CN102076653A - Method for producing optically active amine compound - Google Patents
Method for producing optically active amine compound Download PDFInfo
- Publication number
- CN102076653A CN102076653A CN2009801242221A CN200980124222A CN102076653A CN 102076653 A CN102076653 A CN 102076653A CN 2009801242221 A CN2009801242221 A CN 2009801242221A CN 200980124222 A CN200980124222 A CN 200980124222A CN 102076653 A CN102076653 A CN 102076653A
- Authority
- CN
- China
- Prior art keywords
- substituent
- compound
- described method
- transition metal
- optional
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/62—Preparation of compounds containing amino groups bound to a carbon skeleton by cleaving carbon-to-nitrogen, sulfur-to-nitrogen, or phosphorus-to-nitrogen bonds, e.g. hydrolysis of amides, N-dealkylation of amines or quaternary ammonium compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/25—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Abstract
Disclosed is a commercially advantageous method for producing an optically active amine compound, wherein a chiral transition metal complex, which contains an optically active monophosphine compound as a chiral ligand, is used. Specifically disclosed is a method for producing an optically active amine compound expressed as a compound (V), which is characterized in that R<7>CHO (II), HNR<8>R<9> (III) and HC=CR<10> (IV) are reacted in a solvent containing a carbonic acid ester in the presence of a chiral transition metal complex which contains an optically active form of a compound (I) as a chiral ligand, wherein the symbols are as defined in the description.
Description
Technical field
The present invention relates to use asymmetric transition metal complex to prepare the method for optical activity amine compound as asymmetric catalyst, described asymmetric transition metal complex contains single phosphine (monophosphine) compound of optical activity as asymmetric ligand.
Background technology
Routinely, many asymmetric transition metal complexes have been in the news as being used for the catalyzer of asymmetric catalysis, and the asymmetric ligand that is used for described asymmetric transition metal complex is developed in a large number.
For example, known patent documents 1 discloses a kind of method of using asymmetric transition metal complex to prepare optically active compound, and described asymmetric transition metal complex contains the single phosphine compound of optical activity as asymmetric ligand.Particularly, following method is disclosed: make 3-methyl butyraldehyde, dibenzylamine and 1-hexin react in the presence of title complex in toluene so that optically active N to be provided, N-dibenzyl-2-methyl-5-decine-4-amine, described title complex is by cupric bromide and the preparation of optically active [4-(2-diphenylphosphino (phosphanyl) naphthalene-1-yl)-2-1-yl]-(1-phenylethyl) amine (hereinafter referred to as PINAP).
Quote list
Patent document
Patent document 1:JP-A-2006-347884
Summary of the invention
The problem to be solved in the present invention
In the reaction described in the patent document 1, the reaction times reaches 5 days at 23 ℃.But for industrial practice, preferably is the short reaction times.In addition, reaction yield and optical yield (optical yield) have improved space.
The object of the invention is to provide a kind of can prepare the industrial advantageous method of optical activity amine compound by using asymmetric transition metal complex, and described asymmetric transition metal complex contains the single phosphine compound of optical activity as asymmetric ligand.
The means of dealing with problems
The inventor furthers investigate, attempt to address the above problem, and find, the solvent that comprises carbonic ether by use can shorten the reaction times, and can improve reaction yield and optical yield as the solvent that is used for above-mentioned reaction, in addition, even when less and reaction soln has high density when the amount ratio of carbonic ether, also can keep reaction yield and optical yield, this causes of the present invention finishing.
Therefore, the invention provides following content.
[1] a kind of method for preparing the optical activity amine compound of representing by formula V:
Wherein
R
7Be optional one or more substituent low alkyl groups that have, choose wantonly and have one or more substituent aryl, choose wantonly and have one or more substituent cycloalkyl, choose wantonly and have one or more substituent low-grade alkenyls, choose wantonly and have one or more substituent low-grade alkynyls, choose wantonly to have one or more substituent aralkyl or choose wantonly and have one or more substituent heteroaryls
R
8And R
9Independent separately have one or more substituent low alkyl groups for choosing wantonly, choose wantonly and have one or more substituent low-grade alkenyls, choose wantonly and have one or more substituent cycloalkyl, choose wantonly and have one or more substituent aralkyl, optional have one or more substituent aryl or optionally have one or more substituent heteroaryls, or
R
8And R
9Optional have one or more substituent nitrogen heterocyclic rings with adjacent nitrogen-atoms in conjunction with forming to choose wantonly,
R
10It is hydrogen atom, choose wantonly and have one or more substituent low alkyl groups, choose wantonly and have one or more substituent aryl, trialkylsilkl, choose wantonly and have one or more substituent cycloalkyl, optional have one or more substituent aralkyl or optionally have one or more substituent heteroaryls, and
* represent asymmetric carbon,
(hereinafter referred to as compound (V)), described method comprises makes following compounds reaction in the presence of asymmetric transition metal complex in containing the solvent of carbonic ether: by the compound of formula (II) expression: R
7CHO (II), wherein R
7As above definition (hereinafter referred to as compound (II)) is by the compound of formula (III) expression: HNR
8R
9(III), R wherein
8And R
9As above definition (hereinafter referred to as compound (III)) and by the compound of formula (IV) expression: HC ≡ CR
10(IV), R wherein
10As above definition (hereinafter referred to as compound (IV)), described asymmetric transition metal complex contain the optical activity form by the compound of formula (I) expression as asymmetric ligand:
Encircle wherein that A does not exist or optionally have one or more substituent phenyl ring,
R
1And R
2Independent separately have one or more substituent phenyl for optional, cyclohexyl, and 2-furyl or 3-furyl,
R
3And R
4Independent separately be hydrogen atom, halogen atom, low alkyl group, lower alkoxy, optional have one or more substituent cycloalkyl, optional have one or more substituent aralkyl or choose wantonly have one or more substituent aryl, and
X is by-OR
5Or-NHR
6The residue of expression, wherein R
5And R
6Independent separately have one or more substituent low alkyl groups for choosing wantonly, choose wantonly and have one or more substituent aralkyl, choose wantonly to have one or more substituent aryl or choose wantonly and have one or more substituent heteroaryls, (hereinafter referred to as compound (I)).
[2] method of above-mentioned [1], wherein said carbonic ether are the carbonic ethers with 3 to 10 carbon atoms.
[3] method of above-mentioned [1], wherein said carbonic ether is selected from methylcarbonate, diethyl carbonate and Texacar PC.
[4] method of any one in above-mentioned [1] to [3], wherein said being reflected in the carbonic ether carried out, and described carbonic ether is with respect to compound (II) to be the amount use of 0.5-to 30-times of weight.
