CN105693647B - A kind of compound of chirality An containing Ya oxazoline amines and preparation method thereof - Google Patents

A kind of compound of chirality An containing Ya oxazoline amines and preparation method thereof Download PDF

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CN105693647B
CN105693647B CN201610016368.6A CN201610016368A CN105693647B CN 105693647 B CN105693647 B CN 105693647B CN 201610016368 A CN201610016368 A CN 201610016368A CN 105693647 B CN105693647 B CN 105693647B
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陆展
陈旭
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Zhejiang University ZJU
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    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
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    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
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    • B01J2231/34—Other additions, e.g. Monsanto-type carbonylations, addition to 1,2-C=X or 1,2-C-X triplebonds, additions to 1,4-C=C-C=X or 1,4-C=-C-X triple bonds with X, e.g. O, S, NH/N
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Abstract

The invention discloses a kind of compound of synthesis of chiral Ya An oxazoline amines and preparation method thereof Qi Zhong oxazolines aryl of to be connected with imines aryl by N atoms on amine, and these compounds and metal complex as catalyst in asymmetric syntheses, the especially purposes in the silicon hydrogenation of the prochiral organic compounds containing carbon/hetero atom double bond and carbon carbon atom double bond and hydroboration.

Description

A kind of compound of chirality An containing Ya oxazoline amines and preparation method thereof
Technical field
The present invention relates to compound of the synthesis oxazoline amines of An containing Ya and preparation method thereof, and the compound and metal Altogether in the silicon hydrogenation and hydroboration of prochiral organic compounds of the catalysis containing carbon/hetero atom double bond and carbon carbon atom double bond Purposes.
Background technology
The asymmetric reaction of transient metal complex catalysis has obtained the extensive pass of academia and industrial quarters in world wide Note, wherein the research for central metal institute linking ligand is also very extensive, wherein bisoxazoline (Box) part is that research is more One, Nishiyama in 1989 reports first case pyridine double-oxazoline part [Nishiyama, H.；Sakaguchi,H.； Nakamura,T.；Horihata,M.；Kondo,M.；Itoh, K.Organometallics 1989,8,846.], subsequent pyridine Bisoxazoline part play very big concern [(a) Dalit Rechavi and Marc Lemaire.Chem.Rev., 2002, 102(10),pp 3467–3494.(b)Giovanni Desimoni,Giuseppe Faita,and Paolo Quadrelli.Chem.Rev., 2003,103 (8), pp 3119-3154], some researchers are improved to this part, derivative Some Xin oxazoline ligands.2002, Patrick J.Guiry reported bisoxazoline phenyl amine part first, it Such part is successfully applied to asymmetric Nozaki-Hiyama allylation reactions, henry reactions, friedel-crafts acylation afterwards In a series of asymmetric catalysis such as the Michael addition reaction of nitroolefin.[(a) Angew.Chem.Int.Ed.2009,48,9152–9155.；(b)J.Am.Chem.Soc.2006,128,7418–7419；(c) J.Org.Chem.,2005,70(9),3712–3715；(d)Org.Lett.,2007,9(23),4725–4728].
On the other hand, Busch and Stoufer in 1956 et al. report pyridine diimine for the first time, and subsequent structure obtains Confirmation [(a) Stoufer, R.C. are arrived；Busch,D.H.J.Am.Chem.Soc.1956,78,6016.(b)Lions,F.； Martin,K.V.J.Am.Chem.Soc.1957,79,2733.(c)Figgins,P.E.；Busch, D.H.J.Am.Chem.Soc.1959,82,820.], it is coordinated composition catalyst, extensive use with cheap metal (Fe, Co, Ni) In the polymerisation of alkene, the complex of other transition metal is also synthesized in succession, for being catalyzed in organic reaction.It is based on Imine ligand and the superior catalytic activity shown after metal complex, the present invention have synthesized a kind of chiral Ya An oxazoline amines Compound, it is significant to transition metal asymmetry catalysis.
The content of the invention
The invention discloses a kind of compound of synthesis of chiral Ya An oxazoline amines and preparation method thereof , Suo Shu oxazolines Aryl is connected with imines aryl by N atoms on amine, and these compounds are closed with metal complex as catalyst in asymmetry Into especially the silicon in the prochiral organic compounds containing carbon/hetero atom double bond and carbon carbon atom double bond hydrogenates and hydroboration is anti- Purposes in answering.
The present invention is achieved through the following technical solutions：
A kind of compound of the sub- amine oxazoline amine of chirality, described compound are high optically pure, structural formula such as following formulas (1)
Wherein, R1It is C1-C12- alkyl that is unsubstituted or being substituted by 1-2 C1-C4- alkoxy, or is not taken Cyclopenta or cyclohexyl generation or substituted by 1-3 C1-C4- alkyl or C1-C4- alkoxies, or it is unsubstituted or by Benzyl, the benzene of 1-4 C1-C4- alkyl, C1-C4- alkoxies, C1-C4- fluoroalkyls or C1-C4- Fluoroalkyloxies, F or Cl substitutions Base or naphthyl；
R2It is H or C1-C12- alkyl that is unsubstituted or being substituted by 1-2 C1-C4- alkoxy, or it is unsubstituted Or the cyclopenta or cyclohexyl that are substituted by 1-3 C1-C4- alkyl or C1-C4- alkoxies, it is or unsubstituted or by 1-3 The phenyl or naphthyl of individual C1-C4- alkyl, C1-C4- alkoxies, C1-C4- fluoroalkyls or C1-C4- Fluoroalkyloxies, F or Cl substitutions；
R3, R4, R5, R6, R7, R8, R9, R10Be H or unsubstituted C1-C12- alkyl, C1-C4- Fluoroalkyloxies, F or Cl, or cyclopenta or cyclohexyl, nitro unsubstituted or substituted by 1-3 C1-C4- alkyl or C1-C4- alkoxies；
R11It is H or C1-C12- alkyl that is unsubstituted or being substituted by 1-2 C1-C4- alkoxy, or is not taken Cyclopenta or cyclohexyl generation or substituted by 1-3 C1-C4- alkyl or C1-C4- alkoxies, or it is unsubstituted or by Benzyl, the benzene of 1-3 C1-C4- alkyl, C1-C4- alkoxies, C1-C4- fluoroalkyls or C1-C4- Fluoroalkyloxies, F or Cl substitutions Base or naphthyl；
R12, R13It is H or C1-C12- alkyl that is unsubstituted or being substituted by 1-2 C1-C4- alkoxy, or not Cyclopenta or cyclohexyl substituted or substituted by 1-3 C1-C4- alkyl or C1-C4- alkoxies, or it is unsubstituted Or the benzyl substituted by 1-3 C1-C4- alkyl, C1-C4- alkoxies, C1-C4- fluoroalkyls or C1-C4- Fluoroalkyloxies, F or Cl Base, phenyl or naphthyl；
R14C1-C12- alkyl that is unsubstituted or being substituted by 1-2 C1-C4- alkoxy, or it is unsubstituted or The cyclopenta or cyclohexyl substituted by 1-3 C1-C4- alkyl or C1-C4- alkoxies, or it is unsubstituted or individual by 1-3 Benzyl, phenyl or the naphthalene of C1-C4- alkyl, C1-C4- alkoxies, C1-C4- fluoroalkyls or C1-C4- Fluoroalkyloxies, F or Cl substitutions Base；* asymmetric carbon atom is represented.
