CN112279779B - Preparation method of chiral aryl oxime ether compound - Google Patents
Preparation method of chiral aryl oxime ether compound Download PDFInfo
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Abstract
The invention provides a preparation method of a chiral aryl oxime ether compound, which adopts a chiral copper catalyst to catalyze asymmetric oxime etherification reaction of aryl oxime and a propargyl compound, and a method for preparing a series of chiral aryl oxime ether compounds with high enantioselectivity. The reaction is carried out with Cu (OTf)2And chiral P, N, N-ligand in situ, and can be carried out at-20 deg.C in the presence of methanol, ethanol, etc. The method has the characteristics of relatively mild reaction conditions, easily obtained raw materials, high stereoselectivity, wide substrate application range and the like.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a method for preparing a series of chiral aryl oxime ether compounds by copper-catalyzed asymmetric oxime etherification reaction and high enantioselectivity of aryl oxime and propargyl compounds.
Background
Copper-catalyzed propargyl substitution has attracted attention from researchers since the first copper-catalyzed asymmetric propargyl amination reaction was reported almost simultaneously by van maarseven and Nishibayashi groups in 2008. [ (a) Detz, r.j.; delville, m.m.e.h.; hiemstra, h.; van Maarsesen, J.H.Enantioselective Copper-catalyzed proliferative administration [ J ]. Angew.chem.int.Ed.2008,47(20), 3777-; (b) hattori, G; matsuzawa, h.; miyake, y.; nishibayashi, Y.cope-catalyzed asymmetric prokaryotic reactions [ J ] Angew.chem.Int.Ed.2008,41(20),3781-3783 ] to date, a large number of nitrogen and carbon nucleophiles have been widely used in copper-catalyzed asymmetric propargyl substitution and cycloaddition reactions, but the asymmetric propargyl substitution reactions involving oxygen nucleophiles have been rarely reported.
In 2015, the Nishibayashi group adopted Cu/pybox as a catalyst to realize the first Cu-catalyzed asymmetric propargyl etherification of propargyl alcohol ester with simple alcohol or phenol, and achieved very good yield and enantioselectivity (up to 99% ee). [ (a) Nakajima, k.; shibata, m.; nishibayashi Y.hopper-catalyzed enzymatic proactive evaluation of proactive esters with alcohols [ J ]. J.Am.chem.Soc.2015,137(7), 2472-2475; however, the reaction takes a relatively long time and only aliphatic propargyl alcohol esters are suitable for this reaction. Then, a catalytic method (b) Shao L, which has quicker reaction and wider substrate application range, is developed; zhang d. -y.; wang Y. -H.; hu X. -P.Enantioselective chip-catalyzed polymeric ether chemistry of polymeric esters with phenols by organic base additives [ J ]. adv.Synth.Catal.2016 (15),2558 + 2563; (c) barluenga, j.; trincado, m.; Marco-Arias, m.; ballasteros, a.; rubio, e.; gonz lez, J.M. interferometric amplification reaction of alkyl easy access to derivatives of fused carbohydrate, chem.Commun.2005, (15), 2008-2010; (d) tsuchida, k.; yuki, m.; nakajima, k.; nishibayashi, Y.Copper-and borinic acid-catalyzed particulate catalytic reforming of particulate carbon substrates with benzyl alcohols chem.Lett.2018,47(5),671-673 ], but catalytic asymmetric propargyl conversion reactions using oximes as the oxygen nucleophile have not been achieved.
Disclosure of Invention
The invention aims to provide a method for preparing a series of chiral aryl oxime ether compounds with high enantioselectivity by carrying out copper-catalyzed asymmetric oxime etherification reaction on aryl oxime and propargyl compounds. The reaction takes a metal complex generated in situ by a copper metal precursor and a chiral P, N, N-ligand as a catalyst, and can be carried out at the temperature of minus 20 ℃ by taking methanol and the like as a solvent.
