CN108707144B - Chiral quinoline amine compound and preparation method and application thereof - Google Patents

Chiral quinoline amine compound and preparation method and application thereof Download PDF

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CN108707144B
CN108707144B CN201810207559.XA CN201810207559A CN108707144B CN 108707144 B CN108707144 B CN 108707144B CN 201810207559 A CN201810207559 A CN 201810207559A CN 108707144 B CN108707144 B CN 108707144B
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陆展
陈旭
程朝阳
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Abstract

The invention discloses a chiral quinoline amine compound shown as a formula (1) and discloses a simple and convenient preparation method. The quinoline amine compound shown in the formula (1) provided by the invention can be used for preparing a chiral organic boron ester compound. The chiral oxazoline or imidazoline phenyl quinoline amine compound and the transition metal MY'nThe in-situ complex can be used as a homogeneous catalyst for preparing chiral organic boron compounds by asymmetric hydroboration addition on the double bond of the carbon-carbon atom of prochiral organic compounds, and the prochiral unsaturated compounds used for asymmetric hydroboration are preferably styrene compounds. The chiral organoboron ester compounds which can be prepared according to the present invention are important organic synthesis intermediates, in particular in the production of pharmaceutical formulations, fragrances and odorants, agrochemicals.

Description

Chiral quinoline amine compound and preparation method and application thereof
Technical Field
The invention relates to a chiral quinoline amine compound, a preparation method and application thereof, in particular to a synthetic chiral oxazoline or imidazoline or thiazoline phenyl quinoline amine compound, a preparation method thereof and application of the chiral compound and cobalt or iron in the co-catalysis of asymmetric Ma's hydroboration reaction of aromatic olefin.
Background
The chiral benzyl boron ester is an important synthetic intermediate (C.Sandford, V.K.Aggarwal, chem. Commun.2017,53,5481.), and the asymmetric hydroboration reaction of olefin is an efficient and simple method for preparing the chiral benzyl boron ester, has the advantages of easily obtained raw materials, high reaction atom economy and the like, and is widely concerned by synthetic chemists.
In 1989, Hayashi and Ito et al used chiral BINAP ligand L1, and made a breakthrough in Rh-catalyzed asymmetric hydroboration of styrenic compounds with product ee values as high as 96%, but this reaction used unstable catechol borane reagent and product instability, and required low temperature at-78 ℃ [ t.hayashi, y.matsumoto, y.ito, j.am.chem.soc.1989,111,3426 ]. In 1993, a Brown group uses chiral P and N ligands L2 to realize Rh catalyzed asymmetric Ma's hydroboration reaction of styrene and catechol borane, and the ee value of the reaction can reach 88% [ J.M.Brown, D.I.Hulmes, T.P.Layzell, J.chem.Soc.chem.Commun.1993,1673 ]. In 1995, the Togni group synthesized chiral ferrocene ligand L3 containing a pyrrole ring, which was applied to Rh-catalyzed styrene and catechol boranes
Figure BDA0001596279740000011
Figure BDA0001596279740000021
In asymmetric hydroboration reactions chiral boron can be obtained with ee values up to 98%, but the regioselectivity of the reaction is poor, with a ratio of martensitic to anti-martensitic product of 3 to 2[ a.schnyder, l.hintermann, a.togni, angelw.chem., int.ed.1995,34,931 ]. In 2001, Knochel et al reported a novel method for synthesizing diphosphine ligand L4, and when the diphosphine ligand L4 is used in Rh-catalyzed asymmetric hydroboration reaction of styrene compounds, the ee value of the product can reach up to 93% [ S.Demayy, F.Volant, P.Knochel, Angew. chem., int.Ed.2001,40,1235 ]. In 2002, the Schmalz group applied diphosphine ligand L5 to Rh-catalyzed asymmetric hydroboration of styrene, with an ee of the product of 88% and a yield of 97% [ f. Blume, s.zemolka, t.fey, r.kranich, h.g.schmalz, adv.synth.cat.2002, 344, 868 ]. In 2004, crudeden et al used ligand L6 to achieve Rh-catalyzed asymmetric hydroboration of styrene and HBPin with a maximum ee of 88% to obtain stable chiral boron ester products, but with poor regioselectivity [ c.m. crudeden, y.b. hleba, a.c. chen, j.am.chem.soc.2004,126, 9200 ]. In 2015, the tangwen troops group used phosphine ligand L7 and utilized amide on the substrate as a guiding group to realize Rh-catalyzed asymmetric ma-shi boronation reaction of alpha-acetamido-substituted styrene substrate to generate corresponding chiral quaternary carbon-boron compound with ee value as high as 96% [ n.f.hu, g.q.zhao, y.y.zhang, x.q.liu, g.y.li, w.j.tang, j.am.chem.soc.2015,137,6746 ]. In 2009, Yun groups achieved copper-catalyzed asymmetric mahalanobis reactions (51-95% ee) with high regio-and stereoselectivity of styrenic substrates using chiral phosphine ligands 5-8, but the range of functional group compatibility was narrow (only fluorine-, chlorine-, methoxy-, and methyl-substituted styrene substrates were reported) [ d.noh, h.chea, j.ju, j.yun, angelw.chem.int.ed. 2009,48,6062 ]. Later, they achieved copper-catalyzed, high enantioselectivity, 1, 2-disubstituted aromatic alkenes via mahalanobis hydroboration using a highly hindered 5-9 ligand, with only 6 examples reported, and substrates with substituents on the benzene ring not reported [ d.noh, s.k.yoon, j.won, j.y.lee, j.yun, chem. Asian j.2011,6,1967 ]. In addition, chiral phosphine ligands, which are difficult to prepare and air sensitive, were used in both examples.
From the above review, it can be seen that the use of noble metal catalyst and cheap metal copper to achieve certain extent of high regio-and enantioselectivity of styrenic compounds by means of mahalanobis hydroboration (Scheme 1) still has some limitations, such as most of the cases where air-sensitive catechol borane is used as a boron source, the corresponding chiral boron product is unstable and needs to be separated as alcohol after oxidation; the reaction needs to be carried out at low temperature; when relatively stable HBPin is used as a boron source, the regioselectivity of the reaction is poor; the ligand used in most reactions is a chiral phosphine ligand (Scheme 2). These factors limit the use of asymmetric Mayer's reaction for the synthesis of chiral benzylic boron esters.
The earth's high-yield metal iron and cobalt has low price, low toxicity and environmental protection, and has gained wide attention in the field of asymmetric catalysis [ h.pellisier, h.claimer, chem.rev.2014,114, 2775; K. gopalaiah, chem.Rev.2013,113,3248. In the last five years, iron and cobalt catalyzed asymmetric hydroboration of olefins has made some progress [ l.zhang, z.zuo, x.wan, z.huang, j.am.chem.soc., 2014,136,15501 ]; chen, t.xi, x.ren, b.cheng, j.guo, z.lu, org, chem.front.2014,1,1306; chen, t.xi, z.lu, org.lett.2014,16,6452; h.y. Zhang, z.lu, ACS catal.2016,6,6596; c.h.chen, x.z.shen, j.h.chen, x.hong, z.lu, org.lett.2017,19,5422. From these reported examples, we can see that the earth's high yields of the transition metals iron and cobalt are to a large extent comparable to noble metal catalysts in the anti-Markovnikov asymmetric hydroboration of 1, 1-disubstituted olefins. However, no literature is reported on the iron or cobalt catalyzed asymmetric Ma's hydroboration reaction study of styrene and 1, 2-disubstituted aromatic olefins.
From the perspective of sustainable development and green chemistry, if we can develop a chiral ligand which is simple, convenient and easy to synthesize and is suitable for iron and cobalt, the earth's high yield transition metal iron and cobalt is applied to the Ma's asymmetric hydroboration reaction of aromatic olefin instead of a noble metal catalyst, and simultaneously, the defects in the conversion of the existing noble metal catalyst and copper catalyst are overcome, so that the method has very important theoretical and practical significance.
Disclosure of Invention
The invention discloses a novel amine compound containing chiral oxazoline or imidazoline or thiazoline phenyl quinoline and a preparation method thereof, and application of the compounds in asymmetric synthesis under the co-catalysis of iron and cobalt, in particular to asymmetric Ma's hydroboration reaction of styrene compounds, and realizes the asymmetric Ma's hydroboration reaction of aromatic olefin under the catalysis of cheap metal iron for the first time.
The invention is realized by the following technical scheme:
in a first aspect, the present invention provides a quinoline amine compound represented by the formula (1),
Figure BDA0001596279740000041
in the formula (1), X is O, S or NR14；
R1，R2，R3，R4，R5，R6，R7，R8，R9And R10Each independently is hydrogen, halogen, alkyl of C1-C10, fluoroalkyl of C1-C4, alkoxy of C1-C4, cycloalkyl of C3-C10 or aryl of C6-C14;
R11and R12Each independently hydrogen, C1-C10 alkyl or C6-C14 aryl;
R13is C1-C12 alkyl, C3-C12 cycloalkyl, benzyl or C6-C14 aryl, wherein H on the C1-C12 alkyl is not substituted or is substituted by 1-2C 1-C4 alkoxy; h on the C3-C12 cycloalkyl is not substituted or is substituted by 1-3C 1-C4 alkyl groups or C1-C4 alkoxy groups, H on the C6-C14 aryl is not substituted or is substituted by 1-3 substituent groups A, and the substituent groups A are C1-C4 alkyl groups, C1-C4 alkoxy groups, C1-C4 fluoroalkyl groups, C1-C4 fluoroalkoxy groups, F or Cl;
R14is hydrogen, C1-C10 alkyl, benzyl or C6-C14 aryl, H on the C6-C14 aryl is unsubstituted or substituted by 1-4 substituents B, the substituents B are C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F or Cl;
or R12And R13Is connected with two carbons on the five-membered ring to form a ring C9-C15A benzocycloalkyl group of (1).
The aryl group is generally phenyl or naphthyl, and the x in the formula (1) represents a chiral carbon atom.
As a further improvement, R is1-R10Each independently preferably hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C4 alkoxy or C6-C10 aryl;
R11and R12Each is preferably hydrogen, C1-C6 alkyl or C6-C14 aryl;
R13preferably C1-C6 alkyl, benzyl or C6-C10 aryl.
