131 results about "Asymmetric hydrogenation" patented technology

The invention provides a novel chiral ferrocene bridged binaphthyl skeleton phosphine ligand and application thereof. The ligand has the advantages of low cost, simplicity in synthesis, air stability and the like. The ligands have good catalytic activity and enantioselectivity in the asymmetric hydrogenation reaction of ketone, and have certain industrial application prospects in the synthesis of pharmaceutical molecules.

The invention belongs to the technical field of asymmetric catalysis, and discloses a chiral phosphine nitrogen-nitrogen tridentate ligand based on a ferrocene skeleton as well as a preparation method and application of the chiral phosphine nitrogen-nitrogen tridentate ligand. The structural formula of the ligand is shown as (I) or an enantiomer (II) of the ligand. The preparation method comprises the steps of acylation reaction, oxazoline ring construction, aldehyde group introduction, reductive amination and the like, and application in asymmetric hydrogenation reaction, such as asymmetric hydrogenation of aryl ketone. The ligand has a plurality of chiral factors, simultaneously has a potential hydrogen bond donor, forms secondary interaction with a substrate in an asymmetric catalytic reaction, can further stabilize a reaction transition state, is an efficient novel chiral P, N, N-ligand, has the advantages of high reaction activity, good stereoselectivity, wide substrate range and the like, and has a wide application prospect. # imgabs0 #

The invention relates to a preparation method of (S, S)-2, 8-diazabicyclo [4, 3, 0] nonane and an intermediate of the (S, S)-2, 8-diazabicyclo [4, 3, 0] nonane. Specifically, the invention discloses a method for preparing (S, S)-2, 8-diazabicyclo [4, 3, 0] nonane from a cheap raw material 2-chloronicotinic acid through an esterification reaction, a substitution reaction, a reduction reaction and an asymmetric hydrogenation reaction, and the method is novel in route, simple to operate, high in product yield, good in purity, safe, environment-friendly and very suitable for industrial production.

The invention discloses a method for preparing chiral succinimide through asymmetric hydrogenation of alpha-alkylene succinimide under the catalysis of nickel. The method comprises the following steps: in a solvent, under certain hydrogen pressure and temperature, alpha-alkylene succinimide represented by a general formula (1) is hydrogenated into a chiral succinimide compound represented by a general formula (2) by a nickel chiral catalyst; the structural formulas of the general formulas (1) and (2) are shown in the specification. The method is mild in reaction condition, simple and convenient to operate, capable of achieving good yield and efficiency and wide in application prospect.

This invention discloses a chemical preparation method for pharmaceutical-grade dexborneol. The method employs Noyori asymmetric hydrogenation, asymmetric reduction of camphor, and the use of ruthenium as a catalyst. Under the action of phosphine ligands, dexborneol and a small amount of its isomer, isoborneol, are prepared. Then, under the action of trimethylchlorosilane, dexborneol, due to its spatial configuration, can form a silicon-oxygen bond with TMS, while isoborneol cannot. Isoborneol is removed by recrystallization to obtain a silyl ether protected compound of dexborneol. Dexborneol is then prepared under hydrochloric acid conditions and purified by recrystallization to obtain highly purified dexborneol. This route features mild reaction conditions, does not use highly toxic materials, and has a high yield, meeting the requirements for pharmaceutical-grade dexborneol.

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 phosphorus-containing oxynitride compound based on a cycloarane skeleton and a ferrocene skeleton and a preparation method and application thereof, the phosphorus-containing oxynitride compound based on the cycloarane skeleton and the ferrocene skeleton is selected from at least one of compounds with structural formulas as shown in a formula I and a formula II, wherein Ar is independently selected from phenyl and C7-C15 substituted aryl; the substituent group of the substituted aryl group is selected from one of C1-C4 alkyl groups and methoxyl groups. According to the invention, a class of novel phosphorus-nitrogen-oxygen-containing compounds which have two planar chirality and are based on the cycloarane skeleton and the ferrocene skeleton can be effectively synthesized; as a ligand, the compound shows excellent catalytic activity and enantioselective control ability in asymmetric hydrogenation of an iridium-catalyzed N-aryl indolone compound or a heterobiaryl ketone compound.

Methods for the asymmetric hydrogenation of the trisubstituted olefin in THC are disclosed. The methods disclosed herein can be performed in conventional organic solvents or in water under modified Pickering catalysis conditions. The methods disclosed herein provide improved selectivity over standard industrial conditions with decreased reaction times under ambient conditions.