As a further improvement, described R1Preferably alkyl or aryl, described R2Preferably hydrogen, alkyl or aryl, Described R3-R10Preferably hydrogen, alkyl, described R11Preferably hydrogen, alkyl or aryl, described R12, R13Preferably hydrogen, alkane Base or aryl, R14Preferably alkyl or aryl.
The invention also discloses a kind of preparation method of the compound of chiral Ya An oxazoline amines, described method includes Following steps：
A), formula (2) 2- oxazolinyl amineWith formula (3)
Halides are reacted, to form formula (4)
Wherein R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, * is for example defined in claim 1, X F, Cl, Br, I；
B), formula (4) and formula (5) R1-NH2(5) amine reacts, wherein R1It is as defined above, to produce above-claimed cpd formula (1)。
As a further improvement, step (a) of the present invention be transition metal Ru, Rh, Pd, Ir, Cu inorganic salts and Organophosphorus ligand, the coupling reaction of aminophosphine ligand catalysis.
As a further improvement, the solvent that reaction is participated in step (a) of the present invention is organic solvent, it is polarity Or non-polar solven, described organic solvent are benzene, carbon tetrachloride, petroleum ether, tetrahydrofuran, dimethylformamide, ether, two Any one in chloromethanes, chloroform, toluene, dimethylbenzene, hexamethylene, n-hexane, normal heptane, dioxane, acetonitrile.
As a further improvement, in step (a) of the present invention, reaction temperature 300C to 2000C, reaction time is 30 minutes to 48 hours.
As a further improvement, in step (a) of the present invention, formula (2)：Formula (3)：Metallic catalyst：Part thing Expect that ratio is 1-5:0.01-1:0.02-2：0.02-2.
The invention also discloses a kind of compound by described in claim 1 and transition metal M XnComplexes ira situ is used to lead to Cross the method that asymmetric catalytic reaction prepares chiral organic compound, it is characterised in that described method in catalytic amount at least A kind of Formula (1) and at least one transition metal M XnIn the presence of carry out, wherein,
Catalytic amount refers to the dosage of the catalyst in chemical reaction, and its numerical value is less than a molar equivalent；
M is transition-metal Fe, Co, Ni, Cu, Ag, Au, Ru, Rh, Pd, Os, Ir；
X is selected from halide (F, Cl, Br, I), pseudohalide (cyanide, cyanic acid, salt, isocyanates), carboxylic acid, sulfonic acid, phosphine Acid anion (carbonate, formate, acetate, propionate, pyrovinic acid root, trichloromethyl sulfonate radical, phenylbenzimidazole sulfonic acid root, Tosylate) in any one；
N is X number, is 1,2,3.
As a further improvement, the described method for preparing chiral organic compound is in the presence of a catalyst, by Asymmetric silicon hydrogenation is carried out in the carbon carbon atom double bond or heteroatoms double bond of prochiral organic compounds or hydroboration is real Existing, i.e., described asymmetric silicon hydrogenation or hydroboration addition are at least one Formula (1) of catalytic amount and at least one transition Metal MXnIn the presence of carry out.
Beneficial effects of the present invention are as follows：
The invention provides a kind of compound of novel chiral An containing Ya oxazolines amine.
Present invention also offers an efficient synthetic route, two step gross production rates can reach 60%.
The compound of the chirality oxazoline amines of An containing Ya of the present invention and transition metal M XnComplexes ira situ thing is for non-right Before the outstanding catalyst or catalyst for claiming synthesis (such as asymmetric hydrogenation effect of prochirality, unsaturation, organic compound) Body.Current chiral, unsaturation, organic compound are used, and the excessive optical isomer of height, which can be introduced into, to organise In the synthesis of compound, and it can obtain high chemical conversion rate.
The present invention also provides the compound and transition metal M X of the chirality oxazoline amines of An containing Ya of the present inventionnComplexes ira situ Purposes of the thing as homogeneous catalyst, catalyst are double by the heteroatoms double bond and carbon carbon atom in prochiral organic compounds Silicon hydrogenation is carried out on key or hydroborated asymmetric addition is used to prepare chiral organic compound, ee values can reach>90%.
For silicon hydrogenation or the preferable prochirality of hydoboration, unsaturated compound can be comprising C=C, C=N and/ Or the open chain of C=O bases or the organic compound of ring, wherein C=C, C=N and C=0 group can be loop system a part or It is the outer base of ring.The prochirality unsaturated compound can be alkene, cyclenes, heterocycle alkene and open chain or cyclic ketones, α, beta-diketon, α-or β -one carboxylic acid and its α, β -one acetal or ketal, ester and acid amides, ketimide, ketoxime and ketone hydrazone.
Can chiral organic compound prepared in accordance with the present invention be active material or the intermediate for preparing the material, it is special Be not spices and fumet, pharmaceutical preparation, agricultural chemicals production in terms of.
Embodiment
The invention provides a kind of formula (1) compound, the compound is optically pure for height,
R1, R2, R3, R4, R5, R6, R7, R8It is as defined above.
Term " high optically pure ", which refers to, at least 90%, preferably at least 95%, more preferably at least 99% enantioselectivity Property.
R1It is preferred that selecting cycloalkyl or aryl, the phenyl of substitution is more preferably selectedR16、R18Preferably hydrogen, R15、 R17、R19It is preferred that selecting alkyl or alkoxy, methyl, ethyl, isopropyl, the tert-butyl group, methoxyl group are more preferably selected.
R2It is preferred that being selected as hydrogen, alkyl or aryl, hydrogen, alkyl are more preferably selected, more preferably selects hydrogen, methyl, ethyl, isopropyl Base, the tert-butyl group.
R3, R4, R5, R6,, R7, R8, R9, R10It is preferred that be selected as hydrogen, alkyl, more preferably select hydrogen, methyl, ethyl, isopropyl, The tert-butyl group.
R11It is preferred that being selected as hydrogen, alkyl or aryl, hydrogen, methyl, ethyl, isopropyl, phenyl, benzyl are more preferably selected.
R14It is preferred that optimum selecting is alkyl or aryl, isopropyl, the tert-butyl group, phenyl, benzyl are more preferably selected.
R12, R13It is preferred that being selected as hydrogen, alkyl or aryl, hydrogen and alkyl are more preferably selected, more preferably selects hydrogen, methyl, second Base, isopropyl, the tert-butyl group.
The present invention also provides a kind of method for being used to prepare the compound of high optically pure formula (1), comprises the steps of：
A), formula (2) 2- oxazolinyl amineWith formula (3)
Halides are reacted, to form formula (4)
Wherein R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, * is for example defined in claim 1, X F, Cl, Br, I；
B), formula (4) and formula (5) R1-NH2(5) amine reacts, wherein R1It is high optically pure with production as defined in claim 1 The chiral compound of formula (1).
Step (b) is carried out using known in the art with formula (4) and amine formula (5) reaction method, obtains the chemical combination of formula (1) Thing.
Usual formula (4) is 1 with amine formula (5) mol ratio:1-10.
