CN106905336A - A kind of method of asymmetric synthesis of chiral pyrazol spiral shell furfuran compound - Google Patents
A kind of method of asymmetric synthesis of chiral pyrazol spiral shell furfuran compound Download PDFInfo
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- DTDIUHLZHIPHJX-UHFFFAOYSA-N CCC(C(CC(C(CC(C)(C)C1)=O)C1=O)C1=O)=NN1c1ccccc1 Chemical compound CCC(C(CC(C(CC(C)(C)C1)=O)C1=O)C1=O)=NN1c1ccccc1 DTDIUHLZHIPHJX-UHFFFAOYSA-N 0.000 description 1
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- 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
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Abstract
The method of asymmetric synthesis of the chiral pyrazol spiral shell furfuran compound the invention provides one kind as shown in formula (I), described synthetic method is carried out as follows：By 1 shown in formula (II), 3 benzoylcyclohexandiones and pyrazoles ketene compounds shown in formula (III), chirality side's acid catalyst, organic solvent A mixing, 0.1~48h is reacted at 20~60 DEG C, obtain the compound shown in formula (IV), to addition propiodal additive, alkaline matter and organic solvent B in compound shown in formula (IV), 0.1~48h, the post-treated chiral pyrazol spiral shell furfuran compound obtained shown in formula (I) of reaction solution are reacted at 20~60 DEG C；Reaction condition of the present invention is gentle, 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
(1) technical field
The present invention relates to a kind of method of asymmetric synthesis of chiral pyrazol spiral shell furfuran compound.
(2) background technology
Chiral pyrazol volution compound is largely present in the natural products and clinical medicine with bioactivity, its tool
There is extensive bioactivity, for example, make with bring down a fever, protect nerve, anti-analgesic, antibacterium, antimycotic, anti-inflammatory, antitumor etc.
With.Chiral pyrazol volution compound common structure has pyrazoles spiro cyclopentane, pyrazoles volution hexane, pyrazoles volution hexanone, pyrazoles
Volution hexenone etc., such as：Compound A and B, phosphodiesterase PDE4 inhibitor, one kind contain pyrazoles spiro cyclopentane and pyrazoles spiral shell
The medicine of the skeleton of hexamethylene, it is widely used in the diseases such as treatment heart failure, asthma, while CD-840 is also
There is vasodilative effect by increasing cAMP contents in VSMC；Compound C, Anti-microbial, it is a kind of
The medicine of pyrazoles cyclohexanone skeleton, is effective anti-inflammatory and anti-microbial agents, is conducive to the slow healing of wound.
The molecular structural formula of phosphodiesterase PDE4 inhibitor and Anti-microbial is as follows：
Nearly more than ten years, organocatalysis, particularly square acid catalysis is developed rapidly in organic synthesis field.It is chiral
Square acid catalysis obtains great success in chiral tandem asymmetric reaction, is particularly provided in terms of complicated chiral molecules is built
Fabulous synthesizing mean.2008, professor Rawal reported and is catalyzed levulinic with chirality side's acid catalyst derived from quinine
The asymmetric Michael Reaction of ketone and nitro compds hydrocarbon compound, achieves up to 99% yield and the optics of 98%ee values
Activated product.2010, Du great Ming seminars reported the nitro being catalyzed with chirality side's acid catalyst of cinchona alkaloid-derived ligands
The asymmetric Michael Reaction of methane and chalcone, the yield and corresponding selection of product are up to 99% and 96% respectively.It is chiral
Square acid catalyst is improving reaction efficiency, it is to avoid wasting and improve the aspects such as Atom economy has some superiority, meets green
The requirement of chemistry, with wide development space.
Therefore, the present invention uses chirality side's acid catalyst, under mild conditions by asymmetric Michael Reaction, visits
The route of the easy synthesis of chiral pyrazoles spiral shell furfuran compound of one, rope, reaction equation is as follows.
(3) content of the invention
Present invention aim at a kind of method of asymmetric synthesis of chiral pyrazol spiral shell furfuran compound of offer.
To achieve the above object, the present invention is adopted the following technical scheme that：
A kind of method of asymmetric synthesis of chiral pyrazol spiral shell furfuran compound as shown in formula (I), it is characterised in that institute
The synthetic method stated includes (A) Michael reactions and two steps of (B) cyclization, and described synthetic method presses as follows
Step is carried out：
(A) by hydroresorcinol class compound shown in formula (II) and pyrazoles ketene compounds, chirality shown in formula (III)
Square acid catalyst, organic solvent A mixing, react 0.1~48h at -20~60 DEG C, after reaction terminates, reaction solution are evaporated off molten
Agent obtains the compound shown in formula (IV)；Hydroresorcinol class compound and pyrrole shown in formula (III) shown in described formula (II)
The ratio between azoles ketene compounds, amount of material of chirality side's acid catalyst are 1:1~10:0.01~0.3；
(B) to addition propiodal additive, alkaline matter and organic solvent in compound shown in formula (IV) obtained in step (A)
B, reacts 0.1~48h at -20~60 DEG C, after reaction terminates, the post-treated chiral pyrazol spiral shell furans obtained shown in formula (I)
Class compound；The ratio between compound shown in described formula (IV) and propiodal additive, the amount of material of alkali are 1:0.5~10:1~
10。
In formula (I), formula (II) formula (III) and formula (IV),
Described R1、R2Each stand alone as hydrogen or methyl；
Described R3It is C1~C20Alkyl；
Described R4、R5Each stand alone as：Hydrogen, C1~C20Alkyl, 2- methoxyphenyls, 3- methoxyphenyls, 4- methoxyl groups
Phenyl, 2- aminomethyl phenyls, 3- aminomethyl phenyls, 4- aminomethyl phenyls, 2- nitrobenzophenones, 3- nitrobenzophenones, 4- nitrobenzophenones, 2,2,2-
Trifluoroethyl, phenyl, 2- fluorophenyls, 3- fluorophenyls, 4- fluorophenyls, 2- chlorphenyls, 3- chlorphenyls, 4- chlorphenyls, 2- bromophenyls,
3- bromophenyls, 4- bromophenyls, benzyl, 2- luorobenzyls, 3- luorobenzyls, 4- luorobenzyls, 2- chlorobenzyls, 3- chlorobenzyls, 4- chlorobenzyls,
2- bromobenzyls, 3- bromobenzyls, 4- bromobenzyls, 2- trifluoromethyls, 3- trifluoromethyls, 4- trifluoromethyls, furans
Base, thienyl, pyridine radicals or 3,5- di-trifluoromethyl phenyl.
