CN104387310B - There is optically active 3-vinyl indoline-like derivative and method of asymmetric synthesis thereof - Google Patents

There is optically active 3-vinyl indoline-like derivative and method of asymmetric synthesis thereof Download PDF

Info

Publication number
CN104387310B
CN104387310B CN201410634543.9A CN201410634543A CN104387310B CN 104387310 B CN104387310 B CN 104387310B CN 201410634543 A CN201410634543 A CN 201410634543A CN 104387310 B CN104387310 B CN 104387310B
Authority
CN
China
Prior art keywords
compound
degrees celsius
dibenzalacetone
general formula
chloroform
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN201410634543.9A
Other languages
Chinese (zh)
Other versions
CN104387310A (en
Inventor
肖文精
李天任
谭芬
陆良秋
陈加荣
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Huazhong Normal University
Original Assignee
Huazhong Normal University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Huazhong Normal University filed Critical Huazhong Normal University
Priority to CN201410634543.9A priority Critical patent/CN104387310B/en
Publication of CN104387310A publication Critical patent/CN104387310A/en
Application granted granted Critical
Publication of CN104387310B publication Critical patent/CN104387310B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/12—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Catalysts (AREA)

Abstract

The present invention relates to a class and there is optically active 3-vinyl indoline-like derivative and method of asymmetric synthesis thereof.It has the structural formula represented by formula I, r 1for hydrogen, 4-fluorine, 5-methyl, 5-methoxyl group, 5-bromine, 6-chlorine, 7-fluorine; R 2for phenyl, p-methoxyphenyl, p-methylphenyl, to fluorophenyl, rubigan, adjacent fluorophenyl, a bromophenyl, 2-thiophene, 2-furans, oxyethyl group, styryl, isobutyl-.Synthetic method: under metal catalyst three (dibenzalacetone) two palladium chloroform adducts and ligand i V exist, in chloroform solvent, general formula II and general formula III are represented, and compound obtains through decarboxylation allylation/cyclisation cascade reaction.The present invention, by adopting cycloaddition mode, only needs single stepping, efficient, high enantioselectivity ground synthesis can have optically active 3-vinyl indoline-like derivative, yield 63-99%, dr > 99.5%, ee83-99%.

