CN107417615A - The chiral quinoline ketone derivative novel preparation method that visible ray promotes - Google Patents
The chiral quinoline ketone derivative novel preparation method that visible ray promotes Download PDFInfo
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- CN107417615A CN107417615A CN201710823270.6A CN201710823270A CN107417615A CN 107417615 A CN107417615 A CN 107417615A CN 201710823270 A CN201710823270 A CN 201710823270A CN 107417615 A CN107417615 A CN 107417615A
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- 0 C[C@]([C@](C=C)c1ccccc1*1)(C1=O)c1ccccc1 Chemical compound C[C@]([C@](C=C)c1ccccc1*1)(C1=O)c1ccccc1 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/58—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems with hetero atoms directly attached to the ring nitrogen atom
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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Abstract
The invention discloses a kind of quinoline ketone derivative, more particularly to optically active quinoline ketone derivative shown in Formulas I and preparation method thereof.Such compound can be in three (dibenzalacetone) two palladium chloroform adducts and P S parts as catalyst, 4 alkenyl benzoxazinones, as initiation material, are reset by wolff under the conditions of visible ray photograph with diazonium compound and subsequent decarboxylation [4+2] cyclization are made.When P S are formula IV compound, the quinoline ketone derivative shown in the Formulas I of a variety of different substitutions can be synthesized efficient, high enantioselectivity.
Description
Technical field
The present invention relates to chemical field, specifically, the present invention relates to a kind of Formulas I0Shown quinoline ketone derivative and its
Preparation method, more particularly to optically active quinoline ketone derivative shown in Formulas I and preparation method thereof.
Background technology
Chiral quinoline ketone derivative has important physiologically active, and has in asymmetric catalysis field and extensively should
With therefore, the effective ways of efficient, the high enantioselective synthesis chirality quinoline ketone derivative of development, preparing has biology living
Property natural products ex hoc genus anne derivative turn into the goals in research of numerous organic chemists.
Because of its mild condition, reaction is efficient for the reaction that visible ray promotes, it is green the advantages that and by numerous chemists
Concern.In recent years, the chemical conversion for promoting strategy to realize using visible ray emerges in an endless stream, it is possible to achieve carbon carbon, carbon nitrogen, carbon
The structure of the chemical bonds such as phosphorus, carbon oxygen, or even by cascade reaction, realize the structure of multiple chemical bonds.Asymmetric syntheses quinolinone
The conventional method of class compound has a lot, but is prepared by visible ray promotion with optical activity quinoline ketone derivative
Method is but rarely reported.Investigated by document and patent, it has been found that the chemical conversion of visible optical drive has in organic synthesis
Significant, it is exactly one of them that Wolff of the diazonium compound that aryl ketones substitute under visible optical drive, which is reset, if will
It can be seen that the Wolff under optical drive, which is reset, is applied to the quinoline that transition metal-catalyzed Dipolar Cycloaddition can realize visible ray promotion
The asymmetric structure of quinoline ketone compounds.The chemical conversion in-situ preparation reactive intermediate alkene that we will be promoted using visible ray
Ketone, the shortcomings of ketenes is difficult to prepare purifying and functional group compatibility difference is overcome, in a mild condition efficient high selectivity system
For a series of chiral quinoline ketone derivatives containing various functional groups.It is this to promote mutually to tie with metal catalytic by visible ray
The method of the asymmetric syntheses chirality quinolinone compounds of conjunction is there is not yet document report.
Analysis and the previous work of this seminar, applicant applicant intend from 4- vinyl benzenes simple and easy to get based on more than
Bing oxazinones and α-diazo-ketones set out, and develop continuous visible-light activated and three (dibenzalacetone) two palladium chloroform adduction
Asymmetric decarboxylation [4+2] cycloaddition reaction of thing and chiral P-S ligand catalysis, has synthesized tool efficient, high enantioselectivity
There is optically active quinoline ketone derivative.
The content of the invention
Present invention aims at explore visible-light activated and three (dibenzalacetone) two palladium chloroform adducts and chirality
Asymmetric decarboxylation [4+2] cycloaddition reaction of P-S ligand catalysis, with 4- vinyl benzoxazinone simple and easy to get and α-diazonium
Ketone is initiation material, synthesizes efficient, high enantioselectivity and derives with optically active, highly functional quinolinones
Thing.
Specifically, the invention discloses a kind of quinoline ketone derivative, it is characterized in that the compound is Formulas I0Shownization
Enantiomter, diastereoisomer, racemic modification, pharmaceutically acceptable salt, crystalline hydrate or the solvate of compound：
Wherein, Formulas I0Middle R1For hydrogen, C1-6Alkyl, C1-6Alkoxy, fluorine, chlorine, bromine or trifluoromethyl；
R2For hydrogen, methyl, phenyl, 2- naphthyls, wherein phenyl is alternatively taken by methyl, methoxyl group, fluorine, a chlorine or bromine
Generation；
R3For C1-6Alkyl, phenyl, benzyl, high allyl, high-propargyl, 3- benzyloxies propyl group, cyclopropane or cyclohexene
Base.
According to an embodiment of the invention, preferably：
R1For hydrogen, 6- methyl, 6- methoxyl groups, 6- bromines, 6- chlorine, 7- chlorine, 7- trifluoromethyls or 8- fluorine；
R2For hydrogen, methyl, phenyl, 2- naphthyls, 4- aminomethyl phenyls, 3- chlorphenyls, 4- methoxyphenyls, 4- fluorophenyls, 4-
Chlorphenyl or 4- bromophenyls；
R3For methyl, ethyl, isopropyl, normal-butyl, the tert-butyl group, phenyl, benzyl, high allyl, high-propargyl, 3- benzyloxies
Base propyl group, cyclopropane or cyclohexenyl group.
The invention particularly relates to one kind to have the optically active quinoline ketone derivative of Formulas I, pharmaceutically acceptable salt, knot
Brilliant hydrate or solvate：
According to an embodiment of the invention, more specifically, the present invention relates to the enantiomter of following compounds, diastereomeric are different
Structure body, racemic modification, pharmaceutically acceptable salt, crystalline hydrate or solvate：
In the second aspect of the present invention, the invention provides a kind of method for preparing compound noted earlier, according to this hair
Bright embodiment, this method include：
Compound shown in Formula II is set to be contacted with compound shown in formula III, to obtain Formulas I0Shown compound：
Wherein R1、R2、R3It is as previously described.
Preferably, compound shown in Formula II, III and catalyst and part are dissolved in organic solvent by the contact, in nitrogen
Under gas shielded, reacted under visible ray promotion and Formulas I is made0Compound.
More preferably：
The catalyst is three (dibenzalacetone) two palladium chloroform adducts, optionally, the catalyst and Formula II institute
The mol ratio for showing compound is 1：20.
The part is double (diphenylphosphine) propane of 1,3- or formula IV compound：
Optionally, the mol ratio of compound shown in the part and Formula II is 1：10.
The mol ratio of compound shown in the formula III and compound shown in Formula II is 2:1.
The organic solvent is selected from dichloromethane；Reaction temperature is room temperature；Reaction time is 18-30 hours, and preferably 24 is small
When；Visible ray promotes that 6W blue leds s reactor can be selected.
According to an embodiment of the invention, further include：Silica gel column chromatography purifies, and separates the Formulas I0Shown chemical combination
Thing, wherein, the column chromatography is used as with the mixture of ethyl acetate using petroleum ether and separates phase, and petroleum ether and ethyl acetate
Volume ratio be 30:1~20：1.
