136 results about "Axial chirality" patented technology

The invention discloses two axial chiral isomers, available medicinal salts thereof, a preparation method thereof, and pharmaceutical application of the two axial chiral isomers or medicinal compositions thereof.

The invention discloses a preparation method and an application for phosphine-oxazoline ligand, and ionic metal complex, enantiomer or racemate thereof. The ligand and the ionic metal complex thereof have the following structural formulas. The phosphine ligand related by the invention employs biphenyl as a skeleton, and realizes completely transmission from planar chirality to axial chirality through an asymmetric desymmerization. The synthetic method is simple and economic, omits a common and complex chiral separation process in the preparation of the chiral ligand. The obtained chiral ligand has the advantages of high reactive activity, good enantiomorphous selectivity and the like in a model reaction.

The invention discloses a phosphine ligand and an enantiomer or a racemic body thereof and preparation methods and applications thereof. The structural formulae of the phosphine ligand and the enantiomer or the racemic body are shown in the specifications; a phosphine ligand compound has a novel framework; complete transfer of planar chirality to axial chirality in a synthesis process is realized through a desymmetrization reaction; a synthesis method is simple and economical; during preparation of a chiral ligand, common complex chiral splitting processes are avoided; and an obtained chiral ligand has the advantages of high reaction activity, high enantioselectivity and the like in a model reaction, can be applied to catalytic reactions of a plurality of metals such as palladium, rhodium, nickel, copper, iridium, ruthenium, iron, cobalt, gold, platinum and the like, and can have a very good catalytic effect.

The invention discloses a method for synthetizing axial chirality aryl indole through organocatalysis. The method is characterized in that chiral phosphoric acid is used as a catalyst; a compound 1 and a compound 2 react: the chemical formula is shown as the description, wherein R<1> is hydrogen; R<2> is selected from tertiary butyl, 1-methyl cyclopropyl, 1-methyl cyclobutyl, tertiary pentyl, aryl and heteroaryl; R<3> represents any substituent group; n represents an integer being 1 to 4, and when n is greater than 2, existent two or greater R<3> are identical or different; R<4> selects CO2R, and R is alkyl or benzyl; R<5> represents any substituent group; m represents an integer being 1 to 4, and when m is greater than 2, existent two or greater R<5> are identical or different. The synthesis method is applicable to azobenzene derivatives of various kinds of ester; the axial chirality aryl indole is obtained at good yield and excellent enantioselectivity; the reaction conditions are mild. The method opens up a novel path for organocatalysis of asymmetrical aromatic functionalization.

A spirocyclosulphite is prepared from spirocyclodiphenol through three methods. Its spirodihydroindene structure has axial chirality, so said compound has two mutamers: levo- and dextro- spirocyclosulphite compounds. It can be used for the asymmetrical addition reaction of aldehyde and imine with high stereo activity.

The invention relates to a 3, 3'-position binaphthyl shaft chiral phosphoramidite ligand containing biaryl group and a preparation method thereof. The preparation method comprises the following steps of: leading 3, 3'-dual-biaryl group-2, 2'-dinaphthol to react with hexagon-alkyl group phosphoramidite in organic solvent at the temperature of 0-120 DEG C according to the mol rate of 1:1, or leading 3, 3'- dual-biaryl group-2, 2'-dinaphthol to react with phosphorus trichloride and dialkyl amine in steps, and after complete reaction, the object chiral phosphoramidite ligand can be obtained through washing, extraction and separation. After going through complexation with metallic copper salt, the chiral phosphoramidite ligand can be used for catalyzing the conjugate addition reaction of zinc alkyl with alpha, beta-unsaturated carbonyl compounds, and an additional product is prepared with high yield up to 78-98% and high enantioselectivity ee value up to 80-98%.

The invention relates to a spiro bisimine and a preparation method and application thereof. Spiro diamine is adopted as raw material to generate spiro bisimine. The spiro skeleton structure in the spiro bisimine has axial chirality, therefore, the class of compound has two optical isomers, namely, right spiro bisimine and left spiro bisimine; and the commensurable mixture of the two optical isomers become racemization spiro bisimine. The complex compound of the spiro bisimine and copper can be taken as a chiral catalyst which is used in asymmetric insertion reaction of carbene to silicon-hydrogen bond, and has very high activity and enantio selectivity (as high as 99.2 percent ee). The chemical formula of the spiro bisimine is as follows: n=0-3; and the values of R<1>, R<2>, R<3>, R<4>, R<5>, R<6>, R<7>, R<8>, R<9> and R<10> are defined as claim of right 1.

