, (ii) R^{3 '}, R^{Five '}, R^{6 '}And R^{8 '}Is low
Primary alkyl group (C_1-6Alkyl group), and R^{Four '}And R^7
'Is a lower alkoxy group (C_1-6A compound that is an alkoxy group)
Thing, (iii) R^{3 '}, R^{Five '}, R^{6 '}And R^{8 '}Is a hydrogen atom
R^{Four '}And R^{7 '}Is a fluorine atom or a chlorine atom
Compound, (iv) R^{3 '}, R^{Five '}, R^{6 '}And R^{8 '}Is a hydrogen atom
Yes, R^{Four '}And R^{7 '}Is a lower alkoxy group (C_1-6Arco
Xy group) or (v) R^{3 '}, R^{Five '}, R^{6 '}And
And R^{8 '}Is a hydrogen atom and R^{Four '}And R^{7 '}Is the lower grade
Killamino group (di-C_1-6A compound that is an alkylamino group)
The thing, or these salts etc. are mentioned. Also, (vi)
 R^{Five '}And R^{8 '}Is a hydrogen atom and R^{3 '}And R^{Four '}And R
^{7 '}And R^{8 '}A compound that forms a methylenedioxy group with
i) R^{3 '}, R^{Five '}, R^{6 '}And R^{8 '}Is a hydrogen atom and R^{Four '}
And R^{7 '}Is C_2-6A compound which is an alkyl group, (viii)
R^{Four '}, R^{Five '}, R^{7 '}And R^{8 '}Is a hydrogen atom and R^{3 '}Oh
And R^{6 '}Is a lower alkyl group (C_1-6Is an alkyl group)
Compounds are also preferred.

More specifically, bis (3,5-dimethylphenyl) phosphine-borane complex, bis (3,5-di-tert-butyl-4-methoxyphenyl) phosphine-borane complex, bis (4-fluoro) Phenyl) phosphine-borane complex, bis (4-methoxyphenyl) phosphine-borane complex, bis (4-dimethylaminophenyl) phosphine-borane complex, bis (1,3-benzodioxol-5-yl) phosphine-borane Complex, bis (4-chlorophenyl) phosphine-
Borane complex, bis (4-methoxy-3,5-dimethylphenyl) phosphine-borane complex, bis (4-tert-butylphenyl) phosphine-borane complex, bis (3-methylphenyl) phosphine-borane complex, bis (3 , 5-Di-tert-butylphenyl) phosphine-borane complex and the like are preferable.

[0038] In the compounds (III "), the" lower alkyl group "represented by R ^{9 'and} R ^10' represents a C _{1 -6} alkyl group, e.g., methyl, ethyl, propyl, isopropyl, butyl, Isobutyl, sec-butyl, tert-butyl,
Examples include pentyl and hexyl. Compound (III ”)
Specific examples of bis (2-methylphenyl) phosphine-borane complex and the like.

Examples of the salts of compound (III ') and compound (III ") include the same salts as those of compound (I), compound (II) and compound (III) described above.

The production method of the present invention comprises the compound (II) and the compound (I
II) is reacted with an amine and a nickel catalyst in a solvent to obtain a compound (I). The amount of compound (III) used is about 2 to 5 mol per 1 mol of compound (II),
It is preferably about 2 to 3 mol. The amount of amine used is
It is about 2 to 10 mol, preferably about 2 to 8 mol, relative to 1 mol of compound (II). The amount of nickel catalyst used is approximately 0.01 to 10 mol, preferably approximately 0.05 to 1 mol, with respect to 1 mol of the compound (II). The reaction can be carried out in an inert organic solvent. Examples of the organic solvent include hydrocarbons (eg, hexane, pentane, cyclohexane, etc.), amides (eg, N, N-dimethylformamide (DM
F), N, N-dimethylacetamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, etc.), aromatic hydrocarbons (eg, toluene, benzene, chlorobenzene, etc.), aliphatic esters ( (Eg, ethyl acetate, n-propyl acetate, n-butyl acetate, etc.), ethers (eg, diisopropyl ether, diethyl ether, tetrahydrofuran (THF), 1,4-dioxane, 1,2-dimethoxyethane, etc.), halogenated Hydrocarbons (eg, chloroform, dichloromethane, 1,2-dichloroethane, carbon tetrachloride, etc.), alcohols (eg, methanol, ethanol, isopropanol, tert-butanol, etc.), ketones (eg, acetone, ethyl methyl ketone) Etc.), sulfoxides (eg, dimethyl sulfoxide, etc.), nitriles (eg, acetonitrile, propionitrile) Etc.), phosphoric acid amides (e.g., such as hexamethylphosphoramide) and the like. These solvents may be used alone or as a mixed solvent. Preferred solvents are amides, sulfoxides, phosphoric amides and the like. More preferably, amides (N, N-dimethylformamide (DMF),
N, N-dimethylacetamide, N-methylpyrrolidone, 1,3-
Dimethyl-2-imidazolidinone). The reaction temperature in the reaction is about 30 to 180 ° C, preferably about 80 to 120 ° C. The reaction time in the reaction is about 1 to
It is 240 hours, preferably about 24 to 168 hours. The product can be isolated from the reaction mixture according to a conventional method, and can be easily purified by a separation means such as recrystallization, distillation and chromatography.

Compound (II) can be obtained by a method known per se, for example, Tetrahedron Letters, 31: 985, 1990, Journal of Organic Chemistry, 58: 1945.
Page, 1993, etc. The compound (II) thus obtained may be used for the reaction with the compound (III) as a reaction mixture without isolation. Compound
(III) is a phosphine oxide having a substituent obtained according to the method described in Journal of Organic Chemistry, 33, 3690, 1968, in the presence of cerium chloride, sodium borohydride and lithium aluminum hydride. It can be produced by reacting below.

[Chemical 54] [Wherein each symbol has the same meaning as described above] The amount of cerium chloride used is about 1 to 6 mol, preferably about 3 to 5 mol, per 1 mol of phosphine oxide. The amount of sodium borohydride used is about 2 to 10 mol, preferably about 3 to 5 mol, per 1 mol of phosphine oxide. The amount of lithium aluminum hydride used is about 0.25 with respect to 1 mol of phosphine oxide.
To 5 mol, preferably about 1 to 3 mol. The reaction can be carried out in an inert organic solvent. Examples of the organic solvent include hydrocarbons (eg, hexane, pentane, cyclohexane, etc.), amides (eg, N, N-dimethylformamide (DMF), N, N-dimethylacetamide, N
-Methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, etc.), aromatic hydrocarbons (eg, toluene, benzene, etc.)
Chlorobenzene etc.), ethers (eg diisopropyl ether, diethyl ether, tetrahydrofuran (THF), 1,4-dioxane, 1,2-dimethoxyethane etc.), phosphoric acid amides (eg hexamethylphosphoric acid amide etc.) etc. Is mentioned. These solvents may be used alone or as a mixed solvent. Preferred solvents are ethers, hydrocarbons, aromatic hydrocarbons and the like. More preferably, ethers (eg, diisopropyl ether, diethyl ether, tetrahydrofuran (TH
F), 1,4-dioxane, 1,2-dimethoxyethane, etc.). The reaction temperature in the reaction is about -20 to 50 ° C,
It is preferably about -10 to 35 ° C. The reaction time in the reaction is about 1 to 48 hours, preferably about 1 to 20 hours. Further, diborane may be allowed to act on the phosphine having a substituent according to the method described in US Pat. No. 2,926,194. The product can be isolated from the reaction mixture according to a conventional method, and can be easily purified by a separation means such as recrystallization, distillation and chromatography. The compound (III) thus obtained may be used for the reaction with the compound (II) as a reaction mixture without isolation.

By carrying out this reaction under the above conditions, the compound (I) can be produced without isomerizing the structure of the compound (II). That is, in the present invention, if the optical isomer of either (R) form or (S) form of the optically active compound (II) is appropriately selected, the optical isomer of the target compound (I) is selectively selected. Can be obtained. For example, the compound
When the (R) form of (II) is used, the (R) form of compound (I) can be efficiently produced, and when the (S) form of compound (II) is used, the compound
The (S) form of (I) can be efficiently produced. The compound (I) obtained by the production method of the present invention, particularly its optical isomer, forms a complex with a transition metal (eg, ruthenium, iridium, palladium, nickel, rhodium, etc.) (see, for example, JP-A-3-
By forming a complex according to the method described in JP-B No. 255090, JP-A No. 9-124669, or a method similar thereto, an optically active drug (eg, prophylactic / therapeutic drug for frequent urination / urinary incontinence, Alzheimer's disease) Prophylactic / therapeutic agents, hyperlipidemia preventive / therapeutic agents, etc.) or asymmetric synthetic reactions for producing compounds useful as intermediates thereof (eg, asymmetric reduction of carbon-carbon double bond, β-keto ester It can be used for simultaneous reduction, etc.). The complex exhibits excellent stereoselectivity, chemical yield, catalytic activity and the like in the above asymmetric synthesis reaction. For example, by allowing the compound (I) obtained by the production method of the present invention to coexist in the reduction reaction of the compound to be reduced, a compound useful as an intermediate for a drug can be obtained with excellent stereoselectivity. In particular, among the compounds (I), 2,2'-bis [bis (3,5-di
-tert-butyl-4-methoxyphenyl) phosphino] -1,1'-
Coexistence of binaphthyl or a salt thereof in the reduction reaction of α, β-unsaturated ester can exhibit excellent stereoselectivity, chemical yield, and catalytic activity.

[0043]

BEST MODE FOR CARRYING OUT THE INVENTION Examples and reference examples are given below.
The present invention will be described in more detail below.
It is not limited to. In the present specification, room temperature is 10 ° C.
To 35 ° C. In addition, the measurement of each physical property of the examples is as follows.
Equipment was used.¹H nuclear magnetic resonance spectrum (¹H-NMR): DP
X300 (Brooker), internal reference material: tetramethyl
run. ¹³C nuclear magnetic resonance spectrum (¹³C-NMR): DPX300
(Lucker), internal reference material: CDCl₃.³¹P nuclear magnetic resonance
Spectrum (³¹P-NMR): DPX300 (Brooker), external
Reference substance: 85% H₃PO_FourAqueous solution. Mass spectrometry: JMS-700T (Japan
Made by Electronics). Melting point: 530 (manufactured by Büch).

[0044]

Examples Reference Example 1 (S) -2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (S) -1,1'-bi-2-naphthol (26.2 g, 91 mmoL ) In acetonitrile (130 mL), pyridine (19.5 g, 2.7 eq)
Was added at room temperature. Then trifluoromethanesulfonic anhydride (64.2 g, 2.5 eq) was added at 5 ° C and at 5-10 ° C.
It was stirred for 2 hours. Water (100 mL) was added at 3 ° C., then ethyl acetate (130 mL) was added, and the mixture was stirred at room temperature for 30 min. The reaction solution was separated, the organic layer was washed with water (50 mL), and concentrated under reduced pressure. Diisopropyl ether (150 mL) and activated carbon (0.25 g) were added to the residue, and the mixture was stirred at 60 ° C for 30 min. Activated carbon was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from heptane to obtain the title compound (48.9 g, white crystals). Yield 97% ¹ H-NMR (300MHz, CDCl ₃ , TMS) δ: 7.33 (d, 2H, J =
8.14 Hz), 7.34-7.46 (m, 2H), 7.57-7.63 (m, 2H), 7.6
8 (d, 2H, J = 9.09 Hz), 8.03 (d, 2H, J = 8.23 Hz),
8.16 (d, 2H, J = 9.08 Hz).

Reference Example 2 Bis (3,5-dimethylphenyl) phosphine oxide

[Chemical 55] (Production method 1) Magnesium (25 g,
0.95 eq) and a small amount of iodine in THF (250 mL) was stirred at room temperature for 1 hour. 5-Bromo-m-xylene (200 g, 1.08
(moL) was added at 48 ° C, and the mixture was stirred at 5 ° C for 1 hr. Followed by 5
Diethyl phosphite (78.3 g, 0.52 equivalent) was added at ℃, and the mixture was stirred at 5 ℃ for 2 hours. Water (200 mL) was added at 3 ° C, then toluene (200 mL) and 6M-HCl (160 mL) were added, and the mixture was stirred at room temperature for 30 min. The reaction solution was separated, and the organic layer was washed with water (100
mL), 5% NaHCO ₃ aqueous solution (100 mL), 5% NaCl aqueous solution (100 mL)
Washed sequentially. Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from diisopropyl ether-heptane to obtain the title compound (43.3 g, white crystals). Yield 33.3%. (Production method 2) Magnesium (3.28 g, 4.01
Equivalent) and a small amount of iodine, 1,2-dibromoethane in THF
The (10 mL) solution was stirred at room temperature for 1.5 hours. 5-bromo-m-
Add a solution of xylene (25.2 g, 4.05 eq) in THF (100 mL).
After adding at 25 ° C, the mixture was stirred at 40 ° C for 40 minutes. Then -33 ℃
Diethyl phosphite (4.64 g, 33.6 mmol) in THF (5 m
L) After adding the solution, the mixture was stirred at 0 ° C. for 30 minutes. Water (3
0 mL), then 6M-HCl (20 mL) and toluene (50 mL).
After adding, the mixture was stirred at room temperature for 30 minutes. The reaction solution is separated,
The organic layer was washed with 10% aqueous NaHCO ₃ solution (30 mL), and the organic layer was concentrated under reduced pressure. The residue was recrystallized from heptane and dried (reduced pressure, 50 ° C.) to give the title compound (6.80 g, white powder).
Yield 78.3%. Melting point: 82.4 ° C. ¹ H-NMR (300MHz, CDCl ₃ , TMS) δ: 2.35 (s, 12H), 7.1
8 (s, 2H), 7.28 (s, 2H), 7.33 (s, 2H), 7.94 (d, 1
H, J _HP = 477.0 Hz). ³¹ P-NMR (121MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: 23.89 (d, qu
int, J _HP = 477.1 Hz, J _HCC-P = 13.7 Hz).

