CN110734378B - Method for preparing chiral allylamine compound with high chemistry and stereoselectivity - Google Patents

Method for preparing chiral allylamine compound with high chemistry and stereoselectivity Download PDF

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CN110734378B
CN110734378B CN201910886513.XA CN201910886513A CN110734378B CN 110734378 B CN110734378 B CN 110734378B CN 201910886513 A CN201910886513 A CN 201910886513A CN 110734378 B CN110734378 B CN 110734378B
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chiral
cdcl
nmr
amine
allylamine
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CN110734378A (en
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阴国印
龙姣
王鹏
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Wuhan University WHU
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Abstract

The invention discloses a method for preparing chiral allylamine compounds with high chemistry and stereoselectivity. In the metal reagent Ni (COD)2Chiral diphosphine ligands and

Description

Method for preparing chiral allylamine compound with high chemistry and stereoselectivity
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a method for preparing a chiral allylamine compound with high chemistry and stereoselectivity and application thereof.
Background
Chiral amine fragments are widely present in natural products as well as in biologically active molecules [ a) Lough, w.j.; wainer, i.w. chirality in Natural and Applied Science, Blackwell: Oxford, UK, 2002; b) francotte e e.; lindner, W.Chirality in Drug Research, Wiley-VCH, Weinheim, 2006; c) nugent, T.C. Chiral Amine Synthesis: Methods, Developments and Applications, Wiley-VCH: Weinheim,2010 ]. Based on its important application value, the synthesis of chiral amines has attracted great interest and widespread interest in the field of organic chemistry [ a) Li, w.; zhang, X, Stereoselective Formation of Amines, 2014; b) nugent, t.c.; El-Shazly, m.adv. synth.cat.2010, 352, 753-819; c) patil, M.D.; grogan, g.; bommerius, a.; yun, H.ACS Catal.2018,8, 10985-11015; d) grogan, g.curr.opin.chem.biol.2018,43, 15-22 ]. The hydroamination reaction is a reaction in which a compound having an N-H bond is directly added to an unsaturated carbon-carbon double bond or triple bond to thereby construct a new C-N bond. The reaction conforms to the strategies of atom economy and green chemistry, and is one of the most effective methods for synthesizing chiral amine compounds.
Asymmetric hydroamination reactions of allenes, alkynes and conjugated alkenes catalyzed by transition metals have been reported [ a) Lutete, l.m.; kadota, i.; yamamoto, y.j.am.chem.soc.2004,126, 1622-1623; b) cookie, m.l.; xu, k.; breit, b.angelw.chem.int.ed.2012, 51, 10876-10879; c) xu, k.; wang, y.h.; khakyzadeh, v.; breit, B.Chem.Sci.2016,7, 3313-3316; d) athira, c.; chanmotra, a.; sunoj, R.B.J.org.chem.2018,83, 2627-2639; e) xiong, y.; sun, y.w.; zhang, G.Z.tetrahedron Lett.2018,59, 347-355; f) park, s.; malcolmson, S.J.ACS Catal.2018,8, 8468-; g) berthold, d.; geissler, a.g.a.; giofre, s.; breit, B.Angew.chem.int.Ed.2019,58, 9994-. Furthermore, in order to increase the conversion of the reaction, it is generally necessary to use a large excess of unsaturated substrate.
Therefore, how to realize the cheap metal-catalyzed asymmetric hydroamination reaction with high chemical and stereoselectivity under mild conditions is urgently needed to be solved.
Disclosure of Invention
The invention aims to provide a method for preparing a chiral allylamine compound with cheap metal catalysis and high chemical and stereoselectivity, which has the advantages of simple operation, cheap and easily obtained raw materials, mild reaction conditions, good tolerance of substrate functional groups and excellent chemical selectivity and stereoselectivity.
The invention adopts the following technical scheme for realizing the aim:
a method for preparing chiral allylamine compounds with high chemical and stereoselectivity comprises the following steps: in the metal reagent Ni (COD)2(bis (1, 5-cyclooctadiene) nickel), chiral diphosphine ligands and
Figure BDA0002207447730000022
under the action of an acid additive, dissolving 1, 3-conjugated diene and amine in an organic solvent for reaction, and separating and purifying by column chromatography to obtain a chiral allylamine compound;
the synthetic route of the method is as follows:
Figure BDA0002207447730000021
preferably, the 1, 3-conjugated diene is a 1-aryl or alkyl substituted 1, 3-butadiene, further preferably the substituent R comprises: phenyl, 2-methoxyphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 4-dimethylaminophenyl, 2-furyl, cyclohexyl.
Preferably, the amine comprises: n-butylamine, 2-phenylethylamine, cyclopropylamine, cyclohexylamine, furfurylamine, 2- (1-cyclohexenyl) ethylamine, allylamine, (±) -tetrahydrofurfuryl amine, N-dimethylethylenediamine, benzylamine, glycine methyl ester, (S) -1-phenylethylamine, aniline, 4-methylaniline, 4-bromo-aniline, ethanolamine, N-benzylethylenediamine, 2-hydroxybenzylamine, 4-aminophenylethanol, tryptamine, 4-aminobenzylamine, morpholine, thiomorpholine, piperidine, tetrahydropyrrole, indoline, tetrahydroisoquinoline, 1- (2-pyrimidinyl) piperazine, N-methylallylamine, N-methylbenzylamine, dibenzylamine, ethylenediamine, N-methylaniline.
Preferably, the chiral diphosphine ligand is (S) -BIANP, (S) -SegPhos, (S) -SKP, (R) -SDP, (R) -DIOP, (S, S) -BDPP, (R) -SDPC,SP) -DuanPhos, any one of (S, S) -Me-DuPhos, the specific structure of which is shown below:
Figure BDA0002207447730000031
preferably, said
Figure BDA0002207447730000032
The acid additive is any one of benzoic acid, phenylpropionic acid, phenylphosphoric acid, phthalic acid, p-toluenesulfonic acid, terephthalic acid, naphthylacetic acid and o-hydroxybenzoic acid, and the specific structure of the acid additive is as follows:
Figure BDA0002207447730000033
preferably, the organic solvent is one of methanol, ethanol, isopropanol, trifluoroethanol, hexafluoroisopropanol, toluene, trifluorotoluene, dichloromethane, 1, 2-dichloroethane, chloroform, diethyl ether, 1, 4-dioxane, tetrahydrofuran, methyl tert-butyl ether, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone, ethyl acetate, acetonitrile, benzonitrile, ethylene glycol dimethyl ether, and N-hexane.
Preferably, the preparation method of the chiral allylamine compound comprises the following specific steps: in an inert gas, adding a metal reagent Ni (COD)2The chiral diphosphine ligand is dissolved in a dry organic solvent, and then 1, 3-conjugated diene, amine and
Figure BDA0002207447730000035
and (2) adding an acid additive to obtain a reaction mixture, sealing the reaction mixture, taking out the reaction mixture from the inert gas, concentrating under reduced pressure to remove the organic solvent after the reaction is completed, and separating and purifying by column chromatography to obtain the target product chiral allylamine compound:
Figure BDA0002207447730000034
preferably, the metal reagent Ni (COD)2: chiral diphosphine ligand:
Figure BDA0002207447730000042
acid additive: 1, 3-conjugated diene: amine: the dosage ratio of the organic solvent is 0.01 mmol: 0.01 mmol: 0.01 mmol: 0.2 mmol: 0.3 mmol: 1.0 mL.
The invention also provides a chiral allylamine compound prepared by the method.
Compared with the prior art, the invention has the following advantages and characteristics:
1. the invention discloses a method for synthesizing chiral allylamine compounds, which uses cheap metal nickel to be based on the judgment of the concentration of the alkali metal
Figure BDA0002207447730000043
The acid is a cocatalyst, and the used raw materials are simple and easy to obtain and the operation is simple and convenient.
2. The method for synthesizing the chiral allylamine compound disclosed by the invention has very mild reaction conditions and can be carried out at room temperature.
3. The method for synthesizing the chiral allylamine compound disclosed by the invention has a very wide substrate range, and the aryl alkene substrate, the heteroaryl alkene and even the alkyl substituted alkene are very compatible no matter rich in electrons or poor in electrons, and the primary amine, the secondary amine, the aromatic amine and the aliphatic amine can be converted very efficiently, so that the yield is up to 99%.
4. The method for synthesizing the chiral allyl amine compound disclosed by the invention has excellent chemoselectivity and stereoselectivity, can well identify reaction sites for amine substrates containing two nucleophilic sites, and has an ee value as high as 99%.