The invention relates to a high-optical-activity axial chirality allene compound and a construction method thereof. The construction method is a method for directly constructing an allene compound with axial chirality under the high stereoselectivity by performing a reaction of 2,3-allene functional group compound and a nucleophilic reagent in an organic solvent under the action of a palladium catalyst, a chiral diphosphine ligand and alkali. The method has the advantages of simplicity for operation, easiness for obtaining raw materials and a reagent and the like; the substrate universality iswide; high stereoselectivity of the product is very excellent (90 to 96%ee). The high-optical-activity allene product obtained by the method disclosed by the invention is used as an important intermediate and can be used for constructing chiral compounds, such as gamma-allenoate, gamma-allenoic acid, gamma-allenol and gamma-butyrolactone, and gamma-butyrolactone natural product (R)-traumatic lactone (98%ee) is synthesized under high enantioselectivity for the first time.

The invention provides spiro bis(oxazoline) ligands with a plurality of chiral centers, a preparation method and application. The ligands are provided with axial chirality of a spiro backbone and central chirality of an oxazoline ring. The ligands can be prepared by condensation of chiral spiro diacid and corresponding alkamine. The invention also provides application of the spiro bis(oxazoline) ligands in synthesizing pyrazolidine derivatives in high regioselectivity and high enantioselectivity.

The invention relates to the field of chemical catalysis and discloses a phosphoramidite ligand as well as a preparation method and an application thereof. The synthesized phosphoramidite ligand and an enantiomer or a racemate of the phosphoramidite ligand take biphenyl as a framework and are subjected to an asymmetric induced reaction of axial chirality to realize complete transfer from central chirality to axial chirality. A synthetic method for the phosphoramidite ligand and the enantiomer or the racemate of the phosphoramidite ligand is simple and economic, and a common and complex chiral resolution process is avoided during chiral ligand preparation. The phosphoramidite ligand and the enantiomer or the racemate of the phosphoramidite ligand is employed to form the ligand together with active metal-iridium for catalyzing an asymmetric addition reaction of N-protected isatin and arylboronic acid, a very good catalytic effect is achieved, and a product can obtain the yield of more than 96% and the enantiomeric excess (ee) value of more than 92%.

The invention discloses a method for directly constructing a high optical activity allene compound combing axial chirality and central chirality. Under effects of a palladium catalyst, a chiral diphosphine ligand and alkali, 2,3-allene function group compounds shown in a formula (1) and a nucleophilic reagent in a formula (2) are reacted in an organic solvent, and the high optical activity allene compound combing axial chirality and central chirality can be directly constructed by one step. The method has the advantages of simple operation, easy acquisition of raw material and the reagent, mild reaction condition, wide substrate universality, and good function group compatibility, and the stereoselective performance of the product is excellent (greater than 99:1 d.r., 95-greater than 99% ee). The high optical activity allene compound can be taken as an important intermediate for constructing the compounds such as monofluoro methylation allene, gamma-allene acid ester, gamma-allene acid, gamma-allenol, and gamma-butanolide containing several chiral centers.

The invention relates to central chiral induced axial chiral diphosphine ligand, which adopts the structural formula that in the formula, R1 is benzyl or substituted benzyl; R is tertiary butyl or trifluoromethyl. The invention adopts the preparation method that 1-R-3, 5-dibromo benzene is used as the raw material, to produce 3-R-5- bromophenol; and then methylation is performed to obtain 1-R-3- bromine -5- anisole; after lithium realization of 3-dihydro pjosphinyl-5-R methyl phenoxide which reacts with dihydro phosphonic chloride and is obtained through oxidation, the product of the reaction with iodine reacts with boron tribromide, 2-iodine-3-dihydro pjosphinyl-5-R phenol obtained through demethylation and then reacts with central chiral 2, 4- pentanediol derivative, to obtain 2, 4-di (2-iodine-3- dihydro pjosphinyl-5- substituent phenoxy oxygen) pentane; <6, 61 -(2, 4- pentanediol oxygen)>-(4, 41)- disubstituent -(2, 21)-di (dialkyl pjosphinyl)-(1, 11)- biphenyl is produced through coupling, and finally reaction is performed with tri-butylamine and trichlorosilane, to obtain the diphosphine ligand.