Reference Example 3 Bis (4-methoxyphenyl) phosphine oxide

[Chemical 56] Under an argon atmosphere, a solution of magnesium (6.5 g, 1.0 equivalent) and a small amount of iodine in THF (65 mL) was stirred at room temperature for 1 hour. 4-Bromoanisole (50 g, 0.27 moL) was added at 42 ° C, and the mixture was stirred at 5 ° C for 1 hr. Then add diethyl phosphite (18.4 g, 0.50 eq) at 15-20 ° C and then at 5 ° C.
Stir for 1 hour. Water (60 mL) was added at 3 ° C., then toluene (120 mL) and 6M-HCl (60 mL) were added, and the mixture was stirred at room temperature for 30 min. The reaction mixture was separated, and the aqueous layer was washed with toluene (60 mL).
Extracted twice. Then, the combined organic layers were dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from diisopropyl ether to give the title compound (18.
9 g, white crystals were obtained. Yield 54.1%. Melting point 126.0 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 3.85 (s, 6H), 6.9
9 (d, 2H, J = 8.79 Hz), 7.00 (d, 2H, J = 8.73 Hz),
7.61 (dd, 4H, J = 8.73 Hz, 13.13 Hz), 8.02 (d, 1H,
^{. J = 477.2 Hz) 31 P} -NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: 21.21 (dqui
nt, J = 474.1 Hz, 13.0 Hz). Elemental analysis calculated as C ₁₄ H ₁₅ O ₃ P; C: 64.12, H: 5.77, P: 11.81. .

Reference Example 4 Bis (4-dimethylaminophenyl) phosphine oxide

[Chemical 57] A solution of magnesium (3.0 g, 1.0 equivalent) and a small amount of iodine in THF (30 mL) was stirred at room temperature for 1 hour under an argon atmosphere. 4-Bromo-N, N-dimethylaniline (25 g, 0.125 mo
L) was added at 45 ° C, and the mixture was stirred at 5 ° C for 1 hr. Then 5 ℃
After adding diethyl phosphite (8.63 g, 0.50 eq) at 5.
The mixture was stirred at 0 ° C for 1 hour. Water (30 mL) was added at 3 ° C., then toluene (60 mL) and 6M-HCl (30 mL) were added, and the mixture was stirred at room temperature for 30 min. The reaction solution is separated, the aqueous layer is neutralized with NaOH, and THF is added.
It was extracted with (30 mL). Then, the combined organic layers were dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from diisopropyl ether to give the title compound (9.53 g, slightly brown white crystals). Yield 52.9%. Melting point 152.1 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 3.01 (s, 12H), 6.
71 (d, 2H, J = 8.94 Hz), 6.72 (d, 2H, J = 8.94 H
z), 7.48 (d, 2H, J = 8.91 Hz), 7.52 (d, 2H, J = 8.8
. 8 Hz), 7.96 (d , 1H, J = 470.1 Hz) 31 P-NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: 22.78 (dqui
nt, J = 469.2 Hz, 12.7 Hz). Elemental analysis Calculated as C ₁₆ H ₂₁ N ₂ OP; C: 66.65, H: 7.34, N: 9.72, P: 10.74. Measured value; C: 66.56, H: 7.43 , N: 9.57, P: 10.79.

Reference Example 5 Bis (4-fluorophenyl) phosphine oxide

[Chemical 58] Under an argon atmosphere, a solution of magnesium (6.95 g, 1.0 equivalent) and a small amount of iodine in THF (70 mL) was stirred at room temperature for 1 hour. 1-Bromo-4-fluorobenzene (50 g, 0.286 moL)
Was added at 40 ° C., and then the mixture was stirred at 3 ° C. for 1 hour. Then, diethyl phosphite (19.7 g, 0.50 equivalent) was added at 13 to 19 ° C, and the mixture was stirred at 5 ° C for 1 hr. Water (45 mL) was added at 4 ° C, then toluene (150 mL) and 6M-HCl (45 mL) were added, and the mixture was stirred at room temperature for 30 min. The reaction solution was separated, and the organic layer was washed successively with water, 5% NaHCO ₃ aqueous solution (50 mL), and 5% NaCl aqueous solution (50 mL). The organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was subjected to column chromatography (silica gel 30 g, n-hexane / ethyl acetate =
It was purified by 1/0 → 3/1). The title compound (12.0 g, pale red oil) was obtained. Yield 35.2%. ¹ H-NMR (300MHz, CDCl ₃ , TMS) δ: 7.01-7.03 (m, 4H),
7.64-7.74 (m, 4H), 8.08 (d, 1H, J = 485.8 Hz) 31 P-NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ:. 19.39 (dqui
nt, J = 485.7 Hz, 13.3 Hz).

Reference Example 6 4-Bromo-2,6-di-tert-butylanisole

[Chemical 59] Under an argon atmosphere, 4-bromo-2,6-di-tert-butylphenol (50 g, 0.175 moL) and potassium carbonate (96.7 g,
4.0 equivalents of acetone in 750 mL of dimethyl sulfate (38.6
g, 1.75 eq) was added at 22 ° C., and the mixture was stirred under reflux for 13 hours. After the insoluble matter was filtered off, the solvent was distilled off under reduced pressure. Ethyl acetate (150 mL) and water (100 mL) were added, the layers were separated, and the organic layer was washed with water (1 mL).
00 mL), 5% NaHCO ₃ aqueous solution (100 mL), 5% NaCl aqueous solution (100 m
It wash | cleaned one by one by L). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The title compound (56.1 g, brown oil) was obtained. Yield 95.2% ¹ H-NMR (300MHz, CDCl ₃ , TMS) δ: 1.41 (s, 18H), 3.6
8 (s, 3H), 7.33 (s, 2H).

Reference Example 7 Bis (3,5-di-tert-butyl-4-methoxyphenyl) phosphine oxide

[Chemical 60] A solution of magnesium (4.0 g, 0.95 equivalent) and a small amount of iodine in THF (50 mL) was stirred at room temperature for 1 hour under an argon atmosphere. 4-Bromo-2,6-di-tert-butylanisole (52 g, 0.175 moL) synthesized in Reference Example 6 was added at 46 ° C to 53 ° C, and the mixture was stirred at 5 ° C for 1 hr. Then, diethyl phosphite (11.4 g, 0.52 equivalent) was added at 5 ° C, and the mixture was stirred at 5 ° C for 1 hr. Water (50 mL) was added at 3 ° C, and then toluene (50 m
L) and 6M-HCl (20 mL) were added, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was separated, and the organic layer was washed successively with water (20 mL), 5% NaHCO ₃ aqueous solution (20 mL), and 5% NaCl aqueous solution (20 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from heptane to obtain the title compound (11.6 g, pale yellowish white crystals). Yield 20.
Five%. Melting point 166.1 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 1.38 (s, 36H), 3.
68 (s, 6H), 7.49 (s, 2H), 7.54 (s, 2H), 8.01 (d, 1
. H, J = 474.4 Hz) 31 P-NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: 23.57 (dqui
nt, J = 474.1 Hz, 14.0 Hz). Elemental analysis calculated as C ₃₀ H ₄₇ O ₃ P; C: 74.04, H: 9.73, P: 6.36. Found; C: 74.13, H: 9.93, P: 6.20. .

Reference Example 8 Bis (4-methylphenyl) phosphine oxide

[Chemical formula 61] A solution of magnesium (3.55 g, 1.0 equivalent) and a small amount of iodine in THF (30 mL) was stirred at room temperature for 1 hour under an argon atmosphere. p-Tolylbromide (25 g, 0.146 moL) in THF (5
(mL) solution was added at 30 ° C. Then, the mixture was stirred at 45 ° C for 30 minutes and then at 5 ° C for 1 hour. Then add diethyl phosphite (10.08 g, 0.5 eq) at 5 ° C, then at 5 ° C for 1 hour at room temperature.
It was stirred at (25 ° C) for 30 minutes. Water (10 mL) was added at 3 ° C, then toluene (40 mL) and 6M-HCl (20 mL) were added, and then at room temperature.
Stir for 30 minutes. The reaction solution was separated, and the organic layer was washed with water (10 m
L), 5% NaHCO ₃ aqueous solution (10 mL), and 5% NaCl aqueous solution (10 mL) were sequentially washed. Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from diisopropyl ether-heptane to give the title compound.
(7.78 g, white crystal) was obtained. Yield 46.3%. Melting point 93.7 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 2.41 (s, 6H), 7.2
6-7.31 (m, 4H), 7.54-7.61 (m, 4H), 8.03 (d, 1H, J
= 477.5 Hz). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 22.05, 128.22,
. 129.89, 130.07, 131.06, 131.22 , 143.43 31 P-NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: 22.72 (dqui
nt, J = 477.1 Hz, 13.8 Hz). Elemental analysis Calculated as C ₁₄ H ₁₅ OP; C: 73.03, H: 6.57, P: 13.45. Measured value; C: 72.80, H: 6.58, P: 13.31.

Reference Example 9 Bis (2-methylphenyl) phosphine oxide

[Chemical formula 62] A solution of magnesium (3.55 g, 1.0 equivalent) and a small amount of iodine in THF (40 mL) was stirred at room temperature for 1 hour under an argon atmosphere. o-Tolyl bromide (25 g, 0.146 moL) in THF (5
(mL) solution was added at 30 ° C. Then, the mixture was stirred at 40 ° C for 30 minutes and then at 5 ° C for 1 hour. Then, a solution of diethyl phosphite (10.08 g, 0.5 eq) in THF (10 mL) was added at 5 ° C, followed by 5
The mixture was stirred at 0 ° C for 1 hour. Water (20 mL) was added at 3 ° C, then toluene (50 mL) and 6M-HCl (20 mL) were added, and the mixture was stirred at room temperature for 30 min. The reaction mixture was separated, and the organic layer was mixed with water (10 mL) and 5% N.
It was washed successively with an aHCO ₃ aqueous solution (10 mL) and a 5% NaCl aqueous solution (10 mL). Then, the organic layer was dried over anhydrous magnesium sulfate,
After natural filtration, the filtrate was concentrated under reduced pressure. The residue was recrystallized from heptane to obtain the title compound (6.70 g, white crystals). Yield 3
9.9%. Melting point 91.3 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 2.37 (s, 6H), 7.1
8-7.26 (m, 2H), 7.29-7.34 (m, 2H), 7.43-7.48 (m, 2
H), 7.70 (d, 1H, J = 15.06Hz), 7.72 (d, 1H, J = 14.
82Hz), 8.21 (d, 1H, J = 476.9 Hz). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 20.59, 126.36,
126.53, 129.04, 130.36, 131.55, 131.69, 132.76, 13
^{. 2.93, 141.44, 141.57 31 P} -NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: 16.66-17.93
(m), 20.26-21.86 (m).

Reference Example 10 Bis (4-methoxy-3,5-dimethylphenyl) phosphine oxide

[Chemical formula 63] Magnesium (2.26 g, 0.95 eq), a small amount of iodine and a small amount of 1,2-dibromoethane T under an argon atmosphere.
The HF (25 mL) solution was stirred at room temperature for 1 hour. 4-bromo-2,6-
A solution of dimethylanisole (20 g, 0.093 moL) in THF (10 mL) was added at 20 ° C. Then, after stirring at 40 ° C for 30 minutes, 5
The mixture was stirred at 0 ° C for 30 minutes. Diethyl phosphite (7.
53 g, 0.5 eq) in THF (10 mL), then add 2 at 5 ° C.
Stir for hours. Toluene (50 mL) was added at 3 ° C, and then 3M-
After adding HCl (30 mL), the mixture was stirred at room temperature for 30 minutes. The reaction solution was separated, and the organic layer was mixed with water (10 mL) and 5% NaHCO ₃ aqueous solution (10 m
L) and 5% NaCl aqueous solution (10 mL) were sequentially washed. Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel 20 g, toluene → ethyl acetate).
The title compound (6.91 g, colorless oil) was obtained. Yield 46.7%. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 2.30 (s, 12H), 3.
74 (s, 6H), 7.34 (d, 4H, J = 13.74Hz), 7.91 (d, 1
H, J = 476.8 Hz). ³¹ P-NMR (121 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: 22.63 (dqui
nt, J = 477.0 Hz, 13.6 Hz).

Reference Example 11 Bis (1,3-benzodioxol-5-yl) phosphine oxide

[Chemical 64] Magnesium (3.01 g, 1.0 equivalent) under an argon atmosphere,
Small amounts of iodine and small amounts of 1,2-dibromoethane in THF (3
The solution (0 mL) was stirred at room temperature for 1 hour. Add a solution of 5-bromo-1,3-benzodioxole (25 g, 0.124 moL) in THF (20 mL).
Added at 35 ° C. Then, stir at 40 ° C for 30 minutes and then at 5 ° C for 3 minutes.
Stir for 0 minutes. Diethyl phosphite (10.07
After adding a solution of g (0.5 equivalent) in THF (10 mL), the mixture was stirred at 5 ° C for 1 hr. Water (20 mL) was added at 3 ° C, then toluene (7 mL) was added.
(0 mL) and 6M-HCl (20 mL) were added, and the mixture was stirred at room temperature for 30 minutes. THF (30 mL) was added, the reaction solution was separated, and the organic layer was washed with water (10 mL).
mL), a 5% NaHCO ₃ aqueous solution (10 mL), and a 5% NaCl aqueous solution (10 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from diisopropyl ether to give the title compound (7.75 g,
White crystals) were obtained. Yield 43.1%. Melting point 127.9 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 6.01 (s, 4H), 6.9
0 (dd, 2H, J = 7.86Hz, 2.22Hz), 7.04 (dd, 2H, J = 1
2.87Hz, 1.14Hz), 7.18-7.26 (m, 2H), 7.92 (d, 1H, J
= 483.0 Hz). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 102.14, 109.31,
109.53, 110.25, 110.44, 124.35, 125.76, 126.52, 1
. 26.69, 148.60, 148.85, 151.80 31 P-NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: 22.59 (dqui
nt, J = 483.5 Hz, 13.4 Hz). Elemental analysis calculated as C ₁₄ H ₁₁ O ₅ P; C: 57.94, H: 3.82, P: 10.67. Found; C: 57.88, H: 3.83, P: 10.57 .