The method comprises the following specific steps:
(1) preparation of chiral copper catalyst: under the protection of nitrogen, copper salt and chiral P, N, N-ligand are stirred in a reaction medium for 0.5 to 2 hours according to the molar ratio of 1:0.1 to 10 to prepare a chiral copper catalyst;
(2) preparation of chiral aryl oxime ether compound: dissolving a propargyl compound, an aryl oxime and an alkali additive in a reaction medium to obtain a mixed solution, and then adding the mixed solution into the solution of the chiral copper catalyst stirred in the step (1) under the protection of nitrogen, and stirring and reacting at-20 ℃ for not less than 12 hours; after the reaction is finished, concentrating under reduced pressure until no solvent exists basically, separating by silica gel column chromatography, concentrating under reduced pressure, and drying in vacuum to obtain chiral aryl oxime ether compound;
the molar ratio of the chiral copper catalyst to the propargyl compound in the step (2) is 0.001-1: 1;
the molar ratio of the alkali additive to the propargyl compound is 1-10:1, preferably 1.2: 1;
the molar ratio of the aryl oxime compound to the propargyl compound is 1-2:1, preferably 1.5: 1;
the aryl oxime (I) has the structure:
in the formula: ar is phenyl or substituted phenyl; the substituent on the phenyl is one or more than two of C1-C40 alkyl, C1-C40 alkoxy, halogen, nitro, ester group or cyano.
The propargyl compound has the following structure:
in the formula: r is one or more than two of C1-C40 alkyl, C3-C12 cycloalkyl, C3-C12 cycloalkyl with substituent, phenyl, substituted phenyl, benzyl and substituted benzyl; the substituent on the C3-C12 naphthenic base, the substituent on the phenyl and the substituent on the benzyl are one or more than two of C1-C40 alkyl, C1-C40 alkoxy, halogen, nitro, ester group or cyano; x is one or more of fluorine, chlorine, bromine, iodine, alkyl acetate, alkyl carbonate, alkyl sulfonate, alkyl phosphate, phenyl or substituted phenyl carboxylate, phenyl or substituted phenyl carbonate, phenyl or substituted phenyl sulfonate, and phenyl or substituted phenyl phosphate.
Preferably, when the propargyl compound is preferably aromatic propargyl alcohol ester, the molar ratio of the chiral copper catalyst to the aromatic propargyl alcohol ester compound is 0.001-1: 1.
The chiral P, N, N-ligand has the following structural characteristics:
the dominant configuration of the ligand may be (R) or (S);
in the formula, R1，R2Is one or more than two of alkyl in H, C1-C10, cycloalkyl in C3-C8, phenyl, substituted phenyl, benzyl or substituted benzyl;
R3，R4is one or more than two of H, halogen, alkyl, cycloalkyl, phenyl, substituted phenyl, alkoxy, phenoxy, acyl or nitro;
R5is one or more than two of alkyl, cycloalkyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl and five-membered or six-membered heterocyclic aromatic groups containing one or more than one oxygen atom, sulfur atom and nitrogen atom.
The etherification products of the aryl oximes and various aryl and alkyl propargyl alcohol esters have one of the following two structures:
the reaction medium is dichloromethane, acetonitrile, methanol, ethanol or toluene, preferably one or two of methanol and ethanol;
the copper salt is anhydrous Cu (OTf)2、CuCl,CuBr、CuI、CuBr2、Cu(OTf)2·0.5C6H6、Cu(CH3CN)BF4,Hydrated Cu (OAc)2·H2O、CuF2·H2One or more than two of O, preferably Cu (OAc)2·H2O、Cu(OTf)2One or two of CuCl or CuIAnd (4) performing the steps.
The alkali additive isiPr2NEt、NEt3、tBuOK、KOH、LiOH、Cs2CO3One or more than two of them.
The catalytic reaction conditions in the step (2) are preferably as follows: the temperature is-20 ℃; the reaction medium is methanol; the pressure is normal pressure; the time period required was 24 hours.
