224results about "Asymmetric syntheses" patented technology

This invention discloses a chiral [oxyindole-pyrrolidine-β-lactam] bispirocyclic compound containing trifluoromethyl groups, with the following structural formula: The preparation includes the following steps: 1. Sequentially adding a metal catalyst, a chiral ligand, a base, indigo-derived trifluoromethylimine ylide, and 3-methylene β-lactam, followed by the addition of an organic solvent to obtain a mixture. The mixture is stirred at a reaction temperature of 0℃ to 50℃. 2. After the reaction is complete, the chiral [oxyindole-pyrrolidine-β-lactam] bispirocyclic compound containing trifluoromethyl groups is obtained through post-processing. The chiral [oxyindole-pyrrolidine-β-lactam] bispirocyclic compound containing trifluoromethyl groups prepared in this application lays a material foundation for in-depth drug activity research based on new drug development.

The invention discloses a chiral 1, 4-diazabicyclo [3.1. 1] heptane derivative as well as a synthesis method and application of the chiral 1, 4-diazabicyclo [3.1. 1] heptane derivative. According to the invention, a 1-azabicyclo [1.1. 0] butane derivative is taken as a raw material, under the catalytic action of a chiral iridium complex, the 1-azabicyclo [1.1. 1] butane derivative and an N-allyl carbonate derivative are subjected to [3 + 2] cycloaddition reaction, a series of chiral 1, 4-diazabicyclo [3.1. 1] heptane skeletons with diversified structures are constructed with high stereoselectivity, and the obtained product has the potential of further derivatization. The method has the advantages of easily available raw materials, mild reaction conditions, simplicity and convenience in operation, good functional group compatibility and the like.

The present invention relates to the preparation of amino acid derivatives VII, including the use of catalysts. The structure of the catalyst disclosed by the invention can be shown as a formula (VI), or the catalyst is loaded on a molecular sieve, and the structure of the catalyst is shown as a formula (I). The invention also discloses preparation of the catalyst and intermediates thereof. A plurality of molecules prepared by the method are all of brand new structures, and are of great significance.

The invention discloses a method for preparing a chiral benzhydrol compound through asymmetric hydrogenation of o-amido benzophenone under catalysis of rhodium. The chiral rhodium catalyst is generated in situ from a metal rhodium salt and a chiral phosphine-phosphoramidite ligand in various solvents. Compared with other methods for synthesizing chiral benzhydrol, the method has the characteristics of cheap catalyst, easiness in preparation of chiral ligand, mild reaction conditions, simplicity and convenience in operation, high yield, high enantioselectivity and the like, and can be applied to large-scale preparation of chiral benzhydrol compounds. The method is also suitable for efficient preparation of the rice plant growth regulation inhibitor (S)-Inabenide, the yield can reach 92%, the enantioselectivity can reach 96%, and the method has good industrial application prospects.

The invention discloses a benzoxphosphine ligand and a complex and application thereof. The structure of the benzoxphosphine ligand is shown as a formula (I), in the formula (I), R1 is alkyl or aryl substituted oxazolidinyl or imidazoline, R2 is alkyl and / or aryl, and R3 is at least one of fluorine, carbazolyl and 2, 6-dimethoxyphenyl. According to the benzoxphosphine ligand disclosed by the invention, the metal iridium complex can be used as a catalyst to be applied to an asymmetric hydrogenation reaction of alpha-phenyl vinyl diethyl phosphate, and has excellent activity and relatively high enantioselectivity; moreover, the benzoxphosphine ligand disclosed by the invention can be directly synthesized from simple and easily available chiral aldehyde, and the preparation method is simple and easy to operate.