Reference Example 12 Bis (2-naphthyl) phosphine oxide

[Chemical 65] Magnesium (2.94 g, 1.0 equivalent) under an argon atmosphere,
Small amounts of iodine and small amounts of 1,2-dibromoethane in THF (3
The solution (0 mL) was stirred at room temperature for 1 hour. 2-bromonaphthalene
A solution of (25 g, 0.121 moL) in THF (20 mL) was added at 35 ° C.
Then, the mixture was stirred at 40 ° C for 30 minutes and then at 5 ° C for 30 minutes. Then add diethyl phosphite (9.77 g, 0.5 eq) at 5 ° C.
After adding a THF (10 mL) solution, the mixture was stirred at 5 ° C. for 3 hours. 3 ° C
Water (20 mL) was added, followed by toluene (60 mL) and 6M-HCl (2
(0 mL) was added, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was separated, and the organic layer was mixed with water (10 mL), 5% NaHCO ₃ aqueous solution (10 mL), 5%.
It was washed successively with NaCl aqueous solution (10 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from diisopropyl ether-heptane to obtain the title compound (9.62 g, white crystals). Yield 53.0%. Melting point 98.3 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 7.49-7.64 (m, 6.5
H), 7.86-7.95 (m, 6H), 8.40 (d, 2H, J = 15.75Hz),
9.15 (s, 0.5H). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 125.07, 125.23,
127.13, 127.76, 127.93, 128.81, 128.96, 132.43, 1
. 32.62, 132.82, 132.96, 135.05 31 P-NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: 22.99 (dqui
nt, J = 481.0 Hz, 13.3 Hz).

Reference Example 13 Bis (4-chlorophenyl) phosphine oxide

[Chemical formula 66] Diethyl phosphite (5.40 g,
To a solution of 0.033 mmoL) in THF (30 mL) was added 4-chloromagnesium bromide 1M diethyl ether solution (100 mL, 3.0 equivalents), and the mixture was stirred at 5 ° C for 2 hours. Water (20 mL) was added at 3 ° C., then toluene (80 mL) and 6M-HCl (20 mL) were added, and the mixture was stirred at room temperature for 30 min. The reaction solution was separated, and the organic layer was separated into water (10 mL), 5% NaHCO ₃ aqueous solution (10 mL), and 5% NaCl aqueous solution (10 mL).
It was washed successively with (mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from heptane to obtain the title compound (8.70 g, white crystals). Yield 97.3%. Melting point 124.0 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 7.47-7.52 (m, 4
H), 7.57-7.65 (m, 4H), 8.05 (d, 1H, J = 487.1Hz). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 129.13, 129.77,
. 129.95, 130.49, 132.36, 132.53 , 139.95 31 P-NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: 17.59-18.54
(m), 21.62-22.70 (m).

Reference Example 14 Bis (biphenyl-4-yl) phosphine oxide

[Chemical formula 67] Under an argon atmosphere, magnesium (2.60 g, 1.0 equivalent),
A small amount of iodine and a small amount of 1,2-dibromoethane in THF (2
The solution (0 mL) was stirred at room temperature for 30 minutes. A solution of 4-bromobiphenyl (25 g, 0.107 moL) in THF (20 mL) was added at 35 ° C. Then, the mixture was stirred at 40 ° C for 1 hour and then at 5 ° C for 30 minutes. Then at 5 ° C diethyl phosphite (7.39 g, 0.5 eq)
THF solution (10 mL) was added, and the mixture was stirred at 5 ° C for 2 hr. 3
Toluene (60 mL) was added at 0 ° C, then 3M-HCl (30 mL) was added, and the mixture was stirred at room temperature for 30 min. THF (50 mL) was added, the reaction mixture was separated, and the organic layer was washed with 5% aqueous NaCl solution (10 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from diisopropyl ether to give the title compound (12.47 g, white crystals). Yield 65.8%. ¹ H-NMR (300 MHz, THF-d ₈ , TMS) δ: 7.34-7.43 (m, 7
H), 7.57-7.66 (m, 5H), 7.78-7.87 (m, 6H), 8.11 (d,
1H, J = 479.3Hz). ¹³ C-NMR (75 MHz, THF-d ₈ , CDCl ₃ ) δ: 124.80, 125.0
6, 125.11, 125.29, 125.99, 126.58, 126.80, 128.95,
^{. 129.10 31 P-NMR (121} MHz, THF-d 8, 85% H 3 PO 4) δ: 16.35 (dqu
int, J = 479.5 Hz, 13.3 Hz).

Reference Example 15 Bis (p-tert-butylphenyl) phosphine oxide

[Chemical 68] Under a nitrogen stream, a solution of magnesium (3.62 g, 4.0 equivalents), a small amount of iodine, and 1,2-dibromoethane in THF (24 mL) was stirred at room temperature for 30 minutes. Add a solution of p-tert-butylbromobenzene (31.62 g, 3.99 eq) in THF (130 mL) at 24 ° C.
Then, the mixture was stirred at 40 ° C. for 30 minutes. Then, a solution of diethyl phosphite (5.14 g, 37.2 mmol) in THF (8 mL) was added at 21 ° C, and the mixture was stirred at 22 ° C for 30 min. 6M-HCl (20 m
L) was added, water (20 mL) and toluene (60 mL) were added, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was separated, and the organic layer was mixed with water (20 mL), 10% NaHCO ₃ aqueous solution (20 mL), 10% NaCl aqueous solution.
(20 mL), and the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. N-
The crystals were recrystallized from hexane and dried (reduced pressure, 40 ° C) to give the title compound (9.17 g, white powder). Yield 78.4%. Melting point: 1
42.5 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 1.33 (s, 18H), 7.
50-7.68 (m, 8H), 8.05 (d, 1H, J _HP = 477.2 Hz). ¹³ C-NMR (75MHz, CDCl ₃ , CDCl ₃ ) δ: 31.00, 35.00, 12
5.88, 127.66, 129.04, 130.47, 130.63, 155.94, 155.9
^{8. 31 P-NMR (121 MHz} , CDCl 3, 85% H 3 PO 4) δ: 22.32 (d, q
uint, J _HP = 478.0 Hz, J _HCC-P = 13.2 Hz). Elemental analysis Calculated as C ₂₀ H ₂₇ OP; C: 76.40, H: 8.66, P: 9.85. Measured value; C: 76.44, H: 8.64 , P: 9.53.

Reference Example 16 Bis (3,5-di-tert-butylphenyl) phosphine oxide

[Chemical 69] Under a nitrogen stream, a solution of magnesium (1.21 g, 3.61 equivalent), a small amount of iodine, and 1,2-dibromoethane in THF (8 mL) was stirred at room temperature for 1 hour. A solution of 1-bromo-3,5-di-tert-butylbenzene (12.99 g, 3.49 equivalent) in THF (40 mL) was added at 23 ° C, and the mixture was stirred at 40 ° C for 30 min. Then 24 ° C
Diethyl phosphite (1.90 g, 13.8 mmol) in THF (3 m
L) solution was added and then stirred at 24 ° C. for 30 minutes. 6M-H at 2 ℃
Cl (7 mL) was added, followed by water (7 mL) and toluene (20 m
After adding L), the mixture was stirred at room temperature for 30 minutes. The reaction solution was separated, and the organic layer was mixed with water (7 mL), 10% NaHCO ₃ aqueous solution (7 mL), and 10% Na.
The mixture was washed successively with a Cl aqueous solution (7 mL), the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from n-hexane and dried (vacuum, 40 ° C),
The title compound (3.38 g, white powder) was obtained. Yield 57.5%. Melting point: 184.6 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 1.33 (s, 36H), 7.
53 (s, 1H), 7.53 (s, 1H), 7.58 (s, 1H), 7.58 (s, 1
H), 7.63 (s, 1H), 7.63 (s, 1H), 8.10 (d, 1H, J _HP =
474.9 Hz). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 31.23, 35.00, 1
24.75, 124.91, 126.49, 126.52, 129.96, 131.30, 151.
^{. 30, 151.46 31 P-NMR} (121 MHz, CDCl 3, 85% H 3 PO 4) δ: 24.94 (d, q
uint, J _HP = 474.8 Hz, J _HCC-P = 14.3 Hz). Elemental analysis Calculated as C ₂₈ H ₄₃ OP; C: 78.83, H: 10.16, P: 7.26. Measured value; C: 78.74, H: 9.93 , P: 7.16.

Reference Example 17 Bis (m-tolyl) phosphine oxide

[Chemical 70] Under a nitrogen stream, a solution of magnesium (3.60 g, 3.50 eq), a small amount of iodine, and 1,2-dibromoethane in THF (25 mL) was stirred at room temperature for 30 minutes. m-bromotoluene (25.36 g,
3.51 eq) in THF (130 mL) at 24 ° C, then add
The mixture was stirred at 0 ° C for 30 minutes. Then, a solution of diethyl phosphite (5.84 g, 42.3 mmol) in THF (10 mL) was added at 25 ° C, and the mixture was stirred at 24 ° C for 1.5 hr. After adding 6M-HCl (20 mL) at 4 ° C., then adding water (20 mL) and toluene (60 mL),
The mixture was stirred at room temperature for 30 minutes. Separate the reaction mixture and separate the organic layer with 10% N.
aHCO ₃ aqueous solution (20 mL), water (20 mL), 10% NaCl aqueous solution (20 m
L) sequentially, the organic layer is dried over anhydrous magnesium sulfate, natural filtered, and further filtered with a membrane filter (0.2 μm).
m), the filtrate was concentrated under reduced pressure, and the title compound (9.0
9 g, colorless oil) was obtained. Yield 93.3% ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 2.34 (s, 6H), 7.3
1-7.54 (m, 8H), 7.97 (d, 1H, J _HP = 479.3 Hz). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 21.25, 127.53,
127.69, 128.60, 128.78, 130.93, 131.08, 133.25, 13
3.29, 138.67, 138.84. ³¹ P-NMR (121 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: 23.25 (d, q
uint, J _HP = 479.2 Hz, J _HCC-P = 13.8 Hz).

Reference Example 18 Bis (4-methylphenyl) phosphine-borane complex

[Chemical 71] Of cerium chloride (7.89 g, 3.0 equivalents) under an argon atmosphere
The THF (20 mL) solution was stirred at room temperature (25 ° C) for 30 minutes. Sodium borohydride (1.25 g, 3.1 equivalent) was added, and the mixture was stirred at room temperature for 1 hr. Then, bis (4-methylphenyl) phosphine oxide (2.5 g, 0.1 g) synthesized in Reference Example 8 was prepared at 5 ° C.
011 moL) and lithium aluminum hydride (0.494 g,
(1.2 eq) were added sequentially, and the mixture was stirred at room temperature for 17 hours. 3 ° C
Water (10 mL), and then toluene (20 mL) and 6M-HCl (2
(0 mL) was added, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was separated, and the aqueous layer was extracted with toluene (30 mL). The combined organic layers were washed successively with 5% NaHCO ₃ aqueous solution (20 mL) and 5% NaCl aqueous solution (20 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (alumina 25 g, n-hexane / ethyl acetate = 10/1). The residue was recrystallized from heptane to obtain the title compound (1.28 g, white crystals). Yield 51.
0%. Melting point 78.6 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 0.43-1.61 (m, 3
H), 2.38 (s, 6H), 6.26 (dq, 1H, J = 377.5 Hz, 6.24
Hz), 7.24-7.27 (m, 4H), 7.51-7.58 (m, 4H). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 21.90, 123.02,
. 123.81, 130.14, 130.28, 133.22 , 133.35, 142.44 31 P-NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: -1.44- -0.1
6 (m), 1.62-3.19 (m). Elemental analysis Calculated as C ₁₄ H ₁₈ BP; C: 73.72, H: 7.95, P: 13.58. Found: C: 73.65, H: 7.93, P: 13.54.

Reference Example 19 (S) -6,6'-Dibromo-2,2'-bis (methoxymethyloxy) -1,1'-binaphthyl (S) -6,6'-dibromo-1,1 ' -Bi-2-naphthol (4.0 g, 9.
Diisopropylethylamine (3.49 g, 3.0 equivalents) was added to a dichloromethane (40 mL) solution of 0 mmoL) at room temperature (25 ° C). Then chloromethyl methyl ether (1.59 g, 2.2
Equivalent amount) was added at 5 ° C., and the mixture was stirred at room temperature for 18 hours. Water (10
(mL) and then stirred at room temperature for 30 minutes. The reaction solution was separated, and the organic layer was washed with 5% NaCl aqueous solution (10 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from diisopropyl ether to give the title compound (4.28 g, pale yellowish white crystals).
Yield 89.4%. ¹ H-NMR (300MHz, CDCl ₃ , TMS) δ: 3.16 (s, 6H), 5.04
(dd, 4H, J = 32.32 Hz, 6.85 Hz), 6.98 (d, 2H, J =
9.02 Hz), 7.29 (dd, 2H, J = 9.03 Hz, 2.01 Hz), 7.
60 (d, 2H, J = 9.07 Hz), 7.87 (d, 2H, J = 9.08 H
z), 8.04 (d, 2H, J = 1.93Hz).

Reference Example 20 (S) -2,2'-Bis (methoxymethyloxy) -6,6'-diphenyl-1,1'-binaphthyl (S) -6,6'-dibromo-2,2 ' A solution of -bis (methoxymethyloxy) -1,1'-binaphthyl (2.0 g, 3.76 mmoL) in dimethoxyethane (20 mL) was added with dihydroxyphenylborane (1.
37 g, 3.0 eq), tetrakistriphenylphosphine palladium (0.43 g, 0.1 eq) and sodium carbonate (1.
An aqueous solution (2 mL) was added at room temperature (25 ° C), and the mixture was stirred under reflux for 8 hours. Water (10 mL), ethyl acetate (20
(mL) and then stirred at room temperature for 30 minutes. The reaction solution was separated, and the organic layer was washed with 5% NaCl aqueous solution (10 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. Column chromatography of the residue (silica gel 25 g, n-hexane / ethyl acetate = 5/1)
Purified in. The effective fraction was concentrated under reduced pressure to give the title compound (1.63
g, yellow amorphous) was obtained. Yield 82.2%. ¹ H-NMR (300MHz, CDCl ₃ , TMS) δ: 3.22 (s, 6H), 5.10
(dd, 4H, J = 29.74 Hz, 6.77 Hz), 7.29-7.39 (m, 4
H), 7.45-7.57 (m, 6H), 7.63-7.73 (m, 6H), 8.05 (d,
2H, J = 9.00 Hz), 8.12 (d, 2H, J = 1.66 Hz).