R14Preference is given to hydrogen, C1-C6 alkyl, benzyl or C6-C10 aryl.
Further, R1Preferably hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl or C6-C10 aryl, more preferably hydrogen, C1-C6 alkyl or C3-C6 cycloalkyl, and still more preferably hydrogen, methyl, ethyl, isopropyl, methoxy or cyclohexyl.
R2，R3，R4，R5，R6，R7，R8，R9，R10Preferably hydrogen, C1-C4 alkoxy, C1-C6 alkaneOr phenyl, more preferably hydrogen, methyl, ethyl, propyl, isopropyl, n-butyl, methoxy or phenyl.
R11，R12More preferably H, methyl, ethyl, isopropyl or phenyl, more preferably R11，R12All are H.
R13More preferably methyl, isopropyl, tert-butyl, phenyl, indenyl or benzyl;
or preferably R12And R13And two carbons on the five-membered ring are connected to form a ring, and the indane is formed.
R14More preferably phenyl or substituted phenyl, the substituted phenyl is phenyl with 1-3 substituents B on the phenyl ring, the substituents B are preferably C1-C4 alkyl, C1-C4 alkoxy and trifluoromethyl, and more preferably methyl, ethyl, isopropyl, tert-butyl, methoxy or trifluoromethyl.
Most preferably, the quinoline amine compound is one of the following:
Figure BDA0001596279740000051
Figure BDA0001596279740000061
in a second aspect, the present invention also provides a preparation method of the quinoline amine compound, where the method is:
under the inert gas environment, in the presence of a transition metal catalyst, a ligand and alkali, in an organic solvent A, taking aminoquinoline shown in a formula (2) and a halide shown in a formula (3) as raw materials or taking a quinoline halide shown in a formula (4) and aniline shown in a formula (5) as raw materials to carry out coupling reaction to prepare a quinoline amine compound shown in a formula (1); the transition metal catalyst is a complex of palladium (Pd), preferably a zero-valent palladium complex, more preferably Pd2(dba)3，Pd(dba)2(ii) a The ligand is an organic phosphorus compound, preferably 1,1 '-bis (diphenylphosphino) ferrocene (dppf), (+ -) -2,2' -bis- (diphenylphosphino)1,1' -Binaphthyl (BINAP) or 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene (xanthphos); the alkali is alkali metal salt of alcohol, preferably potassium salt or sodium salt of alcohol, more preferably sodium tert-butoxide and potassium tert-butoxide;
Figure BDA0001596279740000071
x in the formula (3) is O, S or NR14(ii) a Y is F, Cl, Br or I, preferably Br or I;
Figure BDA0001596279740000072
in the formula (5), X is O, S or NR14(ii) a Y in the formula (4) is F, Cl, Br or I, preferably Br or I;
r in the formula (2)1，R2，R3，R4，R5，R6，R7，R8，R9And R10Each independently is hydrogen, halogen, alkyl of C1-C10, fluoroalkyl of C1-C4, alkoxy of C1-C4, cycloalkyl of C3-C10 or aryl of C6-C14;
R11and R12Each independently hydrogen, C1-C10 alkyl or C6-C14 aryl;
R13is C1-C12 alkyl, C3-C12 cycloalkyl, benzyl or C6-C14 aryl, wherein H on the C1-C12 alkyl is not substituted or is substituted by 1-2C 1-C4 alkoxy; h on the C3-C12 cycloalkyl is not substituted or is substituted by 1-3C 1-C4 alkyl groups or C1-C4 alkoxy groups, H on the C6-C14 aryl is not substituted or is substituted by 1-3 substituent groups A, and the substituent groups A are C1-C4 alkyl groups, C1-C4 alkoxy groups, C1-C4 fluoroalkyl groups, C1-C4 fluoroalkoxy groups, F or Cl;
R14is hydrogen, C1-C10 alkyl, benzyl or C6-C14 aryl, H on the C6-C14 aryl is unsubstituted or substituted by 1-4 substituents B, the substituents B are C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F or Cl;
or R12And R13Is connected with two carbons on the five-membered ring to form a ring C9-C15Benzocycloalkyl groups of (a);
r in the formulae (3), (4) and (5)1-R14The same as formula (2). In formula (3) and formula (5)' represents a chiral carbon atom.
That is, the method for producing the quinoline amine compound of the present invention is one of the following: 1) under the inert gas environment, in the presence of a transition metal catalyst, a ligand and alkali, in an organic solvent, carrying out a coupling reaction by taking aminoquinoline shown in a formula (2) and a halide shown in a formula (3) as raw materials to prepare a quinoline amine compound shown in the formula (1); or 2) under the inert gas environment, in the presence of a transition metal catalyst, a ligand and alkali, in an organic solvent, carrying out coupling reaction by using a quinoline halide shown in a formula (4) and an aniline compound shown in a formula (5) as raw materials to prepare the quinoline amine compound shown in the formula (1).
As a further improvement, the reaction temperature of the coupling reaction is 50 ℃ to 200 ℃, and the reaction time is 1 hour to 72 hours.
As a further improvement, the organic solvent A for the coupling reaction is any one of benzene, dimethylformamide, carbon tetrachloride, toluene, petroleum ether, dioxane, tetrahydrofuran, diethyl ether, chloroform, xylene and acetonitrile, and is preferably toluene or xylene.
The inert gas environment is generally under nitrogen.
As a further improvement, the ratio of the amounts of the halide represented by the formula (3), the aminoquinoline represented by the formula (2), the transition metal catalyst, the ligand and the base is 1:0.1-4:0.01-0.5: 1 to 4, preferably 1:1 to 2:0.02 to 0.3:0.1 to 0.3:1 to 3.
As a further improvement, the mass ratio of the quinoline bromide shown in the formula (4), the aniline shown in the formula (5), the transition metal catalyst, the ligand and the base is 1:0.1-4:0.01-0.5: 1 to 4, preferably 1:1 to 2:0.02 to 0.3:0.1 to 0.3:1 to 3.
The volume usage amount of the organic solvent A is 0.5-8 ml/mmol, preferably 2-8ml/mmol, based on the amount of the halide shown in the formula (3) or the quinoline bromide shown in the formula (4).
After the coupling reaction, the heating is stopped, after the reaction solution is returned to the room temperature, silica gel is filtered, ethyl acetate is washed, the filtrate is concentrated, and the product is obtained by column chromatography separation.
The invention also provides an application of the quinoline amine compound shown in the formula (1) in preparing a chiral organic boron ester compound, wherein the application method comprises the following steps: in an organic solvent B and a transition metal compound MYnIn the presence of quinoline amine compound shown as a formula (1), aromatic olefin compound shown as a formula (7) and pinacolborane (HBPin, full chemical name is 4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan) shown as a formula (8) are used as raw materials to carry out asymmetric Ma's hydroboration reaction to prepare chiral organic boron ester compound shown as a formula (6);
Figure BDA0001596279740000081
in the formula (7), Ar is phenyl or substituted phenyl, and the substituent of the substituted phenyl is C1-C6 alkyl, C1-C6 alkoxy, methylthio, CF3F, Cl or Br, preferably methyl, tert-butyl, F or Cl; ar in the formula (6) is the same as the formula (7);
the transition metal compound MYnWherein M is transition metal Fe or Co; y is F, Cl, Br, I, OSO2CH3、OSO2CF3、O(CH3)C＝CHCOCH3、OCOCH2CH3、OCOCH3、ClO4Any one of the above; n is the number of Y and is 2 or 3, and the transition metal compound MY is preferrednFerrous chloride or cobalt acetate;
the organic solvent B is toluene, diethyl ether or 1, 4-dioxane.
Further, when the transition metal compound MYnIn the case of ferrous chloride, NaBHEt is added in the reaction3I.e. in organic solvent B, NaBHEt3An aromatic olefin compound represented by the formula (7) and pinacol represented by the formula (8) in the presence of ferrous chloride and a quinoline amine compound represented by the formula (1)Carrying out asymmetric Markov hydroboration reaction on borane serving as a raw material to prepare a chiral organic boron ester compound shown as a formula (6); the aromatic olefin compound represented by the formula (7) and pinacolborane and NaBHEt represented by the formula (8)3Transition metal compound MYnAnd the amount of the quinoline amine compound substance represented by the formula (1) is 1: 0.2-2.0: 0.01-0.2: 0.005-0.1: 0.005-0.12, preferably 1:1-2:0.1-0.2:0.02-0.05: 0.03-0.06;
when transition metal compound MYnWhen the compound is cobalt acetate, in the presence of an organic solvent B, cobalt acetate and a quinoline amine compound shown in a formula (1), an aromatic olefin compound shown in a formula (7) and pinacol borane shown in a formula (8) are used as raw materials to carry out asymmetric Markov hydroboration reaction to prepare a chiral organic boron ester compound shown in a formula (6); the aromatic olefin compound shown as the formula (7) and pinacolborane and a transition metal compound MY shown as the formula (8)nAnd the amount of the quinoline amine compound substance represented by the formula (1) is 1: 0.2-2.0: 0.005-0.1: 0.005-0.12, preferably 1:1-2:0.02-0.05: 0.03-0.06; .
The volume usage amount of the organic solvent B is 0.25-5 ml/mmol, preferably 1-2ml/mmol, based on the amount of the aromatic olefin substance represented by the formula (7).
Further, the asymmetric Ma's hydroboration reaction condition is 0-50 ℃ for 1-72 h.
After the asymmetric Ma's hydroboration reaction, the reaction liquid is filtered by silica gel, washed by ethyl acetate, concentrated by filtrate, and separated by column chromatography to obtain the product.
Transition metal salt MY of the inventionnAnd the compound (1) is used for asymmetric hydroboration addition on a carbon-carbon double bond of a prochiral organic compound through in-situ complexation to prepare a chiral organic boron ester compound.
The organic solvent A and the organic solvent B are both organic solvents, and the letters have no meaning per se.
The invention has the following beneficial effects:
the invention provides a novel chiral oxazoline or imidazoline phenyl quinoline amine compound and a simple and convenient method for synthesizing the compound.
