CN105541662B - The solid phase synthesis process of dihydro naphthalene compounds - Google Patents
The solid phase synthesis process of dihydro naphthalene compounds Download PDFInfo
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- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
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- C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
- C07C1/321—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen the hetero-atom being a non-metal atom
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Abstract
The solid phase synthesis process of dihydro naphthalenes chemical compounds I, belongs to organic chemistry filed.This method includes：1. being carrier with 1% crosslinked polystyrene resin, loaded by polystyrene seleno succimide reagent III is prepared；2. under trifluoromethayl sulfonic acid trimethyl silicane ester catalysis, molecule inner ring condensation occurs for III induction alkene V, forms 3- loaded by polystyrene selenos -1,2,3,4- naphthanes VI；3. VI oxidized dose of oxidation eliminates, it is not required to further separate, directly obtains dihydronaphthalene I.Raw material of the present invention is easy to get, and products collection efficiency is good, and purity is high, easy to operate, and post processing is simple, has good prospects for commercial application.
Description
Technical field
The invention belongs to organic chemistry filed, and in particular to such as the solid phase synthesis process of the dihydro naphthalenes chemical compounds I of lower structure：
R in formula1=H ,-CN ,-COOCH3；R2=H, C1-4Alkyl ,-COOCH3；R3=H ,-CH3, Ph ,-
C6H4CH3,-C6H4OCH3,-C6H4Cl ,-C6H4Br；R4=H, C1-6Alkyl, Ph ,-C6H4CH3,-C6H4OCH3,-
C6H4Cl ,-C6H4COOCH3,-C6H4NO2；R5=H ,-OCH3,-OBn；R6=H ,-OCH3,-Br.
Background technology
Since first product naproxen of naphthalenes medicine of beginning of the sixties in last century U.S. Syntex company's exploitation comes out,
It shows a variety of pharmacological activity such as the long-acting antipyretic, analgesia of high-efficiency low-toxicity, anti-inflammatory, is widely used by the whole world at present.Grind
Most of compound for showing to include hydrogenated naphthalene nucleus construction unit is studied carefully with pharmacological activity such as antipyretic, analgesia, anti-inflammatories.For this reason,
Build more hydrogenated naphthalene nucleus structures has become the antipyretic of the various high-efficiency low-toxicities of current design synthesis, analgesia, the research hotspot of anti-inflammatory agent.
In synthesis in solid state, selenium is comparatively ideal linker and polymeric reagent.Since the bond energy of carbon-selenium key is weaker, thus Organic Selenium
Compound can be used as important organic synthesis intermediate, and can be with a variety of methods to the product point using selenium as linker
Son carries out " cutting " with polymer and obtains the target molecule of high-purity.Nicolaou etc. (Chem.Commun.1998,1947) with
1% cheap crosslinked polystyrene prepares the seleno bromide of loaded by polystyrene for raw material, and uses it within a short period of time
A benzopyrans compounds (J.Am.Chem.Soc.2000,9954) more than 10,000 are prepared.It has been currently known a variety of methods
Naphthalene skeleton can be synthesized.According to the difference of ring-closure reaction mode, all reactions can temporarily be divided into the reaction of 3 types：Molecule inner ring
Cyclization, rearrangement reaction between splitting or integrating.The method of existing solid phase synthesis technique structure dihydro naphthalene compounds is few, and all deposits
The low yield the shortcomings that.
The content of the invention
Present invention aims at low yield in the solid phase synthesis process for solving the problems, such as existing dihydro naphthalene compounds, there is provided
A kind of solid phase synthesis process of new dihydro naphthalene compounds.
The method is characterized in that：
Synthesized compound formula is I (hereafter same)：
R in formula1=H ,-CN ,-COOCH3；R2=H, C1-4Alkyl ,-COOCH3；R3=H ,-CH3, Ph ,-
C6H4CH3,-C6H4OCH3,-C6H4Cl ,-C6H4Br；R4=H, C1-6Alkyl, Ph ,-C6H4CH3,-C6H4OCH3,-
C6H4Cl ,-C6H4COOCH3,-C6H4NO2；R5=H ,-OCH3,-OBn；R6=H ,-OCH3,-Br；
Under nitrogen protection, 1% crosslinked polystyrene load seleno bromide reagent II in organic solvent with sodium borohydride
Loaded by polystyrene pi-allyl selenide III is prepared with allyl bromide, bromoallylene reaction；Chlorosuccinimide is used in halogenated organic solvent
Processing compound III obtains loaded by polystyrene seleno succimide reagent IV；In trifluoromethayl sulfonic acid trimethyl silicane ester catalysis
Under, reagent IV is in halogenated organic solvent, the ortho position C-H of phenyl ring and the carbon-to-carbon double bond of intramolecular in induced reaction thing V
The selenium virtueization reaction of molecule internal olefin occurs, generates 3- loaded by polystyrene selenos -1,2,3,4- naphthanes VI, without biography
System column chromatography for separation, only need to wash intermediate resin VI by filtering and with different solvents；Again by the analysis of intermediate resin VI
Pure organic solvent immersion, is oxidized to seleno oxide by VI with oxidant, the cis elimination of seleno oxide, Ran Houtong then occurs
Filtering and solvent washing resin, merging filtrate and washing lotion, are extracted, dry organic phase, concentration directly obtains height with organic solvent
The product I of purity；The structural formula of reactant II, III, IV, V, VI is following (hereafter same)：
It is to the technical solution that the method for the present invention further optimizes：
During by compound ii prepare compound III, the molar ratio of compound ii and sodium borohydride is 1：1.5~10.0, chemical combination
The molar ratio of thing II and allyl bromide, bromoallylene is 1：2.0~12.0, organic solvent used is tetrahydrofuran, N, N- dimethyl formyls
The mass volume ratio of one or more in amine, absolute ethyl alcohol, compound ii and organic solvent is 1：10~100, reaction
Temperature is 10~60 DEG C, and it is tetrahydrofuran, water, two that the solvent used in resin is washed when the reaction time is 6~72 small, in post processing
One or more in chloromethanes, ethanol, methanol, ether, acetone；
During by compound III prepare compound IV, the molar ratio of compound III and chlorosuccinimide is 1：3~30, institute
Organic solvent is dry C1-2The mass volume ratio of aliphatic halogenated hydrocarbon class, compound III and organic solvent is 1：10~
100, reaction temperature is -10~60 DEG C, and the solvent washed when the reaction time is 2~72 small, in post processing used in resin is drying
C1-2Aliphatic halogenated hydrocarbon class；
During by V prepare compound VI of compound, the molar ratio of compounds Ⅳ and trifluoromethayl sulfonic acid trimethylsilyl group is 1：
0.05~1.5, the molar ratio of compounds Ⅳ and compound V is 1：3~50, organic solvent used is dry C1-2Aliphatic
The mass volume ratio of halogenated hydrocarbon, compounds Ⅳ and organic solvent is 1：10~100, reaction temperature is -80~0 DEG C, during reaction
Between for 6~48 it is small when, organic solvent for tetrahydrofuran, water, dichloromethane, ethanol, methanol, ether, one kind in acetone or one
More than kind；
When compound VI is converted chemical compounds I, oxidant used is that the hydrogen peroxide that mass volume ratio is 30% is water-soluble
Liquid, or metachloroperbenzoic acid, or sodium metaperiodate；Compound VI and the molar ratio of oxidant are 1：10~40；Used is organic
Solvent is tetrahydrofuran or C1-2The mass volume ratio of aliphatic halogenated hydrocarbon class, compound VI and organic solvent is 1：10~80；Instead
It is 0~70 DEG C to answer temperature, when the reaction time is 1~8 small；The solvent washed used in resin is C1-2Aliphatic halogenated hydrocarbon class.
Substantially identical another statement is done to the method for the present invention below.
The route of synthetic method of the present invention is as follows：
The present invention is raw material with the seleno bromide II and phenyl acrylate V of 1% crosslinked polystyrene load, synthesis
Comprise the following steps that：
1st, under nitrogen protection, II priority of seleno bromide and sodium borohydride and pi-allyl of the load of 1% crosslinked polystyrene
The pi-allyl selenide III of loaded by polystyrene is made in bromine reaction；
2nd, loaded by polystyrene selenium is made with the reaction of N- chlorosuccinimides in the pi-allyl selenide III of loaded by polystyrene
Base succimide IV；
3rd, under Trimethylsilyl trifluoromethanesulfonate (TMSOTf) catalysis, the seleno fourth two of 1% crosslinked polystyrene load
The compound VI of Polymer-supported is made in acid imide IV with alkene V by intramolecular cyclization reaction after being swollen in organic solvent；
4th, compound VI is swollen and is acted on oxidant in organic solvent, and oxidation and cis elimination reaction occurs
Compound I.
Above-mentioned steps are optimized as follows：
In step 1, under nitrogen protection, the seleno bromide II of 1% crosslinked polystyrene load passes through sodium borohydride and alkene
The pi-allyl selenide III of loaded by polystyrene is made after propylated.The seleno bromide II of 1% crosslinked polystyrene load can root
Synthesized according to the method for Nicolaou etc. (Chem.Commun.1998,1947) reports, the content of every gram of resin bromine in compound ii
For 0.9~1.25mmol；The molar ratio of compound ii and sodium borohydride is 1：1.5~10；Compound ii and allyl bromide, bromoallylene rub
You are than being 1：2.0~12.0；Organic solvent used is tetrahydrofuran, n,N-Dimethylformamide, absolute ethyl alcohol；Compound
II with the mass volume ratio of organic solvent is 1：10~100；Reaction temperature is 10~60 DEG C, when the reaction time is 6~72 small；Afterwards
The solvent washed in processing used in resin is tetrahydrofuran, water, dichloromethane, ethanol, methanol, ether, acetone.In the step into
One step optimum condition is：In the seleno bromide II of 1% crosslinked polystyrene load the content of every gram of resin bromine for 0.90~
1.25mmol；II with the molar ratio of sodium borohydride is 1：1.5~10, the molar ratio with allyl bromide, bromoallylene is 1：5~10；Used has
Solvent is the body of the mixed solvent of N, N- dimethyl formyl and tetrahydrofuran, wherein N, N- dimethyl formyl and tetrahydrofuran
Product is than being 1：3~8, the mass volume ratio of compound ii and mixed solvent is 1：10~100；Reaction temperature is 10~60 DEG C, instead
When being 20~48 small between seasonable；It is tetrahydrofuran, water, dichloromethane, ethanol, methanol, ether, third to wash the solvent used in resin
Ketone.
