CN112279770A - Chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound, and preparation method and application thereof - Google Patents

Chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound, and preparation method and application thereof Download PDF

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CN112279770A
CN112279770A CN201910664789.3A CN201910664789A CN112279770A CN 112279770 A CN112279770 A CN 112279770A CN 201910664789 A CN201910664789 A CN 201910664789A CN 112279770 A CN112279770 A CN 112279770A
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王春江
沈冲
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Wuhan University WHU
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Abstract

The invention discloses a chiral alpha-polysubstituted-alpha-fluorine-containing high allylamine compound, a preparation method and application thereof. The structural formula of the chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound is shown in the specification

Description

Chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound, and preparation method and application thereof
Technical Field
The invention belongs to the field of chemical medicine, and particularly relates to a chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound, and a preparation method and application thereof.
Background
Chiral alpha-polysubstituted-alpha-fluoro homoallylamine building blocks are widely present in compounds with important biological activity (e.g. marketed drugs). Therefore, the synthesis method of chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine, which is efficient, universal and easy to use, is always a hot research field in synthetic chemistry. The chiral alpha-tetrasubstituted-alpha-fluorine-containing homoallylamine is difficult to synthesize due to the fact that the chiral alpha-tetrasubstituted-alpha-fluorine-containing homoallylamine contains a quaternary carbon chiral center, and currently, efficient catalytic asymmetric synthesis is rarely reported. Fluorine-containing fluoreneimine has the characteristics of easy obtaining, stability and the like, and is a very good synthon. However, no synthesis of chiral α -polysubstituted- α -fluoro homoallylamines using fluorofluorenimines using asymmetric catalytic allylation has been reported so far.
Disclosure of Invention
One purpose of the invention is to provide a chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound with the structure
Figure BDA0002139747690000011
The chiral alphaThe (poly) substituted-alpha-fluorine-containing homoallylamine compound can be used for synthesizing chiral alpha-poly-substituted-alpha-fluorine-containing homoallylamine compound II
Figure BDA0002139747690000012
And preparing derivatives with chiral pyrrolidine structures, antidepressant drugs, antitumor drugs and natural products with chiral amine structural units.
The second purpose of the invention is to provide a preparation method of chiral alpha-polysubstituted-alpha-fluorine-containing high allylamine compounds, the method has simple synthesis, low cost and high yield, and the obtained reaction target compounds have good corresponding selectivity, the yield is 50-95%, and the corresponding selectivity excess is more than 90%.
The invention also aims to provide application of the chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound in preparation of the chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound II and preparation of derivatives with chiral pyrrolidine structures.
One of the purposes of the invention adopts the following technical scheme:
a chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound has a structure shown as the following formula I,
Figure BDA0002139747690000013
wherein the content of the first and second substances,
R1is any one of substituted or unsubstituted aryl and hydrogen, and the substituent in the substituted aryl is alkyl or halogen;
R2is monofluoromethyl, difluoromethyl, trifluoromethyl, C2-5Any of the perfluoroalkyl groups of (a);
R3is hydrogen, substituted or unsubstituted aryl, substituted or unsubstituted unsaturated heterocyclic radical, C1-C6Any one of a chain or cyclic alkane, wherein a heteroatom contained in the substituted or unsubstituted unsaturated heterocyclic group is N, O, S, and a substituent in the substituted aryl group is an alkyl group, an alkoxy group, or a halogenAny of an element and an alkenyl group;
R4is any one of hydrogen, substituted or unsubstituted aryl and alkane.
The second purpose of the invention is realized by adopting the following technical scheme:
a preparation method of chiral alpha-polysubstituted-alpha-fluorine-containing high allylamine compounds mainly comprises the following steps,
taking an iridium complex as a catalyst, and carrying out catalytic reaction on a substrate-1 and a substrate-2 to obtain a chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound shown in a formula I;
Figure BDA0002139747690000021
wherein the content of the first and second substances,
R1is any one of substituted or unsubstituted aryl and hydrogen, and the substituent in the substituted aryl is alkyl or halogen;
R2is monofluoromethyl, difluoromethyl, trifluoromethyl, C2-5Any of the perfluoroalkyl groups of (a);
R3is hydrogen, substituted or unsubstituted aryl, substituted or unsubstituted unsaturated heterocyclic radical, C1-C6Any one of a chain or cyclic alkane, wherein a heteroatom contained in the substituted or unsubstituted unsaturated heterocyclic group is N, O, S, and a substituent in the substituted aryl group is any one of an alkyl group, an alkoxy group, a halogen group and an alkenyl group;
R4is any one of hydrogen, substituted or unsubstituted aryl and alkane.
Further, the preparation method of the chiral alpha-polysubstituted-alpha-fluorine-containing high allylamine compound comprises the following specific steps:
under the protection of inert gas, dissolving a substrate-1 (allyl carbonate), a substrate-2 (fluorine-containing fluorenylimine), an iridium complex and 1-10 equivalents of organic base in an organic solvent, fully reacting at 0-110 ℃, and performing column chromatography to obtain the chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound shown in the formula I;
wherein the concentration of the substrate-1 is 0.001-3.0M, the concentration of the substrate-2 is 0.001-3.0M, and the molar ratio of the substrate-1 to the substrate-2 is 1: 0.1-10; the dosage of the iridium complex is 0.0001-10 mol% of the lower concentration of the substrate-1 or the substrate-2; the organic base is any one of triethylamine, tetramethylethylenediamine, 1, 5-diazabicyclo [4.3.0] non-5-ene, 1, 8-diazabicycloundecen-7-ene, 1, 4-diazabicyclo [2.2.2] octane, pyridine, 4-dimethylaminopyridine, N-methylmorpholine, triethylenediamine, tetramethylguanidine and 2-tert-butyl-1, 1,3, 3-tetramethylguanidine; the organic solvent is at least one of methanol, ethanol, isopropanol, tert-butanol, sec-butanol, ethyl acetate, isobutyl acetate, isopropyl acetate, N-hexane, cyclohexane, N-heptane, acetone, butanone, diethyl ether, methyl tert-butyl ether, methyl cyclopentyl ether, methyl tetrahydrofuran, acetonitrile, dichloromethane, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, toluene and dioxane.
Further, the iridium complex is prepared by the following method:
dissolving metal iridium salt and chiral ligand L1 in an organic solvent at 50 ℃, adding organic base, and reacting to obtain the iridium complex;
wherein the content of the first and second substances,
the metal iridium salt is [ Ir (COD) Cl]2、[Ir(DBCOT)Cl]2、[Ir(COD)OMe]2Any one of (a);
the structural formula of the chiral ligand L1 is any one of the following formulas:
Figure BDA0002139747690000031
the organic solvent is at least one of methanol, ethanol, isopropanol, tert-butanol, sec-butanol, ethyl acetate, isobutyl acetate, isopropyl acetate, N-hexane, cyclohexane, N-heptane, acetone, butanone, diethyl ether, methyl tert-butyl ether, methyl cyclopentyl ether, methyl tetrahydrofuran, acetonitrile, dichloromethane, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, toluene and dioxane, preferably, the organic solvent is toluene;
the organic base is any one of triethylamine, tetramethylethylenediamine, 1, 5-diazabicyclo [4.3.0] non-5-ene, 1, 8-diazabicycloundecen-7-ene, 1, 4-diazabicyclo [2.2.2] octane, pyridine, 4-dimethylaminopyridine, N-methylmorpholine, triethylenediamine, tetramethylguanidine and 2-tert-butyl-1, 1,3, 3-tetramethylguanidine.
The third technical scheme for realizing the purpose of the invention is as follows:
an application of the chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound is to prepare a chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound II and a derivative with a chiral tetrahydropyrrole structure;
the structural formula of the chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound II is shown in the specification
Figure BDA0002139747690000032
The structural formula of the derivative with the chiral tetrahydropyrrole structure is shown in the specification
Figure BDA0002139747690000033
Wherein R is1Is any one of substituted or unsubstituted aryl and hydrogen, wherein the substituent in the substituted aryl is alkyl or halogen, R2Is monofluoromethyl, difluoromethyl, trifluoromethyl, C2-5Any of the perfluoroalkyl groups of (1), R3Is hydrogen, substituted or unsubstituted aryl, substituted or unsubstituted unsaturated heterocyclic radical, C1-C6Any one of chain or cyclic alkanes, wherein the heteroatom contained in the substituted or unsubstituted unsaturated heterocyclic group is N, O, S, the substituent in the substituted aryl group is any one of alkyl, alkoxy, halogen and alkenyl, and R is4Is any one of hydrogen, substituted or unsubstituted aryl and alkane.
Further, the chiral alpha-polysubstituted-alpha-fluorine-containing high allylamine compound is applied to the preparation of the chiral alpha-polysubstituted-alpha-fluorine-containing high allylamine compound II, and the steps are as follows: hydrolyzing the chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound in the formula I in acid to obtain a chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound II in the following formula II:
Figure BDA0002139747690000041
wherein the content of the first and second substances,
R1is any one of substituted or unsubstituted aryl and hydrogen, and the substituent in the substituted aryl is alkyl or halogen;
R2is monofluoromethyl, difluoromethyl, trifluoromethyl, C2-5Any of the perfluoroalkyl groups of (a);
R3is hydrogen, substituted or unsubstituted aryl, substituted or unsubstituted unsaturated heterocyclic radical, C1-C6Any one of a chain or cyclic alkane, wherein a heteroatom contained in the substituted or unsubstituted unsaturated heterocyclic group is N, O, S, and a substituent in the substituted aryl group is any one of an alkyl group, an alkoxy group, a halogen group and an alkenyl group;
R4is any one of hydrogen, substituted or unsubstituted aryl and alkane.