According to an embodiment of the invention, further, preferred catalyst and part are under nitrogen protection in organic solvent
After middle stirring, Formula II is added, compound shown in III, reacted under visible ray promotion and Formulas I is made0Compound.
Preferably, the temperature that catalyst and part stir in organic solvent under nitrogen protection is room temperature, and the time is half
Hour.
Particularly, when the part is formula IV compound, reaction, which obtains, to be had as the optically active quinolinones of Formulas I spread out
Biology.
Thus, according to an embodiment of the invention, the present invention proposes a synthetic route, can be used for shown in formula I
Optically active quinoline ketone derivative：
Wherein Ts is p-toluenesulfonyl, and dba is dibenzalacetone, CH2Cl2For dichloromethane, yield：Yield, dr：
Cis-selectivity ratio, er：Enantiomeric ratio, Ligand:Part.
In above-mentioned reaction, at room temperature, the palladium chloroform adducts of metallic catalyst three (dibenzalacetone) two and ligand i V
It is dissolved in chloroform, stirs 30 minutes under nitrogen protection.4- vinyl benzoxazinone II are then added, then by α-diazo-ketones
III is added in reaction system, and reactant mixture is placed in 6W blue leds s reactor and reacts at room temperature 24h, with VPetroleum ether/
VEthyl acetate=30:1-20:1 column chromatography directly obtains Formulas I target product, and product dr and er value are determined with chiral HPLC instrument；HPLC points
Analysis chiral OD-H, AD-H, AZ-H, IC-H, IE-H, OX-H, OJ-H, IF-H posts；Raceme is to use the triphen of metallic catalyst four
Base phosphine palladium and ligand 1, double (diphenylphosphine) propane of 3- are catalyzed reaction acquisition.
Detailed description of the invention
Unless stated to the contrary, it is following that there are following implications with term in the specification and in the claims.
" alkyl " refers to the aliphatic hydrocarbon group of saturation.Include the straight or branched group of 1 to 6 carbon atom.Such as methyl, second
Base, propyl group, 2- propyl group, normal-butyl, isobutyl group, the tert-butyl group, amyl group etc..More preferably contain 1 to 4 carbon atom
Low alkyl group, such as methyl, ethyl, propyl group, 2- propyl group, normal-butyl, isobutyl group or tert-butyl group etc..
" alkoxy " expression-O- (unsubstituted alkyl) and-O (unsubstituted cycloalkyl).Representational example include but
It is not limited to methoxyl group, ethyoxyl, propoxyl group, butoxy, ring propoxyl group, cyclobutoxy group, cyclopentyloxy, cyclohexyloxy etc..
Embodiment
The preparation method of compound in the Formulas I of the present invention is illustrated below by example.These examples are only to this hair
It is bright to illustrate, without limiting the invention.
Embodiment 1
Compound I-1
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-1 (32mg, 0.2mmol) is added in reaction system,
Reactant mixture is placed in into room temperature in 6W blue leds s reactor to continue to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:1 post
Chromatography directly obtains the target product 40.1mg of Formulas I -1, yield 98%.
1H NMR(400MHz,CDCl3) δ (ppm) 7.99 (d, J=8.3Hz, 2H), 7.57 (d, J=8.2Hz, 1H), 7.37
(d, J=8.1Hz, 2H), 7.16-7.00 (m, 6H), 6.96 (m, 2H), 5.69 (m, 1H), 5.30-5.04 (m, 2H), 3.79 (d,
J=8.1Hz, 1H), 2.48 (s, 3H), 1.39 (s, 3H)
13C NMR(100MHz,CDCl3)δ(ppm)173.6,145.0,141.0,136.5,134.2,134.1,131.5,
129.3,129.1,128.4,128.0,127.1,126.8,126.1,125.3,123.2,119.4,53.4,52.4,24.7,
21.7。
High-resolution：Calculated value：[M+H]+:418.1480, measured value：418.1471.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 96 of product:4, diastereoisomer ratio 93:7, chiral OD-H posts are (different
Propyl alcohol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=10.59 minutes, t2=19.11
Minute.
Embodiment 2
Compound I-2
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- ethene
Base -6- Jia epoxide benzoxazinone II-2 (36mg, 0.1mmol), then α-diazo-ketones III-1 (32mg, 0.2mmol) is added to
In reaction system, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=
30:1-20:1 column chromatography directly obtains the target product 44.3mg of Formulas I -2, yield 99%.
1H NMR(400MHz,CDCl3) δ (ppm) 8.05-7.90 (m, 2H), 7.48 (d, J=9.0Hz, 1H), 7.36 (d, J
=8.0Hz, 2H), 7.13-6.95 (m, 5H), 6.68-6.55 (m, 2H), 5.59 (m, 1H), 5.26-5.04 (m, 2H), 3.72
(m,4H),2.47(s,3H),1.36(s,3H).
13C NMR(100MHz,CDCl3)δ(ppm)173.5,157.5,144.9,141.0,136.5,134.1,133.1,
129.2,129.1,128.4,127.3,126.8,125.3,124.5,119.4,113.6,111.8,55.4,53.4,52.7,
24.7,21.7
High-resolution：Calculated value：[M+H]+:448.1586, measured value:448.1577.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 97 of product:3er, diastereoisomer ratio 94:6dr, chiral OD-H posts
(isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=11.47 minutes, t2=
27.36 minutes.
Embodiment 3
Compound I-3
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- ethene
Base -6- Jia base benzoxazinone II-3 (35mg, 0.1mmol), then α-diazo-ketones III-1 (32mg, 0.2mmol) is added to instead
Answer in system, reactant mixture is placed in into room temperature in 6W blue leds s reactor continues to react 24h, with VPetroleum ether/VEthyl acetate=
30:1-20:1 column chromatography directly obtains the target product 42.7mg of Formulas I -3, yield 99%.
1H NMR(400MHz,CDCl3) δ (ppm) 7.98 (d, J=8.1Hz, 2H), 7.45 (d, J=8.3Hz, 1H), 7.36
(d, J=8.1Hz, 2H), 7.06 (m, 3H), 6.99-6.83 (m, 4H), 5.63 (m, 1H), 5.28-4.94 (m, 2H), 3.73 (d,
J=8.2Hz, 1H), 2.47 (s, 3H), 2.22 (s, 3H), 1.36 (s, 3H)
13C NMR(100MHz,CDCl3)δ(ppm)173.6,144.9,141.1,136.5,136.0,134.4,131.6,
131.2,129.2,129.1,128.4,128.4,127.8,126.8,125.3,123.0,119.2,53.4,52.4,24.8,
21.7,20.8.
High-resolution：Calculated value：[M+H]+:432.1634, measured value：432.1628.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 97 of product:3er, diastereoisomer ratio 92:8dr, chiral OD-H posts
(isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=8.55 minutes, t2=
17.78 minutes.
Embodiment 4
Compound I-4
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- ethene
Base -6- Xiu benzoxazinones II-4 (41mg, 0.1mmol), then α-diazo-ketones III-1 (32mg, 0.2mmol) is added to reaction
In system, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=30:
1-20:1 column chromatography directly obtains the target product 49.1mg of Formulas I -4, yield 99%.
1H NMR(400MHz,CDCl3) δ (ppm) 7.96 (d, J=7.9Hz, 2H), 7.64-6.67 (m, 10H), 5.58 (m,
1H), 5.16 (m, 2H), 3.75 (d, J=8.0Hz, 1H), 2.48 (s, 3H), 1.37 (s, 3H)
13C NMR(100MHz,CDCl3)δ(ppm)173.0,145.3,140.5,136.1,133.6,133.4,133.2,
130.6,130.1,129.3,129.2,128.6,127.1,125.2,124.7,120.0,119.5,53.2,52.0,24.6,
21.7.
