CN110204491A - A kind of synthetic method of chirality 3,4- dihydro-isoquinoline ketone compound - Google Patents

A kind of synthetic method of chirality 3,4- dihydro-isoquinoline ketone compound Download PDF

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CN110204491A
CN110204491A CN201910524966.8A CN201910524966A CN110204491A CN 110204491 A CN110204491 A CN 110204491A CN 201910524966 A CN201910524966 A CN 201910524966A CN 110204491 A CN110204491 A CN 110204491A
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dihydro
chiral
ketone compound
synthetic method
isoquinoline ketone
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CN110204491B (en
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王治明
丁寒锋
孙嫚嫚
张永刚
吴海建
李金山
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Zhejiang University ZJU
Taizhou University
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Zhejiang University ZJU
Taizhou University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
    • C07D217/24—Oxygen atoms

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Abstract

The invention discloses a kind of chiral 3; the synthetic method of 4- dihydro-isoquinoline ketone compound; it include: under the action of palladium catalyst, chiral ligand, oxidant and alkali; asymmetry C-H functionalization tandem reaction occurs in organic solvent for N- benzoyl sulfamide compound and conjugated diene compound; chirality 3, the 4- dihydro-isoquinoline ketone compound is obtained after fully reacting after post treatment.The synthetic method reaction raw materials are simple, meanwhile, yield with higher and selectivity.

Description

A kind of synthetic method of chirality 3,4- dihydro-isoquinoline ketone compound
Technical field
The invention belongs to organic synthesis fields, and in particular to a kind of synthesis side of chiral 3,4- dihydro-isoquinoline ketone compound Method.
Background technique
Chiral isoquinoline compound and their derivative are a kind of very important compounds, in pharmaceutical chemistry and material There is important application in material chemistry.Wherein chirality 3,4- dihydro-isoquinoline ketone skeleton, which is widely present in, much bioactivity In natural products and drug molecule.In conventional method, chirality 3,4- dihydro-isoquinoline ketone skeleton is all to be with corresponding Chiral Amine Raw material is reacted by the Bischler-Napieralski of intramolecular, Pomeranz-Fritsch-Bobbitt reaction, Friedel-Crafts reaction or Heck reaction are to construct.The major defect of these methods be more synthesis step, starting material and Reagent is relatively expensive, therefore from racemization raw material simple and easy to get, by asymmetric method synthesis of chiral 3,4- dihydro is different Quinolinone compounds become the main task of research.However, the report of this respect is also seldom at present.It reports within 2017 and 2018 [4+2] cycloaddition reaction synthesis of chiral 3,4- dihydro-isoquinoline ketone of the amide and alkene of two kinds of chiral cyclopentadiene rhodium catalysis Method, but rhodium catalyst is more expensive and more difficult synthesis.Therefore development is from raw material simple and easy to get, with asymmetry series connection The method of the mode synthesis of chiral 3,4- dihydro-isoquinoline ketone compound of reaction is still necessary.
In the past more than ten years, the C-H functionalization of the alkene of palladium chtalyst has become building C-C key and C-X key Very efficiently and Atom economy method, especially with the cyclization of connecting of benzamide compounds.In spite of so Big progress, palladium chtalyst benzamide compounds and alkene construct the conjunction of 3,4- dihydro-isoquinoline assimilation in such a way that C-H is functionalized Object or a kind of challenge.It is primarily due to Metal Palladium intermediate and double bond occurs the easy β-H that occurs at once after aoxidizing addition and eliminates Reaction generates C-H alkenyl product, or continues that aza-Wacker-type cyclisation or Michael addition reaction generation five occurs Membered cyclic compound, thus the six-membered cyclic compound that cannot be wanted.Currently, only Booker-Milburn seminar in 2011 Reported that an example palladium chtalyst N- alkoxy benzamides and 1,3- conjugated diene successfully synthesized 3,4- dihydro-isoquinoline ketone compound Method.But yield is all relatively low, substrate spectrum cannot also be expanded and is not asymmetric method.By with N- benzene sulfonyl Base is homing device, and arylamine or fragrant amide and 1,3- conjugated diene pass through sp2C-H functionalization/intramolecular N- allyl of palladium chtalyst The mode of base synthesizes the inspiration of the reaction of hexatomic ring, it is presumed that, asymmetric reaction system is selected by carefully deleting, it can be with N- sulphonyl yl-benzamide and 1,3- conjugated diene are raw material, pass through sp2C-H functionalization/intramolecular N- allyl of palladium chtalyst The mode of change successfully realizes the synthesis of chirality 3,4- dihydro-isoquinoline ketone compound.Therefore it is not right to report this palladium chtalyst for we Claim the C-H method of functionalization tandem reaction synthesis of chiral 3,4- dihydro-isoquinoline ketone compound.
Summary of the invention
The present invention provides a kind of synthetic method of chiral 3,4- dihydro-isoquinoline ketone compound, synthetic method reaction is former Material is simple, meanwhile, yield with higher and selectivity.
A kind of synthetic method of chiral 3,4- dihydro-isoquinoline ketone compound, comprising:
Under the action of palladium catalyst, chiral ligand, oxidant and alkali, N- benzoyl sulfamide compound and conjugation Asymmetry C-H functionalization tandem reaction occurs in organic solvent for diolefinic compounds, obtains after post treatment after fully reacting The chiral 3,4- dihydro-isoquinoline ketone compound；
Shown in the structure such as formula (II) of the N- benzoyl sulfamide compound:
Shown in the structure of the conjugated diene compound such as formula (III):
Shown in the structure such as formula (I) of the chiral 3,4- dihydro-isoquinoline ketone compound:
In formula (I)~(III), R is selected from trifluoromethyl, substitution or unsubstituted aryl, the substituent group on the aryl Selected from C1~C5Alkyl, nitro or trifluoromethyl；
R1Selected from H, C1~C5Alkyl, C1~C5One or more in alkoxy, halogen；
R2Substituent group on H, alkoxy carbonyl group, substitution or unsubstituted phenyl, the phenyl is selected from H, C1~C5Alkane Base, C1~C5One or more in alkoxy, halogen.
Preferably, R is selected from trifluoromethyl, naphthalene, substitution or unsubstituted phenyl, the substituent group on the phenyl is selected from Methyl, nitro or trifluoromethyl.
Preferably, R1One or more in H, methyl, methoxyl group, F, Cl, Br.
Preferably, R2Selected from H, carbethoxyl group, substitution or unsubstituted phenyl, the substituent group on the phenyl is selected from H, methyl, methoxyl group, one or more in F, Cl, Br.
Preferably, the chiral ligand is one in L1~L9:
As a further preference, the chiral ligand is L5.
Preferably, the organic solvent is benzotrifluoride.
Preferably, the oxidant is 2,6- dimethoxy-Isosorbide-5-Nitrae-benzoquinones, 2,5- dimethoxy-Isosorbide-5-Nitrae-benzoquinones, benzene Quinone or silver carbonate, reaction carry out under air atmosphere；As a further preference, the oxidant is 2,6- dimethoxy- 1,4- benzoquinones.
Preferably, the alkali is diisopropylethylamine.