Catalyst is Bronsted acid or molecular sieve.
Step (a) is that the coupling that transition metal Ru, Rh, Pd, Ir inorganic salts and organophosphorus ligand, aminophosphine ligand are catalyzed is anti- Should.
The solvent that reaction is participated in step (a) is organic solvent, can be polarity or non-polar solven.As such as benzene, four Chlorination carbon, petroleum ether, tetrahydrofuran, dimethylformamide, ether, dichloromethane, chloroform, toluene, dimethylbenzene, hexamethylene Alkane, n-hexane, normal heptane, dioxane, acetonitrile etc., 30 DEG C to 200 DEG C of reaction temperature, react 30 minutes to 48 hours.
Step (a) formula (2):Formula (3):Metallic catalyst：Part material ratio is 1:1-5:0.02-2:0.02-2.
The present invention is provided such as the transition metal salt MX defined in the content of the inventionnIt is used for prochirality through complexes ira situ with compound Asymmetric hydrosilation addition is carried out in the heteroatoms double bond of organic compound to prepare chiral organic compound.
Wherein Formula (1) and metal salt MXnEquivalent proportion be preferably from about 2.2:1-0.9:1, more preferably 1.0:1- 1.6:1。
Transition metal salt MXnIt is preferred that usage amount is 0.001-10mol%, more preferably 0.1-5mol%.
Formula (1) preferably usage amount is 0.001-20mol%, more preferably 0.16-15mol%.
Technical scheme is described in further detail below by specific embodiment：
Following examples are used to explain the present invention.All reactions are carried out in airfree argon gas and the solvent of degassing.But It is not intended to limit present invention.
Embodiment：Formula (3) and amine formula (5) are commercially available, and 2- oxazolinyl amine formulas (2) are according to document It is prepared by (Org.Biomol.Chem., 2009,7,1723-1734).
The preparation of Formula (4)
Example A1：Compound A1 preparation
Under nitrogen protection, (S) -2- (4- benzyl -4,5- dihydro-oxazole -2- bases) aniline (2.7753g, 11mmol, 1.1equiv) with 2- bromobenzaldehydes (1.8502g, 10mmol, 1.0equiv) in 20mL dioxane, Pd (dba)2 (0.2875g, 0.5mmol, 5mol%), Xantphos (0.3472g, 0.6mmol, 6mol%), potassium carbonate (2.7642g, 20mmol, 2.0equiv), 100 DEG C are reacted 24 hours, petroleum ether：Ethyl acetate=20:1 crosses post, obtains 2.8289g (7.8mmol, the compound A1 of 78%) Han oxazoline amines.
1H NMR(400MHz,CDCl3):δ 11.38 (s, 1H), 10.04 (s, 1H), 7.81 (dd, J=7.6,1.2Hz, 1H), 7.68 (dd, J=7.6,1.2Hz, 1H), 7.48 (dd, J=18.8,8.4Hz, 2H), 7.43-7.35 (m, 1H), 7.33- 7.25 (m, 1H), 7.24-7.11 (m, 5H), 6.98 (t, J=7.4Hz, 1H), 6.90 (t, J=7.4Hz, 1H), 4.71-4.59 (m, 1H), 4.26 (t, J=8.9Hz, 1H), 4.04 (t, J=7.9Hz, 1H), 3.18 (dd, J=14.0,5.6Hz, 1H), 2.78 (dd, J=13.6,8.0Hz, 1H)
13C NMR(101MHz,CDCl3):δ191.8,163.1,144.5,142.9,138.1,134.9,134.4, 131.7,130.5,129.5,128.6,126.5,124.9,120.6,120.4,118.1,117.6,115.0,70.6,68.2, 41.8.HRMS(EI)calculated for[C23H20N2O2]+requires m/z 356.1525,found m/z 356.1526.
Example A2：Compound A2 preparation
Under nitrogen protection, (S) -2- (4- isopropyl -4,5- dihydro-oxazole -2- bases) aniline (2.2473g, 11mmol, 1.1equiv) with 2- bromobenzaldehydes (1.8502g, 10mmol, 1.0equiv) in 20mL dioxane, Pd (dba)2 (0.2875g, 0.5mmol, 5mol%), Xantphos (0.3472g, 0.6mmol, 6mol%), potassium carbonate (2.7642g, 20mmol, 2.0equiv), 200 DEG C are reacted 30 minutes, petroleum ether：Ethyl acetate=20:1 crosses post, obtains 2.8289g (8.5mmol, the compound A2 of 85%) Han oxazoline amines.
1H NMR(400MHz,CDCl3):δ 11.40 (s, 1H), 10.10 (s, 1H), 7.85 (d, J=8.0Hz, 1H), 7.71 (d, J=7.6Hz, 1H), 7.58-7.48 (m, 2H), 7.42 (t, J=7.4Hz, 1H), 7.36-7.29 (m, 1H), 7.05-6.98 (m, 1H), 6.94 (t, J=7.6Hz, 1H), 4.44-4.32 (m, 1H), 4.22-4.12 (m, 1H), 4.05 (t, J=8.0Hz, 1H), 1.89-1.76 (m, 1H), 1.04 (d, J=6.4Hz, 3H), 0.95 (d, J=6.8Hz, 3H)13C NMR(101MHz, CDCl3):δ191.8,162.6,144.6,142.6,134.7,134.3,131.3,130.3,124.7,120.3,120.3, 118.1,117.6,115.2,73.2,69.3,33.1,18.9,18.6.HRMS(EI)calculated for[C19H20N2O2]+ requires m/z 308.1525,found m/z 308.1520.
Example A3：The preparation of compound A-13
Under nitrogen protection, (S) -2- (4- phenyl -4,5- dihydro-oxazole -2- bases) aniline (2.6213g, 11mmol, 1.1equiv) with 2- bromobenzaldehydes (1.8502g, 10mmol, 1.0equiv) in 20mL dioxane, Pd (dba)2 (0.2875g, 0.5mmol, 5mol%), Xantphos (0.3472g, 0.6mmol, 6mol%), potassium carbonate (2.7642g, 20mmol, 2.0equiv), 120 DEG C are reacted 20 hours, petroleum ether：Ethyl acetate=20:1 crosses post, obtains 2.8289g (8.3mmol, the compound A-13 of 83%) Han oxazoline amines.
1H NMR(400MHz,CDCl3):δ 11.31 (s, 1H), 10.04 (s, 1H), 7.93 (d, J=7.6Hz, 1H), 7.70 (d, J=7.6Hz, 1H), 7.57-7.41 (m, 3H), 7.40-7.31 (m, 5H), 7.30-7.24 (m, 2H), 7.00 (dt, J= 20.0,7.6Hz, 2H), 5.57-5.48 (m, 1H), 4.76 (t, J=8.8Hz, 1H), 4.21 (t, J=8.0Hz, 1H)13C NMR (101MHz,CDCl3):δ191.9,164.0,144.5,143.1,142.2,134.8,134.2,131.8,130.6,128.7, 127.5,126.5,125.0,120.7,120.3,118.6,117.7,114.9,73.41,70.11.HRMS(EI) calculated for[C22H18N2O2]+requires m/z 342.1368,found m/z 342.1367.