The present invention provides a chiral oxazoline or imidazolinylphenylquinoline amine compound of the present invention and a transition metal MY'nUse of an in situ complex as a homogeneous catalyst for the preparation of chiral organoboron compounds by asymmetric hydroboration addition at the carbon-carbon double bond of a prochiral organic compound, the preferred prochiral unsaturated compounds for asymmetric hydroboration being styrenic compounds.
The chiral organoboron ester compounds which can be prepared according to the present invention are important organic synthesis intermediates, in particular in the production of pharmaceutical formulations, fragrances and odorants, agrochemicals.
Detailed Description
The technical solution of the present invention is further described with specific examples, but the scope of the present invention is not limited thereto.
The following examples serve to illustrate the invention. All reactions were carried out under nitrogen and degassed solvent.
In the examples of the invention, formula (2) is commercially available and the halide formula (3) is prepared according to the literature (org. Lett. 2008,10, 917; Tetrahedron: Asymmetry,2016,27, 163.).
The room temperature in the embodiment of the invention is 25-30 ℃.
Example 1: preparation of Compound (1-1)
Figure BDA0001596279740000101
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0700g, 0.075 mmol), bis diphenylphosphinoferrocene (dppf) (0.0745g, 0.13mmol) and toluene (10mL) were stirred at room temperature for 10 minutes, after which 8-aminoquinoline (2-1) (0.2166g, 1.5mmol), (S) -2- (2-bromophenyl) -4-isopropyl-4, 5-dihydro-oxazoline (3-1) (0.4100g, 1.5mmol) and NaO were added to the flask in that ordertBu (0.2780g, 2.9mmol), 3 times with nitrogen, and the reaction was refluxed at 110 ℃ for 48 hours. Stopping heating, after the reaction solution is returned to room temperature, filtering by silica gel, andwashed with ethyl acetate, the washings were concentrated to no liquid flow out and separated (Rf ═ 0.7) by silica gel column chromatography (eluent petroleum ether: ethyl acetate ═ 20:1, v/v) to give the product (1-1) as a pale yellow solid (0.3178g, 64% yield).
1H NMR(400MHz,CDCl3):11.82(s,1H),8.93-8.74(m,1H),8.11(dd,J＝8.4,1.6 Hz,1H),7.95-7.71(m,3H),7.53-7.27(m,4H),6.87(dd,J＝8.0,6.8Hz,1H),4.42 (dd,J＝9.2,8.0Hz,1H),4.18(dd,J＝16.8,8.8Hz,1H),4.02(t,J＝8.4Hz,1H), 1.90-1.69(m,1H),1.19(d,J＝6.4Hz,3H),1.02(d,J＝6.8Hz,3H)；13C NMR:(75.5 MHz,CDCl3):163.0,148.1,143.5,140.6,139.1,135.8,131.5,130.1,129.1,126.7, 121.4,118.6,118.3,115.1,113.3,111.7,73.5,69.5,33.7,19.3,18.9；HRMS(EI) calculated for[C21H21N3O]+requires m/z 331.1685,found m/z 331.1687.
Example 2
Figure BDA0001596279740000111
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.2260g,0.25 mmol), dppf (0.2845g, 0.51mmol) and toluene (10mL) were stirred at room temperature for 10 minutes, after which 8-aminoquinoline (2-1) (0.7228g, 5.0mmol), (S) -2- (2-bromophenyl) -4-tert-butyl-4, 5-dihydro-oxazoline (3-2) (1.4208g, 5.0mmol) and KO were added to the flask in that ordertBu (1.1200g, 10.1mmol), was replaced with nitrogen 3 times and reacted at 60 ℃ for 48 hours. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with ethyl acetate, and the washing solution was concentrated until no liquid flowed out, and subjected to silica gel column chromatography (eluent: petroleum ether: ethyl acetate: 20:1, v/v) (Rf: 0.7) to obtain 1-2(0.5760g, 33% yield) as a pale yellow oily product.
1H NMR(400MHz,CDCl3):11.83(s,1H),8.82(dd,J＝4.0,1.6Hz,1H),8.11(dd, J＝8.4,1.6Hz,1H),7.93-7.75(m,3H),7.47-7.30(m,4H),6.92-6.81(m,1H),4.32 (dd,J＝9.6,7.6Hz,1H),4.24(dd,J＝9.6,8.0Hz,1H),4.15(dd,J＝8.0,7.6Hz,1H), 1.03(s,9H)；13C NMR(101MHz,CDCl3):162.8,148.0,143.5,140.5,139.0,135.8, 131.5,130.1,129.1,126.7,121.4,118.5,118.3,115.1,113.3,111.5,76.6,67.0,33.9, 25.8；HRMS(EI)calculated for[C22H23N3O]+requires m/z 345.1841,found m/z 345.1844.
Example 3
Figure BDA0001596279740000121
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.1308g,0.14 mmol), dppf (0.2845g,0.31mmol) and toluene (6.0mL) were stirred at room temperature for 10 minutes, after which 8-aminoquinoline (2-1) (0.4401g,3.05mmol), (S) -2- (2-bromophenyl) -4-benzyl-4, 5-dihydro-oxazoline (3-3) (0.9528g,3.0mmol) and NaO were added to the flask in that ordertBu (0.5706g,5.94mmol), was replaced with nitrogen 3 times and the reaction was refluxed at 110 ℃ for 12 hours. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with ethyl acetate, and the washing solution was concentrated until no liquid flowed out, and subjected to silica gel column chromatography (eluent: petroleum ether: ethyl acetate: 20:1, v/v) (Rf: 0.7) to obtain 1-3(0.4420g, 38% yield) as a pale yellow oily product.
1H NMR(400MHz,CDCl3):11.59(s,1H),8.79(dd,J＝4.0,1.6Hz,1H),8.04(dd, J＝8.4,1.6Hz,1H),7.85(dd,J＝8.0,1.6Hz,1H),7.78(d,J＝8.0Hz,2H), 7.43-7.20(m,6H),7.14-7.02(m,3H),6.87-6.79(m,1H),4.80-4.63(m,1H),4.29(dd, J＝9.2,8.4Hz,1H),4.00(t,J＝8.0Hz,1H),3.20(dd,J＝13.6,6.0Hz,1H),2.81(dd, J＝13.6,7.6Hz,1H)；13C NMR(101MHz,CDCl3):163.5,148.3,143.7,140.7, 139.1,138.1,135.8,131.6,130.2,129.2,129.1,128.2,126.6,126.2,121.4,118.9, 118.3,115.2,113.2,112.3,70.2,68.0,41.8；HRMS(EI)calculated for[C25H21N3O]+ requires m/z 379.1685,found m/z 379.1685.
Example 4
Figure BDA0001596279740000122
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0972g,0.11 mmol), dppf (0.1128g,0.20mmol) and toluene (5.0mL) were stirred at room temperature for 10 minutes, after which 2-methyl-8-aminoquinoline (2-2) (0.3208g,2.0mmol), (S) -2- (2-bromophenyl) -4-isopropyl-4, 5-dihydro-oxazoline (3-1) (0.5462g,2.0mmol) and NaO were added to the flask in that ordertBu (0.3906g,4.0 mmol), 3 times with nitrogen, and the reaction was refluxed at 110 ℃ for 48 hours. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with ethyl acetate, and the washing solution was concentrated until no liquid flowed out, and subjected to silica gel column chromatography (eluent: petroleum ether: ethyl acetate: 20:1, v/v) (Rf: 0.7) to obtain a pale yellow solid product 1-4(0.5286 g, 75% yield).
1H NMR(400MHz,CDCl3):11.47(s,1H),7.99(d,J＝8.4Hz,1H),7.90-7.76(m, 3H),7.39-7.26(m,4H),6.85(dd,J＝8.0,7.2Hz,1H),4.39(dd,J＝9.6,8.0Hz,1H), 4.20(dd,J＝16.4,8.0Hz,1H),4.04(t,J＝8.0Hz,1H),2.75(s,3H),1.89-1.77(m, 1H),1.11(d,J＝6.8Hz,3H),0.99(d,J＝6.8Hz,3H)；13C NMR(101MHz,CDCl3): 162.9,157.0,143.7,140.1,138.6,136.1,131.4,130.1,127.3,125.6,122.3,118.7, 118.3,115.6,113.5,112.3,73.4,69.1,33.5,25.4,19.2,19.0；HRMS(EI)calculated for[C22H23N3O]+requires m/z 345.1841,found m/z 345.1841.
Example 5
Figure BDA0001596279740000131
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0656g,0.072 mmol), dppf (0.0896g,0.16mmol) and toluene (7.5mL) were stirred at room temperature for 10 minutes, after which time 2-methyl-8-aminoquinoline (2-2) (0.2408g,1.5mmol), (S) -2- (2-bromophenyl) -4-tert-butyl-4, 5-dihydro-oxazoline (3-2) (0.4218g,1.5mmol) and NaO were added to the flask in that ordertBu (0.2779g,2.9 mmol), 3X replacement with nitrogen, 1The reaction was refluxed at 10 ℃ for 48 h. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with ethyl acetate, and the washing solution was concentrated until no liquid flowed out, and subjected to silica gel column chromatography (eluent: petroleum ether: ethyl acetate: 20:1, v/v) (Rf: 0.7) to obtain pale yellow solid products 1 to 5(0.4050 g, 74% yield).
1H NMR(400MHz,CDCl3):11.38(s,1H),7.99(d,J＝8.4Hz,1H),7.89-7.84(m, 1H),7.83-7.75(m,2H),7.39-7.26(m,4H),6.88-6.82(m,1H),4.30(dd,J＝8.8,7.2 Hz,1H),4.24-4.12(m,2H),2.74(s,3H),0.99(s,9H)；13C NMR(101MHz,CDCl3): 162.9,157.1,143.9,140.2,138.6,136.1,131.4,130.1,127.4,125.6,122.4,118.8, 118.3,115.7,113.5,112.6,76.8,67.0,34.0,26.0,25.5；HRMS(ESI)calculated for [M+Na]+[C23H25N3ONa]+requires m/z 382.1895,found m/z 382.1891.