[5] method of any one in above-mentioned [1] to [3], wherein saidly be reflected at carbonic ether and be selected from toluene, 1, carry out in the mixed solvent of the solvent of 2-glycol dimethyl ether and methylene dichloride, and described carbonic ether is with respect to compound (II) to be the amount use of 0.1-to 5-times of weight.
[6] method of any one in above-mentioned [1] to [5], wherein said asymmetric transition metal complex uses with the amount of counting 0.1 to 10 mole of % by per 1 mole compound (II).
[7] method of any one in above-mentioned [1] to [6], wherein said being reflected in 0 to 50 ℃ the scope carried out.
[8] method of any one in above-mentioned [1] to [7] is carried out under the wherein said existence that is reflected at the alkali that is selected from tertiary amine and aromatic amine.
[9] method of above-mentioned [8], wherein said alkali is selected from triethylamine, diisopropylethylamine and aniline.
[10] method of any one in above-mentioned [1] to [9], wherein said being reflected under the siccative existence carried out.
[11] method of above-mentioned [10], wherein said siccative is selected from aluminum oxide and molecular sieve.
[12] method of any one, wherein R in above-mentioned [1] to [11]
1And R
2It all is phenyl.
[13] method of any one, wherein R in above-mentioned [1] to [12]
3And R
4It all is hydrogen atom.
[14] method of any one, wherein R in above-mentioned [1] to [13]
5Or R
6It is residue with asymmetric center.
[15] method of any one, wherein R in above-mentioned [1] to [13]
5Or R
6It is the 1-phenylethyl.
[16] method of any one, wherein R in above-mentioned [1] to [13]
5Or R
6It is chirality 1-phenylethyl.
[17] method of any one in above-mentioned [1] to [16], contained transition metal is to be selected from Ru in the wherein said asymmetric transition metal complex, Pd, Rh, the metal of Cu and Ag.
[18] method of any one in above-mentioned [1] to [16], contained transition metal is Cu in the wherein said asymmetric transition metal complex.
[19] method of any one in above-mentioned [1] to [18], wherein said asymmetric transition metal complex are to prepare with transition metal salt or the reaction of its title complex by the compound by formula (I) expression that makes the optical activity form.
[20] method of any one in above-mentioned [1] to [18], wherein said asymmetric transition metal complex are by making the compound and the CuX by formula (I) expression of optical activity form
1Reaction and preparation, X wherein
1Be to be selected from halogen atom, BF
4, acetoxyl (acetoxy), SbF
6, PF
6And OSO
2CF
3Counter ion.
[21] method of any one, wherein R in above-mentioned [1] to [20]
8And R
9Form 4-piperidone (piperidinone) with adjacent nitrogen-atoms combination.
The invention effect
When the compound that is containing the optical activity form (I) as the asymmetric transition metal complex of asymmetric ligand in the presence of, from compound (II)-(IV) preparation during as the compound (V) of optically active amines, by in containing the solvent of carbonic ether, reacting, reaction times can be shortened, and can improve reaction yield and optical yield, in addition, even when less and reaction soln has high density, also can keep reaction yield and optical yield when the amount ratio of carbonic ether.
Implement mode of the present invention
At length explain the present invention below.
At first, explain the definition of each symbol that in specification sheets, uses.
Be used for R
3Or R
4The example of " halogen atom " comprise fluorine atom, chlorine atom, bromine atoms and iodine atom.R
3And R
4Independent separately is chlorine atom or fluorine atom.
Be used for R
3Or R
4The example of " lower alkoxy " comprise straight or branched C
1-12Alkoxyl group, such as methoxyl group, oxyethyl group, propoxy-, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert.-butoxy, pentyloxy, isopentyloxy, neopentyl oxygen, hexyloxy, heptan the oxygen base, octyloxy, the ninth of the ten Heavenly Stems oxygen base, the last of the ten Heavenly stems oxygen base, undecane oxygen base and dodecyloxy.Lower alkoxy is preferably straight or branched C
1-4Alkoxyl group such as methoxyl group, oxyethyl group, isopropoxy, tert.-butoxy etc.
Be used for R
3Or R
4" low alkyl group " and be used for R
5, R
6, R
7, R
8, R
9Or R
10" optional have one or more substituent low alkyl groups " in the example of " low alkyl group " comprise straight or branched C
1-12Alkyl such as methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl, the tertiary butyl, amyl group, isopentyl, neo-pentyl, hexyl, 2-ethyl-butyl, heptyl, octyl group, nonyl, decyl, undecyl and dodecyl.Low alkyl group is preferably straight or branched C
1-4Alkyl, methyl, ethyl, propyl group, butyl, sec-butyl, the tertiary butyl etc.
Be used for R
5, R
6, R
7, R
8, R
9Or R
10" optional have one or more substituent low alkyl groups " in " low alkyl group " choose wantonly in one or more commutable positions and have one or more substituting groups.Substituent example comprises the halogen atom of above definition, above Ding Yi lower alkoxy, hydroxyl, oxo, amino, nitro, cyano group, carboxyl and wherein moieties be the carbalkoxy of " low alkyl group " of above definition.Substituent number is not particularly limited.It is preferably 1 to 3.Substituting group can be identical or different.
Be used for R
7, R
8Or R
9" optional have one or more substituent low-grade alkenyls " in the example of " low-grade alkenyl " comprise straight or branched C
2-10Thiazolinyl, such as vinyl, 1-propenyl, allyl group, 1-methyl-2-propenyl, 1-butylene base, crotyl, the 3-butenyl, 1-pentenyl, pentenyl, the 1-hexenyl, 2-hexenyl, 1-heptenyl, the 2-heptenyl, 1-octenyl, 2-octenyl, 1-nonene base, 2-nonene base, 1-decene base and 2-decene base.Low-grade alkenyl is preferably allyl group.Alkenyl is chosen wantonly in one or more commutable positions has one or more substituting groups.Substituent example comprises the halogen atom of above definition, above Ding Yi lower alkoxy, hydroxyl, oxo, amino, nitro, cyano group, carboxyl, wherein moieties be above definition " low alkyl group " carbalkoxy and with undefined aryl.Substituent number is not particularly limited.It is preferably 1 to 3.Substituting group can be identical or different.