Example A4：Compound A4 preparation
Under nitrogen protection, (S) -2- (4- tert-butyl group -4,5- dihydro-oxazole -2- bases) aniline (2.4013g, 11mmol, 1.1equiv) with 2- bromobenzaldehydes (1.8502g, 10mmol, 1.0equiv) in 20mL dioxane, Pd (dba)2 (0.2875g, 0.5mmol, 5mol%), Xantphos (0.3472g, 0.6mmol, 6mol%), potassium carbonate (2.7642g, 20mmol, 2.0equiv), 100 DEG C are reacted 24 hours, petroleum ether：Ethyl acetate=20:1 crosses post, obtains 2.8289g (8.0mmol, the compound A4 of 80%) Han oxazoline amines.
1H NMR(400MHz,CDCl3):δ 11.36 (s, 1H), 10.10 (s, 1H), 7.85 (d, J=8.0Hz, 1H), 7.71 (d, J=8.0Hz, 1H), 7.52 (dd, J=17.9,8.4Hz, 2H), 7.42 (t, J=7.7Hz, 1H), 7.32 (t, J= 7.7Hz, 1H), 7.01 (t, J=7.4Hz, 1H), 6.94 (t, J=7.5Hz, 1H), 4.30 (t, J=12.5Hz, 1H), 4.20- 4.10(m,2H),0.95(s,9H).13C NMR(101MHz,CDCl3):δ191.7,162.5,144.6,142.7,134.7, 134.3,131.3,130.3,124.8,120.4,120.3,118.3,117.6,115.1,76.7,67.4,33.9, 25.9.HRMS(EI)calculated for[C20H22N2O2]+requires m/z322.1681,found m/z 322.1680.
Example A5：The preparation of compound A-45
Under nitrogen protection, (S) -2- (4- isopropyl -4,5- dihydro-oxazole -2- bases) aniline (2.2473g, 11mmol, 1.1equiv) with the bromo- 5- chlorobenzaldehydes (2.1950g, 10mmol, 1.0equiv) of 2- in 20mL dioxane, Pd (dba)2 (0.2875g, 0.5mmol, 5mol%), Xantphos (0.3472g, 0.6mmol, 6mol%), potassium carbonate (2.7642g, 20mmol, 2.0equiv), 30 DEG C are reacted 48 hours, petroleum ether：Ethyl acetate=20:1 crosses post, obtains 2.9824g (8.7mmol, the compound A-45 of 87%) Han oxazoline amines.
1H NMR(400MHz,CDCl3):δ 11.42 (s, 1H), 10.05 (s, 1H), 7.85 (dd, J=7.9,1.6Hz, 1H), 7.67 (d, J=2.6Hz, 1H), 7.50 (d, J=8.9Hz, 1H), 7.43 (dd, J=8.3,0.9Hz, 1H), 7.34 (ddd, J=9.8,8.8,2.1Hz, 2H), 7.00-6.94 (m, 1H), 4.38 (dd, J=9.4,8.1Hz, 1H), 4.21-4.11 (m, 1H), 4.05 (t, J=8.1Hz, 1H), 1.82 (dq, J=13.4,6.7Hz, 1H), 1.02 (d, J=6.7Hz, 3H), 0.94 (d, J=6.7Hz, 3H)13C NMR(101MHz,CDCl3):δ190.4,162.6,143.1,142.3,134.7,133.1, 131.5,130.3,125.7,125.2,120.7,119.9,117.4,115.2,76.7,73.1,69.3,33.1,18.8, 18.7.HRMS(EI)calculated for[C19H19ClN2O2]+requires m/z 342.1135,found m/z 356.1139.
Example A6：Compound A6 preparation
Under nitrogen protection, (S) -2- (4- isopropyl -4,5- dihydro-oxazole -2- bases) aniline (2.2473g, 11mmol, 1.1equiv) with the bromo- 4- fluorobenzaldehydes (2.0300g, 10mmol, 1.0equiv) of 2- in 20mL dioxane, Pd (dba)2 (0.2875g, 0.5mmol, 5mol%), Xantphos (0.3472g, 0.6mmol, 6mol%), potassium carbonate (2.7642g, 20mmol, 2.0equiv), 200 DEG C are reacted 30 minutes, petroleum ether：Ethyl acetate=20:1 crosses post, obtains 3.0355g (9.3mmol, the compound A6 of 93%) Han oxazoline amines.
1H NMR(400MHz,CDCl3):δ 11.57 (s, 1H), 9.98 (s, 1H), 7.87 (dd, J=7.9,1.6Hz, 1H), 7.65 (dd, J=8.6,6.6Hz, 1H), 7.55 (d, J=8.3Hz, 1H), 7.44-7.34 (m, 1H), 7.17 (dd, J=12.0, 2.3Hz, 1H), 7.03 (t, J=7.6Hz, 1H), 6.64 (td, J=8.2,2.3Hz, 1H), 4.37 (dd, J=9.4,8.1Hz, 1H), 4.22-4.10 (m, 1H), 4.05 (t, J=8.1Hz, 1H), 1.83 (dd, J=13.4,6.7Hz, 1H), 1.03 (d, J= 6.7Hz, 3H), 0.94 (d, J=6.7Hz, 3H)13C NMR(101MHz,CDCl3):δ190.6,168.4,165.9,162.2, 147.3,147.2,143.3,141.1,138.0,137.9,134.8,131.4,130.5,130.4,129.0,128.4, 125.5,121.7,120.4,120.4,119.1,116.7,107.4,107.1,102.9,102.6,73.2,69.4,33.1, 18.8,18.6.HRMS(EI)calculated for[C19H19FN2O2]+requires m/z 326.1432,found m/z 356.1434.
Example A7：Compound A7 preparation
Under nitrogen protection, (S) -2- (4- isopropyl -4,5- dihydro-oxazole -2- bases) aniline (2.2473g, 11mmol, 1.1equiv) with the bromo- 4- tolyl aldehydes (2.0300g, 10mmol, 1.0equiv) of 2- in 20mL dioxane, Pd (dba)2(0.2875g, 0.5mmol, 5mol%), Xantphos (0.3472g, 0.6mmol, 6mol%), potassium carbonate (2.7642g, 20mmol, 2.0equiv), 30 DEG C are reacted 48 hours, petroleum ether：Ethyl acetate=20:1 crosses post, obtains 3.0950g (9.6mmol, the compound A7 of 96%) Han oxazoline amines.
1H NMR(400MHz,CDCl3):δ 11.32 (s, 1H), 10.04 (s, 1H), 7.84 (dd, J=7.9,1.5Hz, 1H), 7.60 (d, J=7.9Hz, 1H), 7.50 (d, J=8.3Hz, 1H), 7.33 (dt, J=8.5,2.3Hz, 2H), 7.01- 6.87 (m, 1H), 6.82 (d, J=7.9Hz, 1H), 4.37 (dd, J=9.4,8.1Hz, 1H), 4.21-4.09 (m, 1H), 4.04 (t, J=8.1Hz, 1H), 2.33 (s, 3H), 1.82 (dd, J=13.4,6.7Hz, 1H), 1.03 (d, J=6.7Hz, 3H), 0.94 (d, J=6.7Hz, 3H)13C NMR(101MHz,CDCl3):δ191.3,162.5,146.0,144.7,142.7,134.5, 131.3,130.3,122.6,121.6,120.2,118.1,117.9,115.2,73.2,69.3,33.1,22.1,18.9, 18.6.HRMS(EI)calculated for[C20H22N2O2]+requires m/z 322.1681,found m/z 322.1677.