Example 6
Figure BDA0001596279740000141
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0648g,0.071 mmol), dppf (0.0845g,0.15mmol) and toluene (7.5mL) were stirred at room temperature for 10 minutes, after which 2-methyl-8-aminoquinoline (2-2) (0.2408g,1.5mmol), (S) -2- (2-bromophenyl) -4-benzyl-4, 5-dihydro-oxazoline (3-3) (0.4628g,1.5mmol) and NaO were added to the flask in that ordertBu (0.2602g,2.7mmol), 3 times with nitrogen and reacted at 110 ℃ under reflux for 48 h. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with ethyl acetate, and the washing solution was concentrated until no liquid flowed out, and subjected to silica gel column chromatography (eluent: petroleum ether: ethyl acetate: 20:1, v/v) (Rf: 0.7) to obtain pale yellow solid products 1 to 6(0.4024g, 70% yield).
1H NMR(400MHz,CDCl3):11.69(s,1H),8.02(d,J＝8.4Hz,1H),7.90-7.84(m, 2H),7.82-7.77(m,1H),7.42-7.34(m,2H),7.30(d,J＝8.4Hz,2H),7.27-7.24(m, 2H),7.21-7.10(m,3H),6.91-6.77(m,1H),4.81-4.69(m,1H),4.31(dd,J＝8.8,8.8 Hz,1H),4.09(dd,J＝8.0,7.6Hz,1H),3.34(dd,J＝13.6,5.2Hz,1H),2.86(dd,J＝ 13.6,8.4Hz,1H),2.73(s,3H)；13C NMR(101MHz,CDCl3):163.6,156.8,143.8, 140.0,138.5,138.1,136.1,131.7,130.2,129.3,128.4,127.3,126.4,125.7,122.2, 118.5,118.2,115.3,113.2,111.9,70.2,68.3,42.0,25.5；HRMS(ESI)calculated for [M+Na]+[C26H23N3ONa]+requires m/z 416.1739,found m/z 416.1752.
Example 7
Figure BDA0001596279740000151
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0503g,0.055 mmol), dppf (0.0589g,0.11mmol) and toluene (5.0mL) were stirred at room temperature for 10 minutes, after which 2-methyl-8-aminoquinoline (2-2) (0.1589g,1.0mmol), (S) -2- (2-bromophenyl) -4-indenyl-4, 5-dihydro-oxazoline (3-4) (0.3289g,1.05mmol) and NaO were added to the flask in that ordertBu (0.1950g,2.03 mmol), 3 times replaced with nitrogen, and the reaction was refluxed at 110 ℃ for 48 hours. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with ethyl acetate, and the washing solution was concentrated until no liquid flowed out, and subjected to silica gel column chromatography (eluent: petroleum ether: ethyl acetate: 20:1, v/v) (Rf: 0.7) to obtain pale yellow solid products 1 to 7(0.3320 g, 84% yield).
1H NMR(400MHz,CDCl3):11.48(s,1H),8.01(d,J＝8.4Hz,1H),7.87(dd,J＝ 7.6,1.6Hz,1H),7.81-7.70(m,2H),7.61-7.54(m,1H),7.37-7.26(m,4H),7.24-7.17 (m,3H),6.86-6.75(m,1H),5.88(d,J＝8.0Hz,1H),5.48-5.32(m,1H),3.51(dd,J＝ 18.0,6.8Hz,1H),3.39(d,J＝17.2Hz,1H),2.89(s,3H)；13C NMR(101MHz, CDCl3):163.6,156.7,143.7,142.3,140.0,139.7,138.6,136.1,131.6,130.3,128.3, 127.3,125.7,125.2,122.2,118.5,118.3,115.6,113.5,111.9,81.5,77.3,39.7,25.7； HRMS(ESI)calculated for[M+Na]+[C26H21N3ONa]+requires m/z 414.1582,found m/z 414.1592.
Example 8
Figure BDA0001596279740000152
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0691g,0.075 mmol), dppf (0.0853g,0.15mmol) and xylene (7.5mL) were stirred at room temperature for 10 minutes, after which 2-cyclohexyl-8-aminoquinoline (2-3) (0.3390g,1.5mmol), (S) -2- (2-bromophenyl) -4-isopropyl-4, 5-dihydro-oxazoline (3-1) (0.4024g,1.5mmol) and NaO were added to the flask in that ordertBu (0.3021g,3.1 mmol), was replaced with nitrogen 3 times and reacted at 200 ℃ for 1 h. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with ethyl acetate, and the washing solution was concentrated until no liquid flowed out, and subjected to silica gel column chromatography (eluent: petroleum ether: ethyl acetate: 20:1, v/v) (Rf: 0.7) to obtain pale yellow oily products 1 to 8(0.4466g, 72% yield).
1H NMR(400MHz,CDCl3):11.31(s,1H),7.98(d,J＝8.8Hz,1H),7.88(dd,J＝ 8.0,1.2Hz,1H),7.82(d,J＝8.4Hz,1H),7.75(d,J＝7.6Hz,1H),7.37-7.23(m,4H), 6.87-6.80(m,1H),4.36-4.29(m,1H),4.27-4.19(m,1H),4.07(s,J＝7.6Hz,1H), 3.00-2.90(m,1H),2.09-2.00(m,2H),1.91-1.58(m,6H),1.50-1.38(m,2H), 1.37-1.28(m,1H),1.02(d,J＝7.2Hz,3H),0.91(d,J＝6.8Hz,3H)；13C NMR(101 MHz,CDCl3):164.6,162.8,143.8,139.8,138.8,136.1,131.3,130.2,127.7,125.5, 119.9,118.6,118.2,115.6,113.6,112.4,73.1,68.2,47.2,32.8,32.7,26.6,26.1,19.3, 18.0；HRMS(EI)calculated for[C27H31N3O]+requires m/z 377.1528,found m/z 377.1528.
Example 9
Figure BDA0001596279740000161
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0920g,0.10 mmol), dppf (0.1120g,0.20mmol) and toluene (10.0mL) at room temperatureStirring for 10min, after which 2-isopropyl-5, 6-dimethyl-8-aminoquinoline (2-4) (0.3448g,2.0mmol), (S) -2- (2-bromophenyl) -4-isopropyl-4, 5-dihydro-oxazoline (3-1) (0.5318g,2.0mmol) and NaO were added to the flask in that ordertBu (0.3848g, 4.0mmol), 3 times with nitrogen, and the reaction was refluxed at 110 ℃ for 48 hours. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with ethyl acetate, and the washing solution was concentrated until no liquid flowed out, and subjected to silica gel column chromatography (eluent: petroleum ether: ethyl acetate: 20:1, v/v) (Rf: 0.7) to obtain pale yellow oily products 1 to 9 (0.5328g, 66% yield).
1H NMR(400MHz,CDCl3):11.20(s,1H),8.24(d,J＝8.8Hz,1H),7.86(dd,J＝ 8.0,1.6Hz,1H),7.78(d,J＝8.4Hz,1H),7.63(s,1H),7.39-7.29(m,2H),6.81(dd,J ＝8.0,7.2Hz,1H),4.39-4.29(m,1H),4.27-4.17(m,1H),4.07(dd,J＝8.0,7.6Hz, 1H),3.36-3.21(m,1H),2.49(s,3H),2.43(s,3H),1.93-1.79(m,1H),1.40(d,J＝3.2 Hz,3H),1.38(d,J＝3.2Hz,3H),1.01(d,J＝6.8Hz,3H),0.91(d,J＝6.8Hz, 3H)；13C NMR(101MHz,CDCl3):163.9,162.8,144.3,139.0,136.3,132.6,132.4, 131.4,130.2,126.9,122.4,119.1,117.6,116.2,115.3,113.1,73.1,68.5,36.8,33.0, 22.6,22.6,20.9,19.3,18.3,13.7；HRMS(EI)calculated for[C26H31N3O]+requires m/z 401.2467,found m/z 401.2471.
Example 10
Figure BDA0001596279740000171
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0885g,0.097 mmol), dppf (0.1128g,0.20mmol) and toluene (10.0mL) were stirred at room temperature for 10 minutes, after which time 6-methoxy-8-aminoquinoline (2-5) (0.3549g,2.0mmol), (S) -2- (2-bromophenyl) -4-isopropyl-4, 5-dihydro-oxazoline (3-1) (0.5466g,2.0mmol) and NaO were added to the flask in that ordertBu (0.3866g,4.0 mmol), 3 times with nitrogen, and the reaction was refluxed at 110 ℃ for 48 hours. Stopping heating, after the reaction solution returns to room temperature, filtering the silica gel, washing with ethyl acetate, and concentrating the washing solution until no solution is obtainedColumn chromatography on silica gel (eluent petroleum ether: ethyl acetate 20:1, v/v) gave the product 1-10(0.4870 g, 64% yield) as a pale yellow solid.
1H NMR(400MHz,CDCl3):11.83(s,1H),8.71-8.65(m,1H),7.99(dd,J＝8.1,1.5 Hz,1H),7.92-7.85(m,2H),7.47(d,J＝2.4Hz,1H),7.42-7.33(m,2H),6.93-6.85(m, 1H),6.62(d,J＝2.4Hz,1H),4.46-4.38(m,1H),4.23-4.13(m,1H),4.02(dd,J＝8.4, 8.1Hz,1H),3.91(s,3H),1.86-1.72(m,1H),1.19(d,J＝6.6Hz,3H),1.02(d,J＝6.6 Hz,3H)；13C NMR(101MHz,CDCl3):162.9,158.3,145.6,143.1,140.2,137.4, 134.6,131.6,130.1,129.9,121.9,118.7,115.7,113.7,103.5,96.4,77.3,77.0,76.7, 73.5,69.6,55.3,33.7,19.3,18.9；HRMS(EI)calculated for[C22H23N3O2]+requires m/z 361.1790,found m/z 361.1790.