Be used for R
7" optional have one or more substituent low-grade alkynyls " in the example of " low-grade alkynyl " comprise straight or branched C
2-10Alkynyl, such as ethynyl, 1-proyl, 2-propynyl, 1-methyl-2-propynyl, ethyl acetylene base, 2-butyne base, the 3-butynyl, 1-pentynyl, valerylene base, 1-hexin base, 2-hexin base, 1-heptyne base, 2-heptyne base, 1-octyne base, 2-octyne base, 1-n-heptylacetylene base, 2-n-heptylacetylene base, 1-decynyl and 2-decynyl.Alkynyl is chosen wantonly in one or more commutable positions has one or more substituting groups.Substituent example be with for identical substituting group shown in above-mentioned " optional have one or more substituent alkenyls ".Substituent number is not particularly limited.It is preferably 1 to 3.Substituting group can be identical or different.
Be used for R
3, R
4, R
5, R
6, R
7, R
8, R
9Or R
10" optional have one or more substituent aryl " in the example of " aryl " comprise C
6-20Aryl, such as phenyl, 1-or 2-naphthyl and xenyl.
Aryl is chosen wantonly in one or more commutable positions has one or more substituting groups.Substituent example comprises the halogen atom of above definition, above Ding Yi low alkyl group, above Ding Yi lower alkoxy, hydroxyl, amino, nitro, cyano group, carboxyl, moieties is the carbalkoxy of above definition " low alkyl group ", more than Ding Yi aryl and with undefined aralkyl.Substituent number is not particularly limited.It is preferably 1 to 3.Substituting group can be identical or different.
Be used for R
1Or R
2The substituent example of " optional have one or more substituent phenyl " be with identical for the substituting group shown in above-mentioned " optional have one or more substituent aryl ".Substituent number is not particularly limited.It is preferably 1 to 3.Substituting group can be identical or different.
The specific examples of " choosing wantonly and having one or more substituent phenyl " comprises phenyl, p-methylphenyl, and a tolyl, o-tolyl and xylyl (2, the 3-xylyl, 2,4-xylyl, 2,5-xylyl, 2, the 6-xylyl, 3,4-xylyl and 3,5-xylyl).
Be used for R
5, R
6, R
7, R
8, R
9Or R
10" optional have one or more substituent heteroaryls " in the example of " heteroaryl " comprise 5-to 10-unit's aromatic heterocyclic radical and annelated heterocycles base thereof, described 5-to 10-unit aromatic heterocyclic radical also contains 1 to 3 heteroatoms that is selected from Sauerstoffatom, sulphur atom and nitrogen-atoms except that comprising carbon atom.Its specific examples comprises 2-or 3-thienyl, 2-or 3-furyl, 1-, 2-or 3-pyrryl, 1-, 2-, 4-or 5-imidazolyl, 2-, 4-or 5-
The azoles base, 2-, 4-or 5-thiazolyl, 1-, 3-, 4-or 5-pyrazolyl, 3-, 4-or 5-are different
The azoles base, 3-, 4-or 5-isothiazolyl, 1,2,4-triazole-1-, 3-, 4-or 5-base, 1,2,3-triazole-1-, 2-or 4-base, 1H-tetrazolium-1-or 5-base, 2H-tetrazolium-2-or 5-base, 2-, 3-or 4-pyridyl, 2-, 4-or 5-pyrimidyl, 1-, 2-, 3-, 4-, 5-, 6-or 7-indyl, 2-, 3-, 4-, 5-, 6-or 7-benzofuryl, 2-, 3-, 4-, 5-, 6-or 7-benzothienyl, 1-, 2-, 4-, 5-, 6-or 7-benzimidazolyl-, 2-, 3-, 4-, 5-, 6-, 7-or 8-quinolyl and 1-, 3-, 4-, 5-, 6-, 7-or 8-isoquinolyl.
Heteroaryl is chosen wantonly in one or more commutable positions has one or more substituting groups.Substituent example is with identical for the substituting group shown in above-mentioned " choose wantonly and have one or more substituent aryl ".Substituent number is not particularly limited.It is preferably 1 to 3.Substituting group can be identical or different.
Be used for R
3, R
4, R
7, R
8, R
9Or R
10" optional have one or more substituent cycloalkyl " in the example of " cycloalkyl " comprise C
3-7Cycloalkyl, as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and suberyl.Cycloalkyl is chosen wantonly in one or more commutable positions has one or more substituting groups.Substituent example be with for the identical substituting group of substituting group shown in above-mentioned " optional have one or more substituent aryl ", and oxo.Substituent number is not particularly limited.It is preferably 1 to 3.Substituting group can be identical or different.
Be used for R
3, R
4, R
5, R
6, R
7, R
8, R
9Or R
10" optional have one or more substituent aralkyl " in the example of " aralkyl " comprising: " low alkyl group " of above definition aralkyl of being replaced by " aryl " of above definition in any position of this low alkyl group wherein.Its specific examples comprises benzyl, 1-or 2-phenylethyl, 1-, 2-or 3-phenyl propyl, 1-or 2-naphthyl methyl, 1-or 2-(1-naphthyl) ethyl, 1-or 2-(2-naphthyl) ethyl, 2-ethyl-1-phenyl butyl, diphenyl-methyl and trityl.Aralkyl is chosen wantonly in one or more commutable positions has one or more substituting groups.Substituent example be with for the identical substituting group of substituting group shown in above-mentioned " optional have one or more substituent aryl ", and oxo.Substituent number is not particularly limited.It is preferably 1 to 3.Substituting group can be identical or different.
The specific examples of " choosing wantonly and having one or more substituent aralkyl " comprises the 1-phenylethyl, the 2-phenylethyl, 1-(4-tolyl) ethyl, 2-(4-tolyl) ethyl, 2-ethyl-2-hydroxyl-1-phenyl butyl, 1-(1-naphthyl) ethyl, 2-(1-naphthyl) ethyl, 1-(2-naphthyl) ethyl and 2-(2-naphthyl) ethyl.
The substituent example of " phenyl ring " that is used for encircling A " optional have one or more substituent phenyl ring " comprises halogen atom, low alkyl group, lower alkoxy, optional have one or more substituent cycloalkyl, and optional have one or more substituent aralkyl and optionally have one or more substituent aryl.Halogen atom, low alkyl group, lower alkoxy, optional have one or more substituent cycloalkyl, optional have one or more substituent aralkyl and optional example with one or more substituent aryl be with for R
3And R
4The group that shown group is identical.