The molar ratio of the chiral copper catalyst to the propargyl compound is preferably 0.001:1-1: 1;
the molar ratio of the alkali additive to the propargyl compound is preferably 1.2: 1;
the molar ratio of the aryl oxime compound to the propargyl compound is preferably 1.5: 1;
the copper salt is preferably Cu (OAc)2·H2O、Cu(OTf)2One or more than two of CuI or CuBr;
the reaction medium is preferably one or two of methanol and ethanol.
The reaction equation of the invention is as follows:
the invention has the following advantages:
1. the initial raw materials are cheap and easy to obtain;
2. the chiral ligand is simple and convenient to synthesize, the catalyst is cheap and easy to obtain, and the using amount is small;
3. the reaction activity is good, the stereoselectivity is high, and the reaction condition is easy to realize;
4. the substrate has wide application range, and can carry out etherification reaction on various aromatic aryl oximes and aromatic propargyl alcohol esters to obtain ideal effect.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.
FIG. 1 is a NMR spectrum of chiral (E) -benzaldehyde O- (1-phenylpropargyl) oxime III-1 prepared in example 1;
FIG. 2 is a NMR carbon spectrum of chiral (E) -benzaldehyde O- (1-phenylpropargyl) oxime III-1 prepared in example 1;
FIG. 3 is a NMR spectrum of (E) -benzaldehyde O- (1- (4-methoxyphenylpropargyl) oxime III-2 prepared in example 8;
FIG. 4 is a NMR carbon spectrum of (E) -benzaldehyde O- (1- (4-methoxyphenylpropargyl) oxime III-2 prepared in example 8;
FIG. 5 is a NMR spectrum of (E) -benzaldehyde O- (1- (4-trifluoromethylphenylpropargyl) oxime III-3 prepared in example 9;
FIG. 6 is a NMR carbon spectrum of (E) -benzaldehyde O- (1- (4-trifluoromethylphenylpropargyl) oxime III-3 prepared in example 9;
FIG. 7 is a NMR spectrum of (E) -benzaldehyde O- (1- (4-bromophenylpropargyl) oxime III-4 prepared in example 10;
FIG. 8 is a NMR carbon spectrum of (E) -benzaldehyde O- (1- (4-bromophenylpropargyl) oxime III-4 prepared in example 10;
FIG. 9 is a NMR hydrogen spectrum of (E) -4-methylbenzaldehyde O- (phenylpropargyl) oxime III-5 prepared in example 11;
FIG. 10 is a NMR carbon spectrum of (E) -4-methylbenzaldehyde O- (phenylpropargyl) oxime III-5 prepared in example 11;
FIG. 11 is a NMR spectrum of (E) -4-bromobenzaldehyde O- (phenylpropargyl) oxime III-6 prepared in example 12;
FIG. 12 is a NMR carbon spectrum of (E) -4-bromobenzaldehyde O- (phenylpropargyl) oxime III-6 prepared in example 12;
FIG. 13 is a NMR spectrum of (E) -4-tert-butylbenzaldehyde O- (phenylpropargyl) oxime III-7 prepared in example 13;
FIG. 14 is a NMR carbon spectrum of (E) -4-tert-butylbenzaldehyde O- (phenylpropargyl) oxime III-7 prepared in example 13.
Detailed Description
The following examples further illustrate the invention but are not intended to limit the invention thereto. NMR was measured by Bruker 400 NMR and High Performance Liquid Chromatography (HPLC) was measured by Agilent1100 series HPLC.
Example 1
Cu(OTf)2And L-1-1 is complexed as a catalyst for catalytic reaction to generate an etherification product III-1 of (E) -benzaldehyde O- (1-phenyl propargyl) oxime.