B) the compound B of the oxazolines of An containing Ya amine preparation
Example B1：Ya An oxazoline amine B1 preparation
2,6- diisopropyl anilines (1.3370g, 7.5mmol, 1.2equiv) and A1 (2.0538g, 5.8mmol, 1.0equiv) it is dissolved in 12mL toluene, p-methyl benzenesulfonic acid (0.0998g, 0.58mmol, 10mol%) catalysis, reacts 48h, ethanol It is recrystallized to give 1.9978g (3.9mmol, 67%) B1.
1H NMR(400MHz,CDCl3):δ 10.81 (s, 1H), 8.44 (s, 1H), 8.06 (d, J=8.0Hz, 1H), 7.75 (d, J=8.0Hz, 1H), 7.47 (d, J=5.6Hz, 2H), 7.29-7.15 (m, 5H), 7.15-7.01 (m, 6H), 6.77 (t, J =7.5Hz, 1H), 4.52-4.41 (m, 1H), 4.16 (t, J=8.8Hz, 1H), 3.98 (t, J=7.7Hz, 1H), 3.02-2.89 (m, 3H), 2.51 (dd, J=13.6,9.2Hz, 1H), 1.19-1.01 (m, 12H)13C NMR(101MHz,CDCl3):δ 163.8,160.7,149.6,146.0,142.5,137.9,137.7,131.9,131.9,130.1,129.9,129.2, 129.0,128.4,126.4,124.0,123.9,123.6,122.9,118.0,114.8,112.0,70.3,67.9,41.7, 27.9,23.5,23.5.HRMS(EI)calculated for[C35H37N3O]+requires m/z 515.2937,found m/ z 515.2937.
Example B2：Ya An oxazoline amine B2 preparation
2,6- diisopropyl anilines (1.1525g, 6.5mmol, 1.3equiv) and A2 (1.5420g, 5mmol, 1.0equiv) it is dissolved in 15mL toluene, p-methyl benzenesulfonic acid (0.0430g, 0.25mmol, 5mol%) catalysis, reacts 48h, ethanol It is recrystallized to give 1.3431g (2.9mmol, 57%) B2.
1H NMR(400MHz,CDCl3):δ 10.73 (s, 1H), 8.45 (s, 1H), 8.13 (d, J=7.5Hz, 1H), 7.75 (dd, J=7.9,1.4Hz, 1H), 7.51-7.41 (m, 2H), 7.30-7.16 (m, 2H), 7.15-6.98 (m, 4H), 6.76 (t, J =7.5Hz, 1H), 4.30-4.18 (m, 1H), 4.07-3.94 (m, 2H), 3.02-2.88 (m, 2H), 1.72-1.60 (td, J= 13.1,6.6Hz, 1H), 1.09 (t, J=6.4Hz, 12H), 0.84 (d, J=6.8Hz, 3H), 0.75 (d, J=6.8Hz, 3H) .13C NMR(101MHz,CDCl3):δ163.3,160.4,149.6,146.3,142.4,137.7,132.0,131.8,130.0, 129.6,129.4,124.5,124.0,123.9,122.9,117.7,114.4,111.7,72.5,68.5,32.6,27.9, 23.5,23.4,18.9,17.9.HRMS(EI)calculated for[C31H37N3O]+requires m/z 467.2937, found m/z 467.2934.
Example B3：Ya An oxazoline amine B3 preparation
2,6- diisopropyl anilines (3.5460g, 20mmol, 1.3equiv) and A3 (5.3179g, 15.5mmol, 1.0equiv) it is dissolved in 30mL toluene, p-methyl benzenesulfonic acid (0.2580g, 1.5mmol, 10mol%) catalysis, reacts 48h, ethanol It is recrystallized to give 5.9603g (11.8mmol, 76%) B3.
1H NMR(400MHz,CDCl3):δ 10.74 (s, 1H), 8.40 (s, 1H), 8.05 (d, J=7.6Hz, 1H), 7.85 (d, J=7.6Hz, 1H), 7.45 (d, J=4.0Hz, 2H), 7.30-7.20 (m, 3H), 7.15 (s, 4H), 7.10-7.02 (m, 4H), 6.80 (t, J=7.5Hz, 1H), 5.39-5.27 (m, 1H), 4.69-4.59 (m, 1H), 4.08 (t, J=8.0Hz, 1H), 2.88 (dt, J=13.6,6.8Hz, 2H), 1.04 (d, J=6.8Hz, 6H), 0.98 (d, J=6.8Hz, 6H)13C NMR (101MHz,CDCl3):δ164.8,160.6,149.7,146.5,142.4,137.7,132.3,132.0,130.4,129.8, 129.4,128.7,127.5,126.4,124.5,124.1,123.9,123.0,118.0,114.9,111.7,73.4,70.1, 27.9,23.5,23.4；HRMS(EI)calculated for[C34H35N3O]+requires m/z 501.2780,found m/ z 501.2777.
Example B4：Ya An oxazoline amine B4 preparation
2,6- diisopropyl anilines (1.1525g, 6.5mmol, 1.3equiv) and A4 (1.6120g, 5mmol, 1.0equiv) it is dissolved in 10mL toluene, p-methyl benzenesulfonic acid (0.043g, 0.25mmol, 5mol%) catalysis, reacts 48h, ethanol weight Crystallization obtains 1.7256g (3.6mmol, 71%) B4.
1H NMR(400MHz,CDCl3):δ 10.63 (s, 1H), 8.46 (s, 1H), 8.17 (dd, J=7.8,1.4Hz, 1H), 7.75 (dd, J=8.0,1.6Hz, 1H), 7.53-7.44 (m, 1H), 7.39 (d, J=7.6Hz, 1H), 7.27 (t, J=7.4Hz, 1H), 7.23-7.17 (m, 1H), 7.13-7.02 (m, 3H), 6.93 (d, J=8.0Hz, 1H), 6.78-6.72 (m, 1H), 4.19 (dd, J=10.0,8.8Hz, 1H), 4.15-4.05 (m, 1H), 3.99 (dd, J=10.0,7.6Hz, 1H), 3.01-2.88 (m, 2H), 1.08 (t, J=6.8Hz, 12H), 0.79 (s, 9H)13C NMR(101MHz,CDCl3):δ163.5,160.3,149.6, 146.8,142.5,137.7,132.2,132.0,130.4,130.0,129.1,125.3,124.5,124.1,122.9, 117.7,114.3,111.5,76.2,67.2,33.9,27.9,25.8,23.6,23.5.HRMS(EI)calculated for [C32H39N3O]+requires m/z 481.3093,found m/z 481.3098.
Example B5：Ya An oxazoline amine B5 preparation
P-trifluoromethylaniline (3.2222g, 20mmol, 1.3equiv) and A3 (5.3179g, 15.5mmol, 1.0equiv) it is dissolved in 30mL toluene, p-methyl benzenesulfonic acid (0.2580g, 1.5mmol, 10mol%) catalysis, reacts 48h, ethanol It is recrystallized to give 5.7254g (11.8mmol, 76%) B5.