By R
8And R
9The nitrogenous heterocyclic example that forms with adjacent nitrogen-atoms comprises such heterocycle together: except that comprising adjacent nitrogen-atoms, described heterocycle is also chosen wantonly and is contained 1 to 4 heteroatoms that is selected from nitrogen-atoms, Sauerstoffatom and sulphur atom.Its specific examples comprises saturated nitrogen heterocyclic ring such as tetramethyleneimine, piperidines, morpholine, thiomorpholine, piperazine etc.Nitrogen heterocyclic ring is chosen wantonly in one or more commutable positions has one or more substituting groups.Substituent example be with for the identical substituting group of substituting group shown in above-mentioned " optional have one or more substituent aryl ", and oxo.Substituent number is not particularly limited.It is preferably 1 to 3.Substituting group can be identical or different.
By R
8And R
9" choose wantonly and have one or more substituent nitrogen heterocyclic rings " of forming is preferably the 4-piperidone.
Be used for R
10The example of " trialkylsilkl " comprise three (C
1-4Alkyl) silyl is as trimethyl silyl (hereinafter referred to as TMS) group, t-butyldimethylsilyl, triethylsilyl, triisopropyl silyl etc.Trialkylsilkl is preferably TMS group or triethylsilyl.
At compound (V), (Va) and (Vb) in, * represents that with its marked carbon atoms be unsymmetrical carbon.That is to say that compound (V) is (Va) with the optically active compound of (Vb) respectively doing for oneself.
In specification sheets, term " optical activity " expression compound is not the multiple mixture of isomers (for example racemoid) that the steric configuration about asymmetric carbon of equivalent differs from one another.When one of steric isomer during with excessive comprising (for example 6: 4 mixtures), such compound is defined as optical activity.
Compound (I) is an atropisomer, and it shows asymmetric owing to what hinder around single bonded rotation, and described singly-bound is the key between 2 ring and the naphthalene nucleus (following demonstration).Compound (I) can split in room temperature.
The compound that defines in specification sheets can be the form of salt.The example of salt comprises the salt (for example, hydrochloride, vitriol, nitrate, phosphoric acid salt) with mineral acid; With organic acid salt (for example, acetate, propionic salt, mesylate, 4-tosylate, oxalate, maleate); An alkali metal salt (for example, sodium salt, sylvite); Alkaline earth salt (for example, calcium salt, magnesium salts); Salt (for example, front three amine salt, triethylamine salt, pyridinium salt, picoline salt, dicyclohexyl amine salt) with organic bases.
In compound (I), R
1And R
2Be preferably optional have one or more substituent phenyl or cyclohexyl separately, phenyl more preferably, tolyl (p-methylphenyl or a tolyl) or cyclohexyl are preferably phenyl especially.R
3And R
4Be preferably hydrogen atom separately, low alkyl group, lower alkoxy or cycloalkyl, more preferably hydrogen atom or methoxyl group are preferably hydrogen atom especially.
In compound (I), be used for the R of X
5Or R
6Be preferably optional one or more substituent aralkyl that have.In them, the residue with asymmetric center is preferred.Especially, R
5Or R
6Be preferably (R)-or (S)-the 1-phenylethyl, (R)-or (S)-1-(4-tolyl) ethyl, (R)-or (S)-2-ethyl-2-hydroxyl-1-phenyl butyl, (R)-or (S)-1-(1-naphthyl) ethyl, (R)-or (S)-1-(2-naphthyl) ethyl etc., more preferably (R)-or (S)-the 1-phenylethyl.
Compound of the present invention (I) can be for example according to the following method preparation described in the patent document 1.
X wherein
4Be halogen atom, p-toluenesulfonyl oxygen base, methylsulfonyl oxygen base or trifyl oxygen base, and other symbol as above defines.
That is to say that compound (I) can use compound (XIX) to prepare according to the method that comprises the following steps as raw material:
(i) make the reaction of compound (XIX) and compound (XX) or compound (XXI) with X
4Change into the step of X;
Resulting compound and trifluoromethanesulfanhydride anhydride are reacted in the presence of alkali hydroxyl is changed into trifyl oxygen base (hereinafter referred to as-OTf) step; With
(iii) make in above-mentioned steps (i) and the compound that obtains (ii) (XIX ') and compound (XXII) are containing to react in the presence of the transition metal complex of phosphine with general-OTf and change into by-PR
1R
2The step of the residue of expression, wherein R
1And R
2As above definition.
Be used for X
4The example of " halogen atom " comprise as for R
3Or R
4" halogen atom " shown in those examples.
The compound (I) (hereinafter referred to as optically active compound (I)) that contains the optical activity form can be as the catalyzer of asymmetric reaction as the asymmetric transition metal complex of part, that is, and and asymmetric catalyst.
The example of contained transition metal comprises Ru in the asymmetric transition metal complex, Pd, Rh, Cu and Ag.Transition metal is preferably Rh, and Cu or Ag are preferably Cu especially.
Asymmetric transition metal complex can for example prepare by optically active compound (I) is reacted in solvent with transition metal salt or its title complex, described in patent document 1.
Be used for the transition metal salt of asymmetric transition metal complex preparation or the example of its title complex and comprise CuX
1, Cu (X
1)
2, Rh (cod)
2X
1, (nbd) Rh (acac), CyRu (X
1)
2And AgX
1, X wherein
1Be to be selected from halogen atom, BF
4, acetoxyl, SbF
6, PF
6And OSO
2CF
3Counter ion, cod is 1,5-cyclooctadiene, nbd are norbornadienes, Cy is an isopropyltoluene, and acac is a methyl ethyl diketone.Transition metal salt or its title complex are preferably CuX
1, Rh (cod)
2X
1, (nbd) Rh (acac) or AgX
1, be preferably CuX especially
1
Be used for X
1The example of " halogen atom " comprise as for R
3Or R
4" halogen atom " shown in those examples.
As shown in following content, in the preparation method of optical activity amine compound of the present invention, chipal compounds (V) can be by making compound (II), compound (III) and compound (IV) in containing the solvent of carbonic ether, contain optically active compound (I) as the asymmetric transition metal complex of asymmetric ligand in the presence of the reaction and prepare.
In the present invention, asymmetric transition metal complex is preferably by making optically active compound (I) and CuX
1Reaction and prepare X wherein
1As above definition.
Wherein each symbol as above defines.
The addition sequence of reagent is not particularly limited.Preferably, compound (II) to (IV) joins in the solution of asymmetric transition metal complex of preparation successively or simultaneously.
From reactive and cost aspect, with respect to compound (II), the consumption of asymmetric transition metal complex is preferably 0.1 to 10 mole of %, more preferably 1 to 5 mole of %.
With respect to compound (II), the consumption of compound (III) is preferably 1 to 2 equivalent, more preferably 1 to 1.5 equivalent.
With respect to compound (II), the consumption of compound (IV) is preferably 1 to 2 equivalent, more preferably 1 to 1.5 equivalent.
