CN105693647A - Chiral compounds containing imine oxazoline amine and preparing method thereof - Google Patents

Chiral compounds containing imine oxazoline amine and preparing method thereof Download PDF

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CN105693647A
CN105693647A CN201610016368.6A CN201610016368A CN105693647A CN 105693647 A CN105693647 A CN 105693647A CN 201610016368 A CN201610016368 A CN 201610016368A CN 105693647 A CN105693647 A CN 105693647A
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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
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
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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
    • B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
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    • C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
    • C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
    • C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
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    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
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    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • 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
    • B01J2231/341—1,2-additions, e.g. aldol or Knoevenagel condensations
    • B01J2231/342—Aldol type reactions, i.e. nucleophilic addition of C-H acidic compounds, their R3Si- or metal complex analogues, to aldehydes or ketones
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    • B01J2531/0261—Complexes comprising ligands with non-tetrahedral chirality
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Abstract

The invention discloses chiral compounds containing imine oxazoline amine and a preparing method thereof, wherein an oxazoline aryl group and an imine aryl group are connected through N atoms on the amine.The invention further discloses application of the compounds complexing with metal to serve as a catalyst to an asymmetric synthesis reaction, particularly hydrosilation and hydroboration reactions of prochiral organic compounds containing a carbon/heteroatom double bond and a carbon-carbon atom double bond.

Description

A kind of chirality compound containing glyoxalin quinoline amine and preparation method thereof
Technical field
The present invention relates to compound containing glyoxalin quinoline amine of synthesis and preparation method thereof, and this compound and metal catalysis altogether contain the purposes in the hydrosilation of the prochiral organic compounds of carbon/hetero atom double bond and carbon carbon atom double bond and hydroboration。
Background technology
The asymmetric reaction of transient metal complex catalysis obtains the extensive concern of academia and industrial quarters in world wide, wherein for the research of central metal institute linking ligand also widely, wherein bis-oxazoline (Box) part is that research is more, within 1989, Nishiyama reports first case pyridine bis-oxazoline part [Nishiyama, H.；Sakaguchi, H.；Nakamura, T.；Horihata, M.；Kondo, M.；Itoh, K.Organometallics1989,8,846.], pyridine bis-oxazoline part plays very big concern [(a) DalitRechaviandMarcLemaire.Chem.Rev. subsequently, 2002,102 (10), pp3467 3494. (b) GiovanniDesimoni, GiuseppeFaita, andPaoloQuadrelli.Chem.Rev., 2003,103 (8), pp3119 3154], this part is improved by some researcheres, has derived some new azoles quinoline parts。2002; PatrickJ.Guiry reported first bis-oxazoline phenyl amine part; in a series of asymmetric catalysis such as this type of part is successfully applied to asymmetric Nozaki Hiyama allylation reaction afterwards, and henry reacts, the Michael addition reaction of friedel-crafts acylation and 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), 3,712 3715；(d) Org.Lett., 2007,9 (23), 4,725 4728]。
On the other hand, BuschandStoufer in 1956 et al. first time reports pyridine diimine, and structure obtains confirmation [(a) Stoufer, R.C. subsequently；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 forms catalyst with cheap metal (Fe, Co, Ni) coordination, being widely used in the polyreaction of alkene, the coordination compound of other transition metal also is synthesized out in succession, in catalysis organic reaction。Based on the superior catalytic activity shown after imine ligand and metal complex, the present invention has synthesized the compound of a kind of chiral imines azoles quinoline amine, and transition metal asymmetry catalysis is significant。