In synthetic method step (A) of the present invention, described chirality side's acid catalyst may be selected from shown in formula (V)~(XIII)
Compound shown in one of compound, preferably formula (VII)：
Further, in step (A), 1 shown in preferably described formula (II), hydroresorcinol class compound and formula (III) institute
Show that the ratio between amount for the material that feeds intake of pyrazoles ketene compounds, chirality side's acid catalyst is 1:1:0.1.
Further, in step (A), the volumetric usage of the organic solvent A with 1 shown in formula (II), hydroresorcinol class
The amount of the material of compound is calculated as 0.5~15mL/mmol, preferably 5mL/mmol.
Further, in step (B), described propiodal additive is KI, sodium iodide, cupric iodide, cuprous iodide, four fourths
The materials such as base ammonium iodide, elemental iodine, hydrogen iodide, iodobenzene acetate, preferably elemental iodine.
Further, in step (B), described alkali is NaOH, potassium hydroxide, sodium acid carbonate, potassium carbonate, calcium carbonate,
Sodium carbonate, lithium carbonate, cesium carbonate, triethylene diamine, diethylamine, triethylamine, the carbon -7- alkene of 1,8- diazabicylos 11, pyridine,
The materials such as DMAP, N-methylmorpholine, tetramethylethylenediamine, potassium tert-butoxide, n-BuLi, preferably triethylene two
Amine.
Further, in step (B), compound shown in preferably described formula (IV) and propiodal additive, the thing that feeds intake of alkali
The ratio between amount of matter is 1:2:2.
Further, in step (B), the volumetric usage of the organic solvent B is with the material of step (A) gained compound (IV)
Amount be calculated as 0.5~15mL/mmol, preferably 5mL/mmol.
Further, in step (A) and step (B), described organic solvent A and B is selected from dichloromethane, chloroform, 1,
2- dichloroethanes, 1,1,2- trichloroethanes, ether, isopropyl ether, tetrahydrofuran, 1,4- dioxane, ethyl acetate, toluene, two
Toluene, benzotrifluoride, thionyl chloride, DMF, acetonitrile, methyl alcohol, ethanol or isopropanol, are respectively preferably dichloro
Methane and acetonitrile.
Further, in synthetic method step (A) of the present invention and step (B), reaction condition is：In -20~60 DEG C of conditions
0.1~48h of lower reaction, 4h and 0.5h is reacted under the conditions of preferably 25 DEG C respectively.
In step (B), the method for the reaction solution post processing is：After reaction terminates, reaction solution is extracted with ethyl acetate, extraction
After taking liquid distillation desolvation, residue carries out column chromatography for separation with 200~300 mesh silica gel, and eluant, eluent is ethyl acetate and stone
Oily ether volume ratio 1:2~70 mixed liquor, collects the eluent containing target compound, solvent is evaporated off and dries, and obtains final product formula (I) institute
The chiral pyrazol spiral shell furfuran compound for showing.
Further, described chiral pyrazol spiral shell furfuran compound is the compound shown in formula (Ia)：
In formula (Ia), R1、R2、R3、R4、R5The same formula of definition (I).
More specifically, described property pyrazoles spiral shell furfuran compound is one of following：
1) (2S, 3R) -3', 6,6- trimethyl -1', 3- diphenyl -3,5,6,7- tetrahydrochysene -4H- spiral shell [furans -2,4'- pyrroles
Azoles] -4,5'(1'H)-diketone；
2) (2R, 3S) -3- (2- anisyls) -3', 6,6- trimethyls -1', 3- diphenyl -3,5,6,7- tetrahydrochysene -4H- spiral shells
[furans -2,4'- pyrazoles] -4,5'(1'H)-diketone；
3) (2R, 3S) -3', 6,6- trimethyl -1'- phenyl -3- (4- tolyls) -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -
2,4'- pyrazoles] -4,5'(1'H)-diketone；
4) (2R, 3S) -3- (3- fluorophenyls) -3', 6,6- trimethyls -1'- phenyl -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -
2,4'- pyrazoles] -4,5'(1'H)-diketone；
5) (2R, 3S) -3- (3- chlorphenyls) -3', 6,6- trimethyls -1'- phenyl -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -
2,4'- pyrazoles] -4,5'(1'H)-diketone；
6) (2R, 3S) -3- (3- bromophenyls) -3', 6,6- trimethyls -1'- phenyl -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -
2,4'- pyrazoles] -4,5'(1'H)-diketone；
7) (2R, 3S) -3', 6,6- trimethyl -3- (4- nitrobenzophenones) -1'- phenyl -3,5,6,7- tetrahydrochysene -4H- spiral shell [furans
Mutter -2,4'- pyrazoles] -4,5'(1'H)-diketone；
8) (2R, 3S) -3', 6,6- trimethyl -1'- phenyl -3- (2- thienyls) -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -
2,4'- pyrazoles] -4,5'(1'H)-diketone；
9) (2R, 3S) -3'- methyl isophthalic acids '-phenyl -3- (m3- benzyls) -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -2,4'-
Pyrazoles] -4,5'(1'H)-diketone；
10) (2R, 3S) -3'- methyl isophthalic acids '-phenyl -3- (4- bromophenyls) -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -2,4'-
Pyrazoles] -4,5'(1'H)-diketone；
11) (2R, 3S) -3'- ethyls -6,6- diphenyl -1', 3- diphenyl -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -2,
4'- pyrazoles] -4,5'(1'H)-diketone.