Description

There is optically active 3-vinyl indoline-like derivative and method of asymmetric synthesis thereof
Technical field
The present invention relates to and there is optically active 3-vinyl indoline-like derivative and method of asymmetric synthesis thereof.
Background technology
Indoline-like derivative is the very important heterocyclic compound of a class, is extensively present in multiple natural product and drug molecule, its widely biological activity cause the interest of more and more chemist.
The synthetic method of the efficient highly selective of indoline-like compound, is subject to the extensive concern of chemists always.And traditional synthesis has the method for optically active indoline skeleton to mainly contain following three kinds: split racemic indoline, to the asymmetric hydrogenation of Benzazole compounds, and the linked reaction of Amines to halogen substiuted.Although these methods respectively have its characteristics and advantages, all in all, there is raw material and be not easy to obtain, functional group's limitation is large, complex steps, and the shortcoming such as running cost is higher.
We utilize simple starting raw material, take sulfur ylide as key reagents, under the effect of catalyzing by metal palladium, the synthesis of high-efficiency high-stereoselectivity has optically active indoline-like framework compound, and achieve for having the indoline of anti-microbial activity and the synthesis of oxazoline ketone compounds conversion, demonstrate the practicality of the method further.
Summary of the invention
The object of the invention is to provide one to have optically active 3-vinyl indoline-like derivative and preparation method thereof.The method by by three (dibenzalacetone) two palladium chloroform adducts and chiral phosphoramidite ligand catalysis 4-vinyl benzoxazinone with stable sulfur ylide through decarboxylation allylation/cyclisation cascade reaction, can synthesize and have optically active 3-vinyl indoline-like derivative in efficient, high enantioselectivity ground.
The class that the present invention proposes has optically active 3-vinyl indoline-like derivative, it is characterized in that the structural formula had represented by formula I,
R in formula I 1for hydrogen, 4-fluorine, 5-methyl, 5-methoxyl group, 5-bromine, 6-chlorine, 7-fluorine;
R 2for phenyl, p-methoxyphenyl, p-methylphenyl, to fluorophenyl, rubigan, adjacent fluorophenyl, a bromophenyl, 2-thiophene, 2-furans, oxyethyl group, styryl, isobutyl-.
Above-mentioned with the method for asymmetric synthesis with optically active 3-vinyl indoline-like derivative represented by general formula I, the steps include: under the existence of metal catalyst three (dibenzalacetone) two palladium chloroform adducts and ligand i V, in chloroform solvent, the compound that general formula II and general formula III are represented obtains through decarboxylation allylation/cyclisation cascade reaction, and synthetic route is as follows:
R in formula I 1for hydrogen, 4-fluorine, 5-methyl, 5-methoxyl group, 5-bromine, 6-chlorine, 7-fluorine; R 2for phenyl, p-methoxyphenyl, p-methylphenyl, to fluorophenyl, rubigan, adjacent fluorophenyl, a bromophenyl, 2-thiophene, 2-furans, oxyethyl group, styryl, isobutyl-; R in Shi Ⅱ ﹑ III 1, R 2definition and formula I in R 1, R 2definition identical, wherein Ts is p-toluenesulfonyl, and dba is dibenzalacetone, CHCl 3for chloroform.
By such scheme, the mol ratio of the compound that described general formula II represents and the compound that general formula III represents is 1:1.5-1:3.
By such scheme, the consumption of described metal catalyst three (dibenzalacetone) two palladium chloroform adducts is calculated in molar ratio as the 2.5-10wt% of the compound that general formula II represents.
By such scheme, the mol ratio of described ligand i V and metal catalyst three (dibenzalacetone) two palladium chloroform adducts is 2.2-4.4:1.
By such scheme, the described reaction times is 12-72h.
By such scheme, described productive rate: 63-99%, diastereo-isomerism sex ratio dr > 99.5%, enantiomeric excess ee83-99%.
Aforesaid method concrete steps are: at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts and ligand i V are dissolved in chloroform; stir under nitrogen protection; then-40 to-20 degrees Celsius are cooled to; add the compound that general formula II represents subsequently, after continuing to keep temperature to stir, then compound general formula III represented joins in reaction system; reaction mixture is continued to keep thermotonus until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I target product.
Beneficial effect of the present invention: the present invention is by adopting the mode of cycloaddition, only need single stepping, 4-vinyl benzoxazinone and stable sulfur ylide can be made to carry out decarboxylation allylation/cyclisation cascade reaction under palladium chloroform adducts and chiral phosphoramidite ligand catalysis at three (dibenzalacetone) two, efficiently, high enantioselectivity ground synthesis has optically active 3-vinyl indoline-like derivative, yield 63-99%, dr > 99.5%, ee83-99%.
Embodiment
The preparation method of compound in I formula of the present invention is illustrated below by example.Only the present invention will be described for these examples, and do not limit the invention.
The steric configuration of the compound of following embodiment synthesis is through X-ray single crystal diffraction confirmation, and the diastereomer ratio dr of product measures with 400,000,000 nuclear magnetic resonance spectrometers, and enantiomeric excess ee value chirality HPLC instrument measures; HPLC analyzes and uses chirality AD-H, AS-H, OD-H, IC-H post.
The intermediate 4-vinyl benzoxazinone II-1 mentioned in following embodiment, 2,3,4,5,6, the compound shown in 7 is respectively middle R 1for each compound that hydrogen, 5-methoxyl group, 5-methyl, 5-bromine, 6-chlorine, 4-fluorine, 7-fluorine are corresponding;
Sulfur ylide III-1,2,3,4,5,6,7,8,9,10,11, the compound shown in 12 is respectively middle R 2for phenyl, p-methoxyphenyl, p-methylphenyl, rubigan, the compound corresponding to fluorophenyl, adjacent fluorophenyl, a bromophenyl, 2-thiophene, 2-furans, oxyethyl group, styryl, isobutyl-.
Embodiment 1
Compound I-1
preparation