In step 2, polystyrene is made in pi-allyl selenide III and the reaction of N- chlorosuccinimides of loaded by polystyrene
Load seleno succimide IV.Compound III and the molar ratio of chlorosuccinimide are 1：3~30；Organic solvent used
For dry C1-2Aliphatic halogenated hydrocarbon class；The mass volume ratio of compound III and organic solvent is 1：10~100；Reaction temperature
For -10~60 DEG C, when the reaction time is 2~72 small；It is dry C that the solvent used in resin is washed in post processing1-2Aliphatic
Halogenated hydrocarbon.Further preferred condition is in the step：The pi-allyl selenide III of loaded by polystyrene is sub- with N- chloros succinyl
The molar ratio of amine is 1：5~10；Organic solvent used is C1-2The matter of aliphatic halogenated hydrocarbon class, compound III and organic solvent
It is 1 to measure volume ratio：10~50；Reaction temperature is -10~40 DEG C, when the reaction time is 2~12 small；Wash molten used in resin
Agent is dry C1-2Aliphatic halogenated hydrocarbon class.
In step 3, the seleno succimide IV of 1% crosslinked polystyrene load can be according in trifluoromethanesulfonic acid trimethyl
Induce alkene V that molecule inner ring condensation, 1 at the same time generated occurs under the catalysis of estersil, 2,3,4- naphthane molecular skeletons lead to
Cross selenium atom key to be connected on polymer, obtain the compound VI of Polymer-supported.Compound III and trifluoromethayl sulfonic acid trimethyl
The molar ratio of estersil is 1：0.05~1.5；The molar ratio of compound III and compound V is 1：3~50；Organic solvent used
For dry C1-2Aliphatic halogenated hydrocarbon class；The mass volume ratio of compound III and organic solvent is 1：10~100；Reaction temperature
For -80~0 DEG C, when the reaction time is 6~48 small；The solvent washed used in resin is tetrahydrofuran, water, dichloromethane, second
Alcohol, methanol, ether, acetone.Further preferred condition is in the step：Compound III and Trimethylsilyl trifluoromethanesulfonate mole
Than for 1：0.1~0.6；Compound III is 1 with V molar ratio of compound：5~10；Organic solvent used is C1-2Aliphatic halogen
For hydro carbons, the mass volume ratio of compound III and organic solvent is 1：10~50；Reaction temperature is -80~0 DEG C, the reaction time
For 6~24 it is small when；The solvent washed used in resin is tetrahydrofuran, water, dichloromethane, ethanol, methanol, ether, acetone.
In step 4, compound VI is swollen and by oxidizing into seleno oxide in organic solvent, and selenolite then occurs
The cis elimination reaction of compound obtains chemical compounds I.Oxidant used is 30% aqueous hydrogen peroxide solution, m-chloro peroxide benzene first
Acid, sodium metaperiodate；Compound VI and the molar ratio of oxidant are 1：10~40；Organic solvent used is tetrahydrofuran, C1-2Fat
Fat race halogenated hydrocarbon；The mass volume ratio of compound VI and organic solvent is 1：10~80；Reaction temperature is 0~70 DEG C, reaction
When time is 1~8 small；The solvent washed used in resin is C1-2Aliphatic halogenated hydrocarbon class；The drier of organic phase is anhydrous slufuric acid
Magnesium, anhydrous sodium sulfate.Further preferred condition is in the step：Organic solvent used is tetrahydrofuran, C1-2Aliphatic halo
The mass volume ratio of hydro carbons, compound VI and organic solvent is 1：10~40；Oxidant used is water-soluble for 30% hydrogen peroxide
The molar ratio of liquid, metachloroperbenzoic acid, sodium metaperiodate, compound VI and oxidant is 1：20~40；Reaction temperature is 0~40
DEG C, when the reaction time is 1~6 small；The solvent washed used in resin is C1-2Aliphatic halogenated hydrocarbon class；The drier of organic phase is
Anhydrous magnesium sulfate, anhydrous sodium sulfate.
Beneficial effects of the present invention：The shortcomings that overcoming prior art cyclization low yield, raw material is easy to get, products collection efficiency
Good, purity is high, easy to operate, and post processing is simple, has certain prospects for commercial application.
Experiment shows, as long as the present invention carries out can be achieved with goal of the invention as follows：Under nitrogen protection, 1% hand over
The seleno bromide reagent II of polystyrene load prepares polystyrene with sodium borohydride and allyl bromide, bromoallylene reaction in organic solvent
Load pi-allyl selenide III；Polystyrene is obtained in halogenated organic solvent with chlorosuccinimide processing compound III to bear
Carry seleno succimide reagent IV；Under trifluoromethayl sulfonic acid trimethyl silicane ester catalysis, reagent IV is in halogenated organic solvent
In, the selenium virtueization of molecule internal olefin occurs for the ortho position C-H of phenyl ring and the carbon-to-carbon double bond of intramolecular instead in induced reaction thing V
Should, 3- loaded by polystyrene selenos -1,2 are generated, 3,4- naphthanes VI, without traditional column chromatography for separation, only need to pass through filtering
Intermediate resin VI is washed with different solvents；The analytically pure organic solvent of intermediate resin VI is soaked again, uses oxidant
Seleno oxide is oxidized to by VI, the cis elimination of seleno oxide then occurs, resin is then washed by filtering and solvent, is merged
Filtrate and washing lotion, are extracted with organic solvent, and dry organic phase, concentration directly obtains the product I of high-purity.Therefore, implement below
Example is Test explanation, and the scope of the present invention is from the limitation of illustrated embodiment.
Embodiment
Under the protection of 1 nitrogen of embodiment, by 1% crosslinked polystyrene load seleno bromide II (Br%=0.99mmol/g,
2.5g, 2.48mmol), tetrahydrofuran (24mL) and n,N-Dimethylformamide (6mL) put in reaction bulb, stand 4h at room temperature.
After resin swelling, sodium borohydride (189.2mg, 5.0mmol) is added, stirring reaction 8h, is added dropwise allyl bromide, bromoallylene at 40 DEG C
(0.665g, 5.5mmol), continues stirring reaction 12h at 40 DEG C.Reaction is finished, and is filtered with sand core funnel, successively with dichloromethane (3
× 10mL), water (3 × 10mL), water+tetrahydrofuran (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 ×
10mL), methanol (3 × 10mL), ether (3 × 10mL), dichloromethane (10mL), acetone (3 × 10mL) washing resin, after dry
Obtain loaded by polystyrene pi-allyl selenide III (2.36g, 98.2%).
IR(KBr)：υmax=3068,3019,2847,1565,1415,1185,1016,907,751cm–1。
Under the protection of 2 nitrogen of embodiment, by 1% crosslinked polystyrene load seleno bromide II (Br%=0.99mmol/g,
2.5g, 2.48mmol), tetrahydrofuran (80mL) and n,N-Dimethylformamide (20mL) put in reaction bulb, stand at room temperature
4h.After resin swelling, sodium borohydride (0.473g, 12.5mmol) is added, stirring reaction 2h, is added dropwise allyl bromide, bromoallylene at 40 DEG C
(1.572g, 13.0mmol), continues stirring reaction 5h at 40 DEG C.Reaction is finished, and is filtered with sand core funnel, successively with dichloromethane (5
× 10mL), water (3 × 10mL), water+tetrahydrofuran (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 ×
10mL), methanol (3 × 10mL), ether (3 × 10mL), dichloromethane (10mL), acetone (3 × 10mL) washing resin, after dry
Loaded by polystyrene pi-allyl selenide III (2.35g, 98.0%) is obtained, IR is consistent with embodiment 1.
Under the protection of 3 nitrogen of embodiment, by 1% crosslinked polystyrene load seleno bromide II (Br%=0.99mmol/g,
2.5g, 2.48mmol), tetrahydrofuran (80mL) and n,N-Dimethylformamide (20mL) put in reaction bulb, stand at room temperature
4h.After resin swelling, sodium borohydride (0.946g, 25.0mmol) is added, stirring reaction 12h, is added dropwise pi-allyl at 40 DEG C
Bromine (3.08g, 25.5mmol), continues stirring reaction 24h at 40 DEG C.Reaction is finished, and is filtered with sand core funnel, is used dichloromethane successively
(5 × 10mL), water (3 × 10mL), water+tetrahydrofuran (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3
× 10mL), methanol (3 × 10mL), ether (3 × 10mL), dichloromethane (10mL), acetone (3 × 10mL) washing resin, it is dry
Loaded by polystyrene pi-allyl selenide III (2.35g, 98.0%) is obtained afterwards, and IR is consistent with embodiment 1.
Under the protection of 4 nitrogen of embodiment, by 1% crosslinked polystyrene load seleno bromide II (Br%=0.99mmol/g,
2.5g, 2.48mmol), tetrahydrofuran (24mL) and absolute ethyl alcohol (6mL) put in reaction bulb, stand 4h at room temperature.Treat that resin is molten
After swollen, sodium borohydride (189.2mg, 5.0mmol) is added, the stirring reaction 2h at 60 DEG C, dropwise addition allyl bromide, bromoallylene (0.665g,
5.5mmol), stirring reaction 10h is continued at 40 DEG C.Reaction finish, filtered with sand core funnel, successively with dichloromethane (3 × 10mL),
Water (3 × 10mL), water+tetrahydrofuran (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 × 10mL), first
Alcohol (3 × 10mL), ether (3 × 10mL), dichloromethane (10mL), acetone (3 × 10mL) washing resin, polyphenyl second is obtained after dry
Alkene load pi-allyl selenide III (2.30g, 96.0%), IR is consistent with embodiment 1.
Under the protection of 5 nitrogen of embodiment, by 1% crosslinked polystyrene load seleno bromide II (Br%=0.99mmol/g,
2.5g, 2.48mmol), tetrahydrofuran (24mL) and absolute ethyl alcohol (6mL) put in reaction bulb, stand 4h at room temperature.Treat that resin is molten
After swollen, sodium borohydride (189.2mg, 5.0mmol) is added, the stirring reaction 48h at 10 DEG C, dropwise addition allyl bromide, bromoallylene (0.665g,
5.5mmol), stirring reaction 24h is continued at 20 DEG C.Reaction finish, filtered with sand core funnel, successively with dichloromethane (3 × 10mL),
Water (3 × 10mL), water+tetrahydrofuran (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 × 10mL), first
Alcohol (3 × 10mL), ether (3 × 10mL), dichloromethane (10mL), acetone (3 × 10mL) washing resin, polyphenyl second is obtained after dry
Alkene load pi-allyl selenide III (2.2g, 92.0%), IR is consistent with embodiment 1.