Compared with prior art, the beneficial effects of the present invention are：
(1) method of asymmetric synthesis reaction condition of the present invention is gentle, and product yield high, selectivity are excellent, are applicable
In industrial production；
(2) chiral benzodihydropyran compound prepared by the present invention has chirality, can be applied to organic synthesis, material
The fields such as material；
(3) synthetic method of the invention, simple to operate, and reaction condition is gentle, shows good response characteristic, and reaction is received
Rate is high, selectivity is good.
(4) specific embodiment
With reference to specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in
This.
Compound as described below is synthesized in specific embodiment of the invention：
1) (2S, 3R) -3', 6,6- trimethyl -1', 3- diphenyl -3,5,6,7- tetrahydrochysene -4H- spiral shell [furans -2,4'- pyrroles
Azoles] -4,5'(1'H)-diketone；
2) (2R, 3S) -3- (2- anisyls) -3', 6,6- trimethyls -1', 3- diphenyl -3,5,6,7- tetrahydrochysene -4H- spiral shells
[furans -2,4'- pyrazoles] -4,5'(1'H)-diketone；
3) (2R, 3S) -3', 6,6- trimethyl -1'- phenyl -3- (4- tolyls) -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -
2,4'- pyrazoles] -4,5'(1'H)-diketone；
4) (2R, 3S) -3- (3- fluorophenyls) -3', 6,6- trimethyls -1'- phenyl -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -
2,4'- pyrazoles] -4,5'(1'H)-diketone；
5) (2R, 3S) -3- (3- chlorphenyls) -3', 6,6- trimethyls -1'- phenyl -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -
2,4'- pyrazoles] -4,5'(1'H)-diketone；
6) (2R, 3S) -3- (3- bromophenyls) -3', 6,6- trimethyls -1'- phenyl -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -
2,4'- pyrazoles] -4,5'(1'H)-diketone；
7) (2R, 3S) -3', 6,6- trimethyl -3- (4- nitrobenzophenones) -1'- phenyl -3,5,6,7- tetrahydrochysene -4H- spiral shell [furans
Mutter -2,4'- pyrazoles] -4,5'(1'H)-diketone；
8) (2R, 3S) -3', 6,6- trimethyl -1'- phenyl -3- (2- thienyls) -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -
2,4'- pyrazoles] -4,5'(1'H)-diketone.
9) (2R, 3S) -3'- methyl isophthalic acids '-phenyl -3- (m- benzyls) -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -2,4'-
Pyrazoles] -4,5'(1'H)-diketone.
10) (2R, 3S) -3'- methyl isophthalic acids '-phenyl -3- (4- bromophenyls) -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -2,4'-
Pyrazoles] -4,5'(1'H)-diketone.
11) (2R, 3S) -3'- ethyls -6,6- diphenyl -1', 3- diphenyl -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -2,
4'- pyrazoles] -4,5'(1'H)-diketone.
Embodiment 1：(2S, 3R) -3', 6,6- trimethyl -1', 3- diphenyl -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -2,
4'- pyrazoles] -4,5'(1'H)-diketone synthesis；
(A) take the clean small test tubes of 10mL, add 5,5- dimethyl -1, hydroresorcinol (0.2mmol, 0.028g), (E) -
Phenyl-pyrazole ketenes (0.2mmol, 0.0524g), chirality side's acid catalyst V (0.05mmol, 0.0051g), solvent chloroform
(2mL).After reacting 0.5h at 25 DEG C, vacuum distillation removes solvent, obtains midbody compound 1-A (0.0804g)
(B) midbody compound 1-A (0.2mmol, 0.0804g) is taken, cuprous iodide (0.076g, 0.4mmol), carbon is added
Sour potassium (0.6mmol, 0.0828g), solvent acetonitrile (2mL).After 25 DEG C of reaction 8h, extracted with ethyl acetate (3 × 10mL), it is organic
Subtract each other pressure-off molten, use ethyl acetate:Petroleum ether=1:10 mixed solvents are eluant, eluent；200-300 mesh column layer chromatography silicone rubber is to fill out
Material, column chromatography for separation purification obtain target product (0.0696g, 87%yield, 99%ee,>99:1dr),1H NMR
(500MHz,CDCl3):δ=7.90 (d, J=7.5Hz, 2H), 7.45 (t, J=7.5Hz, 2H), 7.33-7.23 (m, 4H),
7.06-7.04 (m, 2H), 4.96 (s, 1H), 2.61 (d, J=15Hz, 2H), 2.47-2.39 (dd, J1=22Hz, J2=
16.5Hz,2H),1.40(s,3H),1.32(s,3H),1.26(s,3H)ppm；13C NMR(125MHz,CDCl3):δ=193.2,
176.7,170.2,157.6,137.4,134.6,128.95(×2),128.85(×2),128.2,127.9(×2),125.5,
118.7(×2),112.7,91.8,53.6,51.4,37.8,34.3,28.71,28.66,14.2ppm。
Embodiment 2：(2R, 3S) -3- (2- anisyls) -3', 6,6- trimethyls -1', 3- diphenyl -3,5,6,7- four
