CN113880822B - Chiral imine quinoline oxazoline-containing compound and metal complex thereof, preparation method and application - Google Patents

Chiral imine quinoline oxazoline-containing compound and metal complex thereof, preparation method and application Download PDF

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CN113880822B
CN113880822B CN202010636101.3A CN202010636101A CN113880822B CN 113880822 B CN113880822 B CN 113880822B CN 202010636101 A CN202010636101 A CN 202010636101A CN 113880822 B CN113880822 B CN 113880822B
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陆展
任翔
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Zhejiang University ZJU
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Abstract

The application discloses a chiral imine-containing quinoline oxazoline compound, which is high in optical purity, has a structural formula shown as a formula (1), and a preparation method thereof. The application also discloses a metal complex obtained by complexing the chiral imine-containing quinoline oxazoline compound with transition metal salt, which is shown as a formula (6). The synthetic route of the application is efficient, and the total yield of the two steps can reach 85%. The chiral metal complex containing the imine quinoline oxazoline compound can be used as a catalyst to catalyze the hydrosilation or hydroboration reaction on carbon-carbon or carbon heteroatom double bonds, and is particularly suitable for preparing chiral organic compounds with high regioselectivity and optical selectivity.

Description

Chiral imine quinoline oxazoline-containing compound and metal complex thereof, preparation method and application
Technical Field
The application relates to a chemical method, in particular to an imine quinoline oxazoline compound and a preparation method thereof, a metal complex compound containing the imine quinoline oxazoline compound and application of the metal complex compound as a catalyst.
Background
Asymmetric reactions catalyzed by transition metal complexes have received extensive academic and industrial interest worldwide, with extensive research into ligands to which central metals are attached. Wherein the bisoxazoline ligand is a very classical ligand that can form complexes with many metals to catalyze many types of reactions [ (a) H.Nishiyama, H.Sakaguchi, T.Nakamura, M.Horihata, M.Kondo, K.Itoh, organometallics 1989,8,846. (b) D.Rechavi, M.Lemaire.Chem.Rev.,2002,1023467. (c) G.Desimoni, G.Faita, P.Quadrelli.Chem.Rev.,2003,103,3119-3154]. [ H.Liu, D. -M.Du, adv.Synth.Catal.2009,351,489 ]. In 1956 Busch and Stoufer et al, a first report on pyridine diimine, the structure of which was subsequently confirmed [ (a) R.C.Stoufer, D.H.Busch J.am.chem.Soc.1956,78,6016 ] (b) F.Lions, K.V.Martin J.am.chem.Soc.1957,79,2733 ] (c) P.E.Figgins, D.H.Busch J.am.chem.Soc.1959,82,820 ], which coordinates mainly with inexpensive metals (Fe, co, ni) to form a catalyst, which is widely used in olefin polymerization reactions, and complexes of other transition metals were successively synthesized for use in catalytic organic reactions, the present inventors synthesized an iminoquinoline oxazoline-containing compound of great significance in the field of transition metal catalysis.
Amines occupy an indispensable part in nitrogen-containing drugs [ Funayama, S. & Cordell, G.A. (eds) alloys: A Treasury of Poisons and Medicines (Waltham, MA, 2014. ], wherein asymmetric reduction of imines is an efficient method for synthesizing chiral amine compounds. However, the reduction of imines involves problems of optical selectivity. Therefore, the development of an inexpensive metal-catalyzed imine hydrogenation reaction with high efficiency and high optical selectivity is of great importance. The widespread presence of chiral secondary alcohols with [ R.Noyori, T.Ohkuma, angew.Chem., int.Ed.,2001,40,40-73 ] in drug molecules, asymmetric reduction of ketones is an important method for obtaining chiral secondary alcohols. However, asymmetric reduction of ketones involves complex optical selectivity problems [ (a) T.Ikariya, K.Murata, R.Noyori, org.Biomol.Chem.,2006,4,393-406; (b) W. -C.zhang, Y. -X.Chi, X. -M.Zhang, acc.Chem.Res.,2007,40,1278-1290]. Therefore, the development of inexpensive metal-catalyzed, highly efficient, highly optically selective ketone reduction reactions is of great importance.
Disclosure of Invention
The application discloses an oxazoline compound containing imine quinoline and a preparation method thereof, and SP in oxazoline ring 2 The carbon atom is attached to the quinoline at position 8 and the quinoline at position 2 is attached to the imine group. The application also discloses a metal complex containing the iminoquinoline oxazoline compound; and to the use of the metal complexes as catalysts in optically selective chemical reactions, in particular in asymmetric reductive transformations comprising at least aryl ketimines and aryl ketones.
The application is realized by the following technical scheme:
a chiral imine quinoline-containing oxazoline compound is high in optical purity, and has a structural formula shown in the following formula (1):
wherein R is 1 Is C1-C12 alkyl which is unsubstituted or substituted by 1 to 2C 1-C4 alkoxy, C5-C12 cycloalkyl which is unsubstituted or substituted by 1 to 3 substituents A, or aryl A which is unsubstituted or substituted by 1 to 4 substituents B; the aryl A is benzyl, phenyl or naphthyl; the substituent A is C1-C4 alkyl or C1-C4 alkoxy; the substituent B is C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F or Cl;
R 2 is H, C1-C12 alkyl which is unsubstituted or substituted by 1-2C 1-C4 alkoxy, C5-C12 cycloalkyl which is unsubstituted or substituted by 1-3 substituents A, or aryl B which is unsubstituted or substituted by 1-3 substituents B; the aryl B is phenyl or naphthyl; the substituent A is C1-C4 alkyl or C1-C4 alkoxy; the substituent B is C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F or Cl;
R 3 、R 4 、R 5 、R 6 、R 7 each independently H, C C12 alkyl, C1C 4 fluoroalkoxy, F, cl, nitro or C5C 12 cycloalkyl which is unsubstituted or substituted by 1 to 3 substituents A which are C1C 4 alkyl or C1C 4 alkoxy;
R 8 、R 9 each independently is H, C1-C12 alkyl which is unsubstituted or substituted by 1-2C 1-C4 alkoxy, C5-C12 cycloalkyl which is unsubstituted or substituted by 1-3 substituents A, or aryl A which is unsubstituted or substituted by 1-3 substituents B; the aryl A is benzyl, phenyl or naphthyl; the substituent A is C1-C4 alkyl or C1-C4 alkoxy; the substituent B is C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F or Cl;
R 10 is C1-C12 alkyl which is unsubstituted or substituted by 1 to 2C 1-C4 alkoxy, C5-C12 cycloalkyl which is unsubstituted or substituted by 1 to 3 substituents A, or aryl A which is unsubstituted or substituted by 1 to 3 substituents B; the aryl A is benzyl, phenyl or naphthyl; the substituent A is C1-C4 alkyl or C1-C4 alkoxy; by a means ofThe substituent B is C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F or Cl;
in formula (1), represents a chiral carbon atom.