5. The method for synthesizing the chiral allylamine compound disclosed by the invention can be used for carrying out gram-scale amplification, and the catalyst load can be reduced to below 1%.
6. The method for synthesizing the chiral allylamine compound disclosed by the invention can also efficiently react drug molecules such as desloratadine and the like, and provides a new method for derivatization of the drug molecules and synthesis of complex drug molecules.
Detailed Description
Advantages and features of the present invention will be further understood by the following detailed description. The examples provided are merely illustrative of the method of the present invention and do not limit the remainder of the disclosure in any way.
In the following examples, the optical rotation of the chiral compound was measured by a Perkin Elmer 343 polarimeter, the ee value was determined by Agilent 1260Series HPLC detection, and HRMS was measured by Waters Micromass GCT mass spectrometer.
Example 1
Figure BDA0002207447730000041
In a glove box filled with argon, bis (1, 5-cyclooctadiene) nickel and (S, S) -Me-DuPhos were mixed at a molar ratio of 1:1, dissolved in dry toluene to prepare a solution having a concentration of 0.01M (multiple reactions were allowed to occur at one time for complexation, and a catalyst solution was prepared in an amount as required), and pre-stirred for 0.5 h. Subsequently, 1mL of the catalyst solution was taken, 1-phenyl-1, 3-butadiene (26. mu.L, 0.2mmol), n-butylamine (30. mu.L, 0.3mmol) and phthalic acid (1.7mg, 0.01mmol) were added thereto, and the reaction vial was sealed and taken out from the glove box and reacted at 25 ℃ for 24 hours. After the reaction is finished, decompressing and concentrating to remove the reaction solvent, and performing column chromatography separation and purification to obtain a product (S, E) -N-butyl-4-phenylbut-3-en-2-amine which is colorless oily liquid and has the yield of 93 percent; ee> 99％；[α]D 25＝-60.3(c＝1.0,CHCl3) (ii) a HPLC detection uses a Chiralpak AD-H chromatographic column, and the mobile phase is n-hexane: isopropanol (volume ratio of 99:1), flow rate of 0.6mL/min, detection wavelength of 254nm, retention time tR＝9.2min(major),9.7min(minor)；1H NMR(400MHz,CDCl3)δ 7.39-7.36(m,2H),7.33-7.29(m,2H),7.24-7.19(m,1H),6.46(d,J＝15.9Hz,1H), 6.08(dd,J＝15.9,8.0Hz,1H),3.39-3.32(m,1H),2.67-2.53(m,2H),1.52-1.43(m, 2H),1.38-1.29(m,2H),1.25(d,J＝6.5Hz,3H),0.91(t,J＝7.3Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ137.1,134.4,129.7,128.5,127.2,126.2,56.4,47.3,32.4, 22.0,20.5,14.0ppm；HRMS(ESI)calculated[M+Na]+for C14H21NNa＝226.1566, found:226.1565.
Example 2
Figure BDA0002207447730000051
In a glove box filled with argon, bis (1, 5-cyclooctadiene) nickel and (S, S) -Me-DuPhos were mixed at a molar ratio of 1:1, dissolved in dry toluene to prepare a solution having a concentration of 0.01M (multiple reactions were allowed to occur at one time for complexation, and a catalyst solution was prepared in an amount as required), and pre-stirred for 0.5 h. Then, 1mL of the catalyst solution was taken, and 1-phenyl-1, 3-butane was added theretoDiene (26. mu.L, 0.2mmol), 2-phenylethylamine (38. mu.L, 0.3mmol) and phthalic acid (1.7mg, 0.01mmol), the reaction vial was sealed and removed from the glove box and reacted at 25 ℃ for 24 hours. After the reaction is finished, decompressing and concentrating to remove the reaction solvent, and performing column chromatography separation and purification to obtain a product (S, E) -N-phenylethyyl-4-phenylbut-3-en-2-amine which is a light yellow oily liquid with the yield of 99 percent; ee is 92%; [ alpha ] to]D 25＝-76.8(c＝1.0,CHCl3) (ii) a HPLC detection uses a Chiralpak AD-H chromatographic column, and the mobile phase is n-hexane: isopropanol (volume ratio of 99:1), flow rate of 0.6mL/min, detection wavelength of 254nm, retention time tR＝13.9min(major),15.0min(minor)；1H NMR (400MHz,CDCl3)δ7.37-7.34(m,2H),7.32-7.26(m,4H),7.23-7.18(m,4H),6.44 (d,J＝15.9Hz,1H),6.05(dd,J＝15.9,8.0Hz,1H),3.41-3.34(m,1H),2.96-2.79(m, 4H),1.23(d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ139.9,136.9, 133.9,129.9,128.7,128.5,128.4,127.3,126.2,126.1,56.2,48.8,36.4,21.9ppm； HRMS(ESI)calculated[M+Na]+for C18H21NNa＝274.1566,found:274.1563.
Example 3
Figure BDA0002207447730000061
In a glove box filled with argon, bis (1, 5-cyclooctadiene) nickel and (S, S) -Me-DuPhos were mixed at a molar ratio of 1:1, dissolved in dry toluene to prepare a solution having a concentration of 0.01M (multiple reactions were allowed to occur at one time for complexation, and a catalyst solution was prepared in an amount as required), and pre-stirred for 0.5 h. Subsequently, 1mL of the catalyst solution was taken, 1-phenyl-1, 3-butadiene (26. mu.L, 0.2mmol), cyclopropylamine (21. mu.L, 0.3mmol) and phthalic acid (1.7mg, 0.01mmol) were added thereto, and the reaction vial was sealed and taken out of the glove box and reacted at 25 ℃ for 24 hours. After the reaction is finished, decompressing and concentrating to remove the reaction solvent, and performing column chromatography separation and purification to obtain a product (S, E) -N- (4-phenylbut-3-en-2-yl) cyclopropanamine which is a colorless oily liquid and has the yield of 61 percent; ee>99％；[α]D 25＝-91.8(c＝1.0,CHCl3) (ii) a HPLC detection uses a Chiralpak OJ-H chromatographic column, and the mobile phase is n-hexane: isopropanol (volume ratio 95:5), flow rate 0.5mL/min, detection wavelength 254nm, retention time tR＝10.5min(major),10.9min(minor)；1H NMR(400 MHz,CDCl3)δ7.39-7.37(m,2H),7.33-7.29(m,2H),7.24-7.20(m,1H),6.49(d,J＝ 15.9Hz,1H),6.12(dd,J＝15.9,7.9Hz,1H),3.52-3.45(m,J＝6.7Hz,1H), 2.18-2.13(m,1H),2.02(br,s 1H),1.25(d,J＝6.5Hz,3H),0.47-0.33(m,4H)ppm；13C NMR(100MHz,CDCl3)δ137.2,134.4,129.4,128.5,127.2,126.2,56.5,28.6, 21.8,6.6,6.4ppm；HRMS(ESI)calculated[M+Na]+for C13H17NNa＝210.1253, found:210.1254.
Example 4
Figure BDA0002207447730000062
In a glove box filled with argon, bis (1, 5-cyclooctadiene) nickel and (S, S) -Me-DuPhos were mixed at a molar ratio of 1:1, dissolved in dry toluene to prepare a solution having a concentration of 0.01M (multiple reactions were allowed to occur at one time for complexation, and a catalyst solution was prepared in an amount as required), and pre-stirred for 0.5 h. Subsequently, 1mL of the catalyst solution was taken, 1-phenyl-1, 3-butadiene (26. mu.L, 0.2mmol), cyclohexylamine (34. mu.L, 0.3mmol) and phthalic acid (1.7mg, 0.01mmol) were added thereto, and the reaction vial was sealed and taken out of the glove box and reacted at 25 ℃ for 24 hours. After the reaction is finished, concentrating under reduced pressure to remove the reaction solvent, and separating and purifying by column chromatography to obtain the product (S, E) -N- (4-phenylbut-3-en-2-yl) cyclohexoxamine as a light yellow oily liquid, wherein the yield is 76%, and the ee is 91%; [ alpha ] to]D 25＝-66.1(c＝1.0,CHCl3) (ii) a HPLC detection uses a Chiralpak AD-H chromatographic column, and the mobile phase is n-hexane: isopropanol (volume ratio of 99:1), flow rate of 0.6mL/min, detection wavelength of 254nm, retention time tR＝8.7min(major),9.5min(minor)；1H NMR(400 MHz,CDCl3)δ7.49-7.37(m,2H),7.33-7.29(m,2H),7.24-7.20(m,1H),6.44(d,J＝ 15.9Hz,1H),6.07(dd,J＝15.9,8.1Hz,1H),3.59-3.52(m,1H),2.55-2.48(m,1H), 2.01-1.97(m,1H),1.84-1.58(m,3H),1.69(br,s,1H),1.26-0.98(m,9H)ppm；13C NMR(100MHz,CDCl3)δ137.1,134.8,129.3,128.5,127.2,126.2,53.5,52.5,34.4, 33.2,26.1,25.3,25.0,22.5ppm；HRMS(ESI)calculated[M+Na]+for C16H23NNa＝ 252.1723,found:252.1722.
