CN110229085A - Alcohol promotes imines and alkynes reductive coupling reaction to construct allylamine derivatives - Google Patents

Alcohol promotes imines and alkynes reductive coupling reaction to construct allylamine derivatives Download PDF

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CN110229085A
CN110229085A CN201910195634.XA CN201910195634A CN110229085A CN 110229085 A CN110229085 A CN 110229085A CN 201910195634 A CN201910195634 A CN 201910195634A CN 110229085 A CN110229085 A CN 110229085A
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叶萌春
姚伟伟
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Nankai University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B45/00—Formation or introduction of functional groups containing sulfur
    • C07B45/04—Formation or introduction of functional groups containing sulfur of sulfonyl or sulfinyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The present invention relates to one kind using alcohol as green and cheap reducing agent, and in the cheap transition metal-catalyzed lower intermolecular reductive coupling reaction for realizing common imines and common interior alkynes, for efficiently preparing polysubstituted allylamine derivatives, this method is economical and practical.The key that the present invention solves the problems, such as is: 1. find a kind of high rich electrical carbenes raising reactivity of big steric hindrance, while the chirality control of part substrate is realized by designing chiral carbenes；2. cheap metal nickel is used in combination with green reducing agent isopropanol, economical and practical and environmental-friendly, meet continuable development principle.

Description

Alcohol promotes imines and alkynes reductive coupling reaction to construct allylamine derivatives
Technical field
The present invention relates to one kind from common interior alkynes and common imines, generates the synthetic method of allylamine derivatives, belongs to In reductive coupling reaction technical field.
Background technique
Allyl amine structure is not only present in many pesticides and drug molecule, and in organic synthesis especially pharmaceutical synthesis In be a kind of important intermediate, therefore it is how cheap and efficiently construct the application with higher of polysubstituted allyl amine structure and grind Study carefully value.In this way, synthesizing a series of three with can be convenient replaces allyl amine structure, substituent group can be aryl on alkenyl It is also possible to alkyl, and electron-donating group and the electrical group of suction are compatible on aryl substituent；α connected groups of alkenyl were both It can be aryl and be also possible to alkyl, aryl substituent inhales electrical group and electron-donating group, and aligns between neighbour It is compatible；By design improvement chirality carbenes, we can realize the chiral regulation of part substrate, therefore study pharmaceutical synthesis It is of great significance.
Currently, polysubstituted allylamine derivatives can be synthesized by the following method:
1) by alkenyl halogen or alkynes in-situ preparation alkenyl metal reagent, then alkenyl metal reagent and imines are anti-by addition Allylamine derivatives should be generated, or are catalyzed by Noble Metal Rhodium, it is derivative to obtain allylamine for alkenyl boron substrate and imine reaction Object: such method condition responsive needs the metal reagent extremely sensitive to air or water, needs anhydrous and oxygen-free condition, and operation is multiple Miscellaneous or alkenyl metal reagent needs pre-synthesis preparation, and needs noble metal catalyst, and reaction system substrate functional group is simultaneous Capacitive is poor.(Brak, K.；J.A.Ellman, J.A.J.Am.Chem.Soc.2009,131,3850)
2) propylamine derivative can be obtained by imines and alkynes direct-reduction coupling cheap and easy to get, when catalyst is When cheap metal Ni, reaction needs the Et of equivalent3B、ZnEt2When Deng being used as reducing agent, and use cleaning reducing agent H2, reaction is then Need noble metal Rh as catalyst: system is all very sensitive to water and oxygen, and metallic reducing agent end of reaction can generate equivalent Debirs, and environmental pollution is serious；And hydrogen as reducing agent when, then must using noble metal Rh as catalyst, Reaction cost is higher, and the system reaction substrate limits to.(Patel, S.J.；Jamison, T.F.Angew. Chem., Int.Ed.2003,42,1364；Zhou, C.Y.；Zhu, S.F；Wang, L.X.；Zhou, Q.L.J.Am.Chem. Soc.2010, 132,10955；Ngai, M-Y.；Barchuk, A.；Krische, M.J.J.Am.Chem.Soc.2007,129,12644)
Although existing synthetic method either walks in conclusion allylamine derivatives are significant in pharmaceutical synthesis Rapid cumbersome, operation requires stringent, and equivalents of metal reagent uses so that preparation cost increases, and environmental pollution is serious, and System is expensive, and production cost is higher, can not be mass produced.
Summary of the invention
The purpose of the present invention is to provide a kind of economical and practical methods, alcohol can be used as green and cheap reducing agent The catalysis of joint cheap metal realizes the reductive coupling reaction of common imines and alkynes to prepare propylamine derivative.
1. efficiently synthesizing the preparation method of allylamine derivatives, it is characterised in that the specific steps of this method are as follows:
It in nitrogen atmosphere, is sequentially added into reaction flask ligand (ligand), alkali (base), metallic catalyst MmXn, molten Agent (solvent) and alcohol (alcohol) are eventually adding raw material 1 and raw material 2 and stir 18 hours under assigned temperature, is cooled to room Temperature, diatomite filtering, concentration, column chromatography for separation obtain target product.
2. it is involved in the present invention to metallic catalyst be Ni (cod)2。
3. the nitrogen heterocycle carbine ligand involved in the present invention arrived, it can be alkyl-substituted carbenes, such as cyclohexyl, Methyl, tert-butyl etc., are also possible to the carbenes of aryl substitution, such as 2,6- diisopropyl phenyl replaces or 2, and 4,6- tri- Aminomethyl phenyl replaces, and can be benzoquinones skeleton electrophilic type carbenes, is also possible to acenaphthenequinone skeleton power supply subtype carbenes； It can also be chiral carbenes, chiral source can be chiral alkylamine, be also possible to chiral aniline.
When chiral carbenes are acenaphthenequinone class skeleton, chiral source is chiral aniline, chiral aniline contraposition R substituent can be with It is methyl or tert-butyl；Aniline pendant aryl substituent group can be the phenyl that phenyl is also possible to the substitution of 3,5- dimethyl.
4. alkali used in the present invention is potassium tert-butoxide etc., but is not only limited to this.
5. it is involved in the present invention to alcohol can be the primary alconols such as methanol, ethyl alcohol, normal propyl alcohol, benzylalcohol, be also possible to isopropanol, The secondary alcohol such as 1- phenylethanol, 2,4- dimethyl -3- amylalcohol, 2 methyl cyclohexanol, but it is not limited to these.
6. solvent for use of the present invention be can be tetrahydrofuran, benzene,toluene,xylene, trimethylbenzene, benzotrifluoride, DMF, Ethyl acetate etc., tetrahydrofuran is optimal, is that every mM of raw material 1 uses 5-10mL to application amount.
7. the reaction temperature involved in the present invention arrived can be within the scope of 60 DEG C to 140 DEG C, 100 DEG C of portion of product are optimal, 60 DEG C of chiral product optimal.
8. the raw materials used in the present invention 1 can be symmetrical alkyl alkynes, it is also possible to symmetrical aryl alkynes, aryl replaces Base can be in aryl in o-, m-, contraposition, and substituent group can be the electron-donating group such as methyl, ethyl and methoxyl group, is also possible to The electron-withdrawing groups such as fluorine or trifluoromethyl；It can also be asymmetric alkylaryl alkynes, be also possible to asymmetric alkyl alkynes Hydrocarbon.
9. R in the raw materials used in the present invention 24Substituent group can be p-methylphenyl and be also possible to tert-butyl, R3Substituent group can be with It is that aryl is also possible to alkyl, alkyl can be cyclohexyl, tert-butyl etc., but be not limited to these；Aryl can be phenyl, naphthalene And thiophene substituent group, wherein the substituent group on aryl can it is o-, m-, contraposition, can be electron-donating methyl, methoxyl group, N, N- dimethyl etc. is also possible to inhale electrical fluorine, trifluoromethyl etc., but is not limited to these groups.
10. R in products therefrom 3 of the present invention4Substituent group can be p-methylphenyl and be also possible to tert-butyl, R3Substituent group can To be alkyl or aryl substituent, R1And R2Can be identical, it can be all aryl be also all alkyl, R1And R2It can also be different, It can be aryl and alkyl, or different alkyl, it is above to be not limited to these groups.