High-resolution：Calculated value：[M+H]+:496.0577, measured value：496.0577.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 97 of product:3er, diastereoisomer ratio 93:7dr, chiral OD-H posts
(isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=9.07 minutes, t2=
16.46 minutes.
Embodiment 5
Compound I-5
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- ethene
Base -6- Lv benzoxazinones II-5 (36mg, 0.1mmol), then α-diazo-ketones III-1 (32mg, 0.2mmol) is added to reaction
In system, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=30:
1-20:1 column chromatography directly obtains the target product 44.6mg of Formulas I -5, yield 99%.
1H NMR(400MHz,CDCl3) δ (ppm) 7.96 (d, J=7.9Hz, 2H), 7.52 (d, J=8.7Hz, 1H), 7.38
(d, J=8.0Hz, 2H), 7.17-7.01 (m, 5H), 6.96 (d, J=7.5Hz, 2H), 5.72-5.48 (m, 1H), 5.16 (m,
2H), 3.76 (d, J=8.1Hz, 1H), 2.48 (s, 3H), 1.37 (s, 3H)
13C NMR(100MHz,CDCl3)δ(ppm)173.1,145.3,140.5,136.1,133.4,133.3,132.7,
131.6,129.3,129.2,128.6,127.7,127.2,127.1,125.2,124.5,120.0,53.2,52.1,24.6,
21.8.
High-resolution：Calculated value：[M+H]+:452.1088, measured value：452.1082.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 96 of product:4er, diastereoisomer ratio 94:6dr, chiral OD-H posts
(isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=8.76 minutes, t2=
15.44 minutes.
Embodiment 6
Compound I-6
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- ethene
Base -7- Lv benzoxazinones II-6 (36mg, 0.1mmol), then α-diazo-ketones III-1 (32mg, 0.2mmol) is added to reaction
In system, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=30:
1-20:1 column chromatography directly obtains the target product 44.8mg of Formulas I -6, yield 99%.
1H NMR(400MHz,CDCl3) δ (ppm) 7.98 (d, J=8.1Hz, 2H), 7.62 (d, J=1.7Hz, 1H), 7.38
(d, J=8.0Hz, 2H), 7.15-6.90 (m, 7H), 5.66 (m, 1H), 5.26-5.06 (m, 2H), 3.78 (d, J=8.1Hz,
1H),2.49(s,3H),1.38(s,3H)
13C NMR(100MHz,CDCl3)δ(ppm)173.1,145.3,140.6,136.3,135.0,133.7,132.6,
130.0,129.4,129.2,128.8,128.6,127.1,126.2,125.2,123.3,119.7,53.3,51.9,24.8,
21.8.
High-resolution：Calculated value：[M+H]+:452.1088, measured value：452.1082.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 95 of product:5er, diastereoisomer ratio>95:5dr, chiral OD-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=8.60 minutes, t2=
17.71 minutes.
Embodiment 7
Compound I-7
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- ethene
Base -7- trifluoromethyl benzo oxazinone II-7 (40mg, 0.1mmol), then α-diazo-ketones III-1 (32mg, 0.2mmol) is added
Into reaction system, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate
=30:1-20:1 column chromatography directly obtains the target product 48.1mg of Formulas I -7, yield 99%.
1H NMR(400MHz,CDCl3) δ (ppm) 7.99 (d, J=8.1Hz, 2H), 7.86 (s, 1H), 7.39 (d, J=
8.1Hz, 2H), 7.29 (m, 1H), 7.18 (d, J=7.9Hz, 1H), 7.12-7.01 (m, 3H), 6.97-6.92 (m, 2H), 5.66
(m, 1H), 5.32-5.05 (m, 2H), 3.86 (d, J=8.0Hz, 1H), 2.49 (s, 3H), 1.40 (s, 3H)
13C NMR(100MHz,CDCl3)δ(ppm)172.9,145.4,140.3,136.1,135.3,134.6,133.3,
(129.7,129.4,129.2,128.7,128.4,127.2,125.1,124.9,122.8 q, J=3.7Hz), 122.2,120.2
(d, J=4.4Hz), 53.2,52.3,24.6,21.7
19F NMR(377MHz,CDCl3)δ(ppm)-62.9.
High-resolution：Calculated value：[M+H]+:486.1350, measured value：486.1345.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 96 of product:4er, diastereoisomer ratio>95:5dr, chiral OD-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=7.85 minutes, t2=
12.42 minutes.
Embodiment 8
Compound I-8
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- ethene
Base -8- Fu benzoxazinones II-8 (35mg, 0.1mmol), then α-diazo-ketones III-1 (32mg, 0.2mmol) is added to reaction
In system, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=30:
1-20:1 column chromatography directly obtains the target product 40.9mg of Formulas I -8, yield 94%.
1H NMR(400MHz,CDCl3) δ (ppm) 8.23 (d, J=8.1Hz, 2H), 7.40 (d, J=8.1Hz, 2H), 7.04
(m, 4H), 6.95-6.90 (m, 2H), 6.87 (d, J=7.8Hz, 2H), 6.07 (m, 1H), 5.49-5.15 (m, 2H), 3.87 (d,
J=8.2Hz, 1H), 2.49 (s, 3H), 1.50 (s, 3H)
13C NMR(100MHz,CDCl3)δ(ppm)174.4,156.3,153.8,145.1,140.9,136.5,135.9,
129.6 (d, J=3.7Hz), 129.2,128.5,127.9 (d, J=8.3Hz), 126.9,125.0,123.3,122.4 (d, J=
11.6Hz), 120.2,115.1 (d, J=21.2Hz), 54.8,53.3,25.3,21.7.
19F NMR(377MHz,CDCl3)δ(ppm)-112.9.
High-resolution：Calculated value：[M+H]+:436.1386, measured value：436.1377.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 97 of product:3er, diastereoisomer ratio>95:5dr, chiral IC-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=22.43 minutes, t2=
30.94 minutes.
Embodiment 9
Compound I-9
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-2 (36mg, 0.2mmol) is added in reaction system,
Reactant mixture is placed in into room temperature in 6W blue leds s reactor to continue to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:1 post
Chromatography directly obtains the target product 44.4mg of Formulas I -9, yield 98%.
1H NMR(400MHz,CDCl3) δ (ppm) 8.08-7.95 (m, 2H), 7.57 (dd, J=8.2,1.0Hz, 1H),
7.36 (d, J=8.2Hz, 2H), 7.16-6.99 (m, 3H), 6.85 (m, 4H), 5.68 (m, 1H), 5.24-5.07 (m, 2H),
3.78 (d, J=8.1Hz, 1H), 2.47 (s, 3H), 2.15 (s, 3H), 1.36 (s, 3H)
13C NMR(100MHz,CDCl3)δ(ppm)173.7,144.9,137.9,136.6,136.4,134.3,134.1,
131.6,129.2,129.1,128.0,127.0,126.1,125.1,123.1,119.3,53.0,52.3,24.8,21.7,
20.8.
High-resolution：Calculated value：[M+H]+:454.1434, measured value:454.1447.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 96 of product:4er, diastereoisomer ratio>95:5dr, chiral OD-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=8.97 minutes, t2=
19.01 minutes.
Embodiment 10
Compound I-10
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-3 (36mg, 0.2mmol) is added in reaction system,
Reactant mixture is placed in into room temperature in 6W blue leds s reactor to continue to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:1 post
Chromatography directly obtains the target product 44.8mg of Formulas I -10, yield 98%.
