CN108997365A - A kind of sequential catalyst preparation method of chiral pyrazol spiral shell furfuran compound - Google Patents

A kind of sequential catalyst preparation method of chiral pyrazol spiral shell furfuran compound Download PDF

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CN108997365A
CN108997365A CN201810997325.XA CN201810997325A CN108997365A CN 108997365 A CN108997365 A CN 108997365A CN 201810997325 A CN201810997325 A CN 201810997325A CN 108997365 A CN108997365 A CN 108997365A
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spiral shell
phenyl
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methyl
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CN108997365B (en
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夏爱宝
汤成科
许丹倩
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Zhejiang University of Technology ZJUT
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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Abstract

The present invention provides the sequential catalyst preparation methods of one kind chiral pyrazol spiral shell furfuran compound as shown in formula (I), the synthetic method carries out as follows: by pyrazoline ketone compounds shown in neighbour's hydroxyl nitro compds hydrocarbon compound shown in formula (II) and formula (III), chirality side's acid catalyst, organic solvent mixing, 1~48h is reacted at -20~60 DEG C, obtain formula (IV) compound represented, propiodal additive is added into compound shown in formula (IV), oxidant, 1~48h is reacted at -20~60 DEG C, reaction solution is post-treated to obtain chiral pyrazol spiral shell furfuran compound shown in formula (I)；Reaction condition of the present invention is mild, and product yield high, selectivity are excellent；The chiral pyrazol spiral shell furfuran compound of preparation has chirality, and core skeleton structure has novelty.

Description

A kind of sequential catalyst preparation method of chiral pyrazol spiral shell furfuran compound
(1) technical field
The present invention relates to a kind of sequential catalyst preparation methods of chiral pyrazol spiral shell furfuran compound.
(2) background technique
Chiral pyrazol volution compound is largely present in biologically active natural products and clinical medicine, tool There is an extensive bioactivity, such as with bringing down a fever, nerve, anti-analgesic, antibacterium, antimycotic, anti-inflammatory, antitumor etc. is protected to make With.Chiral pyrazol volution compound common structure has pyrazoles spiro cyclopentane, pyrazoles loop coil hexane, pyrazoles loop coil hexanone, pyrazoles Loop coil hexenone etc., such as: scientific name is 4- (3,4- Dimethoxyphenyl) -2- (1- (5- hydroxy-2-methyl benzoyl) -4- piperazine Piperidinyl) -2,3- diazaspiracyclic [4.4] nonyl- 3- alkene -1- ketone compound A and scientific name be N- (3- isobutyl group -4- oxa- -2,3- Diazaspiracyclic [4.5] decyl- 1- alkene -8- base) the compound B of -4- (1H- pyrazol-1-yl) benzsulfamide is phosphodiesterase PDE4 inhibitor, a kind of drug of the skeleton containing pyrazoles spiro cyclopentane and pyrazoles loop coil hexane, it is widely used in treating In the diseases such as heart failure, asthma, while phosphodiesterase inhibitors also have and increasing cAMP content in vascular smooth muscle cells There is vasodilative effect；Compound C, Anti-microbial, scientific name is 4- methyl 2- phenyl -2,3- diazaspiracyclic [4.5] decyl- 3- alkene -1,8- diketone, a kind of drug of pyrazoles cyclohexanone skeleton are effective anti-inflammatory and anti-microbial agents, are conducive to wound Slow healing.The molecular structural formula of phosphodiesterase PDE4 inhibitor and Anti-microbial are as follows:
Nearly more than ten years, organocatalysis, especially square acid catalysis achieve very great achievement in the field of asymmetric synthesis Just.2008, professor Rawal reported organic hydrogen-bond catalyst acetylacetone,2,4-pentanedione and nitroolefin derived from quinine The asymmetric Michael Reaction of class compound achieves up to 99% yield and the optical activity product of 98%ee value.2016 Year, Enders professor is catalyzed adjacent alkynyl nitre with the sequential catalyst method of organic hydrogen-bond catalyst derived from cinchona alkaloid and metallic silver The tandem reaction of the Michael and Conia-ene of base alkenes compounds and pyrazoline ketone compounds, it is complicated chiral for building A kind of fabulous synthesizing mean is provided in terms of molecule.2017, our seminars used 1 respectively, hydroresorcinol class compound With 4 hydroxy coumarin class compound and pyrazoline ketone compounds respectively in organic hydrogen-bond catalysis, the work of inorganic base and iodine Under, chiral pyrazol spiral shell furfuran compound is successfully synthesized.This method needs to use the inorganic base and iodine of equivalent, atom Utilization rate is lower, generates more inorganic salts waste.2018, Jiang seminar reported o-quinone methides class chemical combination Michael reaction occurs under the action of organic hydrogen-bond catalyst and sodium carbonate for object and pyrazoline ketone compounds, is then added After chlorosuccinimide and potassium carbonate, cyclization obtains chiral pyrazol spiral shell furfuran compound.This method needs excessive inorganic Alkali and chlorosuccinimide, and react and substep is needed to carry out, complex process.Sequential catalyst method according to the present invention is improving Reaction efficiency avoids waste and improve Atom economy etc. from having some superiority, especially for some complicated chiral compounds The synthesis of object provides a kind of completely new synthetic method, has wide development space.
(3) summary of the invention
It is an object of that present invention to provide a kind of sequential catalyst preparation methods of chiral pyrazol spiral shell furfuran compound.
To achieve the above object, the present invention adopts the following technical scheme:
One kind a kind of sequential catalyst preparation method of chiral pyrazol spiral shell furfuran compound, feature as shown in formula (I) It is, the synthetic method includes (A) Michael reaction and two steps of (B) cyclization, and the synthetic method It carries out as follows:
(A) by pyrazoline ketone compounds, hand shown in neighbour's hydroxyl nitro compds hydrocarbon compound shown in formula (II) and formula (III) Property side's acid catalyst, organic solvent A are uniformly mixed, and 1~48h is reacted at -20~60 DEG C, after reaction, are obtained containing formula (IV) mixture of compound represented；Shown in neighbour's hydroxyl nitro compds hydrocarbon compound shown in the formula (II) and formula (III) The ratio between amount of substance of pyrazoline ketone compounds, chirality side's acid catalyst is 1:1~10:0.01~0.2；
(B) step (A) mixture obtained containing compound shown in formula (IV) is removed into solvent, propiodal addition is then added Agent and oxidant react 1~48h in organic solvent B at -20~60 DEG C, after reaction, obtain reaction mixture warp Post-processing obtains chiral pyrazol spiral shell furfuran compound shown in formula (I)；Described propiodal oxidant, oxidant and formula (IV) institute Show that the ratio between amount of substance of compound is 0.05~10:1~10:1,
In formula (I), formula (III) and formula (IV),
The R1For C1~C20Alkyl, phenyl, benzyl, 2- methoxyphenyl, 3- methoxyphenyl, 4- methoxybenzene Base, 2- aminomethyl phenyl, 3- aminomethyl phenyl, 4- aminomethyl phenyl, 2- nitrobenzophenone, 3- nitrobenzophenone, 4- nitrobenzophenone, 2- fluorobenzene Base, 3- fluorophenyl, 4- fluorophenyl, 2- chlorphenyl, 3- chlorphenyl, 4- chlorphenyl, 2- bromophenyl, 3- bromophenyl, 4- bromophenyl, furan It mutters base, thienyl or pyridyl group；
The R2For C1~C20Alkyl, phenyl, benzyl, 2- methoxyphenyl, 3- methoxyphenyl, 4- methoxybenzene Base, 2- aminomethyl phenyl, 3- aminomethyl phenyl, 4- aminomethyl phenyl, 2- nitrobenzophenone, 3- nitrobenzophenone, 4- nitrobenzophenone, 2- fluorobenzene Base, 3- fluorophenyl, 4- fluorophenyl, 2- chlorphenyl, 3- chlorphenyl, 4- chlorphenyl, 2- bromophenyl, 3- bromophenyl, 4- bromophenyl, 2- Cyano-phenyl, 3- cyano-phenyl, 4- cyano-phenyl, 2- nitrobenzophenone, 3- nitrobenzophenone, 4- nitrobenzophenone, furyl, thienyl Or pyridyl group；
In formula (II), formula (III) and formula (IV), n is the number of substituent group, and n takes 1 or 2；
When n is 1, the R3For 3- methoxyl group, 4- methoxyl group, 5- methoxyl group, 3- ethyoxyl, 5- methyl, 5- fluorine, 3- Chlorine, 5- chlorine, 3- bromine, 5- bromine or 5- nitro；
When n is 2, the R3For 3,5- dichloro or the bromo- 5- chlorine of 3-.
Further, the R1For methyl, ethyl, n-propyl, isopropyl, cyclopropyl, phenyl；The R2For methyl, different Propyl, cyclohexyl, phenyl, 4- aminomethyl phenyl, 2- chlorphenyl, 4- chlorphenyl, 3- bromophenyl, 4- cyano-phenyl, 4- nitrobenzophenone； When n is 1, the R3For H, 3- methoxyl group, 5- methoxyl group, 3- ethyoxyl, 5- methyl, 5- fluorine, 3- chlorine, 5- chlorine, 3- bromine or 5- Bromine；When n is 1 or 2, the R3For 3,5- dichloro or the bromo- 5- chlorine of 3-.