The chiral imine quinoline oxazoline-containing compound provided by the application is high in optical purity, and the high optical purity refers to the enantioselectivity of more than 90%, preferably more than 95%, and more preferably more than 99%.
As a further improvement, R as described in the present application 1 Preferably cyclopentyl or cyclohexyl which are unsubstituted or substituted by 1 to 3 substituents A, or aryl A which is unsubstituted or substituted by 1 to 4 substituents B; more preferably phenyl which is unsubstituted or substituted by 1 to 3 substituents B, more preferably phenyl which is substituted by 1 to 2C 1-C4 alkyl groups, and still more preferably 2, 6-dimethylphenyl, 2, 6-diisopropylphenyl.
R 2 Preferably C1-C12 alkyl which is unsubstituted or substituted by 1 to 2C 1-C4 alkoxy, or aryl B which is unsubstituted or substituted by 1 to 3 substituents B; more preferably C1-C12 alkyl, more preferably methyl, ethyl, isopropyl or tert-butyl;
preferably R 3 、R 4 、R 5 、R 6 、R 7 Each independently is H or C1-C12 alkyl, more preferably H, methyl, ethyl, isopropyl or tert-butyl;
preferably R 8 、R 9 Each independently H, C1-C12 alkyl which is unsubstituted or substituted by 1-2C 1-C4 alkoxy, more preferably R 8 、R 9 Is H, methyl, ethyl, isopropyl or tert-butyl.
Preferably R 10 Is C1-C12 alkyl which is unsubstituted or substituted by 1 to 2C 1-C4 alkoxy, aryl A which is unsubstituted or substituted by 1 to 3 substituents B; more preferably R 10 Is C1-C12 alkyl, phenyl or benzyl, more preferably isopropyl, tert-butyl, phenyl or benzyl.
The application also discloses a preparation method of the chiral imine-containing quinoline oxazoline compound shown in the formula (1), which comprises the following steps:
(a) The 2-acyl-8-bromoquinoline compound shown in the formula (2) and the amine compound shown in the formula (3) are subjected to condensation reaction under the action of a catalyst to prepare a compound shown in the formula (4);
(b) Under the protection of nitrogen, the compound shown in the formula (4) and the oxazoline compound shown in the formula (5) are subjected to coupling reaction under the catalysis of transition metal inorganic salt, an organic phosphine ligand and inorganic base to prepare the chiral imine quinoline oxazoline compound shown in the formula (1).
R 1 ～R 10 As previously described.
In the step (a), the ratio of the amount of the 2-acyl-8-bromoquinoline compound represented by the formula (2) to the amount of the amine compound represented by the formula (3) is 1:1 to 10, preferably 1:1 to 5, more preferably 1:1 to 2.
The step (a) is carried out under the action of a catalyst, wherein the catalyst is protonic acid or molecular sieve, preferably p-toluenesulfonic acid, and the amount of the catalyst is 1-5% of the amount of the 2-acyl-8-bromoquinoline compound shown in the formula (2).
The reaction solvent of step (a) is an organic solvent, preferably toluene, benzene or xylene, more preferably toluene. The volume amount of the reaction solvent in the step (a) is 2-10 mL/mmol based on the amount of the substance of the 2-acyl-8-bromoquinoline compound shown in the formula (2).
The reaction in the step (a) needs to be heated to reflux, and a water separator divides water to react for 15-30 hours.
After the reaction in the step (a) is finished, the reaction solution is post-treated to prepare a compound shown as a formula (4), and the post-treatment method comprises the following steps: the reaction solution is cooled to room temperature, filtered, concentrated and recrystallized by ethanol at the temperature of minus 20 ℃ to prepare the compound shown in the formula (4).
Step (b) is a coupling reaction catalyzed by a transition metal Ru, rh, pd, ir inorganic salt and an organophosphine ligand, and an inorganic base.
The step (b) is performed under the catalysis of transition metal inorganic salt, organic phosphine ligand and inorganic base, wherein the transition metal inorganic salt is inorganic salt of Ru, rh, pd, ir, preferably palladium acetate. The inorganic base may be sodium or potassium t-butoxide, preferably lithium t-butoxide; the organophosphine ligand may be triphenylphosphine, tricyclohexylphosphine, 1, 2-bis (diphenylphosphine) ethane or 1,1' -bis (diphenylphosphine) ferrocene, preferably 1, 2-bis (diphenylphosphine) ethane.
The step (b) is performed in an organic solvent, wherein the organic solvent is any one of benzene, carbon tetrachloride, petroleum ether, tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, chloroform, toluene, xylene, cyclohexane, n-hexane, n-heptane, dioxane and acetonitrile, and preferably dioxane. The volume amount of the reaction solvent in the step (b) is 2-10 mL/mmol in terms of the amount of the substance of the compound represented by the formula (4).
As a further improvement, the reaction temperature of the present application is-0 ℃ to 150 ℃, preferably heated to reflux for reaction, and the reaction time is 1 hour to 48 hours.