Further, the chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound is applied to the preparation of the derivative with the chiral tetrahydropyrrole structure by the following steps:
(1) hydrolyzing the chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound in the formula I in acid to obtain a chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound II in the following formula II:
Figure BDA0002139747690000042
(2) dissolving the chiral alpha-polysubstituted-alpha-fluorine-containing high allylamine compound II obtained in the step (1) in an organic solvent, adding 1 to 10 equivalents of carbonate or bicarbonate and 1 to 5 equivalents of iodine elementary substance, reacting at (-40) -0 ℃, adding a saturated solution of sodium thiosulfate after the reaction reaches balance, quenching, and performing column chromatography to obtain a target product, namely the derivative with the chiral tetrahydropyrrole structure:
Figure BDA0002139747690000051
wherein the content of the first and second substances,
R1is any one of substituted or unsubstituted aryl and hydrogen, and the substituent in the substituted aryl is alkyl or halogen;
R2is monofluoromethyl, difluoromethyl, trifluoromethyl, C2-5Any of the perfluoroalkyl groups of (a);
R3is hydrogen, substituted or unsubstituted aryl, substituted or unsubstituted unsaturated heterocyclic radical, C1-C6Any one of a chain or cyclic alkane, wherein a heteroatom contained in the substituted or unsubstituted unsaturated heterocyclic group is N, O, S, and a substituent in the substituted aryl group is any one of an alkyl group, an alkoxy group, a halogen group and an alkenyl group;
R4is any one of hydrogen, substituted or unsubstituted aryl and alkane.
Furthermore, the hydrolysis temperature is 0-100 ℃, the hydrolysis time is 0.5-24 hours, the acid is any one of citric acid, hydrochloric acid, methanesulfonic acid, p-toluenesulfonic acid, acetic acid, sulfuric acid, hydroxylamine hydrochloride and hydroxylamine acetate, and the dosage of the acid is 1-20 times of that of the lower concentration of the substrate-1 or substrate-2.
Furthermore, in the step (2), silica gel is used as a filler for the column chromatography, a mixed solvent of petroleum ether and ethyl acetate is used as an eluent, and the volume ratio of the petroleum ether to the ethyl acetate is 3-20: 1; the organic solvent is at least one of methanol, ethanol, isopropanol, tert-butanol, sec-butanol, ethyl acetate, isobutyl acetate, isopropyl acetate, N-hexane, cyclohexane, N-heptane, acetone, butanone, diethyl ether, methyl tert-butyl ether, methyl cyclopentyl ether, methyl tetrahydrofuran, acetonitrile, dichloromethane, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, toluene and dioxane.
Furthermore, the chiral alpha-polysubstituted-alpha-fluorine-containing high allylamine compound II can be used for preparing antidepressant drugs, antitumor drugs and natural drugs with chiral amine structural units; the derivative with the chiral pyrrolidine structure can be used as an organic catalyst.
Compared with the prior art, the invention has the following beneficial effects:
(1) the method has the advantages of simple synthesis, low cost and high yield, and the obtained reaction target compound has good corresponding selectivity, the yield is 50-95%, and the corresponding selectivity is over 90%;
(2) the method adopts the iridium complex as the catalyst, and has the advantages of high catalytic reaction speed and low catalyst consumption in the reaction;
(3) the prepared chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound I can be used for synthesizing chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compounds II, and the chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compounds II can be used for preparing antidepressant drugs, antitumor drugs and natural drugs with chiral amine structural units;
(4) the prepared chiral alpha-fluorine-containing homoallylamine compound II can be used for synthesizing derivatives with chiral pyrrolidine structures, which can be used as organic catalysts;
(5) provides a synthesis method with great prospect for chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compounds I, chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compounds II and derivatives with chiral tetrahydropyrrole structures; has great reference value for the synthesis of the medicine containing chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine structural units.
Detailed Description
In order that the invention may be better understood, the invention will now be further described with reference to the following examples. 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.
The chiral ligand (S, S, S) -L1 used in the following examples has the formula
Figure BDA0002139747690000061
The ligand (R, R, R) -L1 used in the following examples has the formula
Figure BDA0002139747690000062
The ligand (rac) -L1 used in the following examples has the formula
Figure BDA0002139747690000063
Chiral ligands (S, S) used in the following examplesa) -L1 has the formula
Figure BDA0002139747690000064
[ example 1 ]
1)
Figure BDA0002139747690000065
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoroethylfluorenone imine, 0.22mmol of cinnamyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 25 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000071
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. After removing the solvent under reduced pressurePurification by column chromatography on silica gel (treated with triethylamine) gave a white solid with a yield of 90%, a melting point of 74-76 ℃ and an enantioselective excess of the product>99％，HPLC(Chiralpak IE,i-propanol/hexane＝10/90,flow rate 1.0mL/min,λ＝248nm)；tr＝6.40and 9.21min.[α]30 D＝-35.8(c 0.26,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.40–7.35(m,2H),7.34–7.28(m,2H),7.25–7.20(m,1H),6.54(dt,J＝16.0,1.2Hz,1H),6.20(dt,J＝16.0,7.2Hz,1H),3.32(dqd,J＝14.4,7.2,4.0Hz,1H),2.65(dddd,J＝14.4,7.2,4.0,1.6Hz,1H),2.37(dddd,J＝14.4,9.2,7.2,1.2Hz,1H),1.51(s,2H).13C NMR(101MHz,CDCl3)δ136.7,134.0,128.6,127.6,126.4(q,J＝28Hz),126.2,124.1,53.5(q,J＝28Hz),33.7(q,J＝2Hz).19F NMR(376MHz,CDCl3) δ -78.18(d, J ═ 8.1 Hz); HRMS (ESI +) calculated value C11H13F3N+([M+H]+) 216.0995, measurement 216.0997.
[ example 2]
1)
Figure BDA0002139747690000072
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoroethylfluorenone imine, 0.22mmol of p-methyl phenyl allyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 25 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000073
Preparation of
Dissolving the product obtained in step 1) in 1mL of dichloroethane, adding a solution of hydroxylamine acetate in methanol (0.5M, 1mL, from salt)Hydroxylamine acid, sodium hydroxide and acetic acid in methanol) and reacted at 50 c for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a white solid in 89% yield, m.p. 52-54 ℃, an enantioselective excess of 99% for the product, HPLC (Chiralpak IE, i-propanol/hexane: 10/90, flow rate 1.0mL/min,. lambda. 264 nm); t is tr＝6.41and 9.73min.[α]30 D＝-46.36(c 0.11,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.26(d,J＝8.0Hz,2H),7.12(d,J＝7.6Hz,2H),6.50(d,J＝15.6Hz,1H),6.13(dt,J＝16.0,7.2Hz,1H),3.31(dqd,J＝12.0,7.6,4.0Hz,1H),2.63(dddd,J＝14.8,7.2,4.0,1.2Hz,1H),2.33(s,3H),1.50(s,2H).13C NMR(101MHz,CDCl3)δ137.4,134.0,133.9,129.2,126.4(q,J＝279Hz),126.1,123.0,53.5(q,J＝28Hz),33.6(q,J＝1Hz),21.1.19F NMR(376MHz,CDCl3) δ -78.12(d, J ═ 7.5 Hz); HRMS (ESI +) calculated value C12H15F3N+([M+H]+) 230.1151, measurement 230.1149.
[ example 3 ]
1)
Figure BDA0002139747690000081
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoroethylfluorenone imine, 0.22mmol of m-methylphenylpropylmethyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 25 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000082
Preparation of
Dissolving the product obtained in the step 1)To 1mL of dichloroethane was added a methanol solution of hydroxylamine acetate (0.5M, 2mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and the reaction was continued at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 81% yield with a product enantioselectivity of 96% and HPLC (Chiralpak IE, i-propanol/hexane: 10/90, flow rate 1.0mL/min,. lambda.254 nm); t is tr＝6.14and 9.78min.[α]30 D＝-33.3(c 0.27,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.24–7.14(m,3H),7.06(d,J＝7.2Hz,1H),6.51(d,J＝15.6Hz,1H),6.18(dt,J＝15.6,7.6Hz,1H),3.42–3.21(m,1H),2.65(dddd,J＝14.2,6.8,4.0,1.2Hz,1H),2.40–2.29(m,1H),2.34(s,3H),1.50(s,2H).13C NMR(101MHz,CDCl3)δ138.1,136.7,134.1,128.5,128.4,126.9,126.4(q,J＝280Hz),123.9,123.4,53.5(q,J＝28Hz),33.7(q,J＝3Hz),21.4.19F NMR(376MHz,CDCl3) δ -78.14(d, J ═ 6.9 Hz); HRMS (ESI +) calculated value C12H15F3N+([M+H]+) 230.1151, measurement 230.1148.
[ example 4 ]
1)
Figure BDA0002139747690000083
Preparation of
0.015mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]2、0.030mmol(S,Sa) L1, 0.5mL deoxygenated THF and 0.5mL deoxygenated n-propylamine, reacted at 50 ℃ for 30 minutes and then the solvent was distilled off under reduced pressure to obtain the iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoroethylfluorenone imine, 0.22mmol of m-methylphenylpropylmethyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 25 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000091
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 2mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 63% yield with 96% enantioselectivity of the product, HPLC (Chiralpak IE, i-propanol/hexane: 10/90, flow rate 1.0mL/min,. lambda.242 nm); t is tr＝5.09and 7.18min.[α]28 D＝16.00(c 0.40,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.46–7.40(m,1H),7.16(dt,J＝6.5,3.4Hz,3H),6.74(d,J＝15.2,1.5Hz,1H),6.07(dt,J＝15.2,7.3Hz,1H),3.40–3.28(m,1H),2.71–2.57(m,1H),2.45–2.38(m,1H),2.34(s,3H).13C NMR(101MHz,CDCl3)δ135.9,135.2,131.9,130.3,127.5,126.5(q,J＝281.3Hz),126.1,125.6,125.5,53.5(q,J＝28.6Hz),33.9,19.8.19F NMR(376MHz,CDCl3) δ -78.06(d, J ═ 7.4 Hz); HRMS (ESI +) calculated value C12H15F3N+([M+H]+) 230.1151, measurement 230.1145.