Embodiment 6 puts loaded by polystyrene pi-allyl selenide III (1.0g, 0.97mmol), anhydrous methylene chloride (15mL)
In reaction bulb, 4h is stood at room temperature.After resin swelling, added at 0 DEG C N- chlorosuccinimides (0.668g,
5.0mmol), at 0 DEG C after stirring reaction 5h, stirring reaction 24h is continued at room temperature.Reaction is finished, and is filtered with sand core funnel, with dry
Dry dichloromethane (4 × 10mL) washs resin, obtains loaded by polystyrene seleno succimide IV.The resin that will be obtained immediately
(IV) continue to be soaked with dry methylene chloride (15mL), be cooled at -78 DEG C, add Trimethylsilyl trifluoromethanesulfonate
(0.022g, 0.10mmol), the stirring reaction 0.5h at -78 DEG C.Add (E) -2- (3,4- Dimethoxyphenyl) -5-
Phenyl-allyl acetonitrile (V) (1.467g, 5.0mmol), after continuing stirring reaction 2h at -78 DEG C, by reaction mixture
8h is placed at -20 DEG C.Reaction is finished, and saturated solution of sodium bicarbonate (5mL) is added, successively with dichloromethane (3 × 10mL), water
(3 × 10mL), water+tetrahydrofuran (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 × 10mL), methanol
(3 × 10mL), ether (3 × 10mL), dichloromethane (10mL), acetone (3 × 10mL), tetrahydrofuran (10mL) washing resin,
Obtain 3- loaded by polystyrene seleno -1- cyano group -4- phenyl -6,7- dimethoxys -1,2,3,4- tetrahydronaphthalenes
Compound VI.Merging filtrate and washing lotion.The most of solvent of recycling, residue are extracted with ethyl acetate, and merge organic layer, anhydrous slufuric acid
Sodium is dried.After recycling design, compound VI is put in reaction bulb, soaks 4h at room temperature with tetrahydrofuran (15mL).In ice bath
In be cooled to 0 DEG C, add 30% aqueous hydrogen peroxide solution 1.2mL, stirring reaction 1h at 0 DEG C, is slowly warmed to room temperature, continues to stir
React 20min.Reaction is finished, and is filtered with sand core funnel, resin is washed with dichloromethane (4 × 10mL).Merging filtrate and washing lotion, add
Enter water (5mL) and saturation aqueous solution of sodium bisulfite (5mL) removes excessive hydrogen peroxide.Organic layer is separated, is washed with water (5mL)
Wash.Water layer is extracted with dichloromethane (2 × 5mL).Merge organic layer, anhydrous sodium sulfate drying, recycling design, obtain 1- cyano group-
(yield 0.249g, 88%, 90%) purity is more than 4- phenyl -6,7- dimethoxys -1,2- dihydronaphthalene I.IR(KBr)：
υmax=2230,1602,1511,1453,1272,1213,885cm- 1；1H NMR (300MHz, CDCl3)：δ=7.41-7.31
(5H, m), 7.05 (1H, s), 6.62 (1H, s), 5.96 (1H, t, J=4.65Hz), 4.02 (1H, dd, J1=3.45Hz, J2=
3.45Hz), 3.95 (3H, s), 3.67 (3H, s), 2.76-2.68 (2H, m)；13C NMR (75MHz, CDCl3)：δ 148.66,
140.48,139.45,128.54,128.43,127.79,126.98,121.88,121.50,120.59,110.41,110.17,
56.20,56.04,30.24,27.63.HRMS m/z [M]+calcd for C19H18NO2[(M+H)+], 292.1338；Found,
292.1328。
Embodiment 7 puts the compound (VI) prepared by the method for embodiment 6 in reaction bulb, with chloroform (20mL) in
4h is soaked at room temperature.Metachloroperbenzoic acid (1.73g, 10.0mmol), heating stirring back flow reaction 6h are added portionwise under stirring.
Reaction is finished, and is filtered with sand core funnel, resin is washed with chloroform (4 × 10mL).Merging filtrate and washing lotion, use saturated potassium carbonate
Aqueous solution (3 × 20mL) washs, anhydrous sodium sulfate drying, and solvent is recovered under reduced pressure, and residue separates (elution through silica gel column chromatography
Liquid：Petrol ether/ethyl acetate=8/1) purifying, obtain 1- cyano group -4- phenyl -6,7- dimethoxy -1,2- dihydronaphthalene
(I) (yield 0.221g, 78%, 90%) purity is more than1H NMR, IR and HRMS and embodiment 6 are consistent.
Embodiment 8 puts the compound VI prepared by the method for embodiment 6 in reaction bulb, with chloroform (80mL) in room
The lower immersion 3h of temperature.Metachloroperbenzoic acid (1.73g, 40.0mmol), heating stirring back flow reaction 6h are added portionwise under stirring.Instead
It should finish, be filtered with sand core funnel, resin is washed with chloroform (5 × 10mL).Merging filtrate and washing lotion, with saturated potassium carbonate water
Solution (3 × 20mL) washs, and anhydrous sodium sulfate drying, is recovered under reduced pressure solvent, residue separates (eluent through silica gel column chromatography：
Petrol ether/ethyl acetate=8/1) purifying, obtain 1- cyano group -4- phenyl -6,7- dimethoxy -1,2- dihydronaphthalene (I)
(yield 0.204g, 72%, 90%) purity is more than, fusing point,1H NMR, IR and HRMS and embodiment 6 are consistent.
Embodiment 9 puts VI 1.16g of compound prepared by the method for embodiment 6 in reaction bulb, uses tetrahydrofuran
(30mL) soaks 4h at room temperature.Stirring is lower plus water (8mL), sodium acid carbonate (0.42g, 5.0mmol) and sodium metaperiodate (2.14g,
10.0mmol), stirring reaction 1.5h is continued at room temperature.Reaction is finished, and is filtered with sand core funnel, with dichloromethane (4 × 10mL) and
Water washing resin.Merging filtrate and washing lotion, add saturated sodium bicarbonate aqueous solution (10mL).Separate organic layer, with brine and
Water washing.Water layer is extracted with dichloromethane (2 × 5mL).Merge organic layer, anhydrous sodium sulfate drying, is recovered under reduced pressure solvent, obtains
1- cyano group -4- phenyl -6,7- dimethoxys -1,2- dihydronaphthalene I (yield 0.227g, 80%, 90%) purity is more than,1H NMR, IR and HRMS and embodiment 6 are consistent.
10 loaded by polystyrene pi-allyl selenide III (1.0g, 0.97mmol) of embodiment, anhydrous methylene chloride (10mL) are put
In reaction bulb, stand 4h at room temperature, after resin swelling, added at -10 DEG C N- chlorosuccinimides (0.4g,
3.0mmol), at -10 DEG C stirring reaction 48h after continuing stirring reaction 24h at room temperature.Reaction is finished, and is filtered with sand core funnel,
Washed with dry methylene chloride (4 × 10mL), obtain loaded by polystyrene seleno succimide IV.The resin IV that will be obtained immediately
Continue to be soaked with dry methylene chloride (10mL), be cooled at -78 DEG C, addition Trimethylsilyl trifluoromethanesulfonate (0.011g,
0.05mmol), the stirring reaction 0.5h at -78 DEG C.Addition (E) -1- methyl -2- (3,4- Dimethoxyphenyl) -
5- phenyl-allyl acetonitrile V (0.922g, 3.0mmol), after continuing stirring reaction 3h at -80 DEG C, by reaction mixture
2.5h is placed at -10 DEG C.Reaction finish, add saturated solution of sodium bicarbonate (5mL), successively with dichloromethane (3 × 10mL),
Water (3 × 10mL), water+tetrahydrofuran (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 × 10mL), first
Alcohol (3 × 10mL), ether (3 × 10mL), dichloromethane (10mL), acetone (3 × 10mL), tetrahydrofuran (10mL) washing tree
Fat, obtains 3- loaded by polystyrene seleno -1- cyano group -1- methyl 4-phenyl -6,7- dimethoxys -1,2, and 3,
4- naphthanes VI.Merging filtrate and washing lotion.The most of solvent of recycling, residue are extracted with ethyl acetate, and merge organic layer, nothing
Aqueous sodium persulfate is dried.After recycling design, recycling obtains V 0.56g of reactant 4- cyano group -4- phenyl -1- butylene.By chemical combination
Thing VI is put in reaction bulb, soaks 4h at room temperature with tetrahydrofuran (15mL).0 DEG C is cooled in ice bath, adds 30% peroxide
Change aqueous solution of hydrogen 1.2mL, stirring reaction 1h at 0 DEG C, is slowly warmed to room temperature, continues stirring reaction 20min.Reaction is finished, and uses sand core
Funnel filters, and resin is washed with dichloromethane (4 × 10mL).Merging filtrate and washing lotion, add water (5mL) and saturation bisulfite
Sodium water solution (5mL) removes excessive hydrogen peroxide.Organic layer is separated, is washed with water (5mL).Water layer with dichloromethane (2 ×
5mL) extract.Merge organic layer, anhydrous sodium sulfate drying, recycling design, obtains 1- cyano group -1- methyl 4-phenyls -6-
(yield 0.237g, 80%, 90%) purity is more than methoxyl group -1,2- dihydronaphthalene I.1H NMR (300MHz, CDCl3)：δ=
7.40-7.12 (6H, m), 7.13 (1H, s), 6.62 (1H, s), 5.84 (1H, dd, J1=3.3Hz, J2=3.3Hz), 3.96
(3H, s), 3.66 (3H, s), 2.94 (1H, dd, J1=3.6Hz, J2=3.6Hz), 2.64 (1H, dd, J1=5.7Hz, J2=
5.7Hz), 1.68 (3H, s)13C NMR (75MHz, CDCl3)：δ=148.85,148.37,139.82,139.62,128.52,
128.43,127.85,127.74,125.72,124.24,120.22,110.61,108.87,55.19,55.97,36.27,
35.32,25.24.IR (KBr)：2235,1603,1566,1509,1460,1453,1272,865.HR-TOFMS calcd
for C20H20NO2[(M+H)+], 306.1494；Found, 306.1494.C20H19NNaO2[(M+Na)+], 328.1314；
Found, 328.1311.11 loaded by polystyrene pi-allyl selenide III (1.0g, 0.97mmol) of embodiment, anhydrous methylene chloride
(95mL) is put in reaction bulb, stands 4h at room temperature, and after resin swelling, N- chlorosuccinimides are added at 0 DEG C
(4.01g, 30.0mmol), at room temperature stirring reaction 0.5h after continue at 30 DEG C stirring reaction 2h.Reaction is finished, and uses sand core funnel
Filtering, is washed with dry methylene chloride (5 × 10mL), obtains loaded by polystyrene seleno succimide IV.It will obtain immediately
Resin IV continues to be soaked with dry methylene chloride (95mL), is cooled at -78 DEG C, adds Trimethylsilyl trifluoromethanesulfonate
(0.33g, 1.50mmol), the stirring reaction 0.5h at -78 DEG C.Add (E) -2- (6- benzyloxy-phenyls) -5- benzene
Base-allyl acetonitrile V (1.70g, 5.0mmol), after continuing stirring reaction 2h at -78 DEG C, by reaction mixture in -20
20h is placed at DEG C, then places 2h at 0 DEG C.Reaction is finished, and is added saturated solution of sodium bicarbonate (10mL), is used dichloromethane successively
Alkane (5 × 10mL), water (3 × 10mL), water+tetrahydrofuran (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol
(3 × 10mL), methanol (3 × 10mL), ether (3 × 10mL), dichloromethane (10mL), acetone (3 × 10mL), tetrahydrofuran
(10mL) washs resin, obtains 3- loaded by polystyrene seleno -1- cyano group -4- phenyl -6- benzyloxies -1,2, and 3,