Summary of the invention
The invention discloses compound of a kind of synthesis of chiral glyoxalin quinoline amine and preparation method thereof, described azoles quinoline aryl is connected by atom N on amine with imines aryl, and these compounds and metal complex as catalyst in asymmetric synthesis, the purposes in the hydrosilation containing carbon/hetero atom double bond and the prochiral organic compounds of carbon carbon atom double bond and hydroboration especially。
The present invention is achieved through the following technical solutions:
The compound of a kind of chiral imines azoles quinoline amine, described compound is high optically pure, structural formula such as following formula (1)
Wherein, R1It it is C1-C12-alkyl that is unsubstituted or that replaced by 1-2 C1-C4-alkoxyl, or unsubstituted or that replaced by 1-3 C1-C4-alkyl or C1-C4-alkoxyl cyclopenta or cyclohexyl, or unsubstituted or by 1-4 C1-C4-alkyl, C1-C4-alkoxyl, C1-C4-fluoroalkyl or C1-C4-Fluoroalkyloxy, the benzyl of F or Cl replacement, phenyl or naphthyl；
R2It is H or C1-C12-alkyl that is unsubstituted or that replaced by 1-2 C1-C4-alkoxyl, or unsubstituted or that replaced by 1-3 C1-C4-alkyl or C1-C4-alkoxyl cyclopenta or cyclohexyl, or unsubstituted or by 1-3 C1-C4-alkyl, C1-C4-alkoxyl, C1-C4-fluoroalkyl or C1-C4-Fluoroalkyloxy, F or Cl replacement phenyl or naphthyl；
R3, R4, R5, R6, R7, R8, R9, R10It is H or unsubstituted C1-C12-alkyl, C1-C4-Fluoroalkyloxy, F or Cl, or cyclopenta that is unsubstituted or that replaced by 1-3 C1-C4-alkyl or C1-C4-alkoxyl or cyclohexyl, nitro；
R11It is H or C1-C12-alkyl that is unsubstituted or that replaced by 1-2 C1-C4-alkoxyl, or unsubstituted or that replaced by 1-3 C1-C4-alkyl or C1-C4-alkoxyl cyclopenta or cyclohexyl, or unsubstituted or by 1-3 C1-C4-alkyl, C1-C4-alkoxyl, C1-C4-fluoroalkyl or C1-C4-Fluoroalkyloxy, the benzyl of F or Cl replacement, phenyl or naphthyl；
R12, R13It is H or C1-C12-alkyl that is unsubstituted or that replaced by 1-2 C1-C4-alkoxyl, or unsubstituted or that replaced by 1-3 C1-C4-alkyl or C1-C4-alkoxyl cyclopenta or cyclohexyl, or unsubstituted or by 1-3 C1-C4-alkyl, C1-C4-alkoxyl, C1-C4-fluoroalkyl or C1-C4-Fluoroalkyloxy, the benzyl of F or Cl replacement, phenyl or naphthyl；
R14It it is C1-C12-alkyl that is unsubstituted or that replaced by 1-2 C1-C4-alkoxyl, or unsubstituted or that replaced by 1-3 C1-C4-alkyl or C1-C4-alkoxyl cyclopenta or cyclohexyl, or unsubstituted or by 1-3 C1-C4-alkyl, C1-C4-alkoxyl, C1-C4-fluoroalkyl or C1-C4-Fluoroalkyloxy, the benzyl of F or Cl replacement, phenyl or naphthyl；* chiral carbon atom is represented。
As improving further, described R1It is preferably alkyl or aryl, described R2It is preferably hydrogen, alkyl or aryl, described R3-R10It is preferably hydrogen, alkyl, described R11It is preferably hydrogen, alkyl or aryl, described R12, R13It is preferably hydrogen, alkyl or aryl, R14It is preferably alkyl or aryl。
The preparation method that the invention also discloses the compound of a kind of chiral imines azoles quinoline amine, described method comprises the steps of
A), formula (2) 2-azoles quinoline base amineWith formula (3)
Halides is reacted, to form formula (4)
Wherein R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, * such as claim 1 defines, and X is F, Cl, Br, I；
B), formula (4) and formula (5) R1-NH2(5) amine reaction, wherein R1As defined above, to produce above-claimed cpd formula (1)。
As improving further, step (a) of the present invention is the coupling reaction of transition metal Ru, Rh, Pd, Ir, Cu inorganic salt and organophosphorus ligand, aminophosphine ligand catalysis。
As improving further, the solvent participating in reaction in step (a) of the present invention is organic solvent, being polarity or non-polar solven, described organic solvent is any one in benzene, carbon tetrachloride, petroleum ether, oxolane, dimethylformamide, ether, dichloromethane, chloroform, toluene, dimethylbenzene, hexamethylene, normal hexane, normal heptane, dioxane, acetonitrile。
As improving further, in step (a) of the present invention, reaction temperature 300C to 2000C, the response time is 30 minutes to 48 hours。
As improving further, in step (a) of the present invention, formula (2): formula (3): metallic catalyst: part material ratio is 1-5:0.01-1:0.02-2:0.02-2。