Hydrogen -4H- spiral shells [furans -2,4'- pyrazoles] -4,5'(1'H)-diketone synthesis；
(A) take the clean small test tubes of 10mL, add 5,5- dimethyl -1, hydroresorcinol (0.2mmol, 0.028g), (E) -
2- anisyls-pyrazoles ketenes (0.3mmol, 0.0876g), chirality side's acid catalyst VI (0.03mmol, 0.0039g), solvent
Toluene (3mL), after 25 DEG C of reaction 5h, after distillation removes solvent, obtains midbody compound 2-A (0.0864g)
(B) take midbody compound 2-A (0.2mmol, 0.0864g), add iodobenzene acetate (0.4mmol,
0.1288g), triethylene diamine (0.6mmol, 0.0606g), solvents tetrahydrofurane (3mL) after 25 DEG C of reaction 6h, uses acetic acid second
Ester (3 × 10mL) is extracted, organic phase decompression precipitation, uses ethyl acetate:Petroleum ether=1:10 mixed solvents are eluant, eluent；200-
300 mesh column layer chromatography silicone rubbers are filler, target product (0.0739g, 86%yield, 99% that column chromatography for separation purification is obtained
Ee,>99:1dr),1H NMR(500MHz,CDCl3):δ=7.95-7.93 (m, 2H), 7.45-7.42 (m, 2H), 7.28-7.20
(m, 2H), 7.00-6.90 (m, 2H), 6.93-6.90 (m, 2H), 6.77 (d, J=8Hz, 1H), 5.19 (s, 1H), 3.45 (s,
3H),2.60-2.55(m,2H),2.48-2.39(dd,J1=28Hz, J2=16.5Hz, 2H), 1.36 (s, 3H), 1.31 (s,
3H),1.24(s,3H)ppm；13C NMR(125MHz,CDCl3):δ=193.4,176.3,170.2,157.1,157.0,
137.8,129.2,129.0(×2),128.6,125.1,123.5,120.3,118.2(×2),112.1,109.8,91.6,
54.9,51.5,48.1,38.0,34.3,28.9,28.5,13.8ppm。
Embodiment 3：(2R, 3S) -3', 6,6- trimethyl -1'- phenyl -3- (4- tolyls) -3,5,6,7- tetrahydrochysene -4H- spiral shells
[furans -2,4'- pyrazoles] -4,5'(1'H)-diketone synthesis；
(A) take the clean small test tubes of 10mL, add 5,5- dimethyl -1, hydroresorcinol (0.2mmol, 0.028g), (E) -
4- tolyls-pyrazoles ketenes (0.24mmol, 0.0662g), chirality side's acid catalyst VII (0.01mmol, 0.0063g), solvent
Acetonitrile (0.5mL), after 25 DEG C of reaction 1h, after distillation removes solvent, obtains midbody compound 3-A (0.0832g)
(B) take midbody compound 3-A (0.2mmol, 0.0832g), add tetrabutylammonium iodide (0.5mmol,
0.1845g), NaOH (0.0672g, 0.8mmol), solvent methanol (0.5mL), after 25 DEG C of reaction 4h, with ethyl acetate (3
× 10mL) extract, organic phase decompression precipitation uses ethyl acetate:Petroleum ether=1:10 mixed solvents are eluant, eluent；200-300 mesh
Column layer chromatography silicone rubber is filler, target product that column chromatography for separation purification is obtained (0.0662g, 80%yield, 93%ee,>20:
1dr),1H NMR(500MHz,CDCl3):δ=7.90-7.88 (m, 2H), 7.46-7.43 (m, 2H), 7.28-7.23 (m, 1H),
7.11 (d, J=7.5Hz, 2H), 6.92 (d, J=8Hz, 2H), 4.92 (s, 1H), 2.64-2.57 (dd, J1=19Hz, J2=
16Hz,2H),2.46-2.38(dd,J1=20Hz, J2=16.5Hz, 2H), 2.32 (s, 3H), 1.43 (s, 3H), 1.32 (s,
3H),1.26(s,3H)ppm；13C NMR(125MHz,CDCl3):δ=193.3,176.5,170.4,157.8,138.0,
137.5,131.6,129.6(×2),129.0(×2),127.8(×2),125.5,118.7(×2),113.0,91.9,
53.4,51.5,37.9,34.4,28.8,28.7,21.1,14.3ppm。
Embodiment 4：(2R, 3S) -3- (3- fluorophenyls) -3', 6,6- trimethyl -1'- phenyl -3,5,6,7- tetrahydrochysene -4H- spiral shells
[furans -2,4'- pyrazoles] -4,5'(1'H)-diketone synthesis；
(A) take the clean small test tubes of 10mL, add 5,5- dimethyl -1, hydroresorcinol (0.2mmol, 0.028g), (E) -
3- fluorophenyls-pyrazoles ketenes (0.28mmol, 0.0784g), chirality side's acid catalyst VIII (0.01mmol, 0.0063g), solvent
1,2- dichloroethanes (1mL), after 25 DEG C of reaction 0.1h, after distillation removes solvent, obtains midbody compound 4-A (0.0840g)
(B) midbody compound 4-A (0.2mmol, 0.0840g) is taken, KI (0.3mmol, 0.0498g) is added,
Triethylamine (0.4mmol, 0.0404g), methylene chloride (1mL) after 25 DEG C of reaction 2h, is extracted with ethyl acetate (3 × 10mL)
Take, organic phase decompression precipitation uses ethyl acetate:Petroleum ether=1:10 mixed solvents are eluant, eluent；200-300 mesh column chromatography silicon
Glue is filler, target product that column chromatography for separation purification is obtained (0.0719g, 78%yield, 99%ee,>99:1dr),1H
NMR(500MHz,CDCl3):δ=7.90-7.88 (dd, J1=9Hz, J2=1Hz, 2H), 7.46-7.43 (dd, J1=8.5Hz, J2
=7Hz, 2H), 7.31-7.23 (m, 2H), 7.03-6.99 (m, 1H), 6.58 (d, J=8Hz, 1H), 6.78-6.75 (m, 1H),