Example 5
Figure BDA0002207447730000071
In a glove box filled with argon, bis (1, 5-cyclooctadiene) nickel and (S, S) -Me-DuPhos were mixed at a molar ratio of 1:1, dissolved in dry toluene to prepare a solution having a concentration of 0.01M (multiple reactions were allowed to occur at one time for complexation, and a catalyst solution was prepared in an amount as required), and pre-stirred for 0.5 h. Subsequently, 1mL of the catalyst solution was taken, 1-phenyl-1, 3-butadiene (26. mu.L, 0.2mmol), furfuryl amine (28. mu.L, 0.3mmol) and phthalic acid (1.7mg, 0.01mmol) were added thereto, and the reaction vial was sealed and taken out of the glove box and reacted at 25 ℃ for 24 hours. After the reaction is finished, decompressing and concentrating to remove the reaction solvent, and performing column chromatography separation and purification to obtain a product (S, E) -N- (furan-2-ylmethyl) -4-phenylbut-3-en-2-amine which is a light yellow oily liquid with the yield of 99 percent; ee is 99%; [ alpha ] to]D 25＝-49.2(c＝1.0,CHCl3) (ii) a HPLC detection uses a Chiralpak OD-H chromatographic column, and the mobile phase is n-hexane: isopropanol (volume ratio of 99:1), flow rate of 0.5mL/min, detection wavelength of 254nm, retention time tR＝17.0min(minor),20.0min(major)；1H NMR(400 MHz,CDCl3)δ7.40-7.36(m,3H),7.33-7.30(m,2H),7.25-7.21(m,1H),6.49(d,J＝ 15.9Hz,1H),6.31(dd,J＝3.1,1.9Hz,1H),6.16(dd,J＝3.1,0.5Hz,1H),6.07(dd,J ＝15.9,8.1Hz,1H),3.83(d,J＝14.4Hz,1H),3.73(d,J＝14.4Hz,1H),3.42-3.35(m, 1H),1.26(d,J＝6.4Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ153.9,141.8, 137.0,133.7,130.5,128.5,127.4,126.3,110.1,106.8,55.3,43.8,22.0ppm；HRMS (ESI)calculated[M+H]+for C15H18NO＝228.1383,found:228.1380.
Example 6 gram Scale reaction
Figure BDA0002207447730000081
In a glove box filled with argon, bis (1, 5-cyclooctadiene) nickel (13.8mg,0.05mmol) and (S, S) -Me-DuPhos (15.3mg,0.05mmol) were dissolved in 5mL of dry toluene and pre-stirred for 0.5 h. To the catalyst solution were then added 1-phenyl-1, 3-butadiene (650. mu.L, 5.0mmol), 2- (1-cyclohexenyl) ethylamine (1043. mu.L, 7.5mmol) and phthalic acid (41.5mg, 0.25mmol), the reaction flask was sealed and removed from the glove box and reacted at 25 ℃ for 96 hours. After the reaction is finished, the reaction solvent is removed by decompression and concentration, and the product (S, E) -N- (2- (cyclohexex-1-en-1-yl) ethyl) -4-phenylbut-3-en-2-amine 1.23g is obtained by column chromatography separation and purification, and is light yellow oily liquid with the yield of 96 percent; ee is 96%; [ alpha ] to]D 25＝-66.1(c＝1.0,CHCl3) (ii) a HPLC detection uses a Chiralpak AD-H chromatographic column, and the mobile phase is n-hexane: isopropanol (volume ratio 95:5), flow rate 0.5mL/min, detection wavelength 254nm, retention time tR＝11.0min(minor),11.6min(major)；1H NMR(400MHz,CDCl3)δ7.39-7.36(m,2H),7.33-7.29(m,2H),7.24-7.20(m,1H), 6.46(d,J＝15.9Hz,1H),6.07(dd,J＝15.9,8.0Hz,1H),5.48-5.45(m,1H), 3.38-3.31(m,1H),2.74-2.59(m,2H),2.14(t,J＝6.9Hz,2H),2.01-1.97(m,2H), 1.92-1.88(m,2H),1.64-1.51(m,4H),1.46(br,s,1H),1.24(d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ137.1,135.4,134.4,129.7,128.5,127.2,126.2,122.8, 56.2,45.2,38.4,28.1,25.2,22.9,22.4,22.1ppm；HRMS(ESI)calculated[M+H]+ for C18H26N＝256.2060,found:256.2057.
The following examples 7-50 were all made using the method steps of examples 1-5 above, and the structures and data of the compounds synthesized were characterized as follows:
example 7
(S, E) -N-allyl-4-phenylbut-3-en-2-amine as pale yellow oily liquid in yield
Figure BDA0002207447730000091
＝11.9min(major),12.7min(minor)；1H NMR(400MHz,CDCl3)δ7.39-7.37(m, 2H),7.33-7.29(m,2H),7.24-7.20(m,1H),6.46(d,J＝15.9Hz,1H),6.06(dd,J＝ 15.9,8.1Hz,1H),5.97-5.87(m,1H),5.20-5.15(m,1H),5.12-5.08(m,1H),3.44-3.36 (m,1H),3.34-3.28(m,1H),3.24-3.18(m,1H),1.86(br,s,1H),1.26(d,J＝6.5Hz, 3H)ppm；13C NMR(100MHz,CDCl3)δ137.0,136.8,133.9,130.1,128.5,127.3, 126.2,115.9,55.6,50.0,22.0ppm；HRMS(ESI)calculated[M+Na]+for C13H17NNa ＝210.1253,found:210.1258.
Example 8
(2S,E)-4-phenyl-N-((tetrahydrofuran-2-yl)methyl)but-3-en-2-a
Figure BDA0002207447730000092
The detection wavelength is 254nm, and the retention time tR1＝15.3min(major),16.9min (minor),tR2＝19.8min(minor),21.2min(major)；3i:1H NMR(400MHz,CDCl3)δ 7.39-7.37(m,2H),7.33-7.29(m,2H),7.24-7.20(m,1H),6.50(d,J＝5.7Hz,1H), 6.08(dd,J＝8.1,3.2Hz,1H),4.08-3.98(m,1H),3.88-3.82(m,1H),3.78-3.72(m, 1H),3.45-3.38(m,1H),2.77(dd,J＝11.9,3.4Hz,1H),2.68(d,J＝1.9Hz,1H), 2.02-1.84(m,3H),1.58-1.46(m,1H),1.29(d,J＝3.3Hz,3H)ppm；13C NMR(100 MHz,CDCl3)δ136.9,133.7,130.4,128.5,127.3,126.3,78.5,67.9,56.8,52.3,29.4, 25.7,21.9ppm；3i′:1H NMR(400MHz,CDCl3)δ7.39-7.37(m,2H),7.33-7.29(m, 2H),7.24-7.20(m,1H),6.46(d,J＝5.7Hz,1H),6.12(dd,J＝8.1,3.2Hz,1H), 4.08-3.98(m,1H),3.88-3.82(m,1H),3.78-3.72(m,1H),3.45-3.38(m,1H),2.70(s, 1H),2.58(dd,J＝11.9,8.5Hz,1H),2.02-1.84(m,3H),1.58-1.46(m,1H),1.27(d,J ＝3.3Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ136.9,133.7,130.2,128.5,127.3, 126.3,77.9,67.9,56.2,51.7,29.3,25.7,21.8ppm；HRMS(ESI)calculated[M+H]+ for C15H22NO＝232.1696,found:232.1693.
Example 9
(S,E)-N1,N1-dimethyl-N2-(4-phenylbut-3-en-2-yl)ethane-1,2-dia
Figure BDA0002207447730000101
90:10), flow rate of 0.5mL/min, detection wavelength of 254nm, retention time tR＝ 43.1min(major),50.8min(minor)；1H NMR(400MHz,CDCl3)δ7.39-7.37(m,2H), 7.32-7.29(m,2H),7.24-7.20(m,1H),6.47(d,J＝15.9Hz,1H),6.08(dd,J＝15.9, 8.0Hz,1H),3.39-3.32(m,1H),2.78-2.62(m,2H),2.46-2.43(m,3H),2.22(s,6H), 1.27(d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ137.0,134.0,130.0, 128.5,127.3,126.2,59.0,56.5,45.4,44.7,22.0ppm；HRMS(ESI)calculated [M+H]+for C14H23N2＝219.1856,found:219.1856.