As a further improvement, in the step (b) of the present application, the ratio of the amounts of the compound represented by the formula (4), the oxazoline compound represented by the formula (5), the transition metal inorganic salt, the organic phosphine ligand, and the inorganic base is 1:1-5:0.01-1:0.02-2:2-10, preferably 1:1-3:0.01-0.1:0.02-0.1:2-4.
The step (b) is carried out under the protection of nitrogen, and the reaction is strictly anhydrous and oxygen-free, so before the reaction, the reaction liquid is frozen by liquid nitrogen, preferably, the reaction liquid is pumped down to vacuum, remelted and circularly operated for 3 times, so that the air is completely removed, and the reaction is carried out under the protection of nitrogen after the nitrogen is supplemented. This is a water-free and oxygen-free treatment commonly used in the art.
In the step (b), after the reaction is finished, the reaction solution is post-treated to prepare the chiral imine-containing quinoline oxazoline compound shown in the formula (1), and the post-treatment method comprises the following steps: and cooling the reaction solution to room temperature, filtering, washing with dichloromethane, concentrating, and separating by column chromatography to obtain the chiral imine-containing quinoline oxazoline compound shown in the formula (1). The eluent used in the column chromatography is petroleum ether and ethyl acetate mixed solvent.
The application also discloses a chiral metal complex containing the imine quinoline oxazoline compound, which is prepared by the complexation reaction of the chiral metal complex containing the imine quinoline oxazoline compound and the transition metal of the subgroup element of the periodic table of the right elements, wherein the general formula of the chiral metal complex containing the imine quinoline oxazoline compound is shown as the following formula (6):
in the formula (6), R 1 -R 10 As described above;
in the formula (6), M is a transition metal Fe, co, ni, cu, ag, au, ru, rh, pd, os or Ir;
the group (E) is any one of halide (F, cl, br, I), pseudohalide (cyanide, cyanate, tetrafluoroborate, isocyanate), carboxylic acid, sulfonic acid, and phosphonic acid anions (carbonate, formate, acetate, propionate, methylsulfonate, trichloromethylsulfonate, phenylsulfonate, toluenesulfonate, phosphate, and hexafluorophosphate);
n is the number of E and is 1,2 or 3.
The chiral metal complex containing the imine quinoline oxazoline compound is prepared by the following method:
under the protection of nitrogen, chiral imine-containing quinoline oxazoline compound shown in formula (1) and transition metal salt ME n Reacting for 1-10 hours in an organic solvent to prepare a chiral metal complex containing imine quinoline oxazoline compounds shown in a formula (6); the organic solvent is tetrahydrofuran or 2-methyltetrahydrofuran
The chiral imine-containing quinoline oxazoline compound shown in the formula (1) and transition metal salt ME n The ratio of the amounts of substances is 2.2 to 0.9:1, preferably 1.1 to 0.9:1, more preferably 1.1 to 1:1.
The synthesis of the chiral imine quinoline oxazoline-containing metal complex can be carried out at a low or high temperature, for example, at a temperature of-20 to 150 ℃, preferably at normal temperature.
The application also provides an application of the chiral metal complex containing the imine quinoline oxazoline compound shown in the formula (6) as a catalyst.
The metal complex is preferably used in an amount of 0.001 to 10mol%, more preferably 0.1 to 5mol%.
More specifically, the catalysis is a hydrosilation or hydroboration reaction on a carbon-carbon or carbon heteroatom double bond of an organic compound in the presence of a catalyst, the reaction being carried out in the presence of a catalytic amount of at least one metal complex of formula (6).
Furthermore, the chiral metal complex containing the imine quinoline oxazoline compound can be used for catalyzing ketone compounds to carry out hydroboration reaction to generate alcohol compounds, wherein the ketone compounds can be alkyl ketone compounds or aryl ketone compounds, alkyl alcohol compounds or aryl alcohol compounds can be generated correspondingly, further, chiral or achiral products can be obtained after the hydroboration reaction, and the chiral products catalyzed by the metal complex have high enantioselectivity and high application value. The metal complex of the chiral imine quinoline oxazoline compound is preferably used for catalyzing the reaction of the hydroboration reaction of the aryl ketone compound to generate chiral aryl alcohol compound.
The chiral metal complex containing the imine quinoline oxazoline compound can be used for catalyzing imine compounds to carry out a hydrosilation reaction to generate amine compounds, wherein the imine compounds can be alkyl imine compounds or aryl imine compounds, and corresponding alkylamine compounds or aryl amine compounds are generated. The chiral or achiral product can be obtained after the hydrosilation reaction, and the chiral product catalyzed by the metal complex has high enantioselectivity and great application value. Preferably, the chiral metal complex containing the imine quinoline oxazoline compound is used for catalyzing the reaction of the aryl imine compound to generate the chiral aryl amine compound through hydrosilation reaction.
Still further, the chiral imine quinoline oxazoline-containing metal complex may be used to catalyze the hydroboration of aryl ketones of the following formula (i) or the hydrosilation of aryl imines of the formula (ii).
Specifically, the hydroboration reaction of formula (i) is carried out as follows: under the protection of nitrogen, stirring a metal complex of the chiral imine-containing quinoline oxazoline compound shown in the formula (6), pinacol borane and sodium triethylborohydride in an organic solvent for 10-30 min, then adding the aryl ketone compound shown in the formula (A), stirring at room temperature for reacting for 1-5 h, and performing column chromatography to obtain the chiral aryl alcohol compound shown in the formula (B). The ratio of the amounts of the aryl ketone compound shown in the formula (A), the pinacol borane, the sodium triethylborohydride and the chiral imine quinoline oxazoline-containing compound shown in the formula (6) is 1:1 to 1.5:0.01 to 0.1:0.01 to 0.1. The organic solvent may be diethyl ether.