4- naphthanes VI.Merging filtrate and washing lotion.The most of solvent of recycling, residue are extracted with ethyl acetate, and merge organic layer, nothing
Aqueous sodium persulfate is dried.After recycling design, recycling obtains reactant 4- cyano group -4- phenyl -1- butylene V.By compound VI
Put in reaction bulb, soak 4h at room temperature with tetrahydrofuran (15mL).0 DEG C is cooled in ice bath, adds 30% hydrogen peroxide
Aqueous solution 1.2mL, stirring reaction 1h at 0 DEG C, is slowly warmed to room temperature, continues stirring reaction 20min.Reaction is finished, and uses sand core funnel
Filtering, resin is washed with dichloromethane (4 × 10mL).Merging filtrate and washing lotion, add water (5mL) and saturation sodium hydrogensulfite water
Solution (5mL) removes excessive hydrogen peroxide.Organic layer is separated, is washed with water (5mL).Water layer is extracted with dichloromethane (2 × 5mL)
Take.Merging organic layer, anhydrous sodium sulfate drying, recycling design obtains 1- cyano group -4- phenyl -6- benzyloxies -1,2, and 3,
(yield 0.281g, 86%, 90%) purity is more than 4- naphthanes (I).1H NMR (300MHz, CDCl3)：δ=7.50 (2H, d, J
=7.2Hz), 7.41-7.25 (8H, m), 6.97 (2H, d, J=8.4Hz), 6.46 (1H, s), 5.05 (2H, s), 3.80 (1H,
T, J=7.65Hz), 3.10-2.81 (2H, m),13C NMR (75MHz, CDCl3)：δ=158.15,136.65,134.30,
134.17,129.09,128.94,128.65,128.25,128.19,128.12,127.73,127.47,116.69,126.38,
124.01,120.00,115.53,70.14,47.68,35.21.IR (KBr)：2238,1605,1507,1449,1242,
830.HR-TOFMS calcd for C24H19NNaO[(M+Na)+], 360.1364；Found, 360.1374. embodiment 12 is poly-
Styrene load pi-allyl selenide III (1.0g, 0.97mmol), anhydrous 1,2- dichloroethanes (45mL) are put in reaction bulb, room temperature
Lower standing 4h, after resin swelling, N- chlorosuccinimides (2.0g, 15.0mmol) is added at 0 DEG C, are stirred at room temperature
After reacting 0.5h, continue stirring reaction 1.5h at 60 DEG C.Reaction finish, filtered with sand core funnel, with dry methylene chloride (4 ×
10mL) wash, obtain loaded by polystyrene seleno succimide IV.Obtained resin IV is continued with dry 1,2- bis- immediately
Chloroethanes (25mL) soaks, and is cooled at -78 DEG C, adds Trimethylsilyl trifluoromethanesulfonate (0.22g, 1.0mmol), in -
Stirring reaction 0.5h at 78 DEG C.Add (E) -1- normal-butyls -2- (3,4- Dimethoxyphenyl) -5- phenyl -4- penta
Alkene nitrile (V) (6.99g, 20.0mmol), after continuing stirring reaction 2h at -78 DEG C, reaction mixture is placed at 0 DEG C
45h.Reaction finish, add saturated solution of sodium bicarbonate (10mL), successively with dichloromethane (5 × 10mL), water (3 × 10mL), water+
Tetrahydrofuran (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 × 10mL), methanol (3 × 10mL), ether
(3 × 10mL), dichloromethane (10mL), acetone (3 × 10mL), tetrahydrofuran (10mL) washing resin, obtain 3- polystyrene
Load seleno -1- normal-butyl -1- cyano group -6,7- dimethoxy-4 '-phenyl -1,2,3,4- naphthanes VI.Merge
Filtrate and washing lotion.The most of solvent of recycling, residue are extracted with ethyl acetate, and merge organic layer, anhydrous sodium sulfate drying.Recycling
After solvent, recycling obtains reactant 4- cyano group -4- phenyl -1- butylene V.Compound VI is put in reaction bulb, uses tetrahydrochysene
Furans (15mL) soaks 4h at room temperature.It is cooled to 0 DEG C in ice bath, adds 30% aqueous hydrogen peroxide solution 1.2mL, at 0 DEG C
Stirring reaction 1h, is slowly warmed to room temperature, and continues stirring reaction 20min.Reaction is finished, and is filtered with sand core funnel, with dichloromethane (4
× 10mL) washing resin.Merging filtrate and washing lotion, add water (5mL) and saturation aqueous solution of sodium bisulfite (5mL) removes excessively
Hydrogen peroxide.Organic layer is separated, is washed with water (5mL).Water layer is extracted with dichloromethane (2 × 5mL).Merge organic layer, nothing
Aqueous sodium persulfate is dried, and recycling design, obtains 1- normal-butyl -1- cyano group -6,7- dimethoxy-4 '-phenyl -1,2- dihydro
(yield 0.287g, 80%, 90%) purity is more than naphthalene (I).1H NMR (300MHz, CDCl3)：δ=7.41-7.30 (5H, m),
7.12 (1H, s), 6.61 (1H, s), 5.81 (1H, dd, J1=3.0Hz, J2=3.0Hz), 3.97 (3H, s), 3.68 (3H, s),
2.95 (1H, dd, J1=3.0Hz, J2=3.0Hz), 2.77 (1H, dd, J1=6.6Hz, J2=6.6Hz), 1.94-1.76 (2H,
M), 1.69-1.58 (2H, m), 1.57-1.40 (2H, m), 1.26-1.22 (3H, m)13C NMR (75MHz, CDCl3)：δ=
148.56,148.27,139.91,139.64,128.43,127.72,127.36,125.57,123.65,119.91,110.61,
110.01,56.24,55.99,42.48,36.45,33.02,29.42,27.92,22.56,13.82.IR (KBr)：2344,
1617,1509,1450,1366,1211,918,741.HR-TOFMS calcd for C23H25NNaO2[(M+Na)+],
370.1783；Found, 370.1780.Embodiment 13 is by loaded by polystyrene pi-allyl selenide III (1.0g, 0.97mmol), nothing
Water dichloromethane (15mL) is put in reaction bulb, stands 4h at room temperature.After resin swelling, N- chloro succinyl is added at 0 DEG C
Imines (0.668g, 5.0mmol), at 0 DEG C after stirring reaction 5h, continues stirring reaction 24h at room temperature.Reaction is finished, and uses sand core
Funnel filters, and washs resin with dry methylene chloride (4 × 10mL), obtains loaded by polystyrene seleno succimide IV.Immediately
Obtained resin IV is continued to be soaked with dry methylene chloride (15mL), is cooled at -78 DEG C, adds trifluoromethanesulfonic acid front three
Base estersil (0.022g, 0.10mmol), the stirring reaction 0.5h at -78 DEG C.Add (E)-Isosorbide-5-Nitrae-diphenyl -1- butylene
V (1.041g, 5.0mmol), after continuing stirring reaction 2h at -78 DEG C, 8h is placed by reaction mixture at -20 DEG C.Instead
It should finish, saturated solution of sodium bicarbonate (5mL) be added, successively with dichloromethane (3 × 10mL), water (3 × 10mL), water+tetrahydrochysene furan
Mutter (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 × 10mL), methanol (3 × 10mL), ether (3 ×
10mL), dichloromethane (10mL), acetone (3 × 10mL), tetrahydrofuran (10mL) washing resin, obtain 2- loaded by polystyrene
Seleno -1- phenyl -1,2,3,4- tetralin quasi-compounds VI.Merging filtrate and washing lotion.The most of solvent of recycling, residue
It is extracted with ethyl acetate, merges organic layer, anhydrous sodium sulfate drying.After recycling design, compound VI is put in reaction bulb, with four
Hydrogen furans (15mL) soaks 4h at room temperature.It is cooled to 0 DEG C in ice bath, adds 30% aqueous hydrogen peroxide solution 1.2mL, 0 DEG C
Lower stirring reaction 1h, is slowly warmed to room temperature, and continues stirring reaction 20min.Reaction is finished, and is filtered with sand core funnel, is used dichloromethane
(4 × 10mL) washs resin.Merging filtrate and washing lotion, add water (5mL) and saturation aqueous solution of sodium bisulfite (5mL) removed
The hydrogen peroxide of amount.Organic layer is separated, is washed with water (5mL).Water layer is extracted with dichloromethane (2 × 5mL).Merge organic layer,
Anhydrous sodium sulfate is dried, recycling design, and obtaining 4- phenyl -1,2- dihydronaphthalene I, (yield 0.17g, 85%, 90%) purity is more than
。1H NMR (300MHz, CDCl3)：δ=2.34-2.40 (m, 2H), 2.82 (t, J=7.8Hz, 2H), 6.05 (t, J=4.5Hz,
1H), 6.98-7.00 (m, 1H), 7.05-7.17 (m, 3H), 7.30-7.35 (m, 5H) .HRMS (ESI)：calcd for
C16H14[(M+H)+], 206.1096；Found, 207.1165.IR (neat)：2932cm- 1。
Embodiment 14 is by loaded by polystyrene pi-allyl selenide III (1.0g, 0.97mmol), anhydrous methylene chloride (15mL)
Put in reaction bulb, stand 4h at room temperature.After resin swelling, added at 0 DEG C N- chlorosuccinimides (0.668g,
5.0mmol), at 0 DEG C after stirring reaction 5h, stirring reaction 24h is continued at room temperature.Reaction is finished, and is filtered with sand core funnel, with dry
Dry dichloromethane (4 × 10mL) washs resin, obtains loaded by polystyrene seleno succimide IV.The resin IV that will be obtained immediately
Continue to be soaked with dry methylene chloride (15mL), be cooled at -78 DEG C, addition Trimethylsilyl trifluoromethanesulfonate (0.022g,
0.10mmol), the stirring reaction 0.5h at -78 DEG C.Add 2- cyano group -2,3- diphenyl -4- amylene-4 acid methyl esters V
(1.456g, 5.0mmol), after continuing stirring reaction 2h at -78 DEG C, 8h is placed by reaction mixture at -20 DEG C.Reaction
Finish, saturated solution of sodium bicarbonate (5mL) is added, successively with dichloromethane (3 × 10mL), water (3 × 10mL), water+tetrahydrofuran
(V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 × 10mL), methanol (3 × 10mL), ether (3 ×
10mL), dichloromethane (10mL), acetone (3 × 10mL), tetrahydrofuran (10mL) washing resin, obtain 3- loaded by polystyrene
Seleno -1- cyano group -2- phenyl -1,2,3,4- naphthane -1- methyl formates VI.Merging filtrate and washing lotion.Recycling is big
Partial solvent, residue are extracted with ethyl acetate, and merge organic layer, anhydrous sodium sulfate drying.After recycling design, by compound VI
Put in reaction bulb, soak 4h at room temperature with tetrahydrofuran (15mL).0 DEG C is cooled in ice bath, adds 30% hydrogen peroxide
Aqueous solution 1.2mL, stirring reaction 1h at 0 DEG C, is slowly warmed to room temperature, continues stirring reaction 20min.Reaction is finished, and uses sand core funnel
Filtering, resin is washed with dichloromethane (4 × 10mL).Merging filtrate and washing lotion, add water (5mL) and saturation sodium hydrogensulfite water
Solution (5mL) removes excessive hydrogen peroxide.Organic layer is separated, is washed with water (5mL).Water layer is extracted with dichloromethane (2 × 5mL)
Take.Merge organic layer, anhydrous sodium sulfate drying, recycling design, obtains 1- cyano group -2- phenyl -1,2- dihydronaphthalene -1- first
(yield 0.23g, 82%, 90%) purity is more than for sour methyl esters I.1H NMR (400MHz, CDCl3)：δ=7.38-7.36 (m, 1H),
7.31-7.26 (m, 7H), 7.23 (d, J=8.0Hz, 1H), 6.72 (dd, J=2.0Hz, J=9.6Hz, 1H), 6.11 (dd, J
=4.4Hz, J=10.4Hz, 1H), 4.47 (dd, J=2.0Hz, J=4.0Hz, 1H), 3.78 (s, 3H) .HRMS (ESI) Calcd
for C19H16NO2[(M+H)+], 290.1181；Found, 290.1181.