Example 10
(S, E) -N-benzyl-4-phenylbut-3-en-2-amine as a pale yellow oily liquid in a yield of 91%; ee is 90%;
Figure BDA0002207447730000102
12.5min(minor)；1H NMR(400MHz,CDCl3)δ7.40-7.38(m,2H),7.33-7.30(m, 6H),7.27-7.20(m,2H),6.48(d,J＝15.9Hz,1H),6.11(dd,J＝15.9,8.0Hz,1H), 3.85(d,J＝13.1Hz,1H)3.73(d,J＝13.1Hz,1H),3.44-3.37(m,1H),1.27(d,J＝ 6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ140.5,137.1,134.2,130.1,128.5, 128.4,128.1,127.3,126.9,126.3,55.5,51.5,22.1ppm；HRMS(ESI)calculated [M+Na]+for C17H19NNa＝260.1410,found:260.1405.
example 11
methyl (S, E) - (4-phenylbut-3-en-2-yl) glycinate is light yellow oily liquid with the yield of 80 percent; ee>
Figure BDA0002207447730000103
The speed is 0.5mL/min, the detection wavelength is 254nm, and the retention time tR＝27.2min(major),28.4min (minor)；1H NMR(400MHz,CDCl3)δ7.38-7.35(m,2H),7.32-7.29(m,2H), 7.24-7.20(m,1H),6.45(d,J＝15.8Hz,1H),6.01(dd,J＝15.8,8.2Hz,1H),3.69(s, 3H),3.42(d,J＝3.1Hz,2H),3.39-3.32(m,1H),2.17(br,s,1H),1.27(d,J＝6.5Hz, 3H)ppm；13C NMR(100MHz,CDCl3)δ173.2,136.8,133.2,130.7,128.5,127.5, 126.3,56.2,51.8,48.4,22.0ppm；HRMS(ESI)calculated[M+H]+for C13H18NO2＝ 220.1332,found:220.1331.
Example 12
(S, E) -4-phenyl-N- ((R) -1-phenyl ethyl) but-3-en-2-amine as pale yellow oily liquid in yield
Figure BDA0002207447730000111
3.38-3.31(m,1H),1.76(br,s,1H),1.37(d,J＝6.6Hz,3H),1.22(d,J＝6.4Hz,3H) ppm；13C NMR(100MHz,CDCl3)δ145.8,137.1,134.6,129.2,128.5,127.2,126.8, 126.5,126.2,54.8,53.0,23.7,21.2ppm；HRMS(ESI)calculated[M+Na]+for C18H21NNa＝274.1566,found:274.1566.
Example 13
(S, E) -N- (4-phenylbut-3-en-2-yl) aniline as yellowish oily liquid
Figure BDA0002207447730000112
Time tR＝11.6min(major),13.4min(minor)；1H NMR(400MHz,CDCl3)δ 7.36-7.34(m,2H),7.30-7.27(m,2H),7.22-7.13(m,3H),6.70-6.63(m,3H),6.57(d, J＝16.0Hz,1H),6.21(dd,J＝16.0,5.8Hz,1H),4.17-4.11(m,1H),1.40(d,J＝6.6 Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ147.4,136.9,133.2,129.2,129.1, 128.5,127.3,126.3,117.3,113.4,50.8,22.1ppm；HRMS(ESI)calculated[M+Na]+ for C16H17NNa＝246.1253,found:246.1253.
Example 14
(S, E) -4-methyl-N- (4-phenylbut-3-en-2-yl) aniline is a reddish brown oily liquid with a yield of 23%; ee
Figure BDA0002207447730000113
＝93％；[α]D 25＝-99.5(c＝1.0,CHCl3) (ii) a HPLC detection uses a Chiralpak AD-H chromatographic column, and the mobile phase is n-hexane: isopropanol (volume ratio 95:5), flow rate 0.5mL/min, detection wavelength 254nm, retention time tR＝14.6min(major),16.5min(minor)；1H NMR(400MHz,CDCl3) δ7.36-7.34(m,2H),7.31-7.27(m,2H),7.22-7.18(m,1H),6.97(d,J＝8.2Hz,2H), 6.59-6.55(m,3H),6.21(dd,J＝16.0,5.9Hz,1H),4.14-4.08(m,1H),2.22(s,3H), 1.39(d,J＝6.6Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ145.1,136.9,133.4, 129.6,129.1,128.5,127.3,126.5,126.3,113.6,51.1,22.1,20.4ppm；HRMS(ESI) calculated[M+Na]+for C17H19NNa＝260.1410,found:260.1405.
Example 15
(S, E) -4-bromo-N- (4-phenylbut-3-en-2-yl) aniline as a reddish brown oily liquid with a yield of 48%; ee
Figure BDA0002207447730000121
Time tR＝13.5min(minor),17.2min(major)；1H NMR(400MHz,CDCl3)δ 7.35-7.32(m,2H),7.31-7.27(m,2H),7.24-7.19(m,3H),6.56-6.49(m,3H),6.16(dd, J＝16.0,5.8Hz,1H),4.12-4.05(m,1H),3.75(br,s,1H),1.40(d,J＝6.7Hz,3H) ppm；13C NMR(100MHz,CDCl3)δ146.3,136.7,132.5,131.8,129.5,128.5,127.5, 126.3,114.9,108.8,50.9,22.0ppm；HRMS(ESI)calculated[M+H]+for C16H17BrN ＝302.0539,found:302.0524.
Example 16
(S, E) -4- (4-phenylbut-3-en-2-yl) morpholine is light yellow oily liquid, and the yield is 99 percent; ee ═
Figure BDA0002207447730000122
(minor),14.4min(major)；1H NMR(400MHz,CDCl3)δ7.39-7.36(m,2H), 7.33-7.29(m,2H),7.25-7.21(m,1H),6.47(d,J＝15.9Hz,1H),6.17(dd,J＝15.9, 8.2Hz,1H),3.73(t,J＝4.7Hz,4H),3.05-2.99(m,1H),2.61-2.52(m,4H),1.26(d,J ＝6.6Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ136.8,132.0,131.2,128.6,127.5, 126.2,67.2,63.1,50.8,17.8ppm；HRMS(ESI)calculated[M+Na]+for C14H19NNaO＝240.1359,found:240.1359.
Example 17
(S, E) -4- (4-phenylbut-3-en-2-yl) thiomorphine as colorless oily liquid,
Figure BDA0002207447730000131
tR＝8.7min(minor),9.7min(major)；1H NMR(400MHz,CDCl3)δ7.39-7.37(m, 2H),7.33-7.30(m,2H),7.25-7.21(m,1H),6.44(d,J＝16.0Hz,1H),6.21(dd,J＝ 16.0,7.2Hz,1H),3.27-3.20(m,1H),2.90-2.80(m,4H),2.69(t,J＝5.0Hz,4H),1.25 (d,J＝6.7Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ136.9,131.7,130.9,128.5, 127.4,126.2,62.7,51.6,28.3,16.3ppm；HRMS(ESI)calculated[M+Na]+for C14H19NNaS＝256.1130,found:256.1130.
example 18
(S, E) -1- (4-phenylbut-3-en-2-yl) piperidine as a pale yellow oily liquid
Figure BDA0002207447730000132
8.6min(minor),9.8min(major)；1H NMR(400MHz,CDCl3)δ7.39-7.37(m,2H), 7.32-7.29(m,2H),7.24-7.19(m,1H),6.43(d,J＝16.0Hz,1H),6.24(dd,J＝15.9, 8.0Hz,1H),3.11-3.05(m,1H),2.52-2.50(m,4H),1.63-1.57(m,4H),1.46-1.42(m, 2H),1.26(d,J＝6.6Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ137.2,132.7, 130.5,128.5,127.2,126.2,63.0,51.0,26.2,24.6,17.7ppm；HRMS(ESI)calculated [M+Na]+for C15H21NNa＝238.1566,found:238.1568.