Reference Example 21 (S) -6,6'-Diphenyl-2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (S) -2,2'-bis (methoxymethyloxy ) -6,6'-Diphenyl-1,1'-binaphthyl (1.63 g, 3.08 mmoL) in THF (5 mL)
6M-HCl aqueous solution (5 mL) was added to the solution, and the mixture was stirred under reflux for 7 hours. After adding a 30% NaOH aqueous solution and ethyl acetate (20 mL) at 3 ° C, the mixture was stirred at room temperature for 30 minutes. The reaction mixture was separated, and the organic layer was washed with water (10 mL) and 5% NaCl aqueous solution (10 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. Column chromatography of the residue (silica gel 25 g, n-hexane / ethyl acetate = 10/1)
Purified in. Pyridine (0.86 g, 2.7 equivalents) was added to a solution of the residue in acetonitrile (15 mL) at room temperature. Then add trifluoromethanesulfonic anhydride (2.84 g, 2.5 eq)
The mixture was added at 5 ° C and stirred at room temperature for 2 hours. Water (10 mL) was added at 3 ° C., then ethyl acetate (30 mL) was added, and the mixture was stirred at room temperature for 30 min. The reaction solution was separated, and the organic layer was washed with water (10 mL) and 5% NaC.
l Washed with aqueous solution (10 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure.
Column chromatography of the residue (silica gel 25 g, n
-Hexane / ethyl acetate = 10/1) for purification. The effective fraction was concentrated under reduced pressure to give the title compound (0.74 g, colorless amorphous).
Got Yield 34.0% ¹ H-NMR (300MHz, CDCl ₃ , TMS) δ: 7.36-7.43 (m, 4H),
7.47-7.52 (m, 4H), 7.65-7.73 (m, 8H), 8.20-8.22
(m, 4H). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 119.75, 125.97,
127.30, 127.39, 127.71, 127.93, 128.97, 132.16, 1
32.24, 132.69, 139.92, 140.03, 145.30. Elemental analysis C ₃₄ H ₂₀ F ₆ O ₆ S Calculated value; C: 58.12, H: 2.87. Measured value; C: 57.86, H: 3.01.

Reference Example 22 7,7'-Dimethoxy-1,1'-bi-2-naphthol 7-Methoxy-2-naphthol (5.0 g, 28.7 mmoL) in dichloromethane (50 mL) was added with Cu (OH) 2. Cl-tetramethylethylenediamine complex (1.33 g, 0.1 equivalent) was added at room temperature (25 ° C), and the mixture was stirred at room temperature for 8 hours. After adding water (20 mL) at 3 ° C., the mixture was stirred at room temperature for 30 minutes. The reaction solution is separated and the organic layer is 5%
It was washed with aqueous NaCl solution (10 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. Ethyl acetate (50 mL) and silica gel (10 g) were added to the residue, the mixture was stirred at room temperature for 1 hr, and the filtrate was concentrated under reduced pressure to give the title compound (5.10 g, tan amorphous). Yield 100
%. ¹ H-NMR (300MHz, CDCl ₃ , TMS) δ: 3.58 (s, 6H), 5.07
(s, 2H), 6.49 (d, 2H, J = 2.43 Hz), 7.03 (dd, 2H, J
= 8.89 Hz, 2.49 Hz), 7.22 (d, 2H, J = 8.84Hz), 7.
78 (d, 2H, J = 8.90 Hz), 7.88 (d, 2H, J = 8.85 H
z). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 55.54, 103.58,
110.47, 115.50, 116.43, 125.20, 130.39, 131.51, 13
5.11, 153.74, 159.52.

Reference Example 23 7,7'-Dimethoxy-2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl 7,7'-dimethoxy-1,1'-bi-2-naphthol ( 5.10 g, 14.
3 mmoL) in acetonitrile (50 mL) and pyridine (3.0 mL).
5 g, 2.7 eq) was added at room temperature (25 ° C). Then add trifluoromethanesulfonic anhydride (10.12 g, 2.5 eq) at 5 ° C.
Then, the mixture was stirred at room temperature for 5 hours. Water (30 mL) was added at 3 ° C., then ethyl acetate (50 mL) was added, and the mixture was stirred at room temperature for 30 min. The reaction solution was separated, and the organic layer was washed with water (10 mL) and 5% NaC.
l Washed with aqueous solution (10 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure.
Ethyl acetate (30 mL) and activated carbon (1.0 g) were added to the residue, the mixture was stirred at room temperature for 1 hr, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from diisopropyl ether to give the title compound (5.80 g,
Reddish brown white crystals) was obtained. Yield 66.5%. ¹ H-NMR (300MHz, CDCl ₃ , TMS) δ: 3.55 (s, 6H), 6.56
(s, 2H), 7.26 (dd, 2H, J = 8.99 Hz, 2.51 Hz), 7.4
8 (d, 2H, J = 8.95 Hz), 7.92 (d, 2H, J = 8.98 Hz),
8.06 (d, 2H, J = 8.95 Hz). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 55.61, 105.41,
117.11, 120.49, 122.63, 128.27, 130.26, 131.86, 13
4.98, 146.39, 159.57. Elemental analysis calculated as C ₂₄ H ₁₆ F ₆ O ₈ S ₂ ; C: 47.22, H: 2.64. Found; C: 46.93, H: 2.55.

Example 1 Bis (3,5-dimethylphenyl) phosphine-borane complex

[Chemical 72] (Production method 1) Under an argon atmosphere, cerium chloride (14.3 g,
A solution of 3.0 equivalents of THF (40 mL) was stirred at room temperature (25 ° C) for 30 minutes. Sodium borohydride (2.19 g, 3.0 equivalents) was added, and the mixture was stirred at room temperature for 1 hr. Then reference example 2 at 5 ℃
After the bis (3,5-dimethylphenyl) phosphine oxide (5.0 g, 19.3 mmoL) and lithium aluminum hydride (0.88 g, 1.2 equivalents) synthesized in Step 1 were sequentially added, the mixture was stirred at room temperature for 3 hours. Water (40 mL) was added at 3 ° C, and then toluene (4 mL
(0 mL) and 6M-HCl (20 mL) were added, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was separated, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from diisopropyl ether to give the title compound (2.8 g, white crystals). Yield 57.4%. (Manufacturing method 2) Cerium chloride (2.87 g, 2.99) under nitrogen stream
A THF (20 mL) solution of equivalent amount) was stirred at room temperature (25 ° C.) for 40 minutes. Sodium borohydride (0.44 g, 2.99 equivalent) was added, and the mixture was stirred at room temperature for 1 hr. Then, at -12 ° C, bis (3,5-dimethylphenyl) phosphine oxide (1.00 g, 3.89 mmol) synthesized in Reference Example 2 and lithium aluminum hydride (0.17 g, 1.16 equivalent) were sequentially added, and then for 4 hours. It was stirred. Water (10 mL) was added at -10 ° C, then toluene (20 mL) and 6M-HCl (3 mL) at -5 ° C.
After adding, the mixture was stirred at room temperature for 30 minutes. The reaction solution is separated,
The organic layer was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (10 g, toluene), and the effective fraction was concentrated under reduced pressure. The residue was recrystallized from heptane to obtain the title compound (0.70 g, white powder). Yield 70.6%. Melting point: 106.5 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 0.30-1.80 (m, 3
H), 2.35 (s, 12H), 6.20 (dq, 1H, J _HP = 377.4 Hz, J
= 6.9 Hz), 7.14 (s, 2H), 7.26 (s, 2H), 7.30 (s, 2
H). ³¹ P-NMR (121 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: 0.88-1.32
(m), 3.32-5.02 (m).

Example 2 (S) -2,2'-bis [bis (3,5-dimethylphenyl) phosphino] -1,1'-binaphthyl

[Chemical formula 73] Under an argon atmosphere, [1,2-bis (diphenylphosphino)
-Ethane] dichloronickel (42 mg, 0.1 equivalent) and (S) -2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (399 mg, 0.73 mmoL) synthesized in Reference Example 1
And 1,4-diazabicyclo [2,2,2] octane (489 mg, 6.
0 equivalents) of DMF solution (5 mL) was added to the bis (3,5-dimethylphenyl) phosphine-borane complex (428
(mg, 2.3 equivalents) was added at room temperature, and then the mixture was stirred at room temperature for 30 minutes. Then, the mixture was stirred at 110 ° C. for 96 hours. DMF was distilled off under reduced pressure,
Methanol was added to the residue to give the title compound (329 mg, pale yellowish white crystals). Yield 62%. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 2.06 (s, 12H), 2.
13 (s, 12H), 6.70-6.73 (m, 10H), 6.81 (s, 2H), 6.90
(d, 2H, J = 8.46 Hz), 7.01 (dd, 2H, J = 7.14Hz,
7.14Hz), 7.39 (dd, 2H, J = 6.99Hz, 6.99Hz), 7.52
(dd, 2H, J = 8.49Hz, 2.28Hz), 7.84-7.88 (m, 4H). ³¹ P-NMR (121 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: -14.25 (s). Reference: ³¹ P-NMR (161 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: -1
4.9. Journal of Organic Chemistry, Vol. 59, page 3064, 1994) Elemental analysis Calculated as C ₅₂ H ₄₈ P ₂ ; C: 84.99, H: 6.58, P: 8.43. Measured value; C: 84.60, H: 6.58, P: 8.07.

Example 3 Bis (4-methoxyphenyl) phosphine-borane complex

[Chemical 74] Of cerium chloride (7.03 g, 3.0 equivalents) under an argon atmosphere
The THF (20 mL) solution was stirred at room temperature (25 ° C) for 30 minutes. Sodium borohydride (1.08 g, 3.1 equivalent) was added, and the mixture was stirred at room temperature for 1 hr. Then, bis (4-methoxyphenyl) phosphine oxide (2.5 g,
9.1 mmoL) and lithium aluminum hydride (0.43 g,
(1.2 eq) were added sequentially, and the mixture was stirred at room temperature for 3 hours. 3 ° C
Water (20 mL) was added, followed by toluene (50 mL) and 6M-HCl (10 mL).
(mL) and then stirred at room temperature for 30 minutes. The reaction solution was separated, and the aqueous layer was extracted with toluene (20 mL) three times. The combined organic layers were washed successively with 5% NaHCO ₃ aqueous solution (20 mL) and 5% NaCl aqueous solution (20 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel 30 g, n-hexane / ethyl acetate = 5/1 → 2/1). The residue was recrystallized from heptane to obtain the title compound (0.98 g, white crystals). Yield 4
1.3%. Melting point 65.8 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 0.43-1.57 (m, 3
H), 3.82 (s, 6H), 6.24 (dq, 1H, J = 377.9Hz, 6.78H
z), 6.95 (dd, 4H, J = 8.71 Hz, 1.72 Hz), 7.53-7.60
(m, 4H). ³¹ P-NMR (121 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: -4.53- -2.7
3 (m), -1.26-0.40 (m),-4.15 (m).

Example 4 (S) -2,2'-Bis [bis (4-methoxyphenyl) phosphino] -1,1'-binaphthyl

[Chemical 75] Under an argon atmosphere, [1,2-bis (diphenylphosphino)-
[Ethane] dichloronickel (53 mg, 0.1 equivalent) and Reference Example 1
(S) -2,2'-Bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (500 mg, 0.91 mmoL) and 1,4-diazabicyclo [2,2,2] octane (613 mg) , 6.0
Equivalent amount of DMF solution (5 mL) was added to bis (4-
(Methoxyphenyl) phosphine-borane complex (543 mg, 2.
(3 equivalents) was added at room temperature, and the mixture was stirred at room temperature for 30 minutes. Then, the mixture was stirred at 110 ° C for 48 hours. DMF was evaporated under reduced pressure, and methanol was added to the residue to give the title compound (444 mg, white crystals). Yield 66%. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 3.73 (s, 12H), 6.
64 (d, 4H, J = 8.35 Hz), 6.69 (d, 4H, J = 8.19 H
z), 6.80 (d, 2H, J = 8.49Hz), 6.92-7.03 (m, 10H),
7.30-7.38 (m, 2H), 7.40-7.45 (m, 2H), 7.82 (d, 2H,
J = 8.13 Hz), 7.87 (d, 2H, J = 8.52 Hz). ³¹ P-NMR (121MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: -17.40 (s). (Ref: ³¹ P-NMR (161 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: -1
6.8. Journal of Organic Chemistry, Vol. 59, p. 3064, 1994)

Example 5 Bis (4-dimethylaminophenyl) phosphine-borane complex

[Chemical 76] Of cerium chloride (7.69 g, 3.0 equivalents) under an argon atmosphere
The THF (25 mL) solution was stirred at room temperature (25 ° C) for 30 minutes. Sodium borohydride (1.22 g, 3.1 equivalent) was added, and the mixture was stirred at room temperature for 1 hr. Then, bis (4-dimethylaminophenyl) phosphine oxide synthesized in Reference Example 4 at 5 ° C.
(3.0 g, 10.4 mmoL) and lithium aluminum hydride
(0.47 g, 1.2 equivalents) were added sequentially, and the mixture was stirred at room temperature for 3 hours. Water (20 mL) was added at 3 ° C, and then toluene (40 m
L) and 6M-HCl (10 mL) were added, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was neutralized with NaOH and separated. The water layer was converted to THF (50 m
L). The combined organic layers were combined with 5% aqueous NaCl (20 mL)
Washed sequentially. Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was subjected to column chromatography (silica gel 5 g, n-hexane /
Purified with ethyl acetate = 1/1). The residue was recrystallized from heptane to obtain the title compound (0.61 g, white crystals). Yield 20.5
%. Melting point 142.6 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 0.43-1.33 (m, 3
H), 3.03 (s, 12H), 6.26 (dq, 1H, J = 375.1 Hz, 6.57
Hz), 7.51 (d, 4H, J = 8.81 Hz), 7.54 (d, 4H, J =
^{. 8.81 Hz) 31 P-NMR} (121 MHz, CDCl 3, 85% H 3 PO 4) δ: -6.40- -4.7
3 (m), -3.33- -1.66 (m).