The invention has the advantages that
1. the business gained of most reagent used in the present invention, the ligand stock that need to be synthesized is from a wealth of sources, cheap, and It can be stabilized under normal temperature and pressure, operation processing is convenient, without specially treated.
2. operation of the present invention is easy, target product is can be obtained in single step reaction, using alcohol cheap and easy to get as reducing agent, is kept away The alkenyl metal reagent of the previously prepared sensitivity of conventional method is exempted from；The zinc alkyl extremely sensitive to air and water is also avoided simultaneously The use of the hazardous agents such as reagent or alkyl boron reagent and silicon hydrogen reagent, it is simple to equipment requirement, facilitate subsequent processing work Sequence greatly reduces the production cost for synthesizing such compound, reduces the pollution to environment.
3. the present invention, as catalyst, avoids the use of Noble Metal Rhodium, iridium or ruthenium reagent using cheap metal.
4. the present invention is using the full carbon skeleton nitrogen heterocycle carbine ligand of stable to air and water chirality, can a step obtain light Learn pure allylamine derivatives.
5. byproduct of reaction of the invention is Ke Xunhuanliyong, no waste by-product is generated, and meets the requirement of Green Chemistry.
Specific implementation method
Following implementation example will better illustrate the present invention, but need to will be it is emphasised that the present invention is by no means limited to these Implement content represented by example.Following examples show not ipsilaterals of the invention.Given data include concrete operations and Reaction condition and product.Product purity is identified by nuclear-magnetism.Product chirality is detected by chiral high performance liquid chromatography.
Embodiment 1:(E) -4-Methyl-N- (1,2,3-triphenylallyl) benzenesulfonamide synthesis
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35.6mg, 0.2mmol) and 2a (62mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 3a, white solid, yield (81%) after concentration.1H NMR (400MHz, CDCl3) δ 7.69 (d, J=8.4Hz, 2H), 7.29-7.24 (m, 5H), 7.24-7.17 (m, 3H), 7.13 (t, J =7.6Hz, 2H), 7.09-6.99 (m, 3H), 6.78-6.72 (m, 2H), 6.8 (d, J=6.8Hz, 2H), 6.48 (s, 1H), 5.36 (d, J=7.6Hz, 1H), 4.83 (d, J=7.6Hz, 1H), 2.36 (s, 3H)13C NMR (100MHz, CDCl3)δ 143.5,139.8,139.2,137.7,137.3,136.0,130.1,129.6,129.5,129.3,128.8,128.7, 128.0,127.9,127.9,127.5,127.4,127.2,64.4,21.6.HRMS (ESI) calcd.for C28H29N2O2S ([M+NH4]+) 457.1944, Found 457.1942.
Embodiment 2:(E) -2-Methyl-N- (1,2,3-triphenylallyl) propane-2-sulfonamide Synthesis
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35.6mg, 0.2mmol) and 2b (54mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 3b, white solid, yield (65%) after concentration.1H NMR (400MHz, CDCl3) δ 7.43-7.33 (m, 4H), 7.32-7.27 (m, 1H), 7.26-7.19 (m, 3H), 7.15-7.06 (m, 3H), 6.98-6.91 (m, 2H), 6.89 (d, J=6.8Hz, 2H), 6.78 (s, 1H), 5.52 (d, J=10.0Hz, 1H), 4.29 (d, J=9.6Hz, 1H), 1.37 (s, 9H)13C NMR (100MHz, CDCl3) δ 141.7,140.2,137.4,136.1, 129.7,129.6,129.4,128.9,128.8,128.1,128.0,127.8,127.3,127.1,65.5,60.3, 24.3.HRMS(ESI)calcd.for C25H31N2O2S ([M+NH4]+) 423.2101, Found 423.2101.
Embodiment 3:(E)-N- (2,3-diphenyl-1- (p-tolyl) allyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35.6mg, 0.2mmol) and 2c (65.5mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, is added Ethyl acetate dilution, diatomite filtering, column chromatography for separation obtains target product 3c, white solid, yield (79%) after concentration.1H NMR (400MHz, CDCl3) δ 7.69 (d, J=8.4Hz, 2H), 7.24-7.17 (m, 3H), 7.17-7.10 (m, 4H), 7.10- 7.01 (m, 5H), 6.79-6.72 (m, 2H), 6.69 (d, J=6.8Hz, 2H), 6.48 (s, 1H), 5.31 (d, J=8.0Hz, 1H), (s, 3H) of 4.77 (d, J=8.0 Hz, 1H), 2.36 (s, 3H), 2.3213C NMR (100MHz, CDCl3) δ 143.4, 139.9,137.7,137.6,137.5,136.2,136.1,129.8,129.6,129.4,129.4,129.3,128.8, 127.9,127.8,127.5,127.3,127.1,64.2,21.6,21.2.HRMS (ESI) calcd.for C29H31N2O2S([M +NH4]+) 471.2101, Found 471.2100.
Embodiment 4:(E)-N- (1- (4-Methoxyphenyl) -2,3-diphenylallyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35.6mg, 0.2mmol) and 2d (69.4mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, is added Ethyl acetate dilution, diatomite filtering, column chromatography for separation obtains target product 3d, white solid, yield (82%) after concentration.1H NMR (400MHz, CDCl3) δ 7.69 (d, J=8.4Hz, 2H), 7.23-7.11 (m, 7H), 7.08-7.01 (m, 3H), 6.80 (d, J=8.8Hz, 2H), 6.77-6.72 (m, 2H), 6.70 (d, J=6.8Hz, 2H), 6.47 (s, 1H), 5.30 (d, J= 7.6Hz, 1H), 4.76 (d, J=7.6 Hz, 1H), 3.79 (s, 3H), 2.36 (s, 3H)13C NMR (100MHz, CDCl3)δ 159.3,143.5,140.0,140.0,137.8,137.5,136.0,131.2,129.6,129.4,129.3,128.8, 128.6,128.0,127.8,127.5,127.1,114.0,63.9,55.4,21.6.HRMS (ESI) calcd.for C29H31N2O3S([M+NH4]+) 487.2050, Found 487.2047.
Embodiment 5:(E)-N- (1- (3-Methoxyphenyl) -2,3-diphenylallyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35.6mg, 0.2mmol) and 2e (69.4mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, is added Ethyl acetate dilution, diatomite filtering, column chromatography for separation obtains target product 3e, white solid, yield (77%) after concentration.1H NMR (400MHz, CDCl3) δ 7.69 (d, J=8.0Hz, 2H), 7.24-7.18 (m, 4H), 7.17-7.10 (m, 2H), 7.09- 7.00 (m, 3H), 6.88 (d, J=7.6Hz, 1H), 6.82-6.73 (m, 4H), 6.70 (d, J=7.2Hz, 2H), 6.48 (s, 1H), 5.32 (d, J=8.0Hz, 1H), 4.79 (d, J=8.0Hz, 1H), 3.72 (s, 3H), 2.36 (s, 3H)13C NMR (100MHz, CDCl3) δ 159.9,143.5,140.8,139.7,137.7,137.3,136.0,130.1,129.7,129.6, 129.5,129.3,128.8,128.0,127.9,127.5,127.2,119.7,113.4,112.9,64.4,55.3, 21.6.HRMS(ESI)calcd.for C29H31N2O3S([M+NH4]+) 487.2050, Founnd 487.2046.
Embodiment 6:(E)-N- (1- (2-Methoxyphenyl) -2,3-diphenylallyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPrHCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35.6mg, 0.2mmol) and 2f (69.4mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, is added Ethyl acetate dilution, diatomite filtering, column chromatography for separation obtains target product 3f, white solid, yield (68%) after concentration.1H NMR (400MHz, CDCl3) δ 7.55 (d, J=8.0Hz, 2H), 7.23-7.10 (m, 4H), 7.08-6.99 (m, 5H), 6.96 (d, J=7.6Hz, 1H), 6.87 (d, J=7.2Hz, 2H), 6.79-6.72 (m, 3H), 6.70 (d, J=8.0Hz, 1H), 6.48 (s, 1H), 5.47 (s, 2H), 3.66 (s, 3H), 2.29 (s, 3H)13C NMR (100MHz, CDCl3) δ 156.7,142.9, 140.4,138.7,137.7,136.5,129.3,129.2,128.9,128.5,128.4,127.8,127.3,127.1, 126.8,126.8,120.5,110.9,61.1,55.4,21.5. HRMS (ESI) calcd.for C29H31N2O3S([M+NH4]+) 487.2050 Found 487.2047.