Embodiment 15 is by loaded by polystyrene pi-allyl selenide III (1.0g, 0.97mmol), anhydrous methylene chloride (15mL)
Put in reaction bulb, stand 4h at room temperature.After resin swelling, added at 0 DEG C N- chlorosuccinimides (0.668g,
5.0mmol), at 0 DEG C after stirring reaction 5h, stirring reaction 24h is continued at room temperature.Reaction is finished, and is filtered with sand core funnel, with dry
Dry dichloromethane (4 × 10mL) washs resin, obtains loaded by polystyrene seleno succimide IV.The resin IV that will be obtained immediately
Continue to be soaked with dry methylene chloride (15mL), be cooled at -78 DEG C, addition Trimethylsilyl trifluoromethanesulfonate (0.022g,
0.10mmol), the stirring reaction 0.5h at -78 DEG C.Add 2- [1- (4 '-methyl) phenyl propyl- 2- alkenyls] -2- benzene
Propylmalonic acid dimethyl ester V (1.692g, 5.0mmol), continue at -78 DEG C stirring reaction 2h after, by reaction mixture in -
8h is placed at 20 DEG C.Reaction finish, add saturated solution of sodium bicarbonate (5mL), successively with dichloromethane (3 × 10mL), water (3 ×
10mL), water+tetrahydrofuran (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 × 10mL), methanol (3 ×
10mL), ether (3 × 10mL), dichloromethane (10mL), acetone (3 × 10mL), tetrahydrofuran (10mL) washing resin, obtain
3- loaded by polystyrene selenos -2- (4 '-methyl) phenyl -1,2,3,4- tetralyl -1,1- dicarboxylic acid dimethyl esters
Ⅵ.Merging filtrate and washing lotion.The most of solvent of recycling, residue are extracted with ethyl acetate, and merge organic layer, anhydrous sodium sulfate is done
It is dry.After recycling design, compound VI is put in reaction bulb, soaks 4h at room temperature with tetrahydrofuran (15mL).It is cold in ice bath
But to 0 DEG C, 30% aqueous hydrogen peroxide solution 1.2mL is added, stirring reaction 1h at 0 DEG C, is slowly warmed to room temperature, continues stirring reaction
20min.Reaction is finished, and is filtered with sand core funnel, resin is washed with dichloromethane (4 × 10mL).Merging filtrate and washing lotion, add water
(5mL) and saturation aqueous solution of sodium bisulfite (5mL) remove excessive hydrogen peroxide.Organic layer is separated, is washed with water (5mL).
Water layer is extracted with dichloromethane (2 × 5mL).Merge organic layer, anhydrous sodium sulfate drying, recycling design, obtains 2- (4 '-methyl)
(yield 0.261g, 80%, 90%) purity is more than phenyl -1,2- ihydro naphthyl -1,1- dicarboxylic acid dimethyl ester I.1H NMR
(400MHz, CDCl3)：δ=7.55 (d, J=7.6Hz, 1H), 7.29-7.20 (m, 2H), 7.10 (d, J=6.8Hz, 1H),
6.96-6.90 (m, 4H), 6.49 (d, J=10.0Hz, 1H), 6.20 (dd, J=5.6,9.6Hz, 1H), 4.48 (d, J=
5.6Hz, 1H), 3.62 (s, 3H), 3.45 (s, 3H), 2.22 (s, 3H) ppm；HRMS m/z[M]+calcd for C21H21O4[(M
+H)+], 337.1440；Found, 337.1440.
Embodiment 16 is by loaded by polystyrene pi-allyl selenide III (1.0g, 0.97mmol), anhydrous methylene chloride (15mL)
Put in reaction bulb, stand 4h at room temperature.After resin swelling, added at 0 DEG C N- chlorosuccinimides (0.668g,
5.0mmol), at 0 DEG C after stirring reaction 5h, stirring reaction 24h is continued at room temperature.Reaction is finished, and is filtered with sand core funnel, with dry
Dry dichloromethane (4 × 10mL) washs resin, obtains loaded by polystyrene seleno succimide IV.The resin IV that will be obtained immediately
Continue to be soaked with dry methylene chloride (15mL), be cooled at -78 DEG C, addition Trimethylsilyl trifluoromethanesulfonate (0.022g,
0.10mmol), the stirring reaction 0.5h at -78 DEG C.Add 2- [1- (4 '-methoxyl group) phenyl propyl- 2- alkenyls] -2-
Phenylmalonic acid dimethyl ester (V) (1.772g, 5.0mmol), after continuing stirring reaction 2h at -78 DEG C, by reaction mixture
8h is placed at -20 DEG C.Reaction is finished, and saturated solution of sodium bicarbonate (5mL) is added, successively with dichloromethane (3 × 10mL), water
(3 × 10mL), water+tetrahydrofuran (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 × 10mL), methanol
(3 × 10mL), ether (3 × 10mL), dichloromethane (10mL), acetone (3 × 10mL), tetrahydrofuran (10mL) washing resin,
Obtain 3- loaded by polystyrene selenos -2- (4 '-methoxyl group) phenyl -1,2,3,4- tetralyl -1,1- dioctyl phthalate
Dimethyl ester VI.Merging filtrate and washing lotion.The most of solvent of recycling, residue are extracted with ethyl acetate, and merge organic layer, anhydrous sulphur
Sour sodium drying.After recycling design, compound VI is put in reaction bulb, soaks 4h at room temperature with tetrahydrofuran (15mL).Yu Bing
It is cooled to 0 DEG C in bath, adds 30% aqueous hydrogen peroxide solution 1.2mL, stirring reaction 1h at 0 DEG C, is slowly warmed to room temperature, continues to stir
Mix reaction 20min.Reaction is finished, and is filtered with sand core funnel, resin is washed with dichloromethane (4 × 10mL).Merging filtrate and washing lotion,
Add water (5mL) and saturation aqueous solution of sodium bisulfite (5mL) removes excessive hydrogen peroxide.Organic layer is separated, with water (5mL)
Washing.Water layer is extracted with dichloromethane (2 × 5mL).Merge organic layer, anhydrous sodium sulfate drying, recycling design, obtain 2- (4 '-
Methoxyl group) (yield 0.274g, 80%, 90%) purity is more than phenyl -1,2- ihydro naphthyl -1,1- dicarboxylic acid dimethyl ester I
。1H NMR (400MHz, CDCl3)：δ=7.55 (d, J=7.6Hz, 1H), 7.30-7.20 (m, 2H), 7.12-7.08 (m,
1H), 6.97 (d, J=8.4Hz, 2H), 6.68 (d, J=8.8Hz, 2H), 6.48 (d, J=9.6Hz, 1H), 6.10 (dd, J=
6.0,9.6Hz, 1H), 4.48 (d, J=5.6Hz, 1H), 3.69 (s, 3H), 3.63 (s, 3H), 3.47 (s, 3H) ppm；HRMS m/
z[M]+calcd for C21H21O5[(M+H)+], 353.1389；Found, 353.1382.
Embodiment 17 is by loaded by polystyrene pi-allyl selenide III (1.0g, 0.97mmol), anhydrous methylene chloride (15mL)
Put in reaction bulb, stand 4h at room temperature.After resin swelling, added at 0 DEG C N- chlorosuccinimides (0.668g,
5.0mmol), at 0 DEG C after stirring reaction 5h, stirring reaction 24h is continued at room temperature.Reaction is finished, and is filtered with sand core funnel, with dry
Dry dichloromethane (4 × 10mL) washs resin, obtains loaded by polystyrene seleno succimide IV.The resin that will be obtained immediately
(IV) continue to be soaked with dry methylene chloride (15mL), be cooled at -78 DEG C, add Trimethylsilyl trifluoromethanesulfonate
(0.022g, 0.10mmol), the stirring reaction 0.5h at -78 DEG C.Add 2- [1- (4 '-bromine) phenyl propyl- 2- alkene
Base] -2- phenylmalonic acids dimethyl ester V (2.017g, 5.0mmol), after continuing stirring reaction 2h at -78 DEG C, it will react
Mixture places 8h at -20 DEG C.Reaction finish, add saturated solution of sodium bicarbonate (5mL), successively with dichloromethane (3 ×
10mL), water (3 × 10mL), water+tetrahydrofuran (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 ×
10mL), methanol (3 × 10mL), ether (3 × 10mL), dichloromethane (10mL), acetone (3 × 10mL), tetrahydrofuran (10mL)
Resin is washed, obtains 3- loaded by polystyrene selenos -2- (4 '-bromine) phenyl -1,2,3,4- tetralyls -1,1- bis-
Formic acid dimethyl ester VI.Merging filtrate and washing lotion.The most of solvent of recycling, residue are extracted with ethyl acetate, and merge organic layer, nothing
Aqueous sodium persulfate is dried.After recycling design, compound VI is put in reaction bulb, soaks 4h at room temperature with tetrahydrofuran (15mL).