Example 19
(S, E) -1- (4-phenylbut-3-en-2-yl) pyrolidine as a pale yellow oily liquid in a yield of 91%; ee ═
Figure BDA0002207447730000133
(minor),8.1min(major)；1H NMR(400MHz,CDCl3)δ7.39-7.36(m,2H),7.32-7.29 (m,2H),7.24-7.20(m,1H),6.47(d,J＝15.9Hz,1H),6.24(dd,J＝15.8,8.6Hz,1H), 2.93-2.86(m,1H),2.61-2.55(m,4H),1.81-1.78(m,4H),1.30(d,J＝6.5Hz,3H) ppm；13C NMR(100MHz,CDCl3)δ137.1,133.9,129.6,128.5,127.2,126.2,63.1, 52.2,23.3,21.0ppm；HRMS(ESI)calculated[M+Na]+for C14H19NNa＝224.1410, found:224.1410.
Example 20
(S, E) -1- (4-phenylbut-3-en-2-yl) indoline as a pale yellow oily liquid in 87% yield; ee is 97%;
Figure BDA0002207447730000141
14.6min(minor)；1H NMR(400MHz,CDCl3)δ7.37-7.34(m,2H),7.31-7.27(m, 2H),7.23-7.19(m,1H),7.07-7.02(m,2H),6.64-6.60(m,1H),6.57-6.52(m,2H), 6.32(dd,J＝16.1,5.6Hz,1H),4.39-4.33(m,1H),3.46-3.36(m,2H),2.95(t,J＝8.4 Hz,2H),1.40(d,J＝6.9Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ151.0,136.9, 130.7,130.4,130.3,128.5,127.4,127.2,126.3,124.4,117.2,107.6,52.2,47.3,28.2, 16.1ppm；HRMS(ESI)calculated[M+Na]+for C18H19NNa＝272.1410,found: 272.1412.
example 21
(S, E) -2- (4-phenylbut-3-en-2-yl) -1,2,3, 4-tetrahydroquinoline as a pale yellow oily liquid,
Figure BDA0002207447730000142
CDCl3)δ7.41-7.39(m,2H),7.34-7.30(m,2H),7.24-7.22(m,1H),7.12-7.07(m,3H), 7.03-7.01(m,1H),6.53(d,J＝16.0Hz,1H),6.30(dd,J＝16.0,7.9Hz,1H), 3.83-3.74(m,2H),3.34-3.27(m,1H),2.97-2.90(m,3H),2.84-2.73(m,1H),1.37(d, J＝6.6Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ137.0,134.9,134.4,132.3, 130.9,128.6,128.5,127.4,126.8,126.3,126.0,125.5,61.9,53.0,47.3,29.4,17.9 ppm；HRMS(ESI)calculated[M+Na]+for C19H21NNa＝286.1566,found:286.1563.
example 22
Figure BDA0002207447730000143
Yellow oily liquid, yield 99%; ee is 95%; [ alpha ] to]D 25＝-68.1(c＝1.0,CHCl3) (ii) a HPLC detection uses a Chiralpak AD-H chromatographic column, and the mobile phase is n-hexane: isopropanol (volume ratio 95:5), flow rate 0.5mL/min, detection wavelength 254nm, retention time tR＝12.7min(major),15.2min (minor)；1H NMR(400MHz,CDCl3)δ8.29(d,J＝4.7Hz,2H),7.39-7.36(m,2H), 7.33-7.29(m,2H),7.25-7.20(m,1H),6.49-6.45(m,2H),6.22(dd,J＝15.9,8.0Hz, 1H),3.85(t,J＝5.2Hz,4H),3.17-3.10(m,1H),2.69-2.59(m,4H),1.30(d,J＝6.6 Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ161.6,157.7,136.9,132.0,131.2, 128.6,127.4,126.3,109.8,62.6,49.9,43.9,17.8ppm；HRMS(ESI)calculated [M+Na]+for C18H22N4Na＝317.1737,found:317.1730.
Example 23
(S, E) -N-allyl-N-methyl-4-phenylbut-3-en-2-amine as pale yellow oil
Figure BDA0002207447730000151
Time tR＝8.0min(minor),9.3min(major)；1H NMR(400MHz,CDCl3)δ7.39-7.36(m, 2H),7.33-7.28(m,2H),7.24-7.20(m,1H),6.45(d,J＝16.0Hz,1H),6.22(dd,J＝ 16.0,7.6Hz,1H),5.93-5.83(m,1H),5.20-5.11(m,2H),3.34-3.27(m,1H),3.19-3.13 (m,1H),3.09-3.03(m,1H),2.25(s,3H),1.25(d,J＝6.7Hz,3H)ppm；13C NMR (100MHz,CDCl3)δ137.2,136.3,131.9,130.8,128.5,127.3,126.3,117.3,60.4,57.4, 37.7,17.2ppm；HRMS(ESI)calculated[M+Na]+for C14H19NNa＝224.1410,found: 224.1412.
Example 24
(S,E)-N-benzyl-N-methyl-4-phenylbut-3-en-2-amine is light yellow oily liquid with the yield of 88 percent;
Figure BDA0002207447730000152
5.0min(minor),6.0min(major)；1H NMR(400MHz,CDCl3)δ7.41-7.39(m,2H), 7.36-7.30(m,6H),7.26-7.21(m,2H),6.47(d,J＝16.1Hz,1H),6.31(dd,J＝16.0, 7.3Hz,1H),3.65(d,J＝13.2Hz,1H),3.51(d,J＝13.2Hz,1H),3.39-3.32(m,1H), 2.22(s,3H),1.30(d,J＝6.7Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ139.8, 137.2,132.0,130.8,128.9,128.5,128.2,127.3,126.8,126.2,60.4,58.2,37.9,16.9 ppm；HRMS(ESI)calculated[M+Na]+for C18H21NNa＝274.1566,found:274.1563.
example 25
(S, E) -N, N-dibenzyl-4-phenylbut-3-en-2-amine as a pale yellow oily liquid in 53% yield; ee ═
Figure BDA0002207447730000161
(major),10.5min(minor)；1H NMR(400MHz,CDCl3)δ7.42-7.38(m,6H), 7.34-7.29(m,6H),7.24-7.20(m,3H),6.43(d,J＝16.2Hz,1H),6.32(dd,J＝16.1, 6.6Hz,1H),3.71(d,J＝13.9Hz,2H),3.59(d,J＝13.9Hz,2H),3.51-3.44(m,1H), 1.29(d,J＝6.8Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ140.6,137.3,131.6, 130.9,128.52,128.50,128.2,127.2,126.7,126.2,54.8,53.7,15.8ppm；HRMS(ESI) calculated[M+Na]+for C24H25NNa＝350.1879,found:350.1873.
Example 26
(S, E) -N, N-diethyl-4-phenylbut-3-en-2-amine as yellowish oily liquid
Figure BDA0002207447730000162
Retention time tR＝7.7min(minor),8.0min(major)；1H NMR(400MHz,CDCl3)δ7.39-7.37(m,2H),7.33-7.29(m,2H),7.24-7.20(m,1H),6.44(d,J＝16.0Hz,1H), 6.24(dd,J＝16.0,7.5Hz,1H),3.50-3.43(m,1H),2.69-2.53(m,4H),1.24(d,J＝6.6 Hz,3H),1.06(t,J＝7.2Hz,6H)ppm；13C NMR(100MHz,CDCl3)δ137.2,133.0, 130.0,128.5,127.2,126.2,57.5,43.4,17.4,12.8ppm；HRMS(ESI)calculated [M+Na]+for C14H21NNa＝226.1566,found:226.1568.
Example 27
(S, E) -N-methyl-N- (4-phenylbut-3-en-2-yl) aniline is light yellow oily liquid, and the yield is 22%; ee
Figure BDA0002207447730000163
95:5), the flow rate is 1.0mL/min, the detection wavelength is 254nm, and the retention time tR＝11.7min(major), 15.0min(minor)；1H NMR(400MHz,CDCl3)δ7.38-7.35(m,2H),7.32-7.20(m, 5H),6.86-6.83(m,2H),6.75-6.71(m,1H),6.48(dd,J＝16.2,1.9Hz,1H),6.30(dd, J＝16.2,4.4Hz,1H),4.69-4.62(m,1H),2.79(s,3H),1.37(d,J＝6.8Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ150.0,137.1,131.3,130.0,129.2,128.6,127.4,126.3, 116.8,113.4,54.9,31.7,16.2ppm；HRMS(ESI)calculated[M+Na]+for C17H19NNa ＝260.1410,found:260.1411.