Example 11
Figure BDA0001596279740000181
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0432g,0.047 mmol),4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene (Xantphos) (0.0568g,0.098mmol) and toluene (3.0mL) were stirred at room temperature for 10 minutes, after which 8-bromo-4-methoxy-2-methylquinoline (4-1) (0.1171g,0.46mmol), (S) -2- (4-isopropyl-4, 5-dihydrooxazolinyl) -2-aniline (5-1) (0.1018g,0.50mmol) and NaO were added to the flask in this ordertBu (0.0954g,1.0mmol), was replaced with nitrogen 3 times and reacted at 110 ℃ under reflux for 48 h. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with ethyl acetate, and the washing solution was concentrated until no liquid flowed out, and subjected to silica gel column chromatography (eluent: petroleum ether: ethyl acetate: 20:1, v/v) (Rf: 0.6) to obtain pale yellow solid products 1 to 11(0.1350g, 77% yield).1H NMR(400 MHz,CDCl3):11.41(s,1H),7.85(dd,1H),7.83-7.73(m,2H),7.63(dd,J＝8.4,0.8 Hz,1H),7.36-7.28(m,2H),6.86-6.79(m,1H),6.64(s,1H),4.38(dd,J＝9.2,8.0Hz, 1H),4.22-4.14(m,1H),4.02(dd,J＝8.4,8.0Hz,1H),3.99(s,3H),2.70(s,3H), 1.86-1.77(m,1H),1.10(d,J＝6.6Hz,3H),0.98(d,J＝6.6Hz,3H)；13C NMR(101 MHz,CDCl3):162.9,162.3,157.9,143.8,141.0,138.3,131.3,130.0,124.6,120.5, 118.1,115.5,113.4,112.9,112.7,100.9,73.4,69.1,55.4,33.4,26.0,19.2,19.0； HRMS(ESI)calculated for[M+Na]+[C23H25N3O2Na]+requires m/z 384.1688,found m/z 384.1700.
Example 12
Figure BDA0001596279740000191
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0450g,0.049 mmol), binaphthyl diphenyl phosphate, 1,1 '-binaphthyl-2, 2' -Bisdiphenylphosphine (BINAP) (0.0618g,0.099mmol) and toluene (3.0mL) were stirred at room temperature for 10 minutes, after which 8-bromo-4-methoxy-2-methylquinoline (4-1) (0.1004g,0.40mmol), (S) -2- (4-isopropyl-4, 5-dihydrooxazolinyl) -2-aniline (5-1) (0.0908g,0.44mmol) and NaO were added to the flask in this ordertBu (0.0956g,1.0mmol), was replaced with nitrogen 3 times and reacted at 110 ℃ under reflux for 48 h. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with ethyl acetate, and the washing solution was concentrated until no liquid flowed out, and subjected to silica gel column chromatography (eluent: petroleum ether: ethyl acetate: 20:1, v/v) (Rf: 0.6) to obtain pale yellow solid products 1 to 11(0.1393g, 93% yield).1H NMR(400 MHz,CDCl3):11.41(s,1H),7.85(dd,1H),7.83-7.73(m,2H),7.63(dd,J＝8.4,0.8 Hz,1H),7.36-7.28(m,2H),6.86-6.79(m,1H),6.64(s,1H),4.38(dd,J＝9.2,8.0Hz, 1H),4.22-4.14(m,1H),4.02(dd,J＝8.4,8.0Hz,1H),3.99(s,3H),2.70(s,3H), 1.86-1.77(m,1H),1.10(d,J＝6.6Hz,3H),0.98(d,J＝6.6Hz,3H)；13C NMR(101 MHz,CDCl3):162.9,162.3,157.9,143.8,141.0,138.3,131.3,130.0,124.6,120.5, 118.1,115.5,113.4,112.9,112.7,100.9,73.4,69.1,55.4,33.4,26.0,19.2,19.0； HRMS(ESI)calculated for[M+Na]+[C23H25N3O2Na]+requires m/z 384.1688,found m/z 384.1700.
Example 13
Figure BDA0001596279740000192
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0445g,0.049 mmol), dppf (0.0547g,0.10mmol) and toluene (5.0mL) were stirred at room temperature for 10 minutes, after which 2-methyl-8-aminoquinoline (2-2) (0.1607g,1.0mmol), (S) - (1-phenyl-2- (2-iodophenyl) yl-4-tert-butyl-4, 5-dihydro) -1H-imidazole (3-5) (0.4051g,1.0mmol) and NaO were added to the flask in that ordertBu (0.1940 g,2.0mmol), 3 times with nitrogen, and the reaction was refluxed at 110 ℃ for 48 hours. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with ethyl acetate, and the washing solution was concentrated until no liquid flowed out, and subjected to silica gel column chromatography (eluent petroleum ether: ethyl acetate: 5:1, v/v) (Rf: 0.4) to obtain pale yellow solid products 1 to 12 (0.3066g, 70% yield).
1H NMR(400MHz,CDCl3):9.93(s,1H),7.97(d,J＝8.4Hz,1H),7.73(d,J＝8.0 Hz,1H),7.50(d,J＝8.0Hz,1H),7.31-7.18(m,5H),7.09(dd,J＝8.0,7.6Hz,2H), 6.91(dd,J＝7.6,7.2Hz,1H),6.85-6.71(m,3H),4.11(dd,J＝10.8,8.4Hz,1H),4.01 (dd,J＝10.8,7.2Hz,1H),3.62(dd,J＝9.2,8.0Hz,1H),2.74(s,3H),1.00(s, 9H)；13C NMR(101MHz,CDCl3):160.0,156.5,143.4,141.7,139.5,139.1,136.0, 130.7,129.8,128.5,127.1,125.7,123.0,122.3,122.2,121.2,120.3,119.1,117.2, 109.8,74.6,54.0,34.0,26.1,25.3；HRMS(EI)calculated for[C29H30N4]+requires m/z 434.2470,found m/z 434.2470.
Example 14
Figure BDA0001596279740000201
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0446g,0.049 mmol), dppf (0.0566g,0.10mmol) and toluene (5.0mL), cellAfter stirring for 10 minutes at room temperature, 2-methyl-8-aminoquinoline (2-2) (0.1596g,1.0mmol), (S) - (1-phenyl-2- (2-iodophenyl) yl-4-isopropyl-4, 5-dihydro) -1H-imidazole (3-6) (0.3378g,0.86mmol) and NaO were added to the flask in that ordertBu (0.1926g, 2.0mmol), 3 times with nitrogen, and the reaction was refluxed at 110 ℃ for 48 hours. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with ethyl acetate, and the washing solution was concentrated until no liquid flowed out, and subjected to silica gel column chromatography (eluent petroleum ether: ethyl acetate: 5:1, v/v) (Rf: 0.4) to obtain pale yellow solid products 1 to 13 (0.2715g, 75% yield).
1H NMR(400MHz,CDCl3):10.06(s,1H),7.97(d,J＝8.8Hz,1H),7.74(d,J＝8.4 Hz,1H),7.50(d,J＝7.6Hz,1H),7.30-7.25(m,3H),7.18(d,J＝8.4Hz,1H),7.07 (dd,J＝8.0,7.6Hz,2H),6.89(dd,J＝7.6,7.2Hz,1H),6.84-6.71(m,3H),4.24-4.12 (m,1H),4.03(dd,J＝10.4,9.2Hz,1H),3.60(dd,J＝8.8,8.4Hz,1H),2.75(s,3H), 2.02-1.93(m,1H),1.09(d,J＝6.8Hz,3H),0.96(d,J＝6.8Hz,3H)；13C NMR(101 MHz,CDCl3):159.7,156.2,142.9,141.4,139.2,138.8,135.9,130.6,129.8,128.4, 126.9,125.7,122.8,122.1,121.8,120.9,120.1,118.8,116.9,109.0,70.7,55.2,33.1, 25.1,19.0,18.2；HRMS(EI)calculated for[C28H28N4]+requires m/z 420.2314,found m/z 420.2314.
Example 15
Figure BDA0001596279740000211
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0450g,0.049 mmol), dppf ((0.0553g,0.10mmol) and toluene (5.0mL), stirred at room temperature for 10 minutes, after which 2-methyl-8-aminoquinoline (2-2) (0.1598g,1.0mmol), (S) - (1-phenyl-2- (2-iodophenyl) yl-4-phenyl-4, 5-dihydro) -1H-imidazole (3-7) (0.4179g,0.98mmol) and NaO were added to the flask in that ordertBu (0.1937g,2.0 mmol), 3 times with nitrogen, and the reaction was refluxed at 110 ℃ for 48 hours. Stopping heating, after the reaction solution returns to room temperature, filtering the silica gel, washing with ethyl acetate, and concentrating the washing solution until no liquid flowsColumn chromatography on silica gel (eluent petroleum ether: ethyl acetate 5:1, v/v) gave the product 1-14(0.2171 g, 48% yield) as a pale yellow solid.
1H NMR(400MHz,CDCl3):10.40(s,1H),7.95(d,J＝8.0Hz,1H),7.78(d,J＝8.4 Hz,1H),7.52-7.44(m,3H),7.36-7.28(m,3H),7.23-7.15(m,3H),7.11-7.04(m,2H), 6.94-6.87(m,1H),6.87-6.73(m,3H),5.51(dd,J＝10.4,9.6Hz,1H),4.42(dd,J＝ 10.4,9.6Hz,1H),3.80(dd,J＝9.2,9.2Hz,1H),2.42(s,3H)；13C NMR(101MHz, CDCl3):161.1,156.3,143.7,142.7,141.5,139.1,138.6,135.8,130.7,130.2,128.5, 128.3,126.9,126.8,126.8,125.7,123.3,122.1,120.6,120.1,118.7,116.8,108.4, 68.0,60.6,24.8；HRMS(EI)calculated for[C31H26N4]+requires m/z 454.2157,found m/z 454.2154.
Example 16
Figure BDA0001596279740000221
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0470g,0.051 mmol), dppf (0.0556g,0.10mmol) and toluene (5.0mL) were stirred at room temperature for 10 minutes, after which 2-methyl-8-aminoquinoline (2-2) (0.1594g,1.0mmol), (S) - (1-phenyl-2- (2-iodophenyl) yl-4-benzyl-4, 5-dihydro) -1H-imidazole (3-8) (0.4277g,0.98mmol) and NaO were added to the flask in that ordertBu (0.1920g,2.0 mmol), 3 times with nitrogen, and the reaction was refluxed at 110 ℃ for 48 hours. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with ethyl acetate, and the washing solution was concentrated until no liquid flowed out, and subjected to silica gel column chromatography (eluent petroleum ether: ethyl acetate: 5:1, v/v) (Rf: 0.4) to obtain pale yellow solid products 1 to 15(0.1926 g, 42% yield).