The metal precursor Cu (OTf) was charged into a reaction flask2(0.005mmol, 5 mol%) and chiral ligand L-1-1(0.011mmol, 5.5 mol%), adding 1.0mL of anhydrous methanol under nitrogen protection, and stirring at room temperature for 1 hour. Then, the propargyl alcohol ester II-1(0.3mmol, 1.0equiv), the aryl benzaldehyde oxime compound I-1(0.45mmol, 1.5equiv) andiPr2NEt (0.36mmol, 1.2equiv) was dissolved in 2.0mL of anhydrous methanol, and the solution was added to the stirred solution of the catalyst under nitrogen protection and stirred at-20 ℃ for 24 h. After the reaction, the mixture is concentrated under reduced pressure until no solvent exists basically, and is separated by silica gel column chromatography, concentrated under reduced pressure and dried in vacuum to obtain white solid with 78 percent of yield and 85 percent of ee.
The hydrogen and carbon nuclear magnetic resonance spectra of the product III-1 are shown in FIGS. 1 and 2:1H NMR(400MHz,CDCl3)δ8.02(s,1H),7.52(dd,J＝7.8,1.4Hz,2H),7.47–7.42(m,2H),7.35–7.28(m,4H),7.25(dd,J＝8.8,2.0Hz,2H),5.86(d,J＝2.2Hz,1H),2.64(d,J＝2.2Hz,1H).13C NMR(101MHz,CDCl3)δ167.9,149.0,136.0,130.8,129.1,127.9,127.6,127.5,127.5,127.0,126.3,80.5,74.9,74.4.HPLC(Chiralpak AD-H,n-hexane/i-PrOH＝99/1,0.8mL/min,254nm,40℃):tR(major)＝14.1min,tR(minor)＝16.3min。
the product is detected to be (E) -benzaldehyde O- (1-phenyl propargyl) oxime etherification product III-1.
The structural formula of I-1, II-1, III-1, L-1-1 is as follows:
example 2: (S, S) -Me-pybox as ligand to produce product III-1
The ligand L-1-1 in example 1 was replaced by the ligand (S, S) -Me-pybox, the remainder being as in example 1. The reaction gave compound III-1 in 65% yield and 68% ee.
The structural formula of (S, S) -Me-pybox is as follows:
example 3: l-1-2 is used as ligand to react to generate a product III-1
The ligand L-1-1 in example 1 was replaced with the ligand L-1-2, and the procedure was otherwise the same as in example 1. The reaction gave compound III-1 in 46% yield, 59% ee.
The structural formula of L-1-2 is as follows:
example 4: l-1-3 as ligand reacts to produce product III-1
The ligand L-1-1 in example 1 was replaced with the ligand L-1-3, and the procedure was otherwise the same as in example 1. The reaction gave compound III-1 in 43% yield and 30% ee.
Example 5: l-1-4 as ligand reacts to produce product III-1
The ligand L-1-1 in example 1 was replaced with the ligand L-1-4, and the procedure was otherwise the same as in example 1. The reaction gave compound III-1 in 60% yield and 85% ee.
Example 6: cu (OAc)2·H2The O and the L-1-1 are catalyzed to generate a product III-1
Cu (OTf) of example 12With Cu (OAc)2·H2The procedure is as in example 1 except that O is replaced. Compound III-1 was obtained in 65% yield, 85% ee.
Example 7: cs2CO3As a base additive to produce the product III-1
Will be as in example 1iPr2Replacement of NEt by Cs2CO3Otherwise, the same procedure as in example 1 was repeated. Compound III-1 was obtained in 50% yield, 80% ee.
Example 8: II-2 is used as a substrate to react to generate a product (E) -benzaldehyde O- (1- (4-methoxyphenyl propargyl) oxime
The same procedure used in example 1 was repeated except for replacing propargyl alcohol acetate II-1 in example 1 with II-2 to give compound III-2 in 56% yield and 78% ee. The hydrogen and carbon nuclear magnetic resonance spectra of the product III-2 are shown in FIGS. 3 and 4:1H NMR(400MHz,CDCl3)δ8.12(s,1H),7.59(dd,J＝6.7,3.0Hz,2H),7.56–7.52(m,2H),7.38–7.33(m,3H),6.94–6.90(m,2H),5.90(d,J＝2.2Hz,1H),3.81(s,3H),2.71(d,J＝2.2Hz,1H).13C NMR(101MHz,CDCl3)δ160.1,149.9,132.0,130.1,129.5,129.2,128.7,127.3,113.9,81.7,75.7,75.1,55.3.HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝98/2,0.8mL/min,254nm,40℃):tR(major)＝12.7min,tR(minor)＝15.4min。
the product is detected to be (E) -benzaldehyde O- (1- (4-methoxyphenyl propargyl) oxime.