The hydrosilylation reaction of formula (ii) is preferably carried out as follows: under the protection of nitrogen, uniformly mixing an aryl imine compound shown in a formula (C), phenylsilane and a metal complex of a chiral imine-containing quinoline oxazoline compound shown in a formula (6) in an organic solvent, then dropwise adding sodium triethylborohydride, stirring at room temperature for reacting for 1-5 h, and performing column chromatography to obtain the chiral aryl amine compound shown in a formula (D). The ratio of the amounts of the aryl imine compound shown in the formula (C), phenylsilane, sodium triethylborohydride and the chiral metal complex containing the imine quinoline oxazoline compound shown in the formula (6) is 1:1-2: 0.1 to 0.5:0.03 to 0.3:0.01 to 0.1. The organic solvent may be diethyl ether.
In the chemical formula (i), the reaction raw material formula (A) is aryl ketone compound, R on phenyl a Represents substituents on the benzene ring, which may be all H or substituted with 1-5 substituents C, which may be various groups including but not limited to alkyl, cycloalkyl, aryl, heteroaryl, hydroxy, F, cl, br, I, nitro, amino, alkoxy, aldehyde, carboxyl, ester, mercapto, sulfonic, silane, siloxaneEtc.
In the formula (ii), R on phenyl in the aryl imine compound shown in the formula (C) b The substituents on the benzene ring may be all H or 1 to 5 substituents C, and the substituents C may be various groups as described above.
In the formula (C), R on imine c May be a variety of groups including, but not limited to, alkyl, cycloalkyl, aryl, heteroaryl, and the like.
The beneficial effects of the application are as follows:
the application provides a novel chiral imine-containing quinoline oxazoline compound.
The application also provides a high-efficiency synthetic route, and the total yield of the two steps can reach 85 percent.
The application provides a novel chiral imine quinoline oxazoline compound which can form a stable metal complex with transition metal Fe, co, ni, cu, ag, au, ru, rh, pd, os, ir.
The application also provides application of the chiral metal complex containing the imine quinoline oxazoline compound as a homogeneous catalyst, the catalyst can be used for preparing chiral or achiral alcohol or amine compounds through catalytic hydrogenation of ketone and ketimine of an organic compound, and particularly can be used for preparing chiral products with high regioselectivity and optical selectivity, and the enantioselectivity of the chiral products can reach more than 85 percent.
Preferred compounds for the reduction of ketones and imines may be open chain or cyclic organic compounds comprising c= C, C =n and/or c=o groups, wherein the c=n and c=o groups may be part of a ring system or an exocyclic group. The unsaturated compounds may be open-chain or cyclic ketones, α, β -diketones, α -or β -ketocarboxylic acids, and α, β -ketoacetals or ketals, esters and amides, ketimines, ketoximes and ketohydrazones.
The chiral or achiral organic compounds prepared by the metal complex catalysts of the application are active substances or intermediates for the preparation of the substances, and are particularly useful in the production of fragrances and flavoring agents, pharmaceutical preparations, agrochemicals.
Detailed Description
The technical scheme of the application is further described in detail through the following specific examples:
the following examples illustrate the application. All reactions were carried out in nitrogen without air and in degassed solvents. But do not limit the present disclosure.
In examples, the amine compound represented by the formula (3) is commercially available, and the 2-acyl-8-bromoquinoline compound represented by the formula (2) is according to the document (K).E.Pump,A.E.Pazio,K./>L.Cavallo, C.Slugovc Beilstein j.org.chem.2015,11,1458). Oxazolines represented by formula (5) are prepared according to literature (J.Chen, T.Xi, Z.Lu org.chem. Front.,2018,5,247.).
Preparation of 8-bromo-2-acetylquinoline
To a 250mL three-necked flask under nitrogen protection was added 8-bromo-formylquinoline (6.9451 g,29.3mmol,1.0 equiv) and diethyl ether (147 mL), methyl magnesium bromide (3M in hex 12.7mL 1.3equiv) was added dropwise at 0℃and after the addition was completed, the reaction was returned to room temperature, stirred for 12 hours, 10mL of saturated ammonium chloride solution was added, 15mL of diethyl ether was used for extraction three times, 10mL of saturated brine was used for washing, and anhydrous sodium sulfate was dried for 1-2 hours. After the reaction mixture was concentrated, 100mL of methylene chloride, 22.31g of PDC (pyridinium dichromate 58.8mmol,2.0 equiv) and silica gel (23.10 g) having the same mass as PDC were added. Stir at room temperature overnight. After the completion of the reaction, the solid was removed by filtration, washed with methylene chloride, and the reaction mixture was concentrated to give a yellow solid, which was separated by column chromatography to give 4.3615g (17.4 mmol, 59%) of 8-bromo-2-acetylquinoline as a white solid
1 H NMR(400MHz,CDCl 3 )δ8.07-7.99(m,2H),7.93(d,J＝8.0Hz,1H),7.65-7.58(m1H), 7.56 (d, j=8.8 hz, 1H), 2.96 (s, 3H); and [ S.Nagy, L.N.Winslow, S.Mihan; L.Lukesova, E.Nifant' ev, P.V.Ivchenko, V.Bagrov, US Patent2012/0016092 2012.]Data matching
Preparation of 8-bromo-2-iminoquinoline of formula (4)
Example A1: preparation of 8-bromo-2-iminoquinolin-A1 (E) -1- (8-bromoquinolin-2-yl) -N- (2, 6-dimethylphenyl) ethane-1-imine
2, 6-dimethylaniline (2.7924 g,23mmol,1.2 equiv) and 8-bromo-2-acetylquinoline (4.7916 g,19mmol,1.0 equiv) were dissolved in 48mL toluene, catalyzed by p-toluenesulfonic acid (0.0738 g,0.38mmol,2 mol%) and heated to reflux, the water separator was allowed to drain off, reacted for 24h, cooled to room temperature after completion of the reaction, filtered, concentrated and recrystallized from ethanol at-20deg.C to afford 4.5437g (12.9 mmol, 67%) as 8-bromo-2-iminoquinoline A1.