The invention also discloses a kind of by the compound described in claim 1 and transition metal M XnComplexes ira situ is for the method for preparing chiral organic compound by asymmetric catalytic reaction, it is characterised in that described method is at least one Formula (1) of catalytic amount and at least one transition metal M XnCarry out under existence, wherein,
Catalytic amount refers to the consumption of 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 any one in the anion (carbonate, formate, acetate, propionate, pyrovinic acid root, trichloromethyl sulfonate radical, phenylbenzimidazole sulfonic acid root, tosylate) of halogenide (F, Cl, Br, I), pseudohalide (cyanide, cyanic acid, salt, isocyanates), carboxylic acid, sulfonic acid, phosphonic acids；
N is the number of X, is 1,2,3。
As improving further, the described method preparing chiral organic compound is in the presence of a catalyst, realizing by carrying out asymmetric hydrosilation or hydroboration in the carbon carbon atom double bond of prochiral organic compounds or heteroatoms double bond, namely described asymmetric hydrosilation or hydroboration addition are at least one Formula (1) of catalytic amount and at least one transition metal M XnCarry out under existence。
Beneficial effects of the present invention is as follows:
The invention provides a kind of novel chiral compound containing glyoxalin quinoline amine。
Present invention also offers an efficient synthetic route, two step gross production rates can reach 60%。
The chirality of the present invention compound containing glyoxalin quinoline amine and transition metal M XnComplexes ira situ thing is the outstanding catalyst for asymmetric synthesis (such as the asymmetric hydrogenation effect of prochirality, unsaturated, organic compound) or catalyst precarsor。Current chiral, unsaturated, organic compound are used, and highly excessive optical isomer can be introduced in the synthesis of organic compound, and can obtain high chemical conversion rate。
The present invention also provides for the chirality of the present invention compound containing glyoxalin quinoline amine and transition metal M XnComplexes ira situ thing is as the purposes of homogeneous catalyst, and catalyst by carrying out hydrosilation or hydroborated asymmetric addition for preparing chiral organic compound in the heteroatoms double bond and carbon carbon atom double bond of prochiral organic compounds, and ee value can reach > 90%。
For the organic compound that the preferred prochirality of hydrosilation or hydoboration, unsaturated compound can be open chain or the rings comprising C=C, C=N and/or C=O base, wherein C=C, C=N and C=0 group can be a part or the outer base of ring of loop systems。This 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 α, β-one acetal thereof or ketal, ester and amide, ketimide, ketoxime and ketone hydrazone。
Can chiral organic compound prepared in accordance with the present invention be active substance or for preparing the intermedium of this material, particularly spice and fumet, pharmaceutical preparation, agricultural chemicals production in。
Detailed description of the invention
The invention provides a kind of formula (1) compound, described compound is high optically pure,
R1, R2, R3, R4, R5, R6, R7, R8As defined above。
Term " high optically pure " refers to have at least 90%, preferably at least 95%, the enantio-selectivity more preferably at 99%。
R1Preferably select cycloalkyl or aryl, more preferably select the phenyl replacedR16、R18It is preferably hydrogen, R15、R17、R19Preferably select alkyl or alkoxyl, more preferably select methyl, ethyl, isopropyl, the tert-butyl group, methoxyl group。
R2Preferably it is selected as hydrogen, alkyl or aryl, more preferably selects hydrogen, alkyl, more preferably select hydrogen, methyl, ethyl, isopropyl, the tert-butyl group。
R3, R4, R5, R6,, R7, R8, R9, R10Preferably it is selected as hydrogen, alkyl, more preferably selects hydrogen, methyl, ethyl, isopropyl, the tert-butyl group。
R11Preferably it is selected as hydrogen, alkyl or aryl, more preferably selects hydrogen, methyl, ethyl, isopropyl, phenyl, benzyl。
R14Preferred optimum selecting is alkyl or aryl, more preferably selects isopropyl, the tert-butyl group, phenyl, benzyl。
R12, R13Preferably it is selected as hydrogen, alkyl or aryl, more preferably selects hydrogen and alkyl, more preferably select hydrogen, methyl, ethyl, isopropyl, the tert-butyl group。