Preferably, reaction temperature is 80~90 DEG C.
Preferably, chirality 3, the 4- dihydro-isoquinoline ketone compound is one of compound 3a~3bf；
The structure of compound 3a~3bf is as follows:
Compared with the existing technology, the beneficial effects of the present invention are embodied in:
Raw material used in the present invention is cheap and easily-available, easy to operate, meanwhile, the high income of reaction, Atom economy is good, and Obtained product selectivity with higher.
Specific embodiment
Examples 1 to 23
Mode of operation is as follows: substituted compound 1a (0.1mmol), palladium trifluoroacetate being added in 10ml Shrek pipe (0.01mmol), chiral ligand (0.012mmol), oxidant (0.03mmol), alkali (0.02mmol), 0.2 milliliter of addition are organic Solvent.Then 80 degree of openings are stirred to react 10 minutes.The 1- benzene butadiene 2a (0.2mmol) replaced is added.80 degree are stirred to react 48 hours.Reaction system is cooled to room temperature, column is crossed with petrol ether/ethyl acetate=5/1 or 3/1 and obtains target product, react Condition and reaction result are shown in Table 1, and reaction equation is as follows:
aReaction condition: 1a (0.1mmol), 2a (0.2mmol), Pd (TFA)2(0.01mmol), ligand (0.012mmol), Alkali (0.02mmol) and oxidant (0.03mmol) are in PhCF348h. is reacted under (0.2ml) air atmospherebSeparation yieldc HPLC MonitordUnder oxygen atmosphereeDIPEA=N, N- diisopropylethylaminefDABCO=1,4- diazabicylo [2.2.2] octane .g11 carbon -7- alkene of DBU=1,8- diazabicyloh2,6-DMBQ=2,6- dimethoxy -1,4- benzoquinonesi2,5-DMBQ= 2,5- dimethoxy -1,4- benzoquinonesj3.0mmol inventory.
Embodiment 24~54
Mode of operation is as follows: substituted compound 1 (0.1mmol), palladium trifluoroacetate being added in 10ml Shrek pipe (0.01mmol), chiral ligand L5 (0.012mmol), 2,6- dimethoxys-Isosorbide-5-Nitrae-benzoquinones (0.03mmol), N, N- diisopropyl 0.2 milliliter of benzotrifluoride is added in ethamine (0.02mmol).Then 80 degree of openings are stirred to react 10 minutes.Compound 2 is added (0.2mmol).80 degree are stirred to react 48 hours.Reaction system is cooled to room temperature, with petrol ether/ethyl acetate=5/1 or 3/1 It crosses column and obtains target product, reaction equation, reaction condition and reaction result are as follows:
Embodiment 55
1a (918mg, 3mmol) is added in 25ml Shrek pipe, palladium trifluoroacetate (99.7mg, 0.3mmol), L5 (97.9mg, 0.36mmol), 2,6- dimethoxys-Isosorbide-5-Nitrae-benzoquinones (151.2mg, 0.9mmol), diisopropylethylamine (77.4mg, 0.6mmol), 6 milliliters of benzotrifluorides are added.Then 80 degree of openings are stirred to react 10 minutes.It is added 2a (780mg, 6mmol).80 Degree is stirred to react 48 hours.Reaction system is cooled to room temperature, column is crossed with petrol ether/ethyl acetate=5/1 and obtains target product 3a (100.2mg, yield 77%, 94:6e.r.).
The characterize data of portion of product is as follows:
(S,E)-2-((4-Nitrophenyl)sulfonyl)-3-styryl-3,4-dihydroisoquinolin-1 (2H)-o ne (3a): faint yellow solid；36mg；83% yield；94:6e.r.；[Daicel CHIRALPAK IC bonding type hand Property chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detector, 1.0mL/min, tR=15.8min (major)and tR=40.0min (minor)]；Mp=198-199 DEG C；[α]D 20=+78.8 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.29-8.24 (m, 4H), 7.99 (d, J=7.9Hz, 1H), 7.53 (t, J=7.5Hz, 1H), 7.36 (t, J=7.6Hz, 1H), 7.31-7.20 (m, 6H), 6.71 (d, J=15.7Hz, 1H), 6.01 (dd, J=15.8, 8.1Hz, 1H), 5.71-5.66 (m, 1H), 3.73 (dd, J=16.3,5.9Hz, 1H), 3.10 (dd, J=16.4,2.0Hz, 1H)；13C{1H}NMR(100MHz,CDCl3)δ162.91,150.46,144.69,136.81,135.15,134.58,134.39, 130.83,129.10,128.79,128.68,128.37,127.83,127.17,126.59,125.32,123.67,58.01, 34.85；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C23H18N2O5SNa) 457.0834, measured value: 457.0836.
(S,E)-6-Methyl-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4- Dihydroisoquinoli n-1 (2H)-one (3b): faint yellow solid；35.8mg；80%yield；92:8e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=18.9min (major) and tR=50.7min (minor)]；Mp=180-181 DEG C；[α]D 20=+ 210.2 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.29-8.23 (m, 4H), 7.86 (d, J=8.0Hz, 1H), 7.31-7.27 (m, 3H), 7.22-7.20 (m, 2H), 7.15 (d, J=8.0Hz, 1H), 7.02 (s, 1H), 6.70 (d, J= 15.7Hz, 1H), 6.01 (dd, J=15.8,8.1Hz, 1H), 5.68-5.64 (m, 1H), 3.68 (dd, J=16.2,5.9Hz, 1H), 3.03 (dd, J=16.3,2.0Hz, 1H), 2.37 (s, 3H)；13C{1H}NMR(100MHz,CDCl3)δ162.97, 150.39,145.57,144.81,136.80,135.19,134.45,130.81,129.17,128.96,128.79,128.75, 128.65,126.58,125.44,124.49,123.65,58.08,34.86,21.79；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C24H20N2O5SNa) 471.0991, measured value: 471.0991.
(S,E)-6-Ethyl-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4- Dihydroisoquinolin-1 (2H)-one (3c): faint yellow solid；35.1mg；76%yield；93:7e.r.；[Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detector, 1.0mL/ min,tR=17.6min (major) and tR=49.5min (minor)]；Mp=137-139 DEG C；[α]D 20=+117.1 (c= 0.9,CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.28-8.23 (m, 4H), 7.89 (d, J=8.1Hz, 1H), 7.33-7.17 (m, 6H), 7.04 (s, 1H), 6.71 (d, J=15.7Hz, 1H), 6.02 (dd, J=15.7,8.1Hz, 1H), 5.69-5.65 (m, 1H), 3.70 (dd, J=16.2,5.9Hz, 1H), 3.05 (dd, J=16.3,2.0Hz, 1H), 2.66 (q, J=7.6Hz, 2H), 1.23 (t, J=7.6Hz, 3H)；13C{1H}NMR(100MHz,CDCl3)δ162.97,151.67,150.38,144.83, 136.91,135.22,134.45,130.80,129.25,128.79,128.65,127.76,127.58,126.59,125.53, 124.67,123.65,58.10,34.91,28.99,14.93；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+ (C25H22N2O5SNa) 485.1147, measured value: 485.1147.