In the present invention, preferably add siccative to promote reaction.The example of siccative comprises molecular sieve (trade(brand)name), aluminum oxide, silica gel and Florosil (florosil).Siccative is preferably aluminum oxide, silica gel or molecular sieve, more preferably aluminum oxide or
Molecular sieve is preferably especially
Molecular sieve.Preferably siccative is carried out pre-treatment, as heating, the degassing etc.With respect to compound (II), the consumption of siccative is preferably 0.5-to 40-times of weight, more preferably 1-to 10-times of weight.
In the present invention, preferably add alkali to promote reaction.The example of alkali comprises tertiary amine such as triethylamine, diisopropylethylamine etc.; With, aromatic amine such as aniline etc.Alkali is preferably triethylamine, diisopropylethylamine or aniline, more preferably aniline.With respect to compound (IV), the consumption of alkali is preferably 0.01 to 2 equivalent, more preferably 0.1 to 1 equivalent.
In the present invention, be reflected in the solvent that contains carbonic ether and carry out.The example of carbonic ether comprises the carbonic ether with 3 to 10 carbon atoms, and its specific examples comprises methylcarbonate, diethyl carbonate, Methyl ethyl carbonate, ethylene carbonate and Texacar PC.Carbonic ether is methylcarbonate more preferably, diethyl carbonate or Texacar PC.Carbonic ether can use separately, or being used in combination with two or more carbonic ethers.Can also use carbonic ether and toluene, 1,2-glycol dimethyl ether, the mixed solvent of methylene dichloride etc.
When independent use carbonic ether, with respect to compound (II), the consumption of carbonic ether is preferably 0.5-to 30-times of weight, more preferably 2-to 20-times of weight.
When using carbonic ether and toluene, 1, when 2-glycol dimethyl ether, the mixed solvent of methylene dichloride etc., with respect to compound (II), the consumption of carbonic ether is preferably 0.1-to 5-times of weight, more preferably 0.5-to 3-times of weight.With respect to toluene, 1, the gross weight of 2-glycol dimethyl ether, methylene dichloride etc., their ratio is preferably 0.01-to 0.2-times of weight, more preferably 0.04-to 0.1-times of weight.
The toluene that uses with routine etc. is compared, and the solvent that contains carbonic ether by use can shorten the reaction times as reaction solvent, and can improve reaction yield and optical yield.In addition, even when less and reaction soln has high density, also can keep reaction yield and optical yield when the amount ratio of carbonic ether.
Temperature of reaction is preferably 0 ℃ to 50 ℃, more preferably 20 to 35 ℃.When temperature of reaction was low, stereoselectivity was tending towards improving, but speed of reaction is tending towards reducing.Reaction times changes according to reagent and the temperature of reaction used.In the present invention, the optically active amines of expectation can prepare with 1 to 30 hour reaction times.
The chipal compounds that obtains like this (V) can separate and purifying according to ordinary method.For example, by making reaction mixture behind extracting operation or directly carry out silica gel column chromatography, can separate and purifying compounds (V).
After reaction is finished, siccative is leached from reaction mixture, in filtrate, add solvent such as hexane, heptane etc., and by filtering the collecting precipitation thing to reclaim asymmetric transition metal complex.The asymmetric transition metal complex that reclaims can be used as the catalyzer of asymmetric catalysis once more.Because asymmetric transition metal complex can reuse as mentioned above, so the present invention is favourable at industrial height.
Compound (Va), the i.e. wherein R that obtains in the present invention
8And R
9In conjunction with the compound (V) that forms the 4-piperidone, is useful with adjacent nitrogen-atoms, because compound (Va) can change into compound (Vb) by the deprotection that shows in the following scheme, this compound (Vb) is a propargyl amine.
Wherein each symbol as above defines.
Even when having unsettled group such as triple bond, the reaction that 4-piperidone ring is changed into primary amine is also carried out with high yield when keeping optical purity.Therefore, even when various unsettled functional groups exist, also think to be reflected under the situation that does not have side reaction and eligibly carry out with high yield.Therefore, this reaction can be applied to the general conversion of 4-derivative of piperidone to sulfonamide derivatives, and can be used as the new preparation process of primary amine.
Deprotection can for example be undertaken by compound (Va) is reacted in alcoholic solvent with ammonia and ammonium salt.Embodiment is explained below, but is not limited to them.
The ammonium salt that uses is preferably ammonium chloride.With respect to compound (Va), the consumption of ammonium salt is preferably 1 to 40 equivalent, more preferably 1 to 5 equivalent.
Ammonia can use with form saturated in the alcoholic solvent that uses.The example of alcoholic solvent comprises methyl alcohol, ethanol, n-propyl alcohol, Virahol and butanols.
With respect to compound (Va), the amount that is used for the alcoholic solvent that ammonia is saturated is 1-to a 100-times of weight.
Temperature of reaction is generally 0 ℃ to 130 ℃, preferred 40 ℃ to 100 ℃.Although the reaction times changes according to reagent and the temperature of reaction used, it typically is 0.5 to 48 hour.
Can be according to the compound (Vb) that ordinary method is separated and purifying obtains.For example, by making reaction mixture behind extracting operation or directly carry out silica gel column chromatography, can separate and purifying compounds (Vb).
In the present invention, as shown in the following content, can use and contain optically active compound (I) and obtain chipal compounds (V) by compound (II) to (IV) as the asymmetric transition metal complex of asymmetric ligand.The steric configuration of chipal compounds (V) is determined according to the steric configuration of optically active compound (I).For example, when optically active compound (I) is following formula,
Obtain the compound (V) of R form.When optically active compound (I) is following formula,
Obtain the compound (V) of S form.
Embodiment
Embodiment explains the present invention below by reference, but the invention is not restricted to these embodiment.
In the NMR data, J represents Hz.
In following examples, there is not the reaction of temperature explanation to carry out in room temperature.
Embodiment 1
With cupric bromide (201mg, 1.4mmol), (R, S)-[4-(2-diphenylphosphino naphthalene-1-yl)-2-1-yl]-(1-phenylethyl) amine ((R, S)-N-PINAP) (862mg, 1.54mmol) and
Molecular sieve (16.8g) is packed in the reaction vessel (500mL).Under argon gas atmosphere, to wherein adding methylcarbonate (50mL), and stir the mixture.After 90 minutes, to wherein add trimethyl silyl acetylene (4.0mL, 28mmol), hexahydrobenzaldehyde (3.37mL, 28.0mmol) and dibenzylamine (5.42mL 28.0mmol), and stirs the mixture.After 21 hours, reaction mixture is concentrated, and by quick silica gel column chromatography (hexane that contains 1% ether) purifying resistates, obtain (R)-N, N-dibenzyl-1-cyclohexyl-3-(trimethyl silyl)-2-propine-1-amine (9.7g).Yield is 89%, and optical yield is 99%.