The structural formulas of II-2 and III-2 are as follows:
example 9: II-3 is used as a substrate to react to generate a product (E) -benzaldehyde O- (1- (4-trifluoromethyl phenyl propargyl) oxime
The same procedure used in example 1 was repeated except for replacing propargyl alcohol acetate II-1 in example 1 with II-3 to give compound III-3 in 68% yield and 84% ee. Product produced by birthThe hydrogen and carbon nuclear magnetic resonance spectra of the compound III-3 are shown in FIGS. 5 and 6:1H NMR(400MHz,CDCl3)δ8.16(s,1H),7.73(d,J＝8.2Hz,2H),7.66(d,J＝8.3Hz,2H),7.58(dd,J＝7.2,2.4Hz,2H),7.44–7.33(m,3H),5.99(d,J＝2.0Hz,1H),2.75(d,J＝2.2Hz,1H).13C NMR(101MHz,CDCl3)δ150.3,135.7,134.8,131.7,130.3,129.4,128.8,128.7,127.36,81.0,76.3,74.6.HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝98/2,0.8mL/min,254nm,40℃):tR(major)＝9.5min,tR(minor)＝13.5min。
the product is detected to be (E) -benzaldehyde O- (1- (4-trifluoromethyl phenyl propargyl) oxime.
The structural formulas of II-3 and III-3 are as follows:
example 10: II-4 is taken as a substrate to react to generate a product (E) -benzaldehyde O- (1- (4-bromophenyl propargyl) oxime
The same procedure used in example 1 was repeated except for substituting propargyl alcohol acetate II-1 in example 1 with II-4 to give compound III-4 in 82% yield and 86% ee. The NMR spectrum and the carbon spectrum of the product III-4 are shown in FIGS. 7 and 8:1H NMR(400MHz,CDCl3)δ7.93(s,1H),7.38(dd,J＝6.6,3.0Hz,2H),7.33(d,J＝8.5Hz,2H),7.28(d,J＝8.5Hz,2H),7.17(dd,J＝5.2,1.8Hz,3H),5.70(d,J＝2.2Hz,1H),2.53(d,J＝2.2Hz,1H).13C NMR(101MHz,CDCl3)δ150.3,136.2,131.7,131.7,130.3,129.7,129.0,128.7,127.4,123.0,80.9,76.3,74.6.HPLC(Chiralpak AD-H,n-hexane/i-PrOH＝98/2,0.8mL/min,254nm,40℃):tR(major)＝9.9min,tR(minor)＝10.8min.
the product was detected to be (E) -benzaldehyde O- (1- (4-bromophenylpropargyl) oxime.
The structural formulas of II-4 and III-4 are as follows:
example 11: i-2 is used as a substrate to react to generate a product (E) -4-methyl benzaldehyde O- (phenyl propargyl) oxime
The same procedure used in example 1 was repeated except for substituting propargyl alcohol acetate I-1 in example 1 with I-2 to give compound III-5 in 89% yield and 85% ee. The hydrogen and carbon nuclear magnetic resonance spectra of the product III-5 are shown in FIGS. 9 and 10:1H NMR(400MHz,CDCl3)δ8.40(s,1H),7.72–7.66(m,1H),7.65–7.58(m,2H),7.43–7.33(m,3H),7.28–7.22(m,1H),7.17(dd,J＝13.6,7.5Hz,2H),5.96(d,J＝2.2Hz,1H),2.71(d,J＝2.2Hz,1H),2.39(s,3H).13C NMR(101MHz,CDCl3)δ149.1,137.1,137.1,130.9,130.1,129.9,128.9,128.6,128.1,127.3,126.1,81.5,77.4,77.1,76.8,75.9,75.4,20.0.HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝98/2,0.8mL/min,254nm,40℃):tR(major)＝11.2min,tR(minor)＝11.9min.
the product was detected to be (E) -4-methylbenzaldehyde O- (phenyl propargyl) oxime.