The present invention also provides for a kind of method for preparing the compound of high optically pure formula (1), comprises the steps of
A), formula (2) 2-azoles quinoline base amineWith formula (3)
Halides is reacted, to form formula (4)
Wherein R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, * such as claim 1 defines, and X is F, Cl, Br, I；
B), formula (4) and formula (5) R1-NH2(5) amine reaction, wherein R1As claim 1 defines, to produce the compound of the chirality of high optically pure formula (1)。
Step (b) uses formula known in the art (4) and amine formula (5) reaction method to carry out, and obtains the compound of formula (1)。
Usual formula (4) and amine formula (5) mol ratio are 1:1-10。
Catalyst is Bronsted acid or molecular sieve。
Step (a) is the coupling reaction of transition metal Ru, Rh, Pd, Ir inorganic salt and organophosphorus ligand, aminophosphine ligand catalysis。
The solvent participating in reaction in step (a) is organic solvent, it is possible to be polarity or non-polar solven。Such as such as benzene, carbon tetrachloride, petroleum ether, oxolane, dimethylformamide, ether, dichloromethane, chloroform, toluene, dimethylbenzene, hexamethylene, normal hexane, normal heptane, dioxane, acetonitrile etc., reaction temperature 30 DEG C to 200 DEG C, reacts 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 provides the transition metal salt MX of definition in summary of the inventionnIn the heteroatoms double bond of prochiral organic compounds, asymmetric hydrosilation addition is carried out to prepare chiral organic compound through complexes ira situ with compound。
Wherein Formula (1) and slaine MXnEquivalent proportion be preferably from about 2.2:1-0.9:1, more preferably 1.0:1-1.6:1。
Transition metal salt MXnThe amount of being preferably used is 0.001-10mol%, more preferably 0.1-5mol%。
Formula (1) amount of being preferably used is 0.001-20mol%, more preferably 0.16-15mol%。
Below by specific embodiment, technical scheme is described in further detail:
Following example are used for explaining the present invention。Responded and carried out in airfree argon and degassed solvent。But it is not limiting as present invention。
Embodiment: formula (3) and amine formula (5) are commercially available, 2-azoles quinoline base amine formula (2) is prepared according to document (Org.Biomol.Chem., 2009,7,1,723 1734)。
The preparation of Formula (4)
Example A1: the preparation of compound A1
Under nitrogen protection, (S)-2-(4-benzyl-4,5-dihydro azoles-2-base) aniline (2.7753g; 11mmol, 1.1equiv) and 2-bromobenzaldehyde (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, obtain the 2.8289g (7.8mmol, 78%) the compound A1 containing azoles quinoline amine。
1HNMR(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).
13CNMR(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)calculatedfor[C23H20N2O2]+requiresm/z356.1525,foundm/z356.1526.
Example A2: the preparation of compound A2
Under nitrogen protection, (S)-2-(4-isopropyl-4,5-dihydro azoles-2-base) aniline (2.2473g; 11mmol, 1.1equiv) and 2-bromobenzaldehyde (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, obtain the 2.8289g (8.5mmol, 85%) the compound A2 containing azoles quinoline amine。
1HNMR(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).13CNMR(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)calculatedfor[C19H20N2O2]+requiresm/z308.1525,foundm/z308.1520.
Example A3: the preparation of compound A-13
Under nitrogen protection, (S)-2-(4-phenyl-4,5-dihydro azoles-2-base) aniline (2.6213g; 11mmol, 1.1equiv) and 2-bromobenzaldehyde (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, obtain the 2.8289g (8.3mmol, the 83%) compound A-13 containing azoles quinoline amine。
1HNMR(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).13CNMR(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)calculatedfor[C22H18N2O2]+requiresm/z342.1368,foundm/z342.1367.
Example A4: the preparation of compound A4
Under nitrogen protection, (S)-2-(the 4-tert-butyl group-4,5-dihydro azoles-2-base) aniline (2.4013g; 11mmol, 1.1equiv) and 2-bromobenzaldehyde (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, obtain the 2.8289g (8.0mmol, 80%) the compound A4 containing azoles quinoline amine。
1HNMR(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).13CNMR(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)calculatedfor[C20H22N2O2]+requiresm/z322.1681,foundm/z322.1680.