Example 28
(S, E) -N- (furan-2-yl) -4- (2-methoxyphenyl) but-3-en-2-amine as pale yellow oil
Figure BDA0002207447730000171
(dd,J＝1.9,0.9Hz,1H),7.23-7.19(m,1H),6.94-6.90(m,1H),6.87(dd,J＝8.2,1.1 Hz,1H),6.81(d,J＝16.0Hz,1H),6.31(dd,J＝3.2,1.8Hz,1H),6.17(dd,J＝3.2, 0.8Hz,1H),6.07(dd,J＝16.0,8.2Hz,1H),3.85(s,3H),3.83(d,J＝14.7Hz,1H), 3.74(d,J＝14.4Hz,1H),3.43-3.36(m,1H),1.26(d,J＝6.4Hz,3H)ppm；13C NMR (100MHz,CDCl3)δ156.6,154.1,141.7,134.3,128.4,126.7,126.0,125.2,120.6, 110.8,110.0,106.8,55.7,55.4,43.8,22.1ppm；HRMS(ESI)calculated[M+H]+for C16H20NO2＝258.1489,found:258.1484.
Example 29
(S,E)-N-(furan-2-ylmethyl)-4-(4-methoxyphenyl)but-3-en-2-amine light yellow oil
Figure BDA0002207447730000172
J＝2.0,0.8Hz,1H),7.34-7.30(m,2H),6.88-6.84(m,2H),6.43(d,J＝15.9Hz,1H), 6.31(dd,J＝3.2,1.8Hz,1H),6.16(dd,J＝3.1,0.8Hz,1H),5.93(dd,J＝15.8,8.2 Hz,1H),3.83(d,J＝13.2Hz,1H),3.81(s,3H),3.73(d,J＝14.4Hz,1H),3.39-3.33 (m,1H),1.86(br,s,1H),1.25(d,J＝6.4Hz,3H)ppm；13C NMR(100MHz,CDCl3) δ159.0,153.9,141.8,131.4,130.0,129.7,127.4,113.9,110.1,106.8,55.33,55.29, 43.8,22.1ppm；HRMS(ESI)calculated[M+Na]+for C16H19NNaO2＝280.1308, found:280.1310.
Example 30
(S, E) -4- (4-fluorophenyl) -N- (furan-2-ylmethyl) but-3-en-2-amine as yellowish oily liquid
Figure BDA0002207447730000181
(m,2H),6.45(d,J＝15.8Hz,1H),6.31(dd,J＝3.1,1.9Hz,1H),6.16(dd,J＝3.2, 0.8Hz,1H),5.99(dd,J＝15.8,8.1Hz,1H),3.82(d,J＝14.4Hz,1H),3.73(d,J＝ 14.4Hz,1H),3.41-3.34(m,1H),1.83(br,s,1H),1.25(d,J＝6.4Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ162.1(d,J＝246.5Hz),153.8,141.8,133.4(d,J＝2.2 Hz),133.1(d,J＝3.2Hz),129.3,127.7(d,J＝7.9Hz),115.4(d,J＝21.4Hz),110.1, 106.8,55.2,43.8,22.0ppm；19F NMR(376MHz,CDCl3)δ-114.82ppm；HRMS (ESI)calculated[M+Na]+for C15H16FNNaO＝268.1108,found:268.1103.
Example 31
(S, E) -N- (furan-2-ylmethyl) -4- (4- (trifluoromethyl) phenyl) but-3-en-2-amine light yellow
Figure BDA0002207447730000182
Hz,2H),7.46(d,J＝8.2Hz,2H),7.37(dd,J＝1.9,0.8Hz,1H),6.52(d,J＝15.9Hz, 1H),6.31(dd,J＝3.2,1.8Hz,1H),6.21-6.15(m,2H),3.82(d,J＝14.5Hz,1H),3.74 (d,J＝14.5Hz,1H),3.45-3.38(m,1H),1.82(br,s,1H),1.27(d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ153.7,141.8,140.5(q,J＝1.6Hz),136.5,129.11(q, J＝32.2Hz),129.09,126.4,125.5(q,J＝3.9Hz),124.2(q,J＝270.5Hz),110.1, 106.9,55.1,43.8,21.8ppm；19F NMR(376MHz,CDCl3)δ-62.36ppm；HRMS (ESI)calculated[M+H]+for C16H17F3NO＝296.1257,found:296.1250.
Example 32
(S, E) -4- (3- ((furan-2-ylmethyl) amino) but-1-en-1-yl) -N, N-dimethyllaniline
Figure BDA0002207447730000191
δ7.36(dd,J＝1.9,0.8Hz,1H),7.29-7.27(m,2H),6.70-6.67(m,2H),6.39(d,J＝ 15.8Hz,1H),6.31(dd,J＝3.2,1.9Hz,1H),6.16(dd,J＝3.1,0.8Hz,1H),5.85(dd, J＝15.8,8.2Hz,1H),3.83(d,J＝14.4Hz,1H),3.73(d,J＝14.4Hz,1H),3.38-3.31 (m,1H),2.95(s,6H),2.24(br,s,1H),1.25(d,J＝6.4Hz,3H)ppm；13C NMR(100 MHz,CDCl3)δ153.9,150.0,141.7,130.6,129.1,127.2,125.4,112.5,110.0,106.8, 55.5,43.6,40.6,22.1ppm；HRMS(ESI)calculated[M+H]+for C17H23N2O＝ 271.1805,found:271.1805.
Example 33
(S, E) -4- (furan-2-yl) -N- (furan-2-ylmethyl) but-3-en-2-amine as yellowish oily liquid
Figure BDA0002207447730000192
MHz,CDCl3)δ7.36(dd,J＝1.9,0.9Hz,1H),7.34(d,J＝1.8Hz,1H),6.36(dd,J＝3.3,1.8Hz,1H),6.34-6.30(m,2H),6.21(d,J＝3.2Hz,1H),6.16(dd,J＝3.2,0.8Hz, 1H),6.02(dd,J＝15.8,8.0Hz,1H),3.82(d,J＝14.5Hz,1H),3.72(d,J＝14.4Hz, 1H),3.37-3.30(m,1H),1.24(d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ 154.0,152.6,141.8,141.7,132.5,118.9,111.2,110.1,107.2,106.8,54.9,43.8,22.0 ppm；HRMS(ESI)calculated[M+H]+for C13H16NO2＝218.1176,found:218.1177.
Example 34
(S, E) -4-cyclohexenyl-N- (furan-2-ylmethyl) but-3-en-2-amine as yellowish oily liquid
Figure BDA0002207447730000201
1H),6.13(dd,J＝3.1,0.9Hz,1H),5.48(dd,J＝15.4,6.6Hz,1H),5.24-5.18m,1H), 3.77(d,J＝14.5Hz,1H),3.67(d,J＝14.4Hz,1H),3.16-3.09(m,1H),1.99-1.90(m, 1H),1.74-1.69(m,4H),1.67-1.64(m,1H),1.29-1.16(m,3H),1.14(d,J＝6.4Hz, 3H),1.11-1.02(m,2H)ppm；13C NMR(100MHz,CDCl3)δ154.2,141.6,137.9, 130.9,110.0,106.6,55.1,43.6,40.4,33.1,33.0,26.2,26.0,22.1ppm；HRMS(ESI) calculated[M+H]+for C15H24NO＝234.1852,found:234.1853.
Example 35
(S, E) -4- (4- (2-methoxyphenyl) but-3-en-2-yl) morpholine as a pale yellow oily liquid in a yield
Figure BDA0002207447730000202
CDCl3)δ7.44(dd,J＝7.6,1.7Hz,1H),7.23-7.19(m,1H),6.93-6.89(m,1H),6.86 (dd,J＝8.2,1.2Hz,1H),6.79(d,J＝16.0Hz,1H),6.17(dd,J＝16.0,8.3Hz,1H), 3.84(s,3H),3.73(t,J＝4.7Hz,4H),3.07-2.99(m,1H),2.62-2.52(m,4H),1.26(d,J ＝6.6Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ156.5,132.5,128.5,126.6,125.9, 125.8,120.6,110.9,67.2,63.6,55.4,50.8,17.9ppm；HRMS(ESI)calculated [M+H]+for C15H22NO2＝248.1645,found:248.1641.
Example 36
(S, E) -4- (4- (furan-2-yl) but-3-en-2-yl) morpholine is a light yellow oily liquid with a yield of 99%; ee
Figure BDA0002207447730000203
Time tR＝16.6min(minor),18.7min(major)；1H NMR(400MHz,CDCl3)δ7.33(d,J ＝1.8Hz,1H),6.36(dd,J＝3.3,1.8Hz,1H),6.31-6.27(m,1H),6.20(d,J＝3.3Hz, 1H),6.11(dd,J＝15.9,8.1Hz,1H),3.72(t,J＝4.7Hz,4H),3.04-2.97(m,1H), 2.60-2.50(m,4H),1.23(d,J＝6.6Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ 152.5,141.7,130.7,119.7,111.2,107.3,67.2,62.7,50.5,17.5ppm；HRMS(ESI) calculated[M+H]+for C12H18NO2＝208.1332,found:208.1333.