1H NMR(400MHz,CDCl3):10.33(s,1H),7.94(d,J＝8.8Hz,1H),7.76(d,J＝8.4 Hz,1H),7.52(d,J＝7.6Hz,1H),7.33-7.10(m,10H),7.04-6.95(m,2H),6.84(dd,J ＝7.6,7.2Hz,1H),6.77(dd,J＝7.6,7.2Hz,1H),6.62(d,J＝7.6Hz,2H),4.80-4.51 (m,1H),3.95(dd,J＝9.6,9.6Hz,1H),3.60(dd,J＝9.2,7.6Hz,1H),3.44(dd,J＝ 14.0,4.0Hz,1H),2.92-2.61(m,4H)；13C NMR(101MHz,CDCl3):160.0,156.1, 142.5,141.3,139.2,138.7,138.3,136.0,130.6,130.0,129.2,128.4,128.2,126.9, 126.1,125.9,122.8,122.1,121.6,120.6,120.0,118.8,116.8,108.3,77.2,65.8,56.7, 42.3,25.3；HRMS(EI)calculated for[C32H28N4]+requires m/z 468.2314,found m/z 468.2314。
Example 17
Figure BDA0001596279740000222
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0919g, 0.10mmol), dppf (0.1087g,0.20mmol) and toluene (10.0mL) were stirred at room temperature for 10 minutes, after which 2-methyl-8-aminoquinoline (2-2) (0.3164g,2.0mmol), (S) -2- (2-iodophenyl) -4-benzyl-4, 5-dihydro-thiazoline (3-9) (0.7650g,2.0mmol) and NaO were added to the bottle in that ordertBu (0.3868g,4.0mmol), was replaced with nitrogen 3 times and reacted at 110 ℃ under reflux for 60 h. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with dichloromethane, the filtrate was concentrated until no liquid flowed out, and silica gel column chromatography (PE/EA ═ 10/1, v/v) was performed to separate (Rf ═ 0.8) to obtain the products 1 to 16(0.4751g, 58% yield) as pale yellow solids.1H NMR(400 MHz,CDCl3):11.86(s,1H),7.98(d,J＝8.4Hz,1H),7.86(d,J＝8.4Hz,1H),7.78 (d,J＝7.6Hz,1H),7.65(d,J＝8.0Hz,1H),7.41-7.31(m,2H),7.30-7.19(m,4H), 7.18-7.01(m,3H),6.86(dd,J＝7.6,7.2Hz,1H),5.20-5.02(m,1H),3.46(dd,J＝ 13.2,4.4Hz,1H),3.24(dd,J＝10.8,8.0Hz,1H),3.06(dd,J＝10.8,7.6Hz,1H), 2.93(dd,J＝13.2,9.2Hz,1H),2.74(d,3H)；13C NMR(101MHz,CDCl3):167.4, 156.7,142.6,139.9,138.5,138.4,136.1,132.6,131.2,129.2,128.3,127.3,126.3, 125.7,122.2,119.1,118.5,115.8,111.7,79.3,40.6,35.8,25.6；HRMS(EI)calculated for[C26H23N3S]+requires m/z 409.1613,found m/z 409.1620.
Example 18
Figure BDA0001596279740000231
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0915g,0.10 mmol), dppf (0.1096g,0.20mmol) and toluene (10.0mL) were stirred at room temperature for 10 minutes, after which 2-methyl-8-aminoquinoline (2-2) (0.3186g,2.0mmol), (S) -2- (2-iodophenyl) -4-tert-butyl-4, 5-dihydro-thiazoline (3-10) (0.6914g,2.0mmol) and NaO were added to the bottle in that ordertBu (0.3837g,4.0 mmol), was replaced with nitrogen 3 times and reacted at 110 ℃ under reflux for 60 h. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with dichloromethane, the filtrate was concentrated until no liquid flowed out, and silica gel column chromatography (PE/EA ═ 10/1 elution, v/v) was performed (Rf ═ 0.8) to obtain the product 3-10(0.6984g, 93% yield) as a pale yellow solid.1H NMR(400MHz,CDCl3):11.18(s,1H),7.97(d,J＝8.4Hz,1H),7.81-7.71(m, 2H),7.65(dd,J＝8.0,1.6Hz,1H),7.38-7.22(m,4H),6.91-6.72(m,1H),4.44(dd,J ＝11.2,8.4Hz,1H),3.21(dd,J＝10.8,8.8Hz,1H),3.10(dd,J＝11.6,10.8Hz,1H), 2.71(s,3H),1.08(s,9H)；13C NMR(101MHz,CDCl3):166.6,157.1,143.0,140.3, 138.6,136.0,132.5,130.8,127.4,125.5,122.4,119.2,118.6,115.9,114.0,88.8,35.1, 32.5,27.1,25.4；HRMS(EI)calculated for[C23H25N3S]+requires m/z 375.1769, found m/z 375.1782.
Example 19
Figure BDA0001596279740000241
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0913g, 0.10mmol), dppf (0.1087g,0.20mmol) and toluene (10.0mL) were stirred at room temperature for 10 minutes, after which 2-methyl-8-aminoquinoline (2-2) (0.3173g,2.0mmol), (S) -2- (2-iodophenyl) -4-isopropyl-4, 5-dihydro-thiazoline (3-11) (0.6648g,2.0mmol) and NaO were added to the bottle in that ordertBu (0.3834g,4.0 mmol), 3X replacement with nitrogen, 110 deg.CThe reaction was refluxed for 60 h. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with dichloromethane, the filtrate was concentrated to no liquid flow, and silica gel column chromatography (PE/EA ═ 10/1 elution, v/v) was performed (Rf ═ 0.8) to obtain the products 1 to 18(0.6362g, 88% yield) as pale yellow solids.1H NMR(400MHz,CDCl3):11.45(s,1H),7.98(d,J＝8.4Hz,1H),7.81(d,J＝8.4 Hz,1H),7.76(d,J＝7.6Hz,1H),7.69-7.61(m,1H),7.38-7.26(m,4H),6.89-6.83(m, 1H),4.59-4.48(m,1H),3.32(dd,J＝10.8,8.4Hz,1H),3.05(dd,J＝10.4,10.4Hz, 1H),2.74(s,3H),2.20-2.07(m,1H),1.14(d,J＝6.8Hz,3H),1.04(d,J＝6.8Hz, 3H)；13C NMR(101MHz,CDCl3):166.6,157.0,142.8,140.2,138.6,136.1,132.6, 130.9,127.3,125.6,122.3,119.3,118.9,118.6,116.0,113.0,85.0,34.2,33.4,25.4, 20.1,19.4；HRMS(EI)calculated for[C22H23N3S]+requires m/z 361.1613,found m/z 361.1618.
Example 20
Figure BDA0001596279740000251
Pd is added into an ultra-dry 50mL-Schlenk tube in turn under the protection of nitrogen2(dba)3(0.0922g, 0.10mmol), dppf (0.1087g,0.20mmol) and toluene (10.0mL) were stirred at room temperature for 10 minutes, after which 2-methyl-8-aminoquinoline (2-2) (0.3165g,2.0mmol), (S) -2- (2-iodophenyl) -4-phenyl-4, 5-dihydro-thiazoline (3-12) (0.7352g,2.0mmol) and NaO were added to the bottle in that ordertBu (0.3882g,4.0 mmol), 3 times with nitrogen, and the reaction was refluxed at 110 ℃ for 48 hours. After the reaction solution was returned to room temperature, the heating was stopped, the reaction solution was filtered through silica gel, washed with dichloromethane, the filtrate was concentrated until no liquid flowed out, and separated by silica gel column chromatography (Rf ═ 0.8) (PE/EA ═ 10/1 by-pass) to give the product 1-19(0.4615g, 58% yield) as a yellow solid.1H NMR (400MHz,CDCl3):11.88(s,1H),7.92(d,J＝8.4Hz,1H),7.88(d,J＝8.4Hz,1H), 7.81-7.72(m,2H),7.50-7.46(m,2H),7.40-7.23(m,6H),7.15(d,J＝8.4Hz,1H), 6.95-6.86(m,1H),5.86(dd,J＝10.4,8.4Hz,1H),3.72(dd,J＝10.8,8.4Hz,1H), 3.19(dd,J＝10.8,10.8Hz,1H),2.19(s,3H)；13C NMR(101MHz,CDCl3):168.8, 157.0,142.7,142.4,139.7,138.5,135.9,132.6,131.4,128.4,127.3,127.1,126.8, 125.6,122.2,119.4,118.6,118.4,116.2,111.4,81.4,39.9,24.6；HRMS(EI)calculated for[C25H21N3S]+requires m/z 395.1456,found m/z 395.1456.
Chiral quinolinamines with MXnIn-situ complex catalyzed asymmetric hydroboration reaction of alkene and pinacol borane
Example 21: (S) -2- (1-phenylethyl) -4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan.
Figure BDA0001596279740000252
Under the protection of nitrogen, FeCl is added into an ultra-dry 25mL-Schlenk tube in sequence2(0.0032g,0.025 mmol), 1-4(0.03mmol) prepared in example 4, and 1mL of toluene were stirred at room temperature for 2 hours, and pinacol borane (HBpin) (90. mu.L, 0.6mmol), styrene (0.5mmol), and NaBHEt were added in this order3(75. mu.L, 1mol/L, solvent THF), stirred at room temperature for 18 h. The reaction solution is filtered by silica gel, washed by ether, the washing solution is concentrated until no liquid flows out, and the product of the mah-jong hydroboration is obtained by silica gel column chromatography (the eluent is petroleum ether: ethyl acetate is 50:1, v/v) and separation (Rf is 0.8). Oily liquid, 31% yield, 59.6% ee,1H NMR (400MHz,CDCl3)7.29-7.18(m,4H),7.16-7.10(m,1H),2.43(q,J＝7.6Hz,1H), 1.33(d,J＝7.2Hz,3H),1.21(s,6H),1.20(s,6H)；13C NMR(101MHz,CDCl3) 144.9,128.3,127.7,125.0,83.2,24.60,24.55,17.0.
example 22
Under the protection of nitrogen, FeCl is added into an ultra-dry 25mL-Schlenk tube in sequence2(0.0032g,0.025 mmol), 1-5(0.03mmol) prepared in example 5, and 1mL of toluene were stirred at room temperature for 2 hours, and then HBpin (90. mu.L, 1.2mmol), styrene (0.5mmol), and NaBHEt were added in this order3(75. mu.L, 1mol/L, solvent THF), stirred at room temperature for 18 h. Filtering the reaction solution with silica gel, washing with diethyl ether, concentrating the washing solution until no liquid flows out, and performing silica gel column chromatography (the eluent is petroleum ether: acetic acid)Ethyl ester 50:1, v/v) isolation (Rf ═ 0.8) afforded the mahalanobis product 6-1. Oily liquid, 52% yield, 63.2% ee.