Embodiment 7:(E)-N- (1- (2,4-Dimethoxyphenyl) -2,3-diphenylallyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35.6mg, 0.2mmol) and 2g (77mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 3g, white solid, yield (87%) after concentration.1H NMR (400MHz, CDCl3) δ 7.56 (d, J=8.4Hz, 2H), 7.23-7.12 (m, 3H), 7.07 (d, J=8.0Hz, 2H), 7.05- 6.98 (m, 3H), 6.93-6.83 (m, 3H), 6.80-6.69 (m, 2H), 6.48 (s, 1H), 6.31-6.24 (m, 2H), 5.41 (d, J=8.4Hz, 1H), 5.36 (d, J=8.4Hz, 1H), 3.75 (s, 3H), 3.62 (s, 3H), 2.30 (s, 3H)13C NMR (100MHz, CDCl3) δ 160.5,157.7,142.8,140.6,138.8,137.8,136.5,129.9,129.3,129.2, 128.5,128.2,127.8,127.2,127.1,126.7,119.4,104.0,98.8,60.6,55.4,55.4, 21.5.HRMS(ESI)calcd.for C30H29NNaO4S ([M+Na]+) 522.1710, Found 522.1700.
Embodiment 8:(E)-N- (2,3-Diphenyl-1- (3,4,5-trimethoxyphenyl) allyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35.6mg, 0.2mmol) and 2h (84mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 3h, white solid, yield (89%) after concentration.1H NMR (400MHz, CDCl3) δ 7.69 (d, J=8.0Hz, 2H), 7.24-7.20 (m, 3H), 7.17 (t, J=7.4Hz, 2H), 7.11- 7.02 (m, 3H), 6,80-6.70 (m, 4H), 6.48 (s, 1H), 6.43 (s, 2H), 5.29 (d, J=7.6Hz, 1H), 4.85 (d, J =7.6Hz, 1H), 3.82 (s, 3H), 3.72 (s, 6H), 2.37 (s, 3H)13C NMR (100MHz, CDCl3) δ 153.2, 143.5,139.8,137.8,137.4,137.3,136.0,134.7,129.8,129.5,129.5,129.3,128.8, 128.0,127.9,127.4,127.2,104.5,64.5,60.9,56.1,21.5.HRMS (ESI) calcd.for C31H35N2O5S([M+NH4]+) 547.2261, Found 547.2257.
Embodiment 9:
(E)-N- (1- (4- (Dimethylamino) phenyl) -2,3-diphenylallyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35.6mg, 0.2mmol) and 2i (72.6mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, is added Ethyl acetate dilution, diatomite filtering, column chromatography for separation obtains target product 3i, white solid, yield (87%) after concentration.1H NMR (400MHz, CDCl3) δ 7.71 (d, J=8.0Hz, 2H), 7.20 (d, J=8.4Hz, 2H), 7.18-7.11 (m, 3H), 7.09 (d, J=8.4Hz, 2H), 7.07-7.01 (m, 3H), 6.81-6.69 (m, 4H), 6.61 (d, J=8.4Hz, 2H), 6.51 (s, 1H), 5.24 (d, J=7.2 Hz, 1H), 4.72 (d, J=7.2Hz, 1H), 2.93 (s, 6H), 2.35 (s, 3H)13C NMR (100MHz, CDCl3) δ 150.2,143.2,140.3,138.1,138.0,136.3,129.6,129.5,129.3,129.1, 128.6,128.4,127.9,127.6,127.5,126.9,126.5,112.5,64.0,40.6,21.6.HRMS (ESI) calcd.for C30H31N2O2S([M+H]+) 483.2101, Found 483.2100.
Embodiment 10:(E)-N- (1- (4-Fluorophenyl) -2,3-diphenylallyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35.6mg, 0.2mmol) and 2j (66.5mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, is added Ethyl acetate dilution, diatomite filtering, column chromatography for separation obtains target product 3j, white solid, yield (74%) after concentration.1H NMR (400MHz, CDCl3) δ 7.67 (d, J=8.4Hz, 2H), 7.24-7.18 (m, 5H), 7.18-7.12 (m, 2H), 7.10- 7.01 (m, 3H), 6.95 (t, J=8.6Hz, 2H), 6.77-6.71 (m, 2H), 6.68 (d, J=7.2Hz, 2H), 6.45 (s, 1H), 5.34 (d, J=8.0Hz, 1H), 4.90 (d, J=8.0Hz, 1H), 2.37 (s, 3H)13C NMR (100MHz, CDCl3)δ 162.3 (d, J=245.1Hz), 143.6,139.7,137.6,137.2,135.8,135.0 (d, J=3.0Hz), 130.1, 129.6,129.4,129.3,129.1 (d, J=8.0Hz), 128.9,128.0,128.0,127.4,127.3,115.5 (d, J =21.4Hz), 63.8,21.6.19F NMR (376MHz, CDCl3)δ-114.9.HRMS(ESI)calcd.for C28H28FN2O2S([M+NH4]+) 475.1850, Found 475.1858.
Embodiment 11:(E)-N- (1- (4-Fluorophenyl) -2,3-diphenylallyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35.6mg, 0.2mmol) and 2k (66.5mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, is added Ethyl acetate dilution, diatomite filtering, column chromatography for separation obtains target product 3k, white solid, yield (64%) after concentration.1H NMR (400MHz, CDCl3) δ 7.68 (d, J=8.4Hz, 2H), 7.26-7.19 (m, 4H), 7.15 (t, J=7.4Hz, 2H), 7.12-7.02 (m, 4H), 7.02-6.91 (m, 2H), 6.75 (d, J=8.0Hz, 2H), 6.67 (d, J=7.2Hz, 2H), 6.45 (s, 1H), 5.35 (d, J=8.0 Hz, 1H), 4.86 (d, J=8.0Hz, 1H), 2.37 (s, 3H)13C NMR (100MHz, CDCl3) δ 163.0 (d, J=245.0 Hz), 143.7,142.1,142.0,139.3,137.6,136.8,135.7,130.7, 130.2 (d, J=8.2Hz), 129.7,129.4 (d, J=5.8Hz), 129.0,128.1,128.0,127.5,127.4, 123.0 (d, J=2.6Hz), 114.8 (d, J=21.1Hz), 114.4 (d, J=22.5Hz), 64.0,21.6.19F NMR (376MHz, CDCl3)δ-111.9.HRMS(ESI)calcd.for C28H28FN2O2S([M+NH4]+) 475.1850, Found 475.1856.
Embodiment 12:(E)-N- (1- (2-Fluorophenyl) -2,3-diphenylallyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35.6mg, 0.2mmol) and 21 (66.5mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 31, white solid, yield (64%) after concentration.1H NMR (400MHz, CDCl3) δ 7.58 (d, J=7.6Hz, 2H), 7.24-7.12 (m, 5H), 7.11 (d, J=7.6Hz, 2H), 7.07- 6.97 (m, 4H), 6.92 (t, J=9.4Hz, 1H), 6.87-6.80 (m, 2H), 6.78-6.69 (m, 2H), 6.42 (s, 1H), 5.55 (d, J=7.6Hz, 1H), 5.04 (d, J=7.6Hz, 1H), 2.33 (s, 3H)13C NMR (100MHz, CDCl3)δ 160.2 (d, J=245.7Hz), 143.3,139.4,137.6,137.1,135.9,129.7,129.5,129.5,129.3, 129.2 (d, J=3.6Hz), 128.8,127.9,127.8,127.2,126.7,126.6,124.1 (d, J=3.4Hz), 115.6 (d, J=21.4Hz), 59.0,21.6.19F NMR (376 MHz, CDCl3)δ-116.7.HRMS(ESI)calcd.for C28H28FN2O2S([M+NH4]+) 475.1850, Found 475.1851.