1H-NMR(300MHz，CDCl
3)：δ＝7.41-7.40(m，4H)，7.39-7.31(m，4H)，7.29-7.20(m，2H)，3.79(d，J＝13.8，2H)，3.35(d，J＝13.8，2H)，3.02(d，J＝10.5，1H)，2.29-2.25(m，1H)，2.00-1.96(m，1H)，1.70-1.51(m，4H)，1.24-1.04(m，3H)，0.81-0.67(m，2H)，0.25(s，9H)
13C-NMR(100MHz，CDCl
3)δ＝139.6，128.7，128.0，126.7，103.5，90.1，58.7，55.0，39.7，31.5，30.5，26.9，26.4，26.2，0.83
Embodiment 2
With cupric bromide (201mg, 1.4mmol), (R, S)-N-PINAP (862mg, 1.54mmol) and
Molecular sieve (84g) is packed in the there-necked flask (1L).Under argon gas atmosphere, to wherein adding methylcarbonate (100mL), and stir the mixture.After 90 minutes, to wherein add trimethyl silyl acetylene (19.8mL, 140mmol), hexahydrobenzaldehyde (16.8mL, 140mmol) and dibenzylamine (27.1mL 140mmol), and stirs the mixture.After 22 hours, reaction mixture is concentrated, and, obtain (R)-N by quick silica gel column chromatography (hexane that contains 1% ether) purifying resistates, N-dibenzyl-1-cyclohexyl-3-(trimethyl silyl)-2-propine-1-amine (49.9g) is white solid.Yield is 91%, and optical yield is 99%.
Embodiment 3
With cupric bromide (3.6mg, 0.025mmol), (R, S)-N-PINAP (15mg, 0.0275mmol) and
Molecular sieve (300mg) is packed in the reaction vessel (10mL).Under argon gas atmosphere, to wherein adding methylcarbonate (1mL), and stir the mixture.After 90 minutes, to wherein add trimethyl silyl acetylene (71 μ L, 0.5mmol), hexahydrobenzaldehyde (60 μ L, 0.5mmol) and dibenzylamine (97 μ L 0.5mmol), and stir the mixture.After 20 hours, reaction mixture is concentrated, and, obtain (R)-N by quick silica gel column chromatography (hexane that contains 1% ether) purifying resistates, N-dibenzyl-1-cyclohexyl-3-(trimethyl silyl)-2-propine-1-amine (168mg) is white solid.Yield is 95%, and optical yield is 99%.
Embodiment 4
Except also add aniline (4.6 μ L, 0.05mmol) outside, with embodiment 3 in identical mode react.After reaction 15 hours, (R)-N, the yield of N-dibenzyl-1-cyclohexyl-3-(trimethyl silyl)-2-propine-1-amine is 91%, and optical yield is 99%.
Embodiment 5
Except after Preparation of Catalyst, adding immediately trimethyl silyl acetylene, hexahydrobenzaldehyde and the dibenzylamine, with embodiment 3 in identical mode react.(R)-and N, the yield of N-dibenzyl-1-cyclohexyl-3-(trimethyl silyl)-2-propine-1-amine is 85%, and optical yield is 99%.
Embodiment 6
Except using aluminum oxide (300mg) substituted molecule sieve, with embodiment 3 in identical mode react.After reaction 20 hours, (R)-N, the yield of N-dibenzyl-1-cyclohexyl-3-(trimethyl silyl)-2-propine-1-amine is 86%, and optical yield is 99%.
Embodiment 7
Except using diethyl carbonate (2mL) to replace the methylcarbonate, with embodiment 3 in identical mode react (solvent divides two parts of addings when Preparation of Catalyst (1mL) and substrate add (1mL)).After reaction 20 hours, (R)-N, the yield of N-dibenzyl-1-cyclohexyl-3-(trimethyl silyl)-2-propine-1-amine is 98%, and optical yield is 96%.
Embodiment 8
Except using Texacar PC (2mL) to replace the methylcarbonate, with embodiment 3 in identical mode react (solvent divides two parts of addings when Preparation of Catalyst (1mL) and substrate add (1mL)).After reaction 20 hours, (R)-N, the yield of N-dibenzyl-1-cyclohexyl-3-(trimethyl silyl)-2-propine-1-amine is 92%, and optical yield is 91%.
Comparative example 1
Except using toluene (2mL) to replace the methylcarbonate, with embodiment 3 in identical mode react (solvent divides two parts of addings when Preparation of Catalyst (1mL) and substrate add (1mL)).After reaction 48 hours, (R)-N, the yield of N-dibenzyl-1-cyclohexyl-3-(trimethyl silyl)-2-propine-1-amine is 74%, and optical yield is 98%.In addition, after reacting under the same conditions 120 hours, yield is 90%, and optical yield is 98%.
Embodiment 9
Except also adding Texacar PC (100 μ L) as the solvent, with comparative example 1 in identical mode react.After reaction 16 hours, (R)-N, the yield of N-dibenzyl-1-cyclohexyl-3-(trimethyl silyl)-2-propine-1-amine is 99%, and optical yield is 96%.
The optical purity measuring method
The silyl compound (67mg, 172 μ mol) that will the method by embodiment obtains be dissolved in anhydrous tetrahydro furan (THF) (2mL) in, and solution is cooled to 0 ℃.Fluoridize tributyl ammonium-THF solution (0.1mL) to wherein adding 1.0M, and mixture was stirred 15 minutes.To wherein adding entry, and with mixture with ether (2mL) extraction three times.Organic layer is merged, use the salt water washing, use anhydrous magnesium sulfate drying, and under reduced pressure concentrate.Resistates is carried out silica gel chromatography (with the hexane wash-out that contains 1% ether), and use optical column (optical column), analyze isolating (R)-N, N-dibenzyl-1-cyclohexyl-2-propine-1-amine by HPLC.