It is cooled to 0 DEG C in ice bath, adds 30% aqueous hydrogen peroxide solution 1.2mL, stirring reaction 1h at 0 DEG C, is slowly warmed to room temperature, after
Continuous stirring reaction 20min.Reaction is finished, and is filtered with sand core funnel, resin is washed with dichloromethane (4 × 10mL).Merging filtrate and
Washing lotion, adds water (5mL) and saturation aqueous solution of sodium bisulfite (5mL) removes excessive hydrogen peroxide.Organic layer is separated, uses water
(5mL) is washed.Water layer is extracted with dichloromethane (2 × 5mL).Merge organic layer, anhydrous sodium sulfate drying, recycling design, obtains 2-
(yield 0.296g, 76%, purity is more than (4 '-bromine) phenyl -1,2- ihydro naphthyl -1,1- dicarboxylic acid dimethyl ester I
90%).1H NMR (400MHz, CDCl3)：δ=7.54-7.50 (m, 1H), 7.31-7.22 (m, 4H), 7.13-7.10 (m,
1H), 6.92 (d, J=8.4Hz, 2H), 6.51 (d, J=9.6Hz, 1H), 6.06 (dd, J=6.0,9.6Hz, 1H), 4.48 (d, J
=5.6Hz, 1H), 3.64 (s, 3H), 3.47 (s, 3H) ppm；HRMS m/z[M]+calcd for C20H18BrO4[(M+H)+],
401.0389；Found, 401.0380.
Embodiment 18 is by loaded by polystyrene pi-allyl selenide III (1.0g, 0.97mmol), anhydrous methylene chloride (15mL)
Put in reaction bulb, stand 4h at room temperature.After resin swelling, added at 0 DEG C N- chlorosuccinimides (0.668g,
5.0mmol), at 0 DEG C after stirring reaction 5h, stirring reaction 24h is continued at room temperature.Reaction is finished, and is filtered with sand core funnel, with dry
Dry dichloromethane (4 × 10mL) washs resin, obtains loaded by polystyrene seleno succimide (IV).The resin that will be obtained immediately
(IV) continue to be soaked with dry methylene chloride (15mL), be cooled at -78 DEG C, add Trimethylsilyl trifluoromethanesulfonate
(0.022g, 0.10mmol), the stirring reaction 0.5h at -78 DEG C.Add 2- [1- (4 '-chlorine) phenyl propyl- 2- alkene
Base] -2- phenylmalonic acids dimethyl ester V (1.794g, 5.0mmol), after continuing stirring reaction 2h at -78 DEG C, it will react
Mixture places 8h at -20 DEG C.Reaction finish, add saturated solution of sodium bicarbonate (5mL), successively with dichloromethane (3 ×
10mL), water (3 × 10mL), water+tetrahydrofuran (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 ×
10mL), methanol (3 × 10mL), ether (3 × 10mL), dichloromethane (10mL), acetone (3 × 10mL), tetrahydrofuran (10mL)
Resin is washed, obtains 3- loaded by polystyrene selenos -2- (4 '-chlorine) phenyl -1,2,3,4- tetralyls -1,1- bis-
Formic acid dimethyl ester VI.Merging filtrate and washing lotion.The most of solvent of recycling, residue are extracted with ethyl acetate, and merge organic layer, nothing
Aqueous sodium persulfate is dried.After recycling design, compound VI is put in reaction bulb, soaks 4h at room temperature with tetrahydrofuran (15mL).
It is cooled to 0 DEG C in ice bath, adds 30% aqueous hydrogen peroxide solution 1.2mL, stirring reaction 1h at 0 DEG C, is slowly warmed to room temperature, after
Continuous stirring reaction 20min.Reaction is finished, and is filtered with sand core funnel, resin is washed with dichloromethane (4 × 10mL).Merging filtrate and
Washing lotion, adds water (5mL) and saturation aqueous solution of sodium bisulfite (5mL) removes excessive hydrogen peroxide.Organic layer is separated, uses water
(5mL) is washed.Water layer is extracted with dichloromethane (2 × 5mL).Merge organic layer, anhydrous sodium sulfate drying, recycling design, obtains 2-
(yield 0.26g, 75%, 90%) purity is more than (4 '-chlorine) phenyl -1,2- ihydro naphthyl -1,1- dicarboxylic acid dimethyl ester I
。1H NMR (400MHz, CDCl3)：δ=7.43-7.41 (m, 1H), 7.25-7.21 (m, 2H), 7.05-7.02 (m, 1H),
6.34 (d, J=9.2Hz, 1H), 5.99 (dd, J=5.2,9.6Hz, 1H), 3.75 (s, 3H), 3.67 (s, 3H), 3.35-3.26
(m, 1H), 1.08 (d, J=7.2Hz, 3H) ppm；HRMS m/z[M]+calcd for C20H18ClO4[(M+H)+],
281.0581；Found, 281.0582.
Embodiment 19 is by loaded by polystyrene pi-allyl selenide III (1.0g, 0.97mmol), anhydrous methylene chloride (15mL)
Put in reaction bulb, stand 4h at room temperature.After resin swelling, added at 0 DEG C N- chlorosuccinimides (0.668g,
5.0mmol), at 0 DEG C after stirring reaction 5h, stirring reaction 24h is continued at room temperature.Reaction is finished, and is filtered with sand core funnel, with dry
Dry dichloromethane (4 × 10mL) washs resin, obtains loaded by polystyrene seleno succimide IV.The resin IV that will be obtained immediately
Continue to be soaked with dry methylene chloride (15mL), be cooled at -78 DEG C, addition Trimethylsilyl trifluoromethanesulfonate (0.022g,
0.10mmol), the stirring reaction 0.5h at -78 DEG C.Add 2- butyl- 3- alkenyl -2- phenylmalonic acids dimethyl ester V
(1.312g, 5.0mmol), after continuing stirring reaction 2h at -78 DEG C, 8h is placed by reaction mixture at -20 DEG C.Reaction
Finish, saturated solution of sodium bicarbonate (5mL) is added, successively with dichloromethane (3 × 10mL), water (3 × 10mL), water+tetrahydrofuran
(V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 × 10mL), methanol (3 × 10mL), ether (3 ×
10mL), dichloromethane (10mL), acetone (3 × 10mL), tetrahydrofuran (10mL) washing resin, obtain 3- loaded by polystyrene
Seleno -2- methyl isophthalic acids, 2,3,4- tetralyl -1,1- dicarboxylic acid dimethyl esters (VI).Merging filtrate and washing lotion.Recycling is big
Partial solvent, residue are extracted with ethyl acetate, and merge organic layer, anhydrous sodium sulfate drying.After recycling design, by compound VI
Put in reaction bulb, soak 4h at room temperature with tetrahydrofuran (15mL).0 DEG C is cooled in ice bath, adds 30% hydrogen peroxide
Aqueous solution 1.2mL, stirring reaction 1h at 0 DEG C, is slowly warmed to room temperature, continues stirring reaction 20min.Reaction is finished, and uses sand core funnel
Filtering, resin is washed with dichloromethane (4 × 10mL).Merging filtrate and washing lotion, add water (5mL) and saturation sodium hydrogensulfite water
Solution (5mL) removes excessive hydrogen peroxide.Organic layer is separated, is washed with water (5mL).Water layer is extracted with dichloromethane (2 × 5mL)
Take.Merge organic layer, anhydrous sodium sulfate drying, recycling design, obtains 2- methyl isophthalic acids, 2- ihydro naphthyls -1,1- dioctyl phthalate two
(yield 0.189g, 75%, 90%) purity is more than methyl esters I.1H NMR (400MHz, CDCl3)：δ=7.43-7.41 (m, 1H),
7.25-7.21 (m, 2H), 7.05-7.02 (m, 1H), 6.34 (d, J=9.2Hz, 1H), 5.99 (dd, J=5.2,9.6Hz,
1H), 3.75 (s, 3H), 3.67 (s, 3H), 3.35-3.26 (m, 1H), 1.08 (d, J=7.2Hz, 3H)；HRMS m/z[M]+
calcd for C15H17O4[(M+H)+], 261.1127；Found, 261.1132.
Embodiment 20 is by loaded by polystyrene pi-allyl selenide III (1.0g, 0.97mmol), anhydrous methylene chloride (15mL)
Put in reaction bulb, stand 4h at room temperature.After resin swelling, added at 0 DEG C N- chlorosuccinimides (0.668g,
5.0mmol), at 0 DEG C after stirring reaction 5h, stirring reaction 24h is continued at room temperature.Reaction is finished, and is filtered with sand core funnel, with dry
Dry dichloromethane (4 × 10mL) washs resin, obtains loaded by polystyrene seleno succimide IV.The resin IV that will be obtained immediately
Continue to be soaked with dry methylene chloride (15mL), be cooled at -78 DEG C, addition Trimethylsilyl trifluoromethanesulfonate (0.022g,
0.10mmol), the stirring reaction 0.5h at -78 DEG C.(E) -1- decyl- 3- alkenyl benzenes V (1.082g, 5.0mmol) are added,
After continuing stirring reaction 2h at -78 DEG C, reaction mixture is placed into 8h at -20 DEG C.Reaction is finished, and is added sodium acid carbonate and is satisfied
With solution (5mL), successively with dichloromethane (3 × 10mL), water (3 × 10mL), water+tetrahydrofuran (V/V=1：1,3 ×
10mL), tetrahydrofuran (3 × 10mL), ethanol (3 × 10mL), methanol (3 × 10mL), ether (3 × 10mL), dichloromethane
(10mL), acetone (3 × 10mL), tetrahydrofuran (10mL) washing resin, obtain 3- loaded by polystyrene selenos -4- just oneself
Base -1,2,3,4- tetralin quasi-compounds VI.Merging filtrate and washing lotion.The most of solvent of recycling, residue ethyl acetate
Extraction, merges organic layer, anhydrous sodium sulfate drying.After recycling design, compound VI is put in reaction bulb, uses tetrahydrofuran
(15mL) soaks 4h at room temperature.It is cooled to 0 DEG C in ice bath, adds 30% aqueous hydrogen peroxide solution 1.2mL, stirred at 0 DEG C
1h is reacted, is slowly warmed to room temperature, continues stirring reaction 20min.Reaction finish, filtered with sand core funnel, with dichloromethane (4 ×
10mL) wash resin.Merging filtrate and washing lotion, add water (5mL) and saturation aqueous solution of sodium bisulfite (5mL) removes excess
Hydrogen peroxide.Organic layer is separated, is washed with water (5mL).Water layer is extracted with dichloromethane (2 × 5mL).Merge organic layer, it is anhydrous
Sodium sulphate is dried, recycling design, and obtaining 4- n-hexyls -1,2- dihydronaphthalene I, (yield 0.162g, 78%, 90%) purity is more than.1H-NMR (300MHz, CDCl3)：δ=7.27-7.12 (m, 4H), 5.85 (t, J=4.4Hz, 1H), 2.76-2.70 (m,
2H), 2.46-2.40 (m, 2H), 2.28-2.20 (m, 2H), 1.56-1.49 (m, 2H), 1.39-1.25 (m, 6H),
0.91-0.87 (m, 3H) ppm；HRMS m/z[M]+calcd for C16H22[M]+, 214.1722；Found, 214.1715.