[ example 5 ]
1)
Figure BDA0002139747690000092
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoroethylfluorenone imine, 0.22mmol of p-methoxyphenylallylmethyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 25 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000093
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by column chromatography on silica gel (treated with triethylamine) gave a pale yellow solid in 90% yield, m.p. 70-72 ℃, with 98% enantioselectivity of the product, HPLC (Chiralpak IE, i-propanol/hexane. 10/90, flow rate 1.0mL/min, λ. 260 nm); t is tr＝10.89and 14.34min.[α]30 D＝-36.5(c 0.54,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.34–7.27(m,2H),6.90–6.79(m,2H),6.47(d,J＝15.6Hz,1H),6.04(dt,J＝15.6,7.2Hz,1H),3.80(s,3H),3.31(dqd,J＝9.2,7.2,4.0Hz,1H),2.63(dddd,J＝14.4,7.2,4.0,1.2Hz,1H),2.34(dddd,J＝14.4,9.2,7.2,1.2Hz,1H),1.43(s,2H).13C NMR(101MHz,CDCl3)δ159.1,133.4,129.6,127.3,126.5(q,J＝280Hz),121.8,113.9,55.3,53.5(q,J＝28Hz),33.6(q,J＝2Hz).19F NMR(376MHz,CDCl3) δ -78.12(d, J ═ 7.9 Hz); HRMS (ESI +) calculated value C12H15F3NO+([M+H]+) 246.1100, measurement 246.1098.
[ example 6 ]
1)
Figure BDA0002139747690000101
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoroethylfluorenone imine, 0.22mmol of p-chlorophenyl allyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 25 ℃. Monitoring the reaction by thin layer chromatography, removing the solvent under reduced pressure after the reaction is finished, and purifying by silica gel (treated with triethylamine) column chromatography to obtain the product。
2)
Figure BDA0002139747690000102
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by column chromatography on silica gel (treated with triethylamine) gave a pale yellow solid in 95% yield, m.p. 36-38 ℃, 96% enantioselectivity of the product, HPLC (Chiralpak IE, i-propanol/hexane: 10/90, flow rate 1.0mL/min, λ 262 nm); t is tr＝7.14and 11.44min.[α]30 D＝-25.6(c 0.39,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.32–7.26(m,4H),6.49(dt,J＝16.0,1.2Hz,1H),6.19(dt,J＝16.0,7.2Hz,1H),3.32(dqd,J＝14.4,7.2,4.0Hz,1H),2.64(dddd,J＝14.4,7.2,4.0,1.2Hz,1H),2.36(dddd,J＝14.4,8.8,7.2,1.2Hz,1H),1.59(s,2H).13C NMR(101MHz,CDCl3)δ135.2,133.1,132.7,128.7,127.4,126.4(q,J＝280Hz),125.0,53.5(q,J＝28Hz),33.6(q,J＝3Hz).19F NMR(376MHz,CDCl3) δ -78.26(d, J ═ 6.8 Hz); HRMS (ESI +) calculated value C11H12ClF3N+([M+H]+) 250.0605, measurement 250.0603.
[ example 7 ]
1)
Figure BDA0002139747690000111
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoroethylfluorenone imine, 0.22mmol of m-chlorophenyl allyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 25 ℃. Monitoring the reaction by thin layer chromatography, after the reaction is complete, decreasingThe product was obtained by column chromatography on silica gel (treated with triethylamine) after removal of the solvent under reduced pressure.
2)
Figure BDA0002139747690000112
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by column chromatography on silica gel (treated with triethylamine) gave a pale yellow liquid in 89% yield with 98% enantioselectivity of the product, HPLC (Chiralpak IE, i-propanol/hexane: 5/95, flow rate 1.0mL/min,. lambda.252 nm); t is tr＝9.63and 16.99min.[α]30 D＝-30.4(c 1.11,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.38–7.33(m,1H),7.26–7.18(m,3H),6.47(dt,J＝16.0,1.2Hz,1H),6.22(dt,J＝16.0,7.2Hz,1H),3.32(dqd,J＝9.2,7.2,4.0Hz,1H),2.65(dddd,J＝14.4,7.2,4.0,1.6Hz,1H),2.36(dddd,J＝14.4,9.2,7.6,1.2Hz,1H),1.45(s,2H).13C NMR(101MHz,CDCl3)δ138.6,134.5,132.6,129.8,127.5,126.4(q,J＝280Hz),126.1,125.9,124.5,53.5(q,J＝28Hz),33.6(q,J＝2Hz).19F NMR(376MHz,CDCl3) δ -78.28(d, J ═ 6.9 Hz); HRMS (ESI +) calculated value C11H12ClF3N+([M+H]+) 250.0605, measurement 250.0603.
[ example 8 ]
1)
Figure BDA0002139747690000113
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Adding 2mL of toluene at 25 ℃ under the protection of nitrogen, and sequentially adding 0.20mmol of N-2,2, 2-trifluoroethylfluorenone imine, 0.22mmol of p-fluorophenylallyl methyl carbonate and 0.20mmol of 1, 8-diazadimCycloundec-7-ene, at 25 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000121
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by column chromatography on silica gel (treated with triethylamine) gave a pale yellow liquid in 95% yield with a product enantioselectivity of 94% excess, HPLC (Chiralpak IE, i-propanol/hexane: 10/90, flow rate 1.0mL/min,. lambda.250 nm); t is tr＝6.82and 10.63min.[α]30 D＝-34.0(c 0.43,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.41–7.28(m,2H),7.00(t,J＝8.8Hz,2H),6.49(d,J＝15.6Hz,1H),6.11(dt,J＝15.6,7.2Hz,1H),3.32(dqd,J＝14.4,7.2,4.0Hz,1H),2.63(dddd,J＝14.4,7.2,4.0,1.2Hz,1H),2.35(dddd,J＝14.4,9.2,7.2,1.2Hz,1H),1.45(s,2H).13C NMR(101MHz,CDCl3)δ162.2(d,J＝246Hz),132.9(d,J＝4Hz),132.7,127.7(d,J＝8Hz),126.4(q,J＝280Hz),123.9(d,J＝2Hz),115.4(d,J＝22Hz),53.5(q,J＝28Hz),33.6(q,J＝2Hz).19F NMR(376MHz,CDCl3) δ -78.23(d, J ═ 8.0Hz), -114.49-114.59 (m); HRMS (ESI +) calculated value C11H12F4N+([M+H]+) 234.0900, measurement 234.0901.
[ example 9 ]
1)
Figure BDA0002139747690000122
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. At 25 deg.CUnder the protection of nitrogen, 2mL of toluene was added, and 0.20mmol of N-2,2, 2-trifluoroethylfluorenone imine, 0.22mmol of 2-naphthylallyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene were sequentially added and reacted at 25 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000123
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by column chromatography on silica gel (treated with triethylamine) gave a pale yellow solid in 88% yield, mp 98-100 ℃, enantioselective excess of product 99%, HPLC (Chiralpak IE, i-propanol/hexane: 10/90, flow rate 1.0mL/min,. lambda.280 nm); t is tr＝6.31and 8.83min.[α]30 D＝-27.3(c 0.40,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.82–7.76(m,3H),7.73–7.70(m,1H),7.59(dd,J＝8.8,1.6Hz,1H),7.49–7.41(m,2H),6.70(dt,J＝15.6,1.2Hz,1H),6.33(dt,J＝15.6,7.2Hz,1H),3.37(dqd,J＝14.4,7.2,4.0Hz,1H),2.71(dddd,J＝14.4,7.2,4.0,1.6Hz,1H),2.42(dddd,J＝14.4,9.2,7.6,1.2Hz,1H),1.44(s,2H).13CNMR(101MHz,CDCl3)δ134.2,134.1,133.5,132.9,128.2,127.9,127.6,126.5(q,J＝280Hz),126.3,126.1,125.9,124.6,123.4,53.6(q,J＝28Hz),33.8(d,J＝2Hz).19F NMR(376MHz,CDCl3) δ -78.14(d, J ═ 7.0 Hz); HRMS (ESI +) calculated value C15H15F3N+([M+H]+) 266.1151, measurement 266.1150.
[ example 10 ]
1)
Figure BDA0002139747690000131
Preparation of
0.00 was added to a 25mL reaction tube5mmol[Ir(COD)Cl]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoroethylfluorenone imine, 0.22mmol of 2-thiophene allyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 25 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000132
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow solid in 80% yield, m.p. 35-37 ℃, with an enantiomeric excess of 98% of the product, HPLC (Chiralpak IE, i-propanol/hexane: 10/90, flow rate 1.0mL/min, λ: 280 nm); t is tr＝6.12and 8.34min.[α]30 D＝-64.7(c 0.62,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.14(dt,J＝5.2,0.8Hz,1H),6.99–6.90(m,2H),6.66(dt,J＝15.6,0.8Hz,1H),6.03(dt,J＝15.6,7.2Hz,1H),3.30(dqd,J＝10.8,5.2,2.8Hz,1H),2.62(dddd,J＝14.4,7.2,4.0,1.6Hz,1H),2.32(dddd,J＝14.4,8.8,7.6,1.2Hz,1H),1.45(s,2H).13C NMR(101MHz,CDCl3)δ141.8,127.1,126.4,125.4(q,J＝280Hz),,124.0,123.9,53.5(q,J＝28.7Hz),33.5(d,J＝1.9Hz).19F NMR(376MHz,CDCl3) δ -74.11(d, J ═ 6.8 Hz); HRMS (ESI +) calculated value C9H11F3NS+([M+H]+) 222.0559, measurement 222.0556.