(S,E)-6-(Tert-butyl)-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4- Dihydroisoqui nolin-1 (2H)-one (3d): faint yellow solid；39.7mg；81%yield；93.5:6.5e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=15.3min (major) and tR=47.9min (minor)]；Mp=110-112 DEG C；[α]D 20=+ 147.4 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.29-8.23 (m, 4H), 7.90 (d, J=8.4Hz, 1H), 7.37 (d, J=8.4Hz, 1H), 7.32-7.22 (m, 5H), 7.20 (s, 1H), 6.73 (d, J=15.7Hz, 1H), 6.03 (dd, J =15.7,8.2Hz, 1H), 5.69-5.65 (m, 1H), 3.72 (dd, J=16.2,5.9Hz, 1H), 3.07 (dd, J=16.4, 2.0Hz,1H),1.31(s,9H)；13C{1H}NMR(100MHz,CDCl3)δ162.90,158.55,150.37,144.84, 136.59,135.25,134.47,130.79,128.98,128.81,128.65,126.61,125.63,125.19,125.17, 124.38,123.64,58.18,35.28,35.12,31.00；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+ (C27H26N2O5SNa) 513.1460, measured value: 513.1461.
(S,E)-6-Methoxy-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4- Dihydroisoquino lin-1 (2H)-one (3e): faint yellow solid；28.8mg；62%yield；93:7e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=22.9min (major) and tR=63.4min (minor)]；Mp=69-70 DEG C；[α]D 20=+ 109.56 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.28-8.22 (m, 4H), 7.93 (d, J=8.7Hz, 1H), 7.32-7.27 (m, 3H), 7.22-7.20 (m, 2H), 6.85-6.82 (m, 1H), 6.70 (d, J=19.3Hz, 1H), 6.68 (s, 1H), 6.02 (dd, J=15.8,8.2Hz, 1H), 5.67-5.63 (m, 1H), 3.84 (s, 3H), 3.69 (dd, J=16.3, 5.9Hz, 1H), 3.03 (dd, J=16.3,2.0Hz, 1H)；13C{1H}NMR(100MHz,CDCl3)δ164.37,162.60, 150.35,144.93,139.25,135.18,134.46,131.53,130.77,128.80,128.67,126.58,125.41, 123.64,119.69,113.63,113.16,58.03,55.60,35.22；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+ (C24H20N2O6SNa) 487.0940 measured value: 487.0944.
(S,E)-7-Methyl-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4- Dihydroisoquinoli n-1 (2H)-one (3f): faint yellow solid；35.8mg；80%yield；91:9e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=17.8min (major) and tR=55.3min (minor)]；Mp=180-181 DEG C；[α]D 20=+ 160.75 (c=0.8, CH2Cl2)；1H NMR(400MHz,CDCl3)δ8.29–8.23(m,4H),7.78(s,1H),7.34– 7.27 (m, 4H), 7.22-7.20 (m, 2H), 7.12 (d, J=7.7Hz, 1H), 6.70 (d, J=15.7Hz, 1H), 6.01 (dd, J =15.7,8.1Hz, 1H), 5.68-5.64 (m, 1H), 3.67 (dd, J=16.2,5.9Hz, 1H), 3.06 (dd, J=16.3, 1.9Hz,1H),2.33(s,3H)；13C{1H}NMR(100MHz,CDCl3)δ163.15,150.40,144.73,137.75, 135.28,135.18,134.46,133.80,130.83,129.34,128.79,128.65,128.28,126.86,126.58, 125.41,123.65,58.12,34.44,21.02；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C24H20N2O5SNa) 471.0991 measured value: 471.0991.
(S,E)-8-Methyl-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4- Dihydroisoquinoli n-1 (2H)-one (3g): faint yellow solid；32.2mg；72%yield；90:10e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=12.2min (major) and tR=31.2min (minor)]；Mp=147-148 DEG C；[α]D 20=+ 174.03 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.30-8.25 (m, 4H), 7.35 (t, J=7.6Hz, 1H), 7.31-7.23 (m, 5H), 7.14 (d, J=7.7Hz, 1H), 7.06 (d, J=7.5Hz, 1H), 6.73 (d, J=15.7Hz, 1H), 6.02 (dd, J=15.8,7.8Hz, 1H), 5.64-5.60 (m, 1H), 3.66 (dd, J=16.0,5.8Hz, 1H), 3.07 (dd, J=16.0,2.1Hz, 1H), 2.54 (s, 3H)；13C{1H}NMR(100MHz,CDCl3)δ163.26,150.33, 145.16,142.92,137.82,135.38,134.51,133.30,131.72,130.46,128.74,128.55,126.64, 126.45,125.36,125.34,123.74,57.38,35.76,22.73；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+ (C24H20N2O5SNa) 471.0991, measured value: 471.0994.
(S,E)-6,8-Dimethyl-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4- Dihydroisoqui nolin-1 (2H)-one (3h): faint yellow solid；34.2mg；74%yield；91:9e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=13.7min (major) and tR=36.1min (minor)]；Mp=194-195 DEG C；[α]D 20=+ 54.6 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3)δ8.29–8.24(m,4H),7.35–7.24(m,5H),6.94 (s, 1H), 6.86 (s, 1H), 6.72 (d, J=15.7Hz, 1H), 6.03 (dd, J=15.8,7.8Hz, 1H), 5.62-5.69 (m, 1H), 3.62 (dd, J=15.9,5.8Hz, 1H), 3.00 (dd, J=16.0,2.2Hz, 1H), 2.50 (s, 3H), 2.31 (s, 3H)；13C{1H}NMR(100MHz,CDCl3)δ163.28,150.28,145.31,144.22,142.92,137.90,135.45, 134.37,132.55,130.43,128.73,128.51,127.16,126.64,125.54,123.70,122.68,57.41, 35.75,22.64,21.46；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C25H22N2O5SNa) 485.1147, measured value: 485.1146.
(S,E)-6-Fluoro-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4- Dihydroisoquinoli n-1 (2H)-one (3i): faint yellow solid；19.4mg；43%yield；81:19e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=14.2min (major) and tR=36.5min (minor)]；Mp=174-175 DEG C；[α]D 20=+ 107.4 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.29-8.24 (m, 4H), 8.01 (dd, J=8.8, 5.6Hz, 1H), 7.32-7.27 (m, 3H), 7.23-7.20 (m, 2H), 7.04 (td, J=8.5,2.5Hz, 1H), 6.94 (dd, J =8.5,2.4Hz, 1H), 6.70 (d, J=15.7Hz, 1H), 5.99 (dd, J=15.7,8.0Hz, 1H), 5.70-5.67 (m, 1H), 3.72 (dd, J=17.0,5.3Hz, 1H), 3.09 (dd, J=16.5,2.0Hz, 1H)；13C{1H}NMR(100MHz, CDCl3) δ 166.22 (d, J=256.1Hz), 162.00,150.48,144.50,140.00 (d, J=9.4Hz), 134.95, (134.82,132.21 d, J=10.0Hz), 130.87,128.84,128.82,126.61,124.86,123.71,123.51 (d, J=2.7Hz), 115.47 (d, J=22.1Hz), 115.35 (d, J=22.2Hz), 57.91,34.93；HRMS(ESI- TOF) m/z theoretical value: [M+Na]+(C23H17N2O5SFNa) 475.0740, measured value: 475.0746.