In synthetic method step (A) of the present invention, chirality side's acid catalyst be can be selected from shown in formula (V)~(XIII) One of compound, preferably formula (VII) compound represented:
Further, in step (A), neighbour's hydroxyl nitro compds hydrocarbon compound and formula (III) shown in the preferably described formula (II) The ratio between amount for the substance that feeds intake of shown pyrazoline ketone compounds, chirality side's acid catalyst is 1:1:0.03.
Further, in step (A), reaction temperature is 25 DEG C, reaction time 6h.
Further, in step (B), the propiodal additive is potassium iodide, sodium iodide, cupric iodide, cuprous iodide, four fourths Base ammonium iodide, elemental iodine, hydrogen iodide or iodobenzene acetate, preferably elemental iodine.
Further, in step (B), the oxidant is the hydrogen peroxide tert-butyl alcohol, di-t-butyl peroxide, m-chloro peroxide Benzoic acid, sodium hypochlorite, sodium chlorite, hydrogen peroxide, oxygen, peroxidized t-butyl perbenzoate or potassium peroxydisulfate, preferably dioxygen Water.
Further, in step (B), the preferably throwing of compound shown in the propiodal additive, oxidant and formula (II) The ratio between amount of material matter is 0.2:2:1.
Further, in step (A) or step (B), the organic solvent is selected from methylene chloride, chloroform, 1,2- bis- Chloroethanes, 1,1,2- trichloroethanes, ether, isopropyl ether, tetrahydrofuran, 1,4- dioxane, ethyl acetate, toluene, dimethylbenzene, Thionyl chloride, n,N-Dimethylformamide, acetonitrile, methanol or ethyl alcohol, preferably chloroform.
Further, in step (A), the volumetric usage of the organic solvent A is with neighbour's hydroxyl nitro compds hydro carbons shown in formula (II) The amount of the substance of compound is calculated as 5~20mL/mmol, preferably 10mL/mmol.
Further, in step (B), the volumetric usage of the organic solvent B is with the formula (II) compound represented The amount of substance be calculated as 5~20mL/mmol, preferably 10mL/mmol.
Further, in synthetic method step (B) of the present invention, reaction temperature is 25 DEG C, reaction time 6h.
Further, in step (B), the method for the post-processing of the reaction mixture are as follows: after reaction, reaction mixing Liquid is extracted with ethyl acetate, and after extract liquor distillation removing solvent, residue carries out column chromatography for separation with 200~300 mesh silica gel, washes De- agent is the mixed liquor of ethyl acetate and petroleum ether volume ratio 1:2~70, collects the eluent containing target compound, solvent is evaporated off And it is dry to get chiral pyrazol spiral shell furfuran compound shown in formula (I).
Further, the chiral pyrazol spiral shell furfuran compound is formula (Ia) compound represented:
In formula (Ia), R1、R2、R3The same formula of definition (I).
More specifically, the chiral pyrazol spiral shell furfuran compound is one of following:
1) (2S, 3R) -3'- methyl-3-nitro methyl-1 '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5'(1' H) -one；
2) (2S, 3R) -3'- ethyl -3- nitromethyla -1'- phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5'(1' H) -one；
3) (2S, 3R) -3- nitromethyla -1'- phenyl -3'- propyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5'(1' H) -one；
4) (2S, 3R) -3'- isopropyl -3- nitromethyla -1'- phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5' (1'H) -one；
5) (2R, 3S) -3'- cyclopropyl -3- nitromethyla -1'- phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5' (1'H) -one；
6) (2R, 3S) -3- nitromethyla -1', 3'- diphenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5'(1'H) - Ketone；
7) (2R, 3S) -3'- methyl-3-nitro methyl-1 '-p-methylphenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] - 5'(1'H) -one；
8) (2R, 3S) -1'- Chloro-O-Phenyl -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5' (1'H) -one；
9) (2R, 3S) -1'- rubigan -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5' (1'H) -one；
10) (2S, 3R) -1'- m-bromophenyl -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] - 5'(1'H) -one；
11) (2S, 3R) -1'- is to cyano-phenyl -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one；
12) (2S, 3R) -1', 3'- dimethyl -3- nitromethyla -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5'(1'H) - Ketone；
13) (2S, 3R) -1'- isopropyl -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5' (1'H) -one；
14) (2R, 3S) -1'- cyclohexyl -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5' (1'H) -one；
15) (2R, 3S) -5- methoxyl group -3'- methyl-3-nitro methyl-1 '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one；
16) (2R, 3S) -7- methoxyl group -3'- methyl-3-nitro methyl-1 '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one；
17) (2R, 3S) -7- ethyoxyl -3'- methyl-3-nitro methyl-1 '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one；
18) (2R, 3S) -3', 5- dimethyl -3- nitromethyla -1'- phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] - 5'(1'H) -one；
19) the fluoro- 3'- methyl-3-nitro methyl-1 of (2S, 3R) -5- '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] - 5'(1'H) -one；
20) the chloro- 3'- methyl-3-nitro methyl-1 of (2S, 3R) -5- '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] - 5'(1'H) -one；
21) the bromo- 3'- methyl-3-nitro methyl-1 of (2S, 3R) -5- '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] - 5'(1'H) -one；
22) the chloro- 3'- methyl-3-nitro methyl-1 of (2S, 3R) -5,7- two '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one；
23) the chloro- 3'- methyl-3-nitro methyl-1 of the bromo- 5- of (2R, 3S) -7- '-phenyl -3H- spiral shell [benzofuran -2,4'- Pyrazoles] -5'(1'H) -one；
24) (2R, 3S) -7- methoxyl group -3'- methyl-3-nitro methyl-1 '-to cyano-phenyl -3H- spiral shell [benzofuran - 2,4'- pyrazoles] -5'(1'H) -one；
25) (2R, 3S) -3'- methyl-3-nitro methyl-1 '-p-nitrophenyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one.
Compared with prior art, the beneficial effects of the present invention are:
(1) synthesising method reacting condition of the present invention is mild, and product yield high, selectivity are excellent, is suitable for industry Production；
(2) chiral chiral pyrazol spiral shell furfuran compound prepared by the present invention has chirality, can be applied to organic synthesis, The fields such as material；
(3) synthetic method of the invention, easy to operate, reaction condition is mild, shows good response characteristic, and reaction is received Rate is high, selectivity is good.
(4) specific embodiment
The present invention is described further combined with specific embodiments below, but protection scope of the present invention is not limited in This.
Compound as described below has been synthesized in specific embodiments of the present invention:
1) (2S, 3R) -3'- methyl-3-nitro methyl-1 '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5'(1' H) -one；
2) (2S, 3R) -3'- ethyl -3- nitromethyla -1'- phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5'(1' H) -one；
3) (2S, 3R) -3- nitromethyla -1'- phenyl -3'- propyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5'(1' H) -one；
4) (2S, 3R) -3'- isopropyl -3- nitromethyla -1'- phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5' (1'H) -one；
5) (2S, 3R) -3'- cyclopropyl -3- nitromethyla -1'- phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5' (1'H) -one；
6) (2S, 3R) -3- nitromethyla -1', 3'- diphenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5'(1'H) - Ketone；
7) (2S, 3R) -3'- methyl-3-nitro methyl-1 '-p-methylphenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] - 5'(1'H) -one；
8) (2S, 3R) -1'- Chloro-O-Phenyl -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5' (1'H) -one；
9) (2S, 3R) -1'- rubigan -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5' (1'H) -one；
10) (2S, 3R) -1'- m-bromophenyl -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] - 5'(1'H) -one；
11) (2S, 3R) -1'- is to cyano-phenyl -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one；
12) (2S, 3R) -1', 3'- dimethyl -3- nitromethyla -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5'(1'H) - Ketone；
13) (2S, 3R) -1'- isopropyl -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5' (1'H) -one；
14) (2S, 3R) -1'- cyclohexyl -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5' (1'H) -one；
15) (2S, 3R) -5- methoxyl group -3'- methyl-3-nitro methyl-1 '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one；
16) (2S, 3R) -7- methoxyl group -3'- methyl-3-nitro methyl-1 '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one；
17) (2S, 3R) -7- ethyoxyl -3'- methyl-3-nitro methyl-1 '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one；
18) (2S, 3R) -3', 5- dimethyl -3- nitromethyla -1'- phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] - 5'(1'H) -one；
19) the fluoro- 3'- methyl-3-nitro methyl-1 of (2S, 3R) -5- '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] - 5'(1'H) -one；
20) the chloro- 3'- methyl-3-nitro methyl-1 of (2S, 3R) -5- '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] - 5'(1'H) -one；
21) the bromo- 3'- methyl-3-nitro methyl-1 of (2S, 3R) -5- '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] - 5'(1'H) -one；
22) the chloro- 3'- methyl-3-nitro methyl-1 of (2S, 3R) -5,7- two '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one；
23) the chloro- 3'- methyl-3-nitro methyl-1 of the bromo- 5- of (2S, 3R) -7- '-phenyl -3H- spiral shell [benzofuran -2,4'- Pyrazoles] -5'(1'H) -one；
24) (2S, 3R) -7- methoxyl group -3'- methyl-3-nitro methyl-1 '-to cyano-phenyl -3H- spiral shell [benzofuran - 2,4'- pyrazoles] -5'(1'H) -one；
25) (2S, 3R) -3'- methyl-3-nitro methyl-1 '-p-nitrophenyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one.