IR(neat):2970,2916,1644,1366,1091,760cm -1
1 H NMR(400MHz,CDCl 3 )δ8.60(d,J＝8.4Hz,1H),8.23(d,J＝8.4Hz,1H),8.09(d,J＝7.6Hz,1H),7.85(d,J＝8.0Hz,1H),7.45(dd,J＝7.6,8.0Hz,1H),7.10(d,J＝7.6Hz,2H),6.96(dd,J＝7.6,7.6Hz,1H),2.40(s,3H),2.05(s,6H). 13 C NMR(100MHz,CDCl 3 )δ167.6,156.5,148.8,144.3,136.7,133.2,130.0,127.9,127.8,127.4,125.9,125.2,123.2,119.4,17.9,16.3.
HRMS(ESI)calculated for[C 19 H 18 BrN 2 ]+requires m/z 353.0648,found m/z353.0663
Example A2: preparation of 8-bromo-2-iminoquinolin-A2 (E) -1- (8-bromoquinolin-2-yl) -N- (2, 6-diisopropylphenyl) ethane-1-imine
2, 6-diisopropylaniline (4.2552 g,24mmol,1.2 equiv) and 8-bromo-2-acetylquinoline (5.0007 g,20mmol,1.0 equiv) were dissolved in 50mL toluene, p-toluenesulfonic acid (0.0760 g,0.4mmol,2 mol%) was catalyzed, heated to reflux, the water separator was allowed to drain, the reaction was completed for 24h, cooled to room temperature, filtered, concentrated and recrystallized from ethanol at-20deg.C to give 7.3078g (18 mmol, 90%) of 8-bromo-2-iminoquinoline A2.
IR(neat):2959,2924,1643,1493,1362,760cm -1
1 H NMR(400MHz,CDCl 3 )δ8.59(d,J＝8.8Hz,1H),8.23(d,J＝8.4Hz,1H),8.09(dd,J＝1.2,7.6Hz,1H),7.84(dd,J＝1.2,8.0Hz,1H),2.49-2.30(m,7H),1.14(t,J＝7.6Hz,3H)；
13 C NMR(100MHz,CDCl 3 )δ167.3,156.5,146.5,144.3,136.6,135.5,133.1,130.0,127.8,127.4,125.9,123.7,123.0,119.4,28.3,23.2,22.8,16.9；
HRMS(ESI)calculated for[C 23 H 26 BrN 2 ]+requires m/z 409.1274,found m/z409.1290.
Example A3: preparation of 8-bromo-2-iminoquinolin-A3 (E) -1- (8-bromoquinolin-2-yl) -N- (2-ethylphenyl) ethane-1-imine
2-Ethylaniline (0.7271 g,6.0mmol,1.2 equiv) and 8-bromo-2-acetylquinoline (1.251 g,5.0mmol,1.0 equiv) were dissolved in 12mL toluene, catalyzed by p-toluenesulfonic acid (0.0294 g,0.15mmol,3 mol%), heated to reflux, water was separated by a water separator, reacted for 24h, cooled to room temperature after completion of the reaction, filtered, concentrated and recrystallized from ethanol at-20deg.C to afford 0.8198g (2.35 mmol, 47%) as 8-bromo-2-iminoquinoline A3.
IR(neat):2962,2924,1696,1493,1462,764cm -1
1 H NMR(400MHz,CDCl 3 )δ8.53(d,J＝8.8Hz,1H),8.22(d,J＝8.8Hz,1H),8.11-8.06(m,1H),7.87-7.81(m,1H),7.48-7.42(m,1H),7.30-7.26(m,1H),`7.25-7.19(m,1H),7.14-7.07(m,1H),6.71-6.66(m,1H),2.57-2.48(m,5H),1.16(t,J＝7.6Hz,3H)； 13 C NMR(100MHz,CDCl 3 )δ.167.3,156.5,147.8,144.3,136.7,133.2,130.9,130.0,127.8,127.4,126.0,123.4,119.4,24.6,16.6,13.7；
HRMS(ESI)calculated for[C 19 H 18 BrN 2 ]+requires m/z 353.0648,found m/z353.0655.
B) Preparation of iminoquinoline oxazoline-containing compound B
Example B1: preparation of imine quinoline oxazoline-containing compound B1
Under the protection of nitrogen, A1 (0.8833 g,2.5mmol,1 equiv) and (S) -tert-butyloxazoline ring (0.5441 g,3.375mmol,1.35 equiv) are mixed in 15mL dioxane, palladium acetate (0.0281 g,0.125mmol,5 mol%), 1, 2-bis (diphenylphosphine) ethane (0.0558 g,0.14mmol,5.6 mol%), lithium tert-butoxide (0.4008 g,5mmol,2.0 equiv) are frozen by liquid nitrogen, pumped to vacuum and remelted, the mixture is circulated for 3 times to completely remove air, the mixture is heated to boiling after the nitrogen is filled, the mixture is reacted for 41 hours, the mixture is cooled to room temperature after the reaction is finished, filtered, washed by methylene chloride, and column chromatography separation (petroleum ether and ethyl acetate are eluted according to the volume ratio of 3:1) after the concentration, and 0.9160g (2.0 mmol, 80%) of the compound B1 containing iminooxazoline is obtained as yellow solid
[α] 20 D ＝-54.8(c 1.08,CHCl 3 )
IR(neat):2970,2904,1644,1493,1054,760cm -1
1 H NMR:(400.1MHz,CDCl 3 )δ8.58(d,J＝8.4Hz,1H),8.24(d,J＝8.8Hz,1H),8.10-8.07(m,1H),7.99-7.93(m,1H),7.64-7.58(m,1H),7.10-7.06(m,2H),6.98-6.91(m,1H),4.53-4.46(m,1H),4.40-4.33(m,1H),4.23-4.17(m,1H),2.31(s,3H),2.06-2.01(m,6H),1.05(s,9H)； 13 C NMR:(100.6MHz,CDCl 3 )δ167.6,163.6,156.2,148.8,145.1,136.2,131.2,130.2,129.0,128.7,127.8,126.6,125.1,125.1,123.0,118.8,76.8,69.0,33.8,26.0,17.9,17.9,16.4；
HRMS(ESI)calculated for[C 26 H 30 N 3 O]+requires m/z 400.2383,found m/z400.2395.