Post: CHIRALCEL OD-H, flow velocity: 0.3mL/min, moving phase: hexane, wavelength: 254nm, R
f(25.3 less), 28.5 (more)
1H-NMR(300MHz，CDCl
3)：δ＝7.45-7.43(m，4H)，7.37-7.32(m，4H)，7.29-7.25(m，2H)，3.86(d，J＝14.1，2H)，3.42(d，J＝14.1，2H)，3.08(dd，J＝10.8，2.1，1H)，2.38(d，J＝2.1，1H)，2.39-2.30(m，2H)，2.08-2.01(m，1H)，1.78-1.62(m，4H)，1.30-1.05(m，3H)，0.92-0.70(m，2H)
13C-NMR(100MHz，CDCl
3)δ＝139.6，128.7，128.1，126.8，81.0，73.5，57.7，54.9，39.6，31.3，30.3，26.6，26.2，26.0
The reference example catalyst recovery method
With cupric bromide (17.9mg, 0.125mmol), (R, S)-N-PINAP (77.0mg, 0.138mmol) and
In molecular sieve (powder 1.5g) reaction vessel of packing into (10mL), under argon gas atmosphere, to wherein adding methylcarbonate (2mL), and stir the mixture.After stirring 90 minutes, to wherein adding trimethyl silyl acetylene (2.50mmol), hexahydrobenzaldehyde (301 μ L, 2.50mmol) and dibenzylamine (484 μ L 2.50mmol), and stir the mixture.After 21 hours, hexane (3mL) is added in the reaction mixture.The yellow mercury oxide that obtains is leached, and with ether/hexane (5mL, 1/1 parts by volume) washed twice.Colourless filtrate is under reduced pressure concentrated, obtain light yellow (R)-N, and N-dibenzyl-1-cyclohexyl-3-(trimethyl silyl)-2-propine-1-amine (930mg) (95%, NMR).The yellow mercury oxide of reaction mixture is dissolved in the dimethyl formamide in the future, and filters.Filtrate is under reduced pressure concentrated, obtain yellow solid (104mg) (stoichiometry, maximum 95mg).By NMR, LCMS and MS analyze and determine that this solid is the cupric bromide title complex of PINAP.
Embodiment 10
Except the catalyzer that will in reference example, reclaim as the catalyzer, with embodiment 3 in identical mode react.Obtain (R)-N, N-dibenzyl-1-cyclohexyl-3-(trimethyl silyl)-2-propine-1-amine (183mg).Yield is 94%, and optical yield is 97%.
Industrial usability
According to the present invention, when the compound that is containing the optical activity form (I) as the asymmetric transient metal complex of asymmetric ligand in the presence of, from compound (II)-(IV) preparation during as the compound (V) of optically active amines, by in containing the solvent of carbonic ester, reacting, can Reaction time shorten, and can improve reaction yield and optical yield, in addition, even when smaller and reaction solution has high concentration when the consumption of carbonic ester, also can keep reaction yield and optical yield.
Therefore, preparation method of the present invention can be the method for industrial useful optical activity intermediate for the preparation of synthetic drug, agrochemical.
The application is based on the patent application 2008-166400 that submits in Japan, and the content of this patent application all is included in herein.
Claims (21)
1. method for preparing the optical activity amine compound of representing by formula V:
Wherein
R
7Be optional one or more substituent low alkyl groups that have, choose wantonly and have one or more substituent aryl, choose wantonly and have one or more substituent cycloalkyl, choose wantonly and have one or more substituent low-grade alkenyls, choose wantonly and have one or more substituent low-grade alkynyls, choose wantonly to have one or more substituent aralkyl or choose wantonly and have one or more substituent heteroaryls
R
8And R
9Independent separately have one or more substituent low alkyl groups for choosing wantonly, choose wantonly and have one or more substituent low-grade alkenyls, choose wantonly and have one or more substituent cycloalkyl, choose wantonly and have one or more substituent aralkyl, optional have one or more substituent aryl or optionally have one or more substituent heteroaryls, or
R
8And R
9Optional have one or more substituent nitrogen heterocyclic rings with adjacent nitrogen-atoms in conjunction with forming to choose wantonly,
R
10It is hydrogen atom, choose wantonly and have one or more substituent low alkyl groups, choose wantonly and have one or more substituent aryl, trialkylsilkl, choose wantonly and have one or more substituent cycloalkyl, optional have one or more substituent aralkyl or optionally have one or more substituent heteroaryls, and
* represent asymmetric carbon,
Described method comprises makes following compounds in containing the solvent of carbonic ether, reaction in the presence of asymmetric transition metal complex: by the compound of formula (II) expression: R
7CHO (II), wherein R
7As above definition is by the compound of formula (III) expression: HNR
8R
9(III), R wherein
8And R
9As above definition and by the compound of formula (IV) expression: HC ≡ CR
10(IV), R wherein
10As above definition, described asymmetric transition metal complex contain the optical activity form by the compound of formula (I) expression as asymmetric ligand:
Encircle wherein that A does not exist or have one or more substituent phenyl ring for optional,
R
1And R
2Independent separately have one or more substituent phenyl for optional, cyclohexyl, and 2-furyl or 3-furyl,
R
3And R
4Independent separately be hydrogen atom, halogen atom, low alkyl group, lower alkoxy, optional have one or more substituent cycloalkyl, optional have one or more substituent aralkyl or choose wantonly have one or more substituent aryl, and
X is by-OR
5Or-NHR
6The residue of expression, wherein R
5And R
6Independent separately have one or more substituent low alkyl groups for optional, and optional have one or more substituent aralkyl, and optional have one or more substituent aryl or optionally have one or more substituent heteroaryls.
2. the described method of claim 1, wherein said carbonic ether is the carbonic ether with 3 to 10 carbon atoms.
3. the described method of claim 1, wherein said carbonic ether is selected from methylcarbonate, diethyl carbonate and Texacar PC.
4. the described method of claim 1, wherein said being reflected in the carbonic ether carried out, and described carbonic ether is being that the amount of 0.5-to 30-times of weight is used with respect to compound (II).
5. the described method of claim 1, wherein saidly be reflected at carbonic ether and be selected from toluene, 1, carry out in the mixed solvent of the solvent of 2-glycol dimethyl ether and methylene dichloride, and described carbonic ether is with respect to compound (II) to be the amount use of 0.1-to 5-times of weight.
6. the described method of claim 1, wherein said asymmetric transition metal complex uses with the amount of counting 0.1 to 10 mole of % by per 1 mole compound (II).
7. the described method of claim 1, wherein said being reflected in 0 to 50 ℃ the scope carried out.
8. the described method of claim 1 is carried out under the wherein said existence that is reflected at the alkali that is selected from tertiary amine and aromatic amine.
9. the described method of claim 8, wherein said alkali is selected from triethylamine, diisopropylethylamine and aniline.
10. the described method of claim 1 is carried out under the wherein said existence that is reflected at siccative.
11. the described method of claim 10, wherein said siccative is selected from aluminum oxide and molecular sieve.