Example 37
(S,E)-4-(4-(4-methoxyphenyl)but-3-en-2-yl)morpholine:
Figure BDA0002207447730000211
(minor),29.0min(major)；1H NMR(400MHz,CDCl3)δ7.31(d,J＝8.7Hz,2H), 6.85(d,J＝8.7Hz,2H),6.41(d,J＝15.9Hz,1H),6.02(dd,J＝15.9,8.3Hz,1H), 3.81(s,3H),3.74(t,J＝4.7Hz,4H),3.03-2.96(m,1H),2.61-2.53(m,4H),1.26(d,J ＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ159.1,130.8,129.6,129.5,127.4, 113.9,67.10,63.2,55.3,50.7,17.8ppm；HRMS(ESI)calculated[M+Na]+for C15H21NNaO2＝270.1465,found:270.1464.
Example 38
(S, E) -4- (4- (4-fluorophenyl) but-3-en-2-yl) morpholine
Figure BDA0002207447730000212
(major)；1H NMR(400MHz,CDCl3)δ7.36-7.31(m,2H),7.03-6.97(m,2H),6.43(d, J＝15.9Hz,1H),6.08(dd,J＝15.9,8.2Hz,1H),3.74(t,J＝4.7Hz,4H),3.04-2.97 (m,1H),2.58-2.54(m,4H),1.25(d,J＝6.6Hz,3H)ppm；13C NMR(100MHz, CDCl3)δ162.2(d,J＝246.6Hz),133.0(d,J＝3.3Hz),131.8(d,J＝2.1Hz),130.0, 127.7(d,J＝7.9Hz),115.4(d,J＝21.6Hz),67.2,63.0,50.7,17.7ppm；19F NMR (376MHz,CDCl3)δ-114.64ppm；HRMS(ESI)calculated[M+H]+for C14H19FNO ＝236.1445,found:236.1442.
Example 39
(S, E) -4- (4- (4- (trifluoromethyl) phenyl) but-3-en-2-yl) morpholine as yellowish oily liquid
Figure BDA0002207447730000221
(minor)；1H NMR(400MHz,CDCl3)δ7.56(d,J＝8.2Hz,2H),7.46(d,J＝8.4Hz, 2H),6.50(d,J＝16.0Hz,1H),6.28(dd,J＝16.0,8.0Hz,1H),3.75-3.72(m,4H), 3.10-3.02(m,1H),2.58-2.55(m,4H),1.27(d,J＝6.6Hz,3H)ppm；13C NMR(100 MHz,CDCl3)δ140.3(q,J＝1.9Hz),135.0,129.9,129.2(q,J＝32.4Hz),126.4, 125.5(q,J＝3.8Hz),124.1(q,J＝270.9Hz),67.1,62.9,50.7,17.5ppm；19F NMR (376MHz,CDCl3)δ-62.38ppm；HRMS(ESI)calculated[M+H]+for C15H19F3NO＝ 286.1413,found:286.1418.
Example 40
(S, E) -N, N-dimethyl-4- (3-morpholinobout-1-en-1-yl) aniline which is a light yellow oily liquid and is produced
Figure BDA0002207447730000222
(minor)；1H NMR(400MHz,CDCl3)δ7.28-7.25(m,2H),6.69-6.67(m,2H),6.37(d, J＝15.8Hz,1H),5.94(dd,J＝15.9,8.3Hz,1H),3.73(t,J＝4.7Hz,4H),3.00-2.97 (m,1H),2.95(s,6H),2.61-2.52(m,4H),1.25(d,J＝6.5Hz,3H)ppm；13C NMR (100MHz,CDCl3)δ150.0,131.2,127.5,127.1,125.4,112.5,67.2,63.4,50.8,40.6, 18.0ppm；HRMS(ESI)calculated[M+H]+for C16H25N2O＝261.1961,found: 261.1960.
EXAMPLE 41
Figure BDA0002207447730000223
Colorless oily liquid, yield 58%; ee is 96%; [ alpha ] to]D 25＝-17.7(c＝1.0,CHCl3) (ii) a HPLC detection uses a Chiralpak OJ-H chromatographic column, and the mobile phase is n-hexane: isopropanol (volume ratio 95:5), flow rate 0.5mL/min, detection wavelength 254nm, retention time tR＝8.8min(minor),9.5min(major)；1H NMR(400MHz,CDCl3)δ8.29(d,J＝4.7Hz,2H),6.46(t,J＝4.7Hz,1H),5.47 (dd,J＝15.6,6.4Hz,1H),5.37-5.31(m,1H),3.83-3.81(m,4H),2.93-2.86(m,1H), 2.62-2.49(m,4H),1.99-1.90(m,1H),1.72-1.69(m,4H),1.66-1.62(m,1H), 1.28-1.22(m,3H),1.18(d,J＝6.6Hz,3H),1.14-1.02(m,2H)ppm；13C NMR(100 MHz,CDCl3)δ161.6,157.7,138.5,128.7,109.6,62.5,49.6,43.8,40.4,33.04,32.97, 26.1,26.0,18.1ppm；HRMS(ESI)calculated[M+H]+for C18H29N4＝301.2387, found:301.2380.
Example 42
(S, E) -2- ((4-phenylbut-3-en-2-yl) amino) ethane-1-ol, namely a light yellow oily liquid with the yield of 91 percent;
Figure BDA0002207447730000231
254nm, retention time tR＝20.0min(major),24.7min(minor)；1H NMR(400MHz, CDCl3)δ7.39-7.37(m,2H),7.32-7.29(m,2H),7.25-7.21(m,1H),6.50(d,J＝15.9 Hz,1H),6.12(dd,J＝15.9,8.1Hz,1H),3.76-3.67(m,2H),3.53-3.41(m,1H),3.41 (br,s,1H),3.32(br,s,1H),2.93-2.79(m,2H),1.35(d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ136.4,131.6,131.5,128.5,127.7,126.4,60.3,56.3,48.5, 21.2ppm；HRMS(ESI)calculated[M+H]+for C12H18NO＝192.1383,found: 192.1381.
Example 43
(S,E)-N1-benzyl-N1-(4-phenylbut-3-en-2-yl)ethane-1,2-diami
Figure BDA0002207447730000232
85:15), the flow rate is 1.0mL/min, the detection wavelength is 254nm, and the retention time t isR＝24.4min (minor),27.6min(major)；1H NMR(400MHz,CDCl3)δ7.37-7.35(m,2H), 7.32-7.28(m,6H),7.25-7.19(m,2H),6.44(d,J＝15.9Hz,1H),6.05(dd,J＝15.9, 7.9Hz,1H),3.79(s,2H),3.35-3.28(m,1H),2.81-2.65(m,4H),1.25(br,s,2H),1.25 (d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ140.3,137.0,134.2,129.9, 128.5,128.4,128.1,127.3,126.9,126.3,56.3,53.8,48.8,46.9,22.0ppm；HRMS (ESI)calculated[M+H]+for C19H25N2＝281.2012,found:282.2011.
Example 44
(S, E) -2- (((4-phenylbut-3-en-2-yl) amino) methyl) phenol as a pale yellow oily liquid in yield
Figure BDA0002207447730000241
δ7.39-7.31(m,4H),7.27-7.23(m,1H),7.19-7.14(m,1H),6.96(dd,J＝7.4,1.7Hz, 1H),6.85(dd,J＝8.1,1.2Hz,1H),6.79-6.75(m,1H),6.46(d,J＝15.9Hz,1H),6.03 (dd,J＝15.9,8.2Hz,1H),4.08(d,J＝14.0Hz,1H),3.91(d,J＝13.9Hz,1H), 3.46-3.38(m,1H),1.32(d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ 158.2,136.5,131.7,131.5,128.6,128.6,128.3,127.7,126.3,122.7,119.1,116.4, 55.1,50.0,21.7ppm；HRMS(ESI)calculated[M+Na]+for C17H19NO＝276.1359, found:276.1361.