Example B2: preparation of imine quinoline oxazoline-containing compound B2
Under nitrogen protection, A2 (1.0210 g,2.5mmol,1 equiv) and (S) -benzyl oxazoline ring (0.5441 g,3.375mmol,1.35 equiv) were separated in 15mL dioxane, palladium acetate (0.0281 g,0.125mmol,5 mol%), 1, 2-bis (diphenylphosphine) ethane (0.0558 g,0.14mmol,5.6 mol%), lithium tert-butoxide (0.4008 g,5mmol,2.0 equiv), then liquid nitrogen was frozen, pumped down to vacuum, remelted, circulated 3 times to completely remove air, after adding nitrogen to boiling, reacted for 41h, cooled to room temperature, filtered, washed with dichloromethane, concentrated and then column chromatographed (petroleum ether, ethyl acetate volume ratio 3:1 elution) to give 1.0227g (2.1 mmol, 84%) of quinoline oxazoline-containing compound B2 as a yellow solid.
[α] 20 D ＝-13.4(c 1.03,CHCl 3 )
IR(neat):2962,2924,1645,1497,1061,764cm -1
1 H NMR:(400.1MHz,CDCl 3 )δ8.59(d,J＝8.8Hz,1H),8.25(d,J＝8.8Hz,1H),8.07(dd,J＝1.2,7.2Hz,1H),7.98(dd,J＝1.2,8.0Hz,1H),7.65-7.59(m,1H),7.35-7.27(m,4H),7.25-7.20(m,1H),7.19-7.16(m,2H),7.14-7.08(m,1H),4.78-4.69(m,1H),4.51(dd,J＝8.8,9.2Hz,1H),4.29(dd,J＝7.6,8.0Hz,1H),3.35(dd,J＝5.2,13.6Hz,1H),2.88(dd,J＝8.8,14.0Hz,1H),2.81-2.70(m,2H),2.34(s,3H),1.18-1.09(m,12H)；
13 C NMR:(100.6MHz,CDCl 3 )δ167.2,164.4,156.2,146.5,145.2,138.0,136.3,135.5,131.0,130.4,129.2,128.8,128.7,128.6,126.7,126.5,123.6,122.9,119.0,72.3,68.1,41.9,28.2,23.2,22.8,16.8；
HRMS(ESI)calculated for[C 33 H 36 N 3 O]+requires m/z 490.2853,found m/z490.2859.
Example B3: preparation of imine quinoline oxazoline-containing compound B3
Under the protection of nitrogen, A2 (1.0213 g,2.52mmol,1 equiv) and (S) -isopropyl oxazoline ring (0.3821 g,3.375mmol,1.35 equiv) are separated by column chromatography (petroleum ether, ethyl acetate volume ratio 3:1 elution) in 15ml1, 4-dioxane, palladium acetate (0.0281 g,0.0125mmol,5 mol%), 1, 2-bis (diphenylphosphine) ethane (0.0558 g,0.14mmol,5.6 mol%), lithium tert-butoxide (0.4005 g,5mmol,2 equiv) are carried out after liquid nitrogen freezing, air suction and melting cycle operation for 3 times, the temperature is raised to boiling after supplementing nitrogen, the reaction is carried out for 41 hours, after the temperature is reduced to room temperature, the filtration, the dichloromethane washing and the concentration are carried out, the column chromatography is carried out, and the yellow solid is obtained, namely 0.8456g (1.9 mmol, 76%) of a compound B3 containing quinoline oxazoline imine oxazoline.
[α] 20 D ＝-55.1(c 1.05,CHCl 3 )
IR(neat):2960,2926,1645,1362,1061,765cm -1
1 H NMR:(400.1MHz,CDCl 3 )δ8.58(d,J＝8.8Hz,1H),8.24(d,J＝8.8Hz,1H),8.09(dd,J＝1.2,7.2Hz,1H),7.96(dd,J＝1.6,8.4Hz,1H),7.61(dd,J＝7.8,8.0Hz,1H),4.60-4.52(m,1H),4.30-4.20(m,2H),2.81-2.69(m,1H),2.34(s,3H),2.02-1.92(m,1H),1.18-1.12(m,12H),1.11(d,J＝6.8Hz,3H),1.03(d,J＝6.8Hz,3H)；； 13 C NMR:(100.6MHz,CDCl 3 )δ167.4,163.7,156.3,146.6,145.2,136.3,135.6,135.5,131.1,130.3,129.0,128.8,126.6,123.6,123.0,122.9,118.9,73.2,70.6,32.8,28.2,23.2,22.8,18.9,18.3,16.9；
HRMS(ESI)calculated for[C 29 H 36 N 3 O]+requires m/z 442.2853,found m/z442.2862.
Example B4: preparation of iminoquinoline oxazoline-containing compound B4
Under the protection of nitrogen, A2 (2.7363 g,6.7mmol,1 equiv) and (S) -tert-butyloxazoline ring (1.1482 g,9.0mmol,1.35 equiv) are separated by column chromatography (petroleum ether, ethyl acetate volume ratio 3:1 elution) in 40mL 1, 4-dioxane, palladium acetate (0.0752 g,0.335mmol,5 mol%), 1, 2-bis (diphenylphosphine) ethane (0.1494 g,0.375mmol,5.6 mol%), lithium tert-butoxide (1.0733 g,13.4mmol,2 equiv) are added after liquid nitrogen freezing, air extraction and melting circulation operation are carried out for 3 times, the mixture is heated to boiling after the reaction is cooled to room temperature for 41h, filtration, dichloromethane washing and column chromatography separation after concentration are carried out, so as to obtain a yellow solid 2.8562g (6.3 mmol, 94%) of a compound B4 containing quinoline oxazoline imine oxazoline.