Embodiment 1:(2S, 3R) -3'- methyl-3-nitro methyl-1 '-phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] - 5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, adjacent hydroxyl nitroolefin (0.2mmol, 0.033g), 5- methyl -2- phenyl-is added Pyrazolone (0.2mmol, 0.0348g), chirality side acid catalyst V (0.002mmol, 0.0012g), methylene chloride (1mL) after 25 DEG C of reaction 6h, obtains the mixture of the 1-A containing midbody compound；
(B) mixture of the 1-A containing midbody compound is removed into solvent, is added cuprous iodide (0.076g, 0.4mmol), 30% hydrogen peroxide solution (0.4mmol, 0.0453g), methylene chloride (1mL), after 25 DEG C of reaction 8h, with ethyl acetate (3 × It 10mL) extracts, organic phase depressurizes precipitation, is eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent；200-300 mesh column Chromatographic silica gel is filler, target product that column chromatography for separation purifies (0.0593g, 88%yield, 92%ee, > 99: 1dr),1H NMR(500MHz,CDCl3): δ 7.82 (d, J=7.6Hz, 2H), 7.44-7.41 (m, 2H), 7.33 (t, J= 7.8Hz, 1H), 7.28-7.23 (m, 1H), 7.20 (d, J=7.5Hz, 1H), 7.05 (t, J=7.5Hz, 1H), 6.99 (d, J= 8.1Hz, 1H), 5.32 (dd, J=15.8,10.3Hz, 1H), 4.74 (dd, J=15.8,4.0Hz, 1H), 4.45 (dd, J= 10.3,4.0Hz,1H),2.13(s,3H)；13C NMR(125MHz,CDCl3):δ167.9,158.2,158.1,137.0, 130.7,128.9(×2),125.9,124.5,122.6,122.3,119.3(×2),110.9,87.3,72.8,44.2, 12.6ppm.
Embodiment 2:(2S, 3R) -3'- ethyl -3- nitromethyla -1'- phenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] - 5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, adjacent hydroxyl nitroolefin (0.2mmol, 0.033g), 5- ethyl -2- phenyl-is added Pyrazolone (0.2mmol, 0.0376g), chirality side acid catalyst VI (0.02mmol, 0.0093g), solvent toluene (2mL), 25 DEG C reaction 48h after, obtain the mixture of the 2-A containing midbody compound；
(B) mixture of the 2-A containing midbody compound is removed into solvent, add iodobenzene acetate (0.8mmol, 0.2576g), 70% hydrogen peroxide tertiary butanol aqueous solution (0.2mmol, 0.0257g), solvent toluene (2mL), 25 DEG C of reaction 48h Afterwards, it is extracted with ethyl acetate (3 × 10mL), organic phase depressurizes precipitation, is to wash with ethyl acetate: petroleum ether=1:10 mixed solvent De- agent；200-300 mesh column chromatography silica gel is filler, and target product that column chromatography for separation purifies (0.0604g, 86% Yield, 92%ee, > 99:1dr),1H NMR(500MHz,CDCl3):δ7.86-7.84(m,2H),7.45-7.41(m,2H), 7.33 (t, J=7.5Hz, 1H), 7.26-7.21 (m, 1H), 7.21 (d, J=7.5Hz, 1H), 7.05 (m, 1H), 6.99 (d, J= 8.1Hz, 1H), 5.33 (dd, J=15.7,10.1Hz, 1H), 4.74 (dd, J=15.7,4.2Hz, 1H), 4.46 (dd, J= 10.1,4.2Hz, 1H), 2.54-2.35 (m, 2H), 1.31 (t, J=7.3Hz, 3H)；13C NMR(125MHz,CDCl3):δ 167.9,161.8,158.3,137.3,130.8,128.9(×2),125.7,124.5,122.6,122.3,119.3(×2), 111.0,87.5,73.0,44.4,20.5,9.2ppm。
Embodiment 3:(2S, 3R) -3- nitromethyla -1'- phenyl -3'- propyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] - 5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, adjacent hydroxyl nitroolefin (0.2mmol, 0.033g), 5- propyl -2- phenyl-is added Pyrazolone (2mmol, 0.404g), chirality side acid catalyst VII (0.01mmol, 0.0060g), solvent acetonitrile (4mL), 40 DEG C After reacting 1h, the mixture of the 3-A containing midbody compound is obtained；
(B) mixture of the 3-A containing midbody compound is removed into solvent, add tetrabutylammonium iodide (0.5mmol, 0.1845g), 85% metachloroperbenzoic acid is molten (2mmol, 0.407g), solvent acetonitrile (4mL), after 40 DEG C of reaction 2h, uses acetic acid Ethyl ester (3 × 10mL) extraction, organic phase depressurize precipitation, are eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent；200- 300 mesh column chromatography silica gels are filler, target product that column chromatography for separation purifies (0.0593g, 81%yield, 92%ee, > 99:1dr),1H NMR(500MHz,CDCl3): δ 7.85-7.83 (m, 2H), 7.44-7.41 (m, 2H), 7.33 (t, J=7.9Hz, 1H), 7.25-7.22 (m, 1H), 7.20 (d, J=7.5Hz, 1H), 7.07-7.04 (m, 1H), 6.99 (d, J=8.1Hz, 1H), 5.34 (dd, J=15.7,10.1Hz, 1H), 4.73 (dd, J=15.7,4.2Hz, 1H), 4.46 (dd, J=10.1,4.2Hz, 1H), 2.56-2.23 (m, 2H), 1.79 (h, J=7.4Hz, 2H), 1.03 (t, J=7.4Hz, 3H)；13C NMR(125MHz, CDCl3):δ167.9,160.7,158.4,137.2,130.8,128.9(×2),125.7,124.5,122.6,122.5, 119.3(×2),111.0,87.6,73.0,44.4,28.9,18.5,13.8ppm。
Embodiment 4:(2S, 3R) -3'- isopropyl -3- nitromethyla -1'- phenyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, adjacent hydroxyl nitroolefin (0.2mmol, 0.033g), 5- isopropyl -2- benzene is added Base-pyrazolone (0.4mmol, 0.0404g), chirality side acid catalyst VIII (0.01mmol, 0.0055g), solvent 1,2- bis- Chloroethanes (3mL) after -20 DEG C of reaction 48h, obtains the mixture of the 4-A containing midbody compound；
(B) mixture of the 4-A containing midbody compound is removed into solvent, adds potassium iodide (0.3mmol, 0.0498g), 5% aqueous sodium hypochlorite solution (1mmol, 1.5g), solvent 1,2- dichloroethanes (3mL) after -20 DEG C of reaction 48h, use ethyl acetate (3 × 10mL) extraction, organic phase depressurize precipitation, are eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent；200-300 Mesh column chromatography silica gel is filler, target product that column chromatography for separation purifies (0.0527g, 72%yield, 90%ee, > 99: 1dr),1H NMR(500MHz,CDCl3): δ 7.86-7.84 (m, 2H), 7.44-7.41 (m, 2H), 7.33 (t, J=7.6Hz, 1H), 7.25-7.22 (m, 1H), 7.20 (d, J=7.6Hz, 1H), 7.07-7.04 (m, 1H), 6.99 (d, J=8.2Hz, 1H), 5.34 (dd, J=15.6,10.1Hz, 1H), 4.75 (dd, J=15.6,4.2Hz, 1H), 4.54 (dd, J=10.1,4.2Hz, 1H), 2.73 (m, 1H), 1.37 (d, J=6.8Hz, 3H), 1.24 (d, J=6.9Hz, 3H) ppm；13C NMR(125MHz, CDCl3):δ167.9,160.7,158.4,137.2,130.8,128.9(×2),125.7,124.5,122.6,122.5, 119.3(×2),111.0,87.6,73.0,44.4,28.9,18.5,13.8ppm。
Embodiment 5:(2R, 3S) -3'- cyclopropyl -3- nitromethyla -1'- phenyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, adjacent hydroxyl nitroolefin (0.2mmol, 0.033g), 5- cyclopropyl -2- benzene is added Base-pyrazolone (0.4mmol, 0.0800g), chirality side acid catalyst IX (0.002mmol, 0.0009g), solvents tetrahydrofurane (1mL) after 60 DEG C of reaction 1h, obtains the mixture of the 5-A containing midbody compound；
(B) by the mixture of the 5-A containing midbody compound, elemental iodine (0.01mmol, 0.0025g) is added, oxygen is molten Agent tetrahydrofuran (1mL) after 60 DEG C of reaction 1h, is extracted with ethyl acetate (3 × 10mL), and organic phase depressurizes precipitation, with acetic acid second Ester: petroleum ether=1:10 mixed solvent is eluant, eluent；200-300 mesh column chromatography silica gel is filler, and column chromatography for separation purifies to obtain Target product (0.0392g, 54%yield, 88%ee, > 99:1dr),1H NMR(500MHz,CDCl3): δ 7.80 (d, J= 7.7Hz, 2H), 7.41 (t, J=8.0Hz, 2H), 7.33 (t, J=7.8Hz, 1H), 7.22 (t, J=7.1Hz, 2H), 7.06 (t, J=7.5Hz, 1H), 7.02 (d, J=8.1Hz, 1H), 5.35 (dd, J=15.6,10.2Hz, 1H), 4.76 (dd, J=15.6, 4.1Hz, 1H), 4.68 (dd, J=10.2,4.1Hz, 1H), 1.54-1.48 (m, 1H), 1.32-1.26 (m, 1H), 1.15-1.08 (m,1H),1.06-0.98(m,1H),0.97-0.90(m,1H)；13C NMR(125MHz,CDCl3):δ167.8,162.9, 158.6,137.3,130.7,128.9(×2),125.7,124.4,122.7,122.5,119.2(×2),111.0,87.6, 73.0,44.7,9.9,7.8,7.0ppm。