Example A5: the preparation of compound A-45
Under nitrogen protection; (S)-2-(4-isopropyl-4; 5-dihydro azoles-2-base) aniline (2.2473g; 11mmol; 1.1equiv) with the bromo-5-chlorobenzaldehyde (2.1950g of 2-; 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), 30 DEG C are reacted 48 hours, petroleum ether: ethyl acetate=20:1 crosses post, obtain the 2.9824g (8.7mmol, the 87%) compound A-45 containing azoles quinoline amine。
1HNMR(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).13CNMR(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)calculatedfor[C19H19ClN2O2]+requiresm/z342.1135,foundm/z356.1139.
Example A6: the preparation of compound A6
Under nitrogen protection; (S)-2-(4-isopropyl-4; 5-dihydro azoles-2-base) aniline (2.2473g; 11mmol; 1.1equiv) with the bromo-4-fluorobenzaldehyde (2.0300g of 2-; 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, obtain the 3.0355g (9.3mmol, 93%) the compound A6 containing azoles quinoline amine。
1HNMR(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).13CNMR(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)calculatedfor[C19H19FN2O2]+requiresm/z326.1432,foundm/z356.1434.
Example A7: the preparation of compound A7
Under nitrogen protection; (S)-2-(4-isopropyl-4; 5-dihydro azoles-2-base) aniline (2.2473g; 11mmol; 1.1equiv) with the bromo-4-tolyl aldehyde (2.0300g of 2-; 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), 30 DEG C are reacted 48 hours, petroleum ether: ethyl acetate=20:1 crosses post, obtain the 3.0950g (9.6mmol, 96%) the compound A7 containing azoles quinoline amine。
1HNMR(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).13CNMR(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)calculatedfor[C20H22N2O2]+requiresm/z322.1681,foundm/z322.1677.
B) containing the preparation of the compound B of glyoxalin quinoline amine
Example B1: the preparation of glyoxalin quinoline amine B1
2,6-diisopropyl aniline (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, reaction 48h, ethyl alcohol recrystallization obtains 1.9978g (3.9mmol, 67%) B1。
1HNMR(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).13CNMR(101MHz,CDCl3):δ163.8,160.7,149.6,146.0,142.5,137.9,137.7,131.9,131.9,130.1,129.9,129.2,129.0,128.4,126.4,124.0,123.9,123.6,122.9,118.0,114.8,112.0,70.3,67.9,41.7,27.9,23.5,23.5.HRMS(EI)calculatedfor[C35H37N3O]+requiresm/z515.2937,foundm/z515.2937.
Example B2: the preparation of glyoxalin quinoline amine B2
2,6-diisopropyl aniline (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, reaction 48h, ethyl alcohol recrystallization obtains 1.3431g (2.9mmol, 57%) B2。
1HNMR(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).13CNMR(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)calculatedfor[C31H37N3O]+requiresm/z467.2937,foundm/z467.2934.
Example B3: the preparation of glyoxalin quinoline amine B3
2,6-diisopropyl aniline (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, reaction 48h, ethyl alcohol recrystallization obtains 5.9603g (11.8mmol, 76%) B3。
1HNMR(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).13CNMR(101MHz,CDCl3): δ 164.8,160.6,149.7,146.5,142.4,137.7,132.3,132.0,130.4,12 9.8,129.4,128.7,127.5,126.4,124.5,124.1,123.9,123.0,118. 0,114.9,111.7,73.4,70.1,27.9,23.5,23.4；HRMS (EI) calculatedfor [C34H35N3O]+requiresm/z501.2780,foundm/z501.2777.
Example B4: the preparation of glyoxalin quinoline amine B4
2,6-diisopropyl aniline (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, reaction 48h, ethyl alcohol recrystallization obtains 1.7256g (3.6mmol, 71%) B4。
1HNMR(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).13CNMR(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)calculatedfor[C32H39N3O]+requiresm/z481.3093,foundm/z481.3098.