Embodiment 13:
(E)-N- (2,3-Diphenyl-1- (4- (trifluoromethyl) phenyl) allyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35,6mg, 0.2mmol) and 2m (78.5mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, is added Ethyl acetate dilution, diatomite filtering, column chromatography for separation obtains target product 3m, white solid, yield (29%) after concentration.1H NMR (400MHz, CDCl3) δ 7.63 (d, J=8.4Hz, 2H), 7.51 (d, J=8.4Hz, 2H), 7.40 (d, J=8.4Hz, 2H), 7.25-7.13 (m, 5H), 7.11-7.00 (m, 3H), 6.74 (d, J=7.6Hz, 2H), 6.66 (d, J=7.2Hz, 2H), 6.44 (s, 1H), 5.41 (d, J=8.0Hz, 1H), 4.92 (d, J=8.0Hz, 1H), 2.37 (s, 3H)13C NMR (100MHz, CDCl3) δ 143.7,143.3,139.2,137.3,136.8,135.6,130.7,129.9 (q, J=32.4Hz), 129.7, 129.3,129.0,128.1,128.0,127.8,127.5,127.4,125.5 (q, J=3.6Hz), 124.1 (q, J= 270.5Hz), 64.1,21.5.19F NMR (376MHz, CDCl3) δ-62.3.HRMS(ESI)calcd.for C29H28F3N2O2S ([M+NH4]+) 525.1818, Found 525.1820.
Embodiment 14:(E) -4-Methyl-N- (1- (naphthalen-1-yl) -2,3-diphenylallyl) The synthesis of benzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35.6mg, 0.2mmol) and 2n (74.2mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, is added Ethyl acetate dilution, diatomite filtering, column chromatography for separation obtains target product 3n, white solid, yield (65%) after concentration.1H NMR (400MHz, CDCl3) δ 8.15-8.05 (m, 1H), 7.88-7.80 (m, 1H), 7.76 (d, J=8.0Hz, 1H), 7.63 (d, J=8.0Hz, 2H), 7.56-7.43 (m, 3H), 7.35 (t, J=7.6Hz, 1H), 7.21-7.11 (m, 3H), 7.08 (d, J =8.0Hz, 2H), 7.06-6.98 (m, 3H), 6.96 (d, J=6.8Hz, 2H), 6.69 (d, J=6.8Hz, 2H), 6.44 (s, 1H), 6.14 (d, J=6.4Hz, 1H), 4.98 (d, J=6.4Hz, 1H), 2.28 (s, 3H)13C NMR (100MHz, CDCl3)δ 143.3,139.1,138.5,137.7,136.1,134.1,134.1,131.1,130.5,129.5,129.3,129.1, 129.0,128.9,128.8,127.9,127.7,127.3,127.1,126.8,126.2,125.9,125.2,123.3, 60.7,21.5.HRMS (ESI) calcd.for C32H31N2O2S ([M+NH4]+) 507.2101, Found 507.2094.
Embodiment 15:(E) -4-Methyl-N- (1- (naphthalen-2-yl) -2,3-diphenylallyl) The synthesis of benzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35.6mg, 0.2mmol) and 2o (74.2mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, is added Ethyl acetate dilution, diatomite filtering, column chromatography for separation obtains target product 3o, white solid, yield (78%) after concentration.1H NMR (400MHz, CDCl3) δ 7.85-7.79 (m, 1H), 7.77 (d, J=8.8Hz, 1H), 7.74-7.64 (m, 4H), 7.52- 7.44 (m, 2H), 7.42 (d, J=8.4Hz, 1H), 7.22-7.14 (m, 3H), 7.14-7.02 (m, 5H), 6.77 (d, J= 6.8Hz, 2H), 6.69 (d, J=7.6Hz, 2H), 6.55 (s, 1H), 5.52 (d, J=8.0Hz, 1H), 4.91 (d, J= 8.0Hz, 1H), 2.32 (s, 3H)13C NMR (100 MHz, CDCl3) δ 143.4,139.7,137.6,137.4,136.4, 135.9,133.2,132.8,130.2,129.5,129,4,129.3,128.8,128.5,128.2,127.9,127.8, 127.6,127.4,127.2,126.4,126.3,126.2,125.2,64.5,21.5. HRMS (ESI) calcd.for C32H31N2O2S([M+NH4]+) 507.2101, Found 507.2099.
Embodiment 16:(E)-N- (2,3-Diphenyl-1- (thiophen-2-yl) allyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35.6mg, 0.2mmol) and 2p (63.6mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, is added Ethyl acetate dilution, diatomite filtering, column chromatography for separation obtains target product 3p, white solid, yield (65%) after concentration.1H NMR (400MHz, CDCl3) δ 7.73 (d, J=8.0Hz, 2H), 7.25-7.20 (m, 4H), 7.16 (t, J=7.4Hz, 2H), 7.12-7.03 (m, 3H), 6.97-6.89 (m, 2H), 6.84-6.78 (m, 2H), 6.76 (d, J=6.8Hz, 2H), 6.56 (s, 1H), 5.59 (d, J=8.4Hz, 1H), 4.89 (d, J=8.4Hz, 1H), 2.37 (s, 3H)13C NMR (100MHz, CDCl3)δ 144.4,143.7,139.6,137.7,136.7,135.8,130.0,129.7,129.5,129.4,128.9,128.1, 128.0,127.5,127.4,127.3,125.9,125.8,60.8,21.6.HRMS (ESI) calcd.for C26H27N2O2S2 ([M+NH4]+) 463.1508, Found 463.1507.
Embodiment 17:(E)-N- (1-Cyclohexyl-2,3-diphenylallyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (35.6mg, 0.2mmol) and 2q (63.6mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, is added Ethyl acetate dilution, diatomite filtering, column chromatography for separation obtains target product 3q, white solid, yield (83%) after concentration.1H NMR (400MHz, CDCl3) δ 7.77 (d, J=8.4Hz, 2H), 7.30-7.24 (m, 3H), 7.21 (d, J=8.0Hz, 2H), 7.09-6.96 (m, 3H), 6.88-6.78 (m, 2H), 6.68-6.59 (m, 2H), 6.19 (s, 1H), 4.43 (d, J=9.6Hz, 1H), 3.92 (t, J=9.0Hz, 1H), 2.30 (s, 3H), 1.96 (d, J=12.4Hz, 1H), 1.86-1.68 (m, 3H), 1.64 (s, 1H), 1.43-1.29 (m, 1H), 1.24-1.02 (m, 4H), 1.01-0.84 (m, 1H)13C NMR (100MHz, CDCl3)δ 143.3,138.8,138.4,137.7,136.1,130.1,129.6,129.4,129.1,128.9,127.8,127.7, 127.4,126.8,66.8,40.1,31.0,28.9,26.4,26.1,21.5.HRMS (ESI) calcd.for C28H35N2O2S ([M+NH4]+) 463.2414, Found 463.2410.
Embodiment 18:(E)-N- (4,4-Dimethyl-1,2-diphenylpent-1-en-3-yl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1a (42.8mg, 0.24mmol) and 2r (47.9mg, 0.2mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, is added Ethyl acetate dilution, diatomite filtering, column chromatography for separation obtains target product 3r, white solid, yield (23%) after concentration.1H NMR (400MHz, CDCl3) δ 7.79 (d, J=8.0Hz, 2H), 7.23-7.15 (m, 3H), 7.09 (d, J=8.0Hz, 2H), 7.06-6.96 (m, 5H), 6.62-6.52 (m, 2H), 6.24 (s, 1H), 5.00 (d, J=9.2Hz, 1H), 4.10 (d, J= 9.2Hz, 1H), 2.18 (s, 3H), 0.84 (s, 9H)13C NMR (100MHz, CDCl3) δ 143.2,140.0,139.1, 138.2,136.6,131.5,129.8,129.6,129.2,128.6,127.7,127.4,126.6,68.8,36.5,27.3, 21.4.HRMS(ESI)calcd.for C26H29NNaO2S ([M+Na]+) 442.1811, Found 442.1815.