Example 23
Under the protection of nitrogen, FeCl is added into an ultra-dry 25mL-Schlenk tube in sequence2(0.0032g,0.025 mmol), 1-6(0.03mmol) prepared in example 6, and 1mL of toluene were stirred at room temperature for 2 hours, and then HBpin (90. mu.L, 0.6mmol), styrene (0.5mmol), and NaBHEt were added in this order3(75. mu.L, 1mol/L, solvent THF), stirred at room temperature for 18 h. The reaction solution is filtered by silica gel, washed by ether, the washing solution is concentrated until no liquid flows out, and the product of the mah-jong hydroboration is obtained by silica gel column chromatography (the eluent is petroleum ether: ethyl acetate is 50:1, v/v) and separation (Rf is 0.8). Oily liquid, 37% yield, 50% ee.
Example 24
Under the protection of nitrogen, FeCl is added into an ultra-dry 25mL-Schlenk tube in sequence2(0.0032g,0.025 mmol), 1-7(0.03mmol) prepared in example 7, and 1mL of toluene were stirred at room temperature for 2 hours, and then HBpin (90. mu.L, 0.6mmol), styrene (0.5mmol), and NaBHEt were added in this order3(75. mu.L, 1mol/L, solvent THF), stirred at room temperature for 18 h. The reaction solution is filtered by silica gel, washed by ether, the washing solution is concentrated until no liquid flows out, and the product of the mah-jong hydroboration is obtained by silica gel column chromatography (the eluent is petroleum ether: ethyl acetate is 50:1, v/v) and separation (Rf is 0.8). Oily liquid, 37% yield, 52% ee.
Example 25
Under the protection of nitrogen, FeCl is added into an ultra-dry 25mL-Schlenk tube in sequence2(0.0032g,0.025 mmol), 1-8(0.03mmol) prepared in example 8, and 1mL of toluene were stirred at room temperature for 2 hours, and then HBpin (90. mu.L, 0.6mmol), styrene (0.5mmol), and NaBHEt were added in this order3(75. mu.L, 1mol/L, solvent THF), stirred at 50 ℃ for 1 h. The reaction solution is filtered by silica gel, washed by ether, the washing solution is concentrated until no liquid flows out, and the product of the mah-jong hydroboration is obtained by silica gel column chromatography (the eluent is petroleum ether: ethyl acetate is 50:1, v/v) and separation (Rf is 0.8). Oily liquid, 34% yield, 57% ee.
Example 26
Under the protection of nitrogen, in the condition of ultra-dry 25mL-ScFeCl is added into an hlenk tube in sequence2(0.0032g,0.025 mmol), 1-9(0.03mmol) prepared in example 9, and 1mL of toluene were stirred at room temperature for 2 hours, and then HBpin (90. mu.L, 0.6mmol), styrene (0.5mmol), and NaBHEt were added in this order3(75. mu.L, 1mol/L, solvent THF), stirred at room temperature for 18 h. The reaction solution is filtered by silica gel, washed by ether, the washing solution is concentrated until no liquid flows out, and the product of the mah-jong hydroboration is obtained by silica gel column chromatography (the eluent is petroleum ether: ethyl acetate is 50:1, v/v) and separation (Rf is 0.8). Oily liquid, 34% yield, 64% ee.
Example 27
Under the protection of nitrogen, FeCl is added into an ultra-dry 25mL-Schlenk tube in sequence2(0.0032g,0.025 mmol), 1-11(0.03mmol) prepared in example 11, and 1mL of toluene were stirred at room temperature for 2 hours, and then HBpin (90. mu.L, 0.6mmol), styrene (0.5mmol), and NaBHEt were added in this order3(75. mu.L, 1mol/L, solvent THF), stirred at room temperature for 18 h. The reaction solution is filtered by silica gel, washed by ether, the washing solution is concentrated until no liquid flows out, and the product of the mah-jong hydroboration is obtained by silica gel column chromatography (the eluent is petroleum ether: ethyl acetate is 50:1, v/v) and separation (Rf is 0.8). Oily liquid, 41% yield, 65% ee,1H NMR(400MHz, CDCl3)7.29-7.18(m,4H),7.16-7.10(m,1H),2.43(q,J＝7.6Hz,1H),1.33(d,J＝ 7.2Hz,3H),1.21(s,6H),1.20(s,6H).
example 28
Under nitrogen protection, cobalt acetate (0.025mmol), 1-4(0.03mmol) prepared in example 4, and diethyl ether (1.0mL) were added to a dry reaction tube at room temperature, stirred at room temperature for 10min, followed by addition of styrene (1.0mmol), pinacolborane (1.2mmol), and then stirred at 0 ℃ for 72 h. The reaction solution was filtered through silica gel, washed with ether, the washing solution was concentrated until no liquid flowed out, and the product was separated by silica gel column chromatography (eluent petroleum ether: ethyl acetate 50:1, v/v) (Rf 0.8) to give 6-1. Oily liquid, 40% yield.
Example 29
Under nitrogen protection, cobalt acetate (0.025mmol), 1-5(0.03mmol) prepared in example 5, and diethyl ether (1.0mL) were added to a dry reaction tube at room temperature, stirred at room temperature for 10min, followed by addition of styrene (1.0mmol), pinacolborane (1.2mmol), and then stirred at room temperature for 18 h. The reaction solution was filtered through silica gel, washed with ether, the washing solution was concentrated until no liquid flowed out, and the product was separated by silica gel column chromatography (eluent petroleum ether: ethyl acetate 50:1, v/v) (Rf 0.8) to give 6-1. Oily liquid, 42% yield, 89% ee.
Example 30
Under nitrogen protection, cobalt acetate (0.025mmol), 1-7(0.03mmol) prepared in example 7, and diethyl ether (1.0mL) were added to a dry reaction tube at room temperature, stirred at room temperature for 10min, followed by addition of styrene (1.0mmol), pinacolborane (1.2mmol), and then stirred at room temperature for 18 h. The reaction solution was filtered through silica gel, washed with ether, the washing solution was concentrated until no liquid flowed out, and the product was separated by silica gel column chromatography (eluent petroleum ether: ethyl acetate 50:1, v/v) (Rf 0.8) to give 6-1. Oily liquid, 68% yield, 72% ee.
Example 31
Under nitrogen protection, cobalt acetate (0.025mmol), 1-11(0.03mmol) prepared in example 11, and diethyl ether (1.0mL) were added to a dry reaction tube at room temperature, stirred at room temperature for 10min, followed by addition of styrene (1.0mmol), pinacolborane (1.2mmol), and then stirred at room temperature for 18 h. The reaction solution was filtered through silica gel, washed with ether, the washing solution was concentrated until no liquid flowed out, and the product was separated by silica gel column chromatography (eluent petroleum ether: ethyl acetate 50:1, v/v) (Rf 0.8) to give 6-1. Oily liquid, 38% yield, 79.2% ee.
Example 32
Figure BDA0001596279740000281
Under nitrogen protection, cobalt acetate (0.025mmol), 1-11(0.03mmol) prepared in example 11, and diethyl ether (1.0mL) were added to a dry reaction tube at room temperature, and stirred at room temperature for 10min, followed by addition of 4-methoxystyrene (1.0mmol), pinacolborane (1.2mmol), and then stirred at room temperature for 18 hours. Filtering the reaction solution with silica gel, washing with diethyl ether, concentrating the washing solution until no liquid flows outSilica gel column chromatography (eluent petroleum ether: ethyl acetate ═ 20:1, v/v) separated (Rf ═ 0.7) to give product 6-2. Oily liquid, 38% yield, 76% ee,1H NMR(400MHz,CDCl3):7.36-7.26(m,2H),6.95-6.80 (m,2H),4.85(q,J＝6.4Hz,1H),3.80(s,3H),1.85(s,1H),1.47(d,J＝6.4Hz, 3H)；13C NMR(101MHz,CDCl3):159.0,138.0,126.6,113.8,69.9,55.3,25.0.
example 33
Figure BDA0001596279740000291
Under nitrogen protection, cobalt acetate (0.025mmol), 1-5(0.03mmol) prepared in example 5, and diethyl ether (1.0mL) were added to a dry reaction tube at room temperature, stirred at room temperature for 10min, followed by addition of 4-acetoxystyrene (1.0mmol), pinacolborane (1.2mmol), and then stirred at room temperature for 18 h. The reaction solution was filtered through silica gel, washed with ether, the washing solution was concentrated until no liquid flowed out, and the product was separated by silica gel column chromatography (eluent petroleum ether: ethyl acetate 50:1, v/v) (Rf 0.5) to give 6-3. Oily liquid, 56% yield, 80% ee,1H NMR(400MHz,CDCl3)7.21(d,J＝8.0Hz,2H), 6.99-6.94(m,2H),2.43(q,J＝7.6Hz,1H),2.27(s,3H),1.31(d,J＝7.6Hz,3H), 1.21(s,6H),1.20(s,6H)；13C NMR(101MHz,CDCl3)169.6,148.2,142.4,128.5, 121.1,83.3,24.53,24.50,21.1,17.0.HRMS(EI)calculated for[C16H23BO4]+requires m/z 290.1689,found m/z 290.1694.
example 34
Figure BDA0001596279740000292
Under nitrogen protection, cobalt acetate (0.025mmol), 1-4(0.03mmol) prepared in example 4, and diethyl ether (1.0mL) were added to a dry reaction tube at room temperature, stirred at room temperature for 10min, followed by 4-fluorostyrene (1.0mmol), pinacol borane (1.2mmol), and then stirred at room temperature for 18 h. The reaction solution was filtered through silica gel, washed with ether, the washing solution was concentrated until no liquid flowed out, and the product was separated by silica gel column chromatography (eluent petroleum ether: ethyl acetate 50:1, v/v) (Rf 0.8) to give 6-4. Oily liquid, 66% yield, 79% ee.