The present invention relates to a process for the enantioselective preparation of chiral 4-substituted 2-oxazolidinones of formula (la) or (lb) via asymmetric hydrogenation of the corresponding 4-substitued 2-oxazolones of formula (II) using a combination of palladium or nickel and a chiral bidentate P-ligand as catalyst. The oxazolidinones can then be converted to important chiral building blocks such as enantiopure chiral aminoalcohols and haloamines via decarboxylative ring opening reaction.

The application belongs to the technical field of glabridin preparation, and particularly relates to a preparation method of R-glabridin, which comprises the following steps: S1, under a protective gas atmosphere, dissolving a glabridin racemate in an organic solvent A, and reacting with a halogenated reagent through a substitution reaction, and after purification, preparing a halogenated intermediate I; S2, under the protective gas atmosphere, dissolving the halogenated intermediate I prepared in S1 in an organic solvent B, and under alkaline conditions, preparing an intermediate II through a dehalogen olefination reaction, and after purification; S3, under a hydrogen atmosphere, dissolving the intermediate II prepared in S2 in an organic solvent C, and under the action of a catalyst, preparing R-glabridin through an asymmetric hydrogenation reaction, and after purification. The method has the advantages of multiple raw material sources, obvious cost advantage, convenient preparation method, high total yield, less waste and high purity, and is beneficial to industrialization.

According to the method, an enamine intermediate (2Z)-4-oxo-4-[3-(trifluoromethyl)-5, 6-dihydro-[1, 2, 4] triazolo [4, 3-a] pyrazine-7 (8H)-yl]-1-(2, 4, 5-trifluorophenyl) butyl-2-ene-2-amine is used as an initial raw material, and the Sitagliptin is synthesized through synergistic catalysis asymmetric hydrogenation of a cobalt catalyst and a chiral ligand. The R-configuration sitagliptin is prepared by one step, the reaction yield and stereoselectivity are high, the catalytic reaction effect is good, the cost is low, and the method is suitable for industrial large-scale production.

The application provides a preparation method and application of a novel ferrocene pyridine hydrazine manganese complex. The manganese complex has multiple advantages such as low cost, simple synthesis and air stability. Meanwhile, the provided manganese complex can be applied to an asymmetric hydrogenation reaction and has certain industrial application prospect.

The application relates to the technical field of chemical synthesis, and particularly discloses a method for constructing cycloalkanol by nickel-catalyzed asymmetric hydrogenation of tri-substituted enone, and a chiral alcohol prepared by the method. The method uses alpha, beta-unsaturated ketone with different molecular structures as a substrate to construct chiral alcohol with double chiral centers, hydrogen is added to reduce the enyl group first, and then hydrogen is added to reduce the carbonyl group. In the case that the hydrogen on the carbon in the conjugated ring is replaced by different substituents, good reduction effect can be obtained. The catalyst has simple preparation mode and stable performance, and good chiral selection effect and conversion rate can still be obtained under the condition of high substrate / catalyst.

The invention discloses a chiral P, N, N-tridentate ligand based on a ferrocene skeleton as shown in a formula I, a preparation method of an iridium catalyst containing the ligand and application of the ligand in preparation of a carbon-nitrogen axial chiral compound and a diltiazem intermediate. According to the present invention, the chiral P, N, N-tridentate ligand based on the ferrocene skeleton and the metal iridium precursor [Ir (COD) Cl] 2 are subjected to complexation to obtain the complex as the iridium catalyst, and the catalyst can be used as the iridium catalyst with characteristics of high yield (up to 99%), high enantioselectivity (up to gt; 99% ee) and high diastereoselectivity (up to gt; according to the method, N-aryl indolal or N-aryl indolone is subjected to asymmetric hydrogenation by using N-aryl indolal or N-aryl indolone (R1, R2, R3, R4, R5, R6, R7, R7, R8, R9, R9, R9, the catalyst can also be applied to asymmetric synthesis of diltiazem intermediate (2R, 3S)-3-(4-methoxyphenyl)-2, 3-epoxidized propionate, has the advantages of short synthesis route, high yield, good stereoselectivity (as high as 99% ee, 97 / 3dr) and the like, and has better economic and social benefits.

The invention provides a method for preparing chiral amine by catalyzing asymmetric hydrogenation of aromatic imine through a manganese / chiral ferrocene P, N, N ligand. The manganese precursor and ligand adopted by the method are easy to obtain, the reaction condition is mild, the operation is simple, the target chiral amine compound can be obtained with high yield and high stereoselectivity, and continuous large-scale preparation can be realized. The catalyst system is high in activity, the molar ratio of imine to the catalyst can reach 100000: 1, and the catalyst has a very good industrial application prospect.