Embodiment 21 is by loaded by polystyrene pi-allyl selenide III (1.0g, 0.97mmol), anhydrous methylene chloride (15mL)
Put in reaction bulb, stand 4h at room temperature.After resin swelling, added at 0 DEG C N- chlorosuccinimides (0.668g,
5.0mmol), at 0 DEG C after stirring reaction 5h, stirring reaction 24h is continued at room temperature.Reaction is finished, and is filtered with sand core funnel, with dry
Dry dichloromethane (4 × 10mL) washs resin, obtains loaded by polystyrene seleno succimide IV.The resin IV that will be obtained immediately
Continue to be soaked with dry methylene chloride (15mL), be cooled at -78 DEG C, addition Trimethylsilyl trifluoromethanesulfonate (0.022g,
0.10mmol), the stirring reaction 0.5h at -78 DEG C.Add (E) -1-4- (2 '-methyl) phenyl -3- cyclobutenyls benzene V
(1.112g, 5.0mmol), after continuing stirring reaction 2h at -78 DEG C, 8h is placed by reaction mixture at -20 DEG C.Reaction
Finish, saturated solution of sodium bicarbonate (5mL) is added, successively with dichloromethane (3 × 10mL), water (3 × 10mL), water+tetrahydrofuran
(V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 × 10mL), methanol (3 × 10mL), ether (3 ×
10mL), dichloromethane (10mL), acetone (3 × 10mL), tetrahydrofuran (10mL) washing resin, obtain 3- loaded by polystyrene
Seleno -4- (2 '-methyl) phenyl -1,2,3,4- tetralin quasi-compounds VI.Merging filtrate and washing lotion.Recycling is most of
Solvent, residue are extracted with ethyl acetate, and merge organic layer, anhydrous sodium sulfate drying.After recycling design, compound (VI) is put
In reaction bulb, 4h is soaked at room temperature with tetrahydrofuran (15mL).0 DEG C is cooled in ice bath, adds 30% aquae hydrogenii dioxidi
Solution 1.2mL, stirring reaction 1h at 0 DEG C, is slowly warmed to room temperature, continues stirring reaction 20min.Reaction is finished, with sand core funnel mistake
Filter, resin is washed with dichloromethane (4 × 10mL).Merging filtrate and washing lotion, add water (5mL) and saturation sodium hydrogensulfite is water-soluble
Liquid (5mL) removes excessive hydrogen peroxide.Organic layer is separated, is washed with water (5mL).Water layer is extracted with dichloromethane (2 × 5mL)
Take.Merge organic layer, anhydrous sodium sulfate drying, recycling design, obtains I (yield of 4- (2 '-methyl) phenyl -1,2- dihydronaphthalene
0.186g, 87%, 90%) purity is more than.1H NMR (400MHz, CDCl3)：δ=7.24-7.33 (m, 5H), 7.19 (dt, J=
7.2,1.2Hz, 1H), 7.19 (dt, J=7.6,1.4Hz, 1H), 6.70 (d, J=7.6Hz, 1H), 6.00 (t, J=4.4Hz,
1H), 2.93-3.01 (m, 2H), 2.46-2.52 (m, 2H), 2.18 (s, 3H) ppm；HRMS m/z calcd for C17H16
[M+], 220.1252；Found, 220.1250.
Embodiment 22 is by loaded by polystyrene pi-allyl selenide III (1.0g, 0.97mmol), anhydrous methylene chloride (15mL)
Put in reaction bulb, stand 4h at room temperature.After resin swelling, added at 0 DEG C N- chlorosuccinimides (0.668g,
5.0mmol), at 0 DEG C after stirring reaction 5h, stirring reaction 24h is continued at room temperature.Reaction is finished, and is filtered with sand core funnel, with dry
Dry dichloromethane (4 × 10mL) washs resin, obtains loaded by polystyrene seleno succimide IV.The resin IV that will be obtained immediately
Continue to be soaked with dry methylene chloride (15mL), be cooled at -78 DEG C, addition Trimethylsilyl trifluoromethanesulfonate (0.022g,
0.10mmol), the stirring reaction 0.5h at -78 DEG C.Add (E) -1-4- (4 '-chlorine) phenyl -3- cyclobutenyls benzene V
(1.214g, 5.0mmol), after continuing stirring reaction 2h at -78 DEG C, 8h is placed by reaction mixture at -20 DEG C.Reaction
Finish, saturated solution of sodium bicarbonate (5mL) is added, successively with dichloromethane (3 × 10mL), water (3 × 10mL), water+tetrahydrofuran
(V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 × 10mL), methanol (3 × 10mL), ether (3 ×
10mL), dichloromethane (10mL), acetone (3 × 10mL), tetrahydrofuran (10mL) washing resin, obtain 3- loaded by polystyrene
Seleno -4- (4 '-chlorine) phenyl -1,2,3,4- tetralin quasi-compounds VI.Merging filtrate and washing lotion.Recycling is most of molten
Agent, residue are extracted with ethyl acetate, and merge organic layer, anhydrous sodium sulfate drying.After recycling design, compound (VI) is put instead
Answer in bottle, soak 4h at room temperature with tetrahydrofuran (15mL).0 DEG C is cooled in ice bath, it is water-soluble to add 30% hydrogen peroxide
Liquid 1.2mL, stirring reaction 1h at 0 DEG C, is slowly warmed to room temperature, continues stirring reaction 20min.Reaction is finished, and is filtered with sand core funnel,
Resin is washed with dichloromethane (4 × 10mL).Merging filtrate and washing lotion, add water (5mL) and saturation aqueous solution of sodium bisulfite
(5mL) removes excessive hydrogen peroxide.Organic layer is separated, is washed with water (5mL).Water layer is extracted with dichloromethane (2 × 5mL).
Merge organic layer, anhydrous sodium sulfate drying, recycling design, obtains I (yield of 4- (4 '-chlorine) phenyl -1,2- dihydronaphthalene
0.198g, 85%, 90%) purity is more than.1H NMR (400MHz, CDCl3)：δ=7.36-7.39 (m, 2H), 7.28-7.32
(m, 2H), 7.17-7.24 (m, 2H), 7.15 (dt, J=7.5,1.7Hz, 1H), 6.98 (d, J=7.4Hz, 1H), 6.10 (t, J
=4.7Hz, 1H), 2.88 (t, J=7.9Hz, 2H), 2.41-2.46 (m, 2H) ppm；HRMS m/z calcd for
C16H13Cl[(M+H)+], calcd for 240.0706；found 240.0700.
Embodiment 23 is by loaded by polystyrene pi-allyl selenide III (1.0g, 0.97mmol), anhydrous methylene chloride (15mL)
Put in reaction bulb, stand 4h at room temperature.After resin swelling, added at 0 DEG C N- chlorosuccinimides (0.668g,
5.0mmol), at 0 DEG C after stirring reaction 5h, stirring reaction 24h is continued at room temperature.Reaction is finished, and is filtered with sand core funnel, with dry
Dry dichloromethane (4 × 10mL) washs resin, obtains loaded by polystyrene seleno succimide IV.The resin IV that will be obtained immediately
Continue to be soaked with dry methylene chloride (15mL), be cooled at -78 DEG C, addition Trimethylsilyl trifluoromethanesulfonate (0.022g,
0.10mmol), the stirring reaction 0.5h at -78 DEG C.Add (E) -1-4- (4 '-methoxyl group) phenyl -3- cyclobutenyl benzene
(V) (1.191g, 5.0mmol), after continuing stirring reaction 2h at -78 DEG C, 8h is placed by reaction mixture at -20 DEG C.
Reaction is finished, and saturated solution of sodium bicarbonate (5mL) is added, successively with dichloromethane (3 × 10mL), water (3 × 10mL), water+tetrahydrochysene
Furans (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 × 10mL), methanol (3 × 10mL), ether (3 ×
10mL), dichloromethane (10mL), acetone (3 × 10mL), tetrahydrofuran (10mL) washing resin, obtain 3- loaded by polystyrene
Seleno -4- (4 '-methoxyl group) phenyl -1,2,3,4- tetralin quasi-compounds VI.Merging filtrate and washing lotion.Recycle big portion
Divide solvent, residue is extracted with ethyl acetate, and merges organic layer, anhydrous sodium sulfate drying.After recycling design, by compound (VI)
Put in reaction bulb, soak 4h at room temperature with tetrahydrofuran (15mL).0 DEG C is cooled in ice bath, adds 30% hydrogen peroxide
Aqueous solution 1.2mL, stirring reaction 1h at 0 DEG C, is slowly warmed to room temperature, continues stirring reaction 20min.Reaction is finished, and uses sand core funnel
Filtering, resin is washed with dichloromethane (4 × 10mL).Merging filtrate and washing lotion, add water (5mL) and saturation sodium hydrogensulfite water
Solution (5mL) removes excessive hydrogen peroxide.Organic layer is separated, is washed with water (5mL).Water layer is extracted with dichloromethane (2 × 5mL)
Take.Merge organic layer, anhydrous sodium sulfate drying, recycling design, obtains (the production of 4- (4 '-methoxyl group) phenyl -1,2- dihydronaphthalene I
Rate 0.202g, 88%, 90%) purity is more than.1H NMR (400MHz, CDCl3)：δ=7.29-7.32 (m, 2H), 7.12-
7.25 (m, 3H), 7.06 (d, J=7.2Hz, 1H), 6.93-6.98 (m, 1H), 6.07 (t, J=4.8Hz, 1H), 3.88 (s,
3H), 2.88 (t, J=8.0Hz, 2H), 2.40-2.45 (m, 2H) ppm；HRMS(AAPI+)m/z calcd for C17H16O[M
+H]+, 236.1201；Found, 236.1205.