Embodiment 19:(E) -4-Methyl-N- (1-phenyl-2,3-di-p-tolylallyl) The synthesis of benzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1b (41.3mg, 0.2mmol) and 2a (62mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 4a, white solid, yield (81%) after concentration.1H NMR (400MHz, CDCl3) δ 7.68 (d, J=8.4Hz, 2H), 7.33-7.26 (m, 5H), 7.20 (d, J=8.0Hz, 2H), 6.94 (d, J=8.0Hz, 2H), 6.87 (d, J=8.0Hz, 2H), 6.66 (d, J=8.0Hz, 2H), 6.54 (d, J=8.0Hz, 2H), 6.38 (s, 1H), 5.33 (d, J=8.0Hz, 1H), 4.83 (d, J=8.0Hz, 1H), 2.37 (s, 3H), 2.28 (s, 3H), 2.22 (s, 3H)13C NMR (100 MHz, CDCl3) δ 143.4,139.5,138.8,137.8,137.5,136.9,134.2, 133.2,129.9,129.5,129.5,129.3,129.2,128.7,128.6,127.7,127.5,127.4,64.5,21.6, 21.3,21.2.HRMS (ESI) calcd.for C30H33N2O2S([M+NH4]+) 485.2257, Found 485.2253.
Embodiment 20:(E) -4-Methyl-N- (1-phenyl-2,3-di-m-tolylallyl) The synthesis of benzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1c (41.3mg, 0.2mmol) and 2a (62mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 4b, white solid, yield (77%) after concentration.1H NMR (400MHz, CDCl3) δ 7.68 (d, J=8.0Hz, 2H), 7.33-7.26 (m, 5H), 7.21 (d, J=8.0Hz, 2H), 7.04- 6.97 (m, 2H), 6.95-6.84 (m, 2H), 6.60 (s, 1H), 6.52 (d, J=7.2Hz, 1H), 6.48-6.41 (m, 2H), 6.40 (s, 1H), 5.34 (d, J=7.6Hz, 1H), 4.81 (d, J=7.6Hz, 1H), 2.37 (s, 3H), 2.14 (s, 6H)13C NMR (100MHz, CDCl3) δ 143.3,139.8,139.4,138.3,137.8,137.3,137.2,135.9,130.3, 130.0,129.9,129.6,128.6,128.5,128.5,127.9,127.8,127.7,127.4,127.4,126.5, 126.2,64.5,21.6,21.4,21.4.HRMS (ESI) calcd. for C30H33N2O2S([M+NH4]+) 485.2257, Found 485.2255.
Embodiment 21:(E/Z) -4-Methyl-N- (1-phenyl-2,3-di-o-tolylallyl) The synthesis of benzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1d (41.3mg, 0.2mmol) and 2a (62mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 4c after concentration, white solid, yield (64%, Z/E=1: 1)。1H NMR (400 MHz, CDCl3) δ 7.62 (d, J=8.4Hz, 2H), 7.60 (d, J=8.0Hz, 2H), 7.25-7.17 (m, 8H), 7.17-7.11 (m, 4H), 7.10-7.00 (m, 7H), 6.99-6.80 (m, 7H), 6.75-6.65 (m, 3H), 6.62 (d, J =7.6Hz, 1H), 6.49 (d, J=7.6Hz, 1H), 6.43 (d, J=7.6Hz, 1H), 5.33 (d, J=6.8Hz, 1H), 5.10 (d, J=6.0Hz, 1H), 5.07-4.98 (m, 2H), 2.37 (s, 3H), 2.33 (s, 3H), 2.28 (s, 3H), 2.20 (s, 3H), 1.78 (s, 3H), 1.55 (s, 3H)13C NMR (100MHz, CDCl3) δ 143.3,143.2,140.2,139.7,139.3, 139.2,137.5,137.3,136.9,136.7,136.4,136.4,136.3,136.2,135.5,135.4,130.5, 130.3,130.0,129.7,129.5,128.5,128.4,128.4,128.3,128.3,128.1,127.8,127.6, 127.6,127.3,127.3,127.2,127.2,127.0,125.7,125.4,125.1,64.3,64.3,21.5,21.5, 20.0,19.9,19.3,19.0.HRMS (ESI) calcd.for C30H33N2O2S([M+NH4]+) 485.2257, Found 485.2252.
Embodiment 22:(E)-N- (2,3-bis (4-ethylphenyl) -1-phenylallyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1e (47mg, 0,2 mmol) and 2a (62mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, acetic acid is added Ethyl ester dilution, diatomite filtering, column chromatography for separation obtains target product 4d, white solid, yield (72%) after concentration.1H NMR (400MHz, CDCl3) δ 7.69 (d, J=8.4Hz, 2H), 7.35-7.24 (m, 5H), 7.21 (d, J=8.0Hz, 2H), 6.97 (d, J=8.0Hz, 2H), 6.89 (d, J=8.0Hz, 2H), 6.67 (d, J=8.0Hz, 2H), 6.56 (d, J=8.0Hz, 2H), 6.37 (s, 1H), 5.33 (d, J=8.0Hz, 1H), 4.79 (d, J=8.0Hz, 1H), 2.59 (q, J=7.6Hz, 2H), 2.52 (q, J=7.6Hz, 2H), 2.37 (s, 3H), 1.20 (t, J=7.6Hz, 3H), 1.14 (t, J=7.6Hz, 3H)13C NMR (100MHz, CDCl3) δ 143.8,143.4,143.3,139.6,138.7,137.8,134.4,133.4,130.0,129.6, 129.3,129.3,128.6,128.3,127.7,127.5,127.4,64.6,28.6,28.6,21.6,15.4,15.3.HRMS (ESI)calcd.for C32H37N2O2S([M+NH4]+) 513.2570, Found 513.2564.
Embodiment 23:(E)-N- (2,3-bis (4-methoxyphenyl) -1-phenylallyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1f (47.7mg, 0.2mmol) and 2a (62mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 4e, white solid, yield (74%) after concentration.1H NMR (400MHz, CDCl3) δ 7.68 (d, J=8.0Hz, 2H), 7.31-7.23 (m, 5H), 7.20 (d, J=8,0Hz, 2H), 6.73- 6.64 (m, 4H), 6.63-6.54 (m, 4H), 6.35 (s, 1H), 5.31 (d, J=8.0Hz, 1H), 4.82 (d, J=8.0Hz, 1H), 3.76 (s, 3H), 3.72 (s, 3H), 2.37 (s, 3H)13C NMR (100MHz, CDCl3) δ 159.1,158.7,143.4, 139.6,137.8,137.4,137.3,130.7,130.6,129.6,129.3,128.7,128.6,127.7,127.5, 127.3,114.3,113.4,64.6,55.3,21.6. HRMS (ESI) calcd.for C30H29NNaO4S([M+Na]+) 522.1710 Found 522.1713.
Embodiment 24:(E)-N- (2,3-bis (4-fluorophenyl) -1-phenylallyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1g (42.8mg, 0.2mmol) and 2a (62mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 4f, white solid, yield (73%) after concentration.1H NMR (400MHz, CDCl3) δ 7.68 (d, J=7.2Hz, 2H), 7.33-7.15 (m, 8H), 6.85 (t, J=8.0Hz, 2H), 6.80- 6.63 (m, 5H), 6.52 (s, 1H), 5.31 (d, J=8.0Hz, 1H), 4.80 (d, J=8.0Hz, 1H), 2.37 (s, 3H)13C NMR (100MHz, CDCl3) δ 162.3 (d, J=246.0Hz), 161.8 (d, J=246.2Hz), 143.6,139.0,138.8, 137.7,133.2 (d, J=3.3Hz), 131.9 (d, J=3.3Hz), 131.2 (d, J=7.8Hz), 130.9 (d, J= 7.8Hz), 129.6,129.0,128.8,128.0,127.4,127.3,115.9 (d, J=21.3Hz), 115.0 (d, J= 21.1Hz), 64.4,21.6.19F NMR (376MHz, CDCl3) δ -113.4, -114.0.HRMS (ESI) calcd.for C28H27F2N2O2S([M+NH4]+) 493.1756, Found 493.1752.