Example 6 (S) -2,2'-bis [bis (4-dimethylaminophenyl) phosphino] -1,1'-binaphthyl

[Chemical 77] Under an argon atmosphere, [1,2-bis (diphenylphosphino)-
[Ethane] dichloronickel (48 mg, 0.1 equivalent) and Reference Example 1
(S) -2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (507 mg, 0.92 mmoL) and 1,4-diazabicyclo [2,2,2] octane (620 mg , 6.0
Equivalent amount of DMF solution (5 mL) was added to bis (4-
Dimethylaminophenyl) phosphine-borane complex (606
(mg, 2.3 equivalents) was added at room temperature, and then the mixture was stirred at room temperature for 30 minutes. Then, the mixture was stirred at 110 ° C. for 129 hours. DMF was evaporated under reduced pressure, methanol was added to the residue to give the title compound (461 mg,
Yellowish white crystals) was obtained. Yield 62.9%. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 2.88 (s, 24H), 6.
43 (d, 4H, J = 6.79 Hz), 6.50-6.59 (m, 4H), 6.77-
7.03 (m, 12H), 7.18-7.26 (m, 2H), 7.51 (d, 2H, J =
7.13 Hz), 7.78 (d, 2H, J = 7.56 Hz), 7.83 (d, 2H,
^{. J = 8.28 Hz) 31 P} -NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: -18.00 (s).

Example 7 Bis (4-fluorophenyl) phosphine-borane complex

[Chemical 78] Of cerium chloride (9.31 g, 3.0 equivalents) under an argon atmosphere
The THF (25 mL) solution was stirred at room temperature (25 ° C) for 30 minutes. Sodium borohydride (1.48 g, 3.1 equivalent) was added, and the mixture was stirred at room temperature for 1 hr. Then, at 5 ° C., bis (4-fluorophenyl) phosphine oxide synthesized in Reference Example 5 (3.0 g,
12.6 mmoL) and lithium aluminum hydride (0.57 g,
(1.2 eq) were added sequentially, and the mixture was stirred at room temperature for 3 hours. 3 ° C
Water (10 mL) was added, and then toluene (30 mL) and 6M-HCl (2
(0 mL) was added, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was separated, and the aqueous layer was extracted with toluene (20 mL). The combined organic layers were washed with 5% aqueous NaCl solution (20 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (alumina 25 g, n-hexane / ethyl acetate = 20/1).
The residue was recrystallized from heptane to obtain the title compound (0.61 g, white crystals). Yield 20.4%. Melting point 71.7 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 0.42-1.36 (m, 3
H), 6.32 (dq, 1H, J = 380.4 Hz, 6.89 Hz), 7.14-7.2
0 (m, 4H), 7.62-7.70 (m, 4H). ³¹ P-NMR (121 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: -3.29- -1.2
1 (m), -0.29-1.91 (m).

Example 8 (S) -2,2'-Bis [bis (4-fluorophenyl) phosphino] -1,1'-binaphthyl

[Chemical 79] Under an argon atmosphere, [1,2-bis (diphenylphosphino)-
[Ethane] dichloronickel (48 mg, 0.1 equivalent) and Reference Example 1
(S) -2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (507 mg, 0.92 mmoL) and 1,4-diazabicyclo [2,2,2] octane (620 mg , 6.0
Equivalent amount of DMF solution (5 mL) was added to bis (4-
(Fluorophenyl) phosphine-borane complex (500 mg, 2.
(3 equivalents) was added at room temperature, and the mixture was stirred at room temperature for 30 minutes. Then, the mixture was stirred at 110 ° C. for 129 hours. DMF was evaporated under reduced pressure, and methanol was added to the residue to give the title compound (344 mg, yellowish white crystals). Yield 53.8%. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 6.74-7.07 (m, 16
H), 7.34-7.41 (m, 4H), 7.41-7.93 (m, 4H), 7.85 (d,
2H, J = 8.20 Hz), 7.91 (d, 2H, J = 8.47 Hz). ³¹ P-NMR (121 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: -16.63 (s). (Ref: ³¹ P-NMR (161 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: -1
7.0. Journal of Organic Chemistry, Vol. 59, p. 3064, 1994)

Example 9 Bis (3,5-di-tert-butyl-4-methoxyphenyl) phosphine-borane complex

[Chemical 80] Of cerium chloride (4.55 g, 3.0 equivalents) under an argon atmosphere
The THF (25 mL) solution was stirred at room temperature (25 ° C) for 30 minutes. Sodium borohydride (0.72 g, 3.1 equivalent) was added, and the mixture was stirred at room temperature for 1 hr. Then, at 5 ° C., bis (3,5-di-tert-butyl-4-methoxyphenyl) phosphine oxide (3.0 g, 6.16 mmoL) synthesized in Reference Example 7 and lithium aluminum hydride (0.28 g, 1.2 equivalents) were added. After adding sequentially, the mixture was stirred at room temperature for 18 hours. Water (10 mL) was added at 3 ° C., then toluene (30 mL) and 6M-HCl (20 mL) were added, and the mixture was stirred at room temperature for 30 min. The reaction solution was separated, and the aqueous layer was extracted with toluene (30 mL). The combined organic layers were washed successively with 5% aqueous NaCl solution (20 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (alumina 25 g, n-hexane). The residue was recrystallized from heptane to give the title compound (1.1
(8 g, white crystal) was obtained. Yield 39.6%. Melting point 134.7 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 0.37-1.08 (m, 3
H), 1.39 (s, 36H), 3.69 (s, 6H), 6.23 (dq, 1H, J =
. 376.2 Hz, 6.78 Hz), 7.50 (d, 4H, J = 12.18 Hz) 31 P-NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: -3.33- -1.4
6 (m), -0.13-1.80 (m).

Example 10 (S) -2,2'-Bis [bis (3,5-di-tert-butyl-4-methoxyphenyl) phosphino] -1,1'-binaphthyl

[Chemical 81] Under an argon atmosphere, [1,2-bis (diphenylphosphino)-
[Ethane] dichloronickel (48 mg, 0.1 equivalent) and Reference Example 1
Synthesized in (S) -2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (507 mg, 0.91 mmoL) and 1,4-diazabicyclo [2,2,2] octane (620 mg , 6.0
Equivalent amount of DMF solution (5 mL) was added to bis (3,
5-di-tert-butyl-4-methoxyphenyl) phosphine-borane complex (1.03 g, 2.3 eq) was added at room temperature and then at room temperature.
Stir for 30 minutes. Then, the mixture was stirred at 110 ° C. for 153 hours. DMF
Was distilled off under reduced pressure, and methanol was added to the residue to give the title compound.
(737 mg, yellowish white crystals) was obtained. Yield 69%. Melting point 129.5
° C. Optical rotation: [α] _D = -232 ° (25 ° C, c = 1.0, CHCl ₃ ) ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 1.21 (s, 36H), 1.
24 (s, 36H), 3.58 (s, 6H), 3.64 (s, 6H), 6.64 (d, 2
H, J = 7.60 Hz), 6.77 (d, 2H, J = 7.10 Hz), 6.92-7.
00 (m, 4H), 7.13-7.20 (m, 4H), 7.30-7.37 (m, 2H),
7.42-7.51 (m, 2H), 7.77 (d, 2H, J = 6.91 Hz), 7.86
(d, 2H, J = 8.02 Hz). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 33.34, 33.49, 3
6.96, 37.19, 65.44, 65.53, 126.64, 127.23, 128.76,
128.80, 128.92, 131.84, 132.95, 134.51, 144.02, 1
^{. 60.37, 161.31 31 P-NMR} (121 MHz, CDCl 3, 85% H 3 PO 4) δ: -15.02 (s).

Example 11 (S) -2,2'-bis [bis (4-methylphenyl) phosphino]-
1,1'-binaphthyl

[Chemical formula 82] Under an argon atmosphere, [1,2-bis (diphenylphosphino)-
[Ethane] dichloronickel (48 mg, 0.1 equivalent) and Reference Example 1
(S) -2,2'-Bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (500 mg, 0.91 mmoL) and 1,4-diazabicyclo [2,2,2] octane (610 mg , 6.0 equivalents) of DMF solution (5 mL) was added to bis (4-
Methylphenyl) phosphine-borane complex (0.476 g, 2.3
(Equivalent weight) was added at room temperature, and the mixture was stirred at room temperature for 30 minutes. Then, the mixture was stirred at 110 ° C for 73 hours. DMF was evaporated under reduced pressure, and methanol was added to the residue to give the title compound (488 mg, white crystals). Yield 79.2%. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 2.27 (s, 6H), 2.2
9 (s, 6H), 6.86-7.03 (m, 20H), 7.38-7.41 (m, 2H),
7.47-7.50 (m, 2H), 7.85 (d, 2H, J = 8.16 Hz), 7.89
. (d, 2H, J = 8.48 Hz) 31 P-NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ:. -15.73 (s) Calculated elemental analysis C ₄₈ H ₄₀ P _2; C : 84.93, H: 5.94, P: 9.13. Actual value; C: 84.52, H: 5.90, P: 9.09.

Example 12 Bis (2-methylphenyl) phosphine-borane complex

[Chemical 83] Of cerium chloride (8.66 g, 3.0 equivalents) under an argon atmosphere
The THF (80 mL) solution was stirred at room temperature (25 ° C) for 30 minutes. Sodium borohydride (1.37 g, 3.1 equivalent) was added, and the mixture was stirred at room temperature for 1 hr. Then, bis (2-methylphenyl) phosphine oxide (2.7 g, 1
1.72 mmoL) and lithium aluminum hydride (0.53 g,
(1.2 eq) were added sequentially, and the mixture was stirred at room temperature for 4 hours. 3 ° C
Toluene (80 mL) was added, and then 3M-HCl (30 mL) was added, followed by stirring at room temperature for 30 minutes. The reaction solution was separated, and the aqueous layer was extracted with toluene (20 mL). Combined organic layers with 5% NaC
l Washed with aqueous solution (20 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure.
Toluene (20 mL) and silica gel (10 g) were added to the residue, and the mixture was stirred at room temperature for 10 minutes. After natural filtration, the filtrate was concentrated under reduced pressure. THF (5 mL) and BH ₃ · THF (5 mL) were added to the residue at 5 ° C., and the mixture was stirred at room temperature for 1 hr. After concentration under reduced pressure, the residue was recrystallized from heptane to obtain the title compound (1.15 g, white crystals). Yield 4
3.0%. Melting point 78.0 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 0.42-1.63 (m, 3
H), 2.32 (s, 6H), 6.47 (dq, 1H, J = 377.5 Hz, 6.63
Hz), 7.21-7.31 (m, 4H), 7.38-7.43 (m, 2H), 7.59
(d, 1H, J = 13.56Hz), 7.61 (d, 1H, J = 13.53Hz). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 20.81, 20.88, 1
26.36, 126.52, 130.85, 130.95, 131.67, 131.70, 133.
^{. 82, 134.01, 141.42 31 P} -NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: -15.58- -1
4.22 (m), -12.67- -11.33 (m).

Example 13 (S) -2,2'-bis [bis (2-methylphenyl) phosphino]-
1,1'-binaphthyl

[Chemical 84] Under an argon atmosphere, [1,2-bis (diphenylphosphino)-
[Ethane] dichloronickel (96 mg, 0.1 equivalent) and Reference Example 1
(S) -2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (1.0 g, 1.81 mmoL) and 1,4-diazabicyclo [2,2,2] octane (1.22 g , 6.0 equivalents) of DMF solution (5 mL) was added to the bis (2-
Methylphenyl) phosphine-borane complex (0.95 g, 2.3
(Equivalent weight) was added at room temperature, and the mixture was stirred at room temperature for 30 minutes. Then, the mixture was stirred at 110 ° C. for 96 hours. DMF was evaporated under reduced pressure, and methanol was added to the residue to give the title compound (684 mg, white crystals). Yield 55.5%. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 2.01 (s, 6H), 2.0
3 (s, 6H), 6.91-7.31 (m, 24H), 7.68-7.89 (m, 4H). ³¹ P-NMR (121 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: -28.67 (s) .

Example 14 Bis (4-methoxy-3,5-dimethylphenyl) phosphine-
Borane complex

[Chemical 85] Cerium chloride (10.54 g, 3.0 equivalents) under an argon atmosphere
A THF (80 mL) solution of was stirred at room temperature (25 ° C.) for 30 minutes. Sodium borohydride (1.67 g, 3.1 equivalent) was added, and the mixture was stirred at room temperature for 1 hr. Then, bis (4-methoxy-3,5-dimethylphenyl) phosphine oxide (4.54 g, 0.014 moL) and lithium aluminum hydride (0.65 g, 1.2 equivalents) synthesized in Reference Example 10 were sequentially added at 5 ° C. The mixture was stirred at room temperature for 4 hours. Toluene (100 mL) was added at 3 ° C., and then 3M-HCl (40 mL) was added, followed by stirring at room temperature for 30 minutes. The reaction solution was separated, and the aqueous layer was extracted with toluene (20 mL). The combined organic layers were washed with 5% aqueous NaCl solution (20 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. Toluene (20 m
L) and silica gel (10 g) were added, and the mixture was stirred at room temperature for 10 minutes.
After natural filtration, the filtrate was concentrated under reduced pressure. The residue was recrystallized from heptane to obtain the title compound (3.14 g, white crystals). yield
69.6%. Melting point 81.6 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 0.37-1.56 (m, 3
H), 2.27 (s, 12H), 3.72 (s, 6H), 6.13 (dq, 1H, J =
377.5 Hz, 6.84 Hz), 7.27 (d, 4H, J = 15.30 Hz). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 16.07, 59.59, 1
20.59, 121.37, 131.97, 132.12, 133.32, 133.45, 159.
^{87. 31 P-NMR (121 MHz} , CDCl 3, 85% H 3 PO 4) δ: -1.57- -0.3
2 (m), 1.38-2.83 (m).

Example 15 (S) -2,2'-Bis [bis (4-methoxy-3,5-dimethylphenyl) phosphino] -1,1'-binaphthyl

[Chemical 86] Under an argon atmosphere, [1,2-bis (diphenylphosphino)-
[Ethane] dichloronickel (96 mg, 0.1 equivalent) and Reference Example 1
(S) -2,2'-Bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (1.0 g, 1.81 mmoL) and 1,4-diazabicyclo [2,2,2] octane (1.22 g , 6.0 equivalents) of DMF solution (5 mL) was added to the bis (4-
Methoxy-3,5-dimethylphenyl) phosphine-borane complex (1.32 g, 2.3 equivalents) was added at room temperature and then stirred at room temperature for 30 minutes. Then, the mixture was stirred at 110 ° C. for 96 hours. DMF was evaporated under reduced pressure, and methanol was added to the residue to give the title compound (513 mg, white crystals). Yield 33.1%. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 2.07 (s, 24H), 3.
64 (s, 6H), 3.66 (s, 6H), 6.70-6.96 (m, 12H), 7.30
-7.40 (m, 2H), 7.51-7.53 (m, 2H), 7.79-7.92 (m, 4
H). ³¹ P-NMR (121 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: -14.47 (s).