At room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg, 0.01mmol) and ligand i V (12.6mg, 0.022mmol) are dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-1 (66mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-1 (54mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-1 target product 80.7mg, productive rate 99%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝8.00(d,J＝7.5Hz,2H),7.75(d,J＝8.0Hz,2H),7.62(t,J＝9.6Hz,2H),7.50(t,J＝7.6Hz,2H),7.27(d,J＝7.8Hz,3H),7.02(t,J＝7.2Hz,1H),6.97(d,J＝7.4Hz,1H),5.44–5.35(m,1H),5.32(d,J＝4.9Hz,1H),4.98(dd,J＝32.0,13.4Hz,2H),3.83–3.77(m,1H),2.40(s,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)194.2,144.3,141.3,136.6,134.6,134.0,133.6,131.1,129.7,128.9,128.8,128.7,127.4,125.4,124.1,117.4,115.0,71.0,50.2,21.5。
IR：3064,1701,1597,1478,1350,1168,1088,663,577cm -1。
High resolution: calculated value: [M+Na] +: 426.1134, measured value: 426.1134.
[ α ] D = - 4.0250 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 94% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=13.18 minutes, t 2=21.88 minutes.
Embodiment 2
Compound I-2
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-1 (66mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-2 (63mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-2 target product 86.6mg, productive rate 99%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.98(d,J＝8.5Hz,2H),7.74(d,J＝7.9Hz,2H),7.64(d,J＝8.0Hz,1H),7.25(d,J＝7.2Hz,3H),7.03–6.97(m,1H),6.95(d,J＝8.3Hz,3H),5.39-5.33(m,1H),5.29(d,J＝4.7Hz,1H),5.00-4.92(m,2H),3.85(s,3H),3.79-3.76(m,1H),2.37(s,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)192.8,163.9,144.3,141.3,136.7,134.6,131.3,129.7,128.8,127.4,126.8,125.4,124.1,117.4,115.0,114.0,70.7,55.5,50.5,21.5。
IR：3445,2929,1688,1599,1358,1259,1167,755,664,576cm -1。
High resolution: calculated value: [M+Na] +: 456.1240, measured value: 456.1248.
[ α ] D = 70.2250 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 92% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=16.100 minutes, t 2=41.838 minutes.
Embodiment 3
Compound I-3
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-1 (66mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-3 (60mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-3 target product 74.6mg, productive rate 92%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.90(d,J＝7.2Hz,2H),7.74(d,J＝7.2Hz,2H),7.64(d,J＝7.9Hz,1H),7.29-7.25(m,5H),7.04–6.92(m,2H),5.41-5.37(m,1H),5.32(s,1H),4.97(dd,J＝21.5,13.4Hz,2H),3.78(s,1H),2.42(s,3H),2.38(s,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝193.7,144.6,144.3,141.3,136.6,134.6,131.4,131.2,129.6,129.4,129.0,128.7,127.3,125.3,124.0,117.3,115.0,70.8,50.3,21.6,21.5。
IR：3447,2958,2923,1694,1601,1360,1167,1093,816,663,578。
High resolution: calculated value: [M+Na] +: 440.1291, measured value: 440.1295.
[ α ] D = 70.2250 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 94% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=13.369 minutes, t 2=25.607 minutes.
Embodiment 4
Compound I-4
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-1 (66mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-4 (62mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-4 target product 84.4mg, productive rate 98%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.94(d,J＝8.5Hz,2H),7.73(d,J＝8.1Hz,2H),7.64(d,J＝8.1Hz,1H),7.44(d,J＝8.4Hz,2H),7.26(t,J＝7.1Hz,3H),7.04–6.92(m,2H),5.42–5.29(m,1H),5.23(d,J＝5.2Hz,1H),4.98(dd,J＝23.7,13.4Hz,2H),3.79(dd,J＝8.2,5.4Hz,1H),2.37(s,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝193.3,144.6,141.1,140.1,136.4,134.2,132.4,131.0,130.4,129.8,129.1,128.9,127.4,125.5,124.3,117.8,115.0,71.1,50.2,21.5。
IR：3063,2914,1697,1593,1479,1404,1165,1092,754,662,578,536cm -1。
High resolution: calculated value: [M+Na] +: 460.0745, measured value: 460.0739.
[ α ] D = 18.0500 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 91% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=12.330 minutes, t 2=24.346 minutes.
Embodiment 5
Compound I-5
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-1 (66mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-5 (60mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-5 target product 84.0mg, productive rate 99%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝8.06–8.02(m,2H),7.74(d,J＝8.0Hz,2H),7.64(d,J＝8.0Hz,1H),7.27(d,J＝7.6Hz,3H),7.16(t,J＝8.4Hz,2H),7.04-6.97(m,2H),5.43–5.31(m,1H),5.23(d,J＝5.1Hz,1H),5.00(dd,J＝22.3,13.4Hz,2H),3.84–3.74(m,1H),2.39(s,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝192.9,166.0(d,J＝255Hz),144.5,141.2,136.5,134.3,131.8(d,J＝10Hz),131.0,130.4,129.7,128.9,127.4,125.4,124.2,117.7,115.9(d,J＝22Hz),115.0,71.0,50.3,21.5。
IR：3442,2957,2923,1702,1598,1352,1238,1167,1092,761,663,576cm -1。
High resolution: calculated value: [M+Na] +: 444.1040, measured value: 444.1047.
[ α ] D = - 14.8750 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 95% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=11.115 minutes, t 2=12.139 minutes.
Embodiment 6
Compound I-6
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-1 (66mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-6 (60mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-6 target product 78.3mg, productive rate 90%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝8.03(dd,J＝8.6,5.4Hz,2H),7.73(d,J＝8.2Hz,2H),7.63(d,J＝8.1Hz,1H),7.26(d,J＝8.0Hz,3H),7.14(t,J＝8.5Hz,2H),7.04–6.95(m,2H),5.45–5.32(m,1H),5.25(d,J＝5.2Hz,1H),4.98(dd,J＝23.8,13.4Hz,2H),3.79(dd,J＝8.3,5.3Hz,1H),2.38(s,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝192.9,166.0(d,J＝255Hz),144.5,141.2,136.5,134.3,131.7(d,J＝9Hz),131.0,130.5,130.4,129.8,128.9,127.4,125.4,124.2,117.7,115.9(d,J＝22Hz),115.0,71.1,50.3,21.5
IR：3444,3083,1702,1597,1360,1235,1165,1093,757,664,575cm -1。
High resolution: calculated value: [M+Na] +: 444.1040, measured value: 444.1049.
[ α ] D = - 13.9000 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 95% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=10.259 minutes, t 2=24.023 minutes.
Embodiment 7
Compound I-7
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-1 (66mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-7 (70mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-7 target product 73.5mg, productive rate 75%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝8.13(s,1H),7.92(d,J＝7.6Hz,1H),7.74(d,J＝8.0Hz,3H),7.62(d,J＝8.1Hz,1H),7.37(t,J＝7.8Hz,1H),7.29–7.26(m,3H),7.03(t,J＝7.4Hz,1H),6.98(d,J＝7.1Hz,1H),5.42–5.34(m,1H),5.22(d,J＝5.1Hz,1H),5.02(dd,J＝35.9,13.4Hz,2H),3.83–3.77(m,1H),2.41(s,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝193.2,144.5,141.2,136.5,136.4,135.8,134.4,132.0,130.9,130.3,129.7,129.0,127.4,125.4,124.2,123.1,119.3,117.8,115.0,71.2,50.2,21.5。
IR：3442,2923,1703,1359,1167,932,663,577,539cm -1。
High resolution: calculated value: [M+Na] +: 504.0239, measured value: 504.0240.
[ α ] D = 18.0000 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 96% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=10.463 minutes, t 2=15.647 minutes.。
Embodiment 8
Compound I-8