(S,E)-6-Chloro-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4- Dihydroisoquinoli n-1 (2H)-one (3j): faint yellow solid；21.5mg；46%yield；86.5:13.5e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=14.9min (major) and tR=34.8min (minor)]；Mp=220-222 DEG C；[α]D 20=+ 244.2 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.29-8.24 (m, 4H), 7.92 (d, J=8.4Hz, 1H), 7.35-7.20 (m, 7H), 6.69 (d, J=15.7Hz, 1H), 5.97 (dd, J=15.7,8.0Hz, 1H), 5.70-5.67 (m, 1H), 3.70 (dd, J=16.4,5.9Hz, 1H), 3.08 (dd, J=16.8,2.0Hz, 1H)；13C{1H}NMR(100MHz, CDCl3)δ162.13,150.52,144.40,140.86,138.49,134.90,134.88,130.90,130.67,128.85, 128.44,128.37,126.61,125.61,124.76,123.72,57.90,34.71；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C23H17N2O5SClNa) 491.0444, measured value: 491.0444.
(S,E)-6-Bromo-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4- Dihydroisoquinoli n-1 (2H)-one (3k): faint yellow solid；16.9mg；33%yield；89:11e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=16.0min (major) and tR=35.9min (minor)]；Mp=201-202 DEG C；[α]D 20=+ 208.5 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.28-8.24 (m, 4H), 7.84 (d, J=8.4Hz, 1H), 7.50 (d, J=8.4z, 1H), 7.42 (s, 1H), 7.32-7.26 (m, 3H), 7.23-7.20 (m, 2H), 6.69 (d, J= 15.7Hz, 1H), 5.97 (dd, J=15.7,8.0Hz, 1H), 5.70-5.66 (m, 1H), 3.71 (dd, J=16.4,5.9Hz, 1H), 3.07 (dd, J=16.4,2.0Hz, 1H)；13C{1H}NMR(100MHz,CDCl3)δ162.28,150.52,144.38, 138.55,134.90,131.41,131.35,130.90,130.67,129.64,128.85,126.62,126.05,124.75, 123.73,57.91,34.63；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C23H17N2O5SBrNa) 534.9939, measurement Value: 534.9941.
(S,E)-7-Fluoro-6-methoxy-2-((4-nitrophenyl)sulfonyl)-3-styryl-3,4- Dihydr oisoquinolin-1 (2H)-one (3l): faint yellow solid；26.0mg；54%yield；91:9e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=18.9min (major) and tR=45.4min (minor)]；Mp=175-176 DEG C；[α]D 20=+ 100.0 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.28-8.23 (m, 4H), 7.67 (d, J=11.2Hz, 1H), 7.32-7.28 (m, 3H), 7.24-7.21 (m, 2H), 6.74-6.69 (m, 2H), 6.01 (dd, J=15.7,8.2Hz, 1H), 5.68-5.64 (m, 1H), 3.93 (s, 3H), 3.69 (dd, J=16.5,6.0,1H), 3.02 (dd, J=16.4,2.0Hz, 1H)；13C{1H}NMR(100MHz,CDCl3) δ 161.75,152.77,151.59 (d, J=257.6Hz), 150.45,144.58, (135.00,134.74,134.51 d, J=3.5Hz), 130.86,128.86,128.84 (d, J=4.0Hz), 126.58, 125.02,123.67,119.65 (d, J=6.5Hz), 116.34 (d, J=40Hz), 112.02 (d, J=1.2Hz), 58.11, 56.41,34.81；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C24H19N2O6FSNa) 505.0846, measured value: 505.0854.
(S,E)-3-(4-Methylstyryl)-2-((4-nitrophenyl)sulfonyl)-3,4- Dihydroisoquinoli n-1 (2H)-one (3m): faint yellow solid；36.7mg；82%yield；92.5:7.5e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=16.1min (major) and tR=46.1min (minor)]；Mp=189-190 DEG C；[α]D 20=+ 103.0 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.29-8.23 (m, 4H), 7.98 (d, J=7.8Hz, 1H), 7.53 (t, J=7.5Hz, 1H), 7.35 (t, J=7.6Hz, 1H), 7.23 (d, J=7.5Hz, 1H), 7.12-7.07 (m, 4H), 6.68 (d, J=15.7Hz, 1H), 5.94 (dd, J=15.7,8.2Hz, 1H), 5.69-5.64 (m, 1H), 3.72 (dd, J= 16.3,5.9Hz, 1H), 3.09 (dd, J=16.3,2.0Hz, 1H), 2.32 (s, 3H)；13C{1H}NMR(100MHz,CDCl3)δ 162.93,150.42,144.70,138.77,136.90,134.57,134.37,132.31,130.86,129.49,129.09, 128.39,127.79,127.15,126.51,124.12,123.65,58.20,34.93,21.26；HRMS(ESI-TOF)m/z Theoretical value: [M+Na]+(C24H20N2O5SNa) 471.0991, measured value: 471.0993.
(S,E)-3-(4-Methoxystyryl)-2-((4-nitrophenyl)sulfonyl)-3,4- Dihydroisoquin olin-1 (2H)-one (3n): faint yellow solid；32.1mg；69%yield；92:8e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=25.7min (major) and tR=59.1min (minor)]；Mp=141-142 DEG C；[α]D 20=+ 178.0 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.29-8.22 (m, 4H), 7.98 (d, J=7.9Hz, 1H), 7.53 (t, J=7.5Hz, 1H), 7.36 (t, J=7.6Hz, 1H), 7.23 (d, J=7.6Hz, 1H), 7.16-7.14 (m, 2H), 6.82-6.80 (m, 2H), 6.67 (d, J=15.7Hz, 1H), 5.85 (dd, J=15.7,8.3Hz, 1H), 5.67-5.63 (m, 1H), 3.80 (s, 3H), 3.72 (dd, J=16.3,5.8Hz, 1H), 3.08 (dd, J=16.3,2.0Hz, 1H)；13C{1H}NMR (100MHz,CDCl3)δ162.94,159.99,150.42,144.74,136.94,134.34,134.18,130.84, 129.09,128.39,127.90,127.78,127.16,123.63,122.81,114.17,58.31,55.33,35.01； HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C24H20N2O6SNa) 487.0940, measured value: 487.0943.