The invention provides a chirality phosphine nitrogen compound containing N-aryl as well as a synthetic method and application thereof. The phosphine nitrogen compound is based on axial chirality or comprises a helical chirality skeleton, and is synthetized by taking optically pure axial chirality or helical chirality glycols compound, phosphorus trichloride and aromatic secondary amine as raw material for reaction. The raw material used in the method is easy to obtain, the reaction condition is mild, and the products are easy to separate and purify. The N-aryl phosphine nitrogen compound base on the axial chirality or the helical chirality skeleton synthetized by the method can be effectively applied in substitution reaction of allyl catalyzed by metal iridium, so that the product can be obtained with high enantioselectivity and regioselectivity, and the substrate scope of the product is greatly widened.

The invention relates to a method for preparing a chiral dihydrobenzofuran compound and a catalyst used by the same, which belongs to the technical field of chemical industry. The method prepares a chiral dihydrobenzofuran derivative IV by using a 2-allyl phenols compound III as a raw material and using an axial chiral metal complex as a catalyst in a reaction solvent in the presence of an oxidant, wherein the structural formula of the compounds III and IV are as above. The method uses the metal complex as the catalyst which has higher reactivity and enantioselectivity up to 99 percent and can be applied to various asymmetric catalytic reactions, wherein R5 is hydrogen, phenyl, naphthyl, halogen, benzyl, or alkyl with carbons of between 1 and 8; and R6 is hydrogen, phenyl, naphthyl, benzyl, or alkyl with carbons of between 1 and 8.

The invention relates to dipyridine ligands with axial chirality. A synthetic method adopts 3-hydroxy-2-halogen pyridine as an initial raw material, and includes loading a chiral skeleton with the pyridine through a Mitsunobu reaction with a chiral diol, and achieving pyridine coupling through an Ullman reaction catalyzed by nickel (0) or copper (0) to obtain the dipyridine ligands induced by the chiral diol. The method is simple and convenient in operation and high in yield. The synthetic method is more practical when being compared with traditional methods.

The invention provides an axially chiral imidazole salt compound and a preparation method thereof. The axially chiral imidazole salt compound has a structural formula shown in the specifications. The technical scheme of the preparation method comprises the following steps of: dissolving a binaphthyl axially chiral imidazole diamine compound in an alcohol acid mixed solvent for acidification, and removing the solvent by evaporation so as to obtain a solid intermediate product; drying the solid intermediate product in a drier which contains P2O5, and dissolving in raw acid trialkyl ester for reaction under the protection of inert gas; and after the reaction is finished, cooling reaction liquid to room temperature, precipitating a solid product, filtering the solid product, and washing with Et2O. The alcohol is absolute methanol or absolute ethanol; and the acid is any one of haloid acid, HBF4, HPF6 or HOTf. The axially chiral imidazole salt compound can be applied to asymmetric oxidation reactions, asymmetric coupling reactions and asymmetric addition reactions.

The invention relates to an axis chiral ligand containing bis-Schiff bases in the field of chemical technology, the structural formula thereof is as follows, in the formula, R1 equals to hydrogen, chlorine, methyl, ethyl, isopropyl, tertiary butyl or alkoxyl with1 to 3 carbons; R2 equals to hydrogen, chlorine, methyl, ethyl, isopropyl, tertiary butyl or alkoxyl with1 to 3 carbons. The invention has the axis chirality of biphenyl compounds, can be applied to asymmetric reactions catalyzed by metals, such as asymmetric cyclopropanation and the like, and has higher reactivity ( can achieve more than 90 percent ) and stereoselectivity ( can achieve more than 85 percent ).

The invention discloses a chiral binaphthalene aza-polycyclic ligand and a preparation method thereof. The ligand has the following structure. The preparation method comprises the following steps: (1)by taking 1, 1 '-binaphthalene 2, 2'-diphenol as a raw material, carrying out methyl protection, Tf2O protection, methylation, aromatic ring substitution and bromination reaction to obtain a 2-bromomethyl -2'-methoxy 1, 1'-binaphthalene derivative (compound V); (2) starting from aza-polycyclic carboxylic acids such as L -or D-proline, L -or D-2-piperidinecarboxylic acid, L- or D-acridine -acid and the like, carrying out derivatization to obtain various amino alcohols (compounds B); and (3) coupling the compound V and the compound B under an alkaline condition and a catalyst, and removing a protecting group to obtain the binaphthalene aza-polycyclic chiral ligand L. The ligand has central chirality and axial chirality at the same time, and can obtain higher reaction activity and enantioselectivity in asymmetric catalytic reaction. The ligands are simple to prepare, raw materials are easy to obtain, and the ligands have important significance for asymmetric synthesis.