Embodiment 6:(2R, 3S) -3- nitromethyla -1', 3'- diphenyl -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5' (1'H) -one；
(A) the clean small test tube of 10mL is taken, adjacent hydroxyl nitroolefin (0.2mmol, 0.033g), 2,5- diphenyl-pyrrole is added Oxazoline ketone (0.2mmol, 0.0472g), chirality side acid catalyst X (0.04mmol, 0.024g), solvent ethyl acetate (3mL), 0 DEG C reaction 20h after, obtain the mixture of the 6-A containing midbody compound；
(B) mixture of the 6-A containing midbody compound is removed into solvent, added hydrogen iodide (2mmol, 0.256g), it is sub- Sodium chlorate (2mmol, 0.18g), solvent ethyl acetate (3mL) after 0 DEG C of reaction 20h, are extracted with ethyl acetate (3 × 10mL), are had It is molten that machine subtracts each other pressure-off, is eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent；200-300 mesh column chromatography silica gel is to fill out Material, the target product (0.0599g, 75%yield, 97%ee, 62:1dr) that column chromatography for separation purifies,1H NMR (500MHz,CDCl3):δ7.97-7.95(m,2H),7.77-7.75(m,2H),7.49-7.46(m,3H),7.42-7.39(m, 3H), 7.30-7.27 (m, 1H), 7.19 (d, J=7.6Hz, 1H), 7.12-7.09 (m, 2H), 5.36 (dd, J=15.6, 10.6Hz, 1H), 4.85 (dd, J=15.6,4.0Hz, 1H), 4.70 (dd, J=10.6,4.1Hz, 1H) ppm；13C NMR (125MHz,CDCl3):δ168.1,158.3,156.3,137.1,131.2,130.8,129.1(×2),129.0(×2), 128.6,126.6(×2),126.0,124.4,122.6,122.5,119.5(×2),111.2,88.0,73.1,45.8ppm。
Embodiment 7:(2R, 3S) -3'- methyl-3-nitro methyl-1 '-p-methylphenyl -3H- spiral shell [benzofuran -2,4'- Pyrazoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, adjacent hydroxyl nitroolefin (0.2mmol, 0.033g) is added, 5- methyl -2- is to first Base phenyl (0.2mmol, 0.0376g), chirality side acid catalyst XI (0.006mmol, 0.0038g), solvent toluene (1mL), 25 DEG C reaction 20h after, obtain the mixture (0.0706g) of the 7-A containing midbody compound；
(B) mixture of midbody compound 7-A is removed into solvent, added hydrogen iodide (2mmol, 0.256g), oxygen, Solvent toluene (1mL) after 25 DEG C of reaction 20h, is extracted with ethyl acetate (3 × 10mL), and organic phase depressurizes precipitation, with acetic acid second Ester: petroleum ether=1:10 mixed solvent is eluant, eluent；200-300 mesh column chromatography silica gel is filler, and column chromatography for separation purifies to obtain Target product (0.0388g, 55%yield, 95%ee, > 99:1dr),1H NMR(500MHz,CDCl3):δ7.69-7.67 (m, 2H), 7.35-7.31 (m, 1H), 7.22 (t, J=8.7Hz, 3H), 7.07-7.04 (m, 1H), 7.00 (d, J=8.1Hz, 1H), 5.33 (dd, J=15.7,10.1Hz, 1H), 4.73 (dd, J=15.7,4.2Hz, 1H), 4.43 (dd, J=10.1, 4.2Hz,1H),2.37(s,3H),2.13(s,3H)；13C NMR(125MHz,CDCl3):δ167.6,158.3,157.8, 135.6,134.7,130.8,129.5(×2),124.5,122.6,122.5,119.4(×2),111.0,87.3,72.9, 44.2,21.0,12.7ppm。
Embodiment 8:(2R, 3S) -1'- Chloro-O-Phenyl -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, adjacent hydroxyl nitroolefin (0.2mmol, 0.033g), 5- methyl -2- neighbour's chlorine is added Phenyl (0.6mmol, 0.1248g), chirality side acid catalyst XII (0.02mmol, 0.0102g), solvent chloroform (2mL), 10 DEG C After reacting 40h, the mixture of the 8-A containing midbody compound is obtained；
(B) mixture of the 8-A containing midbody compound is removed into solvent, adds elemental iodine (0.1mmol, 0.0106g), 98% peroxidized t-butyl perbenzoate (0.3mmol, 0.0582g), solvent chloroform (1mL), after 10 DEG C of reaction 10h, with acetic acid second Ester (3 × 10mL) extraction, organic phase depressurize precipitation, are eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent；200- 300 mesh column chromatography silica gels are filler, target product that column chromatography for separation purifies (0.0319g, 43%yield, 90%ee, > 99:1dr),1H NMR(500MHz,CDCl3):δ7.55-7.50(m,1H),7.46-7.42(m,1H),7.40-7.36(m,2H), 7.35-7.32 (m, 1H), 7.21 (d, J=7.6Hz, 1H), 7.07-7.04 (m, 1H), 7.02 (d, J=8.2Hz, 1H), 5.34 (dd, J=15.8,9.9Hz, 1H), 4.77 (dd, J=15.8,4.5Hz, 1H), 4.51 (dd, J=9.9,4.4Hz, 1H), 2.14 (s,3H)；13C NMR(125MHz,CDCl3):δ168.4,158.3,158.0,133.7,131.8,130.8,130.5,130.2, 128.6,127.7,124.5,122.6,122.5,111.1,86.2,73.0,44.1,12.7ppm。
Embodiment 9:(2R, 3S) -1'- rubigan -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, adjacent hydroxyl nitroolefin (0.2mmol, 0.033g) is added, 5- methyl -2- is to chlorine Phenyl (0.3mmol, 0.624g), chirality side acid catalyst XIII (0.01mmol, 0.0064g), solvent ethyl acetate (3mL), After 25 DEG C of reaction 40h, the mixture of the 9-A containing midbody compound is obtained；
(B) mixture of the 9-A containing midbody compound is removed into solvent, adds elemental iodine (0.1mmol, 0.0106g), 98% peroxidized t-butyl perbenzoate (0.3mmol, 0.0582g), solvent ethyl acetate (1mL) after 25 DEG C of reaction 8h, use acetic acid Ethyl ester (3 × 10mL) extraction, organic phase depressurize precipitation, are eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent；200- 300 mesh column chromatography silica gels are filler, target product that column chromatography for separation purifies (0.0482g, 65%yield, 88%ee, > 99:1dr),1H NMR(500MHz,CDCl3): δ 7.81-7.78 (m, 2H), 7.40-7.37 (m, 2H), 7.34 (t, J=7.8Hz, 1H), 7.21 (d, J=6.5Hz, 1H), 7.08-7.05 (m, 1H), 7.00 (d, J=8.1Hz, 1H), 5.33 (dd, J=15.8, 10.4Hz, 1H), 4.73 (dd, J=15.8,4.0Hz, 1H), 4.43 (dd, J=10.4,4.0Hz, 1H), 2.14 (s, 3H)；13C NMR(125MHz,CDCl3):δ167.7,158.3,158.2,135.7,130.9,130.8,129.0(×2),124.5, 122.7,122.2,120.3(×2),111.1,87.2,72.8,44.3,12.7ppm。
Embodiment 10:(2S, 3R) -1'- m-bromophenyl -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- Pyrazoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, adjacent hydroxyl nitroolefin (0.2mmol, 0.033g), bromine between 5- methyl -2- is added Phenyl-pyrazole quinoline ketone (0.2mmol, 0.0504g), chirality side acid catalyst V (0.004mmol, 0.0024g), solvent dichloromethane Alkane (2mL) after 25 DEG C of reaction 8h, obtains the mixture of the 10-A containing midbody compound；
(B) mixture of the 10-A containing midbody compound is removed into solvent, is added cuprous iodide (0.076g, 0.4mmol), 30% hydrogen peroxide (0.2mmol, 0.0227g), methylene chloride (2mL), after 25 DEG C of reaction 8h, with ethyl acetate (3 × It 10mL) extracts, organic phase depressurizes precipitation, is eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent；200-300 mesh column Chromatographic silica gel is filler, target product that column chromatography for separation purifies (0.0606g, 73%yield, 96%ee, > 99: 1dr),1H NMR(500MHz,CDCl3): δ 8.04 (t, J=2.0Hz, 1H), 7.85-7.83 (m, 1H), 7.39-7.31 (m, 2H), 7.28 (t, J=8.1Hz, 1H), 7.21 (d, J=7.5Hz, 1H), 7.06 (t, J=7.1Hz, 1H), 7.00 (d, J= 8.1Hz, 1H), 5.32 (dd, J=15.8,10.4Hz, 1H), 4.73 (dd, J=15.8,4.0Hz, 1H), 4.43 (dd, J= 10.4,3.9Hz,1H),2.14(s,3H)；13C NMR(125MHz,CDCl3):δ167.8,158.3,158.2,138.3, 130.9,130.3,128.6,124.5,122.7,122.6,122.2,121.8,117.3,111.0,87.2,72.7,44.3, 12.7ppm.