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-1 (66mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-8 (55mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-8 target product 61.2mg, productive rate 79%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.87(d,J＝3.7Hz,1H),7.73(d,J＝8.3Hz,2H),7.70–7.67(m,2H),7.29(d,J＝7.5Hz,1H),7.25(d,J＝8.1Hz,2H),7.16–7.12(m,1H),7.05–6.98(m,2H),5.44–5.35(m,1H),5.00(d,J＝10.0Hz,1H),4.98–4.92(m,2H),3.93–3.87(m,1H),2.38(s,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝188.2,144.6,141.2,140.2,136.5,135.0,133.8,133.4,131.2,129.7,128.8,128.2,127.6,125.4,124.4,117.7,115.1,72.3,50.8,21.5。
IR：3089,2923,1755,1676,1598,1413,1359,1167,931,817,755,665,578cm -1。
High resolution: calculated value: [M+Na] +: 432.0699, measured value: 432.0697.
[ α ] D = - 57.2000 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 91% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=13.524 minutes, t 2=24.145 minutes.
Embodiment 9
Compound I-9
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-1 (66mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-9 (51mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-9 target product 69.6mg, productive rate 86%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.73(d,J＝7.9Hz,2H),7.65(d,J＝7.5Hz,2H),7.37(d,J＝3.5Hz,1H),7.29-7.24(m,3H),7.06–6.96(m,2H),6.61–6.54(m,1H),5.50–5.34(m,1H),5.03(d,J＝5.5Hz,1H),4.93(dd,J＝25.0,13.5Hz,2H),3.88–3.83(m,1H),2.38(s,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝183.9,150.1,147.4,144.5,141.3,136.6,133.9,131.1,129.7,128.8,127.5,125.4,124.2,119.7,117.4,115.1,112.6,71.1,50.3,21.5。
IR：2964,2926,1696,1462,1351,1165,1035,1010,754,670,581cm -1。
High resolution: calculated value: [M+Na] +: 416.0927, measured value: 416.0932.
[ α ] D = - 99.6550 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 99% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=12.828 minutes.
Embodiment 10
Compound I-10
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-1 (66mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-10 (50mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-10 target product 66.9mg, productive rate 91%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.70(d,J＝8.2Hz,2H),7.59(d,J＝8.1Hz,1H),7.25-7.21(m,3H),7.04–6.97(m,2H),5.45–5.29(m,1H),4.99–4.90(m,2H),4.40(d,J＝5.6Hz,1H),4.32–4.23(m,2H),3.94–3.85(m,1H),2.36(s,3H),1.31(t,J＝7.1Hz,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝170.4,144.4,141.0,136.5,134.0,131.1,129.6,128.6,127.5,125.1,124.1,117.3,115.0,68.2,61.8,50.1,21.4,14.0。
IR：2982,2928,1753,1598,1475,1361,1168,1090,931,755,664,579cm -1。
High resolution: calculated value: [M+Na] +: 394.1084, measured value: 394.1087.
[ α ] D = - 193.4900 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 93% of product, diastereomer ratio >95:5, chirality AS-H post (Virahol: normal hexane is 10:90, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=8.339 minutes, t 2=10.274 minutes.
Embodiment 11
Compound I-11
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-1 (66mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-11 (126mg, 0.6mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-11 target product 74.6mg, productive rate 86%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.78(d,J＝10.3Hz,1H),7.75(d,J＝2.4Hz,1H),7.65(d,J＝8.3Hz,2H),7.60(dd,J＝6.5,2.9Hz,2H),7.40–7.38(m,3H),7.34–7.27(m,2H),7.22(d,J＝8.2Hz,2H),7.09–7.01(m,2H),5.26–5.14(m,1H),4.90–4.83(m,2H),4.47(d,J＝5.1Hz,1H),4.02–3.91(m,1H),2.37(s,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝195.3,145.1,144.6,141.1,136.7,134.4,133.4,132.3,130.8,129.7,128.8,128.7,128.7,127.7,125.6,124.8,120.6,117.0,116.1,74.0,48.7,21.5。
IR：3448,2923,1697,1610,1359,1166,1093,854,623,577cm -1。
High resolution: calculated value: [M+Na] +: 452.1291, measured value: 452.1279.
[ α ] D = - 185.0300 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 87% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=10.175 minutes, t 2=14.542 minutes.
Embodiment 12
Compound I-12
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-1 (66mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-12 (104mg, 0.6mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-12 target product 64.8mg, productive rate 86%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.64(d,J＝8.1Hz,1H),7.51(d,J＝8.3Hz,2H),7.21-7.17(m,1H),7.11(d,J＝8.2Hz,2H),6.97(t,J＝7.3Hz,1H),6.91(d,J＝7.4Hz,1H),5.09-5.00(m,1H),4.78–4.66(m,2H),4.16(d,J＝5.0Hz,1H),3.77–3.60(m,1H),2.72(dd,J＝17.9,6.6Hz,1H),2.48(dd,J＝17.9,6.9Hz,1H),2.25(d,J＝10.0Hz,3H),2.11(dt,J＝13.4,6.7Hz,1H),0.87(d,J＝6.7Hz,3H),0.81(d,J＝6.7Hz,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)207.4,144.6,141.1,137.0,133.4,132.0,129.6,128.7,127.6,125.6,124.8,116.8,116.1,74.5,48.6,47.4,23.7,22.5,21.5。
IR：3448,2959,1717,1462,1360,1168,1091,757,664,578cm -1。
High resolution: calculated value: [M+Na] +: 406.1447, measured value: 406.1447.
[ α ] D = - 171.3800 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 95% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 10:90, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=8.260 minutes, t 2=9.631 minutes.
Embodiment 13
Breathe out compound I-13
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-2 (72mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-1 (54mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-13 target product 76.6mg, productive rate 86%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.98(d,J＝7.5Hz,2H),7.68(d,J＝8.2Hz,2H),7.64–7.56(m,2H),7.48(t,J＝7.7Hz,2H),7.26(d,J＝8.0Hz,2H),6.82(dd,J＝8.8,2.4Hz,1H),6.50(d,J＝2.2Hz,1H),5.22(t,J＝4.3Hz,1H),5.21–5.10(m,1H),4.96-4.89(m,2H),3.74(s,1H),3.72(s,3H),2.39(s,3H).。
13CNMR(100MHz,CDCl 3)δ(ppm)194.1,157.0,144.3,136.4,134.6,134.0,133.9,133.6,132.9,129.7,128.9,128.7,127.4,117.5,116.5,114.2,110.9,71.2,55.5,50.4,21.5。
IR：3443,2958,1703,1598,1487,1356,1164,668,548cm -1。
High resolution: calculated value: [M+Na] +: 456.1240, measured value: 456.1233.
[ α ] D = - 146.6250 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 93% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=17.779 minutes, t 2=25.864 minutes.
Embodiment 14
Compound I-14
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-3 (74mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-1 (54mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-14 target product 82.6mg, productive rate 98%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝8.03–7.95(m,2H),7.71(d,J＝8.3Hz,2H),7.61-7.55(m,2H),7.47(t,J＝7.7Hz,2H),7.28–7.23(m,2H),7.07(d,J＝8.4Hz,1H),6.76(s,1H),5.32–5.20(m,2H),4.95(dd,J＝18.2,13.4Hz,2H),3.74(dd,J＝8.6,4.8Hz,1H),2.37(s,3H),2.24(s,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝194.1,144.3,138.9,136.6,134.2,134.0,133.9,133.6,131.2,129.6,129.4,128.9,128.7,127.3,125.9,117.3,115.0,71.1,50.2,21.5,20.8。
IR：3443,2922,1704,1596,1487,1357,1165,784,666,588,543cm -1。
High resolution: calculated value: [M+Na] +: 440.1291, measured value: 440.1298.