4.92 (s, 1H), 2.61 (d, J=2Hz, 2H), 2.47-2.39 (dd, J1=24.5Hz, J2=16.5Hz, 2H) 1.45 (s, 3H),
1.32(s,3H),1.26(s,3H)ppm。
Embodiment 5：(2R, 3S) -3- (3- chlorphenyls) -3', 6,6- trimethyl -1'- phenyl -3,5,6,7- tetrahydrochysene -4H- spiral shells
[furans -2,4'- pyrazoles] -4,5'(1'H)-diketone synthesis；
(A) take the clean small test tubes of 10mL, add 5,5- dimethyl -1, hydroresorcinol (0.2mmol, 0.028g), (E) -
3- chlorphenyls-pyrazoles ketenes (0.2mmol, 0.0592g), chirality side's acid catalyst IX (0.002mmol, 0.0009g), solvent four
Hydrogen furans (1mL), after 25 DEG C of reaction 8h, after distillation removes solvent, obtains midbody compound 5-A (0.0872g)
(B) midbody compound 5-A (0.2mmol, 0.0872g) is taken, elemental iodine (0.1mmol, 0.0106g) is added,
Potassium carbonate (0.2mmol, 0.0276g), solvent ethyl acetate (1mL) after 25 DEG C of reaction 2h, is extracted with ethyl acetate (3 × 10mL)
Take, organic phase decompression precipitation uses ethyl acetate:Petroleum ether=1:10 mixed solvents are eluant, eluent；200-300 mesh column chromatography silicon
Glue is filler, target product that column chromatography for separation purification is obtained (0.0798g, 84%yield, 94%ee,>99:1dr),1H
NMR(500MHz,CDCl3):δ=7.88 (d, J=8Hz, 2H), 7.45 (t, J=7.5Hz, 2H), 7.31-7.24 (m, 3H),
7.03 (s, 1H), 6.94 (d, J=7.5Hz, 2H), 4.89 (s, 1H), 2.65-2.58 (m, 2H), 2.47-2.39 (dd, J1=
26.5Hz,J2=16.5Hz, 2H), 1.46 (s, 3H), 1.32 (s, 3H), 1.26 (s, 3H) ppm；13C NMR(125MHz,
CDCl3):δ=193.1,177.1,170.0,157.1,137.4,136.9,135.0,130.2,129.0 (× 2), 128.6,
128.1,126.2,125.7,118.8(×2),112.4,91.7,53.2,51.4,37.9,34.5,28.8,28.6,
14.4ppm。
Embodiment 6：(2R, 3S) -3- (3- bromophenyls) -3', 6,6- trimethyl -1'- phenyl -3,5,6,7- tetrahydrochysene -4H- spiral shells
[furans -2,4'- pyrazoles] -4,5'(1'H)-diketone synthesis；
(A) take the clean small test tubes of 10mL, add 5,5- dimethyl -1, hydroresorcinol (0.2mmol, 0.028g), (E) -
3- bromophenyls-pyrazoles ketenes (0.2mmol, 0.0592g), chirality side's acid catalyst X (0.1mmol, 0.0109g), solvent acetic acid
Ethyl ester (3mL), after 25 DEG C of reaction 20h, after distillation removes solvent, obtains midbody compound 6-A (0.0960g)
(B) midbody compound 6-A (0.2mmol, 0.0960g) is taken, hydrogen iodide (2mmol, 0.256g), diethyl is added
Amine (0.8mmol, 0.0584g), solvent ethyl acetate (3mL) after 25 DEG C of reaction 18h, is extracted with ethyl acetate (3 × 10mL),
Organic phase decompression precipitation, uses ethyl acetate:Petroleum ether=1:10 mixed solvents are eluant, eluent；200-300 mesh column layer chromatography silicone rubbers
It is filler, target product that column chromatography for separation purification is obtained (0.0842g, 88%yield, 96%ee,>99:1dr),1H NMR
(500MHz,CDCl3):δ=7.88 (d, J=7.5Hz, 2H), 7.46-7.43 (m, 3H), 7.28-7.18 (m, 3H), 6.99 (d,
J=7.5Hz, 1H), 4.87 (s, 1H), 2.65-2.57 (m, 2H), 2.47-2.38 (dd, J1=27.5Hz, J2=16.5Hz,
2H),1.46(s,3H),1.31(s,3H),1.26(s,3H)ppm；13C NMR(125MHz,CDCl3):δ=193.1,177.1,
170.0,157.1,137.4,137.1,131.5,131.0,130.4,129.0(×2),126.7,125.7,123.0,118.8
(×2),112.4,91.7,53.1,51.4,37.8,34.4,28.8,28.5,14.4ppm。
Embodiment 7：(2R, 3S) -3', 6,6- trimethyl -3- (4- nitrobenzophenones) -1'- phenyl -3,5,6,7- tetrahydrochysenes -4H-
Spiral shell [furans -2,4'- pyrazoles] -4,5'(1'H)-diketone synthesis；
(A) take the clean small test tubes of 10mL, add 5,5- dimethyl -1, hydroresorcinol (0.2mmol, 0.028g), (E) -
4- nitrobenzophenones-pyrazoles ketenes (0.4mmol, 0.1228g), chirality side's acid catalyst XI (0.1mmol, 0.0112g), solvent first
Benzene (1mL), after 25 DEG C of reaction 20h, after distillation removes solvent, obtains midbody compound 7-A (0.0894g)
(B) midbody compound 7-A (0.2mmol, 0.0894g) is taken, hydrogen iodide (2mmol, 0.256g), diethyl is added
Amine (0.8mmol, 0.0584g), solvent ethyl acetate (1mL) after 25 DEG C of reaction 20h, is extracted with ethyl acetate (3 × 10mL),
Organic phase decompression precipitation, uses ethyl acetate:Petroleum ether=1:10 mixed solvents are eluant, eluent；200-300 mesh column layer chromatography silicone rubbers
It is filler, target product that column chromatography for separation purification is obtained (0.0659g, 65%yield, 91%ee,>99:1dr),1H NMR