1H NMR(400MHz,CDCl3) δ (ppm) 7.98 (d, J=8.5Hz, 2H), 7.58 (d, J=8.1Hz, 1H), 7.37
(d, J=8.1Hz, 2H), 7.16 (m, 1H), 7.10-7.03 (m, 2H), 6.98-6.88 (m, 2H), 6.80-6.72 (m, 2H),
5.65 (m, 1H), 5.25-5.05 (m, 2H), 3.74 (d, J=8.1Hz, 1H), 2.48 (s, 3H), 1.36 (s, 3H)
13C NMR(100MHz,CDCl3) δ (ppm) 173.4,162.5,160.1,145.1,136.8 (d, J=3.5Hz),
(136.4,134.1,133.9,131.3,129.2 d, J=13.2Hz), 127.9,127.3,127.0 (d, J=8.1Hz),
(126.3,123.2,119.6,115.3 d, J=21.3Hz), 52.9,52.5,24.6,21.7
19F NMR(377MHz,CDCl3)δ(ppm)-115.6.
High-resolution：Calculated value：[M+H]+:458.1204, measured value:458.1197.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 97 of product:3er, diastereoisomer ratio 91:9dr, chiral AZ-H posts
(isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=17.16 minutes, t2=
18.49 minutes.
Embodiment 11
Compound I-11
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-4 (39mg, 0.2mmol) is added in reaction system,
Reactant mixture is placed in into room temperature in 6W blue leds s reactor to continue to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:1 post
Chromatography directly obtains the target product 44.8mg of Formulas I -11, yield 99%.
1H NMR(400MHz,CDCl3) δ (ppm) 7.98 (d, J=8.4Hz, 2H), 7.58 (d, J=8.2Hz, 1H), 7.37
(d, J=8.1Hz, 2H), 7.16 (m, 1H), 7.10-7.02 (m, 4H), 6.89 (d, J=8.7Hz, 2H), 5.65 (m, 1H),
5.22-5.10 (m, 2H), 3.75 (d, J=8.1Hz, 1H), 2.48 (s, 3H), 1.35 (s, 3H)
13C NMR(100MHz,CDCl3)δ(ppm)173.1,145.2,139.6,136.3,134.0,133.8,132.6,
131.2,129.3,129.1,128.6,127.9,127.4,126.8,126.3,123.2,119.7,53.0,52.2,24.6,
21.7.
High-resolution：Calculated value：[M+H]+:452.1081, measured value:452.1082.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 94 of product:6er, diastereoisomer ratio 89:11dr, chiral IF-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=13.69 minutes, t2=
15.26 minutes.
Embodiment 12
Compound I-12
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-5 (48mg, 0.2mmol) is added in reaction system,
Reactant mixture is placed in into room temperature in 6W bule LEDs reactor to continue to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:1
Column chromatography directly obtains the target product 50.8mg of Formulas I -12, yield 99%.
1H NMR(400MHz,CDCl3) δ (ppm) 8.09-7.84 (m, 2H), 7.58 (d, J=8.1Hz, 1H), 7.37 (d, J
=8.1Hz, 2H), 7.23-7.14 (m, 3H), 7.07 (d, J=4.5Hz, 2H), 6.86-6.82 (m, 2H), 5.65 (m, 1H),
5.25-5.08 (m, 2H), 3.74 (d, J=8.1Hz, 1H), 2.48 (s, 3H), 1.35 (s, 3H)
13C NMR(100MHz,CDCl3)δ(ppm)173.1,145.2,140.1,136.3,133.9,133.7,131.6,
131.1,129.3,129.1,127.9,127.4,127.1,126.4,123.3,120.8,119.8,53.1,52.2,24.5,
21.8.
High-resolution：Calculated value：[M+H]+:518.0391, measured value:518.0396.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 96 of product:4er, diastereoisomer ratio 88:12dr, chiral IF-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=14.63 minutes, t2=
16.75 minutes.
Embodiment 13
Breathe out compound I-13
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-6 (39mg, 0.2mmol) is added in reaction system,
Reactant mixture is placed in into room temperature in 6W blue leds s reactor to continue to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:1 post
Chromatography directly obtains the target product 46.9mg of Formulas I -13, yield 99%.
1H NMR(400MHz,CDCl3) δ (ppm) 7.98 (d, J=8.1Hz, 2H), 7.61 (d, J=8.2Hz, 1H), 7.38
(d, J=8.0Hz, 2H), 7.21-7.14 (m, 1H), 7.08 (d, J=6.5Hz, 2H), 7.01 (d, J=4.7Hz, 2H), 6.89
(s, 1H), 6.86-6.81 (m, 1H), 5.80-5.57 (m, 1H), 5.29-5.06 (m, 2H), 3.75 (d, J=8.2Hz, 1H),
2.48(s,3H),1.37(s,3H).
13C NMR(100MHz,CDCl3)δ(ppm)173.0,145.2,143.1,136.3,134.2,133.9,133.6,
131.1,129.6,129.4,129.0,127.9,127.4,127.2,126.3,125.7,123.7,123.2,119.9,53.3,
52.2,24.2,21.7.
High-resolution：Calculated value：[M+H]+:474.0902, measured value:474.0901.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 96 of product:4er, diastereoisomer ratio 92:8dr, chiral OX-H posts
(isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=23.95 minutes, t2=
27.51 minutes.
Embodiment 14
Compound I-14
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-7 (42mg, 0.2mmol) is added in reaction system,
Reactant mixture is placed in into room temperature in 6W blue leds s reactor to continue to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:1 post
Chromatography directly obtains the target product 47.5mg of Formulas I -14, yield 97%.
1H NMR(400MHz,CDCl3) δ (ppm) 8.00 (d, J=8.0Hz, 2H), 7.87-7.65 (m, 4H), 7.51-
7.10(m,9H),5.80(s,1H),5.01(m,2H),3.65(s,1H),2.45(s,3H),1.63(s,3H).
13C NMR(100MHz,CDCl3)δ(ppm)174.4,144.9,136.7,135.8,135.4,135.2,134.5,
131.7,131.1,129.4,129.1,129.0,128.8,127.9,127.4,127.2,126.2,126.2,125.0,
124.8,124.4,122.3,119.5,54.4,52.9,26.4,21.7.
High-resolution：Calculated value：[M+H]+:490.1450, measured value:490.1447.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 97 of product:3er, diastereoisomer ratio>95:5dr, chiral AD-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=12.01 minutes, t2=
18.13 minutes.
Embodiment 15
Compound I-15
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-8 (35mg, 0.2mmol) is added in reaction system,
Reactant mixture is placed in into room temperature in 6W blue leds s reactor to continue to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:1 post
Chromatography directly obtains the target product 42.8mg of Formulas I -15, yield 99%.
1H NMR(400MHz,CDCl3) δ (ppm) 8.07 (d, J=8.4Hz, 2H, minor), 8.00-7.89 (m, 2H,
), major 7.64 (m, 1H, minor), 7.58-7.47 (m, 1H, major), 7.34 (d, J=8.2Hz, 2H, major+
minor),7.21–7.15(m,1H,major+minor),7.13–7.00(m,5H,major+minor),6.98–6.91(m,
2H,major),6.89(m,2H,minor),5.71(m,1H,minor),5.59(m,1H,major),5.31(m 1H,
), minor 5.21 (m, 1H, major), 5.08 (dt, J=10.0,1.0Hz, 1H, major+minor), 3.93 (d, J=
8.1Hz, 1H, major), 3.77 (d, J=8.7Hz, 1H, minor), 2.46 (s, 3H, major+minor), 1.94 (dt, J=
14.9,7.4Hz, 1H, major+minor), 1.74 (dt, J=14.4,7.4Hz, 1H, major+minor), 0.61 (t, J=
7.5Hz,3H,major+minor).