The application belongs to the technical field of chemical synthesis, and specifically provides a chiral hydroxyphosphonate, a preparation method and application thereof. The chiral hydroxyphosphonate has a structure as shown in formula II: each R is independently H, an alkyl group, an alkenyl group, an alkynyl group or a halogenated alkyl group; Ar is an aromatic ring or a heteroaromatic ring; X is a bond, -O-, -N(R 1 )- 2 q , -S(=O) m -; the chiral hydroxyphosphonate is obtained by reducing an alpha phosphonate substituted benzocycloalkanone compound through an asymmetric hydrogenation method, has two chiral centers, and has a yield of up to 99% and an enantiomeric selectivity of up to 99%. The chiral hydroxyphosphonate has wide application potential and value in skin tissue soothing, repairing, anti-aging and the like.​

The invention discloses a preparation method of an optically pure mepivacaine hydrochloride intermediate. According to the method, N-(2, 6-dimethylphenyl) pyridine carboxamide is used as a starting material, hydrogenation reduction is carried out in the presence of a ligand and a catalyst to obtain the mepivacaine hydrochloride intermediate ((S)-N-(2, 6-dimethylphenyl) piperidine-2-carboxamide), the ee value of the obtained mepivacaine hydrochloride intermediate can reach 93%, the yield can reach 95%, post-treatment is simple, and the method is suitable for industrial production. The method is very suitable for large-scale workshop production. The ligand used in the invention is cheap and easily available, and can be refined and recovered through column chromatography, and the catalytic effect of the recovered ligand is consistent with that of a newly purchased ligand.

This invention belongs to the field of organic synthesis technology and relates to a precursor of an obisec key intermediate and a method for preparing the key intermediate. The method involves a [4+2] cycloaddition reaction of 4-trifluoromethylaniline, propionaldehyde, and N-vinylformamide under the catalysis of chiral phosphoric acid, yielding the obisec key intermediate precursor with high enantioselectivity. N -((2) R 4 S )-2-ethyl-6-trifluoromethyl-1,2,3,4-tetrahydroquinoline-4-yl)formamide; subsequently, the key intermediate of obisetri can be obtained through a deprotection reaction under acidic conditions. The method provided by this invention uses a small amount of chiral catalyst and commercially available reagents to efficiently obtain the key intermediate of obisetri in just two steps. R 4 S )-2-ethyl-6-trifluoromethyl-1,2,3,4-tetrahydroquinoline-4-amine; under mild conditions without the need for chiral resolution, the utilization of starting materials is greatly improved, thereby significantly increasing the yield of the target product and the economic efficiency of the process.

The application provides a kind of plane chiral boronic acid compound based on cycloaralkane skeleton and its synthesis method and application, the plane chiral compound has the structure shown in formula I;R 1 It is selected from one of C1-C8 alkyl, C1-C8 alkoxy, C1-C20 aryloxy.R 2 It is selected from one of hydrogen, fluorine, methyl, ethyl, methoxy, ester group, nitro group, phenyl, benzyl, tert-butyl, isopropyl.The application can effectively synthesize plane chiral boronic acid catalyst based on cycloaralkane skeleton, and the plane chiral boronic acid catalyst based on cycloaralkane skeleton can realize diol desymmetrization reaction.

The application belongs to the technical field of asymmetric catalytic synthesis, and particularly relates to an alpha-carbon chiral phosphine compound and a preparation method thereof. In a protective gas atmosphere, an asymmetric boron protonation reaction is carried out on a dienyl phosphine oxide compound shown in a structure of formula II, pinacol borate, a copper (I) catalyst, a chiral ligand, an organic alkaline compound and a proton additive in a polar organic solvent to obtain an alpha-carbon chiral phosphine compound shown in a structure of formula I; the chiral ligand is a cyclic phosphine ligand (S, S)-Ph-BPE or a cyclic phosphine ligand (R, R)-Ph-BPE. The preparation method provided by the application can synthesize the alpha-carbon chiral phosphine compound shown in the structure of formula I with high yield and excellent enantioselectivity, the synthesis method is simple and low in cost, and the alpha-carbon chiral phosphine compound can be further converted into a new optically active product.