Embodiment 11:(2S, 3R) -1'- to cyano-phenyl -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2, 4'- pyrazoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, adjacent hydroxyl nitroolefin (0.2mmol, 0.033g) is added, 5- methyl -2- is to cyanogen Base phenyl-pyrazole quinoline ketone (0.2mmol, 0.0398g), chirality side acid catalyst VI (0.02mmol, 0.0093g), solvent toluene (2mL) after 25 DEG C of reaction 48h, obtains the mixture of the 11-A containing midbody compound；
(B) mixture of the 11-A containing midbody compound is removed into solvent, add iodobenzene acetate (0.4mmol, 0.1283g), the 70% hydrogen peroxide tert-butyl alcohol (0.4mmol, 0.0514g), solvent toluene (2mL) after 25 DEG C of reaction 48h, use second Acetoacetic ester (3 × 10mL) extraction, organic phase depressurize precipitation, are eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent； 200-300 mesh column chromatography silica gel is filler, target product (0.0514g, 71%yield, 96% that column chromatography for separation purifies Ee, > 99:1dr),1H NMR(500MHz,CDCl3): δ 8.04-8.02 (m, 2H), 7.72-7.69 (m, 2H), 7.35 (t, J= 7.8Hz, 1H), 7.23 (d, J=7.6Hz, 1H), 7.10-7.07 (m, 1H), 7.01 (d, J=8.2Hz, 1H), 5.33 (dd, J= 15.9,10.7Hz, 1H), 4.74 (dd, J=15.9,3.7Hz, 1H), 4.44 (dd, J=10.7,3.7Hz, 1H), 2.16 (s, 3H)；13C NMR(125MHz,CDCl3):δ167.9,161.8,158.3,137.3,130.8,128.9(×2),125.7, 124.5,122.6,122.3,119.3(×2),111.0,87.5,73.0,44.4,20.5,9.2ppm。
Embodiment 12:(2S, 3R) -1', 3'- dimethyl -3- nitromethyla -3H- spiral shell [benzofuran -2,4'- pyrazoles] -5' (1'H) -one；
(A) the clean small test tube of 10mL is taken, adjacent hydroxyl nitroolefin (0.2mmol, 0.033g), 2,5- dimethyl-pyrrole is added Oxazoline ketone (2mmol, 0.404g), chirality side acid catalyst VII (0.01mmol, 0.0060g), solvent acetonitrile (4mL), 20 DEG C anti- After answering 15h, the mixture of the 12-A containing midbody compound is obtained；
(B) mixture of the 12-A containing midbody compound is removed into solvent, add tetrabutylammonium iodide (0.5mmol, 0.1845g), 85% metachloroperbenzoic acid (2mmol, 0.407g), solvent acetonitrile (4mL), after 60 DEG C of reaction 2h, with acetic acid second Ester (3 × 10mL) extraction, organic phase depressurize precipitation, are eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent；200- 300 mesh column chromatography silica gels are filler, target product that column chromatography for separation purifies (0.0263g, 58%yield, 86%ee, > 99:1dr),1H NMR(500MHz,CDCl3): δ 7.30 (t, J=7.8Hz, 1H), 7.18 (d, J=7.5Hz, 1H), 7.02 (t, J =7.5Hz, 1H), 6.96 (d, J=8.1Hz, 1H), 5.27 (dd, J=15.7,10.1Hz, 1H), 4.68 (dd, J=15.7, 4.2Hz, 1H), 4.35 (dd, J=10.1,4.2Hz, 1H), 3.28 (s, 3H), 2.02 (s, 3H)；13C NMR(125MHz, CDCl3):δ169.4,158.4,157.2,130.7,124.5,122.5,122.4,111.0,86.2,73.0,43.8,31.3, 12.5ppm。
Embodiment 13:(2S, 3R) -1'- isopropyl -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, adjacent hydroxyl nitroolefin (0.2mmol, 0.033g), 2- isopropyl -5- first is added Base-pyrazolone (0.4mmol, 0.0280g), chirality side acid catalyst VIII (0.01mmol, 0.0055g), solvent 1,2- bis- Chloroethanes (3mL) after 15 DEG C of reaction 48h, obtains the mixture of the 13-A containing midbody compound；
(B) mixture of the 13-A containing midbody compound is removed into solvent, add potassium iodide (0.3mmol, 0.0498g), 5% aqueous sodium hypochlorite solution (1mmol, 1.5g), solvent 1,2- dichloroethanes (3mL) after 15 DEG C of reaction 48h, are used Ethyl acetate (3 × 10mL) extraction, organic phase depressurize precipitation, are eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent； 200-300 mesh column chromatography silica gel is filler, target product (0.0321g, 53%yield, 90% that column chromatography for separation purifies Ee, > 99:1dr),1H NMR(500MHz,CDCl3): δ 7.33-7.28 (m, 1H), 7.18 (d, J=7.5Hz, 1H), 7.04- 7.01 (m, 1H), 6.96 (d, J=8.1Hz, 1H), 5.34 (dd, J=15.8,10.3Hz, 1H), 4.66 (dd, J=15.8, 3.9Hz, 1H), 4.41-4.29 (m, 2H), 2.03 (s, 3H), 1.32 (dd, J=13.2,6.7Hz, 6H)；13C NMR(125MHz, CDCl3):δ168.2,158.5,156.9,130.6,124.4,122.6,122.4,111.0,87.0,72.9,45.6,43.7, 20.3,20.1,12.6ppm。
Embodiment 14:(2R, 3S) -1'- cyclohexyl -3'- methyl-3-nitro methyl -3H- spiral shell [benzofuran -2,4'- pyrrole Azoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, adjacent hydroxyl nitroolefin (0.2mmol, 0.033g), 2- cyclohexyl -5- first is added Base-pyrazolone (0.4mmol, 0.0720g), chirality side acid catalyst IX (0.002mmol, 0.0009g), solvents tetrahydrofurane (1mL) after 25 DEG C of reaction 8h, obtains the mixture of the 14-A containing midbody compound；
(B) mixture of the 14-A containing midbody compound is removed into solvent, add elemental iodine (0.01mmol, 0.0025g), 30% hydrogen peroxide solution (0.5mmol, 0.0567g), solvents tetrahydrofurane (1mL) after 25 DEG C of reaction 1h, use second Acetoacetic ester (3 × 10mL) extraction, organic phase depressurize precipitation, are eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent； 200-300 mesh column chromatography silica gel is filler, target product (0.0391g, 57%yield, 92% that column chromatography for separation purifies Ee, > 99:1dr),1H NMR(500MHz,CDCl3): δ 7.32-7.28 (m, 1H), 7.18 (d, J=7.6Hz, 1H), 7.04- 7.01 (m, 1H), 6.96 (d, J=8.5Hz, 1H), 5.33 (dd, J=15.8,10.4Hz, 1H), 4.66 (dd, J=15.8, 3.9Hz, 1H), 4.35 (dd, J=10.4,3.9Hz, 1H), 3.94 (m, 1H), 2.02 (s, 3H), 1.89-1.77 (m, 4H), 1.74 (dd, J=11.9,3.9Hz, 1H), 1.71-1.65 (m, 2H), 1.41-1.29 (m, 2H), 1.24-1.15 (m, 1H)；13C NMR(125MHz,CDCl3):δ168.3,158.5,156.7,130.6,124.4,122.6,122.4,111.0,87.0,72.8, 53.0,43.7,30.5,30.2,25.4,25.3,25.2,12.6ppm。
Embodiment 15:(2R, 3S) -5- methoxyl group -3'- methyl-3-nitro methyl-1 '-phenyl -3H- spiral shell [benzofuran - 2,4'- pyrazoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, 5- methoxyl group-neighbour's hydroxyl nitroolefin (0.2mmol, 0.039g), 5- first is added Base -2- phenyl-pyrazole quinoline ketone (0.2mmol, 0.0348g), chirality side acid catalyst X (0.04mmol, 0.024g), solvent acetic acid Ethyl ester (3mL) after 20 DEG C of reaction 20h, obtains the mixture of 15-A containing midbody compound；