The invention discloses an axial chirality-based binaphthol-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene complex and a preparation method thereof. The preparation method comprises the following steps: adding binaphthol into a first solvent, adding sodium carbonate and iodomethane, and performing a reaction so as to obtain 2,2'-dimethoxy-1,1'-binaphthalene; adding the 2,2'-dimethoxy-1,1'-binaphthalene into a second solvent, adding n-butyllithium and N,N-dimethyl formamide at -78 DEG C to 0 DEG C, increasing the temperature to room temperature, and performing a reaction so as to obtain 2,2'-dimethoxy-[1,1'-binaphthalene]-carboxaldehyde; adding the 2,2'-dimethoxy-[1,1'-binaphthalene]-carboxaldehyde into a third solvent, adding 2,4-dimethylpyrrole and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, and performing a stirring reaction; and adding triethylamine and a boron trifluoride diethyl etherate solution, and performing a reaction continuously for 5-10 hours, so as to obtain the desired complex. Through simple synthesis steps, the axial chirality-based binaphthol-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene complex is prepared, the preparation cost is low, the reaction condition is mild, purification is easy, and the synthesized compound has both an axial chirality structure of binaphthol and a fluorescence characteristic of a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene complex.

The invention discloses an axial-chirality bidentate ligand and application thereof in a copper-catalyzed coupling reaction. The structural formula of the axial-chirality bidentate ligand is shown inthe original specification, wherein R is 2-Me or 3-Ome or 32-t-Bu or 32-F or 32, 3, 4-F. The application of the axial-chirality bidentate ligand in the copper-catalyzed coupling reaction comprises thefollowing steps: stirring the ligand and copper salt in diethyl ether for coordination, concentrating and performing spin drying, so as to obtain a catalyst; adding trimethoxyphenyl-silicon and bromobenzene into a 10mL single aperture reaction flask, adding ethanol into the reaction flask for dissolving, adding alkali into the reaction flask and 5mol% of the catalyst, rising the temperature of the reaction to 60-100 DEG C, performing a reaction for 6-12h and directly performing column chromatography after the reaction is ended, so as to obtain a white solid product. According to the axial-chirality bidentate ligand and the application thereof in the copper-catalyzed coupling reaction, the technical problem that how the relatively high yield is obtained under a mild condition can be solved.

Axial chirality diamine compound induced by central chirality, in formula, X and Y are hydrogen, bromine, chlorine, iodine, methyl or aryl. The invention comprises the following steps: reacting 2-iodine-3-nitrophenol with 2,4-pentanediol with central chirality or derivate to gain 2,4-bi[(2-iodine-3-nitryl)phenoxy]pentane; coupling and restoring to gain (S)-[6,6'-((R,R)-2,4-pentanediol oxygen)]-2,2'-biamino-1,1'-biphenyl or (R)-[6,6'-((S,S)-2,4-pentanediol oxygen)]-2,2'-biamino-1,1'-biphenyldiamine; reacting the axial chirality biphenyldiamine induced by central chirality with the halogenating reagent to gain enantiomer pure 3,3'-dihalo or 3,3', 5,5'-tetrahalo axial chirality biphenyldiamine; and then Suzuki coupling enantiomer pure 3,3'-dihalo or 3,3', 5,5'-tetrahalo axial chirality biphenyldiamine to produce enantiomer pure 3,3'-dimethyl or aryl or 3,3', 5,5'-tetramethyl or aryl axial chirality biphenyldiamine. The invention has advantages of easily-gained raw material and simple operation. A series of enantiomer pure diamine produced by the invention can be applied to a series of asymemetric reaction.

The invention discloses a measurement method of an optical purity of 4-(3H)-quinazolinone compound alkaloid, wherein with chiral phosphoric acid as a chiral recognizer, the optical purity of the quinazolinone alkaloid is measured through nuclear magnetic resonance (1H NMR). The method includes the steps of: directly performing measurement and analysis on 1H NMR spectrum with a 4-(3H)-quinazolinonecompound, which has axial chirality, as a recognition object in a deuteration reagent with chiral phosphoric acid as the recognizer. The method can quickly, easily and accurately detect the optical purity of 4-(3H)-quinazolinone compound alkaloid having axial chirality. The invention, for the first time, provides the method for directly measuring the optical purity of 4-(3H)-quinazolinone compound alkaloid having axial chirality through the 1H NMR with the chiral phosphoric acid ((S)-3,3'-bis(1-naphthyl)-1,1'-binaphthol phosphate) as the recognizer. The method has the following advantages: 1)the method is simple in operations; 2) the method can quickly measure the optical purity of the 4-(3H)-quinazolinone compound alkaloid having axial chirality; 3) the method has excellent effect on compatibility of the recognition issue and is high in accuracy.