Embodiment 25:
(E) -4-Methyl-N- (1-phenyl-2,3-bis (4- (trifluoromethyl) phenyl) allyl) The synthesis of benzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1h (62.8mg, 0.2mmol) and 2a (62mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 4g, white solid, yield (53%) after concentration.1H NMR (400MHz, CDCl3) δ 7.68 (d, J=8.0Hz, 2H), 7.42 (d, J=8.0Hz, 2H), 7.33 (d, J=8.0Hz, 2H), 7.30-7.26 (m, 3H), 7.20 (d, J=8.0Hz, 2H), 7.18-7.13 (m, 2H), 6.89 (d, J=8.0Hz, 2H), 6.85 (d, J=8.0Hz, 2H), 6.71 (s, 1H), 5.32 (d, J=6.8Hz, 1H), 4.89 (d, J=6.8Hz, 1H), 2.36 (s, 3H).13C NMR (100MHz, CDCl3) δ 143.8,141.6,141.4,139.1,138.1,137.4,130.1 (q, J= 32.4Hz), 129.7,129.7,129.4,129.2 (q, J=32.2Hz), 129.1,129.0,128.3,127.4,127.3, 125.8 (q, J=3.6Hz), 125.0 (q, J=3.6 Hz), 124.0 (q, J=270.6Hz), 124.1 (q, J=270.3Hz), 64.1,21.5.HRMS (ESI) calcd.for C30H27F6N2O2S([M+NH4]+) 593.1692, Found 593.1691.
Embodiment 26:(E) -4-Methyl-N- (1-phenyl-2-propylhex-2-en-1-yl) The synthesis of benzenesulfonamide
In nitrogen atmosphere, ligand AnIPrHCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect li (22mg, 0.2 mmol) and 2a (62mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, acetic acid is added Ethyl ester dilution, diatomite filtering, column chromatography for separation obtains target product 4h, white solid, yield (52%) after concentration.1H NMR (400MHz, CDCl3) δ 7.62 (d, J=8.4Hz, 2H), 7.23-7.16 (m, 5H), 7.12-7.06 (m, 2H), 5.24 (t, J =7.2Hz, 1H), 4.88 (d, J=7.6Hz, 1H), 4.72 (d, J=7.6Hz, 1H), 2.39 (s, 3H), 1.97-1.84 (m, 3H), 1.76-1.64 (m, 1H), 1.25 (q, J=7.2Hz, 2H), 1.20 (q, J=7.2Hz, 2H), 0.83 (t, J=7.2Hz, 3H), 0.78 (t, J=7.2Hz, 3H)13C NMR (100MHz, CDCl3) δ 143.0,140.0,137.9,137.9,129.4, 128.9,128.4,127.4,127.4,127.3,62.0,31.0,29.8,22.8,22.1,21.5,14.3,14.0.HRMS (ESI)calcd.for C22H29NNaO2S([M+Na]+) 394.1811, Found 394.1815.
Embodiment 27:
(E)-N-(1-(4-(dimethylamino)phenyl)-2-propylhex-2-en-1-yl)-4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect li (22mg, 0.2 mmol) and 2i (72.6mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 4i, white solid, yield (78%) after concentration.1H NMR (400MHz, CDCl3) δ 7.63 (d, J=8.4Hz, 2H), 7.20 (d, J=8.4Hz, 2H), 6.91 (d, J=8.8Hz, 2H), 6.55 (d, J=8.8Hz, 2H), 5.33 (t, J=7.0Hz, 1H), 4.77 (d, J=6.8Hz, 1H), 4.64 (d, J=6.8Hz, 1H), 2.90 (s, 6H), 2.39 (s, 3H), 2.00-1.83 (m, 3H), 1.70-1.56 (m, 1H), 1.34-1.13 (m, 4H), 0.85 (t, J=7.2Hz, 3H), 0.78 (t, J=7.2Hz, 3H)13C NMR (100MHz, CDCl3) δ 150.0,142.8, 138.1,138.0,129.3,128.3,127.7,127.6,127.4,112.4,61.5,40.6,31.2,29.8,22.9, 22.0,21.6,14.3,14.0.HRMS (ESI) calcd.for C24H35N2O2S([M+H]+) 415.2414, Found 415.2413.
Embodiment 28:
(E)-N-(1-(4-(dimethylamino)phenyl)-2-methylbut-2-en-1-yl)-4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1j (10.8mg, 0.2mmol) and 2i (72.6mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, is added Ethyl acetate dilution, diatomite filtering, column chromatography for separation obtains target product 4j, white solid, yield (55%) after concentration.1H NMR (400MHz, CDCl3) δ 7.64 (d, J=8.0Hz, 2H), 7.21 (d, J=8.0Hz, 2H), 6.94 (d, J=8.8Hz, 2H), 6.57 (d, J=8.8Hz, 2H), 5.45 (q, J=6.8Hz, 1H), 4.75 (d, J=7.2Hz, 1H), 4.64 (d, J= 7.2Hz, 1H), 2.90 (s, 6H), 2.40 (s, 3H), 1.49 (d, J=6.8Hz, 3H), 1.33 (s, 3H)13C NMR (100MHz, CDCl3) δ 150.0,142.9,137.9,134.0,129.3,127.8,127.5,127.2,122.5,112.4, 64.0,40.6,21.6,13.3,13.0.HRMS (ESI) calcd.for C20H27N2O2S([M+H]+) 359.1788, Found 359.1784.
Embodiment 29:
(E)-N-(1-(4-(dimethylamino)phenyl)-2-methyl-3-phenylallyl)-4- Methylbenzenesulfonamide and (E)-N- (1- (4- (dimethylamino) phenyl) -2-phenylbut-2- En-1-yl) the synthesis of -4-methylbenzenesulfonamide (2.6: 1 mixture)
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 1k (23.2mg, 0.2mmol) and 2i (72.6mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, is added Ethyl acetate dilution, diatomite filtering, column chromatography for separation obtains target product 4k, yellow oil, yield (48%) after concentration.1H NMR (400MHz, CDCl3) δ 7.71 (d, J=8.4Hz, 2H), 7.62 (d, J=8.4Hz, 0.78H), 7.23-7.26 (m, 1.95H), 7.24-7.15 (m, 5H), 7.07 (d, J=7.6Hz, 2H), 7.05 (d, J=8.8Hz, 2H), 6.99 (d, J= 8.8Hz, 0.78H), 6.80-6.74 (m, 0.78H), 6.61 (d, J=8.8Hz, 2H), 6.57 (d, J=8.8Hz, 0.78H), 6.46 (s, 1H), 5.66 (q, J=6.6Hz 0.39H), 5.11 (d, J=7.2Hz, 0.39H), 4.94 (d, J=7.2Hz, 1H), 4.81 (d, J=7.2Hz, 1H), 4.63 (d, J=7.2Hz, 0.39H), 2.92 (s, 6H), 2.91 (s, 2.34H), 2.41 (s, 1.17H), 2.37 (s, 3H), 1.58 (s, 3H), 1.43 (d, J=7.2Hz, 1.17H)13C NMR (100MHz, CDCl3)δ 150.1,150.0,143.1,142.9,140.3,138.0,137.9,137.4,136.2,129.5,129.4,129.3, 129.0,128.2,128.1,128.0,127.9,127.6,127.5,127.4,127.1,127.0,126.7,126.5, 125.0,112.5,112.4,64.4,63.1,40.6,40.6,21.6,21.5,15.2,14.5.HRMS (ESI) calcd. for C25H29N2O2S([M+H]+) 421.1944, Found 421.1948.