1H NMR(400MHz,CDCl3) δ 11.21 (s, 1H), 8.59 (s, 1H), 7.89 (dd, J=16.2,7.8Hz, 2H), 7.53 (d, J=8.2Hz, 1H), 7.39 (dd, J=10.2,6.5Hz, 4H), 7.34 (dd, J=11.2,4.1Hz, 1H), 7.27- 7.15 (m, 5H), 7.08 (t, J=7.4Hz, 1H), 6.98 (d, J=8.2Hz, 2H), 6.91 (t, J=7.4Hz, 1H), 5.38 (dd, J=9.8,8.4Hz, 1H), 4.68 (dd, J=9.9,8.5Hz, 1H), 4.13 (t, J=8.3Hz, 1H)13C NMR (101MHz,CDCl3):δ160.5,155.9,151.5,150.4,147.6,143.4,132.8,131.9,128.6,128.4, 128.3,128.1,128.1,125.6,125.5,125.2,124.9,124.7,123.1,119.8,119.5,119.1, 118.3,74.7,72.4.HRMS(EI)calculated for[C29H22F3N3O]+requires m/z 485.1715,found m/z 485.1720.
Example B6：Ya An oxazoline amine B6 preparation
P-nethoxyaniline (2.4640g, 20mmol, 1.3equiv) and A3 (5.3179g, 15.5mmol, 1.0equiv) It is dissolved in 30mL toluene, p-methyl benzenesulfonic acid (0.2580g, 1.5mmol, 10mol%) catalysis, reacts 48h, ethyl alcohol recrystallization obtains 5.0006g (11.2mmol, 72%) B6.
1H NMR (400MHz, CDCl3) δ 11.10 (s, 1H), 8.67 (d, J=3.2Hz, 1H), 8.02-7.80 (m, 2H), 7.47 (d, J=8.2Hz, 1H), 7.39-7.28 (m, 3H), 7.29-7.19 (m, 5H), 7.14-6.99 (m, 3H), 6.87 (qd, J =5.4,2.4Hz, 1H), 6.73 (dd, J=9.0,2.6Hz, 2H), 5.41 (dd, J=9.9,8.3Hz, 1H), 4.68 (dd, J= 9.8,8.5Hz, 1H), 4.14 (td, J=8.3,1.5Hz, 1H), 3.77 (d, J=1.1Hz, 3H)13C NMR(101MHz, CDCl3):δ160.5,158.9,155.9,150.3,147.6,143.4,140.9,132.6,131.9,128.6,128.4, 128.1,125.6,125.5,124.9,123.1,120.9,119.8,119.5,119.1,118.3,115.1,74.7,72.4, 56.1.HRMS(EI)calculated for[C29H25N3O2]+requires m/z 447.1947,found m/z 447.1956.
Example B7：Ya An oxazoline amine B7 preparation
2,6- diisopropyl anilines (1.1525g, 6.5mmol, 1.3equiv) and A5 (1.7140g, 5mmol, 1.0equiv) it is dissolved in 10mL toluene, p-methyl benzenesulfonic acid (0.043g, 0.25mmol, 5mol%) catalysis, reacts 48h, ethanol weight Crystallization obtains 1.8043g (3.6mmol, 71%) B7.
1H NMR(400MHz,CDCl3):δ 10.65 (s, 1H), 8.31 (s, 1H), 8.05 (d, J=2.3Hz, 1H), 7.68 (dd, J=7.9,1.5Hz, 1H), 7.35-7.26 (m, 2H), 7.18-7.11 (m, 1H), 7.06-6.85 (m, 4H), 6.75- 6.63 (m, 1H), 4.22-4.04 (m, 1H), 3.99-3.79 (m, 2H), 2.93-2.70 (m, 2H), 1.54 (ddd, J=16.0, 13.2,6.6Hz, 1H), 1.01 (t, J=6.6Hz, 12H), 0.74 (d, J=6.8Hz, 3H), 0.66 (d, J=6.7Hz, 3H) .13C NMR(101MHz,CDCl3):δ162.3,158.0,148.1,145.0,139.9,136.5,131.4,130.9,130.8, 130.0,129.0,128.4,127.6,124.9,123.2,121.9,121.7,117.5,117.0,113.1,110.7,71.4, 67.5,31.6,26.9,22.4,22.4,17.8,16.8.HRMS(EI)calculated for[C30H33ClN3O]+requires m/z 501.2547,found m/z 501.2543.
Example B8：Ya An oxazoline amine B8 preparation
2,6- diisopropyl anilines (1.1525g, 6.5mmol, 1.3equiv) and A6 (1.6320g, 5mmol, 1.0equiv) it is dissolved in 10mL toluene, p-methyl benzenesulfonic acid (0.043g, 0.25mmol, 5mol%) catalysis, reacts 48h, ethanol weight Crystallization obtains 1.6490g (3.4mmol, 68%) B7.
1H NMR(400MHz,CDCl3):δ 11.09 (s, 1H), 8.38 (s, 1H), 7.93 (dd, J=8.7,6.8Hz, 1H), 7.80 (dd, J=7.9,1.4Hz, 1H), 7.37-7.22 (m, 1H), 7.20-7.01 (m, 5H), 6.95-6.86 (m, 1H), 6.81 (qd, J=8.7,3.4Hz, 1H), 4.26-4.15 (m, 1H), 4.03-3.95 (m, 1H), 2.95 (tt, J=13.6,6.9Hz, 2H), 1.11 (dd, J=6.8,4.9Hz, 12H), 0.79 (d, J=6.8Hz, 3H), 0.70 (d, J=6.8Hz, 3H)13C NMR (101MHz,CDCl3):δ163.0,160.0,149.4,144.9,144.1,137.8,132.5,132.5,131.78,130.3, 124.0,122.9,122.8,119.5,118.5,116.4,114.1,109.7,109.7,107.9,107.7,72.4,68.6, 32.4,27.9,23.5,23.5,18.8,17.6.HRMS(EI)calculated for[C30H33FN3O]+requires m/z 485.2842,found m/z485.2838.
Example B9：Ya An oxazoline amine B9 preparation
2,6- diisopropyl anilines (1.1525g, 6.5mmol, 1.3equiv) and A7 (1.6120g, 5mmol, 1.0equiv) it is dissolved in 10mL toluene, p-methyl benzenesulfonic acid (0.043g, 0.25mmol, 5mol%) catalysis, reacts 48h, ethanol weight Crystallization obtains 1.6354g (3.4mmol, 68%) B9.