13C NMR(100MHz,CDCl3)δ(ppm)173.4,144.9,137.2,136.6,133.9,131.6,129.2,
129.1,128.2,128.0,127.8,127.7,127.0,126.8,126.1,123.3,119.0,55.9,48.2,29.2,
21.7,7.5.
High-resolution：Calculated value：[M+H]+:432.1635, measured value:432.1628.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 94 of product:6er, diastereoisomer ratio 88:12dr, chiral IC-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=16.76 minutes, t2=
20.59 minutes.
Embodiment 16
Compound I-16
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-9 (41mg, 0.2mmol) is added in reaction system,
Reactant mixture is placed in into room temperature in 6W blue leds s reactor to continue to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:1 post
Chromatography directly obtains the target product 44.6mg of Formulas I -16, yield 97%.
1H NMR(400MHz,CDCl3) δ (ppm) 8.06 (d, J=8.1Hz, 2H, minor), 7.93 (d, J=8.0Hz,
2H, major), 7.65 (m, 1H, minor), 7.54-7.47 (m, 1H, major), 7.35 (d, J=8.0Hz, 2H, major+
minor),7.20–7.14(m,1H,major+minor),7.13–6.99(m,5H,major+minor),6.96–6.90(m,
2H, major+minor), 5.76-5.67 (m, 1H, minor), 5.61 (m, 1H, major), 5.33 (d, J=10.1Hz, 1H,
), minor 5.20 (d, J=16.8Hz, 1H, major), 5.09 (d, J=10.1Hz, 1H, major+minor), 3.95 (d, J=
8.0Hz, 1H, major), 3.76 (d, J=8.6Hz, 1H, minor), 2.47 (s, 3H, major+minor), 1.87 (td, J=
13.1,4.5Hz, 1H, major+minor), 1.69 (td, J=13.5,13.0,4.6Hz, 1H, major+minor), 1.12 (q,
J=7.4Hz, 2H, major+minor), 0.93 (dt, J=19.5,5.8Hz, 2H, major+minor), 0.73 (t, J=
7.3Hz,3H,major+minor)
13C NMR(100MHz,CDCl3)δ(ppm)173.3,144.8,137.5,136.6,133.9,133.8,131.6,
129.2,129.0,128.2,127.9,127.0,126.7,126.6,126.0,123.2,119.0,55.6,48.4,35.9,
25.0,22.8,21.6,13.8.
High-resolution：Calculated value：[M+H]+:460.1946, measured value:460.1941.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 96 of product:4er, diastereoisomer ratio 88:12dr, chiral IE-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=16.19 minutes, t2=
17.37 minutes.
Embodiment 17
Compound I-17
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-10 (37mg, 0.2mmol) is added to reaction system
In, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:
1 column chromatography directly obtains the target product 35.7mg of Formulas I -17, yield 80%.
1H NMR(400MHz,CDCl3) δ (ppm) 8.01 (d, J=8.1Hz, 2H, major), 7.88 (d, J=8.1Hz,
2H, minor), 7.62 (d, J=8.1Hz, 1H, major), 7.49 (d, J=8.8Hz, 1H, minor), 7.35 (d, J=
8.1Hz, 4H, major+minor), 7.23 (d, J=7.9Hz, 1H, major), 7.23-6.92 (m, 14H, major+minor),
6.90 (dd, J=7.7,2.0Hz, 1H, minor), 5.93 (dt, J=17.1,9.5Hz, 1H, major), 5.52 (d, J=
7.5Hz, 1H, minor), 5.32 (dd, J=34.4,13.6Hz, 2H, major), 5.17 (d, J=16.8Hz, 1H, minor),
5.01 (d, J=10.1Hz, 1H, minor), 4.08 (dd, J=7.1,5.1Hz, 1H, minor), 4.03 (d, J=8.8Hz, 1H,
), major 2.46 (s, 3H, minor), 2.45 (s, 3H, major), 2.31 (h, J=7.0Hz, 2H, major+minor), 0.86
(d, J=6.9Hz, 3H, minor), 0.75 (dd, J=11.1,6.8Hz, 6H, major), 0.68 (d, J=6.5Hz, 3H,
minor).
13C NMR(100MHz,CDCl3)δ(ppm)173.4,173.2,144.9,137.0,136.5,136.1,134.4,
134.2,133.8,133.8,132.3,131.5,129.3,129.2,129.1,128.5,128.2,127.9,127.6,
127.4,127.0,126.9,126.8,126.3,126.1,125.9,123.5,122.5,120.8,119.3,59.8,59.1,
48.6,47.5,33.5,30.5,21.7,20.8,19.1,18.4,16.7,16.5.
High-resolution：Calculated value：[M+H]+:446.1784, measured value:446.1780.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 98 of product:2er, diastereoisomer ratio 90:10dr, chiral IF-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=13.55 minutes, t2=
15.80 minutes.
Embodiment 18
Compound I-18
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-11 (48mg, 0.2mmol) is added to reaction system
In, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:
1 column chromatography directly obtains the target product 45.4mg of Formulas I -18, yield 88%.
1H NMR(400MHz,CDCl3) δ (ppm) 7.95 (d, J=8.2Hz, 2H, major), 7.70 (d, J=8.2Hz,
2H, minor), 7.50-7.44 (m, 1H, major), 7.38 (d, J=8.1Hz, 2H, major), 7.30 (d, J=8.1Hz, 3H,
), minor 7.15-6.90 (m, 20H, major+minor), 6.69 (d, J=7.9Hz, 2H, minor), 6.62 (d, J=
7.5Hz, 2H, major), 6.49 (d, J=7.4Hz, 2H, major), 5.83 (m, 1H, major), 5.69 (m, 1H, minor),
5.37-5.22 (m, 3H, major+minor), 4.99 (d, J=17.2Hz, 1H, minor), 3.83 (d, J=7.8Hz, 1H,
), major 3.43 (d, J=14.0Hz, 1H, minor), 3.27-3.03 (m, 2H, major), 2.49 (s, 3H, major), 2.46
(s,3H,minor).
13C NMR(100MHz,CDCl3)δ(ppm)172.9,145.0,144.9,137.9,136.6,136.5,136.5,
136.2,135.7,135.5,134.6,134.4,133.8,133.8,132.1,130.9,130.7,130.6,129.3,
129.3,129.2,129.1,128.6,128.1,127.8,127.8,127.6,127.4,127.1,127.0,127.0,
126.9,126.5,126.4,126.1,123.3,122.1,121.1,120.3,65.5,57.0,56.8,46.7,42.6,
41.2,21.7,21.7.
High-resolution：Calculated value：[M+H]+:516.1604, measured value:516.1607.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 94 of product:6er, diastereoisomer ratio 88:12dr, chiral AD-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=8.68 minutes, t2=
10.43 minutes.
Embodiment 19
Compound I-19
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-12 (45mg, 0.2mmol) is added to reaction system
In, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:
1 column chromatography directly obtains the target product 49.2mg of Formulas I -19, yield 98%.