[ example 11 ]
1)
Figure BDA0002139747690000133
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoroethylfluorenone imine, 0.22mmol of 2-furallylmethyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 25 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000141
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 75% yield with 98% enantioselectivity of the product, HPLC (Chiralpak IE, i-propanol/hexane: 10/90, flow rate 1.0mL/min,. lambda.: 276 nm); t is tr＝6.28and 8.45min.[α]30 D＝-56.9(c 0.16,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.44(d,J＝2.0Hz,1H),7.37(d,J＝8.4Hz,1H),7.18(dd,J＝8.4,2.4Hz,1H),6.43(dt,J＝16.0,1.6Hz,1H),6.22(dt,J＝16.0,7.2Hz,1H),3.32(dqd,J＝14.4,7.2,4.0Hz,1H),2.64(dddd,J＝14.4,7.2,4.0,1.2Hz,1H),2.36(dddd,J＝14.4,8.8,7.2,1.2Hz,1H),1.46(s,2H).13C NMR(101MHz,CDCl3)δ152.2,141.8,126.4(q,J＝281.4Hz),123.0,122.3,111.2,107.4,53.5(q,J＝28.6Hz),33.5(t,J＝2.1Hz).19F NMR(376MHz,CDCl3) δ -78.25(d, J ═ 6.9 Hz); HRMS (ESI +) calculated value C9H11F3NO+([M+H]+) 206.0787, measurement 206.0792.
[ example 12 ]
Figure BDA0002139747690000142
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoroethylfluorenone imine, 0.22mmol of 2-pyridylallylcarbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added and reacted at 25 ℃. The reaction was monitored by thin layer chromatography, after completion of the reaction, the solvent was removed under reduced pressure and purified by column chromatography on silica gel (treated with triethylamine) to give a yellow solid in 80% yield, melting point 46-48 ℃, enantioselectivity of the product 95%, HPLC (Chiralpak AD-H, i-propanol/hexane: 4/94, flow rate 1.0mL/min,. lambda.: 254 nm); t is tr＝7.66and 11.12min.[α]30 D＝-56.4(c 0.36,CH2Cl2)；1H NMR(400MHz,CDCl3)δ8.48(ddd,J＝4.8,1.6,0.8Hz,1H),7.87(dt,J＝7.6,0.8Hz,1H),7.77(d,J＝7.6Hz,1H),7.65–7.57(m,1H),7.52(qd,J＝5.2,4.8,1.6Hz,2H),7.45–7.35(m,2H),7.29(td,J＝7.6,1.2Hz,1H),7.22(td,J＝7.6,1.2Hz,1H),7.11(dd,J＝8.0,1.2Hz,1H),7.06(ddd,J＝7.6,4.8,1.2Hz,1H),6.73(dt,J＝15.6,7.2Hz,1H),6.61(d,J＝15.6Hz,1H),5.22–5.08(m,1H),3.16–3.03(m,1H),2.93–2.81(m,1H).13C NMR(101MHz,CDCl3)δ165.4,155.1,149.3,144.3,140.9,138.0,136.3,133.4,132.0,131.6,131.2,128.8,128.5,128.1,126.9,125.6(q,J＝279Hz),123.4,122.0,121.2,120.6,119.3,62.1(q,J＝27Hz),34.1.19F NMR(376MHz,CDCl3) δ -73.79(d, J ═ 6.8 Hz); HRMS (ESI +) theoretical value C23H18F3N2 +([M+H]+) 379.1417, measurement 379.1421.
[ example 13 ]
Figure BDA0002139747690000151
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoroethylfluorenone imine, 0.22mmol of 3-pyridylallylcarbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 25 ℃. The reaction was monitored by thin layer chromatography, after completion of the reaction, the solvent was removed under reduced pressure and purified by silica gel (treated with triethylamine) column chromatography to give a yellow solid in 67% yield, mp 37-39 ℃, enantioselectivity of the product 91%, HPLC (Chiralpak AD-H, i-propanol/hexane: 5/95, flow rate 1.0mL/min,. lambda.252 nm); t is tr＝11.73and 15.02min.[α]30 D＝-44.8(c 0.33,CH2Cl2)；1H NMR(400MHz,CDCl3)δ8.38(dt,J＝3.2,1.6Hz,2H),7.87(dt,J＝7.6,1.2Hz,1H),7.76(d,J＝8.0Hz,1H),7.61(dt,J＝7.6,0.8Hz,1H),7.53(dt,J＝7.6,0.8Hz,1H),7.48–7.36(m,3H),7.29(td,J＝7.6,1.2Hz,1H),7.21(td,J＝7.6,1.2Hz,1H),7.11(ddd,J＝8.0,4.8,0.8Hz,1H),6.46(d,J＝16.0Hz,1H),6.23(dt,J＝16.0,7.6Hz,1H),5.15(td,J＝7.2,5.6Hz,1H),3.04(dddd,J＝14.4,7.2,5.6,1.2Hz,1H),2.86(dddd,J＝14.4,9.2,7.6,7.2,1.2Hz,1H).13C NMR(101MHz,CDCl3)δ165.4,148.3,147.9,144.3,140.9,137.9,132.6,132.4,132.1,131.7,131.2,130.0,128.5,128.0,126.8,126.6,125.5(q,J＝279Hz),123.32,123.25,120.7,119.3,61.9(q,J＝27Hz),34.1(d,J＝2.1Hz).19F NMR(376MHz,CDCl3) δ -74.11(d, J ═ 6.8 Hz); HRMS (ESI +) calculated value C23H18F3N2 +([M+H]+) 379.1417, measurement 379.1436.
[ example 14 ]
Figure BDA0002139747690000152
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]2、0.010mmol (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine, reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoroethylfluorenone imine, 0.22mmol of 6-quinoline allyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added to react at 25 ℃. The reaction was monitored by thin layer chromatography, after completion of the reaction, the solvent was removed under reduced pressure and purified by silica gel (treated with triethylamine) column chromatography to give a yellow solid in 80% yield, melting point 74-76 ℃, enantioselectivity of the product 97%, HPLC (Chiralpak AD-H, i-propanol/hexane: 5/95, flow rate 1.0mL/min, λ: 254 nm); t is tr＝21.67and 24.08min.[α]25 D＝-90.2(c 0.60,CH2Cl2)；1H NMR(400MHz,CDCl3)δ8.79(dd,J＝4.3,1.7Hz,1H),7.99–7.86(m,3H),7.79(d,J＝7.8Hz,1H),7.61–7.53(m,2H),7.53–7.48(m,1H),7.46–7.34(m,3H),7.33–7.26(m,2H),7.20(td,J＝7.6,1.2Hz,1H),6.63(d,J＝15.7Hz,1H),6.30(dt,J＝15.3,7.4Hz,1H),5.24–5.12(m,1H),3.09(dddd,J＝14.5,7.2,5.7,1.3Hz,1H),2.88(dddd,J＝14.7,7.4,1.4Hz,1H).13C NMR(101MHz,CDCl3)δ165.4,149.9,147.7,144.3,140.9,137.9,135.8,135.0,132.8,132.0,131.6,131.3,129.4,128.5,128.2,128.0,127.1,126.9,125.8,125.5(q,J＝281.8Hz,1H),125.3,123.3,121.3,120.6,119.3,62.1(q,J＝27.5Hz),34.2.19F NMR(376MHz,CDCl3) δ -74.02(d, J ═ 6.7 Hz); HRMS (ESI +) calculated value C27H20F3N2([M+H]+) 429.1573, measurement 429.1578.
[ example 15 ]
Figure BDA0002139747690000161
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20 is added in sequencemmol of N-2,2, 2-trifluoroethylfluorenone imine, 0.22mmol of phenethylallyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundec-7-ene were reacted at 25 ℃. The reaction was monitored by thin layer chromatography, after completion of the reaction, the solvent was removed under reduced pressure and purified by silica gel (treated with triethylamine) column chromatography to give a yellow liquid in 56% yield with a product having an enantioselectivity of 92% HPLC (chiralpak od-H, i-propanol/hexane: 3/97, flow rate 1.0mL/min,. lambda.252 nm); t is tr＝6.83and 10.98min.[α]30 D＝-12.1(c0.34,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.87(dt,J＝7.6,0.8Hz,1H),7.75(d,J＝7.6Hz,1H),7.66(dt,J＝7.6,0.8Hz,1H),7.56(dt,J＝7.6,0.8Hz,1H),7.44(dtd,J＝8.8,7.6,1.2Hz,2H),7.31(td,J＝7.6,1.2Hz,2H),7.26(td,J＝7.6,1.2Hz,3H),7.25–7.15(m,4H),7.17–7.08(m,1H),7.07–6.99(m,2H),5.58(dt,J＝15.6,6.4Hz,1H),5.47(dt,J＝15.6,7.2Hz,1H),5.08–4.93(m,1H),2.82(dt,J＝14.0,6.4Hz,1H),2.58(dt,J＝14.4,7.2Hz,1H),2.45(t,J＝8.0Hz,2H),2.24–2.13(m,2H).13C NMR(101MHz,CDCl3)δ164.9,144.3,141.7,140.9,138.1,134.0,131.9,131.6,131.5,128.5,128.3,128.2,127.9,127.2,125.7,124.6,123.4,120.6,119.3,62.4(q,J＝27Hz),35.4,34.2,33.6(q,J＝1Hz).19F NMR(376MHz,CDCl3)δ-74.28(d,J＝6.8Hz).；HRMS(ESI+)Calcd.For C26H22F3NNa+([M+Na]+):428.1597,found:428.1600。
[ example 16 ]
1)
Figure BDA0002139747690000171
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Adding 2mL of toluene at 25 ℃ under the protection of nitrogen, sequentially adding 0.20mmol of N-2,2, 2-trifluoro-1- (p-chlorophenyl) ethyl fluorenone imine, 0.22mmol of cinnamyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundec-7-ene, and reacting at 50 DEG C. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000172
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 90% yield with a product enantioselectivity of 98%, HPLC (Chiralpak IE, i-propanol/hexane: 5/95, flow rate 1.0mL/min,. lambda.260 nm); t is tr＝4.58and 4.89min.[α]25 D＝166.8(c 0.34,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.58–7.52(m,2H),7.39–7.33(m,2H),7.29–7.23(m,4H),7.23–7.17(m,1H),6.46(dt,J＝15.8,1.4Hz,1H),5.96–5.82(m,1H),3.00(ddd,J＝14.3,7.0,1.4Hz,1H),2.80(ddd,J＝14.3,7.9,1.3Hz,1H),1.78(s,2H).13C NMR(101MHz,CDCl3)δ136.6,136.2,135.3,134.3,128.6,128.5,128.4,127.6,126.8(q,J＝285.8Hz),126.2,122.0,61.2(q,J＝26.0Hz),40.2.19F NMR(376MHz,CDCl3) Delta-77.58.; HRMS (ESI +) calculated value C17H16ClF3N([M+H]+) 326.0918, theoretical value 326.0928.