The invention belongs to the technical field of organic synthesis, and particularly discloses a modified ChiraPhos type diphosphine ligand and a preparation method and application thereof.The modified ChiraPhos type diphosphine ligand is modified on the basis of a ChiraPhos ligand, naphthyl is introduced into the structure, the chiral recognition effect of a catalyst formed by the naphthyl and rhodium is better, and the catalytic activity of the catalyst is improved. A higher ee value can be induced to be generated in synthesis of an L-menthol key intermediate (R)-citronellal. The invention further provides a specific preparation method of the modified ChiraPhos type diphosphine ligand, and the modified ChiraPhos type diphosphine ligand is obtained from cheap and easily available raw materials through simple and convenient operation. The diphosphine ligand is used for a reaction for preparing (R)-citronellal through asymmetric hydrogenation of citral under rhodium catalysis, the (R)-citronellal with the ee value higher than that of a traditional rhodium catalysis system can be obtained through citral (E / Z = 90: 10) with cis-trans isomers mixed, and a certain foundation is laid for further reducing the industrial production cost of the (R)-citronellal.

The present invention provides a class of novel chiral benzene-ring framework phosphine-1,2-diphenylethylenediamine ligands, their preparation methods, and their applications in asymmetric hydrogenation reactions. 2-Diphenylphosphinobenzaldehyde and 1,2-diphenylethylenediamine are added to a Schlenk flask in a molar ratio of 1:1.2. After filling with nitrogen, methanol (0.2 M) is added. The resulting mixture is refluxed at 80 °C for 1-2 hours. After cooling to room temperature, 2 equiv. of NaBH4 is added, and then the mixture is refluxed again at 80 °C for 3-4 hours. After cooling to room temperature, water is added to the reaction solution, and then extracted with dichloromethane, dried over anhydrous sodium sulfate. After removing the solvent, the desired chiral benzene-ring framework phosphine-1,2-diphenylethylenediamine ligand is obtained by column chromatography. The catalysts formed by the chiral ligands of the present invention and metal precursors such as Ir- and Ru- have excellent catalytic activity and stereoselectivity in the catalytic asymmetric hydrogenation reactions of C=C, C=N, and C=O double bonds, with an enantioselectivity of up to 99% ee and a TON of up to 100,000.

The key intermediate of brivaracetam was synthesized by the ruthenium-catalyzed asymmetric hydrogenation of unsaturated cyclobutanone esters, which features high yield, high ee value, mild reaction conditions, low catalyst dosage, and can be scaled up to gram scale, showing great potential application value.

The present invention relates to a stable equivalent body of 2, 2 ''-bis (1-phosphinoethyl)-1, 1''-diferrocene, which is useful as a ligand in various catalytic reactions including aromatic asymmetric hydrogenation, but is difficult to synthesize and / or separate and purify, and a method for efficiently producing the same, and more particularly, to a stable equivalent body of 2, 2 ''-bis (1-phosphinoethyl)-1, 1''-diferrocene, which is useful as a ligand in various catalytic reactions including aromatic asymmetric hydrogenation. The present invention provides: a diphosphine-diborane complex represented by general formula (1) (BH3) 2); and a method for producing the diphosphine-diborane complex, the method comprising reacting a magnesium source and an oxidizing agent with a phosphine-borane complex in this order.

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.

The invention relates to the field of asymmetric catalytic hydrogenation, in particular to an asymmetric hydrogenation kinetic resolution method of racemic polysubstituted three-membered ring imine, which is characterized by comprising the following steps: in the presence of a chiral diamine metal catalyst, carrying out asymmetric hydrogenation kinetic resolution on racemic polysubstituted three-membered ring imine; the method comprises the following steps: carrying out asymmetric hydrogenation treatment on a mixture containing enantiomers of the multi-substituted three-membered cyclic imine compound by adopting hydrogen to obtain a single optical isomer of the multi-substituted chiral aziridine compound and / or the multi-substituted chiral three-membered cyclic imine compound; wherein the polysubstituted three-membered cyclic imine compound is a compound as shown in a formula (1), and the polysubstituted chiral aziridine compound is a compound as shown in a formula (2). According to the method disclosed by the invention, the resolution of the racemic polysubstituted three-membered cyclic imine compound is realized in an asymmetric hydrogenation manner, and a polysubstituted chiral aziridine compound with certain optical purity and a single optical isomer of the polysubstituted chiral three-membered cyclic imine compound can be obtained at the same time.