1H NMR(400MHz,CDCl3) δ (ppm) 8.00 (d, J=8.1Hz, 2H), 7.52 (d, J=7.8Hz, 1H), 7.34
(d, J=8.1Hz, 2H), 7.24 (d, J=7.7Hz, 1H), 7.21-7.10 (m, 5H), 7.09-6.95 (m, 7H), 5.79 (m,
1H), 5.07 (d, J=10.3Hz, 1H), 4.97 (d, J=17.0Hz, 1H), 4.25 (d, J=6.8Hz, 1H), 2.47 (s, 3H)
13C NMR(100MHz,CDCl3)δ(ppm)171.5,145.0,139.8,139.5,136.5,134.8,134.0,
131.7,129.9,129.4,129.2,128.1,128.0,127.9,127.4,127.2,127.0,126.7,126.2,
123.2,119.7,61.7,50.9,21.7.
High-resolution：Calculated value：[M+H]+:502.1452, measured value:502.1447.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 96 of product:4er, chiral OD-H posts (isopropanol:N-hexane is 10:90,
v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=9.26 minutes, t2=10.68 minutes.
Embodiment 20
Compound I-20
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-13 (40mg, 0.2mmol) is added to reaction system
In, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:
1 column chromatography directly obtains the target product 44.9mg of Formulas I -20, yield 98%.
1H NMR(400MHz,CDCl3) δ (ppm) 8.06 (d, J=8.3Hz, 2H, minor), 7.96-7.90 (m, 2H,
), major 7.64 (d, J=8.1Hz, 1H, minor), 7.52 (dd, J=7.6,1.7Hz, 1H, major), 7.35 (d, J=
8.2Hz, 4H, major+minor), 7.15 (dd, J=6.8,2.3Hz, 2H, major+minor), 7.11-7.02 (m, 10H,
), major+minor 6.97-6.91 (m, 2H, major), 6.88 (dd, J=6.6,3.1Hz, 2H, minor), 5.73 (dt, J=
18.0,9.4Hz, 1H, minor), 5.66-5.53 (m, 3H, major+minor), 5.33 (d, J=10.2Hz, 1H, minor),
5.21 (d, J=16.8Hz, 2H, major+minor), 5.09 (d, J=10.1Hz, 1H, major), 4.89-4.76 (m, 4H,
), major+minor 3.92 (d, J=8.2Hz, 1H, major), 3.73 (d, J=8.8Hz, 1H, minor), 2.47 (s, 3H,
major),2.46(s,3H,minor),2.09–1.96(m,2H,major+minor),1.81–1.64(m,6H,major+
minor).
13C NMR(100MHz,CDCl3)δ(ppm)173.1,144.9,138.0,137.8,137.3,136.5,133.9,
131.5,130.5,129.4,129.4,129.3,129.2,129.1,128.9,128.8,128.4,128.2,128.1,
127.9,127.6,127.3,127.1,126.9,126.6,126.3,126.1,125.4,123.4,122.5,119.2,
114.6,114.5,55.6,49.3,35.6,35.4,27.9,27.7,21.7,21.7.
High-resolution：Calculated value：[M+H]+:458.1784, measured value:458.1785.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 95 of product:5er, diastereoisomer ratio 84:16dr, chiral IC-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=12.18 minutes, t2=
14.02 minutes.
Embodiment 21
Compound I-21
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-14 (45mg, 0.2mmol) is added to reaction system
In, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:
1 column chromatography directly obtains the target product 41.4mg of Formulas I -21, yield 88%.
1H NMR(400MHz,CDCl3) δ (ppm) 8.05 (d, J=8.4Hz, 2H, minor), 7.97-7.91 (m, 2H,
), major 7.64 (dd, J=8.2,1.1Hz, 1H, minor), 7.52 (dd, J=7.5,1.8Hz, 1H, major), 7.36 (t, J
=9.0Hz, 4H, major+monor), 7.16-7.01 (m, 12H, major+minor), 6.95-6.91 (m, 2H, major),
6.90–6.86(m,2H,minor),5.77–5.67(m,1H,minor),5.62(m,1H,major),5.36–5.31(m,1H,
), minor 5.22 (dt, J=16.7,1.2Hz, 2H, major+minor), 5.11 (dt, J=10.1,0.9Hz, 1H, major),
3.92 (d, J=8.1Hz, 1H, major), 3.71 (d, J=8.8Hz, 1H, minor), 2.47 (s, 6H, major+minor),
2.03-1.90 (m, 4H, major), 1.88 (t, J=2.6Hz, 1H, minor), 1.84 (t, J=2.6Hz, 1H, major),
1.81–1.74(m,4H,minor),1.23(m,4H,major+minor).
13C NMR(100MHz,CDCl3)δ(ppm)173.3,173.1,145.2,144.9,137.6,137.2,136.5,
134.9,134.1,133.8,133.7,133.3,131.4,131.3,130.7,129.4,129.4,129.3,129.2,
129.0,128.2,128.2,127.9,127.6,127.3,127.1,127.1,126.9,126.5,126.3,126.2,
123.3,122.5,119.3,84.0,83.7,68.4,68.3,56.7,55.5,49.3,35.7,35.3,26.9,22.7,
21.7,21.7,18.6.
High-resolution：Calculated value：[M+H]+:470.1784, measured value:470.1782.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 94 of product:6er, diastereoisomer ratio 84:16dr, chiral OX-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=17.48 minutes, t2=
22.01 minutes.
Embodiment 22
Compound I-22
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-15 (59mg, 0.2mmol) is added to reaction system
In, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:
1 column chromatography directly obtains the target product 53.0mg of Formulas I -22, yield 96%.
1H NMR(400MHz,CDCl3)δ(ppm)8.09–8.02(m,2H,minor),7.96–7.90(m,2H,major),
7.64 (dd, J=8.2,1.1Hz, 1H, minor), 7.52 (dd, J=7.5,1.7Hz, 1H, major), 7.37-7.20 (m,
14H,major+minor),7.16–7.01(m,12H,major+minor),6.96–6.88(m,4H,major+minor),
5.71 (m, 1H, minor), 5.59 (m, 1H, major), 5.30 (d, J=10.1Hz, 1H, minor), 5.21 (m, 2H, minor+
), major 5.08 (m, 1H, major), 4.36 (s, 2H, minor), 4.34 (s, 2H, major), 3.92 (d, J=8.1Hz, 1H,
), major 3.71 (d, J=8.6Hz, 1H, minor), 3.26 (m, 4H, major+mnior), 2.47 (s, 3H, major), 2.42
(s,3H,minor),2.04(m,1H,minor),1.94(m,2H,major+minor),1.75(m,1H,major),1.32(m,
2H,major+minor).
13C NMR(100MHz,CDCl3)δ(ppm)173.4,173.2,145.1,144.9,138.5,138.4,137.7,
137.4,136.7,136.5,134.2,133.9,133.8,133.6,131.5,130.8,129.3,129.3,129.2,
129.1,128.2,128.1,127.9,127.7,127.5,127.5,127.4,127.3,127.1,127.0,127.0,
126.9,126.6,126.2,126.1,123.4,122.4,120.5,119.2,72.6,72.4,70.4,70.1,56.8,
55.5,49.2,32.9,32.8,30.3,23.9,23.7,21.7,21.6.
High-resolution：Calculated value：[M+H]+:552.2203, measured value:552.2212.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 95 of product:5er, diastereoisomer ratio 87:13dr, chiral IA-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=15.35 minutes, t2=
16.20 minutes.
Embodiment 23
Compound I-23
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-16 (35mg, 0.2mmol) is added to reaction system
In, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:
1 column chromatography directly obtains the target product 42.6mg of Formulas I -23, yield 99%.