Example 16 Bis (1,3-benzodioxol-5-yl) phosphine-borane complex

[Chemical 87] Of cerium chloride (8.66 g, 3.0 equivalents) under an argon atmosphere
The THF (80 mL) solution was stirred at room temperature (25 ° C) for 30 minutes. Sodium borohydride (1.37 g, 3.1 equivalent) was added, and the mixture was stirred at room temperature for 1 hr. Then, bis (1,3-benzodioxol-5-yl) phosphine oxide (3.4 g, 0.012 moL) synthesized in Reference Example 11 and lithium aluminum hydride (0.53 g, 1.2 equivalents) were sequentially added at 5 ° C. After that, the mixture was stirred at room temperature for 4 hours. Toluene (80 mL) was added at 3 ° C, and then 3M
After adding HCl (30 mL), the mixture was stirred at room temperature for 30 minutes. The reaction solution was separated, and the aqueous layer was extracted with toluene (20 mL). The combined organic layers were washed with 5% aqueous NaCl solution (20 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel 25 g, toluene). The residue was recrystallized from heptane to obtain the title compound (2.33 g, white crystals). Yield 69.1%. Melting point 88.8 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 0.42-1.61 (m, 3
H), 5.58 (q, 0.5H, J = 6.78 Hz), 6.01 (s, 4H), 6.8
4-6.90 (m, 2.5H), 7.04 (dd, 2H, J = 10.79Hz, 1.44H
z), 7.18 (dd, 1H, J = 12.37Hz, 1.45Hz), 7.21 (dd,
1H, J = 12.37Hz, 1.46Hz). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 102.10, 109.53,
109.70, 112.43, 112.59, 118.95, 119.75, 128.37, 1
. 28.51, 148.70, 148.90, 151.15 31 P-NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: 1.42-2.83
(m), 4.55-6.00 (m). Elemental analysis Calculated as C ₁₄ H ₁₄ BO ₄ P; C: 58.38, H: 4.90, P: 10.75. Found; C: 58.36, H: 4.92, P: 10.67. .

Example 17 (S) -2,2'-Bis [bis (1,3-benzodioxol-5-yl) phosphino] -1,1'-binaphthyl

[Chemical 88] Under an argon atmosphere, [1,2-bis (diphenylphosphino)-
[Ethane] dichloronickel (86 mg, 0.1 equivalent) and Reference Example 1
(S) -2,2'-Bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (0.9 g, 0.91 mmoL) and 1,4-diazabicyclo [2,2,2] octane (1.1 g , 6.0 equivalents) of DMF solution (5 mL) was added to bis (1,
3-benzodioxol-5-yl) phosphine-borane complex
(1.08 g, 2.3 eq) was added at room temperature and then stirred at room temperature for 30 minutes. Then, the mixture was stirred at 110 ° C. for 96 hours. DMF was evaporated under reduced pressure, methanol was added to the residue to give the title compound (310 mg,
Greenish white crystals) were obtained. Yield 23.8%. ³¹ P-NMR (121 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: -12.46 (s). (Ref: ³¹ P-NMR (162 MHz, CDCl ₃ ) δ: -12.1.
9-124669 bulletin)

Example 18 Bis (2-naphthyl) phosphine-borane complex

[Chemical 89] Of cerium chloride (8.66 g, 3.0 equivalents) under an argon atmosphere
The THF (80 mL) solution was stirred at room temperature (25 ° C) for 30 minutes. Sodium borohydride (1.37 g, 3.1 equivalent) was added, and the mixture was stirred at room temperature for 1 hr. Then, bis (2-naphthyl) phosphine oxide (3.54 g, 0.012
moL) and lithium aluminum hydride (0.53 g, 1.2
(Equivalent weight) were sequentially added, and the mixture was stirred at room temperature for 3 hours. Toluene (80 mL) was added at 0 ° C., and then 3M-HCl (30 mL) was added, followed by stirring at room temperature for 30 minutes. The reaction solution was separated, and the aqueous layer was extracted with toluene (40 mL). The combined organic layers were washed with 5% aqueous NaCl solution (20 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. Toluene (30 mL) and silica gel (10 g) were added to the residue, and the mixture was stirred at room temperature for 10 minutes. After natural filtration, the filtrate was concentrated under reduced pressure.
The residue was recrystallized from heptane to obtain the title compound (2.23 g, white crystals). Yield 63.3%. Melting point 113.2 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 0.68-1.85 (m, 3
H), 6.58 (dq, 1H, J = 378.6Hz, 6.88 Hz), 7.56-7.61
(m, 6H), 7.88-7.91 (m, 6H), 8.32 (d, 2H, J = 13.56
Hz). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 123.41, 127.53,
128.23, 128.31, 128.61, 128.97, 129.30, 129.43, 1
^{. 33.22, 135.00, 135.15 31 P} -NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: 1.11-2.42
(m), 4.30-5.48 (m). Elemental analysis Calculated as C ₂₀ H ₁₈ BP; C: 80.03, H: 6.04, P: 10.32. Measured value; C: 80.40, H: 5.92, P: 9.95.

Example 19 (S) -2,2'-Bis [bis (2-naphthyl) phosphino] -1,1'-
Binaphthyl

[Chemical 90] Under an argon atmosphere, [1,2-bis (diphenylphosphino)-
[Ethane] dichloronickel (96 mg, 0.1 equivalent) and Reference Example 1
(S) -2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (1.0 g, 1.81 mmoL) and 1,4-diazabicyclo [2,2,2] octane (1.22 g , 6.0 equivalents of DMF solution (5 mL) was added to the bis (2-
Naphthyl) phosphine-borane complex (1.25 g, 2.3 eq)
Was added at room temperature and then stirred at room temperature for 30 minutes. Then 110
The mixture was stirred at 0 ° C for 101 hours. DMF was evaporated under reduced pressure, and methanol was added to the residue to give the title compound (875 mg, white crystals). Yield 58.7%. ³¹ P-NMR (121 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: -12.99 (s). (Ref: ³¹ P-NMR (162 MHz, CDCl ₃ ) δ: -13.57. JP 9-124669 Issue)

Example 20 Bis (4-chlorophenyl) phosphine-borane complex

[Chemical Formula 91] Of cerium chloride (8.66 g, 3.0 equivalents) under an argon atmosphere
The THF (80 mL) solution was stirred at room temperature (25 ° C) for 30 minutes. Sodium borohydride (1.37 g, 3.1 equivalent) was added, and the mixture was stirred at room temperature for 1 hr. Then, at 5 ° C., bis (4-chlorophenyl) phosphine oxide synthesized in Reference Example 13 (3.18 g,
0.012 moL) and lithium aluminum hydride (0.53
(g, 1.2 equivalents) were added sequentially, and the mixture was stirred at room temperature for 4 hours. 0
Toluene (80 mL) was added at 0 ° C, and then 3M-HCl (30 mL) was added, followed by stirring at room temperature for 30 minutes. The reaction solution was separated, and the aqueous layer was extracted with toluene (20 mL). Combined organic layers 5% N
It was washed with aCl aqueous solution (20 mL). Then, the organic layer was dried over anhydrous magnesium sulfate, naturally filtered, and the filtrate was concentrated under reduced pressure. Toluene (20 mL) and silica gel (10 g) were added to the residue, and the mixture was stirred at room temperature for 10 minutes. After natural filtration, the filtrate was concentrated under reduced pressure. THF (5 mL) and BH ₃ · THF (5 mL) were added to the residue at 5 ° C., and the mixture was stirred at room temperature for 1 hr. After concentration under reduced pressure, the residue was recrystallized from heptane to obtain the title compound (1.58 g, white crystals). Yield 50.3%. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 0.41-1.60 (m, 3
H), 6.28 (dq, 1H, J = 381.6Hz, 6.96 Hz), 7.36-7.44
(m, 4H), 7.54-7.65 (m, 4H). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 123.83, 124.60,
128.92, 129.46, 129.61, 132.17, 134.10, 134.24, 1
^{. 38.62 31 P-NMR (121} MHz, CDCl 3, 85% H 3 PO 4) δ: -1.06-0.33
(m), 2.08-3.47 (m).

Example 21 (S) -2,2'-bis [bis (4-chlorophenyl) phosphino]-
1,1'-binaphthyl

[Chemical Formula 92] Under an argon atmosphere, [1,2-bis (diphenylphosphino)-
[Ethane] dichloronickel (96 mg, 0.1 equivalent) and Reference Example 1
(S) -2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (1.0 g, 1.81 mmoL) and 1,4-diazabicyclo [2,2,2] octane (1.22 g , 6.0 equivalents) of DMF solution (5 mL) was added with bis (4-
Chlorophenyl) phosphine-borane complex (1.29 g, 2.6
(Equivalent weight) was added at room temperature, and the mixture was stirred at room temperature for 30 minutes. Then, the mixture was stirred at 110 ° C. for 96 hours. The reaction mixture was subjected to ³¹ P-NMR measurement to confirm the title compound. ³¹ P-NMR (121 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: -15.80 (s). (Ref: ³¹ P-NMR (161 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ:- 1
6.8. Journal of Organic Chemistry, Vol. 59, p. 3064, 1994)

Example 22 Bis (p-tert-butylphenyl) phosphine-borane complex

[Chemical formula 93] TH of cerium chloride (19.84 g, 2.98 equivalents) under nitrogen flow
The F (160 mL) solution was stirred at room temperature (25 ° C) for 30 minutes. After adding sodium borohydride (3.11 g, 3.04 equivalent), the mixture was stirred at room temperature for 1.5 hours. Then, at -17 ° C, Reference Example 1
Bis (p-tert-butylphenyl) phosphine oxide (8.49 g, 27.0 mmol) synthesized in 5 and lithium aluminum hydride (1.55 g, 1.21 equivalent) were sequentially added, and then the mixture was stirred at room temperature for 2 hours. Toluene (80 mL) at -10 ° C
Was added, and then 6M-HCl (25 mL) and water (25 mL) were added at 4 ° C., and the mixture was stirred at room temperature for 30 minutes. The reaction solution was separated, and the organic layer was washed successively with water (30 mL), 10% NaHCO ₃ aqueous solution (30 mL) and 10% NaCl aqueous solution (30 mL), the organic layer was dried over anhydrous magnesium sulfate, and naturally filtered. After filtration under reduced pressure with a membrane filter (0.2 μm), the filtrate was concentrated under reduced pressure. Dissolve the residue in THF (100 mL), and add borane-THF complex (10 mL) at room temperature.
(mL, 0.38 eq) was added, and the mixture was stirred for 16 hr and concentrated under reduced pressure. Toluene (30 mL) was added to the residue to dissolve it, and the residue was purified by silica gel column chromatography (silica gel 100 g, toluene), and the effective fraction was concentrated under reduced pressure. The residue
The crystals were recrystallized from n-hexane and dried (reduced pressure, 40 ° C) to give the title compound (6.33 g, white powder). Yield 75.0%. Melting point 15
1.5 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 0.43-1.52 (m, 3
H), 1.33 (s, 18H), 6.28 (dq, 1H, J _HP = 384 Hz, J =
6.9 Hz), 7.46 (s, 1H), 7.47 (s, 1H), 7.49 (s, 1H),
7.50 (s, 1H), 7.59 (s, 1H), 7.62 (s, 1H), 7.63 (s,
1H), 7.65 (s, 1H). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 31.04, 34.91, 1
22.46, 123.24, 125.99, 126.13, 132.68, 132.81, 154.
^{. 99, 155.02 31 P-NMR} (121 MHz, CDCl 3, 85% H 3 PO 4) δ: -2.42- -1.5
2 (m), 0.82-1.52 (m).

Example 23 (S) -2,2'-bis [bis (p-tert-butylphenyl) phosphino] -1,1'-binaphthyl

[Chemical 94] Under an argon atmosphere, [1,2-bis (diphenylphosphino) ethane] dichloronickel (0.08 g, 0.10 equivalent)
And (S) -2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (0.78 g, 1.
Example 2 in a DMF solution (5 mL) of 41 mmol) and 1,4-diazabicyclo [2,2,2] octane (0.94 g, 5.97 eq).
The bis (p-tert-butylphenyl) phosphine-borane complex (1.02 g, 2.31 equivalent) synthesized in 2 was added at room temperature, and then the mixture was stirred at room temperature for 30 minutes. Then, the mixture was stirred at 110 ° C. for 96 hours. The DMF solution was evaporated under reduced pressure, and methanol was added to the residue to give the title compound (0.79 g, pale yellow powder). Yield 66
% ¹ H-NMR (300MHz, CDCl ₃ , TMS) δ: 1.25 (s, 18H), 1.2
7 (s, 18H), 6.68-6.73 (m, 4H), 6.94-6.96 (m, 4H),
7.07 (d, 4H, J = 8.0 Hz), 7.11-7.13 (m, 4H), 7.23-
7.27 (m, 6H), 7.47 (d, 2H, J = 8.4 Hz), 7.81 (d, 2
H, J = 8.1 Hz), 7.86 (d, 2H, J = 8.5 Hz). ¹³ C-NMR (75 MHz, DMSO, DMSO) δ: 30.91, 30.94, 34.
13, 34.15, 124.49, 124.54, 124.59, 124.72, 125.00,
125.66, 127.00, 127.09, 130.10, 132.33, 132.46, 1
32.59, 132.71, 132.97, 133.72, 133.86, 134.01, 13
. 6.21, 144.10, 150.03, 150.80 31 P-NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: -16.04 (s).