(B) mixture of the 15-A containing midbody compound is removed into solvent, added hydrogen iodide (2mmol, 0.256g), it is sub- Sodium chlorate (1mmol, 0.09g), solvent ethyl acetate (3mL) after 20 DEG C of reaction 20h, are extracted with ethyl acetate (3 × 10mL), Organic phase depressurizes precipitation, is eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent；200-300 mesh column chromatography silica gel is Filler, the target product (0.0683g, 93%yield, 99%ee, > 99:1dr) that column chromatography for separation purifies,1H NMR (500MHz,CDCl3):δ7.97-7.95(m,2H),7.77-7.75(m,2H),7.49-7.46(m,3H),7.42-7.39(m, 3H), 7.30-7.27 (m, 1H), 7.19 (d, J=7.6Hz, 1H), 7.12-7.09 (m, 2H), 5.36 (dd, J=15.6, 10.6Hz, 1H), 4.85 (dd, J=15.6,4.0Hz, 1H), 4.70 (dd, J=10.6,4.1Hz, 1H)；13C NMR(125MHz, CDCl3):δ167.8,158.0,155.6,152.1,137.1,128.9(×2),125.8,123.3,119.3(×2), 115.8,111.2,110.4,87.6,72.8,56.1,44.6,12.7ppm。
Embodiment 16:(2R, 3S) -7- methoxyl group -3'- methyl-3-nitro methyl-1 '-phenyl -3H- spiral shell [benzofuran - 2,4'- pyrazoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, 3- methoxyl group-neighbour's hydroxyl nitroolefin (0.2mmol, 0.039g), 5- first is added Base -2- phenyl-pyrazole quinoline ketone (0.4mmol, 0.0696g), chirality side acid catalyst XI (0.006mmol, 0.0038g), solvent Toluene (1mL) after 25 DEG C of reaction 20h, obtains the mixture of the 16-A containing midbody compound；
(B) mixture of the 16-A containing midbody compound is removed into solvent, adds hydrogen iodide (2mmol, 0.256g), oxygen Gas, solvent toluene (1mL) after 25 DEG C of reaction 20h, are extracted with ethyl acetate (3 × 10mL), and organic phase depressurizes precipitation, uses acetic acid Ethyl ester: petroleum ether=1:10 mixed solvent is eluant, eluent；200-300 mesh column chromatography silica gel is filler, and column chromatography for separation purifies The target product (0.0361g, 49%yield, 98%ee, > 99:1dr) arrived,1H NMR(500MHz,CDCl3):δ7.83-7.80 (m, 2H), 7.44-7.40 (m, 2H), 7.25-7.22 (m, 1H), 6.91 (d, J=8.8Hz, 1H), 6.86 (dd, J=8.8, 2.6Hz, 1H), 6.76 (d, J=2.5Hz, 1H), 5.33 (dd, J=15.7,10.0Hz, 1H), 4.72 (dd, J=15.7, 4.3Hz, 1H), 4.39 (dd, J=10.0,4.3Hz, 1H), 3.80 (s, 3H), 2.13 (s, 3H)；13C NMR(125MHz, CDCl3):δ167.8,158.0,155.6,152.1,137.1,128.9(×2),125.8,123.3,119.3(×2), 115.8,111.2,110.4,87.6,72.8,56.1,44.6,12.7ppm。
Embodiment 17:(2R, 3S) -7- ethyoxyl -3'- methyl-3-nitro methyl-1 '-phenyl -3H- spiral shell [benzofuran - 2,4'- pyrazoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, 3- ethyoxyl-neighbour's hydroxyl nitroolefin (0.2mmol, 0.0418g), 5- first is added Base -2- phenyl-pyrazole quinoline ketone (0.2mmol, 0.0348g), chirality side acid catalyst XII (0.02mmol, 0.0102g), solvent Chloroform (2mL) after 25 DEG C of reaction 15h, obtains the mixture of the 17-A containing midbody compound；
(B) midbody compound 17-A mixture removing solvent will be contained, add elemental iodine (0.1mmol, 0.0106g), 98% peroxidized t-butyl perbenzoate (0.3mmol, 0.0582g), solvent chloroform (1mL) after 25 DEG C of reaction 4h, use ethyl acetate (3 × 10mL) extraction, organic phase depressurize precipitation, are eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent；200-300 Mesh column chromatography silica gel is filler, target product that column chromatography for separation purifies (0.0655g, 86%yield, 96%ee, > 99: 1dr),1H NMR(500MHz,CDCl3):δ7.80-7.78(m,2H),7.43-7.40(m,2H),7.25-7.21(m,1H), 6.98 (t, J=7.8Hz, 1H), 6.91 (d, J=8.1Hz, 1H), 6.78 (d, J=7.5Hz, 1H), 5.35 (dd, J=15.8, 10.2Hz, 1H), 4.73 (dd, J=15.8,4.1Hz, 1H), 4.46 (dd, J=10.2,4.1Hz, 1H), 4.31-4.06 (m, 2H), 2.16 (s, 3H), 1.45 (t, J=7.0Hz, 3H)；13C NMR(125MHz,CDCl3):δ167.5,157.7,146.8, 144.5,137.1,128.9(×2),125.8,123.7,123.5,119.4(×2),115.9,114.8,87.5,72.8, 64.8,44.7,14.8,12.7ppm。
Embodiment 18:(2R, 3S) -3', 5- dimethyl -3- nitromethyla -1'- phenyl -3H- spiral shell [benzofuran -2,4'- Pyrazoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, 5- methyl-neighbour's hydroxyl nitroolefin (0.2mmol, 0.0358g), 5- first is added Base -2- phenyl-pyrazole quinoline ketone (0.2mmol, 0.0348g), chirality side acid catalyst XIII (0.01mmol, 0.0064g), solvent Ethyl acetate (3mL) after 25 DEG C of reaction 40h, obtains the mixture of the 18-A containing midbody compound；
(B) midbody compound 18-A mixture removing solvent will be contained, add elemental iodine (0.1mmol, 0.0106g), Potassium peroxydisulfate (0.4mmol, 0.108g), solvent ethyl acetate (3mL) after 25 DEG C of reaction 4h, are extracted with ethyl acetate (3 × 10mL) It takes, organic phase depressurizes precipitation, is eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent；200-300 mesh column chromatography silica gel For filler, the target product (0.0625g, 89%yield, 90%ee, > 99:1dr) that column chromatography for separation purifies,1H NMR (500MHz,CDCl3):δ7.83-7.80(m,2H),7.44-7.40(m,2H),7.25-7.22(m,1H),7.13-7.11(m, 1H), 7.00 (s, 1H), 6.88 (d, J=8.2Hz, 1H), 5.32 (dd, J=15.7,10.1Hz, 1H), 4.72 (dd, J= 15.7,4.2Hz, 1H), 4.39 (dd, J=10.1,4.2Hz, 1H), 2.35 (s, 3H), 2.13 (s, 3H)；13C NMR(125MHz, CDCl3):δ167.9,158.0,156.3,137.2,132.3,131.3,128.9(×2),125.8,124.9,122.4, 119.3(×2),110.6,87.4,73.0,44.3,20.8,12.7ppm。
Embodiment 19:(2S, 3R) the fluoro- 3'- methyl-3-nitro methyl-1 of -5- '-phenyl -3H- spiral shell [benzofuran -2,4'- Pyrazoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, the fluoro- adjacent hydroxyl nitroolefin (0.2mmol, 0.0366g) of 5-, 5- methyl-is added 2- phenyl-pyrazole quinoline ketone (0.5mmol, 0.0870g), chirality side acid catalyst V (0.002mmol, 0.0012g), solvent dichloro Methane (1mL) after 25 DEG C of reaction 6h, obtains the mixture of the 19-A containing midbody compound；
(B) it takes the mixture of the 19-A containing midbody compound to remove solvent, is added cuprous iodide (0.4mmol, 0.076g), 70% hydrogen peroxide tertiary butanol aqueous solution (0.2mmol, 0.0257g), methylene chloride (1mL) after 25 DEG C of reaction 8h, use second Acetoacetic ester (3 × 10mL) extraction, organic phase depressurize precipitation, are eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent； 200-300 mesh column chromatography silica gel is filler, target product (0.0596g, 84%yield, 90% that column chromatography for separation purifies Ee, 47:1dr),1H NMR(500MHz,CDCl3):δ7.82-7.79(m,2H),7.45-7.41(m,2H),7.26-7.23(m, 1H), 7.06-7.02 (m, 1H), 6.95-6.92 (m, 2H), 5.33 (dd, J=15.7,10.0Hz, 1H), 4.71 (dd, J= 15.7,4.3Hz, 1H), 4.43 (dd, J=10.1,4.4Hz, 1H), 2.15 (s, 3H)；13C NMR(125MHz,CDCl3):δ 167.4,159.3,157.5(d,1JC-F=20.1Hz), 154.2 (d,4JC-F=1.4Hz), 137.0,129.0 (× 2), 125.9, 123.8(d,2JC-F=8.6Hz), 119.2 (× 2), 117.4 (d,3JC-F=24.2Hz), 111.8 (d,3JC-F=25.6Hz), 111.5(d,2JC-F=8.5Hz), 87.9,72.6,44.2,12.7ppm.