[ α ] D = 38.8600 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 98% of product, diastereomer ratio >95:5, chirality AS-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=13.793 minutes, t 2=20.249 minutes.
Embodiment 15
Compound I-15
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-4 (80mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-1 (54mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-15 target product 88.0mg, productive rate 91%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.98(d,J＝7.5Hz,2H),7.73(d,J＝8.2Hz,2H),7.64(t,J＝7.3Hz,1H),7.51(t,J＝7.9Hz,3H),7.38(d,J＝7.1Hz,1H),7.30(d,J＝8.0Hz,2H),7.08(s,1H),5.38–5.28(m,2H),5.00(dd,J＝29.6,13.4Hz,2H),3.76(dd,J＝8.3,4.7Hz,1H),2.42(s,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝193.7,144.7,140.6,135.9,134.2,133.9,133.7,133.4,131.8,129.8,128.9,128.8,128.5,127.3,118.1,116.7,116.5,70.9,49.9,21.6。
IR：3446,1699,1595,1468,1356,1165,1087,1003,785,665,580,541cm -1。
High resolution: calculated value: [M+Na] +: 504.0239, measured value: 504.0225.
[ α ] D = - 3.4600 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 93% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 20:80, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=18.381 minutes, t 2=31.711 minutes.
Embodiment 16
Compound I-16
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-5 (74mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-1 (54mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-16 target product 83.0mg, productive rate 96%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.99–7.95(m,2H),7.75(d,J＝8.2Hz,2H),7.62(dd,J＝10.7,4.3Hz,2H),7.50(t,J＝7.8Hz,2H),7.30(d,J＝8.0Hz,2H),6.98(dd,J＝8.0,1.7Hz,1H),6.87(d,J＝8.0Hz,1H),5.40-5.35(m,2H),5.02(d,J＝10.0Hz,1H),4.94(d,J＝16.9Hz,1H),3.74(dd,J＝8.4,4.6Hz,1H),2.41(s,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝193.8,144.7,142.6,136.3,134.7,134.6,133.9,133.8,129.9,129.7,128.9,128.9,127.4,126.2,124.2,117.8,115.2,71.3,49.7,21.6。
IR：3448,1696,1594,1357,1167,938,788,667,587cm -1。
High resolution: calculated value: [M+Na] +: 460.0745, measured value: 460.0744.
[ α ] D = - 43.7100 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 95% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 15:85, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=61.020 minutes, t 2=64.626 minutes.
Embodiment 17
Compound I-17
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-6 (70mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-1 (54mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-17 target product 62.6mg, productive rate 79%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.98(d,J＝7.5Hz,2H),7.75(d,J＝8.2Hz,2H),7.63(t,J＝7.4Hz,1H),7.51(t,J＝7.7Hz,2H),7.42(d,J＝8.1Hz,1H),7.30–7.22(m,3H),6.69(t,J＝8.6Hz,1H),5.49(d,J＝3.2Hz,1H),5.46–5.37(m,1H),4.96(dd,J＝32.5,13.4Hz,2H),3.90(dd,J＝7.8,2.8Hz,1H),2.40(s,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝193.4,159.4(d,J＝248Hz),144.5,143.9(d,J＝8Hz),135.3,135.0,133.9,133.7,130.9,130.8,129.8,128.9,127.3,117.7(d,J＝20Hz),117.3,111.1(d,J＝20Hz),110.9(d,J＝3Hz),71.1,46.8,21.5。
IR：3395,3064,2963,2924,1701,1597,1462,1361,1168,1093,578cm -1。
High resolution: calculated value: [M+Na] +: 444.1040, measured value: 444.1039.
[ α ] D = 30.8700 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 91% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=17.337 minutes, t 2=30.989 minutes.
Embodiment 18
Compound I-18
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-7 (70mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-1 (54mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-18 target product 68.9mg, productive rate 89%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝8.01(d,J＝8.2Hz,2H),7.91(d,J＝8.0Hz,2H),7.63(t,J＝7.4Hz,1H),7.51(t,J＝7.7Hz,2H),7.29(d,J＝8.0Hz,2H),7.00–6.95(m,1H),6.96-6.90(m,1H),6.82(d,J＝7.1Hz,1H),6.10(d,J＝3.8Hz,1H),6.01-5.93(m,1H),5.17(dd,J＝24.5,13.4Hz,2H),3.84(dd,J＝8.4,3.7Hz,1H),2.41(s,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝194.5,151.0(d,J＝249Hz),143.9,137.2(d,J＝2Hz),136.1,135.9,134.0,133.9,129.3,128.9,128.9,127.7,125.5(d,J＝6Hz),120.9,117.7,116.6,116.4,71.2,50.6,21.6。
IR：3445,2964,1687,1484,1336,1262,1157,1091,547cm -1。
High resolution: calculated value: [M+Na] +: 444.1040, measured value: 444.1039.
[ α ] D = 70.2250 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 88% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=13.677 minutes, t 2=42.761 minutes.
Embodiment 19
Compound I-19
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-2 (73mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-10 (51mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-19 target product 74.1mg, productive rate 92%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.64(d,J＝7.8Hz,2H),7.55(d,J＝8.8Hz,1H),7.22(d,J＝7.8Hz,2H),6.79(d,J＝8.8Hz,1H),6.52(s,1H),5.23-5.17(m,1H),4.97–4.87(m,2H),4.34(d,J＝5.3Hz,1H),4.31-4.25(m,2H),3.85–3.80(m,1H),3.73(s,3H),2.37(s,3H),1.31(t,J＝7.1Hz,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)170.4,157.0,144.3,136.4,134.5,133.6,132.9,129.6,127.5,117.2,116.4,114.0,110.7,68.5,61.8,55.5,50.2,21.5,14.1。
IR：3477,2930,1738,1598,1487,1360,1168,1089,1032,666cm -1。
High resolution: calculated value: [M+Na] +: 424.1189, measured value: 424.1199.
[ α ] D 23 = - 154.7400 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 94% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=11.164 minutes, t 2=12.037 minutes.
Embodiment 20
Compound I-20
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-3 (69mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-10 (51mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-20 target product 72.6mg, productive rate 96%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.68(d,J＝8.2Hz,2H),7.49(d,J＝8.2Hz,1H),7.22(d,J＝8.0Hz,2H),7.04(d,J＝8.2Hz,1H),6.79(s,1H),5.32–5.26(m,1H),4.97–4.92(m,2H),4.35(d,J＝5.5Hz,1H),4.31–4.24(m,2H),3.84(t,J＝6.7Hz,1H),2.36(s,3H),2.25(s,3H),1.31(t,J＝7.1Hz,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝170.4,144.3,138.7,136.6,133.9,133.8,131.3,129.6,129.2,127.5,125.6,117.2,114.9,68.3,61.8,50.1,21.5,20.8,14.1。
IR：2981,2916,1749,1486,1359,1202,1170,1086,663,599,546cm -1。
High resolution: calculated value: [M+Na] +: 408.1240, measured value: 408.1239.
[ α ] D = - 146.7000 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 97% of product, diastereomer ratio >95:5, chirality IC-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=31.287 minutes, t 2=36.358 minutes.
Embodiment 21
Compound I-21