Example B5: the preparation of glyoxalin quinoline amine B5
P-trifluoromethylaniline (3.2222g, 20mmol, 1.3equiv) it is dissolved in 30mL toluene with A3 (5.3179g, 15.5mmol, 1.0equiv), p-methyl benzenesulfonic acid (0.2580g, 1.5mmol, 10mol%) catalysis, react 48h, ethyl alcohol recrystallization obtains 5.7254g (11.8mmol, 76%) B5。
1HNMR(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).13CNMR(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)calculatedfor[C29H22F3N3O]+requiresm/z485.1715,foundm/z485.1720.
Example B6: the preparation of glyoxalin quinoline amine B6
P-nethoxyaniline (2.4640g, 20mmol, 1.3equiv) it is dissolved in 30mL toluene with A3 (5.3179g, 15.5mmol, 1.0equiv), p-methyl benzenesulfonic acid (0.2580g, 1.5mmol, 10mol%) catalysis, react 48h, ethyl alcohol recrystallization obtains 5.0006g (11.2mmol, 72%) B6。
1HNMR (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).13CNMR(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)calculatedfor[C29H25N3O2]+requiresm/z447.1947,foundm/z447.1956.
Example B7: the preparation of glyoxalin quinoline amine B7
2,6-diisopropyl aniline (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, reaction 48h, ethyl alcohol recrystallization obtains 1.8043g (3.6mmol, 71%) B7。
1HNMR(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).13CNMR(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)calculatedfor[C30H33ClN3O]+requiresm/z501.2547,foundm/z501.2543.
Example B8: the preparation of glyoxalin quinoline amine B8
2,6-diisopropyl aniline (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, reaction 48h, ethyl alcohol recrystallization obtains 1.6490g (3.4mmol, 68%) B7。
1HNMR(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).13CNMR(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)calculatedfor[C30H33FN3O]+requiresm/z485.2842,foundm/z485.2838.
Example B9: the preparation of glyoxalin quinoline amine B9
2,6-diisopropyl aniline (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, reaction 48h, ethyl alcohol recrystallization obtains 1.6354g (3.4mmol, 68%) B9。
1HNMR(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).13CNMR(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)calculatedfor[C31H36N3O]+requiresm/z481.3093,foundm/z481.3096.
C) silicon hydrogenation of the ketone of the compound B4 of glyoxalin quinoline amine and cobalt dichloride complexes ira situ catalysis and triethoxysilane
Under room temperature, a reaction tube dried adds compound cobalt dichloride (0.10mmol), B4 (0.16mmol), dichloromethane (1.0mL), at room temperature stirring 2 hours, rear addition ketone (1.0mmol), triethoxysilane (2.0mmol), sodium triethylborohydride (0.10mmol), then at room temperature stir 12 hours, the saturated K2CO3/MeOH of rear addition, after at room temperature stirring 2 hours, column chromatography for separation obtains product。
Example C1:(R) the bromo-α-methylbenzylalcohol of-4-
Oily liquids, 89% productivity, [α]20 D=+38.8 (c1.33, CHCl3), 97.2%eedeterminedbyHPLC, HPLCconditions:ChiralcelAS-H, n-hexane/i-PrOH=98/2,1.0mL/min, n=220nm, tr16.0 (major), 16.9 (minor)；1HNMR(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% productivity, [α]20 D=+37.7 (c1.03, CHCl3), 97.6%eedeterminedbyHPLC, HPLCconditions:ChiralcelAS-H, n-hexane/i-PrOH=98/2,1.0mL/min, n=220nm, tr21.2 (major), 24.9 (minor)；1HNMR(400MHz,CDCl3): δ 7.96 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) hydroboration of the ketone of the compound B4 of glyoxalin quinoline amine and cobalt dichloride complexes ira situ catalysis and pinacol borine
Under room temperature, a reaction tube dried adds compound cobalt dichloride (0.10mmol), B4 (0.16mmol), ether (1.0mL), at room temperature stirring 2 hours, add ketone (1.0mmol), pinacol borine (2.0mmol) afterwards, sodium triethylborohydride (0.10mmol), after then at room temperature stirring 12 hours, column chromatography for separation obtains product。
Example D1:(R)-α-methylbenzylalcohol
Oily liquids, 82% productivity, 98.1%ee；1HNMR(400MHz,CDCl3) δ 7.58 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 group-α-methylbenzylalcohol
Oily liquids, 88% productivity, 97.6%ee；1HNMR(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) hydroboration of the alkene of the compound B4 of glyoxalin quinoline amine and cobalt dichloride complexes ira situ catalysis and pinacol borine
Under room temperature, a reaction tube dried adds compound cobalt dichloride (0.10mmol), B4 (0.16mmol), ether (1.0mL), at room temperature stirring 2 hours, add alkene (1.0mmol), pinacol borine (2.0mmol) afterwards, sodium triethylborohydride (0.10mmol), after then at room temperature stirring 12 hours, column chromatography for separation obtains product。
Example E1:(S)-(+)-4,4,5,5-tetramethyl-2-(2-phenylpropyl)-1,3,2-dioxy boron pentane.