Provided is a method for efficiently producing a fluorinated alkyl compound by directly converting an aliphatic alkylamine widely existing in nature into a fluorine substituent, the method being characterized in that an alkylamine compound in which at least one amino group is bonded to an alkyl carbon is reacted with a deamination-fluorination agent to produce the fluorinated alkyl compound.

The invention discloses an efficient synthesis method of ephedrine hydrochloride, and belongs to the technical field of pharmaceutical chemistry synthesizing.A self-synthesized chiral zinc oxide nanoflower composite catalyst is added in the synthesis process of the ephedrine hydrochloride, and the composite catalyst has a chiral function, is large in pore and surface area, easy to recover and not prone to blockage, and can be used for preparing a chiral zinc oxide nanoflower catalyst. Compared with a traditional Lewis acid type catalyst, the catalyst has the advantages that keto groups in ephedrine hydrochloride synthesis can be precisely reduced, and hexadecyl trimethyl ammonium bromide is intercalated on the surface, so that the catalyst is not easy to agglomerate in a catalytic system, and the yield of a product is further improved; according to the composite catalyst, through hexadecyl trimethyl ammonium bromide, the surface hydrophilicity and hydrophobicity of the composite catalyst are regulated and controlled, the composite catalyst is dispersed more uniformly and makes contact with a compound II more sufficiently, the speed and selectivity of a reductive amination reaction are improved, and the hexadecyl trimethyl ammonium bromide can intercalate mica lamellas, so that the mica lamellas are peeled off, the interlayer spacing is increased, and therefore the composite catalyst is more stable in performance. And the reaction sites are increased, so that the catalytic active center is loaded more stably.

The application belongs to the technical field of organic chemical synthesis, and particularly relates to a nitrogen center chiral base derivative, a preparation method and application thereof. The preparation method of the nitrogen center chiral base derivative provided by the application can effectively synthesize a base with only a nitrogen chiral center by using a tetrahydrodibenzo-diazocine compound as a raw material and through chiral phosphoric acid catalyzed amination reaction. Moreover, the synthesis method provided by the application has the advantages of high efficiency, simple steps and strong enantioselectivity, is suitable for industrialized production of chiral bases and derivatives thereof, and provides a new approach for research and application of chiral compounds. Meanwhile, the base derivative prepared by the application is a base molecule with a nitrogen center chirality, and has wide application prospects in the fields of molecular recognition, DNA binding, supramolecular chemistry, material science, asymmetric catalysis and drug development.

The invention provides a preparation method of a novel chiral thiourea / phosphine bifunctional organic catalyst with a cis-cyclic 1, 2-phosphinamine skeleton and application of the novel chiral thiourea / phosphine bifunctional organic catalyst in an asymmetric catalytic reaction. The chiral organic catalyst is prepared by taking cis chiral 2-(diphenylphosphine)-1, 2, 3, 4-tetrahydro-1-naphthylamine and an isothiocyanate compound as raw materials through a one-step reaction under a mild condition. The chiral thiourea / phosphine bifunctional organic catalyst is simple to prepare and stable in property, and shows excellent catalytic activity and stereoselectivity in an asymmetric hydrosilylation reaction of o-amido benzophenone.

The invention aims to establish a synergistic catalytic system in which catalysts cannot coexist. The amide chiral catalyst is prepared through a series of synthesis. The hollow mesoporous COF-carboxylic acid / chiral amide multi-catalyst is prepared by a hydrothermal method. The morphology and the structure of the material are characterized by using a scanning electron microscope, a transmission electron microscope, an X-ray diffractometer, a specific surface instrument, an infrared spectrometer and the like, an asymmetric tandem-addition reaction is catalyzed to construct a chiral acetal compound, high performance liquid chromatography analysis is combined, and multiple catalysts are continuously recycled. Results show that the hollow mesoporous COF-carboxylic acid / chiral amide multi-catalyst not only has good morphology, excellent specific surface area and high porosity, but also enables contradictory catalysts to coexist for synergistic catalysis. The catalyst can be used for rapidly catalyzing an asymmetric tandem-addition reaction, high selectivity of ee = 99% and high yield of 98% are achieved, and the catalyst can be repeatedly used for 10 times. The method is green, environment-friendly, low in cost and suitable for concerted catalysis of catalysts which cannot coexist.