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-4 (80mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-10 (51mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-21 target product 61.6mg, productive rate 81%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.60(d,J＝8.2Hz,2H),7.41(d,J＝8.6Hz,1H),7.28(dd,J＝8.7,1.8Hz,1H),7.18(d,J＝8.1Hz,2H),7.03(s,1H),5.27–5.20(m,1H),4.89(dd,J＝17.5,13.5Hz,2H),4.31(d,J＝5.5Hz,1H),4.24–4.18(m,2H),3.81–3.77(m,1H),2.31(s,3H),1.24(t,J＝7.1Hz,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝170.0,144.7,140.3,135.8,133.7,133.5,131.6,129.7,128.2,127.4,117.9,116.8,116.5,68.4,62.0,49.7,21.5,14.1。
IR：2986,1752,1469,1358,1194,1165,1090,665,585cm -1。
High resolution: calculated value: [M+Na] +: 472.0189, measured value: 472.0193.
[ α ] D = - 192.2200 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 93% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=9.462 minutes, t 2=10.878 minutes.
Embodiment 22
Compound I-22
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-5 (74mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-10 (51mg, 0.3mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-22 target product 75.6mg, productive rate 84%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.71(d,J＝8.2Hz,2H),7.60(d,J＝1.6Hz,1H),7.27(d,J＝8.1Hz,2H),6.98(dd,J＝8.0,1.7Hz,1H),6.91(d,J＝8.1Hz,1H),5.40-5.32(m,1H),4.94(dd,J＝17.6,13.5Hz,2H),4.42(d,J＝5.3Hz,1H),4.31-4.25(m,2H),3.86–3.82(m,1H),2.39(s,3H),1.31(t,J＝7.1Hz,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝170.0,144.7,142.3,136.2,134.4,134.0,129.8,129.7,127.4,126.0,124.1,117.5,115.2,68.7,61.9,49.5,21.5,14.0。
IR：2982,2927,1755,1597,1475,1366,1167,1089,988,940,816,666,585cm -1。
High resolution: calculated value: [M+Na] +: 428.0694, measured value: 428.0688.
[ α ] D = - 436.1600 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 89% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=6.163 minutes, t 2=8.162 minutes.
Embodiment 23
Compound I-23
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-6 (70mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-10 (102mg, 0.6mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-23 target product 70.6mg, productive rate 87%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.69(d,J＝8.3Hz,2H),7.41(d,J＝8.1Hz,1H),7.23(dt,J＝4.6,3.0Hz,3H),6.72(t,J＝8.5Hz,1H),5.42-5.33(m,1H),4.95–4.74(m,2H),4.53(d,J＝3.6Hz,1H),4.29-4.22(m,2H),4.03(dd,J＝7.0,3.5Hz,1H),2.38(s,3H),1.30(t,J＝7.1Hz,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝169.9,159.3(d,J＝247Hz),144.6,143.5(d,J＝8Hz),135.2,134.5,130.7(d,J＝8Hz),129.7,127.3,117.8(d,J＝20Hz),116.7,111.4(d,J＝1Hz),111.2(d,J＝1Hz),68.5,62.0,46.7,21.5,14.1。
IR：2983,1753,1621,1461,1363,1168,1092,751,579cm -1。
High resolution: calculated value: [M+Na] +: 412.0989, measured value: 412.0986.
[ α ] D = - 22.5700 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 83% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 15:85, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=11.024 minutes, t 2=13.453 minutes.
Embodiment 24
I-24
preparation
At room temperature; at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts (10.35mg; 0.01mmol) with ligand i V (12.6mg; 0.022mmol) be dissolved in chloroform; stir 20 minutes under nitrogen protection, be then cooled to-40 degrees Celsius.Add 4-vinyl benzoxazinone II-7 (70mg subsequently, 0.2mmol), continue to stir after 5 minutes under-40 degrees Celsius, again by sulfur ylide III-10 (102mg, 0.6mmol) join in reaction system, reaction mixture continues reaction under-40 degrees Celsius until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I-24 target product 52.6mg, productive rate 62%.
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.97(d,J＝8.0Hz,2H),7.30(d,J＝8.1Hz,2H),7.02-6.98(m,1H),6.94–6.90(m,1H),6.89(d,J＝7.4Hz,1H),5.88-5.82(m,1H),5.17(dd,J＝16.3,13.5Hz,2H),5.09(d,J＝4.4Hz,1H),4.28–4.20(m,2H),4.04–3.99(m,1H),2.42(s,3H),1.28(t,J＝7.1Hz,3H)。
13CNMR(100MHz,CDCl 3)δ(ppm)＝170.1,144.8,142.3,136.2,134.1(d,J＝56Hz),129.8,129.8(d,J＝8Hz),127.4(d,J＝4Hz),126.1(d,J＝1Hz),124.23(d,J＝1Hz),119.4,117.7,115.3(d,J＝5Hz),68.7,62.0,49.5,21.6,14.1。
IR：2962,2925,1746,1623,1483,1163,1089,752,586cm -1。
High resolution: calculated value: [M+Na] +: 412.0989, measured value: 412.0993.
[ α ] D = - 5.5900 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 83% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 30:70, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=7.806 minutes, t 2=15.651 minutes.
Synthesis application example:
Above-claimed cpd can be used as synthesis precursor, and transform simple and fast get Dao oxazoline [3,4-a] indoles-3-ketone compounds through three steps, it is easy and simple to handle, and comprehensive yield is higher.Oxazoline [3,4-a] indoles-3-ketone compounds is a kind of very important antibacterial agent, but is not easily prepared by traditional method.
Target compound:
wherein R 4for r 3for H.
Synthetic method:
At room temperature, Compound I (0.2mmol, 80.7mg) is dissolved in 2ml methyl alcohol, system is cooled to 0 degree Celsius, then sodium borohydride (0.8mmol, 30.3mg) is added in reaction system.This system is stirred 2 hours under 0 degree Celsius.Add 5ml acetone cancellation excess sodium borohydrate, except desolventizing.Column chromatography for separation obtains target product V (80%yield, 93%ee, >95:5d.r.).
At room temperature, compound V (0.16mmol, 64.5mg) is dissolved in 1.6ml methyl alcohol, oxygen in removing system, then magnesium powder (1.6mmol, 38mg) is added in reaction system.By this system in 25 degrees Celsius of lower ultrasonic vibration 5 hours.After question response is complete, suction filtration, uses washed with dichloromethane filter cake, merges organic phase, except desolventizing.Gained crude product directly applies to next step operation.
At room temperature, previous action gained crude product is dissolved in 2ml methylene dichloride, carbonyl dimidazoles (CDI) (0.16mmol, 26mg) is joined in reaction system, in stirred at ambient temperature, until starting raw material completely consumed.By direct for reaction system column chromatography purification, obtain target product VI.
The steric configuration of target product VI is confirmed through two dimensional NMR, and other characterization information are as follows:
1HNMR(600MHz,CDCl 3)δ(ppm)＝7.49(d,J＝7.8Hz,1H),7.46–7.38(m,5H),7.35–7.29(m,1H),7.17–7.10(m,2H),5.88–5.75(m,1H),5.56(d,J＝7.3Hz,1H),5.36(dd,J＝16.5,13.6Hz,2H),4.44(dd,J＝9.0,7.3Hz,1H),4.20(t,J＝8.9Hz,1H).
13CNMR(100MHz,CDCl 3)δ(ppm)＝155.2,139.7,137.4,135.6,135.00,129.0,128.9,128.7,125.5,125.1,124.9,119.6,115.4,83.7,72.7,53.8.。
IR：2958,2923,1758,1480,1352,1167,1002,800,626cm -1。
High resolution: calculated value: [M+H] +: 278.1176, measured value: 278.1175.
[ α ] D = - 55.5800 ( c = 1.0 , CH Cl 3 ) .
Optical purity analysis: the enantiomeric excess 93% of product, diastereomer ratio >95:5, chirality AD-H post (Virahol: normal hexane is 15:85, v:v), 1.0mL/min, 254nm, 25 DEG C, retention time is t 1=10.876 minutes, t 2=13.489 minutes.