Embodiment 20:(2S, 3R) the chloro- 3'- methyl-3-nitro methyl-1 of -5- '-phenyl -3H- spiral shell [benzofuran -2,4'- Pyrazoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, the chloro- adjacent hydroxyl nitroolefin (0.2mmol, 0.033g) of 5-, 5- methyl -2- is added Phenyl-pyrazole quinoline ketone (0.2mmol, 0.0348g), chirality side acid catalyst VI (0.006mmol, 0.0028g), solvent chloroform (2mL) after 25 DEG C of reaction 6h, obtains the mixture of the 20-A containing midbody compound；
(B) mixture of the 20-A containing midbody compound is removed into solvent, add elemental iodine (0.04mmol, 0.0102g), 30% hydrogen peroxide (0.4mmol, 0.0453g), solvent toluene (2mL), after 25 DEG C of reaction 6h, with ethyl acetate (3 × 10mL) extraction, it is eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent that organic phase, which depressurizes precipitation,；200-300 mesh Column chromatography silica gel is filler, target product that column chromatography for separation purifies (0.0558g, 75%yield, 90%ee, > 99: 1dr),1H NMR(500MHz,CDCl3):δ7.82-7.79(m,2H),7.45-7.41(m,2H),7.32-7.29(m,1H), 7.26-7.23 (m, 1H), 7.20 (dd, J=2.2,1.0Hz, 1H), 6.94 (d, J=8.6Hz, 1H), 5.34 (dd, J=15.8, 10.1Hz, 1H), 4.72 (dd, J=15.8,4.3Hz, 1H), 4.43 (dd, J=10.1,4.2Hz, 1H), 2.16 (s, 3H)；13C NMR(125MHz,CDCl3):δ167.3,157.4,157.0,137.0,130.9,129.0(×2),127.7,126.0, 124.7,124.4,119.3(×2),112.0,87.8,72.6,44.0,12.7ppm。
Embodiment 21:(2S, 3R) the bromo- 3'- methyl-3-nitro methyl-1 of -5- '-phenyl -3H- spiral shell [benzofuran -2,4'- Pyrazoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, the bromo- adjacent hydroxyl nitroolefin (0.2mmol, 0.0486g) of 5-, 5- methyl-is added 2- phenyl-pyrazole quinoline ketone (2mmol, 0.348g), chirality side acid catalyst VII (0.01mmol, 0.0060g), solvent acetonitrile (4mL) after 40 DEG C of reaction 1h, obtains the mixture of the 21-A containing midbody compound；
(B) mixture of the 21-A containing midbody compound is removed into solvent, add tetrabutylammonium iodide (0.5mmol, 0.1845g), 85% metachloroperbenzoic acid (2mmol, 0.407g), solvent acetonitrile (4mL), after 40 DEG C of reaction 2h, with acetic acid second Ester (3 × 10mL) extraction, organic phase depressurize precipitation, are eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent；200- 300 mesh column chromatography silica gels are filler, target product that column chromatography for separation purifies (0.0489g, 59%yield, 88%ee, > 99:1dr),1H NMR(500MHz,CDCl3):δ7.83-7.78(m,2H),7.47-7.38(m,3H),7.34(s,1H),7.25 (t, J=7.4Hz, 1H), 6.89 (d, J=8.6Hz, 1H), 5.34 (dd, J=15.8,10.1Hz, 1H), 4.72 (dd, J= 15.8,4.2Hz, 1H), 4.44 (dd, J=10.1,4.1Hz, 1H), 2.15 (s, 3H)；13C NMR(125MHz,CDCl3):δ 167.2,157.5,157.3,137.0,133.8,129.0(×2),127.6,126.0,124.9,119.3(×2),114.6, 112.6,87.8,72.6,43.9,12.7ppm。
Embodiment 22:(2S, 3R) two chloro- 3'- methyl-3-nitro methyl-1 '-phenyl -3H- spiral shell [benzofuran-of -5,7- 2,4'- pyrazoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, the chloro- adjacent hydroxyl nitroolefin (0.2mmol, 0.0466g) of 3,5- bis-, 5- first is added Base -2- phenyl-pyrazole quinoline ketone (0.4mmol, 0.0696g), chirality side acid catalyst VIII (0.01mmol, 0.0055g), solvent 1,2- dichloroethanes (3mL) after 20 DEG C of reaction 12h, obtains the mixture of the 22-A containing midbody compound；
(B) mixture of the 22-A containing midbody compound is removed into solvent, add potassium iodide (0.3mmol, 0.0498g), 5% aqueous sodium hypochlorite solution (0.5mmol, 0.75g), solvent 1,2- dichloroethanes (3mL), after 20 DEG C of reaction 8h, It is extracted with ethyl acetate (3 × 10mL), organic phase depressurizes precipitation, is elution with ethyl acetate: petroleum ether=1:10 mixed solvent Agent；200-300 mesh column chromatography silica gel is filler, target product that column chromatography for separation purifies (0.0497g, 61%yield, 97%ee, > 99:1dr),1H NMR(500MHz,CDCl3):δ7.81-7.78(m,2H),7.45-7.41(m,2H),7.36(d,J =1.9Hz, 1H), 7.27-7.24 (m, 1H), 7.09 (d, J=1.0Hz, 1H), 5.35 (dd, J=15.8,10.1Hz, 1H), 4.73 (dd, J=15.8,4.3Hz, 1H), 4.50 (dd, J=10.1,4.2Hz, 1H), 2.18 (s, 3H)；13C NMR(125MHz, CDCl3):δ166.6,156.7,153.3,136.9,130.9,129.0(×2),128.1,126.1,125.5,123.1, 119.3(×2),117.3,88.0,72.3,44.4,12.7ppm。
Embodiment 23:(2S, 3R) the chloro- 3'- methyl-3-nitro methyl-1 of the bromo- 5- of -7- '-phenyl -3H- spiral shell [benzofuran - 2,4'- pyrazoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, the chloro- adjacent hydroxyl nitroolefin (0.2mmol, 0.0554g) of the bromo- 5- of 3-, 5- is added Methyl -2- phenyl-pyrazole quinoline ketone (0.4mmol, 0.0696g), chirality side acid catalyst IX (0.002mmol, 0.0009g) are molten Agent tetrahydrofuran (1mL) after 60 DEG C of reaction 1h, obtains the mixture of the 23-A containing midbody compound；
(B) mixture of the 23-A containing midbody compound is removed into solvent, add elemental iodine (0.01mmol, 0.0025g), 30% hydrogen peroxide solution (2mmol, 0.2267g), solvents tetrahydrofurane (1mL) after 60 DEG C of reaction 1h, use acetic acid Ethyl ester (3 × 10mL) extraction, organic phase depressurize precipitation, are eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent；200- 300 mesh column chromatography silica gels are filler, target product that column chromatography for separation purifies (0.0537g, 74%yield, 88%ee, > 99:1dr),1H NMR(500MHz,CDCl3): δ 7.80 (d, J=7.7Hz, 2H), 7.41 (t, J=8.0Hz, 2H), 7.33 (t, J =7.8Hz, 1H), 7.22 (t, J=7.1Hz, 2H), 7.06 (t, J=7.5Hz, 1H), 7.02 (d, J=8.1Hz, 1H), 5.35 (dd, J=15.6,10.2Hz, 1H), 4.76 (dd, J=15.6,4.1Hz, 1H), 4.68 (dd, J=10.2,4.1Hz, 1H), 1.54-1.48(m,1H),1.32-1.26(m,1H),1.15-1.08(m,1H),1.06-0.98(m,1H),0.97-0.90(m, 1H)；13C NMR(125MHz,CDCl3):δ167.8,162.9,158.6,137.3,130.7,128.9(×2),125.7, 124.4,122.7,122.5,119.2(×2),111.0,87.6,73.0,44.7,9.9,7.8,7.0ppm。
Embodiment 24:(2R, 3S) -7- methoxyl group -3'- methyl-3-nitro methyl-1 '-to cyano-phenyl -3H- spiral shell [benzo Furans -2,4'- pyrazoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, 3- methoxyl group-neighbour's hydroxyl nitroolefin (0.2mmol, 0.039g), 5- first is added - 2 pairs of cyano-phenyl-pyrazolones (0.4mmol, 0.0796g) of base, chirality side acid catalyst X (0.04mmol, 0.024g) are molten Agent ethyl acetate (3mL) after 40 DEG C of reaction 10h, obtains the mixture of the 24-A containing midbody compound；
(B) mixture of the 24-A containing midbody compound is removed into solvent, added hydrogen iodide (2mmol, 0.256g), it is sub- Sodium chlorate (2mmol, 0.18g), solvent ethyl acetate (3mL) after 40 DEG C of reaction 5h, are extracted with ethyl acetate (3 × 10mL), are had It is molten that machine subtracts each other pressure-off, is eluant, eluent with ethyl acetate: petroleum ether=1:10 mixed solvent；200-300 mesh column chromatography silica gel is to fill out Material, the target product (0.0580g, 74%yield, 90%ee, > 99:1dr) that column chromatography for separation purifies,1H NMR (500MHz,CDCl3): δ 8.02-7.99 (m, 2H), 7.71-7.68 (m, 2H), 7.04 (dd, J=8.2,7.6Hz, 1H), 6.94 (d, J=8.2Hz, 1H), 6.83-6.81 (m, 1H), 5.35 (dd, J=15.9,10.7Hz, 1H), 4.75 (dd, J=15.9, 3.7Hz, 1H), 4.47 (dd, J=10.8,3.7Hz, 1H), 3.92 (s, 3H), 2.19 (s, 3H)；13C NMR(125MHz, CDCl3):δ168.0,158.4,146.4,145.2,140.6,133.1(×2),123.9,123.1,118.7,118.6(× 2),116.0,113.6,108.5,87.5,72.4,56.2,44.8,12.7ppm。
Embodiment 25:(2S, 3R) -3'- methyl-3-nitro methyl-1 '-p-nitrophenyl -3H- spiral shell [benzofuran -2, 4'- pyrazoles] -5'(1'H) -one；