Embodiment 30:
(E)-N-(1-(4-(dimethylamino)phenyl)-2-ethylidenepentyl)-4- Methylbenzenesulfonamide and (E)-N- (1- (4- (dimethylamino) phenyl) -2-methylhex-2- En-1-yl) the synthesis of -4-methylbenzenesulfonamide (1.4: 1 mixture)
In nitrogen atmosphere, ligand AnIPr.HCl (5.5mg, 5mol%), t-BuOK are sequentially added into reaction flask (2.3mg, 10 mol%), Ni (cod)2(5.5mg, 10mol%), THF (1.0mL), i-PrOH (1.0mL) are eventually adding original Expect 11 (16.4mg, 0.2mmol) and 2i (72.6mg, 0.24mmol), stir 18 hours, be cooled to room temperature at 100 DEG C, is added Ethyl acetate dilution, diatomite filtering, column chromatography for separation obtains target product 41, yellow oil, yield (49%) after concentration.1H NMR (400MHz, CDCl3) δ 7.66 (d, J=8.0Hz, 1.42H), 7.62 (d, J=8.0Hz, 2H), 7.21 (d, J=7.2Hz, 1.42H), 7.19 (d, J=7.6 Hz, 2H), 6.96 (d, J=8.8Hz, 1.42H), 6.89 (d, J=8.8Hz, 2H), 6.57 (d, J=8.8Hz, 1.42H), 6.54 (d, J=8.8Hz, 2H), 5.40 (q, J=6.8Hz, 1H), 5.36 (t, J=6.8Hz, 0.71H), 4.79-4.71 (m, 2.42H), 4.65 (d, J=6.8Hz, 1H), 2.90 (s, 4.26H), 2.90 (s, 6H), 2.40 (s, 2.13H), 2.39 (s, 3H), 2.00-1.83 (m, 2H), 1.74-1.62 (m, 1H), 1.52 (d, J=6.4Hz, 3H), 1.35 (s, 2.13H), 1.32-1.17 (m, 3.84H), 0.85 (t, J=7.2 Hz, 2.13H), 0.79 (t, J=7.2Hz, 3H) .13C NMR (100MHz, CDCl3) δ 149.9,142.8,142.7,138.9,138.0,133.3,129.9,129.6,129.5, 129.3,129.2,128.2,128.0,127.8,127.6,127.3,126.4,121.9,112.4,112.4,63.9,61.6, 40.6,30.7,29.8,22.5,21.6,21.5,14.2,13.9,13.3.HRMS (ESI) calcd.for C22H31N2O2S([M+ H]+) 387.2101, Found 387.2090.
Embodiment 31:
(S, E)-N- (1- (4- (Dimethylamino) phenyl) -2,3-diphenylallyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr-1 (9.4mg, 10mol%), t-BuOK are sequentially added into reaction flask (1.4mg, 12 mol%), Ni (cod)2(2.8mg, 10mol%), THF (1.5mL), i-PrOH (1.5mL) are eventually adding original Expect 1a (17.8mg, 0.1mmol) and 2i (36.3mg, 0.12mmol), stir 18 hours, be cooled to room temperature at 60 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 3i, white solid, yield (55%) after concentration.HPLC Condition:Chiralpak AD-H column, n-hexane/i-PrOH=90: 10,1.0mL/min, 254nm, tr-major=19.7min, tr-minor=23.5min, 91%ee.(c 0.2, CHCl3).
Embodiment 32:
(S, E)-N- (1- (4- (Diethylamino) phenyl) -2,3-diphenylallyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr-1 (9.4mg, 10mol%), t-BuOK are sequentially added into reaction flask (1.4mg, 12 mol%), Ni (cod)2(2.8mg, 10mol%), THF (1.5mL), i-PrOH (1.5mL) are eventually adding original Expect 1a (17.8mg, 0.1mmol) and 2s (39.6mg, 0.12mmol), stir 18 hours, be cooled to room temperature at 60 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 5a, white solid, yield (60%) after concentration.1H NMR (400MHz, CDCl3) δ 7.70 (d, J=8.0Hz, 2H), 7.23-7.11 (m, 5H), 7.09-7.02 (m, 5H), 6.79 (d, J =8.0Hz, 2H), 6.77-6.73 (m, 2H), 6.54 (d, J=8.8Hz, 2H), 6.51 (s, 1H), 5.22 (d, J=7.2Hz, 1H), 4.72 (d, J=7.2 Hz, 1H), 3.32 (q, J=7.2Hz, 4H), 2.35 (s, 3H), 1.14 (t, J=7.2Hz, 6H) .13C NMR (100MHz, CDCl3) δ 147.4,143.2,140.3,138.2,137.9,136.4,129.5,129.4,129.3, 128.9,128.6,128.6,127.8,127.5,127.4,126.8,125.2,111.7,63.9,44.4,21.5, 12.6.HRMS(ESI)calcd.for C32H35N2O2S ([M+H]+) 511.2414, Found 511.2417.HPLC Condition:Chiralpak AD-H column, n-hexane/i-PrOH=90: 10,1.0mL/min, 254nm, tr-major=12.5min, tr-minor=16.2min, 95%ee. (c 1.0, CHCl3).
Embodiment 33:(S, E) -4-Methyl-N- (1- (4-morpholinophenyl) -2,3-diphenylallyl) The synthesis of benzenesulfonamide
In nitrogen atmosphere, ligand AnIPr-1 (9.4mg, 10mol%), t-BuOK are sequentially added into reaction flask (1.4mg, 12 mol%), Ni (cod)2(2.8mg, 10mol%), THF (1.5mL), i-PrOH (1.5mL) are eventually adding original Expect 1a (17.8mg, 0.1mmol) and 2t (39.6mg, 0.12mmol), stir 18 hours, be cooled to room temperature at 60 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 5b, white solid, yield (35%) after concentration.1H NMR (400MHz, CDCl3) δ 7.69 (d, J=8.4Hz, 2H), 7.23-7.10 (m, 7H), 7.08-7.00 (m, 3H), 6.81 (d, J =8.0Hz, 2H), 6.78-6.68 (m, 4H), 6.47 (s, 1H), 5.28 (d, J=7.6Hz, 1H), 4.81 (d, J=7.6Hz, 1H), (s, 3H) of 3.86 (t, J=4.4 Hz, 4H), 3.14 (t, J=4.4Hz, 4H), 2.3613C NMR (100MHz, CDCl3)δ 150.7,143.3,140.0,137.8,137.7,136.1,130.3,129.5,129.4,129.4,129.3,128.7, 128.4,127.9,127.7,127.4,127.0,115.5,66.9,63.9,49.2,21.6.HRMS (ESI) calcd.for C32H33N2O3S([M+H]+) 525.2206, Found 525.2211.HPLC condition:Chiralpak AD-H Column, n-hexane/i-PrOH=85: 15,1.0mL/min, 254 nm, tr-major=23.3min, tr-minor= 46.1min 51%ee.(c 0.5, CHCl3).
Embodiment 34:
(S, E)-N- (1- (4- (Diethylamino) phenyl) -2,3-di-p-tolylallyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr-1 (9.4mg, 10mol%), t-BuOK are sequentially added into reaction flask (1.4mg, 12 mol%), Ni (cod)2(2.8mg, 10mol%), THF (1.5mL), i-PrOH (1.5mL) are eventually adding original Expect 1b (20.6mg, 0.1mmol) and 2s (39.6mg, 0.12mmol), stir 18 hours, be cooled to room temperature at 60 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 5c, white solid, yield (37%) after concentration.1H NMR (400MHz, CDCl3) δ 7.68 (d, J=8.4Hz, 2H), 7.19 (d, J=8.0Hz, 2H), 7.07 (d, J=8.4Hz, 2H), 6.95 (d, J=8.0Hz, 2H), 6.86 (d, J=8.0Hz, 2H), 6.66 (d, J=8.0Hz, 4H), 6.55 (d, J=8.4Hz, 2H), 6.40 (s, 1H), 5.20 (d, J=7.2Hz, 1H), 4.72 (d, J=7.2Hz, 1H), 3.32 (q, J=7.2Hz, 4H), 2.35 (s, 3H), 2.28 (s, 3H), 2.22 (s, 3H), 1.14 (t, J=6.8Hz, 6H)13C NMR (100MHz, CDCl3)δ 147.3,143.1,139.2,138.0,137.1,136.5,135.0,133.5,129.4,129.3,129.3,129.1, 128.8,128.6,127.4,125.6,111.7,64.0,44.4,21.5,21.3,21.2,12.6.HRMS (ESI) calcd.for C34H39N2O2S([M+H]+) 539.2727, Found 539.2730.HPLC condition:Chiralpak AD-H column, n-hexane/i-PrOH=90: 10,1.0mL/min, 254 nm, tr-major=10.9min, tr-minor= 16.1min 87%ee.(c 0.5, CHCl3).