1H NMR(400MHz,CDCl3)7.20-7.12(m,2H),7.00-6.86(m,2H),2.41(q,J＝7.6 Hz,1H),1.30(d,J＝7.6Hz,3H),1.21(s,6H),1.20(s,6H).
Example 35
Figure BDA0001596279740000301
Under nitrogen protection, cobalt acetate (0.025mmol), 1-7(0.03mmol) prepared in example 7, and diethyl ether (1.0mL) were added to a dry reaction tube at room temperature, and stirred at room temperature for 10min, followed by addition of 3-methylstyrene (1.0mmol), pinacolborane (1.2mmol), and then stirred at room temperature for 18 hours. The reaction solution was filtered through silica gel, washed with ether, the washing solution was concentrated until no liquid flowed out, and the product was isolated by silica gel column chromatography (eluent petroleum ether: ethyl acetate 50:1, v/v) (Rf 0.8) to give 6-5. Oily liquid, 69% yield, 89% ee.1H NMR(400MHz,CDCl3)7.15(t,J＝7.6Hz,1H),7.05-6.99 (m,2H),6.94(d,J＝7.6Hz,1H),2.39(q,J＝7.6Hz,1H),2.31(s,3H),1.31(d,J＝ 7.6Hz,3H),1.21(s,6H),1.20(s,6H)；13C NMR(101MHz,CDCl3)144.8,137.7, 128.6,128.1,125.8,124.8,83.2,24.6,24.5,21.4,17.1.HRMS(EI)calculated for [C15H23BO2]+requires m/z 246.1791,found m/z 246.1795.
Example 36
Figure BDA0001596279740000302
Under nitrogen protection, cobalt acetate (0.025mmol), 1-5(0.03mmol) prepared in example 5, and diethyl ether (1.0mL) were added to a dry reaction tube at room temperature, stirred at room temperature for 10min, followed by 3-fluorostyrene (1.0mmol), pinacol borane (1.2mmol), and then stirred at room temperature for 18 h. The reaction solution was filtered through silica gel, washed with ether, the washing solution was concentrated until no liquid flowed out, and the product was isolated by silica gel column chromatography (eluent petroleum ether: ethyl acetate 50:1, v/v) (Rf 0.8) to give 6-6. Oily liquid, 70% yield, 80% ee.
1H NMR(400MHz,CDCl3)7.23-7.16(m,1H),7.00-6.90(m,2H),6.85-6.75(m, 1H),2.49-2.37(m,1H),1.32(d,J＝7.2Hz,3H),1.21(s,6H),1.20(s,6H).
Example 37
Figure BDA0001596279740000311
Under nitrogen protection, cobalt acetate (0.025mmol), 1-5(0.03mmol) prepared in example 5, and diethyl ether (1.0mL) were added to a dry reaction tube at room temperature, and stirred at room temperature for 10min, followed by addition of 3-chlorostyrene (1.0mmol), pinacol borane (1.2mmol), and then stirred at room temperature for 18 hours. The reaction solution was filtered through silica gel, washed with ether, the washing solution was concentrated until no liquid flowed out, and the product was isolated by silica gel column chromatography (eluent petroleum ether: ethyl acetate 50:1, v/v) (Rf 0.8) to give 6-7. Oily liquid, 62% yield, 82% ee.
1H NMR(400MHz,CDCl3)7.23-7.15(m,2H),7.13-7.06(m,2H),2.41(q,J＝7.2 Hz,1H),1.31(d,J＝7.2Hz,3H),1.21(s,6H),1.20(s,6H).
Example 38
Under the protection of nitrogen, FeCl is added into an ultra-dry 25mL-Schlenk tube in sequence2(0.0016g,0.0125 mmol), 1-16(0.015mmol) prepared in example 16, and 0.5mL of 1, 4-dioxane were stirred at room temperature for 2 hours, and then styrene (0.5mmol), HBpin (90. mu.L, 0.6mmol), and NaBHEt were added thereto in this order3(25. mu.L, 1mol/L, solvent THF), stirred at room temperature for 18 h. The reaction solution is filtered by silica gel, washed by ether, the washing solution is concentrated until no liquid flows out, and the product of the mah-jong hydroboration is obtained by silica gel column chromatography (the eluent is petroleum ether: ethyl acetate is 50:1, v/v) and separation (Rf is 0.8). Oily liquid, 78% yield, 79% ee.
Example 39
Under the protection of nitrogen, FeCl is added into an ultra-dry 25mL-Schlenk tube in sequence2(0.0016g,0.0125 mmol), 1-18 prepared in example 18(0.015mmol), and 0.5mL of 1, 4-dioxane were stirred at room temperature for 2 hours, and then styrene (0.5mmol), HBpin (90. mu.L, 0.6mmol), and NaBHEt were added thereto in this order3(25. mu.L, 1mol/L, solvent THF), stirred at room temperature for 18 h. The reaction solution is filtered by silica gel, washed by ether, the washing solution is concentrated until no liquid flows out, and the product of the mah-jong hydroboration is obtained by silica gel column chromatography (the eluent is petroleum ether: ethyl acetate is 50:1, v/v) and separation (Rf is 0.8). Oily liquid, 29% yield, 74.2% ee.

Claims (7)

1. A chiral quinoline amine compound represented by the formula (1),
Figure FDA0002591690730000011
formula (1): represents a chiral carbon atom;
in the formula (1), X is O, S or NR14；
R1Is hydrogen, methyl, ethyl, isopropyl, methoxy or cyclohexyl;
R2is H;
R3，R4，R5，R6is H, methyl or methoxy;
R7，R8，R9、R10is hydrogen;
R11and R12Is hydrogen;
R13is methyl, isopropyl, tert-butyl, phenyl, indenyl or benzyl;
R14is phenyl;
or R12And R13Is connected with two carbons on the five-membered ring to form a ring C9A benzocycloalkyl group of (1).
2. The chiral quinolinamine compound of claim 1, characterized in that said quinolinamine compound is one of the following:
Figure FDA0002591690730000012
Figure FDA0002591690730000021
3. a method for preparing the chiral quinoline amine compound of claim 1, which is characterized by comprising:
under the inert gas environment, in the presence of a transition metal catalyst, a ligand and alkali, in an organic solvent A, taking aminoquinoline shown in a formula (2) and a halide shown in a formula (3) as raw materials or taking a quinoline halide shown in a formula (4) and aniline shown in a formula (5) as raw materials to carry out coupling reaction to prepare a quinoline amine compound shown in a formula (1); the transition metal catalyst is a Pd complex; the ligand is an organic phosphorus compound; the alkali is alkali metal salt of alcohol;
Figure FDA0002591690730000031
x in the formula (3) is O, S or NR14(ii) a Y is F, Cl, Br or I;
Figure FDA0002591690730000032
in the formula (5), X is O, S or NR14(ii) a In the formula (4), Y is F, Cl, Br or I;
r in the formula (2), the formula (3), the formula (4) and the formula (5)1-R14The same as formula (1).
4. The method according to claim 3, wherein the coupling reaction is carried out at a reaction temperature of 50 ℃ to 200 ℃ for a reaction time of 1 hour to 72 hours.
5. The method according to claim 3, wherein the organic solvent A is any one of benzene, dimethylformamide, carbon tetrachloride, toluene, petroleum ether, dioxane, tetrahydrofuran, diethyl ether, chloroform, xylene or acetonitrile; the transition metal catalyst is Pd2(dba)3Or Pd (dba)2(ii) a The ligand is 1,1' -bis (diphenylphosphino) ferrocene, (+ -) -2,2' -bis (diphenylphosphino) -1,1' -binaphthyl or 4, 5-bis-diphenylphosphino-9, 9-dimethylxanthene; the alkali is sodium tert-butoxide or potassium tert-butoxide.
6. The process according to claim 3, wherein the ratio of the amounts of the halogen compound represented by the formula (3), the aminoquinoline represented by the formula (2), the transition metal catalyst, the ligand and the base is 1:0.1 to 4:0.01 to 0.5: 1-4; the mass ratio of the quinoline bromide shown in the formula (4), the aniline shown in the formula (5), the transition metal catalyst, the ligand and the base is 1:0.1-4:0.01-0.5: 1 to 4.
7. The use of a chiral quinoline amine compound represented by the formula (1) as claimed in claim 1 for the preparation of a chiral organoboron ester compound, characterized in that the method for the use comprises: in an organic solvent B and a transition metal compound MYnIn the presence of quinoline amine compound shown as a formula (1), carrying out asymmetric Markov hydroboration reaction on aromatic olefin compound shown as a formula (7) and pinacol borane shown as a formula (8) serving as raw materials to prepare chiral organic boron ester compound shown as a formula (6);
Figure FDA0002591690730000041
in the formula (7), Ar is phenyl or substituted phenyl, and the substituent of the substituted phenyl is C1-C6 alkyl, C1-C6 alkoxy, methylthio, CF3F, Cl or Br; ar in the formula (6) is the same as the formula (7);
the transition metal compoundMYnWherein M is transition metal Fe or Co; y is F, Cl, Br, I, OSO2CH3、OSO2CF3、O(CH3)C＝CHCOCH3、OCOCH2CH3、OCOCH3、ClO4Any one of the above; n is the number of Y and is 2 or 3;
the transition metal compound MYnFerrous chloride or cobalt acetate; the organic solvent B is toluene, diethyl ether or 1, 4-dioxane.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013096151A1 (en) * 2011-12-22 2013-06-27 Glaxosmithkline Llc Chemical compounds
CN105693647A (en) * 2016-01-11 2016-06-22 浙江大学 Chiral compounds containing imine oxazoline amine and preparing method thereof

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013096151A1 (en) * 2011-12-22 2013-06-27 Glaxosmithkline Llc Chemical compounds
CN105693647A (en) * 2016-01-11 2016-06-22 浙江大学 Chiral compounds containing imine oxazoline amine and preparing method thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
"Iminophenyl Oxazolinylphenylamine for Enantioselective Cobalt-Catalyzed Hydrosilylation of Aryl Ketones";Xu Chen et al.;《Organic Letters》;20160830;第18卷(第18期);第4658-4661页 *

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