12. the described method of claim 1, wherein R
1And R
2It all is phenyl.
13. the described method of claim 1, wherein R
3And R
4It all is hydrogen atom.
14. the described method of claim 1, wherein R
5Or R
6It is residue with asymmetric center.
15. the described method of claim 1, wherein R
5Or R
6It is the 1-phenylethyl.
16. the described method of claim 1, wherein R
5Or R
6It is chirality 1-phenylethyl.
17. the described method of claim 1, contained transition metal is to be selected from Ru in the wherein said asymmetric transition metal complex, Pd, Rh, the metal of Cu and Ag.
18. the described method of claim 1, contained transition metal is Cu in the wherein said asymmetric transition metal complex.
19. the described method of claim 1, wherein said asymmetric transition metal complex are to prepare with transition metal salt or the reaction of its title complex by the compound by formula (I) expression that makes the optical activity form.
20. the described method of claim 1, wherein said asymmetric transition metal complex are by making the compound and the CuX by formula (I) expression of optical activity form
1Reaction and preparation, X wherein
1Be to be selected from halogen atom, BF
4, acetoxyl, SbF
6, PF
6And OSO
2CF
3Counter ion.
21. the described method of claim 1, wherein R
8And R
9Form the 4-piperidone with adjacent nitrogen-atoms combination.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2008-166400 | 2008-06-25 | ||
| JP2008166400 | 2008-06-25 | ||
| PCT/JP2009/061230 WO2009157386A1 (en) | 2008-06-25 | 2009-06-19 | Method for producing optically active amine compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102076653A true CN102076653A (en) | 2011-05-25 |
Family
ID=41444454
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009801242221A Pending CN102076653A (en) | 2008-06-25 | 2009-06-19 | Method for producing optically active amine compound |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JP2010030992A (en) |
| CN (1) | CN102076653A (en) |
| WO (1) | WO2009157386A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103748067A (en) * | 2011-07-06 | 2014-04-23 | 新加坡科技研究局 | Process for producing aminopropyne or enaminone |
| CN112079865A (en) * | 2019-06-13 | 2020-12-15 | 中国科学院上海有机化学研究所 | Phosphine nitrogen ligand with multiple chiral centers and synthetic method and application thereof |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11618751B1 (en) | 2022-03-25 | 2023-04-04 | Ventus Therapeutics U.S., Inc. | Pyrido-[3,4-d]pyridazine amine derivatives useful as NLRP3 derivatives |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4704812B2 (en) * | 2004-06-09 | 2011-06-22 | エム． カレイラ エリック | Monophosphine compound, transition metal complex thereof and method for producing optically active compound using the complex as asymmetric catalyst |
-
2009
- 2009-06-19 JP JP2009146772A patent/JP2010030992A/en not_active Ceased
- 2009-06-19 WO PCT/JP2009/061230 patent/WO2009157386A1/en active Application Filing
- 2009-06-19 CN CN2009801242221A patent/CN102076653A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103748067A (en) * | 2011-07-06 | 2014-04-23 | 新加坡科技研究局 | Process for producing aminopropyne or enaminone |
| CN112079865A (en) * | 2019-06-13 | 2020-12-15 | 中国科学院上海有机化学研究所 | Phosphine nitrogen ligand with multiple chiral centers and synthetic method and application thereof |
| WO2020248756A1 (en) * | 2019-06-13 | 2020-12-17 | 中国科学院上海有机化学研究所 | Phosphine nitrogen ligand having multiple chiral centers, synthesis method therefor and use thereof |
| CN112079865B (en) * | 2019-06-13 | 2022-03-01 | 中国科学院上海有机化学研究所 | Phosphine nitrogen ligand with multiple chiral centers and synthetic method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009157386A1 (en) | 2009-12-30 |
| JP2010030992A (en) | 2010-02-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102712585B (en) | Intermediates of neutral endopeptidase inhibitors and preparation method thereof | |
| Bandini et al. | The First Catalytic Enantioselective Nozaki–Hiyama Reaction | |
| JP3497165B2 (en) | Chiral catalyst, catalytic oxidation and disproportionation reaction, and method for producing epoxy chroman and taxol | |
| CN106831550A (en) | A kind of optical activity two（It is miscellaneous）Aryl methyl alcohol and its method of asymmetric synthesis | |
| Shi et al. | Chiral diphenylthiophosphoramides: a new class of chiral ligands for the silver (I)-promoted enantioselective allylation of aldehydes | |
| CN104402718B (en) | A kind of chiral allyl ester type compound and preparation method thereof | |
| CN108558635B (en) | Preparation method of 3-aryl propiolic acid and 3-aryl propiolic acid ester compound | |
| CN102076653A (en) | Method for producing optically active amine compound | |
| JP6054108B2 (en) | Process for producing optically active 2,3-dihydrofarnesal | |
| CN109503670B (en) | Chiral monophosphine ligand WJ-Phos of ferrocene skeleton, preparation method and application | |
| CN111646985A (en) | Synthetic method of pyrimidine heterocyclic antitumor drug molecule AZD6738 | |
| CN101098878B (en) | Monophosphine compound, transition metal complex thereof and method for producing optically active compound by using the same complex as asymmetric catalyst | |
| CN112430228B (en) | Chiral 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide, derivative and preparation method | |
| US6476250B1 (en) | Optically active fluorinated binaphthol derivative | |
| CN111217847B (en) | Thiosilane ligand, preparation method thereof and application thereof in aryl boronization catalytic reaction | |
| CN115322100A (en) | Delta, epsilon-alkenyl ketone compound and preparation method and application thereof | |
| CN107915653A (en) | Catalysis ester and amine carry out the method that reaction prepares acid amides | |
| Blumenstein et al. | Enantioselective hydrogen transfer reactions from chiral binaphthyl variants of tin hydrides to prochiral radicals | |
| KR102366890B1 (en) | Method for producing iron complex and method for producing ester compound using iron complex | |
| CN104193667A (en) | Synthesis method of divergently oriented azacycles | |
| JP2006089493A (en) | Optically active cobalt (ii) complex | |
| Fan et al. | Rhodium catalyzed asymmetric Pauson-Khand reaction using SDP ligands | |
| CN113582797B (en) | Method for synthesizing trifluoromethyl-1, 3-eneyne compound by copper catalysis | |
| CN115650824B (en) | Chiral diol and preparation method thereof, prepared catalyst and preparation method and application thereof | |
| CN105622544A (en) | Synthetic method of N-sulfonyl-3,4-dihydro-2H-1,4-thiazine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20110525 |