(500MHz,CDCl3):δ=8.19 (d, J=8.5Hz, 2H), 7.89-7.87 (m, 2H), 7.47-7.44 (m, 2H), 7.28-
7.22(m,3H),5.02(s,1H),2.67-2.59(m,2H),2.48-2.40(dd,J1=24Hz, J2=16.5Hz, 2H),
1.49(s,3H),1.33(s,3H),1.27(s,3H)ppm；13C NMR(125MHz,CDCl3):δ=193.1,177.5,
169.6,156.5,147.8,142.0,137.2,129.1(×4),129.0(×2),125.9(×2),124.0(×2),
118.7,111.9,91.6,53.4,51.3,37.9,34.5,28.7,28.6,14.4ppm。
Embodiment 8：(2R, 3S) -3', 6,6- trimethyl -1'- phenyl -3- (2- thienyls) -3,5,6,7- tetrahydrochysene -4H- spiral shells
[furans -2,4'- pyrazoles] -4,5'(1'H)-diketone synthesis；
(A) the clean small test tubes of 10mL are taken, 5,5- dimethyl -1, hydroresorcinol (0.2mmol, 0.028g), (E) -2 is added
Thienyl-pyrazoles ketenes (0.2mmol, 0.0536g), chirality side's acid catalyst XII (0.004mmol, 0.0021g), solvent chlorine
Imitative (1mL), after 25 DEG C of reaction 20h, after distillation removes solvent, obtains midbody compound 8-A (0.0816g)
(B) midbody compound 8-A (0.2mmol, 0.0816g) is taken, elemental iodine (0.1mmol, 0.0106g) is added,
Sodium carbonate (0.3mmol, 0.0414g), solvents tetrahydrofurane (1mL) after 25 DEG C of reaction 1h, is extracted with ethyl acetate (3 × 10mL)
Take, organic phase decompression precipitation uses ethyl acetate:Petroleum ether=1:10 mixed solvents are eluant, eluent；200-300 mesh column chromatography silicon
Glue is filler, target product that column chromatography for separation purification is obtained (0.0755g, 93%yield, 98%ee,>99:1dr),1H
NMR(500MHz,CDCl3):δ=7.89 (d, J=8.0Hz, 2H), 7.44 (t, J=7.5Hz, 2H), 7.28-7.22 (m, 2H),
6.99-6.98 (m, 1H), 6.83 (d, J=3.5Hz, 1H), 5.11 (s, 1H), 2.64-2.56 (m, 2H), 2.41 (s, 2H),
1.50(s,3H),1.31(s,3H),1.25(s,2H)ppm；13C NMR(125MHz,CDCl3):δ=192.9,176.7,
169.6,157.5,139.0,137.4,129.0(×2),127.7,126.4,125.6,125.5(×2),118.7,113.8,
91.6,51.4,48.4,37.8,34.3,28.8,28.5,14.0ppm。
Embodiment 9：(2R, 3S) -3'- methyl isophthalic acids '-phenyl -3- (3- benzyls) -3,5,6,7- tetrahydrochysene -4H- spiral shells [furans -
2,4'- pyrazoles] -4,5'(1'H)-diketone；
(A) the clean small test tubes of 10mL are taken, 1, hydroresorcinol (0.2mmol, 0.0224g), (E) -3- benzyls-pyrrole is added
Azoles ketenes (2mmol, 0.552g), chirality side's acid catalyst XII (0.06mmol, 0.0315g), solvent chloroform (3mL), -20 DEG C
After reaction 48h, after distillation removes solvent, midbody compound 9-A (0.0776g) is obtained
(B) midbody compound 9-A (0.2mmol, 0.0776g) is taken, elemental iodine (2mmol, 0.212g), carbonic acid is added
Sodium (2mmol, 0.276g), solvents tetrahydrofurane (3mL) after 60 DEG C of reaction 0.1h, is extracted with ethyl acetate (3 × 10mL), is had
It is molten that machine subtracts each other pressure-off, uses ethyl acetate:Petroleum ether=1:10 mixed solvents are eluant, eluent；200-300 mesh column layer chromatography silicone rubbers are
Filler, column chromatography for separation purification obtain target product (0.0625g, 81%yield, 93%ee,>99:1dr),1H NMR
(500MHz,CDCl3):δ=7.90-7.88 (m, 2H), 7.46-7.43 (m, 2H), 7.28-7.18 (m, 2H), 7.10 (d, J=
7.5Hz,1H),6.85-6.83(m,2H),4.90(s,1H),2.76-273(m,2H),2.57-2.51(m,2H),2.30(m,
5H),1.40(s,3H)ppm；13C NMR(125MHz,CDCl3):δ=193.8,177.5,170.3,157.8,138.5,
137.5,134.4,129.1,128.9(×2),128.7,128.5,125.5,124.9,118.8(×2),114.2,91.6,
53.7,37.0,24.1,21.6,21.4,14.3ppm。
Embodiment 10：(2R, 3S) -3'- methyl isophthalic acids '-phenyl -3- (4- bromophenyls) -3,5,6,7- tetrahydrochysene -4H- spiral shell [furans
Mutter -2,4'- pyrazoles] -4,5'(1'H)-diketone；
(A) the clean small test tubes of 10mL are taken, 1, hydroresorcinol (0.2mmol, 0.0224g), (E) -4- bromophenyls-pyrrole is added
Azoles ketenes (1mmol, 0.340g), chirality side's acid catalyst XII (0.06mmol, 0.0315g), methylene chloride (0.1mL),
After 60 DEG C of reaction 0.1h, after distillation removes solvent, midbody compound 10-A (0.09g) is obtained
(B) midbody compound 10-A (0.2mmol, 0.09g) is taken, KI (0.1mmol, 0.0166g), carbon is added
Sour sodium (0.2mmol, 0.0276g), solvents tetrahydrofurane (0.1mL), after -20 DEG C of reaction 48h, with ethyl acetate (3 × 10mL)
Extraction, organic phase decompression precipitation, uses ethyl acetate:Petroleum ether=1:10 mixed solvents are eluant, eluent；200-300 mesh column chromatographies