(S,E)-3-(4-Fluorostyryl)-2-((4-nitrophenyl)sulfonyl)-3,4- Dihydroisoquinoli n-1 (2H)-one (3o): faint yellow solid；35.7mg；79%yield；88:12e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=19.9min (major) and tR=39.7min (minor)]；Mp=163-164 DEG C；[α]D 20=+ 76.2 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.27-8.26 (m, 4H), 7.98 (d, J=7.9Hz, 1H), 7.54 (t, J=7.5Hz, 1H), 7.37 (t, J=7.6Hz, 1H), 7.25-7.18 (m, 3H), 7.00-6.94 (m, 2H), 6.69 (d, J=15.7Hz, 1H), 5.94 (dd, J=15.8,8.1Hz, 1H), 5.69-5.65 (m, 1H), 3.72 (dd, J=16.3, 5.9Hz, 1H), 3.10 (dd, J=16.3,2.0Hz, 1H)；13C{1H}NMR(100MHz,CDCl3)δ162.85,162.84(d,J =247.3Hz), 150.47,144.67,136.71,134.43,133.40,131.30 (d, J=3.4Hz), 130.78, (129.12,128.37,128.27 d, J=8.0Hz), 127.88,127.13,125.04 (d, J=2.3Hz), 123.70, 115.80 (d, J=21.6Hz), 57.91,34.80；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C23H17N2O5SFNa) 475.0740 measured value: 475.0743.
(S,E)-3-(4-Chlorostyryl)-2-((4-nitrophenyl)sulfonyl)-3,4- Dihydroisoquinoli n-1 (2H)-one (3p): faint yellow solid；34.2mg；73%yield；92.5:7.5e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=18.8min (major) and tR=37.2min (minor)]；Mp=170-171 DEG C；[α]D 20=+ 115.6 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.29-8.25 (m, 4H), 7.98 (d, J=7.9Hz, 1H), 7.54 (t, J=7.5Hz, 1H), 7.37 (t, J=7.6Hz, 1H), 7.26-7.23 (m, 3H), 7.17-7.13 (m, 2H), 6.68 (d, J=15.7Hz, 1H), 6.01 (dd, J=15.8,8.0Hz, 1H), 5.69-5.65 (m, 1H), 3.71 (dd, J=16.3, 5.9Hz, 1H), 3.10 (dd, J=16.4,2.0Hz, 1H)；13C{1H}NMR(100MHz,CDCl3)δ162.82,150.48, 144.63,136.64,134.46,134.42,133.61,133.32,130.77,129.13,128.98,128.36,127.92, 127.83,127.10,125.96,123.72,57.81,34.72；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+ (C23H17N2O5SClNa) 491.0444, measured value: 491.0443.
(S,E)-3-(4-Bromostyryl)-2-((4-nitrophenyl)sulfonyl)-3,4- Dihydroisoquinoli n-1 (2H)-one (3q): faint yellow solid；30.3mg；59%yield；91.5:8.5e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=19.9min (major) and tR=38.9min (minor)]；Mp=174-175 DEG C；[α]D 20=+ 64.4 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.30-8.25 (m, 4H), 7.98 (d, J=7.8Hz, 1H), 7.54 (t, J=7.5Hz, 1H), 7.41-7.35 (m, 3H), 7.24 (d, J=7.5Hz, 1H), 7.09 (d, J=8.4Hz, 2H), 6.66 (d, J=15.7Hz, 1H), 6.02 (dd, J=15.7,7.9Hz, 1H), 5.69-5.65 (m, 1H), 3.71 (dd, J= 16.3,6.0Hz, 1H), 3.09 (dd, J=16.3,2.0Hz, 1H)；13C{1H}NMR(100MHz,CDCl3)δ162.82, 150.48,144.63,136.64,134.46,134.42,133.61,133.32,130.77,129.13,128.98,128.36, 127.92,127.83,127.10,125.96,123.72,57.81,34.72；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+ (C23H17N2O5SBrNa) 534.9939, measured value: 534.9937.
(S,E)-3-(3-Bromostyryl)-2-((4-nitrophenyl)sulfonyl)-3,4- Dihydroisoquinoli n-1 (2H)-one (3r): faint yellow solid；33.8mg；66%yield；91.5:8.5e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=17.1min (major) and tR=36.4min (minor)]；Mp=96-97 DEG C；[α]D 20=+ 32.8 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.30-8.25 (m, 4H), 7.99 (d, J=7.8Hz, 1H), 7.54 (t, J=7.5Hz, 1H), 7.39-7.35 (m, 3H), 7.24 (d, J=7.6Hz, 1H), 7.17-7.11 (m, 2H), 6.63 (d, J=15.7Hz, 1H), 6.03 (dd, J=15.8,7.8Hz, 1H), 5.69-5.66 (m, 1H), 3.71 (dd, J=16.3, 6.0Hz, 1H), 3.10 (dd, J=16.4,2.0Hz, 1H)；13C{1H}NMR(100MHz,CDCl3)δ162.80,150.51, 144.61,137.29,136.54,134.49,133.02,131.50,130.77,130.29,129.33,129.17,128.35, 127.96,127.11,127.00,125.39,123.75,122.93,57.65,34.65；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C23H17N2O5SBrNa) 534.9939, measured value: 534.9945.
(S,E)-3-(2-Methylstyryl)-2-((4-nitrophenyl)sulfonyl)-3,4- Dihydroisoquinoli n-1 (2H)-one (3s): faint yellow solid；35.8mg；80%yield；96:4e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=15.8min (major) and tR=33.0min (minor)]；Mp=134-135 DEG C；[α]D 20=+ 48.2 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.31-8.27 (m, 4H), 7.98 (d, J=7.8Hz, 1H), 7.52 (t, J=15.1Hz, 1H), 7.35 (t, J=7.6Hz, 1H), 7.23 (d, J=7.6Hz, 1H), 7.24-7.06 (m, 4H), 6.94 (d, J=15.6Hz, 1H), 5.90 (dd, J=15.6,7.6Hz, 1H), 5.72-5.69 (m, 1H), 3.72 (dd, J= 16.3,5.8Hz, 1H), 3.12 (dd, J=16.3,2.0Hz, 1H), 2.22 (s, 3H)；13C{1H}NMR(100MHz,CDCl3)δ 162.97,150.47,144.79,136.81,135.85,134.43,134.36,132.43,130.74,130.53,129.03, 128.47,128.35,127.82,127.26,126.74,126.19,125.48,123.74,57.99,34.89,19.58； HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C24H20N2O5SNa) 471.0991, measured value: 471.0999.
(S,E)-3-(2-Methoxystyryl)-2-((4-nitrophenyl)sulfonyl)-3,4- Dihydroisoquin olin-1 (2H)-one (3t): faint yellow solid；29.6mg；64%yield；95:5e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=20.8min (major) and tR=54.8min (minor)]；Mp=126-127 DEG C；[α]D 20=+ 167.0 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3)δ8.33–8.31(m,2H),8.24–8.22(m,2H),7.98 (d, J=7.9Hz, 1H), 7.52 (t, J=7.5Hz, 1H), 7.35 (t, J=7.6Hz, 1H), 7.26-7.22 (m, 2H), 7.10 (d, J=7.7Hz, 1H), 7.07 (d, J=15.8Hz, 1H), 6.86 (d, J=8.4Hz, 1H), 6.83 (t, J=7.6Hz, 1H), 5.95 (dd, J=15.8,8.5Hz, 1H), 5.71-5.67 (m, 1H), 3.80 (s, 3H), 3.73 (dd, J=16.0,5.6Hz, 1H), 3.10 (dd, J=16.3,2.0Hz, 1H)；13C{1H}NMR(100MHz,CDCl3)δ162.99,156.84,150.38, 144.66,137.08,134.31,131.03,129.82,129.08,128.42,127.73,127.18,126.80,125.52, 124.17,123.57,120.65,110.94,58.57,55.46,35.02；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+ (C24H20N2O6SNa) 487.0940, measured value: 487.0944.