[α] 20 D ＝-57.8(c 1.05,CHCl 3 )
IR(neat):2970,2903,1647,1400,1254,1060cm -1
1 H NMR:(400.1MHz,CDCl 3 )δ8.58(d,J＝8.8Hz,1H),8.24(d,J＝8.8Hz,1H),8.09(dd,J＝1.2,7.2Hz,1H),7.96(dd,J＝1.6,8.4Hz,1H),7.61(dd,J＝7.8,8.0Hz,1H),4.60-4.52(m,1H),4.30-4.20(m,2H),2.81-2.69(m,1H),2.34(s,3H),2.02-1.92(m,1H),1.18-1.12(m,12H),1.11(d,J＝6.8Hz,3H),1.03(d,J＝6.8Hz,3H)； 13 C NMR:(100.6MHz,CDCl 3 )δ167.4,163.7,156.3,146.6,145.2,136.3,135.6,135.5,131.1,130.3,129.0,128.8,126.6,123.6,123.0,122.9,118.9,73.2,70.6,32.8,28.2,23.2,22.8,18.9,18.3,16.9；
HRMS(ESI)calculated for[C 30 H 38 N 3 O]+requires m/z 456.3009，found m/z456.3021.
c) Preparation of Metal Complex C
Example C1:
under the protection of nitrogen, B1 (0.2117 g,0.53mmol,1.05 equiv) and cobalt chloride (0.0639 g,0.5mmol,1.0 equiv) were reacted in 2.5mL tetrahydrofuran at room temperature for 6 hours, dried by spinning, washed with a small amount of diethyl ether, filtered off with suction, and dried to give 0.2171g (0.41 mmol, 82%) of metal complex C1.
Anal.Calcd for C 26 H 29 Cl 2 CoN 3 O:Found:C,58.99；H,5.52；Cl,13.39；Co,11.13；N,7.94；O,3.02
The same process gives the following metal complexes (C2-C5)
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d) Metal complex C4 catalyzed asymmetric hydroboration of arylalkyl ketones
Metal complex C4 (0.0125 mmol), anhydrous diethyl ether (1 mL), pinacolborane (0.6 mmol), sodium triethylborohydride (0.0125 mmol) were added to a dry reaction tube under nitrogen at room temperature, and acetophenone (0.5 mmol) was added after stirring for 10min and then stirred at room temperature for 1h before column chromatography to give the product.
Example D1: 1-phenylethane-1-ol
1-Phenylethanol
Oily liquid, 55% yield, 73%ee HPLC conditions:Chiralcel AS-H, n-hexane/i-PrOH=98/2, 1.0mL/min, n=220 nm, t r 11.9(major),13.1(minor)； 1 HNMR:(400.1MHz,CDCl 3 ) Delta 7.40-7.31 (m, 4H), 7.30-7.24 (m, 1H), 4.92-4.83 (m, 1H), 1.98 (d, j=2.0 hz, 1H), 1.48 (d, j=6.4 hz, 3H); the product data is consistent with the known [ J.Guo, J.Chen, Z.Lu chem. Commun.2015,51,5725-5727.]
e) Asymmetric hydrosilation of aryl alkyl ketimines catalyzed by metal complexes C1
Metal complex C1 (0.01 mmol), aryl ketimine (0.2 mmol), phenylsilane (0.3 mmol), sodium triethylborohydride (0.03 mmol), anhydrous diethyl ether (0.4 mL) were added to a dry reaction tube at room temperature under nitrogen, and the product was isolated by column chromatography after stirring at room temperature for 1 hour.
Example E1: n- (1- (4-chlorophenyl) ethyl) aniline
N-phenyl-1- (4-methylphenyl) ethylamine
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An oily liquid comprising82％ee；HPLCconditions:Chiralcel OD-H,n-hexane/i-PrOH＝95/5,1.0mL/min,n＝220nm,t r 6.3(minor),6.8(major)； 1 H NMR:(400.1MHz,CDCl 3 ) δ1.51 (d, j=6.73 hz, 3H), 4.07 (brs, 1H), 4.44 (q, j=6.69 hz, 1H), 6.42 (d, j=8.75 hz, 2H), 7.02 (d, j=8.73 hz, 2H), 7.22-7.24 (m, 1H), 7.30-7.33 (m, 4H); the method comprises the steps of carrying out a first treatment on the surface of the The product data are consistent with the known [ Z.Wang, X.Ye, S.Wei, P.Wu, A.Zhang, J.Sun org. Lett.2006,8,999-1001.]
f) Metal complex C1 catalyzed aryl ketimine asymmetric hydrosilation reaction
Metal complex C1 (0.01 mmol), aryl ketimine (0.2 mmol), phenylsilane (0.3 mmol), sodium triethylborohydride (0.03 mmol), anhydrous diethyl ether (0.4 mL) were added to a dry reaction tube at room temperature under nitrogen, and the product was isolated by column chromatography after stirring at room temperature for 1 hour.
Example F1:
N-(1-(4-chlorophenyl)ethyl)aniline
n-phenyl-1- (4-chlorophenyl) ethylamine
An oily liquid comprising85％ee；HPLCconditions:Chiralcel OD-H,n-hexane/i-PrOH＝90/10,1.0mL/min,n＝220nm,t r 8.6(minor),10.2(major)； 1 H NMR:(400.1MHz,CDCl 3 ) δ1.51 (d, j=6.73 hz, 3H), 4.07 (brs, 1H), 4.44 (q, j=6.69 hz, 1H), 6.42 (d, j=8.75 hz, 2H), 7.02 (d, j=8.73 hz, 2H), 7.22-7.24 (m, 1H), 7.30-7.33 (m, 4H); the product data are consistent with the known [ Z.Wang, X.Ye, S.Wei, P.Wu, A.Zhang, J.Sun org. Lett.2006,8,999-1001.]
g) Asymmetric hydrosilation of aryl ketimines catalyzed by metal complexes C1
Metal complex C1 (0.01 mmol), aryl ketimine (0.2 mmol), phenylsilane (0.3 mmol), sodium triethylborohydride (0.03 mmol), anhydrous diethyl ether (0.4 mL) were added to a dry reaction tube at room temperature under nitrogen, and the product was isolated by column chromatography after stirring at room temperature for 1 hour.