1H NMR(400MHz,CDCl3):δ 10.65 (s, 1H), 8.39 (s, 1H), 8.03 (d, J=7.9Hz, 1H), 7.75 (dd, J=7.9,1.6Hz, 1H), 7.23-7.18 (m, 1H), 7.13-6.98 (m, 6H), 6.80 (t, J=7.7Hz, 1H), 6.77-6.71 (m, 1H), 4.23 (tt, J=8.1,3.9Hz, 1H), 4.00 (dq, J=10.3,7.6Hz, 2H), 3.02-2.86 (m, 2H), 1.08 (dd, J=6.6,6.1Hz, 12H), 0.85 (d, J=6.8Hz, 3H), 0.76 (d, J=6.7Hz, 3H)13C NMR(101MHz,CDCl3):δ163.4,160.2,149.7,146.4,142.7,142.3,137.7,132.5,131.8, 130.0,129.2,127.2,125.1,125.0,123.8,122.8,122.8,118.5,117.6,114.4,111.6,72.5, 68.5,32.7,27.9,23.5,23.4,21.6,18.9,17.9.HRMS(EI)calculated for[C31H36N3O]+ requires m/z 481.3093,found m/z481.3096.
C the ketone of the compound B4 of) Ya An oxazoline amines and cobaltous dichloride complexes ira situ catalysis and triethoxysilane Silicon hydrogenation
At room temperature, the addition compound cobaltous dichloride (0.10mmol) in a reaction tube dried, B4 (0.16mmol), Dichloromethane (1.0mL), is stirred at room temperature 2 hours, adds ketone (1.0mmol) afterwards, triethoxysilane (2.0mmol), and three Ethyl sodium borohydride (0.10mmol), then it is stirred at room temperature 12 hours, it is rear to add saturation K2CO3/MeOH, stir at room temperature Column chromatography for separation obtains product after mixing 2 hours.
Example C1：(R) the bromo- α-methylbenzylalcohols of -4-
Oily liquids, 89% yield, [α]20 D=+38.8 (c 1.33, CHCl3), 97.2%ee determined by HPLC,HPLC conditions:Chiralcel AS-H, n-hexane/i-PrOH=98/2,1.0mL/min, n=220nm, tr 16.0(major),16.9(minor)；1H NMR(400MHz,CDCl3):δ 7.46 (d, J=8.4Hz, 2H), 7.24 (d, J =8.4Hz, 2H), 4.85 (q, J=6.0Hz, 1H), 1.96 (s, 1H), 1.46 (d, J=6.4Hz, 3H)
Example C2：(R)-alpha-methyl-2-naphthalene methanol
White solid, 97% yield, [α]20 D=+37.7 (c 1.03, CHCl3), 97.6%ee determined by HPLC,HPLC conditions:Chiralcel AS-H, n-hexane/i-PrOH=98/2,1.0mL/min, n=220nm, tr 21.2(major),24.9(minor)；1H NMR(400MHz,CDCl3):δ7.96–7.75(m,4H),7.63–7.40(m, 3H), 5.12-4.99 (m, 1H), 1.99 (d, J=2.4Hz, 1H), 1.57 (d, J=6.4Hz, 3H)
D the compound B4 of) Ya An oxazoline amines and the ketone of cobaltous dichloride complexes ira situ catalysis and the boron of pinacol borine Hydrogenation
At room temperature, the addition compound cobaltous dichloride (0.10mmol) in a reaction tube dried, B4 (0.16mmol), Ether (1.0mL), it is stirred at room temperature 2 hours, adds ketone (1.0mmol), pinacol borine (2.0mmol), boron triethyl afterwards Sodium hydride (0.10mmol), column chromatography for separation obtains product after being then stirred at room temperature 12 hours.
Example D1：(R)-α-methylbenzylalcohol
Oily liquids, 82% yield, 98.1%ee；1H NMR(400MHz,CDCl3)δ7.58–7.05(m,5H),4.89 (d, J=6.5Hz, 1H), 1.88 (s, 1H), 1.49 (d, J=6.5Hz, 3H)
Example D2：(R) -4- the tert-butyl groups-α-methylbenzylalcohol
Oily liquids, 88% yield, 97.6%ee；1H NMR(400MHz,CDCl3) δ 7.34-7.20 (d, J=8.0Hz, 2H), 7.13 (d, J=8.0Hz, 2H), 4.88 (m, 1H), 2.46 (d, J=6.1Hz, 2H), 1.85 (m, 1H), 1.72 (s, 1H), 1.50 (d, J=6.4Hz, 3H), 0.90 (d, J=6.6Hz, 6H)
E the alkene of the compound B4 of) Ya An oxazoline amines and cobaltous dichloride complexes ira situ catalysis and pinacol borine Hydroboration
At room temperature, the addition compound cobaltous dichloride (0.10mmol) in a reaction tube dried, B4 (0.16mmol), Ether (1.0mL), it is stirred at room temperature 2 hours, adds alkene (1.0mmol), pinacol borine (2.0mmol), triethyl group afterwards Sodium borohydride (0.10mmol), column chromatography for separation obtains product after being then stirred at room temperature 12 hours.
Example E1：(S)-(+) -4,4,5,5- tetramethyls -2- (2- phenylpropyls) -1,3,2- dioxy boron pentanes
Oily liquids, 98% yield, [α]20 D=+21.9 (c 1.0, CHCl3), 96.1%ee, HPLC conditions: Chiralcel OD-H, n-hexane/i-PrOH=99/1,0.25mL/min, n=254nm, tr 16.7(minor),18.0 (major)；IR(neat):2978,1453,1370,1323,1146cm-1；1H NMR(CDCl3,400MHz):δ7.28-7.21 (m, 4H), 7.16-7.11 (m, 1H), 3.08-2.98 (m, 1H), 1.27 (d, J=6.8Hz, 3H), 1.17-1.13 (m, 14H)；13C NMR(CDCl3,100MHz):δ149.1,128.1,126.5,125.6,82.8,35.7,24.8,24.7,24.6.11B NMR (CDCl3,128MHz):δ33.7；HRMS(EI)calculated for[C15H23BO2]+requires m/z 246.1791, found m/z 246.1791.
Example E2：(S)-(+) -4,4,5,5- tetramethyls -2- (2- (4- methylphenyls)-propyl group) -1,3,2- dioxies boron penta Alkane
Oily liquids, 93% yield, [α]20 D=+24.9 (c 0.97, CHCl3), 98.3%ee；1H NMR(CDCl3, 400MHz):δ 7.05 (d, J=8.4Hz, 2H), 6.99 (d, J=8.4Hz, 2H), 2.97-2.87 (m, 1H), 2.22 (s, 3H), 1.18 (d, J=6.8Hz, 3H), 1.10-1.03 (m, 14H)；13C NMR:(100.6MHz,CDCl3):δ146.2,134.9, 128.8,126.4,82.9,35.3,24.8,24.7,24.6,21.4,20.9；11B NMR(CDCl3,128MHz):δ33.7； HRMS(EI)calculated for[C16H25BO2]+requires m/z 260.1948,found m/z 260.1951.
Listed above is only some specific embodiments of the present invention, it is clear that the invention is not restricted to above example, may be used also To have many deformations, all changes that one of ordinary skill in the art directly can export or associate from present disclosure Shape, it is considered as protection scope of the present invention.