(S,E)-2-((4-Nitrophenyl)sulfonyl)-3-(2-(trifluoromethoxy)styryl)-3,4- Dihyd roisoquinolin-1 (2H)-one (3u): faint yellow solid；40.4mg；78%yield；95:5e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=10.3min (major) and tR=19.7min (minor)]；Mp=76-77 DEG C；[α]D 20=+ 55.0 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.31-8.26 (m, 4H), 7.98 (d, J=7.5Hz, 1H), 7.53 (t, J=7.5Hz, 1H), 7.36 (t, J=7.6Hz, 1H), 7.31-7.16 (m, 5H), 6.89 (d, J=15.8Hz, 1H), 6.08 (dd, J=15.9,7.6Hz, 1H), 5.75-5.70 (m, 1H), 3.73 (dd, J=16.3,5.8Hz, 1H), 3.12 (dd, J =16.4,2.0Hz, 1H)；13C{1H}NMR(100MHz,CDCl3)δ162.84,150.50,144.61,136.63,134.41, 130.78,129.72,129.10,128.69,128.61,128.30,127.87,127.43,127.18,127.12,127.03, (123.70,121.54,120.38 q, J=257.0Hz), 57.70,34.66；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+ (C24H17N2O6F3SNa) 541.0657, measured value: 541.0665.
(S,E)-3-(2-Fluorostyryl)-2-((4-nitrophenyl)sulfonyl)-3,4- Dihydroisoquinoli n-1 (2H)-one (3v): faint yellow solid；34.8mg；77%yield；96:4e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=20.4min (major) and tR=38.5min (minor)]；Mp=180-181 DEG C；[α]D 20=+ 86.8 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.32-8.26 (m, 4H), 7.99 (d, J=7.9Hz, 1H), 7.53 (t, J=7.5Hz, 1H), 7.36 (t, J=7.6Hz, 1H), 7.26-7.15 (m, 3H), 7.05-7.00 (m, 2H), 6.81 (d, J=15.9Hz, 1H), 6.08 (dd, J=15.9,7.9Hz, 1H), 5.72-5.68 (m, 1H), 3.73 (dd, J=16.3, 5.9Hz, 1H), 3.12 (dd, J=16.4,1.9Hz, 1H)；13C{1H}NMR(100MHz,CDCl3)δ162.86,160.27(d,J =248.7Hz), 150.50,144.61,136.72,134.41,130.84,130.02 (d, J=8.4Hz), 129.14, 128.34,128.21 (d, J=5.2Hz), 127.86,127.70 (d, J=3.4Hz), 127.23 (d, J=3.2Hz), 127.15,124.29 (d, J=3.5Hz), 123.71,123.07 (d, J=12.0Hz), 115.96 (d, J=21,7Hz), 58.04,34.75；HRMS(ESI-TOF)m/z calcd for[M+Na]+(C23H17N2O5SFNa) 475.0740, measured value: 475.0746.
(S,E)-3-(2-Chlorostyryl)-2-((4-nitrophenyl)sulfonyl)-3,4- Dihydroisoquinoli n-1 (2H)-one (3w): faint yellow solid；36.5mg；78%yield；94.5:5.5e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=17.9min (major) and tR=35.2min (minor)]；Mp=153-154 DEG C；[α]D 20=+ 61.4 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.34-8.25 (m, 4H), 7.99 (d, J=7.7Hz, 1H), 7.53 (t, J=7.5Hz, 1H), 7.38-7.33 (m, 2H), 7.26-7.07 (m, 5H), 5.97 (dd, J=15.7,8.0Hz, 1H), 5.75-5.72 (m, 1H), 3.74 (dd, J=16.3,5.8Hz, 1H), 3.13 (dd, J=16.4,2.1Hz, 1H)；13C {1H}NMR(100MHz,CDCl3)δ162.85,150.50,144.58,136.75,134.43,133.51,133.31,130.92, 130.90,129.89,129.64,129.14,128.39,128.21,127.87,127.19,126.99,126.91,123.72, 57.80,34.71；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C23H17N2O5SClNa) 491.0444, measured value: 491.0453.
(S,E)-3-(2-Bromostyryl)-2-((4-nitrophenyl)sulfonyl)-3,4- Dihydroisoquinoli n-1 (2H)-one (3x): faint yellow solid；34.9mg；68%yield；98:2e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=17.9min (major) and tR=35.9min (minor)]；Mp=240-241 DEG C；[α]D 20=+ 76.0 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.34 (d, J=9.0Hz, 2H), 8.27 (d, J=9.0Hz, 2H), 7.99 (d, J=7.8Hz, 1H), 7.56-7.52 (m, 2H), 7.36 (t, J=7.6Hz, 1H), 7.26-7.09 (m, 4H), 7.05 (d, J=15.6Hz, 1H), 5.93 (dd, J=15.6,8.0Hz, 1H), 5.75-5.72 (m, 1H), 3.74 (dd, J= 16.3,5.8Hz, 1H), 3.13 (dd, J=16.4,2.0Hz, 1H)；13C{1H}NMR(100MHz,CDCl3)δ162.84, 150.51,144.56,136.72,135.28,134.42,133.49,133.13,130.94,129.86,129.17,128.38, 128.29,127.88,127.61,127.20,127.09,123.77,123.72,57.67,34.69；HRMS(ESI-TOF)m/z Theoretical value: [M+Na]+(C23H17N2O5SBrNa) 534.9939, measured value: 534.9945.
(S,E)-3-(2-Bromo-5-methoxystyryl)-2-((4-nitrophenyl)sulfonyl)-3,4- Dihydr oisoquinolin-1 (2H)-one (3y): faint yellow solid；33.6mg；62%yield；98:2e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=20.6min (major) and tR=41.9min (minor)]；Mp=152-153 DEG C；[α]D 20=+ 75.6 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.35-8.27 (m, 4H), 7.99 (d, J=7.7Hz, 1H), 7.54 (t, J=7.5Hz, 1H), 7.43-7.41 (m, 1H), 7.36 (t, J=7.6Hz, 1H), 7.25 (d, J=7.6Hz, 1H), 6.98 (d, J=15.6Hz, 1H), 6.71-6.68 (m, 2H), 5.90 (dd, J=15.6,7.9Hz, 1H), 5.75-5.70 (m, 1H), 3.77-3.72 (m, 4H), 3.12 (dd, J=16.4,2.0Hz, 1H)；13C{1H}NMR(100MHz,CDCl3)δ162.83, 158.90,150.52,144.53,136.67,135.99,134.44,133.69,133.47,130.95,129.18,128.39, 128.37,127.90,127.18,123.73,115.05,114.35,113.12,57.64,55.55,34.65；HRMS(ESI- TOF) m/z theoretical value: [M+Na]+(C24H19N2O6SBrNa) 565.0045, measured value: 565.0051.