Silica gel is filler, target product (0.0756g, 84%yield, 88%ee, 95 that column chromatography for separation purification is obtained:5dr),1H
NMR(500MHz,CDCl3):δ=7.89-7.87 (dd, J1=9Hz, J2=1.51Hz, 1H), 7.46-7.43 (m, 4H), 7.28-
7.24 (m, 1H), 6.93 (d, J=8Hz, 3H), 4.89 (s, 1H), 2.76-2.73 (m, 2H), 2.55-2.50 (m, 2H), 2.30-
2.45(m,2H),1.48(s,3H)ppm；13C NMR(125MHz,CDCl3):δ=193.8,178.5,169.7,156.6,
148.4,137.2,136.9,134.1,130.1,129.1(×2),125.9,123.4,122.7,118.9(×2),113.1,
91.2,53.4,36.9,24.1,21.6,14.4ppm。
Embodiment 11：(2R, 3S) -3'- ethyl -6,6- diphenyl -1', 3- diphenyl -3,5,6,7- tetrahydrochysene -4H- spiral shell [furans
Mutter -2,4'- pyrazoles] -4,5'(1'H)-diketone；
(A) take the clean small test tubes of 10mL, add 5.5- dimethyl -1, hydroresorcinol (0.2mmol, 0.028g), (E) -
Phenyl-pyrazole ketenes (1mmol, 0.276g), chirality side's acid catalyst XII (0.06mmol, 0.0315g), solvent acetonitrile
(0.1mL), after -20 DEG C of reaction 0.1h, after distillation removes solvent, obtains midbody compound 11-A (0.0832g)
(B) midbody compound 11-A (0.2mmol, 0.0832g) is taken, KI (0.1mmol, 0.0166g) is added,
Sodium carbonate (0.2mmol, 0.0276g), solvents tetrahydrofurane (3mL), after 60 DEG C of reaction 0.1h, with ethyl acetate (3 × 10mL)
Extraction, organic phase decompression precipitation, uses ethyl acetate:Petroleum ether=1:10 mixed solvents are eluant, eluent；200-300 mesh column chromatographies
Silica gel is filler, target product that column chromatography for separation purification is obtained (0.0720g, 87%yield, 96%ee,>99:1dr),1H
NMR(500MHz,CDCl3):δ=7.94-7.92 (dd, J1=8.5Hz, J2=1Hz, 2H), 7.47-7.43 (m, 2H), 7.32-
7.23(m,4H),7.04-7.02(m,2H),4.97(s,1H),2.64-2.55(m,2H),2.47-2.39(dd,J1=
22.5Hz,J2=16.5Hz, 2H), 1.91-1.83 (m, 1H), 1.47-1.39 (m, 1H), 1.32 (s, 3H), 1.26 (s, 3H),
0.86 (t, J=7.5Hz, 3H) ppm；13C NMR(125MHz,CDCl3):δ=193.2,176.8,170.4,161.6,137.6,
134.7,128.9(×2),128.8(×2),128.1,127.8(×2),125.4,118.7(×2),112.5,92.2,
53.8,51.4,37.9,34.3.,28.7,28.6,22.0,9.1ppm。
Claims (10)
1. the method for asymmetric synthesis of chiral pyrazol spiral shell furfuran compound of the one kind as shown in formula (I), it is characterised in that described
Synthetic method carry out as follows：
(A) by hydroresorcinol class compound shown in formula (II) and pyrazoles ketene compounds shown in formula (III), the acid of chirality side
Catalyst, organic solvent A mixing, react 0.1~48h at -20~60 DEG C, after reaction terminates, reaction solution is evaporated off into solvent and is obtained
To the compound shown in formula (IV)；Hydroresorcinol class compound and pyrazoles alkene shown in formula (III) shown in described formula (II)
The ratio between ketone compounds, amount of material of chirality side's acid catalyst are 1:1~10:0.01~0.3；
(B) to addition propiodal additive, alkaline matter and organic solvent B in compound shown in formula (IV) obtained in step (A),
0.1~48h is reacted at -20~60 DEG C, after reaction terminates, the post-treated chiral pyrazol spiral shell furans obtained shown in formula (I)
Compound；The ratio between compound shown in described formula (IV) and propiodal additive, the amount of material of alkali are 1:0.5~10:1~10.
In formula (I), formula (II) formula (III) and formula (IV),
Described R1、R2Each stand alone as hydrogen or methyl；
Described R3It is C1~C20Alkyl；
Described R4、R5Each stand alone as：Hydrogen, C1~C20Alkyl, 2- methoxyphenyls, 3- methoxyphenyls, 4- methoxybenzenes
Base, 2- aminomethyl phenyls, 3- aminomethyl phenyls, 4- aminomethyl phenyls, 2- nitrobenzophenones, 3- nitrobenzophenones, 4- nitrobenzophenones, 2,2,2- tri-
Fluoro ethyl, phenyl, 2- fluorophenyls, 3- fluorophenyls, 4- fluorophenyls, 2- chlorphenyls, 3- chlorphenyls, 4- chlorphenyls, 2- bromophenyls, 3-
Bromophenyl, 4- bromophenyls, benzyl, 2- luorobenzyls, 3- luorobenzyls, 4- luorobenzyls, 2- chlorobenzyls, 3- chlorobenzyls, 4- chlorobenzyls, 2-
Bromobenzyl, 3- bromobenzyls, 4- bromobenzyls, 2- trifluoromethyls, 3- trifluoromethyls, 4- trifluoromethyls, furyl,
Thienyl, pyridine radicals or 3,5- di-trifluoromethyl phenyl.