Embodiment 24 is by loaded by polystyrene pi-allyl selenide III (1.0g, 0.97mmol), anhydrous methylene chloride (15mL)
Put in reaction bulb, stand 4h at room temperature.After resin swelling, added at 0 DEG C N- chlorosuccinimides (0.668g,
5.0mmol), at 0 DEG C after stirring reaction 5h, stirring reaction 24h is continued at room temperature.Reaction is finished, and is filtered with sand core funnel, with dry
Dry dichloromethane (4 × 10mL) washs resin, obtains loaded by polystyrene seleno succimide IV.The resin IV that will be obtained immediately
Continue to be soaked with dry methylene chloride (15mL), be cooled at -78 DEG C, addition Trimethylsilyl trifluoromethanesulfonate (0.022g,
0.10mmol), the stirring reaction 0.5h at -78 DEG C.Addition (E) -2- (3,4- Dimethoxyphenyl) -5- phenyl -
Allyl acetonitrile V (1.467g, 5.0mmol), after continuing stirring reaction 2h at -78 DEG C, by reaction mixture at -20 DEG C
Place 8h.Reaction finish, add saturated solution of sodium bicarbonate (5mL), successively with dichloromethane (3 × 10mL), water (3 × 10mL),
Water+tetrahydrofuran (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 × 10mL), methanol (3 × 10mL),
Ether (3 × 10mL), dichloromethane (10mL), acetone (3 × 10mL), tetrahydrofuran (10mL) washing resin, obtain 3- polyphenyl
Ethene loads the bromo- 4- phenyl -1,2 of seleno -7-, 3,4- tetralin quasi-compounds VI.Merging filtrate and washing lotion.Recycling is big
Partial solvent, residue are extracted with ethyl acetate, and merge organic layer, anhydrous sodium sulfate drying.After recycling design, by compound VI
Put in reaction bulb, soak 4h at room temperature with tetrahydrofuran (15mL).0 DEG C is cooled in ice bath, adds 30% hydrogen peroxide
Aqueous solution 1.2mL, stirring reaction 1h at 0 DEG C, is slowly warmed to room temperature, continues stirring reaction 20min.Reaction is finished, and uses sand core funnel
Filtering, resin is washed with dichloromethane (4 × 10mL).Merging filtrate and washing lotion, add water (5mL) and saturation sodium hydrogensulfite water
Solution (5mL) removes excessive hydrogen peroxide.Organic layer is separated, is washed with water (5mL).Water layer is extracted with dichloromethane (2 × 5mL)
Take.Merge organic layer, anhydrous sodium sulfate drying, recycling design, obtains bromo- 4- phenyl -1,2- dihydronaphthalene (the I) (yields of 7-
0.221g, 80%, 90%) purity is more than.1H NMR (500MHz, CDCl3)：δ=7.33-7.42 (m, 6H), 7.25 (dd, J=
8.3,2.05Hz, 1H), 6.89 (d, J=8.2Hz, 1H), 6.13 (t, J=4.7Hz, 1H), 2.86 (t, J=7.9Hz, 2H),
(2.40-2.45 m, 2H) ppm；HRMS m/z calcd for C16H13Br[M+], 284.0201；Found, 284.0209.
Embodiment 25 is by loaded by polystyrene pi-allyl selenide III (1.0g, 0.97mmol), anhydrous methylene chloride (15mL)
Put in reaction bulb, stand 4h at room temperature.After resin swelling, added at 0 DEG C N- chlorosuccinimides (0.668g,
5.0mmol), at 0 DEG C after stirring reaction 5h, stirring reaction 24h is continued at room temperature.Reaction is finished, and is filtered with sand core funnel, with dry
Dry dichloromethane (4 × 10mL) washs resin, obtains loaded by polystyrene seleno succimide IV.The resin IV that will be obtained immediately
Continue to be soaked with dry methylene chloride (15mL), be cooled at -78 DEG C, addition Trimethylsilyl trifluoromethanesulfonate (0.022g,
0.10mmol), the stirring reaction 0.5h at -78 DEG C.Add (E) -2- (4 '-phenyl -1 '-butylene) -1- benzoic acid
Methyl esters (V) (1.331g, 5.0mmol), after continuing stirring reaction 2h at -78 DEG C, by reaction mixture in -20 DEG C of decentralizations
Put 8h.Reaction finish, add saturated solution of sodium bicarbonate (5mL), successively with dichloromethane (3 × 10mL), water (3 × 10mL), water+
Tetrahydrofuran (V/V=1：1,3 × 10mL), tetrahydrofuran (3 × 10mL), ethanol (3 × 10mL), methanol (3 × 10mL), ether
(3 × 10mL), dichloromethane (10mL), acetone (3 × 10mL), tetrahydrofuran (10mL) washing resin, obtain 2- (2 '-it is poly-
Styrene loads seleno) -1 ', 2 ', 3 ', 4 ＇-tetralyl -1- methyl benzoates VI.Merging filtrate and washing lotion.Recycling is big
Partial solvent, residue are extracted with ethyl acetate, and merge organic layer, anhydrous sodium sulfate drying.After recycling design, by compound VI
Put in reaction bulb, soak 4h at room temperature with tetrahydrofuran (15mL).0 DEG C is cooled in ice bath, adds 30% hydrogen peroxide
Aqueous solution 1.2mL, stirring reaction 1h at 0 DEG C, is slowly warmed to room temperature, continues stirring reaction 20min.Reaction is finished, and uses sand core funnel
Filtering, resin is washed with dichloromethane (4 × 10mL).Merging filtrate and washing lotion, add water (5mL) and saturation sodium hydrogensulfite water
Solution (5mL) removes excessive hydrogen peroxide.Organic layer is separated, is washed with water (5mL).Water layer is extracted with dichloromethane (2 × 5mL)
Take.Merge organic layer, anhydrous sodium sulfate drying, recycling design, obtains (the production of 2- (3,4- ihydro naphthyl) -1- methyl benzoates I
Rate 0.2g, 78%, 90%) purity is more than.1H NMR (400MHz, CDCl3)：δ=7.87 (dd, J=7.6,1.2Hz, 1H),
7.52 (dt, J=7.6,1.4Hz, 1H), 7.40 (dt, J=7.8,1.4Hz, 1H), 7.34 (dd, J=7.6,0.9Hz, 1H),
7.17 (d, J=6.6Hz, 1H), 7.10 (dt, J=7.4,1.2Hz, 1H), 7.02 (dt, J=7.8,1.4Hz, 1H), 6.62 (d,
J=7.5Hz, 1H), 5.98 (t, J=4.6Hz, 1H), 3.46 (s, 3H), 2.85-2.90 (m, 2H), 2.41 (m, 2H).HRMS
(ES+)：calcd for C18H17O2[(M+H)+], 265.1229；Found, 265.1223.
Claims (4)
1. a kind of solid phase synthesis process of dihydro naphthalene compounds, it is characterised in that synthesized compound formula is I：
R in formula1=H ,-CN ,-COOCH3；R2=H, C1-4Alkyl ,-COOCH3；R3=H ,-CH3, Ph ,-C6H4CH3,-
C6H4OCH3,-C6H4Cl ,-C6H4Br；R4=H, C1-6Alkyl, Ph ,-C6H4CH3,-C6H4OCH3,-C6H4Cl ,-
C6H4COOCH3,-C6H4NO2；R5=H ,-OCH3,-OBn；R6=H ,-OCH3,-Br；
Under nitrogen protection, 1% crosslinked polystyrene load seleno bromide reagent II in organic solvent with sodium borohydride and alkene
Propyl group bromine reaction prepares loaded by polystyrene pi-allyl selenide III；
In halogenated organic solvent loaded by polystyrene seleno succinyl is obtained with chlorosuccinimide processing compound III
Imines reagent IV；
Under trifluoromethayl sulfonic acid trimethyl silicane ester catalysis, reagent IV is in halogenated organic solvent, benzene in induced reaction thing V
The selenium virtueization that molecule internal olefin occurs for the ortho position C-H of ring and the carbon-to-carbon double bond of intramolecular is reacted, and generation 3- polystyrene is born
Seleno -1,2 is carried, 3,4- naphthanes VI, without traditional column chromatography for separation, need to only wash middle by filtering and with different solvents
Body resin VI；
The analytically pure organic solvent of intermediate resin VI is soaked again, with the aqueous hydrogen peroxide solution that mass volume ratio is 30%
Seleno oxide is oxidized to by VI, the cis elimination of seleno oxide then occurs, resin is then washed by filtering and solvent, is merged
Filtrate and washing lotion, are extracted with organic solvent, and dry organic phase, concentration directly obtains the product I of high-purity；
The compound VI and the molar ratio of oxidant are 1:10~40；Organic solvent used is tetrahydrofuran or C1-2Fat
The mass volume ratio of race's halogenated hydrocarbon, compound VI and organic solvent is 1:10~80；Reaction temperature is 0~70 DEG C, during reaction
Between for 1~8 it is small when；
The structural formula of reactant II, III, IV, V, VI is as follows：
2. the solid phase synthesis process of dihydro naphthalene compounds as claimed in claim 1, it is characterised in that：Prepared by compound ii
During compound III, the molar ratio of compound ii and sodium borohydride is 1:1.5~10.0, the molar ratio of compound ii and allyl bromide, bromoallylene
For 1:2.0~12.0, organic solvent used is tetrahydrofuran, n,N-Dimethylformamide, one kind in absolute ethyl alcohol or one
More than kind, the mass volume ratio of compound ii and organic solvent is 1:10~100, reaction temperature is 10~60 DEG C, the reaction time
For 6~72 it is small when, in post processing wash resin used in solvent for tetrahydrofuran, water, dichloromethane, ethanol, methanol, ether,
One or more in acetone.
3. the solid phase synthesis process of dihydro naphthalene compounds as claimed in claim 1, it is characterised in that：Prepared by compound III
During compounds Ⅳ, the molar ratio of compound III and chlorosuccinimide is 1:3~30, organic solvent used is dry
C1-2The mass volume ratio of aliphatic halogenated hydrocarbon class, compound III and organic solvent is 1:10~100, reaction temperature for -10~
60 DEG C, it is dry C that the solvent used in resin is washed when the reaction time is 2~72 small, in post processing1-2Aliphatic halogenated hydrocarbon class.
4. the solid phase synthesis process of dihydro naphthalene compounds as claimed in claim 1, it is characterised in that：Prepared by compound V
During compound VI, the molar ratio of compounds Ⅳ and trifluoromethayl sulfonic acid trimethylsilyl group is 1:0.05~1.5, compounds Ⅳ is with changing
The molar ratio of compound V is 1:3~50, organic solvent used is dry C1-2Aliphatic halogenated hydrocarbon class, compounds Ⅳ is with having
The mass volume ratio of solvent is 1:10~100, reaction temperature is -80~0 DEG C, when the reaction time is 6~48 small, You Jirong
Agent is tetrahydrofuran, the one or more in water, dichloromethane, ethanol, methanol, ether, acetone.
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