Claims (8)

1. a class has optically active 3-vinyl indoline-like derivative, it is characterized in that the structural formula had represented by formula I,
R in formula I 1for hydrogen, 4-fluorine, 5-methyl, 5-methoxyl group, 5-bromine, 6-chlorine, 7-fluorine;
R 2for phenyl, p-methoxyphenyl, p-methylphenyl, to fluorophenyl, rubigan, adjacent fluorophenyl, a bromophenyl, 2-thiophene, 2-furans, oxyethyl group, styryl, isobutyl-.
2. according to claim 1 with the method for asymmetric synthesis with optically active 3-vinyl indoline-like derivative represented by general formula I, it is characterized in that: step is: under the existence of metal catalyst three (dibenzalacetone) two palladium chloroform adducts and ligand i V, in chloroform solvent, the compound that general formula II and general formula III are represented obtains through decarboxylation allylation/cyclisation cascade reaction, and synthetic route is as follows:
R in formula I 1for hydrogen, 4-fluorine, 5-methyl, 5-methoxyl group, 5-bromine, 6-chlorine, 7-fluorine; R 2for phenyl, p-methoxyphenyl, p-methylphenyl, to fluorophenyl, rubigan, adjacent fluorophenyl, a bromophenyl, 2-thiophene, 2-furans, oxyethyl group, styryl, isobutyl-; R in Shi Ⅱ ﹑ III 1, R 2definition and formula I in R 1, R 2definition identical, wherein Ts is p-toluenesulfonyl, and dba is dibenzalacetone, CHCl 3for chloroform.
3. method of asymmetric synthesis according to claim 2, is characterized in that: the mol ratio of the compound that described general formula II represents and the compound that general formula III represents is 1:1.5-1:3.
4. method of asymmetric synthesis according to claim 2, is characterized in that: the consumption of described metal catalyst three (dibenzalacetone) two palladium chloroform adducts is calculated in molar ratio as the 2.5-10% of the compound that general formula II represents.
5. method of asymmetric synthesis according to claim 2, is characterized in that: the mol ratio of described ligand i V and metal catalyst three (dibenzalacetone) two palladium chloroform adducts is 2.2-4.4:1.
6. method of asymmetric synthesis according to claim 2, is characterized in that: the described reaction times is 12-72h.
7. method of asymmetric synthesis according to claim 2, is characterized in that: described synthetic method productive rate: 63-99%, diastereo-isomerism sex ratio dr > 99.5%, enantiomeric excess ee83-99%.
8. method of asymmetric synthesis according to claim 2; it is characterized in that: concrete steps are: at room temperature; metal catalyst three (dibenzalacetone) two palladium chloroform adducts and ligand i V are dissolved in chloroform; stir under nitrogen protection; then-40 to-20 degrees Celsius are cooled to; add the compound that general formula II represents subsequently; after continuing to keep temperature to stir; again the compound that general formula III represents is joined in reaction system; reaction mixture is continued to keep thermotonus until TLC detection reaction is complete, with V sherwood oil/ V ethyl acetate=30:1-12:1 column chromatography directly obtains formula I target product.
CN201410634543.9A 2014-11-12 2014-11-12 There is optically active 3-vinyl indoline-like derivative and method of asymmetric synthesis thereof Expired - Fee Related CN104387310B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201410634543.9A CN104387310B (en) 2014-11-12 2014-11-12 There is optically active 3-vinyl indoline-like derivative and method of asymmetric synthesis thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410634543.9A CN104387310B (en) 2014-11-12 2014-11-12 There is optically active 3-vinyl indoline-like derivative and method of asymmetric synthesis thereof