[ example 17 ]
1)
Figure BDA0002139747690000173
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Adding 2mL of toluene at 25 ℃ under the protection of nitrogen, and sequentially adding 0.20mmol of N-2,2, 2-trifluoro-1- (m-chlorophenyl) ethyl fluorenone imine and 0.22mmol of cinnamyl methyl carbonateAnd 0.20mmol of 1, 8-diazabicycloundec-7-ene, at 50 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000181
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 85% yield with 98% enantioselectivity of the product, HPLC (Chiralpak IE, i-propanol/hexane: 5/95, flow rate 1.0mL/min,. lambda.260 nm); t is tr＝4.29and 4.59min.[α]25 D＝137.1(c 0.93,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.67–7.62(m,1H),7.54–7.47(m,1H),7.33(dd,J＝5.2,1.1Hz,2H),7.29–7.24(m,4H),7.23–7.16(m,1H),6.48(dt,J＝15.8,1.3Hz,1H),5.88(dddd,J＝15.8,7.9,7.0,0.9Hz,1H),2.99(ddd,J＝14.4,7.0,1.4Hz,1H),2.82(ddd,J＝14.3,7.9,1.3Hz,1H),1.80(s,2H).13C NMR(101MHz,CDCl3)δ139.9,136.6,135.5,134.5,129.6,128.5,128.4,127.7,127.3,126.7(q,J＝285.7Hz),126.2,125.1,121.9,61.3(q,J＝25.9Hz),40.2.19F NMR(376MHz,CDCl3) Delta-77.30; HRMS (ESI +) calculated value C17H16ClF3N([M+H]+) 326.0918, measurement 326.0925.
[ example 18 ]
1)
Figure BDA0002139747690000182
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 DEG C2mL of toluene was added, and 0.20mmol of N-2,2, 2-trifluoro-1- (p-trifluoromethylphenyl) ethylfluorenone imine, 0.22mmol of cinnamyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundec-7-ene were sequentially added and reacted at 50 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000191
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 75% yield with 98% enantioselectivity of the product, HPLC (Chiralpak ID, i-propanol/hexane: 2/98, flow rate 1.0mL/min,. lambda.260 nm); t is tr＝4.11and 4.47min.[α]25 D＝95.8(c 0.45,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.77(d,J＝8.7Hz,2H),7.66(d,J＝8.5Hz,2H),7.30–7.24(m,4H),7.23–7.18(m,1H),6.48(dt,J＝15.7,1.3Hz,1H),5.96–5.81(m,1H),3.02(ddd,J＝14.4,7.1,1.4Hz,1H),2.86(ddd,J＝14.4,7.7,1.2Hz,1H),1.84(s,2H).13C NMR(101MHz,CDCl3)δ141.8,136.5,135.6,130.4(q,J＝32.7Hz),128.5,127.7,127.4,126.7(q,J＝284.4Hz),126.2,125.4(q,J＝3.7Hz),124.0(q,J＝279.4Hz),121.7,61.5(q,J＝26.1Hz),40.3.19F NMR(376MHz,CDCl3) δ -62.68, -77.20.; HRMS (ESI +) calculated value C18H16F6N([M+H]+) 360.1181, measurement 360.1198.
[ example 19 ]
1)
Figure BDA0002139747690000192
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol (S, S, S) -L1, 0.5mLTHF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoro-1- (p-methylphenyl) ethyl fluorenone imine, 0.22mmol of cinnamyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 50 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000193
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 80% yield with 98% enantioselectivity of the product, HPLC (Chiralpak IE, i-propanol/hexane: 5/95, flow rate 1.0mL/min,. lambda.254 nm); t is tr＝4.92and 5.41min.[α]25 D＝129.0(c 0.61,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.49(d,J＝8.0Hz,2H),7.25(d,J＝4.4Hz,4H),7.20(dd,J＝8.3,4.1Hz,3H),6.48(dt,J＝15.8,1.4Hz,1H),5.91(ddd,J＝15.3,7.9,6.7Hz,1H),3.05(ddd,J＝14.3,6.7,1.5Hz,1H),2.81(ddd,J＝14.3,8.1,1.2Hz,1H),2.36(s,3H),1.79(s,2H).13C NMR(101MHz,CDCl3)δ137.9,136.8,135.0,134.5,129.1,128.5,127.5,127.0(q,J＝285.2Hz),126.7,126.2,122.7,61.1(q,J＝25.7Hz),40.1,21.0.19F NMR(376MHz,CDCl3) Delta-77.75.; HRMS (ESI +) calculated value C18H19F3N([M+H]+) 306.1464, measurement 306.1465.
[ example 20 ]
1)
Figure BDA0002139747690000201
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoro-1- (p-methylphenyl) ethyl fluorenone imine, 0.22mmol of cinnamyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 50 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000202
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 83% yield with 98% enantioselectivity of the product, HPLC (Chiralpak IE, i-propanol/hexane: 5/95, flow rate 1.0mL/min,. lambda.: 260 nm); t is tr＝4.50and 4.95min.[α]25 D＝114.9(c 0.91,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.44–7.38(m,2H),7.32–7.23(m,5H),7.22–7.14(m,2H),6.49(dt,J＝15.8,1.4Hz,1H),5.99–5.84(m,1H),3.05(ddd,J＝14.3,6.7,1.5Hz,1H),2.82(ddd,J＝14.3,8.1,1.2Hz,1H),2.38(s,3H),1.80(s,2H).13C NMR(101MHz,CDCl3)δ138.0,137.5,136.7,135.1,128.9,128.5,128.2,127.5,127.4,127.0(q,J＝285.8Hz),126.2,123.9,122.7,61.2(q,J＝25.6Hz),40.2,21.6.19F NMR(376MHz,CDCl3) Delta-77.45.; HRMS (ESI +) calculated value C18H19F3N([M+H]+) 306.1464, measurement 306.1466.
[ example 21 ]
1)
Figure BDA0002139747690000211
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoro-1- (p-tert-butylphenyl) ethyl fluorenone imine, 0.22mmol of cinnamyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundec-7-ene are added in sequence and reacted at 50 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000212
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 72% yield with a product enantioselectivity of 97% excess, HPLC (Chiralpak IE, i-propanol/hexane: 5/95, flow rate 1.0mL/min,. lambda.260 nm); t is tr＝4.35and 4.82min.[α]25 D＝142.6(c 0.47,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.55–7.50(m,2H),7.43–7.38(m,2H),7.26(d,J＝4.4Hz,4H),7.22–7.16(m,1H),6.49(dt,J＝15.8,1.4Hz,1H),6.00–5.89(m,1H),3.04(ddd,J＝14.4,6.8,1.6Hz,1H),2.84(ddd,J＝14.4,8.0,1.2Hz,1H),1.80(s,2H),1.33(s,9H).13C NMR(101MHz,CDCl3)δ151.0,136.8,135.1,134.5,128.5,127.5,127.0(q,J＝284.4Hz),126.5,126.2,125.3,122.8,61.0(q,J＝25.8Hz),40.2,34.4,31.2.19F NMR(376MHz,CDCl3) Delta-77.48; HRMS (ESI +) calculated value C21H24F3N([M+H]+) 348.1934, measurement 348.1933.
[ example 22 ]
1)
Figure BDA0002139747690000213
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoro-1- (2-naphthylethyl) fluorenone imine, 0.22mmol of cinnamyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 50 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000221
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 84% yield with 98% enantioselectivity of the product, HPLC (Chiralpak IE, i-propanol/hexane: 5/95, flow rate 1.0mL/min,. lambda.260 nm); t is tr＝5.23and 5.68min.[α]25 D＝156.3(c 0.19,CH2Cl2)；1H NMR(400MHz,CDCl3)δ8.11(d,J＝1.9Hz,1H),7.87(td,J＝8.6,3.4Hz,3H),7.72(dq,J＝8.7,1.1Hz,1H),7.56–7.45(m,2H),7.23–7.14(m,5H),6.51(dt,J＝15.6,1.4Hz,1H),5.91(dt,J＝15.6,7.4Hz,1H),3.19(ddd,J＝14.3,6.6,1.5Hz,1H),2.91(ddd,J＝14.3,8.1,1.2Hz,1H),1.95(s,2H).13C NMR(101MHz,CDCl3)δ136.6,135.2,135.0,132.9,132.8,128.4,128.1,127.5,127.4,127.0(d,J＝285.4Hz),126.6,126.5,126.3,126.2,124.3,122.4,61.5(q,J＝25.7Hz),40.2.19F NMR(376MHz,CDCl3) Delta-77.23; HRMS (ESI +) theoretical value C21H24F3N([M+H]+) 342.1464, measurement 342.1469.