Example G1: n- (1- (4-bromobenzyl) ethyl) aniline
N- (1-p-bromophenyl ethyl) -aniline
An oily liquid comprising76％ee；HPLCconditions:Chiralcel OD-H,n-hexane/i-PrOH＝90/10,1.0mL/min,n＝220nm,t r 13.1 (major), 13.8 (minor); the product data are consistent with the known [ Z.—J.Yao, N.Lin, X.—C.Qiao, J.—W.Zhu, W.Deng Organometallics 2018,37,3883-3892 ].]
Example H comparative experiments on the catalytic Properties and reaction conditions of various catalysts
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a The reaction conditions were aryl ketimine (0.2 mmol), phenylsilane (1.5 equiv), catalyst (5 mol%), reducing agent sodium triethylborohydride (15 mol%), anhydrous diethyl ether (0.2M), and reaction at room temperature (r.t.) for 1 hour. b Product identification and yield were determined by nuclear magnetic resonance hydrogen spectroscopy using an internal standard method (trimethylphenylsilane). c The ee value was measured by liquid chromatography OD-H column.
The above list is only some specific embodiments of the present application, and it is obvious that the present application is not limited to the above embodiments, but many variations are possible, and all modifications that can be directly derived or suggested from the disclosure of the present application by a person having ordinary skill in the art should be considered as the scope of the present application.

Claims (7)

1. The chiral imine-containing quinoline oxazoline compound is high in optical purity, wherein the high optical purity refers to enantioselectivity of more than 90%, and the structural formula is shown as the following formula (1):
wherein R is 1 Phenyl which is unsubstituted or substituted by 1 to 3 substituents B; the substituent B is C1-C4 alkyl and C1-C4 alkoxy;
R 2 methyl, ethyl, isopropyl or tert-butyl;
R 3 、R 4 、R 5 、R 6 、R 7 each independently is H, methyl, ethyl, isopropyl or tert-butyl;
R 8 、R 9 each independently is H, methyl, ethyl, isopropyl or tert-butyl;
R 10 is C1-C12 alkyl, phenyl or benzyl;
in formula (1), represents a chiral carbon atom.
2. The process for preparing chiral iminoquinoline oxazoline-containing compounds of claim 1, comprising the steps of:
(a) The 2-acyl-8-bromoquinoline compound shown in the formula (2) and the amine compound shown in the formula (3) are subjected to condensation reaction under the action of a catalyst to prepare a compound shown in the formula (4); the catalyst is p-toluenesulfonic acid;
(b) Under the protection of nitrogen, carrying out coupling reaction on a compound shown in the formula (4) and an oxazoline compound shown in the formula (5) under the catalysis of transition metal inorganic salt and an organic phosphine ligand and inorganic base to obtain a chiral imine quinoline oxazoline compound shown in the formula (1); the transition metal inorganic salt is an inorganic salt of Ru, rh, pd, ir; the organic phosphine ligand is triphenylphosphine, tricyclohexylphosphine, 1, 2-bis (diphenylphosphine) ethane or 1,1' -bis (diphenylphosphine) ferrocene;
R 1 -NH2(3)/>
in the formulas (2) to (5), R 1 -R 10 Is defined as set forth in claim 1.
3. The production method according to claim 2, wherein in the step (a), the ratio of the amount of the 2-acyl-8-bromoquinoline compound represented by the formula (2) to the amount of the amine compound represented by the formula (3) is 1:1 to 10; in the step (b), the ratio of the amounts of the compound represented by the formula (4), the oxazoline compound represented by the formula (5), the transition metal inorganic salt, the organic phosphine ligand and the inorganic base is 1:1-5:0.01-1:0.02-2:2-10.
4. A chiral metal complex containing iminoquinoline oxazoline compound is prepared fromThe chiral iminoquinoline oxazoline-containing compound and transition metal salt ME as claimed in claim 1 n The complex reaction is carried out, and the structural formula is shown as the following formula (6):
in the formula (6), R 1 -R 10 Is defined as set forth in claim 1;
in the formula (6), M is a transition metal Fe, co, ni, cu, ag, au, ru, rh, pd, os or Ir;
and (E) is any one of F, cl, br, I, CN, cyanate, tetrafluoroborate, isocyanate, carbonate, formate, acetate, propionate, methylsulfonate, trichloromethylsulfonate, phenylsulfonate, toluenesulfonate, phosphate and hexafluorophosphate;
n is the number of E and is 1,2 or 3.
5. The method for preparing the chiral metal complex containing the iminoquinoline oxazoline compound according to claim 4, which is characterized in that the method comprises the following steps:
under the protection of nitrogen, chiral imine-containing quinoline oxazoline compound shown in formula (1) and transition metal salt ME n The chiral imine quinoline oxazoline compound containing metal complex shown in the formula (6) is prepared after the reaction for 1 to 10 hours in an organic solvent.
6. The use of a metal complex of a chiral iminoquinoline oxazoline-containing compound of claim 4 as a catalyst for catalyzing a hydrosilylation or boronation reaction on a carbon-carbon or carbon heteroatom double bond, characterized in that the method of use is: the chiral metal complex containing the imine quinoline oxazoline compound is used for catalyzing a reaction of generating an alcohol compound by carrying out hydroboration reaction on a ketone compound, or the chiral metal complex containing the imine quinoline oxazoline compound is used for catalyzing a reaction of generating an amine compound by carrying out hydrosilation reaction on an imine compound.
7. The application according to claim 6, characterized in that the method of application is: the chiral metal complex containing the imine quinoline oxazoline compound is used for catalyzing the reaction of the aryl ketone compound to generate chiral aryl alcohol compound through the hydroboration reaction, or the chiral metal complex containing the imine quinoline oxazoline compound is used for catalyzing the reaction of the aryl imine compound to generate chiral aryl amine compound through the hydrosilation reaction.
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