Publications (2)

Publication Number Publication Date
CN104387310A CN104387310A (en) 2015-03-04
CN104387310B true CN104387310B (en) 2016-04-27

Family

ID=52605288

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201410634543.9A Expired - Fee Related CN104387310B (en) 2014-11-12 2014-11-12 There is optically active 3-vinyl indoline-like derivative and method of asymmetric synthesis thereof

Country Status (1)

Country Link
CN (1) CN104387310B (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107573285B (en) * 2017-09-13 2019-12-17 华中师范大学 Novel method for asymmetric synthesis of quinolinone containing quaternary carbon center and derivatives thereof under catalysis of palladium
CN108440526B (en) * 2018-05-11 2020-10-16 北京工业大学 Chiral barbiturate spiro tetrahydroquinoline compound and preparation method thereof
CN115010644B (en) * 2022-06-09 2024-03-26 五邑大学 Preparation method of 2, 3-disubstituted indoline compound
CN115626926A (en) * 2022-11-01 2023-01-20 西安交通大学 Method for synthesizing spiro-skeleton containing three continuous stereocenters through stereo divergence
CN115894523A (en) * 2022-11-04 2023-04-04 西安交通大学 Method for synthesizing fused nitrogen heterocycle containing 1,3 discontinuous stereo center [7,6] by stereo divergence

Also Published As

Publication number Publication date
CN104387310A (en) 2015-03-04

Similar Documents

Publication Publication Date Title
CN104387310B (en) There is optically active 3-vinyl indoline-like derivative and method of asymmetric synthesis thereof
CN109748841B (en) Method for catalyzing asymmetric synthesis of chiral beta-aminoketone derivative
JP6266509B2 (en) Z-selective ring-closing metathesis reaction
Alcaide et al. Allenyl‐β‐lactams: versatile scaffolds for the synthesis of heterocycles
Nie et al. Chiral bifunctional thiourea-catalyzed enantioselective aldol reaction of trifluoroacetaldehyde hemiacetal with aromatic ketones
Karpov et al. A diversity oriented four-component approach to tetrahydro-β-carbolines initiated by Sonogashira coupling
CN110437128B (en) Synthetic method of 3-thioether-based isoindolinone compound
CN114437103B (en) Method for synthesizing chiral tetrahydrobenzoxepin compound through gold-catalyzed asymmetric cycloaddition reaction
CN102503976A (en) Alpha-quaternary carbon contained alpha, beta-diamino acid derivative, synthetic method thereof and application thereof
CN107286202A (en) Synthetic method and the application of chiral Ugi ' s amine and its derivative and optical isomer
Magar et al. Synthesis of substituted chiral chromans via organocatalytic kinetic resolution of racemic 3-nitro-2-aryl-2H-chromenes with ketones catalyzed by pyrrolidinyl-camphor-derived organocatalysts
CN105732495B (en) Tetrahydroquinolinesas with optical activation and preparation method thereof
CN107417615B (en) Novel preparation method of chiral quinolinone derivative promoted by visible light
CN111662158A (en) Preparation method of axial chiral biaryl compound and chiral fluorenol compound
CN108148021A (en) 2- imines (3H) furane derivative or thiophene derivant and its synthesis
EP1731509B1 (en) Process for producing nitrogenous 5-membered cyclic compound
CN105820174A (en) Polysubstituted thienoindole derivative and preparation method thereof
CN106892826A (en) A kind of preparation method and application of amine and imines N-methyl
CN113321675B (en) Chiral 3-methylene indoline compound and preparation method thereof
CN107417685A (en) Non-corresponding selectivity synthesis 1 aryl 1H pyridines [3,4 b] indole derivatives
CN103342674B (en) One class optical activity pyrrole derivative and synthetic method thereof
CN114644663A (en) Chiral tridentate nitrogen phosphine ligand and application thereof in asymmetric hydrogenation reaction of ketone
CN110655456B (en) Method for preparing chiral alkyl compound by asymmetric catalytic hydrogenation of E/Z mixed or single-configuration tri-substituted olefin
CN113200905A (en) Chiral indolone derivative and synthesis method thereof
CN111793017A (en) Preparation method of lactam compound

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20160427

Termination date: 20181112