Example 24 Bis (3,5-di-tert-butylphenyl) phosphine-borane complex

[Chemical 95] THF of cerium chloride (4.88 g, 3.00 eq) under nitrogen stream
The (40 mL) solution was stirred at room temperature (25 ° C) for 30 minutes. Sodium borohydride (0.75 g, 3.00 equivalent) was added, and the mixture was stirred at room temperature for 1 hr. Then, at -9 ° C, Reference Example 16
The bis (3,5-di-tert-butylphenyl) phosphine oxide (2.81 g, 6.6 mmol) and the lithium aluminum hydride (0.39 g, 1.23 equivalent) synthesized in Step 1 were sequentially added, and the mixture was stirred for 1.5 hours. Toluene (20 mL) was added at 4 ° C, 6M-HCl (6 mL) was added, and water (10 mL) was added at 4 ° C, followed by stirring at room temperature for 30 minutes. The reaction solution was separated, the organic layer was dried over anhydrous magnesium sulfate, natural filtered, and vacuum filtered with a membrane filter (0.2 μm). Borane-THF complex (7 mL, 1.08 equivalent) was added to the filtrate at room temperature. After the 1
The mixture was stirred for 6 hours and concentrated under reduced pressure. Borane-TH at room temperature in concentrate
After the F complex (10 mL, 1.55 equivalent) was added, the mixture was concentrated under reduced pressure. Toluene (10 mL) was added to the residue to dissolve it, and the residue was purified by silica gel column chromatography (silica gel 25 g, toluene), and the effective fraction was concentrated under reduced pressure. N-
The crystals were recrystallized from hexane and dried (reduced pressure, 40 ° C) to give the title compound (2.03 g, white powder). Yield 72.7%. Melting point 135.
4 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 0.55-1.80 (m, 3
H), 1.34 (s, 36H), 6.33 (dq, 1H, J _HP = 375.5 Hz, J
= 6.8 Hz), 7.51 (s, 1H), 7.51 (s, 1H), 7.55 (s, 1
H), 7.55 (s, 1H), 7.58 (s, 1H), 7.59 (s, 1H). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 31.26, 34.91, 1
22.46, 123.24, 125.99, 126.13, 132.68, 132.81, 154.
^{. 99, 155.02 31 P-NMR} (121 MHz, CDCl 3, 85% H 3 PO 4) δ: 0.95-1.22
(m), 3.88-4.75 (m).

Example 25 (S) -2,2'-bis [bis (3,5-di-tert-butylphenyl)
Phosphino] -1,1'-binaphthyl

[Chemical 96] Under an argon atmosphere, [1,2-bis (diphenylphosphino) ethane] dichloronickel (0.07 g, 0.10 equivalent)
And (S) -2,2′-bis (trifluoromethanesulfonyloxy) -1,1′-binaphthyl (0.77 g,
1.41 mmol) and 1,4-diazabicyclo [2,2,2] octane (0.94 g, 5.96 equivalents) in DMF solution (5 mL) were added to bis (3,5-di-tert-butyl) synthesized in Example 24. Phenyl) phosphine-borane complex (1.00 g, 1.68 equivalents) was added at room temperature, and the mixture was stirred at room temperature for 30 minutes. Then, the mixture was stirred at 110 ° C. for 96 hours. The DMF solution was evaporated under reduced pressure, and methanol was added to the residue to give the title compound (0.38 g, white powder). yield
30%. Melting point: 217.8 ° C. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 1.11 (s, 36H), 1.
14 (s, 36H), 6.71 (d, 2H, J = 8.3 Hz), 6.77-6.80
(m, 2H), 6.95-6.98 (m, 4H), 7.14-7.23 (m, 8H), 7.2
5-7.28 (m, 2H), 7.54 (d, 2H, J = 8.5 Hz), 7.77 (d,
2H, J = 8.1 Hz), 7.85 (d, 2H, 8.5 Hz). ¹³ C-NMR (75 MHz, DMSO, DMSO) δ: 31.03, 34.32, 34.
44, 120.71, 121.90, 125.03, 125.55, 126.95, 127.0
6, 127.18, 127.23, 128.08, 128.23, 128.38, 130.41,
132.79, 136.79, 137.65, 145.03, 145.82, 149.22, 1
^{. 49.30, 149.35, 149.40 31 P} -NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: -12.16 (s).

Example 26 Bis (m-tolyl) phosphine-borane complex

[Chemical 97] TH in cerium chloride (26.40 g, 3.00 eq) under nitrogen flow
The F (220 mL) solution was stirred at room temperature (25 ° C) for 30 minutes. After adding sodium borohydride (4.06 g, 3.00 equivalent), the mixture was stirred at room temperature for 1.5 hours. Then at -9 ° C Reference Example 1
Bis (m-tolyl) phosphine oxide (8.22 g, 35.7 mmol) and lithium aluminum hydride (2.06 g, 1.22 equivalents) synthesized in 7 were sequentially added, and the mixture was stirred for 3 hours. 6M-HCl (33 mL) was added at -3 ° C, and then water (33 m
L) and toluene (130 mL) were added at 4 ° C., and the mixture was stirred at room temperature for 30 minutes. The reaction solution was separated, and the organic layer was washed with water (50 mL), 10%.
It was washed successively with NaHCO ₃ aqueous solution (50 mL) and 10% NaCl aqueous solution (50 mL), the organic layer was dried over anhydrous magnesium sulfate, natural filtered, filtered under reduced pressure with a membrane filter (0.2 μm), and the filtrate was filtered to 0 Borane-THF complex (36 mL, 1.02
(Equivalent) was added, and the mixture was stirred at room temperature for 13.5 hours, further, borane-THF complex (6.2 mL, 0.18 equivalent) was added at room temperature, and the mixture was concentrated under reduced pressure. The residue was recrystallized from n-hexane and dried (reduced pressure, 40 ° C) to give the title compound (1.70 g, white powder). Yield 21% ¹ H-NMR (300 MHz, DMSO, TMS) δ: 0.58-1.75 (m, 3H),
2.34 (s, 6H), 5.88-5.98 (m, 0.5H), 7.20-7.31 (m,
0.5H), 7.37-7.53 (m, 8H). ¹³ C-NMR (75 MHz, DMSO, DMSO) δ: 21.24, 126.48, 12
9.45, 129.60, 130.03, 130.15, 132.76, 133.07, 133.2
^{. 0, 139.00, 139.18 31 P} -NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: -4.22- -3.0
0 (m), -0.89-0.23 (m).

Example 27 (S) -2,2'-bis [bis (m-tolyl) phosphino] -1,1'-
Binaphthyl

[Chemical 98] Under an argon atmosphere, [1,2-bis (diphenylphosphino) ethane] dichloronickel (0.10 g, 0.10 equivalent)
And (S) -2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (1.05 g, 1.
Example 2 was added to a solution of 91 mmol) and 1,4-diazabicyclo [2,2,2] octane (1.28 g, 5.99 eq) in DMF (5 mL).
The bis (m-tolyl) phosphine-borane complex (1.00 g, 2.31 equivalent) synthesized in 6 was added at room temperature, and then the mixture was stirred at room temperature for 30 minutes. Then, the mixture was stirred at 110 ° C. for 96 hours. The reaction mixture was subjected to ³¹ P-NMR measurement to confirm the title compound. ³¹ P-NMR (121 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: -14.5 (s). (Ref: ³¹ P-NMR (161 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ:- 1
4.4. Journal of Organic Chemistry, 59, 3064, 1994)

Example 28 (S) -2,2'-bis (diphenylphosphino) -6,6'-diphenyl-1,1'-binaphthyl

[Chemical 99] Under an argon atmosphere, [1,2-bis (diphenylphosphino)-
Ethane] dichloronickel (52 mg, 0.1 equivalent) and Reference Example 2
(S) -6,6'-Diphenyl-2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (700
mg, 0.99 mmoL) and 1,4-diazabicyclo [2,2,2] octane (670 mg, 6.0 eq) in DMF solution (5 mL) was added diphenylphosphine-borane complex (0.458 g, 2.3 eq) at room temperature. After that, the mixture was stirred at room temperature for 30 minutes. Then, the mixture was stirred at 110 ° C for 90 hours. DMF was evaporated under reduced pressure, and methanol was added to the residue to give the title compound (412 mg, slightly brown white crystals). Yield 5
3.4%. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 6.93 (d, 2H, J =
8.76 Hz), 7.12-7.22 (m, 20H), 7.29 (s, 2H), 7.35-
7.51 (m, 8H), 7.64-7.67 (m, 4H), 7.99 (d, 2H, J =
8.76 Hz), 8.07 (d, 2H, J = 1.64 Hz). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 125.99, 127.74,
. 128.51, 128.83, 129.21, 134.66 , 141.35 31 P-NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: -13.82 (s).

Example 29 2,2'-Bis (diphenylphosphino) -7,7'-dimethoxy-
1,1'-binaphthyl

[Chemical 100] Under an argon atmosphere, [1,2-bis (diphenylphosphino)-
[Ethane] dichloronickel (53 mg, 0.1 equivalent) and Reference Example 2
7,7'-dimethoxy-2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl synthesized in 3 (610 mg,
0.99 mmoL) and 1,4-diazabicyclo [2,2,2] octane
The diphenylphosphine-borane complex (0.458 g, 2.3 equivalents) was added to a DMF solution (5 mL) of (670 mg, 6.0 equivalents) at room temperature, and then the mixture was stirred at room temperature for 30 minutes. Then, the mixture was stirred at 110 ° C. for 77 hours. DMF was distilled off under reduced pressure, methanol was added to the residue,
The title compound (120 mg, yellowish white crystals) was obtained. Yield 17.7%. ¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ: 3.16 (s, 6H), 6.0
5 (d, 2H, J = 2.26Hz), 7.01 (dd, 2H, J = 9.00Hz, 2.
49Hz), 7.12-7.19 (m, 20H), 7.38 (d, 2H, J = 8.44H
z), 7.74 (d, 2H, J = 8.88 Hz), 7.83 (d, 2H, J = 8.
38 Hz). ¹³ C-NMR (75 MHz, CDCl ₃ , CDCl ₃ ) δ: 54.98, 106.07,
119.52, 127.77, 128.18, 128.41, 128.97, 129.63, 13
. 2.90, 134.78, 135.08, 146.39 , 159.56 31 P-NMR (121 MHz, CDCl 3, 85% H 3 PO 4) δ: -13.82 (s).

Example 30 (S) -2,2'-bis (diphenylphosphino) -1,1'-binaphthyl

[Chemical 101] Under an argon atmosphere, [1,2-bis (diphenylphosphino)-
[Ethane] dichloronickel (53 mg, 0.1 equivalent) and Reference Example 1
(S) -2,2'-Bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl (500 mg, 0.91 mmoL) and 1,4-diazabicyclo [2,2,2] octane (613 mg) , 6.0
Diphenylphosphine-borane complex (418 mg, 2.3 eq) was added to a DMF solution (5 mL) of (eq.
Stir for minutes. Then, the mixture was stirred at 110 ° C. for 96 hours. DMF was distilled off under reduced pressure, and methanol was added to the residue to give the title compound (4
(01 mg, pale yellowish white crystals) was obtained. Yield 71%. ¹ H-NMR (300MHz, CDCl ₃ , TMS) δ: 6.83 (d, 2H, J =
8.26 Hz), 6.89-6.94 (m, 2H), 7.07-7.20 (m, 20H), 7.
32-7.37 (m, 2H), 7.43-7.47 (m, 2H), 7.85 (d, 2H, J
= 8.14 Hz), 7.89 (d, 2H, J = 8.49 Hz). ³¹ P-NMR (121 MHz, CDCl ₃ , 85% H ₃ PO ₄ ) δ: -14.90 (s).

Example 31 (S) -2,2'-bis [bis (3,5-dimethylphenyl) phosphino] -1,1'-binaphthyl

[Chemical 102] Following the same procedure as in Example 2, the amine used was changed to tetramethylethylenediamine, triethylamine, diisopropylethylamine, diethylamine or pyridine, and (S) -2,2′-bis [bis (3,5-dimethylphenyl) phosphino was used. ] -1,1'-Binaphtyl was produced.
The results are shown in Table 1.

[Table 1]

Example 32 (S) -2,2'-bis [bis (3,5-dimethylphenyl) phosphino] -1,1'-binaphthyl

[Chemical 103] Following the same procedure as in Example 2, the nickel catalyst was replaced with NiC.
l ₂ , NiCl ₂ · bis (diphenyl) phosphinylferrocene or NiCl ₂ , bis (diphenyl) phosphinoethane, and changed to (S) -2,2′-bis [bis (3,5-dimethylphenyl) phosphino] -1,1'-binaphthyl was produced. The results are shown in Table 2. To calculate the HPLC area percentage, the HPLC conditions (column: ZORBAX Rx-C8, 4.6 × 250 mm, solution: MeCN / H ₂
O = 90/10, flow rate: 1.0 mL / min, detection wavelength: 254 nm) was used. In, NiCl ₂ and bis (diphenyl)
Phosphinoethane was added individually.

[Table 2]

Example 33 Asymmetric hydrogenation of methyl (Z) -α-acetamidocinnamate Rh (cod) ₂ OTf (4.27 mg, 0.0091 mmoL) in methanol (1 m
(S) -2,2′-bis [bis (3,
5-Di-tert-butyl-4-methoxyphenyl) phosphino]-
After adding 1,1′-binaphthyl (12.65 mg, 0.011 mmoL), the mixture was stirred at room temperature (25 ° C.) for 30 minutes. Methyl (Z) -α-acetamidocinnamate (0.10 g, 0.456 mmoL) in methanol (4 m
(L) Add the Rh complex solution prepared above to the solution, and add hydrogen pressure 1.0
Hydrogenation was carried out at MPa and 25 ° C. for 24 hours. GC the reaction mixture
(Column: CHIRASIL VAL, 0.25 mm × 30 m), the conversion was> 99.9% and the optical purity was 91.43% ee (R).

Comparative Example 1 Asymmetric hydrogenation of methyl (Z) -α-acetamidocinnamate Rh (cod) ₂ OTf (4.27 mg, 0.0091 mmoL) in methanol (1 m
(S) -2,2'-bis (diphenylphosphino) -1,1'-binaphthyl (6.79 mg, 0.011 mmo) synthesized in Example 30 in solution L).
After L) was added, the mixture was stirred at room temperature (25 ° C) for 30 minutes. Methyl
(Z) -α-acetamidocinnamate (0.10 g, 0.456 mmo
The Rh complex solution prepared above was added to a solution of L) in methanol (4 mL), and hydrogenation was carried out at a hydrogen pressure of 1.0 MPa at 25 ° C. for 24 hours. The reaction mixture was analyzed by GC (column: CHIRASIL VAL, 0.25 mm
X 30 m), conversion rate> 99.9%, optical purity 15.33%
It was ee (R).