This invention discloses an amorphous aluminum-nickel catalyst synergistically modified with rare earth and chiral ligands and its application in asymmetric hydrogenation, belonging to the field of catalyst technology. The catalyst comprises nickel, aluminum, boron, rare earth elements, and chiral ligands, and possesses an amorphous structure. The chiral ligands coordinate with nickel atoms on the catalyst surface through their coordinating atoms, with the rare earth elements located within the coordination range of the ligands, forming a nickel-ligand-rare earth bridging structure that synergistically regulates the stereoelectronic environment of the catalytic center. The catalyst preparation method includes steps such as chemical reduction and double quenching to prepare an amorphous alloy precursor, gradient alkaline leaching activation to form a porous structure, chiral ligand modification, and passivation protection. The catalyst of this invention can be used in the asymmetric hydrogenation reaction of unsaturated compounds such as unsaturated ketones, aromatic ketones, and imines, achieving high conversion rates and high enantioselectivity, and can be recycled multiple times without significant performance degradation, showing promising industrial application prospects.

The application discloses a kind of plane chiral [2.2] paracyclophanane monophosphine ligand pEPCP and preparation method and application thereof, it is related to chemical catalysis technical field, and its technical scheme main points are as follows: including racemate or enantiomer, the structural formula-I of the monophosphine ligand pEPCP of the application is as follows: [2.2] paracyclophanane skeleton containing monophosphine ligand pEPCP of the application, with two benzene rings in para position by two ethylene connection unique big steric hindrance, electron-rich rigid skeleton, different types ether substituent group is introduced in structure, change the electron cloud density and steric hindrance of aromatic ring directly connected by phosphine ligand.In addition, ether substituent group can also be used as weak coordination group, participate in adjusting ligand chelate dihedral angle.This makes metal, ligand and substrate form the most suitable coordination environment in catalytic process, so that corresponding catalytic reaction has the advantages such as high reactivity, good enantioselectivity, substrate universal range is wide, especially suitable for transition metal catalyzed asymmetric coupling reaction, with economic practicability and industrial application prospect.

The present invention relates to an asymmetric catalytic hydrogenation synthesis method for a brivaracetam intermediate. The synthesis method comprises the step of: in a hydrogen atmosphere, in a solvent, a compound represented by formula I is subjected to asymmetric hydrogenation reduction in the presence of an alkali and a catalyst which is formed by a planar chiral metallocene ligand and a ruthenium salt to form a compound as represented by formula II, wherein the reaction formula is shown below. In the present invention, the catalyst used in the asymmetric catalytic hydrogenation synthesis method has low cost, the conversion rate of raw materials is high, and the DR value of the obtained final product can reach 99: 1 or above; and the present invention is suitable for industrial production

The present invention provides chiral pyridinium salt carbonyl catalysts and methods for their preparation and use. The general structural formula of the catalyst is [Formula 1] TIFF2026501952000195.tif36170[where, R 1 Structural formula of [chemical 2] TIFF2026501952000196.tif25170X 1-6 is N or CR 6-11 Including, R 2 , R 4 , R 6-11 is hydrogen, C 1~24 alkyl groups, alkoxy groups, [C3] TIFF2026501952000197.tif7170 groups, [C4] TIFF2026501952000198.tif14170, [C5] TIFF2026501952000199.tif14170 [6] TIFF2026501952000200.tif14170, CO2R d , halogen, nitro group, cyano group or trifluoromethyl group, R 3 is a substituted or unsubstituted C 1~24 The alkyl group may be substituted with halogen or C 1~10 Alkyl groups of C 3~10 cycloalkyl or aryl group, C 1~8 carbonyl group, C 1~8 a sulfonyl group or a phosphoryl group of C 1~10 The carbonyl group includes an aldehyde group, a ketocarbonyl group, an estercarbonyl group, a carboxyl group, or an amide group; R 5 Structural formula of [C7] TIFF2026501952000201.tif18170X - is an anion] Compared with the prior art, the catalyst of the present invention can be used in the biomimetic aldol reaction of amino acid derivatives to synthesize a series of β-hydroxy-α-amino acid compounds with extremely high enantioselectivity.