The structural formula of I-2 and III-5 is as follows:
example 12: i-3 is taken as a substrate to react to generate a product (E) -4-bromobenzaldehyde O- (phenyl propargyl) oxime
The same procedure used in example 1 was repeated except for substituting propargyl alcohol acetate I-1 in example 1 with I-3 to give compound III-6 in 87% yield and 86% ee. The hydrogen and carbon nuclear magnetic resonance spectra of the product III-6 are shown in FIGS. 11 and 12:1H NMR(400MHz,CDCl3)δ7.98(s,1H),7.70(t,J＝7.2Hz,1H),7.55–7.48(m,2H),7.43–7.37(m,2H),7.36–7.24(m,3H),7.14(t,J＝7.9Hz,1H),5.87(d,J＝2.2Hz,1H),2.65(d,J＝2.2Hz,1H).13C NMR(101MHz,CDCl3)δ149.1,137.1,137.1,130.9,130.1,129.9,128.9,128.6,128.1,127.3,126.1,81.5,77.4,77.1,76.8,75.9,75.4,20.0.HPLC(Chiralpak AS-H,n-hexane/i-PrOH＝98/2,0.8mL/min,254nm,40℃):tR(major)＝10.4min,tR(minor)＝16.0min.
the product is detected to be (E) -4-bromobenzaldehyde O- (phenyl propargyl) oxime.
The structural formula of I-3 and III-6 is as follows:
example 13: i-4 is used as a substrate to react to generate a product (E) -4-tert-butyl benzaldehyde O- (phenyl propargyl) oxime
The same procedure used in example 1 was repeated except for substituting propargyl alcohol acetate I-1 in example 1 with I-4 to give compound III-6 in 86% yield and 89% ee. The NMR spectrum of the product III-7 is shown in FIGS. 13 and 14:1H NMR(400MHz,CDCl3)δ7.93(s,1H),7.43–7.38(m,2H),7.33(d,J＝8.4Hz,2H),7.18(dd,J＝6.0,4.5Hz,5H),5.74(d,J＝2.1Hz,1H),2.50(d,J＝2.2Hz,1H),1.11(s,9H).13C NMR(101MHz,CDCl3)δ153.8,150.2,137.4,129.3,129.1,128.8,128.2,127.4,125.9,81.8,76.1,75.5,35.1,31.4.HPLC(Chiralpak AD-H,n-hexane/i-PrOH＝98/2,0.8mL/min,254nm,40℃):tR(major)＝8.4min,tR(minor)＝9.0min.
the product is detected to be (E) -4-tert-butyl benzaldehyde O- (phenyl propargyl) oxime.
The structural formula of I-4 and III-7 is as follows:
examples 14 to 24: reaction substrate suitability
The invention has wide substrate applicability, and according to the reaction conditions in the example 1, a plurality of substrates can participate in the reaction, and the (E) -benzaldehyde O- (1-phenyl propargyl) oxime compound can be obtained with high yield and high selectivity, and the reaction formula is as follows:
TABLE 1
| Examples of the invention | I(Ar) | II(R) | Yield (%) | Excess of the counterparts (%) |
| 1 | Ph | Ph | 78 | 85 |
| 14 | 4-FC6H4 | Ph | 78 | 88 |
| 15 | 4-ClC6H4 | Ph | 80 | 86 |
| 16 | 4-NO2C6H4 | Ph | 75 | 89 |
| 17 | 1-naphthyl4 | Ph | 86 | 89 |
| 18 | 2-MeC6H4 | Ph | 65 | 88 |
| 19 | Ph | 4-FC6H4 | 81 | 84 |
| 20 | Ph | 4-ClC6H4 | 78 | 85 |
| 21 | Ph | 3-ClC6H4 | 61 | 91 |
| 22 | Ph | 2- |
50 | 90 |
| 23 | Ph | Cy | 45 | 95 |
| 24 | Ph | 4-MeC6H4 | 75 | 84 |
In examples 14 to 24, when Ar and R were replaced, respectively, the yield and enantiomeric excess were as shown in Table 1 above.