Oily liquids, 98% productivity, [α]20 D=+21.9 (c1.0, CHCl3), 96.1%ee, HPLCconditions:ChiralcelOD-H, n-hexane/i-PrOH=99/1,0.25mL/min, n=254nm, tr16.7 (minor), 18.0 (major)；IR (neat): 2978,1453,1370,1323,1146cm-1；1HNMR(CDCl3, 400MHz): δ 7.28-7.21 (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)；13CNMR(CDCl3,100MHz):δ149.1,128.1,126.5,125.6,82.8,35.7,24.8,24.7,24.6.11BNMR(CDCl3, 128MHz): δ 33.7；HRMS (EI) calculatedfor [C15H23BO2]+requiresm/z246.1791,foundm/z246.1791.
Example E2:(S)-(+)-4,4,5,5-tetramethyl-2-(2-(4-methylphenyl)-propyl group)-1,3,2-dioxy boron pentane.
Oily liquids, 93% productivity, [α]20 D=+24.9 (c0.97, CHCl3), 98.3%ee；1HNMR(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)；13CNMR:(100.6MHz,CDCl3): δ 146.2,134.9,128.8,126.4,82.9,35.3,24.8,24.7,24.6,21.4,20 .9；11BNMR(CDCl3, 128MHz): δ 33.7；HRMS (EI) calculatedfor [C16H25BO2]+requiresm/z260.1948,foundm/z260.1951.
Listed above is only some specific embodiments of the present invention; it is clear that the invention is not restricted to above example, it is also possible to there are many deformation; all deformation that those of ordinary skill in the art can directly derive from present disclosure or associate, are all considered as protection scope of the present invention。

Claims (9)

1. the chirality compound containing glyoxalin quinoline amine, it is characterised in that described compound is high optically pure, structural formula such as following formula (1)
Wherein, R1It it is C1-C12-alkyl that is unsubstituted or that replaced by 1-2 C1-C4-alkoxyl, or unsubstituted or that replaced by 1-3 C1-C4-alkyl or C1-C4-alkoxyl cyclopenta or cyclohexyl, or unsubstituted or by 1-4 C1-C4-alkyl, C1-C4-alkoxyl, C1-C4-fluoroalkyl or C1-C4-Fluoroalkyloxy, the benzyl of F or Cl replacement, phenyl or naphthyl；
R2It is H or C1-C12-alkyl that is unsubstituted or that replaced by 1-2 C1-C4-alkoxyl, or unsubstituted or that replaced by 1-3 C1-C4-alkyl or C1-C4-alkoxyl cyclopenta or cyclohexyl, or unsubstituted or by 1-3 C1-C4-alkyl, C1-C4-alkoxyl, C1-C4-fluoroalkyl or C1-C4-Fluoroalkyloxy, F or Cl replacement phenyl or naphthyl；
R3, R4, R5, R6, R7, R8, R9, R10It is H or unsubstituted C1-C12-alkyl, C1-C4-Fluoroalkyloxy, F or Cl, or cyclopenta that is unsubstituted or that replaced by 1-3 C1-C4-alkyl or C1-C4-alkoxyl or cyclohexyl, nitro；
R11It is H or C1-C12-alkyl that is unsubstituted or that replaced by 1-2 C1-C4-alkoxyl, or unsubstituted or that replaced by 1-3 C1-C4-alkyl or C1-C4-alkoxyl cyclopenta or cyclohexyl, or unsubstituted or by 1-3 C1-C4-alkyl, C1-C4-alkoxyl, C1-C4-fluoroalkyl or C1-C4-Fluoroalkyloxy, the benzyl of F or Cl replacement, phenyl or naphthyl；
R12, R13It is H or C1-C12-alkyl that is unsubstituted or that replaced by 1-2 C1-C4-alkoxyl, or unsubstituted or that replaced by 1-3 C1-C4-alkyl or C1-C4-alkoxyl cyclopenta or cyclohexyl, or unsubstituted or by 1-3 C1-C4-alkyl, C1-C4-alkoxyl, C1-C4-fluoroalkyl or C1-C4-Fluoroalkyloxy, the benzyl of F or Cl replacement, phenyl or naphthyl；
R14It it is C1-C12-alkyl that is unsubstituted or that replaced by 1-2 C1-C4-alkoxyl, or unsubstituted or that replaced by 1-3 C1-C4-alkyl or C1-C4-alkoxyl cyclopenta or cyclohexyl, or unsubstituted or by 1-3 C1-C4-alkyl, C1-C4-alkoxyl, C1-C4-fluoroalkyl or C1-C4-Fluoroalkyloxy, the benzyl of F or Cl replacement, phenyl or naphthyl；* chiral carbon atom is represented。