The embodiment of the invention relates to the technical field of synthesis of organic compounds, and particularly discloses a tryptophan derivative and a preparation method thereof, and the tryptophan derivative comprises the following raw materials: 4-methyl phenyl sulfonyl indole, 4-methyl-5-oxazolone and a proper amount of chiral catalyst. According to the embodiment of the invention, sulfuryl indole can be converted into a vinyl imine intermediate with unstable chemical properties after being treated by an alkaline reagent, and then 5-oxazolone is used as a nucleophilic reagent and is added onto the vinyl imine intermediate to synthesize the alpha, beta-substituted tryptophan derivative. According to the synthetic route provided by the embodiment of the invention, the raw materials are cheap and easy to obtain, the price is low, the reaction steps are simple, the conditions are mild, the yield is also greatly improved, the problems of harsh related synthetic reaction conditions and lower yield in the existing scheme for preparing the tryptophan derivative by adopting a chemical synthesis method are solved, and the synthetic route has a wide market prospect.

This invention discloses chiral hydroxymethylpyridine-sulfonated imidazolidine ligands (HmPy-Sulidines). The invention involves a condensation reaction between the corresponding sulfonated (R,R)-diphenylethylenediamine 1 and chiral hydroxymethylpyridine-formaldehyde 2 to generate the target product, chiral hydroxymethylpyridine-sulfonated imidazolidine ligands (HmPy-Sulidines). These ligands contain a hydroxymethylpyridine group and an imidazolyl group (the nitrogen atom of hydroxymethylpyridine and the oxygen atom of the hydroxyl group, the tertiary amine nitrogen atom of the imidazolidine being an electron-rich coordination site, and the N-H of the imidazolidine participating in hydrogen bonding). They can form five-membered ring coordination with Lewis metals, thereby generating chiral ligand-metal complexes, which can be used as chiral ligands in asymmetric catalytic reactions. Therefore, they have significant application value in the field of asymmetric catalytic synthesis, and their synthetic method is very economical and simple. They also exhibit good air stability, wide applicability, and good compatibility with various substituents.

This invention provides a class of general-purpose chiral catalysts containing a cinchona primary amine arylformamide skeleton, along with their preparation methods and applications, belonging to the field of catalytic materials technology. The chiral catalysts provided by this invention link cinchona primary amine with oxazole / thiazole / imidazolium formamide structural units capable of coordination. Through the coordination of the oxazole / thiazole / imidazolium and amide coordinating groups with the central metal, they act as chiral ligands to catalyze a wider range of asymmetric reactions. They can also be used alone as chiral small-molecule catalysts for cinchona-like tertiary amine (thiourea) and square amides to catalyze asymmetric organic reactions. Furthermore, they can achieve synergistic (co-catalytic) catalysis of small molecules and metals in the same reaction system through different combinations. These chiral catalysts can be widely used as Lewis bases, Lewis acids, or small-molecule chiral catalysts and chiral ligands, possessing potential scientific and applied value in chiral sciences such as asymmetric catalysis, chiral synthesis, and chiral resolution.