Claims (9)

1. a kind of compound of the sub- amine oxazoline amine of chirality, it is characterised in that described compound is high optically pure, structure Formula such as following formula (1)
Wherein, R1C1-C12- alkyl that is unsubstituted or being substituted by 1-2 C1-C4- alkoxy, or it is unsubstituted or The cyclopenta or cyclohexyl substituted by 1-3 C1-C4- alkyl or C1-C4- alkoxies, or it is unsubstituted or individual by 1-4 Benzyl, phenyl or the naphthalene of C1-C4- alkyl, C1-C4- alkoxies, C1-C4- fluoroalkyls or C1-C4- Fluoroalkyloxies, F or Cl substitutions Base；
R2H or C1-C12- alkyl that is unsubstituted or being substituted by 1-2 C1-C4- alkoxy, or it is unsubstituted or by 1-3 C1-C4- alkyl or the cyclopenta or cyclohexyl of the substitution of C1-C4- alkoxies, or it is unsubstituted or by 1-3 C1- The phenyl or naphthyl of C4- alkyl, C1-C4- alkoxies, C1-C4- fluoroalkyls or C1-C4- Fluoroalkyloxies, F or Cl substitutions；
R3, R4, R5, R6, R7, R8, R9, R10It is H or unsubstituted C1-C12- alkyl, C1-C4- Fluoroalkyloxies, F or Cl, or Cyclopenta or cyclohexyl, nitro unsubstituted or substituted by 1-3 C1-C4- alkyl or C1-C4- alkoxies；
R11It is H or C1-C12- alkyl that is unsubstituted or being substituted by 1-2 C1-C4- alkoxy, or it is unsubstituted Or the cyclopenta or cyclohexyl substituted by 1-3 C1-C4- alkyl or C1-C4- alkoxies, or it is unsubstituted or individual by 1-3 Benzyl, phenyl or the naphthalene of C1-C4- alkyl, C1-C4- alkoxies, C1-C4- fluoroalkyls or C1-C4- Fluoroalkyloxies, F or Cl substitutions Base；
R12, R13It is H or C1-C12- alkyl that is unsubstituted or being substituted by 1-2 C1-C4- alkoxy, or it is unsubstituted Or the cyclopenta or cyclohexyl that are substituted by 1-3 C1-C4- alkyl or C1-C4- alkoxies, it is or unsubstituted or by 1-3 Individual C1-C4- alkyl, C1-C4- alkoxies, C1-C4- fluoroalkyls or C1-C4- Fluoroalkyloxies, F or Cl substitution benzyl, phenyl or Naphthyl；
R14It is C1-C12- alkyl that is unsubstituted or being substituted by 1-2 C1-C4- alkoxy, or it is unsubstituted or by 1- 3 C1-C4- alkyl or the cyclopenta or cyclohexyl of the substitution of C1-C4- alkoxies, or it is unsubstituted or by 1-3 C1-C4- Benzyl, the phenyl or naphthyl of alkyl, C1-C4- alkoxies, C1-C4- fluoroalkyls or C1-C4- Fluoroalkyloxies, F or Cl substitutions；* generation Table asymmetric carbon atom.
A kind of 2. compound of chiral Ya An oxazoline amines according to claim 1, it is characterised in that described R1It is excellent Elect C1-C12- alkyl that is unsubstituted or being substituted by 1-2 C1-C4- alkoxy as, or it is unsubstituted or individual by 1-4 Benzyl, phenyl or the naphthalene of C1-C4- alkyl, C1-C4- alkoxies, C1-C4- fluoroalkyls or C1-C4- Fluoroalkyloxies, F or Cl substitutions Base；
Described R2Preferably hydrogen, or C1-C12- alkyl that is unsubstituted or being substituted by 1-2 C1-C4- alkoxy, or It is unsubstituted or by 1-3 C1-C4- alkyl, C1-C4- alkoxies, C1-C4- fluoroalkyls or C1-C4- Fluoroalkyloxies, F or Cl Substituted phenyl or naphthyl；
Described R3-R10Preferably hydrogen, or unsubstituted C1-C12- alkyl；
Described R11Preferably hydrogen, or C1-C12- alkyl that is unsubstituted or being substituted by 1-2 C1-C4- alkoxy, or Be it is unsubstituted or by 1-3 C1-C4- alkyl, C1-C4- alkoxies, C1-C4- fluoroalkyls or C1-C4- Fluoroalkyloxies, F or The phenyl of Cl substitutions；
Described R12, R13Preferably hydrogen or C1-C12- alkyl that is unsubstituted or being substituted by 1-2 C1-C4- alkoxy, It is or unsubstituted or by 1-3 C1-C4- alkyl, C1-C4- alkoxies, C1-C4- fluoroalkyls or C1-C4- Fluoroalkyloxies, F Or the phenyl of Cl substitutions；
R14C1-C12- alkyl that is preferably unsubstituted or being substituted by 1-2 C1-C4- alkoxy, or it is unsubstituted or The benzyl that is substituted by 1-3 C1-C4- alkyl, C1-C4- alkoxies, C1-C4- fluoroalkyls or C1-C4- Fluoroalkyloxies, F or Cl, Phenyl or naphthyl.
3. a kind of compounds process for production thereof according to claim 1 or 2, it is characterised in that described method includes following step Suddenly：
A), formula (2) 2- oxazolinyl amineWith formula (3)
Halides are reacted, to form formula (4)
Wherein R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, * is for example defined in claim 1, X F, Cl, Br, I；
B), formula (4) and formula (5) R1-NH2(5) amine reacts, wherein R1As defined in claim 1, to form formula (1), i.e. right will Seek the compound described in 1.
4. preparation method according to claim 3, it is characterised in that described step (a) is in organophosphorus ligand or nitrogen In the presence of part, using transition metal Ru, Rh, Pd, Ir, Cu inorganic salts as metallic catalyst, the coupling reaction of catalysis.
5. preparation method according to claim 3, it is characterised in that the solvent of participation reaction is in described step (a) Organic solvent, is polarity or non-polar solven, and described organic solvent is benzene, carbon tetrachloride, petroleum ether, tetrahydrofuran, diformazan Base formamide, ether, dichloromethane, chloroform, toluene, dimethylbenzene, hexamethylene, n-hexane, normal heptane, dioxane, second Any one in nitrile.
6. preparation method according to claim 3, it is characterised in that in described step (a), reaction temperature be 30 DEG C extremely 200 DEG C, the reaction time is 30 minutes to 48 hours.
7. preparation method according to claim 4, it is characterised in that in described step (a), formula (2)：Formula (3)：Metal Catalyst：Part material ratio is 1-5:0.01-1:0.02-2：0.02-2.
8. a kind of compound by described in claim 1 and transition metal M XnComplexes ira situ is used to pass through asymmetric catalytic reaction system The method of standby chiral organic compound, it is characterised in that described at least one claim 1 of the described method in catalytic amount Formula (1) and at least one transition metal M XnIn the presence of carry out, wherein,
M is transition metal Co；
X is F, Cl, Br, I, OCOH, OCOCH3、OCOCH2CH3、OSO2CH3、OSO2CF3In any one；
N is X number, is 1,2,3.
9. the method according to claim 8 for preparing chiral organic compound, it is characterised in that described preparation chirality has The method of machine compound in the presence of a catalyst, by the carbon-carbon double bond of prochiral organic compounds or heteroatoms double bond Asymmetric silicon hydrogenation or hydroboration are carried out to realize, i.e., the hydrogenation of described asymmetric silicon or hydroboration addition in catalytic amount at least Carried out in the presence of a kind of Formula (1) and at least one transition metal M Xn.
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