1H NMR(400MHz,CDCl3) δ (ppm) 8.03 (d, J=8.1Hz, 2H, minor), 7.98 (d, J=8.1Hz,
2H, major), 7.76 (d, J=8.2Hz, 1H, major), 7.72 (d, J=8.1Hz, 1H, minor), 7.46-7.40 (m, 2H,
), major+minor 7.33 (d, J=8.0Hz, 4H, major+minor), 7.29-7.23 (m, 2H, major+minor),
7.18-7.06 (m, 6H, major+minor), 6.97-6.90 (m, 1H, minor), 6.82 (t, J=7.6Hz, 1H, major),
6.37 (d, J=7.7Hz, 1H, minor), 5.94 (d, J=7.8Hz, 1H, major), 5.81-5.68 (m, 1H, major),
5.62 (dt, J=17.8,9.3Hz, 1H, major), 5.22 (d, J=10.2Hz, 1H, minor), 5.18-5.04 (m, 3H,
), major+minor 3.52 (d, J=8.4Hz, 1H, major), 3.48 (d, J=9.2Hz, 1H, minor), 3.06 (dt, J=
15.6,7.7Hz, 1H, major), 2.91 (d, J=8.2Hz, 1H, minor), 2.89-2.79 (m, 2H, major+minor),
2.52–2.45(m,1H,major),2.44(s,6H,major+minor),2.39–2.31(m,1H,minor),2.00(ddd,J
=13.4,8.5,7.0Hz, 1H, major), 1.91 (d, J=6.0Hz, 1H, minor)
13C NMR(100MHz,CDCl3)δ(ppm)173.3,144.9,144.6,142.2,136.6,134.9,134.5,
131.2,129.3,129.0,128.5,128.1,127.7,126.5,126.4,124.9,123.9,123.4,119.3,60.6,
51.6,33.9,30.8,21.7.
High-resolution：Calculated value：[M+H]+:430.1471, measured value:430.1464.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 94 of product:6er, diastereoisomer ratio>95:5dr, chiral IF-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=17.30 minutes, t2=
18.32 minutes.
Embodiment 24
Compound I-24
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-17 (42mg, 0.5mmol) is added to reaction system
In, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:
1 column chromatography directly obtains the target product 28.7mg of Formulas I -24, yield 84%.
1H NMR(400MHz,CDCl3) δ (ppm) 7.93 (d, J=7.9Hz, 2H), 7.71 (d, J=8.1Hz, 1H),
7.37-7.30 (m, 3H), 7.23 (d, J=7.0Hz, 2H), 5.67 (ddd, J=17.4,10.2,7.5Hz, 1H), 5.31-5.02
(m, 2H), 3.19 (t, J=7.7Hz, 1H), 2.52 (p, J=7.3Hz, 1H), 2.44 (s, 3H), 1.03 (d, J=7.1Hz,
3H).
13C NMR(100MHz,CDCl3)δ(ppm)173.0,144.9,136.6,136.2,134.5,131.1,129.2,
129.0,127.3,127.3,126.2,123.4,118.9,46.6,43.5,21.7,14.2.
High-resolution：Calculated value：[M+H]+:342.1158, measured value:342.1150.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 95 of product:5er, diastereoisomer ratio>95:5dr, chiral IE-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=22.67 minutes, t2=
25.26 minutes.
Embodiment 25
Compound I-25
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-18 (23mg, 0.2mmol) is added to reaction system
In, reactant mixture is placed in room temperature in 6W bule LEDs reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=30:1-
20:1 column chromatography directly obtains the target product 27.8mg of Formulas I -25, yield 75%.
1H NMR(400MHz,CDCl3) δ (ppm) 7.91-7.84 (m, 2H), 7.79 (dd, J=8.3,1.1Hz, 1H),
7.36 (td, J=7.8,1.8Hz, 1H), 7.28 (d, J=8.2Hz, 2H), 7.21 (m, 2H), 5.62 (m, 1H), 4.96-4.80
(m, 2H), 3.45 (m, 1H), 2.42 (s, 3H), 2.24 (dd, J=9.7,2.4Hz, 1H), 1.37-1.27 (m, 1H), 0.87 (d,
J=6.7Hz, 3H), 0.81 (d, J=6.6Hz, 3H)
13C NMR(100MHz,CDCl3)δ(ppm)171.5,144.8,137.3,136.2,134.7,129.6,129.4,
128.9,128.7,127.4,126.3,123.7,117.2,56.5,43.5,26.8,21.6,20.8,20.4.
High-resolution：Calculated value：[M+H]+:370.1471, measured value:370.1479.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 92 of product:8er, diastereoisomer ratio>95:5dr, chiral IF-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=12.44 minutes, t2=
13.30 minutes.
Embodiment 26
Compound I-26
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-19 (26mg, 0.2mmol) is added to reaction system
In, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:
1 column chromatography directly obtains the target product 30.1mg of Formulas I -26, yield 78%.
1H NMR(400MHz,CDCl3) δ (ppm) 7.88 (d, J=8.1Hz, 2H), 7.73 (d, J=8.2Hz, 1H), 7.35
(m, 1H), 7.29 (d, J=8.2Hz, 2H), 7.25-7.17 (m, 2H), 5.66 (m, 1H), 5.01-4.75 (m, 2H), 3.56
(dd, J=4.9,2.0Hz, 1H), 2.43 (s, 4H), 0.73 (s, 9H)
13C NMR(100MHz,CDCl3)δ(ppm)171.2,144.8,138.8,136.3,135.5,129.6,129.6,
128.9,128.5,127.5,126.5,123.7,116.5,58.7,42.4,34.0,28.6,21.7.
High-resolution：Calculated value：[M+H]+:384.1628, measured value:384.1630.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 93 of product:7er, diastereoisomer ratio>95:5dr, chiral IE-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=20.77 minutes, t2=
22.46 minutes.
Embodiment 27
Compound I-27
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-20 (22mg, 0.2mmol) is added to reaction system
In, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:
1 column chromatography directly obtains the target product 29.8mg of Formulas I -27, yield 81%.
1H NMR(400MHz,CDCl3) δ (ppm) 7.92-7.85 (m, 2H), 7.78 (d, J=8.2Hz, 1H), 7.40-
7.33 (m, 1H), 7.29 (d, J=8.1Hz, 2H), 7.26-7.23 (m, 2H), 5.65 (m, 1H), 5.01-4.82 (m, 2H),
3.45(m,1H),2.43(s,3H),1.85–1.71(m,1H),0.54–0.35(m,4H),0.16–0.08(m,1H).
13C NMR(100MHz,CDCl3)δ(ppm)171.6,144.9,137.0,136.1,134.4,129.8,129.6,
129.0,128.8,127.4,126.3,123.7,117.1,54.6,46.3,21.6,11.4,4.4,4.0.
High-resolution：Calculated value：[M+H]+:368.1315, measured value:368.1310.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 93 of product:7er, diastereoisomer ratio>95:5dr, chiral IF-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=23.18 minutes, t2=
29.09 minutes.
Embodiment 28
Compound I-28
Preparation
At room temperature, the palladium chloroform adducts (5.2mg, 0.005mmol) of metallic catalyst three (dibenzalacetone) two with
Ligand i V (7.6mg, 0.011mmol) is dissolved in dichloromethane, is stirred 30 minutes under nitrogen protection.Then add 4- vinyl
Benzoxazinone II-1 (33mg, 0.1mmol), then α-diazo-ketones III-21 (30mg, 0.2mmol) is added to reaction system
In, reactant mixture is placed in room temperature in 6W blue leds s reactor and continues to react 24h, with VPetroleum ether/VEthyl acetate=30:1-20:
1 column chromatography directly obtains the target product 38.8mg of Formulas I -28, yield 95%.