(A) the clean small test tube of 10mL is taken, 3- methoxyl group-neighbour's hydroxyl nitroolefin (0.2mmol, 0.039g), 5- first is added The pyrazolone (0.2mmol, 0.0438g) of base -2- p-nitrophenyl -, chirality side acid catalyst XI (0.006mmol, 0.0038g), after solvent toluene (1mL), 25 DEG C of reaction 20h, the mixture of the 25-A containing midbody compound is obtained；
(B) mixture of the 25-A containing midbody compound is removed into solvent, adds hydrogen iodide (2mmol, 0.256g), oxygen Gas, solvent toluene (1mL) after 25 DEG C of reaction 4h, are extracted with ethyl acetate (3 × 10mL), and organic phase depressurizes precipitation, with acetic acid second Ester: petroleum ether=1:10 mixed solvent is eluant, eluent；200-300 mesh column chromatography silica gel is filler, and column chromatography for separation purifies to obtain Target product (0.0536g, 65%yield, 91%ee, > 99:1dr),1H NMR(500MHz,CDCl3):δ8.30-8.27 (m, 2H), 8.08-8.05 (m, 2H), 7.05 (dd, J=8.2,7.6Hz, 1H), 6.94 (d, J=8.2,0.8Hz, 1H), 6.83- 6.81 (m, 1H), 5.36 (dd, J=15.9,10.8Hz, 1H), 4.77 (dd, J=16.0,3.6Hz, 1H), 4.49 (dd, J= 10.8,3.7Hz,1H),3.92(s,3H),2.21(s,3H)；13C NMR(125MHz,CDCl3):δ168.1,158.7,146.3, 145.2,144.4,142.2,124.9(×2),123.9,122.9,118.3(×2),116.0,113.6,87.5,72.4, 56.2,44.8,12.7ppm。

Claims (10)

1. a kind of sequential catalyst preparation method of the chiral pyrazol spiral shell furfuran compound as shown in formula (I), which is characterized in that institute The synthetic method stated carries out as follows:
(A) by pyrazoline ketone compounds, chirality side shown in neighbour's hydroxyl nitro compds hydrocarbon compound shown in formula (II) and formula (III) Acid catalyst, organic solvent A are uniformly mixed, and 1~48h is reacted at -20~60 DEG C, after reaction, are obtained containing formula (IV) institute The mixture of the compound shown；Pyrazoline shown in neighbour's hydroxyl nitro compds hydrocarbon compound shown in the formula (II) and formula (III) The ratio between amount of substance of ketone compounds, chirality side's acid catalyst is 1:1~10:0.01~0.2；
(B) by after step (A) the mixture removing solvent obtained containing compound shown in formula (IV), propiodal additive is then added And oxidant reacts 1~48h at -20~60 DEG C and obtains reaction mixture after after reaction in organic solvent B Processing obtains chiral pyrazol spiral shell furfuran compound shown in formula (I)；The propiodal oxidant, oxidant and formula (IV) institute Show that the ratio between amount of combinations of materials is 0.05~10:1~10:1,
In formula (I), formula (III) and formula (IV),
The R1For C1~C20Alkyl, phenyl, benzyl, 2- methoxyphenyl, 3- methoxyphenyl, 4- methoxyphenyl, 2- first Base phenyl, 3- aminomethyl phenyl, 4- aminomethyl phenyl, 2- nitrobenzophenone, 3- nitrobenzophenone, 4- nitrobenzophenone, 2- fluorophenyl, 3- fluorobenzene Base, 4- fluorophenyl, 2- chlorphenyl, 3- chlorphenyl, 4- chlorphenyl, 2- bromophenyl, 3- bromophenyl, 4- bromophenyl, furyl, thiophene Base or pyridyl group；
The R2For C1~C20Alkyl, phenyl, benzyl, 2- methoxyphenyl, 3- methoxyphenyl, 4- methoxyphenyl, 2- first Base phenyl, 3- aminomethyl phenyl, 4- aminomethyl phenyl, 2- nitrobenzophenone, 3- nitrobenzophenone, 4- nitrobenzophenone, 2- fluorophenyl, 3- fluorobenzene Base, 4- fluorophenyl, 2- chlorphenyl, 3- chlorphenyl, 4- chlorphenyl, 2- bromophenyl, 3- bromophenyl, 4- bromophenyl, 2- cyano-phenyl, 3- cyano-phenyl, 4- cyano-phenyl, 2- nitrobenzophenone, 3- nitrobenzophenone, 4- nitrobenzophenone, furyl, thienyl or pyridyl group；
In formula (II), formula (III) and formula (IV), n is the number of substituent group, and n takes 1 or 2；
When n is 1, the R3For H, 3- methoxyl group, 4- methoxyl group, 5- methoxyl group, 3- ethyoxyl, 5- methyl, 5- fluorine, 3- chlorine, 5- Chlorine, 3- bromine, 5- bromine or 5- nitro；
When n is 2, the R3For 3,5- dichloro or the bromo- 5- chlorine of 3-.
2. the sequential catalyst preparation method of chiral pyrazol spiral shell furfuran compound as described in claim 1, it is characterised in that: institute The R stated1For methyl, ethyl, n-propyl, isopropyl, cyclopropyl, phenyl；The R2For methyl, isopropyl, cyclohexyl, phenyl, 4- aminomethyl phenyl, 2- chlorphenyl, 4- chlorphenyl, 3- bromophenyl, 4- cyano-phenyl, 4- nitrobenzophenone；When n is 1, the R3For H, 3- methoxyl group, 5- methoxyl group, 3- ethyoxyl, 5- methyl, 5- fluorine, 3- chlorine, 5- chlorine, 3- bromine or 5- bromine；When n is 2, the R3 For 3,5- dichloro or the bromo- 5- chlorine of 3-.
3. the sequential catalyst preparation method of chiral pyrazol spiral shell furfuran compound as described in claim 1, it is characterised in that: step Suddenly in (A), chirality side's acid catalyst is selected from one of compound shown in formula (V)~(XIII):
4. the sequential catalyst preparation method of chiral pyrazol spiral shell furfuran compound as described in claim 1, it is characterised in that: step Suddenly in (B), the propiodal additive be potassium iodide, sodium iodide, cupric iodide, cuprous iodide, tetrabutylammonium iodide, elemental iodine, Hydrogen iodide or iodobenzene acetate.
5. the sequential catalyst preparation method of chiral pyrazol spiral shell furfuran compound as claimed in claim 4, it is characterised in that: step Suddenly in (B), the propiodal additive is elemental iodine.
6. the sequential catalyst preparation method of chiral pyrazol spiral shell furfuran compound as described in claim 1, it is characterised in that: step Suddenly in (B), the oxidant is tertbutanol peroxide, di-t-butyl peroxide, metachloroperbenzoic acid, sodium hypochlorite, Asia Sodium chlorate, hydrogen peroxide, oxygen, peroxidized t-butyl perbenzoate or potassium peroxydisulfate.
7. the sequential catalyst preparation method of string chiral pyrazol spiral shell furfuran compound as described in claim 1, which is characterized in that In step (A) or step (B), the organic solvent is selected from methylene chloride, chloroform, 1,2- dichloroethanes, 1,1,2- trichlorine Ethane, ether, isopropyl ether, tetrahydrofuran, 1,4- dioxane, ethyl acetate, toluene, dimethylbenzene, thionyl chloride, N, N- diformazan Base formamide, acetonitrile, methanol or ethyl alcohol.
8. the sequential catalyst preparation method of chiral pyrazol spiral shell furfuran compound as described in claim 1, it is characterised in that: step Suddenly in (A), the volumetric usage of the organic solvent A is with the meter of the substance of neighbour's hydroxyl nitro compds hydrocarbon compound shown in formula (II) For 5~20mL/mmol.
9. the sequential catalyst preparation method of chiral pyrazol spiral shell furfuran compound as described in claim 1, it is characterised in that: step Suddenly in (B), the volumetric usage of the organic solvent B is calculated as 5 with the amount of the substance of the formula (II) compound represented~ 20mL/mmol。
10. the sequential catalyst preparation method of chiral pyrazol spiral shell furfuran compound as described in claim 1, it is characterised in that: In step (B), the method for the reaction solution post-processing are as follows: after reaction, reaction solution is extracted with ethyl acetate, extract liquor distillation After removing solvent, residue carries out column chromatography for separation with 200~300 mesh silica gel, and eluant, eluent is ethyl acetate and petroleum ether volume Than the mixed liquor of 1:2~70, the eluent containing target compound is collected, solvent is evaporated off and dry to get chirality shown in formula (I) Pyrazoles spiral shell furfuran compound.
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