Embodiment 35:
(S, E)-N- (1- (4- (Diethylamino) phenyl) -2,3-bis (4-ethylphenyl) allyl) -4- The synthesis of methylbenzenesulfonamide
In nitrogen atmosphere, ligand AnIPr-1 (9.4mg, 10mol%), t-BuOK are sequentially added into reaction flask (1.4mg, 12 mol%), Ni (cod)2(2.8mg, 10mol%), THF (1.5mL), i-PrOH (1.5mL) are eventually adding original Expect 1e (23.4mg, 0.1mmol) and 2s (39.6mg, 0.12mmol), stir 18 hours, be cooled to room temperature at 60 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 5d, white solid, yield (60%) after concentration.1H NMR (400MHz, CDCl3) δ 7.70 (d, J=7.6Hz, 2H), 7.20 (d, J=7.6Hz, 2H), 7.09 (d, J=7.6Hz, 2H), 6.99 (d, J=7.6Hz, 2H), 6.89 (d, J=7.6Hz, 2H), 6.69 (d, J=7.6Hz, 4H), 6.56 (d, J=8.0Hz, 2H), 6.41 (s, 1H), 5.22 (d, J=7.6Hz, 1H), 4.77 (d, J=7.2Hz, 1H), 3.33 (q, J=6.8Hz, 4H), 2.59 (q, J=7.6Hz, 2H), 2.53 (q, J=7.6Hz, 2H), 2.35 (s, 3H), 1.21 (t, J=7.6Hz, 3H), 1.18- 1.10 (m, 9H)13C NMR (100MHz, CDCl3) δ 147.4,143.5,143.1,142.9,139.2,138.0,135.3, 133.8,129.5,129.4,129.3,129.0,128.6,128.1,127.5,127.4,125.7,111.8,64.1,44.4, 28.6,28.6,21.6,15.4,15.4,12.6. HRMS (ESI) calcd.for C36H43N2O2S([M+H]+) 567.3040, Found 567.3044.HPLC condition:Chiralpak AD-H column, n-hexane/i-PrOH=90: 10, 1.0mL/min, 254nm, tr-major=8.5min, tr-minor=10.6min, 90%ee.(c 1.0, CHCl3).
Embodiment 36:
(S, E)-N- (1- (4- (Diethylamino) phenyl) -2,3-bis (4-methoxyphenyl) allyl) -4- The synthesis of methylbenzenesulfona mide
In nitrogen atmosphere, ligand AnIPr-1 (9.4mg, 10mol%), t-BuOK are sequentially added into reaction flask (1.4mg, 12 mol%), Ni (cod)2(2.8mg, 10mol%), THF (1.5mL), i-PrOH (1.5mL) are eventually adding original Expect 1f (23.8mg, 0.1mmol) and 2s (39.6mg, 0.12mmol), stir 18 hours, be cooled to room temperature at 60 DEG C, second is added Acetoacetic ester dilution, diatomite filtering, column chromatography for separation obtains target product 5e, white solid, yield (28%) after concentration.1H NMR (400MHz, CDCl3) δ 7.69 (d, J=8.4Hz, 2H), 7.19 (d, J=8.0Hz, 2H), 7.06 (d, J=8.8Hz, 2H), 6.71 (d, J=8.8Hz, 2H), 6.69 (s, 4H), 6.60 (d, J=8.8Hz, 2H), 6.55 (d, J=8.8Hz, 2H), 6.37 (s, 1H), 5.18 (d, J=7.2Hz, 1H), 4.72 (d, J=7.2Hz, 1H), 3.76 (s, 3H), 3.72 (s, 3H), 3.32 (q, J=7.2Hz, 4H), 2.35 (s, 3H), 1.14 (t, J=7.2Hz, 6H)13C NMR (100MHz, CDCl3) δ 158.9, 158.3,147.3,143.1,138.0,137.8,130.7,130.5,130.3,129.4,129.1,128.5,128.4, 127.5,125.6,114.1,113.3,111.7,64.1,55.2,44.4,21.6,12.6.HRMS (ESI) calcd.for C34H39N2O4S([M+H]+) 571.2625, Found 571.2628. HPLC condition:Chiralpak AD-H Column, n-hexane/i-PrOH=85: 15,1.0mL/min, 254nm, tr-major=13.8min, tr-minor=19.5min, 75%ee.(c 0.5, CHCl3).

Claims (10)

1. efficiently synthesizing the preparation method of allylamine derivatives, it is characterised in that the specific steps of this method are as follows:
It in nitrogen atmosphere, is sequentially added into reaction flask ligand (ligand), alkali (base), metallic catalyst MmXn, solvent (solvent) and alcohol (alcohol), raw material 1 and raw material 2 are eventually adding and is stirred 18 hours under assigned temperature, is cooled to room temperature, Diatomite filtering, concentration, column chromatography for separation obtain target product.
2. it is involved in the present invention to metallic catalyst be Ni (cod)2。
3. the nitrogen heterocycle carbine ligand involved in the present invention arrived can be alkyl-substituted carbenes, such as cyclohexyl, first Base, tert-butyl etc. are also possible to the carbenes of aryl substitution, such as 2,6- diisopropyl phenyl substitution or 2,4,6- front threes Base phenyl replaces, and can be benzoquinones skeleton electrophilic type carbenes, is also possible to acenaphthenequinone skeleton power supply subtype carbenes；Also It can be chiral carbenes, chiral source can be chiral alkylamine, be also possible to chiral aniline.
When chiral carbenes are acenaphthenequinone class skeleton, chiral source is chiral aniline, chiral aniline contraposition R substituent can be first Base or tert-butyl；Aniline pendant aryl substituent group can be the phenyl that phenyl is also possible to the substitution of 3,5- dimethyl.
4. alkali used in the present invention is potassium tert-butoxide etc., but is not only limited to this.
5. it is involved in the present invention to alcohol can be the primary alconols such as methanol, ethyl alcohol, normal propyl alcohol, benzylalcohol, be also possible to isopropanol, 1- benzene The secondary alcohol such as base ethyl alcohol, 2,4- dimethyl -3- amylalcohol, 2 methyl cyclohexanol, but it is not limited to these.
6. solvent for use of the present invention is to can be tetrahydrofuran, benzene,toluene,xylene, trimethylbenzene, benzotrifluoride, DMF, acetic acid Ethyl ester etc., tetrahydrofuran is optimal, is that every mM of raw material 1 uses 5-10mL to application amount.
7. the reaction temperature involved in the present invention arrived can be within the scope of 60 DEG C to 140 DEG C, 100 DEG C or 60 DEG C of portion of product are It is optimal.
8. the raw materials used in the present invention 1 can be symmetrical alkyl alkynes, it is also possible to symmetrical aryl alkynes, aryl substituent can With aryl is o-, m-, in contraposition, substituent group can be the electron-donating group such as methyl, ethyl and methoxyl group, be also possible to fluorine or The electron-withdrawing groups such as trifluoromethyl；It can also be asymmetric alkylaryl alkynes, be also possible to asymmetric alkyl alkynes.
9. R in the raw materials used in the present invention 24Substituent group can be p-methylphenyl and be also possible to tert-butyl, R3Substituent group can be virtue Base is also possible to alkyl, and alkyl can be cyclohexyl, tert-butyl etc., but be not limited to these；Aryl can be phenyl, naphthalene and Thiophene substituent group, wherein the substituent group on aryl can be electron-donating methyl, methoxyl group, N, N- in o-, m-, contraposition Dimethyl etc. is also possible to inhale electrical fluorine, trifluoromethyl etc., but is not limited to these groups.
10. R in products therefrom 3 of the present invention4Substituent group can be p-methylphenyl and be also possible to tert-butyl, R3Substituent group can be Alkyl or aryl substituent, R1And R2Can be identical, it can be all aryl be also all alkyl, R1And R2It can also be different, it can be with For aryl and alkyl, or different alkyl, it is above to be not limited to these groups.
CN201910195634.XA 2019-03-14 2019-03-14 Alcohol promotes imines and alkynes reductive coupling reaction to construct allylamine derivatives Pending CN110229085A (en)

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