[ example 23 ]
1)
Figure BDA0002139747690000222
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoro-1-phenylfluorenone imine, 0.22mmol of methyl p-methyl phenylpropenoate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 50 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000223
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 97% yield with 98% enantioselectivity of the product, HPLC (Chiralpak IE, i-propanol/hexane: 5/95, flow rate 1.0mL/min,. lambda.254 nm); t is tr＝4.81and 5.91min.[α]25 D＝156.3(c 0.19,CH2Cl2)；[]25 D＝84.7(c 0.60,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.66–7.59(m,2H),7.44–7.32(m,3H),7.14(t,J＝7.5Hz,1H),7.09–6.97(m,3H),6.45(dt,J＝15.3,1.3Hz,1H),5.90(dt,J＝15.3,7.4Hz,1H),3.05(ddd,J＝14.3,6.9,1.4Hz,1H),2.83(ddd,J＝14.3,8.0,1.3Hz,1H),2.29(s,3H),1.83(s,2H).13C NMR(101MHz,CDCl3)δ138.1,137.6,136.7,135.3,128.4,128.4,128.3,128.2,127.0(q,J＝285.5Hz),126.9,126.8,123.3,122.3,61.3(q,J＝25.7Hz),40.2.19F NMR(376MHz,CDCl3) Delta-77.49.; HRMS (ESI +) calculated value C18H19F3N([M+H]+) 306.1464, measurement 306.1462.
[ example 24 ]
1)
Figure BDA0002139747690000231
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoro-1-phenylfluorenone imine, 0.22mmol of m-methyl phenylpropenyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 50 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000232
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 94% yield with a product enantioselectivity of 98%, HPLC (Chiralpak IE, i-propanol/hexane: 5/95, flow rate 1.0mL/min,. lambda.: 254 nm); t is tr＝4.99and 5.66min.[α]25 D＝118.2(c 0.22,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.62(dd,J＝7.5,1.8Hz,2H),7.43–7.32(m,3H),7.14(d,J＝8.2Hz,2H),7.06(d,J＝7.9Hz,2H),6.45(d,J＝15.6Hz,1H),5.85(dt,J＝15.6,7.4Hz,1H),3.04(ddd,J＝14.2,6.8,1.4Hz,1H),2.82(ddd,J＝14.2,8.0,1.2Hz,1H),2.30(s,3H),1.83(s,2H).113C NMR(101MHz,CDCl3)δ137.7,137.4,135.0,133.9,129.2,128.4,128.2,127.0(d,J＝285.5Hz),126.8,126.1,121.4,40.2,21.1.19F NMR(376MHz,CDCl3) Delta-77.45.; HRMS (ESI +) calculated value C18H19F3N([M+H]+) 306.1464, measurement 306.1466.
[ example 25 ]
1)
Figure BDA0002139747690000241
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoro-1-phenylfluorenone imine, 0.22mmol of p-methoxyphenylene methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 50 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000242
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 85% yield with a product enantioselectivity of 97% excess, HPLC (Chiralpak ID, i-propanol/hexane: 5/95, flow rate 1.0mL/min,. lambda.: 260 nm); t is tr＝6.35and 6.86min.[α]25 D＝105.0(c 0.16,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.66–7.58(m,2H),7.46–7.31(m,3H),7.23–7.14(m,2H),6.84–6.75(m,2H),6.65–6.29(m,1H),5.82–5.69(m,1H),3.78(s,3H),3.04(ddd,J＝14.2,6.4,1.2Hz,2H),2.82(ddd,J＝14.2,8.0,1.2Hz,1H),1.81(s,2H).13C NMR(101MHz,CDCl3)δ159.1,137.7,134.6,129.6,128.4,128.2,127.4,127.0(d,J＝285.5Hz),126.8,120.2,113.9,55.3,40.2.19F NMR(376MHz,CDCl3) Delta-77.45.; HRMS (ESI +) calculated value C18H19F3NO([M+H]+) 322.1413, measurement 322.1412.
[ example 26 ]
1)
Figure BDA0002139747690000243
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoro-1-phenylfluorenone imine, 0.22mmol of p-chlorophenylphenyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 50 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000251
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 87% yield with 98% enantioselectivity of the product, HPLC (Chiralpak IE, i-propanol/hexane: 5/95, flow rate 1.0mL/min,. lambda.260 nm); t is tr＝4.71and 6.46min.[α]25 D＝119.7(c 0.63,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.63–7.57(m,2H),7.43–7.33(m,3H),7.22–7.10(m,4H),6.41(dd,J＝15.6,1.4Hz,1H),5.88(dt,J＝15.6,7.3Hz,1H),3.04(ddd,J＝14.3,6.8,1.5Hz,1H),2.81(ddd,J＝14.3,7.9,1.2Hz,1H),1.82(s,2H).13C NMR(101MHz,CDCl3)δ137.4,135.2,133.7,133.1,128.6,128.4,128.2,127.4,126.9(q,J＝285.3Hz),126.7,123.4,61.3(q,J＝25.7Hz),40.1.19F NMR(376MHz,CDCl3) Delta-77.57.; HRMS (ESI +) calculated value C17H16ClF3N([M+H]+) 326.0918, measurement 326.0919.
[ example 27 ]
1)
Figure BDA0002139747690000252
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoro-1-phenylfluorenone imine, 0.22mmol of m-chloropropene methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 50 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000253
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 94% yield with a product enantioselectivity of 98%, HPLC (Chiralpak IE, i-propanol/hexane: 5/95, flow rate 1.0mL/min,. lambda.260 nm); t is tr＝5.48and 6.88min.[α]25 D＝86.2(c 0.66,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.61(dd,J＝7.5,1.8Hz,2H),7.43–7.34(m,3H),7.21(q,J＝1.4Hz,1H),7.19–7.12(m,2H),7.09(ddd,J＝6.1,3.1,1.7Hz,1H),6.40(dt,J＝15.6,1.4Hz,1H),5.92(dt,J＝15.6,7.5Hz,1H),3.05(ddd,J＝14.4,6.9,1.5Hz,1H),2.82(ddd,J＝14.4,7.9,1.3Hz,1H),1.82(s,2H).13C NMR(101MHz,CDCl3)δ138.6,137.3,134.4,133.6,129.7,128.4,128.3,127.4,126.9(q,J＝285.4Hz),126.7,126.2,126.1,124.4,124.3,61.3(q,J＝25.9Hz),40.0.19F NMR(376MHz,CDCl3) Delta-77.62; HRMS (ESI +) calculated value C17H16ClF3N([M+H]+) 326.0918, measurement 326.0923.
[ example 28 ]
1)
Figure BDA0002139747690000261
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoro-1-phenylfluorenone imine, 0.22mmol of p-bromophenyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 50 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000262
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 88% yield with a product enantioselectivity of 96% and HPLC (Chiralpak IE, i-propanol/hexane: 5/95, flow rate 1.0mL/min,. lambda.260 nm); t is tr＝5.63and 6.98min.[α]25 D＝116.0(c 0.42,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.61(d,J＝7.3Hz,2H),7.45–7.31(m,5H),7.14–7.05(m,2H),6.40(d,J＝15.6Hz,1H),5.90(dt,J＝15.6,7.3Hz,1H),3.04(ddd,J＝14.3,6.8,1.5Hz,1H),2.81(ddd,J＝14.3,7.9,1.3Hz,1H),1.82(s,2H).13C NMR(101MHz,CDCl3)δ137.4,135.6,133.8,131.5,128.4,128.3,127.7,126.9(q,J＝285.4Hz),126.7,123.5,121.2,61.3(q,J＝25.9Hz),40.1.19F NMR(376MHz,CDCl3) Delta-77.56.; HRMS (ESI +) calculated value C17H15BrF3N([M+H]+) 370.0413, measurement 370.0416.
[ example 29 ]
1)
Figure BDA0002139747690000271
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoro-1-phenylfluorenone imine, 0.22mmol of 2-naphthalene propylene methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 50 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000272
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a white solid in 85% yield, m.p. 80-82 ℃, 98% enantioselectivity of the product, HPLC (Chiralpak IE, i-propanol/hexane ═ 5/95, flow rate 1.0mL/min,. lambda. 260 nm); t is tr＝6.56and 7.86min.[α]25 D＝133.5(c 0.78,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.79–7.71(m,3H),7.71(d,J＝8.6Hz,1H),7.69–7.59(m,3H),7.48–7.33(m,6H),6.64(dd,J＝15.8,1.4Hz,1H),6.11–5.96(m,1H),3.12(ddd,J＝14.4,6.8,1.5Hz,1H),2.90(ddd,J＝14.4,7.9,1.2Hz,1H),1.86(s,2H).13C NMR(101MHz,CDCl3)δ137.6,135.2,134.2,133.4,132.9,128.4,128.2,128.1,127.9,127.6,127.0(q,J＝284.4Hz),126.8,126.3,126.0,125.8,123.4,123.0,61.4(q,J＝25.4Hz),40.3.19F NMR(376MHz,CDCl3) Delta-77.47.; HRMS (ESI +) calculated value C21H19F3N([M+H]+) 342.1464, measurement 342.1467.