(S,E)-Ethyl3-(2-((4-nitrophenyl)sulfonyl)-1-oxo-1,2,3,4- Tetrahydroisoquin olin-3-yl) acrylate (3z): white solid；24.1mg；56%yield；87.5: 12.5e.r.；[Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50, 254nm UV detector, 1.0mL/min, tR=20.5min (major) and tR=29.8min (minor)]；Mp=168-169 ℃；[α]D 20=+80.6 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3)δ8.38–8.28(m,4H),7.96(dd,J =7.9,1.3Hz, 1H), 7.53 (td, J=7.5,1.4Hz, 1H), 7.36 (t, J=7.7Hz, 1H), 7.21 (d, J=7.6Hz, 1H), 6.76 (dd, J=15.6,6.1Hz, 1H), 5.93 (dd, J=15.6,1.5Hz, 1H), 5.70-5.66 (m, 1H), 4.19- 4.06 (m, 2H), 3.66 (dd, J=16.4,6.2Hz, 1H), 3.10 (dd, J=16.5,2.0Hz, 1H), 1.23 (t, J= 7.1Hz,3H)；13C{1H}NMR(100MHz,CDCl3)δ165.17,162.61,150.65,144.24,143.28,135.86, 134.59,130.78,129.17,128.25,128.11,126.96,124.81,123.89,60.99,55.99,33.58, 14.12；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C20H18N2O7SNa) 453.0732, measured value: 453.0733.
(S,E)-2-((4-Nitrophenyl)sulfonyl)-3-(3-phenylprop-1-en-1-yl)-3,4- Dihydroi soquinolin-1 (2H)-one (3ba): faint yellow solid；28.7mg；64%yield；95:5e.r.； [Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=50/50,254nm UV detection Device, 1.0mL/min, tR=19.2min (major) and tR=49.8min (minor)]；Mp=176-177 DEG C；[α]D 20=+ 246.0 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.15-8.08 (m, 4H), 7.95 (d, J=7.8Hz, 1H), 7.54 (t, J=7.5Hz, 1H), 7.36 (t, J=7.7Hz, 1H), 7.29-7.23 (m, 4H), 6.97 (d, J=6.4Hz, 2H), 5.88-5.80 (m, 1H), 5.56-5.53 (m, 1H), 5.45 (dd, J=15.1,7.2Hz, 1H), 3.63 (dd, J=16.2, 5.7Hz, 1H), 3.29 (dd, J=15.0,6.8Hz, 1H), 3.16 (dd, J=15.0,7.6Hz, 1H), 3.02 (dd, J= 16.0,2.0Hz,1H)；13C{1H}NMR(100MHz,CDCl3)δ163.02,150.34,144.50,138.96,136.95, 134.27,134.12,130.69,129.01,128.70,128.38,128.31,127.71,127.68,127.34,126.55, 123.61,57.20,38.51,34.79；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C24H20N2O5SNa)471.0991, Measured value: 471.0996.
(S, E) -3-Styryl-2-tosyl-3,4-dihydroisoquinolin-1 (2H)-one (3bb): white is solid Body；12.9mg；32%yield；90:10e.r.；[Daicel CHIRALPAK IC bonded chiral chromatography post detection, n- Hexane/i-PrOH=70/30,254nm UV detector, 1.0mL/min, tR=20.7min (major) and tR= 31.0min(minor)]；Mp=112-113 DEG C；[α]D 20=+72.6 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.01-8.98 (m, 3H), 7.47 (t, J=7.5Hz, 1H), 7.31 (t, J=7.6Hz, 1H), 7.26-7.17 (m, 8H), 6.63 (d, J=15.9Hz, 1H), 6.01 (dd, J=15.7,7.4Hz, 1H), 5.71-5.67 (m, 1H), 3.66 (dd, J=16.2, 5.9Hz, 1H), 3.05 (dd, J=16.3,1.9Hz, 1H), 2.38 (s, 3H)；13C{1H}NMR(100MHz,CDCl3)δ 162.87,144.71,136.81,136.23,135.67,133.82,133.75,129.39,129.18,128.98,128.57, 128.20,128.15,127.89,127.55,126.61,126.21,57.38,34.85,21.66；HRMS(ESI-TOF)m/z Theoretical value: [M+Na]+(C24H21NO3SNa) 426.1140, measured value: 426.1140.
(S,E)-2-(Naphthalen-2-ylsulfonyl)-3-styryl-3,4-dihydroisoquinolin-1 (2H)-one (3bc): yellow solid；28.5mg；65%yield；91.5:8.5e.r.；[Daicel CHIRALPAK IC bonding Type chiral chromatogram post detection, n-hexane/i-PrOH=70/30,254nm UV detector, 1.0mL/min, tR=19.3min (major)and tR=28.9min (minor)]；Mp=160-161 DEG C；[α]D 20=+33.6 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.67 (s, 1H), 8.07 (d, J=8.8Hz, 1H), 7.97 (d, J=7.9Hz, 1H), 7.87 (d, J =9.3Hz, 2H), 7.74 (d, J=8.3Hz, 1H), 7.61 (t, J=7.6Hz, 1H), 7.53-7.47 (m, 2H), 7.32-7.19 (m, 7H), 6.74 (d, J=15.8Hz, 1H), 6.04 (dd, J=15.7,7.8Hz, 1H), 5.79-5.75 (m, 1H), 3.73 (dd, J=16.2,5.8Hz, 1H), 3.09 (d, J=16.2Hz, 1H)；13C{1H}NMR(100MHz,CDCl3)δ162.82, 136.79,136.03,135.57,135.28,134.09,133.88,131.77,131.54,129.67,129.22,129.02, 128.62,128.46,128.32,128.16,127.78,127.74,127.59,127.28,126.68,126.08,124.07, 57.70,34.90；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C27H21NO3SNa) 462.1140, measured value: 462.1141.
(S,E)-3-Styryl-2-((4-(trifluoromethyl)phenyl)sulfonyl)-3,4- Dihydroisoquino lin-1 (2H)-one (3bd): white solid；35.2mg；77%yield；93:7e.r.；[Daicel CHIRALPAK IC bonded chiral chromatography post detection, n-hexane/i-PrOH=70/30,254nm UV detector, 1.0mL/ min,tR=7.8min (major) and tR=12.1min (minor)]；Mp=237-238 DEG C；[α]D 20=+48.0 (c= 1.0,CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.23 (d, J=8.3Hz, 2H), 8.00 (d, J=8.0Hz, 1H), 7.70 (d, J=8.3Hz, 2H), 7.51 (t, J=7.5Hz, 1H), 7.35 (t, J=7.6Hz, 1H), 7.29-7.16 (m, 6H), 6.64 (d, J=15.8Hz, 1H), 6.01 (dd, J=15.8,7.8Hz, 1H), 5.71-5.67 (m, 1H), 3.71 (dd, J=16.3, 5.9Hz, 1H), 3.09 (dd, J=16.3,2.0Hz, 1H)；13C{1H}NMR(100MHz,CDCl3)δ162.92,142.57, (136.78,135.27,135.06 q, J=32.9Hz), 134.28,134.22,129.99,129.08,128.70,128.51, (128.30,127.75,127.37,126.60,125.68 q, J=3.7Hz), 125.54,123.12 (q, J=268.5Hz), 57.81,34.85；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C24H18NO3SF3Na) 480.0857, measured value: 480.0859.