Example 45
(S, E) -2- (2- ((4-phenylbut-3-en-2-yl) amino) phenyl) ethan-1-ol as a white solid in 59% yield;
Figure BDA0002207447730000242
MHz,CDCl3)δ7.37-7.34(m,2H),7.31-7.27(m,2H),7.23-7.19(m,1H),7.03-7.00 (m,2H),6.63-6.60(m,2H),6.57(dd,J＝15.9,1.3Hz,1H),6.20(dd,J＝15.9,5.9Hz, 1H),4.15-4.08(m,1H),3.78(t,J＝6.5Hz,2H),2.74(t,J＝6.5Hz,2H),1.40(d,J＝ 6.6Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ146.0,136.9,133.2,129.8,129.2, 128.5,127.3,126.7,126.3,113.6,63.9,51.0,38.2,22.1ppm；HRMS(ESI) calculated[M+Na]+for C18H21NNaO＝290.1532,found:290.1531.
example 46
(S, E) -N- (2- (1H-indol-3-yl) ethyl) -4-phenylbut-3-en-2-amine
Figure BDA0002207447730000251
NMR(400MHz,CDCl3)δ8.12(s,1H),7.62(d,J＝7.9Hz,1H), 7.37-7.27(m,5H),7.23-7.17(m,2H),7.10(t,J＝7.5Hz,1H),7.04(d,J＝2.3Hz, 1H),6.42(d,J＝15.9Hz,1H),6.06(dd,J＝15.9,8.0Hz,1H),3.41-3.34(m,1H), 3.04-2.92(m,4H),1.97(br,s,1H),1.22(d,J＝6.4Hz,3H)ppm；13C NMR(100 MHz,CDCl3)δ137.0,136.4,134.1,129.9,128.5,127.4,127.3,126.2,122.02,121.98, 119.2,118.9,113.8,111.1,56.2,47.4,25.8,22.0ppm；HRMS(ESI)calculated [M+Na]+for C20H22N2Na＝313.1675,found:313.1675.
Example 47
(S, E) -4- (((4-phenylbut-3-en-2-yl) amino) methyl) aniline as a pale yellow oily liquid in yield
Figure BDA0002207447730000252
7.12-7.09(m,2H),6.67-6.63(m,2H),6.47(d,J＝15.9Hz,1H),6.11(dd,J＝15.9, 8.0Hz,1H),3.73(d,J＝12.8Hz,1H),3.61(d,J＝12.9Hz,1H),3.43-3.36(m,1H), 1.25(d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ145.2,137.1,134.2, 130.4,130.1,129.3,128.5,127.3,126.2,115.1,55.3,51.0,22.0ppm；HRMS(ESI) calculated[M+H]+for C17H21N2＝253.1699,found:253.1670.
Example 48
(S, E) -4- (4-cyclohexylbut-3-en-2-yl) morpholine as a pale yellow oily liquid in a yield of 67%; ee
Figure BDA0002207447730000253
(m,1H),3.71(t,J＝4.7Hz,4H),2.81-2.74(m,1H),2.55-2.42(m,4H),1.97-1.89(m, 1H),1.74-1.67(m,4H),1.67-1.62(m,1H),1.32-1.16(m,3H),1.14(d,J＝6.5Hz, 3H),1.12-1.01(m,2H)ppm；13C NMR(100MHz,CDCl3)δ138.6,128.9,67.2,62.9, 50.5,40.4,33.1,33.0,26.2,26.0,18.0ppm；HRMS(ESI)calculated[M+H]+for C14H26NO＝224.2009,found:224.2011.
Example 49
(S, E) -1- (4-phenylbut-3-en-2-yl) piperidine-4-carboxamide white
Figure BDA0002207447730000261
3.05-3.00(m,1H),2.18-2.09(m,3H),1.94-1.87(m,2H),1.80-1.67(m,2H),1.25(d, J＝6.6Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ177.7,137.0,132.2,130.7, 128.5,127.3,126.2,62.4,49.7,49.5,43.0,29.2,29.1,17.6ppm；HRMS(ESI) calculated[M+H]+for C16H23N2O＝218.1176,found:218.1177.
Example 50
(S,E)-8-chloro-11-(1-(4-phenylbut-3-en-2-yl)piperidin-4-ylidene)-6,11-dihydro-5
Figure BDA0002207447730000262
6.42(d,J＝15.9Hz,1H),6.25-6.19(m,1H),3.44-3.32(m,2H),3.20-3.11(m,1H), 2.93-2.74(m,4H),2.56-2.32(m,6H),1.26(d,J＝6.6Hz,3H)ppm；13C NMR(100 MHz,CDCl3)δ157.62,146.57,139.46,139.09,137.72,137.20,136.93,133.40, 132.56,132.38,132.08,130.90,130.82,128.93,128.51,127.34,126.24,125.94, 122.04,62.38,51.63,51.42,31.83,31.40,31.08,30.87,17.83ppm；3ay′:1H NMR (400MHz,CDCl3)δ8.40-8.38(m,1H),7.42(dd,J＝7.7,1.7Hz,1H),7.37-7.28(m, 4H),7.24-7.20(m,1H),7.14-7.11(m,3H),7.09-7.06(m,1H),6.42(d,J＝15.9Hz, 1H),6.25-6.19(m,1H),3.44-3.32(m,2H),3.20-3.11(m,1H),2.93-2.74(m,4H), 2.56-2.32(m,6H),1.26(d,J＝6.6Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ 157.57,146.57,139.46,139.09,137.67,137.16,136.92,133.40,132.56,132.38, 131.97,130.87,130.77,128.90,128.51,127.34,126.22,125.94,122.04,62.35,51.63, 51.37,31.81,31.38,31.08,30.80,17.78ppm；HRMS(ESI)calculated[M+Na]+for C29H29ClN2Na＝463.1911,found:463.1907。

Claims (3)

1. A method for preparing chiral allylamine compounds with high chemical and stereoselectivity is characterized by comprising the following steps: in the metal reagent Ni (COD)2Chiral diphosphine ligands and
Figure FDA0003429036560000016
under the action of an acid additive, dissolving 1, 3-conjugated diene and amine in an organic solvent for reaction, and separating and purifying by column chromatography to obtain a chiral allylamine compound; the synthetic route of the method is as follows:
Figure FDA0003429036560000011
the 1, 3-conjugated diene substituent R is optionally selected from: phenyl, 2-methoxyphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 4-dimethylaminophenyl, 2-furyl, cyclohexyl;
the R is1、R2Is selected such that the structure of the amine is any selected from: n-butylamine, 2-phenylethylamine, cyclopropylamine, cyclohexylamine, furfurylamine, 2- (1-cyclohexenyl) ethylamine, allylamine, (±) -tetrahydrofurfuryl amine, N-dimethylethylenediamine, benzylamine, glycine methyl ester, (S) -1-phenylethylamine, aniline, 4-methylaniline, 4-bromo-aniline, ethanolamine, N-benzylethylenediamine, 2-hydroxybenzylamine, 4-aminophenylethanol, tryptamine, 4-aminobenzylamine, morpholine, thiomorpholine, piperidine, tetrahydropyrrole, indoline, tetrahydroisoquinoline, 1- (2-pyrimidinyl) piperazine, N-methylallylamine, N-methylbenzylamine, dibenzylamine, ethylenediamine, N-methylaniline;
the chiral diphosphine ligand is (S, S) -Me-DuPhos, and the specific structure is as follows:
Figure FDA0003429036560000012
the above-mentioned
Figure FDA0003429036560000013
The acid additive is phthalic acid, and the specific structure of the acid additive is as follows:
Figure FDA0003429036560000014
the metalReagent Ni (COD)2: chiral diphosphine ligand:
Figure FDA0003429036560000015
acid additive: 1, 3-conjugated diene: amine: the dosage ratio of the organic solvent is 0.01 mmol: 0.01 mmol: 0.01 mmol: 0.2 mmol: 0.3 mmol: 1.0 mL.
2. The process for the highly chemo-and stereoselective preparation of chiral allylamine compounds of claim 1, wherein: the organic solvent is one of methanol, ethanol, isopropanol, trifluoroethanol, hexafluoroisopropanol, toluene, trifluorotoluene, dichloromethane, 1, 2-dichloroethane, chloroform, diethyl ether, 1, 4-dioxane, tetrahydrofuran, methyl tert-butyl ether, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone, ethyl acetate, acetonitrile, benzonitrile, ethylene glycol dimethyl ether and N-hexane.
3. The process for the highly chemo-and stereoselective preparation of chiral allylamine compounds of claim 1, wherein: the preparation method of the chiral allylamine compound comprises the following specific steps: in an inert gas, adding a metal reagent Ni (COD)2The chiral diphosphine ligand is dissolved in a dry organic solvent, and then 1, 3-conjugated diene, amine and
Figure FDA0003429036560000021
and (2) adding an acid additive to obtain a reaction mixture, sealing the reaction mixture, taking out the reaction mixture from the inert gas, concentrating under reduced pressure to remove the organic solvent after the reaction is completed, and separating and purifying by column chromatography to obtain the target product chiral allylamine compound:
Figure FDA0003429036560000022
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