[ example 30 ]
1)
Figure BDA0002139747690000273
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoro-1-phenylfluorenone imine, 0.22mmol of 2-thiopheneacrylmethyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 50 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000281
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by column chromatography on silica gel (treated with triethylamine) gave a yellow liquid in 76% yield with 96% enantioselectivity of the product, HPLC (Chiralpak IE,i-propanol/hexane＝5/95,flow rate 1.0mL/min,λ＝290nm)；tr＝5.59and 5.97min.[α]25 D＝94.8(c 0.27,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.61(ddd,J＝8.1,1.8,1.0Hz,2H),7.44–7.32(m,3H),7.08(dt,J＝5.0,0.9Hz,1H),6.90(dd,J＝5.0,3.5Hz,1H),6.88–6.83(m,1H),6.63–6.54(m,1H),5.74(dt,J＝15.3,7.5Hz,1H),3.05–2.96(m,1H),2.80(ddd,J＝14.3,7.9,1.2Hz,1H),1.82(s,2H).13C NMR(101MHz,CDCl3)δ141.8,137.5,128.4,128.2,128.1,127.2,126.9(q,J＝285.4Hz),126.7,125.3,124.0,122.2,61.3(q,J＝25.7Hz),40.1.19F NMR(376MHz,CDCl3) Delta-77.45.; HRMS (ESI +) calculated value C15H15F3NS([M+H]+) 298.0872, measurement 298.0866.
[ example 31 ]
Figure BDA0002139747690000282
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoro-1-phenylfluorenone imine, 0.22mmol of 3-pyridylpropenylmethyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 50 ℃. The reaction was monitored by thin layer chromatography, after completion of the reaction, the solvent was removed under reduced pressure and purified by silica gel (treated with triethylamine) column chromatography to give a yellow liquid in 72% yield with an enantioselectivity of the product of 97% excess, HPLC (Chiralpak AD-H, i-propanol/hexane: 5/95, flow rate 1.0mL/min, λ: 220 nm); t is tr＝8.82and 10.08min.[α]25 D＝168.4(c0.45,CH2Cl2)；1H NMR(400MHz,CDCl3)δ8.32(dd,J＝4.8,1.6Hz,1H),8.21(d,J＝2.2Hz,1H),7.95(d,J＝7.4Hz,1H),7.52(dd,J＝11.8,7.1Hz,4H),7.44–7.38(m,1H),7.37–7.29(m,5H),7.21(t,J＝7.5Hz,1H),7.04(ddd,J＝7.9,4.8,0.8Hz,1H),6.80–6.71(m,1H),6.25(d,J＝7.9Hz,1H),6.23–6.10(m,2H),3.67–3.54(m,2H).13C NMR(101MHz,CDCl3)δ165.1,148.1,147.9,144.9,140.7,139.0,137.6,132.6,132.5,131.5,131.4,129.7,128.7,128.6,128.5,127.9,127.3,127.0,126.8(d,J＝285.2Hz),123.4,123.1,120.0,119.0,70.6(q,J＝25.1Hz),36.9.19F NMR(376MHz,CDCl3) Delta-77.25.; HRMS (ESI +) calculated value C29H22F3N2([M+H]+) 455.1730, measurement 455.1732.
[ example 32 ]
Figure BDA0002139747690000291
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoro-1-phenylfluorenone imine, 0.22mmol of crotyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 50 ℃. The reaction was monitored by thin layer chromatography, after completion of the reaction, the solvent was removed under reduced pressure and purified by silica gel (treated with triethylamine) column chromatography to give a yellow liquid in 50% yield with 99% enantioselectivity excess of the product, HPLC (Chiralpak IF-3, i-propanol/hexane: 2/98, flow rate 1.0mL/min,. lambda.254 nm); t is tr＝7.07and 10.08min.[α]25 D＝71.1(c 0.94,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.96(d,J＝7.4Hz,1H),7.55–7.48(m,4H),7.42(d,J＝7.4Hz,1H),7.36–7.29(m,4H),7.21(t,J＝7.5Hz,1H),6.76(t,J＝7.7Hz,1H),6.24(d,J＝7.9Hz,1H),5.41(dt,J＝14.8,7.3Hz,1H),5.29–5.17(m,1H),3.35(t,J＝6.5Hz,2H),1.36(d,J＝4.9Hz,3H).13C NMR(101MHz,CDCl3)δ164.3,144.7,140.7,139.2,137.9,131.3,131.1,129.2,128.7,128.5,128.4,128.0,127.1,126.9(q,J＝285.2Hz),124.9,123.4,119.8,118.9,70.6(q,J＝24.8Hz),36.4,17.8.19F NMR(376MHz,CDCl3)δ-7723.; HRMS (ESI +) calculated value C25H21F3N([M+H]+) 392.1621, measurement 392.1614.
[ example 33 ]
1)
Figure BDA0002139747690000292
Preparation of
0.005mmol of [ Ir (COD) Cl was added to a 25mL reaction tube]20.010mmol of (S, S, S) -L1, 0.5mL of deoxygenated THF and 0.5mL of deoxygenated n-propylamine were reacted at 50 ℃ for 30 minutes, and then the solvent was distilled off under reduced pressure to obtain an iridium catalyst. Under the protection of nitrogen at 25 ℃, 2mL of toluene is added, and 0.20mmol of N-2,2, 2-trifluoro-1-phenylethylfluorenone imine, 0.22mmol of cinnamyl methyl carbonate and 0.20mmol of 1, 8-diazabicycloundecen-7-ene are sequentially added for reaction at 50 ℃. The reaction was monitored by thin layer chromatography and, after completion of the reaction, the solvent was removed under reduced pressure and the product was purified by silica gel (treated with triethylamine) column chromatography.
2)
Figure BDA0002139747690000293
Preparation of
The product obtained in step 1) was dissolved in 1mL of dichloroethane, added with a methanol solution of hydroxylamine acetate (0.5M, 1mL, prepared from hydroxylamine hydrochloride, sodium hydroxide and acetic acid in methanol), and reacted at 50 ℃ for 3 hours. Removal of the solvent under reduced pressure followed by purification by column chromatography on silica gel (treated with triethylamine) gave a yellow solid in 90% yield, m.p. 36-38 ℃, with 98% enantioselectivity of the product, HPLC (Chiralpak IE, i-propanol/hexane: 5/95, flow rate 1.0mL/min,. lambda. 254 nm); t is tr＝4.92and 5.62min.[α]25 D＝117.0(c 0.53,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.62(dd,J＝7.6,1.7Hz,2H),7.45–7.32(m,3H),7.24(d,J＝3.6Hz,4H),7.22–7.16(m,1H),6.48(dt,J＝15.7,1.4Hz,1H),5.96–5.84(m,1H),3.06(ddd,J＝14.2,6.8,1.4Hz,1H),2.83(ddd,J＝14.2,8.0,1.2Hz,1H),1.82(s,2H).13C NMR(101MHz,CDCl3)δ137.6,136.7,135.1,128.5,128.4,128.2,127.5,127.0(q,J＝285.1Hz),126.8,126.2,122.6,61.3(q,J＝25.8Hz),40.2.19F NMR(376MHz,CDCl3) Delta-77.51.; HRMS (ESI +) calculated value C17H17F3N([M+H]+) 292.1308, measurement 292.1304.
3)
Figure BDA0002139747690000301
Preparation of
0.5mmol of the compound prepared in the step 2) was added to a 25mL reaction tube
Figure BDA0002139747690000302
1mmol NaHCO3And 3mL of acetonitrile, placing the reaction tube at a low temperature of-20 ℃, and adding 1mmol of I2After 12h of reaction, the reaction was quenched by the addition of 5mL of dichloromethane and 2mL of saturated sodium thiosulfate solution. The phases were separated, the aqueous phases were extracted with dichloromethane and combined, the solvent was evaporated and the product was chromatographed on a silica gel column (petrol ether/ethyl acetate 5:1) to give a pale yellow solid in 95% yield, melting point 62-64 ℃, enantioselectivity of the product 97%, HPLC (Chiralpak OD-H, i-propanol/hexane: 3/97, flow rate 1.0mL/min,. lambda.260 nm); t is tr＝28.02and 32.50min.[α]25 D＝-3.4(c16.1,CH2Cl2)；1H NMR(400MHz,CDCl3)δ7.54(d,J＝7.5Hz,2H),7.41–7.36(m,2H),7.36–7.26(m,5H),4.56(dd,J＝9.9,5.2Hz,1H),3.66(td,J＝10.4,8.0Hz,1H),3.07–2.92(m,2H),2.53(d,J＝5.4Hz,1H).13C NMR(101MHz,CDCl3)δ139.2,138.7,128.6,128.4,128.3,127.5,127.2,127.0(d,J＝297.9Hz),72.1,68.5(q,J＝27.2Hz),47.0,25.1.19F NMR(376MHz,CDCl3) Delta-77.02.; HRMS (ESI +) calculated value C17H16F3IN([M+H]+) 418.0274, measurement 418.0264.

Claims (10)

1. A chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound is characterized in that: the structure of the compound is shown in the following formula I,
Figure FDA0002139747680000011
wherein the content of the first and second substances,
R1is any one of substituted or unsubstituted aryl and hydrogen, and the substituent in the substituted aryl is alkyl or halogen;
R2is monofluoromethyl, difluoromethyl, trifluoromethyl, C2-5Any of the perfluoroalkyl groups of (a);
R3is hydrogen, substituted or unsubstituted aryl, substituted or unsubstituted unsaturated heterocyclic radical, C1-C6Any one of a chain or cyclic alkane, wherein a heteroatom contained in the substituted or unsubstituted unsaturated heterocyclic group is N, O, S, and a substituent in the substituted aryl group is any one of an alkyl group, an alkoxy group, a halogen group and an alkenyl group;
R4is any one of hydrogen, substituted or unsubstituted aryl and alkane.