2. the method for asymmetric synthesis of chiral pyrazol spiral shell furfuran compound as claimed in claim 1, it is characterised in that step
(A) in, described chirality side's acid catalyst is selected from formula (V)~one of compound shown in (XIII)：
3. the method for asymmetric synthesis of chiral pyrazol spiral shell furfuran compound as claimed in claim 1, it is characterised in that step
(A) in, the volumetric usage of the organic solvent A is so that 1 shown in formula (II), the amount of the material of hydroresorcinol class compound is calculated as
0.5~15mL/mmol.
4. the method for asymmetric synthesis of chiral pyrazol spiral shell furfuran compound compound as claimed in claim 1, its feature exists
In step (B), described propiodal additive is KI, sodium iodide, cupric iodide, cuprous iodide, tetrabutylammonium iodide, iodine list
Matter, hydrogen iodide or iodobenzene acetate.
5. the method for asymmetric synthesis of chiral pyrazol spiral shell furfuran compound compound as claimed in claim 4, its feature exists
In step (B), described propiodal additive is elemental iodine.
6. the method for asymmetric synthesis of chiral pyrazol spiral shell furfuran compound as claimed in claim 1, it is characterised in that step
(B) in, described alkaline matter is NaOH, potassium hydroxide, sodium acid carbonate, potassium carbonate, calcium carbonate, sodium carbonate, lithium carbonate,
Cesium carbonate, triethylene diamine, diethylamine, triethylamine, the carbon -7- alkene of 1,8- diazabicylos 11, pyridine, 4- dimethylamino pyrroles
Pyridine, N-methylmorpholine, tetramethylethylenediamine, potassium tert-butoxide or n-BuLi.
7. the method for asymmetric synthesis of chiral pyrazol spiral shell furfuran compound as claimed in claim 6, it is characterised in that step
(B) in, described alkaline matter is triethylene diamine.
8. the method for asymmetric synthesis of chiral pyrazol spiral shell furfuran compound as claimed in claim 1, it is characterised in that step
(B) in, the volumetric usage of the organic solvent B is calculated as 0.5~15mL/ with the amount of the material of step (A) gained compound (IV)
mmol。
9. the method for asymmetric synthesis of chiral pyrazol spiral shell furfuran compound as claimed in claim 1, it is characterised in that step
(A) and in step (B), described organic solvent be selected from dichloromethane, chloroform, 1,2- dichloroethanes, 1,1,2- trichloroethanes,
Ether, isopropyl ether, tetrahydrofuran, 1,4- dioxane, ethyl acetate, toluene, dimethylbenzene, benzotrifluoride, thionyl chloride, N, N-
Dimethylformamide, acetonitrile, methyl alcohol, ethanol or isopropanol.
10. the method for asymmetric synthesis of chiral pyrazol spiral shell furfuran compound as claimed in claim 1, it is characterised in that step
(B) in, the method for the reaction solution post processing is：After reaction terminates, reaction solution is extracted with ethyl acetate, extract distillation removing
After solvent, residue carries out column chromatography for separation with 200~300 mesh silica gel, and eluant, eluent is ethyl acetate and petroleum ether volume ratio 1:2
~70 mixed liquor, collects the eluent containing target compound, solvent is evaporated off and dries, and obtains final product the chiral pyrazol shown in formula (I)
Spiral shell furfuran compound.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109053532A (en) * | 2018-09-21 | 2018-12-21 | 武汉理工大学 | The synthetic method of R-3- amino -2,5 dioxypyrrole -3- carboxylic acid, ethyl ester |
| CN109970752A (en) * | 2019-04-10 | 2019-07-05 | 浙江工业大学 | A kind of synthetic method of chirality 4- loop coil pyrazole compound |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1154697A (en) * | 1995-05-19 | 1997-07-16 | 协和发酵工业株式会社 | Oxygen-contg. heterocyclic compound |
-
2017
- 2017-01-22 CN CN201710053586.1A patent/CN106905336B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1154697A (en) * | 1995-05-19 | 1997-07-16 | 协和发酵工业株式会社 | Oxygen-contg. heterocyclic compound |
Non-Patent Citations (6)
| Title |
|---|
| CHUNLI XU,等: "High Surface Area MgO as a Highly Effective Heterogeneous Base Catalyst for Michael Addition and Knoevenagel Condensation Reactions", 《SYNTHESIS》 * |
| XU WANG，等: "Synthesis of Trifiluoromethylated Tetrahydrochromeno[2,3-c]pyrazol-5(1H)-ones via a One-Pot Multicomponent Reaction in the Presence of 4-Toluenesulfonic Acid", 《SYNTHESIS》 * |
| YI SUN, 等: "Facile Construction of Oxa-Aza Spirobicycles via a Tandem Carbon-Hydrogen Bond Oxidation", 《ADVANCED SYNTHESIS & CATALYSIS》 * |
| 刘建波: "手性方酰胺催化的不对称Michael加成反应研究", 《武汉理工大学硕士学位论文》 * |
| 刘斌: "新型手性方酰胺催化剂的设计合成及其在不对称催化反应中的应用", 《武汉大学博士学位论文》 * |
| 王益锋: "基于手性叔胺-氮方酸催化的不对称催化反应研究", 《浙江工业大学博士学位论文》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109053532A (en) * | 2018-09-21 | 2018-12-21 | 武汉理工大学 | The synthetic method of R-3- amino -2,5 dioxypyrrole -3- carboxylic acid, ethyl ester |
| CN109970752A (en) * | 2019-04-10 | 2019-07-05 | 浙江工业大学 | A kind of synthetic method of chirality 4- loop coil pyrazole compound |
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