The invention discloses a preparation method of a chiral fluorine-containing alkyl nitrile compound, and particularly provides a preparation method of a compound shown as a formula III. The preparation method provided by the invention can realize common terminal olefin asymmetric fluorine-containing alkyl cyanidation reaction, and has one or more of the following advantages: mild reaction conditions, good regioselectivity, high enantioselectivity, wide substrate universality and good functional group compatibility.

The present invention relates to a chiral pyridinium salt carbonyl catalyst, a preparation method therefor and applications thereof. The catalyst has a general structural formula of: wherein R1 has a structural formula of: X1-6 are each independently N or C-R6-11; R2, R4, and R6-11 each comprise hydrogen, C1-24 alkyl, alkyloxy, (CH2)m, CO2Rd, halogen, nitro, cyano or trifluoromethyl; R3 comprises substituted or unsubstituted C1-24 alkyl, the substituent comprises halogen, C1-10 alkyl, C3-10 cycloalkyl or aryl, C1-8 carbonyl, C1-8 sulfonyl or phosphoryl, or C1-10 alkoxy or amino, and the carbonyl comprises aldehyde group, ketone carbonyl, ester carbonyl, carboxyl or amido; R5 has a structural formula of: X- is an anion. Compared with the prior art, the catalyst of the present invention is applied to the biomimetic aldol reaction of amino acid derivatives to synthesize a series of β-hydroxy-α-amino acid compounds having extremely high enantioselectivity.

The application provides a preparation method of high-optical-purity piperlongumin, characterized by the following steps: 2H-pyrane-2,4(3H)-dione and styrene are used to generate a corresponding chiral intermediate under the catalysis of a transition metal and a chiral phosphoric acid ligand, and then the chiral intermediate is subjected to etherification to obtain high-optical-purity piperlongumin; the process is simple, efficient, high in yield, green and environment-friendly, and is suitable for large-scale industrial production.

The invention discloses a method for synthesizing a five-membered lactam skeleton bulk drug with high optical purity under the catalysis of rhodium, which is characterized in that racemic and cheap gamma-substituted alpha, beta-unsaturated gamma-lactam is used as a raw material, a dicyclooctene hydroxyl rhodium (I) dimer is used as a catalyst, a cheap chiral phosphine ligand is used as a ligand, and the raw material is synthesized by a one-step method. The high enantioselectivity arylation reaction with arylboronic acid is realized. According to the method, the optical purity limit of a traditional route is successfully broken through, the specific rotation of the obtained trans-beta, gamma-disubstituted gamma-lactams with three single configurations is remarkably higher than the highest value in the literature, and a high-enantioselectivity key synthesis building block is provided for synthesis of a protein kinase C regulator, a glutamate receptor antagonist and CGN-10100. The method provided by the invention is simple and easy to operate, mild in reaction condition, high in yield and strong in derivation ability, and provides a new method for efficient and high-enantioselectivity preparation of chiral bulk drugs.

This invention relates to the field of pharmaceutical intermediates, and in particular to a method for synthesizing chiral indane. The method uses indane as a raw material, synthesizes an oxime, then an enamine, and subsequently synthesizes the trans-chiral indane via an asymmetric hydrogenation reaction using a ruthenium chiral bisphosphine catalyst, achieving high yield and high stereoselectivity. The advantages of this invention are: in the asymmetric hydrogenation reaction of the enamine, the trans-chiral indane is obtained with a content greater than 97%, an ee of 95%, and a yield greater than 90%; the catalyst is readily available; the operation is simple; the raw materials are readily available; there is minimal pollution from waste; and energy consumption is low, making it suitable for industrial production.

Disclosed is a method for preparing enantiomerically enriched compound 1, which involves chiral salt resolution of compound 1, or intermediate INT 1f or intermediate INT 1g. Compound 1 is useful for treating diseases or conditions, such as cancer, particularly diseases or conditions dependent on the activity of membrane-bound tyrosine- and threonine-specific cdc2 inhibitory kinase (Myt1). JPEG2025542335000078.jpg43170