1H NMR(400MHz,CDCl3) δ (ppm) 7.97 (d, J=8.1Hz, 2H), 7.65 (d, J=8.1Hz, 1H), 7.33
(dd, J=8.3,5.6Hz, 3H), 7.24-7.17 (m, 2H), 5.64 (m, 1H), 5.31 (d, J=3.8Hz, 1H), 5.24-5.02
(m, 2H), 3.56 (t, J=7.6Hz, 1H), 3.01 (d, J=7.8Hz, 1H), 2.44 (s, 3H), 1.88 (m, 2H), 1.71-
1.65(m,2H),1.45(m,4H).
13C NMR(100MHz,CDCl3)δ(ppm)171.2,144.9,136.6,136.1,134.7,131.7,131.1,
129.2,129.1,127.2,127.2,127.2,126.2,123.2,118.3,57.4,43.4,25.5,25.2,22.5,
21.8,21.6.
High-resolution：Calculated value：[M+H]+:408.1628, measured value:408.1630.
(c=1.0, CHCl3).
Optical purity analysis：The enantiomeric ratio 95 of product:5er, diastereoisomer ratio>95:5dr, chiral IE-H
Post (isopropanol:N-hexane is 10:90, v:V), 1.0mL/min, 254nm, 25 DEG C, retention time t1=35.08 minutes, t2=
37.29 minutes.
III-1~III-21 structures are as follows：
In the description of this specification, reference term " one embodiment ", " some embodiments ", " example ", " specifically show
The description of example " or " some examples " etc. means specific features, structure, material or the spy for combining the embodiment or example description
Point is contained at least one embodiment or example of the present invention.In this manual, to the schematic representation of above-mentioned term not
Identical embodiment or example must be directed to.Moreover, specific features, structure, material or the feature of description can be with office
Combined in an appropriate manner in one or more embodiments or example.In addition, in the case of not conflicting, the skill of this area
Art personnel can be tied the different embodiments or example and the feature of different embodiments or example described in this specification
Close and combine.
Although embodiments of the invention have been shown and described above, it is to be understood that above-described embodiment is example
Property, it is impossible to limitation of the present invention is interpreted as, one of ordinary skill in the art within the scope of the invention can be to above-mentioned
Embodiment is changed, changed, replacing and modification.
Claims (12)
- A kind of 1. quinoline ketone derivative, it is characterized in that the compound is Formulas I0Enantiomter, the diastereomeric of shown compound Isomers, racemic modification, pharmaceutically acceptable salt, crystalline hydrate or solvate：Wherein, Formulas I0Middle R1For hydrogen, C1-6Alkyl, C1-6Alkoxy, fluorine, chlorine, bromine or trifluoromethyl；R2For hydrogen, methyl, phenyl, 2- naphthyls, wherein phenyl is alternatively substituted by methyl, methoxyl group, fluorine, a chlorine or bromine；R3For C1-6Alkyl, phenyl, benzyl, high allyl, high-propargyl, 3- benzyloxies propyl group, cyclopropane or cyclohexenyl group.
- 2. according to Formulas I0Described quinoline ketone derivative, it is characterised in that：R1For hydrogen, 6- methyl, 6- methoxyl groups, 6- bromines, 6- chlorine, 7- chlorine, 7- trifluoromethyls or 8- fluorine；R2For hydrogen, methyl, phenyl, 2- naphthyls, 4- aminomethyl phenyls, 3- chlorphenyls, 4- methoxyphenyls, 4- fluorophenyls, 4- chlorphenyls Or 4- bromophenyls；R3For methyl, ethyl, isopropyl, normal-butyl, the tert-butyl group, phenyl, benzyl, high allyl, high-propargyl, 3- benzyloxies third Base, cyclopropane or cyclohexenyl group.
- 3. according to Formulas I0Described quinoline ketone derivative, it is characterised in that：Formulas I0For with the optically active quinolinone of such as Formulas I Analog derivative, pharmaceutically acceptable salt, crystalline hydrate or solvate：
- 4. quinoline ketone derivative according to claim 1, it is characterised in that the compound is pair of following compounds Reflect isomers, diastereoisomer, racemic modification, pharmaceutically acceptable salt, crystalline hydrate or solvate：
- A kind of 5. method for preparing any one of Claims 1-4 quinoline ketone derivative, it is characterised in that including：Compound shown in Formula II is set to be contacted with compound shown in formula III, to obtain Formulas I0Shown compound：Wherein R1、R2、R3It is as defined in any one of Claims 1 to 4.
- 6. preparation method according to claim 5, it is characterised in that the contact is by compound shown in Formula II, III with urging Agent and part are dissolved in organic solvent, under nitrogen protection, are reacted under visible ray promotion and Formulas I is made0Compound.
- 7. preparation method according to claim 6, it is characterised in that the catalyst is three (dibenzalacetone) two palladium Chloroform adducts, optionally, the mol ratio of compound shown in the catalyst and Formula II are 1：20.
- 8. preparation method according to claim 6, it is characterised in that the part be double (diphenylphosphine) propane of 1,3- or Formula IV compound：Optionally, the mol ratio of compound shown in the part and Formula II is 1：10；When the part is formula IV compound, instead It should obtain with such as the optically active quinoline ketone derivative of Formulas I.
- 9. preparation method according to claim 6, it is characterised in that compound shown in formula III and compound shown in Formula II Mol ratio be 2:1.
- 10. preparation method according to claim 6, it is characterised in that organic solvent is selected from dichloromethane；Reaction temperature is Room temperature；Reaction time is 18-30 hours, preferably 24 hours；Visible ray promotes that 6W blue leds s reactor can be selected.
- 11. preparation method according to claim 6, it is characterised in that catalyst and part are under nitrogen protection organic After being stirred in solvent, Formula II is added, compound shown in III, reacted under visible ray promotion and Formulas I is made0Compound.
- 12. preparation method according to claim 11, it is characterised in that catalyst and part are under nitrogen protection organic The temperature stirred in solvent is room temperature, and the time is half an hour.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108440526A (en) * | 2018-05-11 | 2018-08-24 | 北京工业大学 | A kind of chirality barbital spiral shell Tetrahydroquinolinesas and preparation method |
| CN109970638A (en) * | 2019-05-15 | 2019-07-05 | 扬州大学 | A kind of method of high enantioselectivity catalytically synthesizing chiral quinolinone compounds |
Citations (1)
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| CN105732495A (en) * | 2015-12-16 | 2016-07-06 | 华中师范大学 | Tetrahydroquinoline compound having optical activity and preparation method thereof |
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| CN105732495A (en) * | 2015-12-16 | 2016-07-06 | 华中师范大学 | Tetrahydroquinoline compound having optical activity and preparation method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108440526A (en) * | 2018-05-11 | 2018-08-24 | 北京工业大学 | A kind of chirality barbital spiral shell Tetrahydroquinolinesas and preparation method |
| CN108440526B (en) * | 2018-05-11 | 2020-10-16 | 北京工业大学 | Chiral barbiturate spiro tetrahydroquinoline compound and preparation method thereof |
| CN109970638A (en) * | 2019-05-15 | 2019-07-05 | 扬州大学 | A kind of method of high enantioselectivity catalytically synthesizing chiral quinolinone compounds |
| CN109970638B (en) * | 2019-05-15 | 2022-05-31 | 扬州大学 | Method for catalytically synthesizing chiral quinolinone compound with high enantioselectivity |
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| CN107417615B (en) | 2019-12-13 |
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