2. a chirality according to claim 1 compound containing glyoxalin quinoline amine, it is characterised in that described R1It is preferably alkyl or aryl, described R2It is preferably hydrogen, alkyl or aryl, described R3-R10It is preferably hydrogen, alkyl, described R11It is preferably hydrogen, alkyl or aryl, described R12, R13, it is preferred to hydrogen, alkyl or aryl, R14It is preferably alkyl or aryl。
3. a compounds process for production thereof according to claim 1 and 2, it is characterised in that described method comprises the steps of
A), formula (2) 2-azoles quinoline base amineWith formula (3)Halides is reacted, to form formula (4)
Wherein R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, * such as claim 1 defines, and X is F, Cl, Br, I；
B), formula (4) and formula (5) R1-NH2(5) amine reaction, wherein R1As claim 1 defines, to form formula (1), i.e. compound described in claim 1。
4. preparation method according to claim 3, it is characterised in that described step (a) is the coupling reaction of transition metal Ru, Rh, Pd, Ir, Cu inorganic salt and organophosphorus ligand, aminophosphine ligand catalysis。
5. preparation method according to claim 3, it is characterized in that, the solvent participating in reaction in described step (a) is organic solvent, being polarity or non-polar solven, described organic solvent is any one in benzene, carbon tetrachloride, petroleum ether, oxolane, dimethylformamide, ether, dichloromethane, chloroform, toluene, dimethylbenzene, hexamethylene, normal hexane, normal heptane, dioxane, acetonitrile。
6. preparation method according to claim 3, it is characterised in that in described step (a), reaction temperature is 30 DEG C to 200 DEG C, and the response time is 30 minutes to 48 hours。
7. preparation method according to claim 3, it is characterised in that in described step (a), formula (2): formula (3): metallic catalyst: part material ratio is 1-5:0.01-1:0.02-2:0.02-2。
8. one kind by the compound described in claim 1 and transition metal M XnThe complexes ira situ method for preparing chiral organic compound by asymmetric catalytic reaction, it is characterised in that described method is at the Formula (1) described at least one claim 1 of catalytic amount and at least one transition metal M XnCarry out under existence, wherein,
M is transition-metal Fe, Co, Ni, Cu, Ag, Au, Ru, Rh, Pd, Os, Ir；
X is selected from any one in the anion (carbonate, formate, acetate, propionate, pyrovinic acid root, trichloromethyl sulfonate radical, phenylbenzimidazole sulfonic acid root, tosylate) of halogenide (F, Cl, Br, I), pseudohalide (cyanide, cyanic acid, salt, isocyanates), carboxylic acid, sulfonic acid, phosphonic acids；
N is the number of X, is 1,2,3。
9. the method preparing chiral organic compound according to claim 8, it is characterized in that, the described method preparing chiral organic compound is in the presence of a catalyst, by carrying out asymmetric hydrosilation on the carbon-carbon double bond of prochiral organic compounds or heteroatoms double bond or hydroboration realizes, namely described asymmetric hydrosilation or hydroboration addition are at least one Formula (1) of catalytic amount and at least one transition metal M XnCarry out under existence。
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