[0101]

Industrial Applicability According to the production method of the present invention, an optically active drug (eg, prophylactic / therapeutic drug for frequent urination / urinary incontinence, prophylactic / therapeutic drug for Alzheimer's disease, prophylactic / therapeutic drug for hyperlipidemia, etc.) or an intermediate thereof The compound (I) or a salt thereof, which is useful for the asymmetric synthesis reaction when producing a compound useful as the above, can be efficiently produced. Compound (I) or a salt thereof, particularly a complex of an optical isomer thereof and a transition metal, in the above asymmetric synthesis reaction,
It shows excellent stereoselectivity, chemical yield, catalytic activity, etc.

Claims (36)

[Claims] 1. The formula: (In the formula, R ^1a , R ^1b , R ^1c , R ^1d , R ^1e , R ^1f , R ^2a , R ^2b , R
^2c , R ^2d , R ^2e and R ^2f are the same or different and each is a hydrogen atom, a fluorine atom, a chlorine atom, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, or an optionally substituted An aryl group, an optionally substituted hydroxy group, an optionally substituted amino group,
An optionally substituted alkylcarbonyl group, an optionally substituted alkoxycarbonyl group, a carboxyl group or an optionally substituted carbamoyl group, wherein X represents a leaving group] or a salt thereof. Formula [2] [In the formula, R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ and R ¹⁰ are the same or different and each is a hydrogen atom, a fluorine atom, a chlorine atom, or an optionally substituted hydrocarbon. Represents a group, an optionally substituted hydroxy group or an optionally substituted amino group, and R ³ and R ⁴ and R ⁷ and R ⁸ together are a 5- to 8-membered homolog with an adjacent carbon atom. Or a heterocycle may be formed] with a phosphine-borane complex represented by the formula or a salt thereof in the presence of an amine and a nickel catalyst in a solvent. [Wherein the symbols have the same meanings as defined above], or a method for producing a salt thereof. 2. The process according to claim 1, wherein X is an optionally substituted alkylsulfonyloxy group or an optionally substituted arylsulfonyloxy group. 3. R ^1a , R ^1b , R ^1c , R ^1d , R ^1e , R ^1f , R ^2a ,
R ^2b , R ^2c , R ^2d , R ^2e and R ^2f are the same or different and each is a hydrogen atom, a fluorine atom, a chlorine atom, an optionally substituted alkyl group, an optionally substituted cycloalkyl group or a substituted Optionally substituted hydroxy group, optionally substituted amino group, optionally substituted alkylcarbonyl group, optionally substituted alkoxycarbonyl group, carboxyl group or optionally substituted carbamoyl group, R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ are the same or different and each is a hydrogen atom, a fluorine atom, a chlorine atom,
An optionally substituted hydrocarbon group, an optionally substituted hydroxy group or an optionally substituted amino group,
The production method according to claim 1, wherein both R ⁹ and R ¹⁰ are a hydrogen atom, and X is an optionally substituted alkylsulfonyloxy group or an optionally substituted arylsulfonyloxy group. 4. R^1aAnd R^2a, R^1bAnd R^2b, R^1cAnd R^2c, R^1dWhen
R^2d, R^1eAnd R^2eAnd R^1fWhen R^2fAre the same groups
The method according to claim 3, wherein 5. The method according to claim ¹ , wherein R ^1a , R ^1f , R ^2a and R ^2f are hydrogen atoms. 6. R ^1a , R ^1b , R ^1c , R ^1d , R ^1e , R ^1f , R ^2a ,
The process according to claim 3, wherein R ^2b , R ^2c , R ^2d , R ^2e and R ^2f are hydrogen atoms. 7. The process according to claim ³ , wherein R ³ , R ⁵ , R ⁶ and R ⁸ are lower alkyl groups, and R ⁴ and R ⁷ are hydrogen atoms or lower alkoxy groups. 8. R ³ , R ⁵ , R ⁶ and R ⁸ are hydrogen atoms, and R ⁴
The production method according to claim 3, wherein R ⁷ is a lower alkyl group or a lower alkoxy group. 9. The method according to claim ³ , wherein R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ are hydrogen atoms. 10. The process according to claim 1, wherein X is trifluoromethanesulfonyloxy, methanesulfonyloxy or p-toluenesulfonyloxy. 11. The nickel catalyst is NiCl ₂ · bis (diphenyl) phosphino C _1-4 alkane, NiBr ₂ , NiCl ₂ , NiCl ₂ ·.
Bis (diphenyl) phosphinylferrocene, NiCl ₂ ·
Bis (triphenylphosphine), Ni ・ tetrakistriphenylphosphine, Ni ・ tetrakistriphenylphosphite or Ni ・ dicarbonylbis (triphenyl)
The method according to claim 1, which is phosphine. 12. The method according to claim 1, wherein the nickel catalyst is NiCl ₂ .bis (diphenyl) phosphino C _1-4 alkane. 13. The method according to claim 1, wherein the nickel catalyst is NiCl ₂ .bis (diphenyl) phosphinoethane. 14. The method according to claim 1, wherein the amine is a tertiary amine. 15. The amine is 1,4-diazabicyclo [2.2.2].
The method according to claim 1, which is octane. 16. The solvent is N, N-dimethylformamide, N, N-
Dimethylacetamide, 1-methyl-2-pyrrolidone or 1,3
-One or two selected from dimethyl-2-imidazolidinone
4. The method according to claim 1, wherein the mixed solvent is one or more kinds. 17. R ^1a , R ^1b , R ^1c , R ^1f , R ^2a , R ^2b , R ^2c and R ^2f are hydrogen atoms, and R ^1d and R ^2d are hydrogen atoms or C.
_6-10 aryl group, R ^1e and R ^2e are hydrogen atoms or C _1-6 alkoxy groups, R ³ is hydrogen atom or C _1-6 alkyl group, R ⁴ is hydrogen atom, fluorine atom, chlorine atom, C _{1- 6} alkyl group, C
_6-10 aryl group, C _1-6 alkoxy group or a di-C _1-6 alkylamino group, or a benzene ring or a 1,3-dioxolane ring is formed together with the carbon atom to which R ³ and R ⁴ are adjacent, the R ⁵ Hydrogen atom or C _1-6 alkyl group, R ⁶ is hydrogen atom or C _1-6
Alkyl group, R ⁷ is hydrogen atom, fluorine atom, chlorine atom, C
_1-6 alkyl group, C _6-10 aryl group, C _1-6 alkoxy group or a di-C _1-6 alkylamino group, R ⁸ is a hydrogen atom or a C _1-6
An alkyl group, or R ⁷ and R ⁸ form a benzene ring or a 1,3-dioxolane ring together with adjacent carbon atoms, R ⁹ is a hydrogen atom or a C _1-6 alkyl group, R ¹⁰ is a hydrogen atom or C
The production method according to claim 1, wherein the _1-6 alkyl group, X is trifluoromethanesulfonyloxy, and the nickel catalyst is NiCl ₂ .bis (diphenyl) phosphinoethane. 18. The formula: [Wherein each symbol has the same meaning as in claim 1] and a compound represented by the formula: The production method according to claim 1, wherein the compound represented by the formula [wherein each symbol has the same meaning as in claim 1] has a (R) body in both axial asymmetric parts. 19. The process according to claim 18, wherein the reaction is carried out without racemization. 20. The formula: [Wherein each symbol has the same meaning as in claim 1] and a compound represented by the formula: The production method according to claim 1, wherein the compound represented by the formula (wherein each symbol has the same meaning as in claim 1) has an (S) -form in both axial asymmetric portions. 21. The method according to claim 20, wherein the reaction is carried out without racemization. 22. The formula: [Wherein each symbol has the same meaning as in claim 1] and a compound represented by the formula: The compound represented by the formula [wherein each symbol has the same meaning as in claim 1], wherein both axial asymmetric parts are racemic.
The manufacturing method described. 23. 2,2′-Bis [bis (3,5-di-tert-butyl-4-
Methoxyphenyl) phosphino] -1,1′-binaphthyl or a salt thereof. 24. The formula: [In the formula, R ^{3 ′} , R ^{5 ′} , R ^{6 ′} and R ^{8 ′} are a hydrogen atom, a lower alkyl group or a lower alkoxy group respectively, and R ^{4 ′} and R ^{7 ′} are a hydrogen atom, a fluorine atom and a chlorine atom, respectively. ,
C _2-6 alkyl group, lower alkoxy group, mono-lower alkylamino group or di-lower alkylamino group (R ^{3 '} and
R ^{4 '} and R ^{7 '} and R ^{8 '} may form a lower alkylenedioxy group (provided that R ^{3 '} , R ^{4 '} , R ^{5 '} , R ^{6 '} , R ^{7 '}
And R ^{8 '} excludes all hydrogen atoms)]] or a salt thereof. 25. R ^{3 ′} , R ^{5 ′} , R ^{6 ′} and R ^{8 ′} are each a hydrogen atom or a lower alkyl group, and R ^{4 ′} and R ^{7 ′} are each a hydrogen atom, a fluorine atom, a chlorine atom or a lower alkoxy group. 25. The phosphine-borane complex according to claim 24, which is a mono-lower alkylamino group or a di-lower alkylamino group. 26. R ^{3 ′} , R ^{5 ′} , R ^{6 ′} and R ^{8 ′} are hydrogen atoms, and R ^{4 ′} and R ^{7 ′} are a fluorine atom, a chlorine atom, a lower alkoxy group or a di-lower alkylamino group. The phosphine-borane complex according to claim 25. 27. The phosphine-borane complex according to claim 25, wherein R ^{3 ′} , R ^{5 ′} , R ^{6 ′} and R ^{8 ′} are lower alkyl groups and R ^{4 ′} and R ^{7 ′} are hydrogen atoms. 28. The phosphine-borane complex according to claim 25, wherein R ^{3 ′} , R ^{5 ′} , R ^{6 ′} and R ^{8 ′} are lower alkyl groups and R ^{4 ′} and R ^{7 ′} are lower alkoxy groups. 29. R ^{5 '} and R ^{6 '} are hydrogen atoms, and R ^{3 '}
Phosphine of claim 24, wherein forming a methylenedioxy group R ^{4 'and} R ^7' and R ^{8 '-} borane complex. 30. The phosphine-borane according to claim 24, wherein R ^{3 ′} , R ^{5 ′} , R ^{6 ′} and R ^{8 ′} are hydrogen atoms and R ^{4 ′} and R ^{7 ′} are C _2-6 alkyl groups. Complex. 31. The phosphine-borane complex according to claim 24, wherein R ^{4 ′} , R ^{5 ′} , R ^{7 ′} and R ^{8 ′} are hydrogen atoms and R ^{3 ′} and R ^{6 ′} are lower alkyl groups. 32. The formula: A phosphine-borane complex represented by the formula: wherein R ^{9 '} and R ^{10 '} each represent a lower alkyl group. 33. The formula: [In the formula, R ^{3 ′} , R ^{5 ′} , R ^{6 ′} and R ^{8 ′} are a hydrogen atom, a lower alkyl group or a lower alkoxy group respectively, and R ^{4 ′} and R ^{7 ′} are a hydrogen atom, a fluorine atom and a chlorine atom, respectively. ,
A C _2-6 alkyl group, a lower alkoxy group, a mono-lower alkylamino group or a di-lower alkylamino group, R ^{9 '} and
R ^{10 '} represents a hydrogen atom or a lower alkyl group (R ^{3 '} and R ^{4 '} and R ^{7 '} and R ^{8 '} may form a lower alkylenedioxy group) (provided that R ^{3 '} , R ^{4 '} , R ^{5 '} , R ^{6
', R 7', R 8} ', R 9' compound represented by and except when R ^{10 'are} all hydrogen atoms)] or a salt thereof in the presence of cerium chloride and sodium borohydride, hydrogen Formula characterized by reduction with lithium aluminum iodide A process for producing a phosphine-borane complex represented by [wherein each symbol has the same meaning as defined above] or a salt thereof. 34. The formula: (In the formula, R ^1a , R ^1b , R ^1c , R ^1d , R ^1e , R ^1f , R ^2a , R ^2b , R
^2c , R ^2d , R ^2e and R ^2f are the same or different and each is a hydrogen atom, a fluorine atom, a chlorine atom, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, or an optionally substituted An aryl group, an optionally substituted hydroxy group, an optionally substituted amino group,
An optionally substituted alkylcarbonyl group, an optionally substituted alkoxycarbonyl group, a carboxyl group or an optionally substituted carbamoyl group, and X represents a leaving group] or an optically active compound thereof Salt and formula [In the formula, R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ and R ¹⁰ are the same or different and each is a hydrogen atom, a fluorine atom, a chlorine atom, or an optionally substituted hydrocarbon. Represents a group, an optionally substituted hydroxy group or an optionally substituted amino group, and R ³ and R ⁴ and R ⁷ and R ⁸ together are a 5- to 8-membered homolog with an adjacent carbon atom. A ring or a heterocycle may be formed] with a phosphine-borane complex represented by the formula or a salt thereof in the presence of an amine and a nickel catalyst in a solvent. A process for producing an optically active compound, which comprises reducing the compound to be reduced in the presence of an optically active compound represented by the formula: wherein the symbols have the same meanings as defined above, or a salt thereof. 35. A formula for producing an optically active compound by asymmetric reduction: [In the formula, R ^{3 ′} , R ^{5 ′} , R ^{6 ′} and R ^{8 ′} are a hydrogen atom, a lower alkyl group or a lower alkoxy group respectively, and R ^{4 ′} and R ^{7 ′} are a hydrogen atom, a fluorine atom and a chlorine atom, respectively. ,
C _2-6 alkyl group, lower alkoxy group, mono-lower alkylamino group or di-lower alkylamino group (R ^{3 '} and
R ^{4 '} and R ^{7 '} and R ^{8 '} may form a lower alkylenedioxy group (provided that R ^{3 '} , R ^{4 '} , R ^{5 '} , R ^{6 '} , R ^{7 '}
And R ^{8 ′} are all hydrogen atoms)]] or a phosphine-borane complex represented by the formula: Use of a phosphine-borane complex represented by the formula: wherein R ^{9 '} and R ^{10 '} each represent a lower alkyl group, or a salt thereof. 36. (S) -2,2′-Bis [bis (3,5-di-tert-butyl-4-methoxyphenyl) phosphino] -1, for producing an optically active compound by asymmetric reduction 1'-binaphthyl or
Use of (R) -2,2'-bis [bis (3,5-di-tert-butyl-4-methoxyphenyl) phosphino] -1,1'-binaphthyl or salts thereof.