(S,E)-2-((2-Nitrophenyl)sulfonyl)-3-styryl-3,4-dihydroisoquinolin-1 (2H)-o ne (3be): faint yellow solid；30.4mg；70%yield；90.5:9.5e.r.；[Daicel CHIRALPAK IC Bonded chiral chromatography post detection, n-hexane/i-PrOH=80/20,254nm UV detector, 1.0mL/min, tR= 14.7min(minor)and tR=16.0min (major), the absolute configuration of the stereogenic center was determined by the product of removing the N- protectinggroup,which was consistent with 4]；Mp=188-189 DEG C；[α]D 20=+5.6 (c= 1.0,CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.67 (d, J=7.7Hz, 1H), 8.01 (d, J=7.8Hz, 1H), 7.85- 7.75 (m, 3H), 7.51 (t, J=7.5Hz, 1H), 7.35-7.18 (m, 7H), 6.77 (d, J=15.8Hz, 1H), 6.22 (dd, J =15.8,6.6Hz, 1H), 5.53-5.49 (m, 1H), 3.95 (dd, J=16.3,6.0Hz, 1H), 3.10 (d, J=16.1Hz, 1H)；13C{1H}NMR(100MHz,CDCl3)δ163.09,148.19,137.17,135.83,135.47,134.73,134.19, 133.48,132.82,132.11,128.79,128.51,128.26,128.11,127.58,127.51,126.77,126.33, 124.53,57.73,33.56；HRMS (ESI-TOF) m/z theoretical value: [M+Na]+(C23H18N2O5SNa) 457.0834, measurement Value: 457.0836.
(S,E)-3-styryl-2-((trifluoromethyl)sulfonyl)-3,4-dihydroisoquinolin-1 (2H)-one (3bf): faint yellow solid；17.1mg；45%yield；88.5:11.5e.r.；[determined by HPLC Analysis Daicel Chirapak IB, n-hexane/i-PrOH=90/10,254nm UV detector, 1.0mL/min, tR=8.1min (minor) and tR=8.5min (major)]；Mp=155-156 DEG C；[α]D 20=+33 (c=1.0, CH2Cl2)；1H NMR(400MHz,CDCl3) δ 8.17 (d, J=7.9Hz, 1H), 7.60 (t, J=7.5Hz, 1H), 7.45 (t, J =7.6Hz, 1H), 7.30-7.21 (m, 6H), 6.67 (d, J=15.8Hz, 1H), 6.07 (dd, J=15.7,7.9Hz, 1H), 5.54-5.37 (m, 1H), 3.71 (dd, J=16.4,5.7Hz, 1H), 3.11 (dd, J=16.5,2.0Hz, 1H)；13C{1H}NMR (100MHz,CDCl3)δ162.65,137.03,135.27,135.06,134.92,129.81,128.65,128.60, (128.56,128.13,126.76,126.73,124.10,119.4 q, J=322.8Hz), 59.90,34.66；HRMS(ESI- TOF) m/z theoretical value: [M+Na]+(C18H14NO3SF3Na) 404.0544, measured value: 404.0546.

Claims (10)

1. a kind of synthetic method of chiral 3,4- dihydro-isoquinoline ketone compound characterized by comprising
Under the action of palladium catalyst, chiral ligand, oxidant and alkali, N- benzoyl sulfamide compound and conjugated diene Asymmetry C-H functionalization tandem reaction occurs in organic solvent for class compound, obtains after post treatment after fully reacting described Chiral 3,4- dihydro-isoquinoline ketone compound；
Shown in the structure such as formula (II) of the N- benzoyl sulfamide compound:
Shown in the structure of the conjugated diene compound such as formula (III):
Shown in the structure such as formula (I) of the chiral 3,4- dihydro-isoquinoline ketone compound:
In formula (I)~(III), R is selected from trifluoromethyl, substitution or unsubstituted aryl, and the substituent group on the aryl is selected from C1 ~C5Alkyl, nitro or trifluoromethyl；
R1Selected from H, C1~C5Alkyl, C1~C5One or more in alkoxy, halogen；
R2Substituent group on H, alkoxy carbonyl group, substitution or unsubstituted phenyl, the phenyl is selected from H, C1~C5Alkyl, C1 ~C5One or more in alkoxy, halogen.
2. the synthetic method of chiral 3,4- dihydro-isoquinoline ketone compound according to claim 1, which is characterized in that R choosing Methyl, nitro or trifluoromethyl are selected from from the substituent group on trifluoromethyl, naphthalene, substitution or unsubstituted phenyl, the phenyl.
3. the synthetic method of chiral 3,4- dihydro-isoquinoline ketone compound according to claim 1, which is characterized in that R1Choosing From one or more in H, methyl, methoxyl group, F, Cl, Br.
4. the synthetic method of chiral 3,4- dihydro-isoquinoline ketone compound according to claim 1, which is characterized in that R2Choosing H, methyl, methoxyl group, F, Cl, Br are selected from from the substituent group on H, carbethoxyl group, substitution or unsubstituted phenyl, the phenyl In one or more.
5. the synthetic method of chiral 3,4- dihydro-isoquinoline ketone compound according to claim 1, which is characterized in that described Chiral ligand be L1~L9 in one:
6. the synthetic method of chiral 3,4- dihydro-isoquinoline ketone compound according to claim 1, which is characterized in that described Organic solvent be benzotrifluoride.
7. the synthetic method of chiral 3,4- dihydro-isoquinoline ketone compound according to claim 1, which is characterized in that described Oxidant be 2,6- dimethoxy-Isosorbide-5-Nitrae-benzoquinones, 2,5- dimethoxy-Isosorbide-5-Nitrae-benzoquinones, benzoquinones or silver carbonate, react in air It is carried out under atmosphere.
8. the synthetic method of chiral 3,4- dihydro-isoquinoline ketone compound according to claim 1, which is characterized in that described Alkali be diisopropylethylamine.
9. the synthetic method of chiral 3,4- dihydro-isoquinoline ketone compound according to claim 1, which is characterized in that reaction Temperature is 80~90 DEG C.
10. the synthetic method of chiral 3,4- dihydro-isoquinoline ketone compound according to claim 1, which is characterized in that institute The chiral 3,4- dihydro-isoquinoline ketone compound stated is one of compound 3a~3bf；
The structure of compound 3a~3bf is as follows:
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CN113149895A (en) * 2021-03-12 2021-07-23 台州学院 Method for synthesizing isoquinolone compounds or pyridone compounds
CN113149895B (en) * 2021-03-12 2022-07-05 台州学院 Method for synthesizing isoquinolone compounds or pyridone compounds
CN115260096A (en) * 2022-08-19 2022-11-01 武汉大学 Method for synthesizing dihydroisoquinolinone compound based on carbon monoxide gas or carbon monoxide alternative source
CN115260096B (en) * 2022-08-19 2024-04-09 武汉大学 Method for synthesizing dihydroisoquinolinones based on carbon monoxide gas or carbon monoxide substitution source

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