Claims (3)
1. A preparation method of chiral aryl oxime ether compound is characterized in that: the method adopts a chiral copper catalyst to catalyze asymmetric oxime etherification reaction of aryl oxime compound and propargyl ester compound to prepare a series of chiral aryl oxime ether compounds;
the method specifically comprises the following steps:
(1) preparation of chiral copper catalyst: under the protection of nitrogen, copper salt and chiral P, N, N-ligand are stirred in a reaction medium for 0.5 to 2 hours according to the molar ratio of 1:0.1 to 10 to prepare a chiral copper catalyst;
(2) preparation of chiral aryl oxime ether compound: dissolving a propargyl ester compound, aryl oxime and an alkali additive in a reaction medium to obtain a mixed solution, and then adding the mixed solution into the solution of the chiral copper catalyst stirred in the step (1) under the protection of nitrogen, and stirring and reacting at-20 ℃ for not less than 12 hours; after the reaction is finished, concentrating under reduced pressure until no solvent exists basically, separating by silica gel column chromatography, concentrating under reduced pressure, and drying in vacuum to obtain chiral aryl oxime ether compound;
the molar ratio of the chiral copper catalyst to the propargyl ester compound in the step (2) is 0.001-1: 1;
the molar ratio of the alkali additive to the propargyl ester compound is 1-10: 1;
the molar ratio of the aryl oxime compound to the propargyl ester compound is 1-2: 1;
the aryl oxime (I) has the structure:
in the formula: ar is phenyl or substituted phenyl; the substituent on the phenyl is one or more than two of C1-C40 alkyl, C1-C40 alkoxy, halogen, nitro and cyano;
the propargyl ester compound (II) has the following structure:
in the formula: r is phenyl or substituted phenyl, and the substituent on the phenyl is one or more than two of C1-C40 alkyl, C1-C40 alkoxy, halogen, nitro and cyano; x is OAc;
the chiral P, N, N-ligand has the following structural characteristics:
the ligand configuration is R or S;
in the formula, R1Is alkyl in C1-C10 or cycloalkyl in C3-C8; r2Is H or phenyl;
R3，R4is H;
R5is phenyl;
the chiral aryl oxime ether compound has one of the following two structures:
the reaction medium is dichloromethane, acetonitrile, methanol, ethanol or toluene; the copper salt is anhydrous Cu (OTf)2、CuCl,CuBr、CuI、CuBr2、Cu(OTf)2·0.5C6H6、Cu(CH3CN)BF4，Cu(OAc)2·H2O、CuF2·H2One or more than two of O;
the alkali additive isiPr2NEt、NEt3、tBuOK、KOH、LiOH、Cs2CO3One or more than two of them.
2. The process for the preparation of chiral aryl oxime ether compounds of claim 1 wherein:
the catalytic reaction conditions in the step (2) are as follows: the temperature is-20 ℃; the reaction medium is methanol; the pressure is normal pressure; the time period required was 24 hours.
3. The process for the preparation of chiral aryl oxime ether compounds of claim 1 wherein:
the molar ratio of the chiral copper catalyst to the propargyl ester compound is 0.001-1: 1;
the molar ratio of the base additive to the propargyl ester compound is 1.2: 1;
the molar ratio of the aryl oxime compound to the propargyl alcohol ester compound is 1.5: 1;
the copper salt is Cu (OAc)2·H2O、Cu(OTf)2One or more than two of CuCl or CuI;
the reaction medium in the step (1) is one or two of methanol and ethanol.
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