2. A method for preparing the chiral α -polysubstituted- α -fluoro-homoallylamine compound of claim 1, wherein: the method mainly comprises the following steps of,
taking an iridium complex as a catalyst, and carrying out catalytic reaction on a substrate-1 and a substrate-2 to obtain a chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound shown in a formula I;
Figure FDA0002139747680000012
wherein the content of the first and second substances,
R1is any one of substituted or unsubstituted aryl and hydrogen, and the substituent in the substituted aryl is alkyl or halogen;
R2is monofluoromethyl, difluoromethyl, trifluoromethyl, C2-5Any of the perfluoroalkyl groups of (a);
R3is hydrogen, substituted or unsubstituted aryl, substituted or unsubstituted unsaturated heterocyclic radical, C1-C6Any of chain or cyclic alkanesWherein the heteroatom contained in the substituted or unsubstituted unsaturated heterocyclic group is N, O, S, and the substituent in the substituted aryl group is any one of alkyl, alkoxy, halogen and alkenyl;
R4is any one of hydrogen, substituted or unsubstituted aryl and alkane.
3. The process for preparing chiral α -polysubstituted- α -fluoro-homoallylamines of claim 2, wherein: the method comprises the following specific steps:
under the protection of inert gas, dissolving a substrate-1, a substrate-2, an iridium complex and 1-10 equivalent of organic base in an organic solvent, completely reacting at 0-110 ℃, and performing column chromatography to obtain a chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound with the structure of the formula I;
wherein the concentration range of the substrate-1 is 0.001-3.0M, the concentration range of the substrate-2 is 0.001-3.0M, and the molar ratio of the substrate-1 to the substrate-2 is 1: 0.1-10; the dosage of the iridium complex is 0.0001-10 mol% of the lower concentration of the substrate-1 or the substrate-2; the organic base is any one of triethylamine, tetramethylethylenediamine, 1, 5-diazabicyclo [4.3.0] non-5-ene, 1, 8-diazabicycloundecen-7-ene, 1, 4-diazabicyclo [2.2.2] octane, pyridine, 4-dimethylaminopyridine, N-methylmorpholine, triethylenediamine, tetramethylguanidine and 2-tert-butyl-1, 1,3, 3-tetramethylguanidine; the organic solvent is at least one of methanol, ethanol, isopropanol, tert-butanol, sec-butanol, ethyl acetate, isobutyl acetate, isopropyl acetate, N-hexane, cyclohexane, N-heptane, acetone, butanone, diethyl ether, methyl tert-butyl ether, methyl cyclopentyl ether, methyl tetrahydrofuran, acetonitrile, dichloromethane, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, toluene and dioxane.
4. The process for preparing chiral α -polysubstituted- α -fluoro-homoallylamines of claim 2 or 3, wherein: the iridium complex is prepared by the following method:
dissolving metal iridium salt and chiral ligand L1 in an organic solvent at a molar ratio of 1:2 at 50 ℃, adding organic base, and reacting to obtain the iridium complex;
wherein the content of the first and second substances,
the metal iridium salt is [ Ir (COD) Cl]2、[Ir(DBCOT)Cl]2、[Ir(COD)OMe]2Any one of (a);
the structural formula of the chiral ligand L1 is any one of the following formulas:
Figure FDA0002139747680000021
the organic solvent is at least one of methanol, ethanol, isopropanol, tert-butanol, sec-butanol, ethyl acetate, isobutyl acetate, isopropyl acetate, N-hexane, cyclohexane, N-heptane, acetone, butanone, diethyl ether, methyl tert-butyl ether, methyl cyclopentyl ether, methyl tetrahydrofuran, acetonitrile, dichloromethane, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, toluene and dioxane;
the organic base is any one of triethylamine, tetramethylethylenediamine, 1, 5-diazabicyclo [4.3.0] non-5-ene, 1, 8-diazabicycloundecen-7-ene, 1, 4-diazabicyclo [2.2.2] octane, pyridine, 4-dimethylaminopyridine, N-methylmorpholine, triethylenediamine, tetramethylguanidine and 2-tert-butyl-1, 1,3, 3-tetramethylguanidine.
5. The use of a chiral α -polysubstituted- α -fluoro-homoallylamine compound of claim 1, wherein: the chiral alpha-polysubstituted-alpha-fluorine-containing high allylamine compound is applied to the preparation of a chiral alpha-polysubstituted-alpha-fluorine-containing high allylamine compound II and the preparation of a derivative with a chiral tetrahydropyrrole structure;
the structural formula of the chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound II is shown in the specification
Figure FDA0002139747680000031
Said has chiralityThe structural formula of the derivative with the tetrahydropyrrole structure is shown in the specification
Figure FDA0002139747680000032
Wherein R is1Is any one of substituted or unsubstituted aryl and hydrogen, wherein the substituent in the substituted aryl is alkyl or halogen, R2Is monofluoromethyl, difluoromethyl, trifluoromethyl, C2-5Any of the perfluoroalkyl groups of (1), R3Is hydrogen, substituted or unsubstituted aryl, substituted or unsubstituted unsaturated heterocyclic radical, C1-C6Any one of chain or cyclic alkanes, wherein the heteroatom contained in the substituted or unsubstituted unsaturated heterocyclic group is N, O, S, the substituent in the substituted aryl group is any one of alkyl, alkoxy, halogen and alkenyl, and R is4Is any one of hydrogen, substituted or unsubstituted aryl and alkane.
6. The use of chiral α -polysubstituted- α -fluoro homoallylamines according to claim 5 wherein: the application of the chiral alpha-polysubstituted-alpha-fluorine-containing high allylamine compound to the preparation of the chiral alpha-polysubstituted-alpha-fluorine-containing high allylamine compound II comprises the following steps:
hydrolyzing the chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound in the formula I in acid to obtain a chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound II in the following formula II,
Figure FDA0002139747680000033
wherein the content of the first and second substances,
R1is any one of substituted or unsubstituted aryl and hydrogen, and the substituent in the substituted aryl is alkyl or halogen;
R2is monofluoromethyl, difluoromethyl, trifluoromethyl, C2-5Any of the perfluoroalkyl groups of (a);
R3is hydrogen, substituted or unsubstituted aryl, substituted or unsubstitutedSubstituted unsaturated heterocyclic radical, C1-C6Any one of a chain or cyclic alkane, wherein a heteroatom contained in the substituted or unsubstituted unsaturated heterocyclic group is N, O, S, and a substituent in the substituted aryl group is any one of an alkyl group, an alkoxy group, a halogen group and an alkenyl group;
R4is any one of hydrogen, substituted or unsubstituted aryl and alkane.
7. The use of chiral α -polysubstituted- α -fluoro homoallylamines according to claim 5 wherein: the application of the chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound in preparing derivatives with chiral tetrahydropyrrole structures comprises the following steps:
(1) hydrolyzing the chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound in the formula I in acid to obtain a chiral alpha-polysubstituted-alpha-fluorine-containing homoallylamine compound II in the following formula II:
Figure FDA0002139747680000041
(2) dissolving the chiral alpha-polysubstituted-alpha-fluorine-containing high allylamine compound II obtained in the step (1) in an organic solvent, adding 1 to 10 equivalents of carbonate or bicarbonate and 1 to 5 equivalents of iodine elementary substance, reacting at (-40) -0 ℃, adding a saturated solution of sodium thiosulfate after the reaction reaches balance, quenching, and performing column chromatography to obtain a target product, namely the derivative with the chiral tetrahydropyrrole structure:
Figure FDA0002139747680000042
wherein the content of the first and second substances,
R1is any one of substituted or unsubstituted aryl and hydrogen, and the substituent in the substituted aryl is alkyl or halogen;
R2is monofluoromethyl, difluoromethyl, trifluoromethyl, C2-5Any of the perfluoroalkyl groups of (a);
R3is hydrogen, substituted or unsubstituted aryl, substituted or unsubstituted unsaturated heterocyclic radical, C1-C6Any one of a chain or cyclic alkane, wherein a heteroatom contained in the substituted or unsubstituted unsaturated heterocyclic group is N, O, S, and a substituent in the substituted aryl group is any one of an alkyl group, an alkoxy group, a halogen group and an alkenyl group;
R4is any one of hydrogen, substituted or unsubstituted aryl and alkane.
8. The use of chiral α -polysubstituted- α -fluoro homoallylamines according to claim 6 or 7 wherein: the hydrolysis temperature is 0-100 ℃, the hydrolysis time is 0.5-24 hours, the acid is any one of citric acid, hydrochloric acid, methanesulfonic acid, p-toluenesulfonic acid, acetic acid, sulfuric acid, hydroxylamine hydrochloride and hydroxylamine acetate, and the dosage of the acid is 1-20 times of that of the substrate-1 or substrate-2 with lower concentration.
9. The use of chiral α -polysubstituted- α -fluoro homoallylamines according to claim 7 wherein: in the step (2), silica gel is used as a filling material for the column chromatography, a mixed solvent of petroleum ether and ethyl acetate is used as an eluent, and the volume ratio of the petroleum ether to the ethyl acetate is 3-20: 1; the organic solvent is at least one of methanol, ethanol, isopropanol, tert-butanol, sec-butanol, ethyl acetate, isobutyl acetate, isopropyl acetate, N-hexane, cyclohexane, N-heptane, acetone, butanone, diethyl ether, methyl tert-butyl ether, methyl cyclopentyl ether, methyl tetrahydrofuran, acetonitrile, dichloromethane, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, toluene and dioxane.
10. The use of chiral α -polysubstituted- α -fluoro homoallylamines according to claim 5 wherein: the chiral alpha-polysubstituted-alpha-fluorine-containing high allylamine compound II can be used for preparing antidepressant drugs, antitumor drugs and natural drugs with chiral amine structural units; the derivatives having a chiral tetrahydropyrrole structure are useful as organic catalysts.
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