This invention discloses a palladium-catalyzed asymmetric hydrogenation method for synthesizing chiral dihydrocoumarin from tetrasubstituted olefins. The method uses a chiral bisphosphine complex of palladium as a catalyst and a tetrasubstituted olefin as a substrate to synthesize chiral dihydrocoumarin via asymmetric hydrogenation. This invention employs a homogeneous palladium catalytic system to achieve asymmetric hydrogenation of tetrasubstituted olefins with high yield, high enantioselectivity (up to 99% enantiomeric excess), and high diastereoselectivity (diastereomer ratio >20:1), producing chiral dihydrocoumarin. The method is simple and practical, the catalyst is commercially available, the reaction conditions are mild, energy consumption is low, and it is environmentally friendly.

The present invention relates to the field of pesticide chemistry technology, and in particular, to a method for selectively and asymmetrically hydrogenating 4-substituted-1,2-dihydroquinoline and use thereof. The present invention discloses a selective, asymmetric hydrogenation reaction conducted on 4-substituted-1,2-dihydroquinoline in the presence of a chiral ligand and a rhodium catalyst. The selective, asymmetric hydrogenation method features ease to operate, a higher conversion rate, and higher enantioselectivity.

The present invention belongs to the technical field of biological catalysis and organic synthesis, and in particular, relates to an imine reductase mutant, application thereof and an application method therefor. The imine reductase mutant has an amino acid sequence derived by a mutation occurring to an amino acid sequence as set forth in SEQ ID NO. 1, and an mutation site includes one of the following sites: position 44 with G mutating into V, or position 89 with L mutating into V, or positions 44 and 89 with G and L simultaneously mutating into V, respectively. The imine reductase mutant of the present invention binds to glucose dehydrogenase to prepare an intermediate (S)-2-methyl-5-(pyrrol-2-yl)pyridine through asymmetric hydrogenation reduction by taking β-nicotinamide adenine dinucleotide disodium salt as a coenzyme and 5-(3,4-dihydro-2H-pyrrol-5-yl)-2-methylpyridine as a substrate, with a chemical conversion rate up to above 99.5% and e.e. % up to 99.6%.

The invention provides a novel chiral phosphine-phosphoramidite ester ligand which is based on an achiral methylene bisphenol phosphoramidite ester structural unit and only has skeleton single-center chirality, and a preparation method and application thereof. Different from a traditional chiral phosphine-phosphoramidite ester ligand, the novel chiral phosphine-phosphoramidite ester ligand has the advantage that a phosphoramidite ester structural unit in the novel chiral phosphine-phosphoramidite ester ligand does not have a chiral element. The novel ligand is prepared by taking a chiral phosphine / amine intermediate (R)-or (S)-DPPNHMe, a methylene bisphenol compound and PC13 as raw materials under a mild condition. The novel chiral phosphine-phosphoramidite ligand provided by the invention has the characteristics of cheap and easily available raw materials, simple synthesis, stable properties, adjustable space structure and electronic properties, excellent activity and enantioselectivity in catalysis of asymmetric hydrogenation reaction, and the like.

The invention comprises chiral aminophosphine ligands of the formula I, iridium catalysts containing the chiral aminophosphine ligands of the formula I, of the formula II or III;, and the use of the iridium catalysts in the asymmetric hydrogenation of a compound, containing at least one prochiral keto group preparation and the formation of chiral alcohols.

The invention relates to a synthesis method of (S)-2, 2, 4-trimethyl pyrrolidine hydrochloride, which comprises the following steps: step a, carrying out Michael addition reaction on a compound 10 and a compound 11 in the presence of a solvent to prepare a compound 12; b, the compound 12 and ethyl bromoacetate are subjected to an affinity substitution reaction under the alkaline and solvent conditions, and a compound 13 is prepared; c, carrying out condensation ring closing reaction on the compound 13 under alkaline and solvent conditions to prepare a compound 14; step d, the compound 14 is subjected to a decarboxylation reaction under the acidic condition, and a compound 15 is prepared; e, the compound 15 is subjected to Wittig reaction under the alkaline condition, and a compound 16 is prepared; and step f, carrying out asymmetric hydrogenation reaction on the compound 16 to prepare a target compound 1, namely (S)-2, 2, 4-trimethylpyrrolidine hydrochloride. According to the synthetic method of the (S)-2, 2, 4-trimethylpyrrolidine hydrochloride, the reaction type of the whole synthetic route is safe, the yield of each step is relatively high, and industrial production is convenient to realize.

This invention provides a method for preparing chiral N-tert-butylsulfonamide compounds. The method uses N-tert-butylsulfonylimide as a starting material, employs Mn(CO)₅Br and a chiral PNN ligand as catalysts, and an alcohol as a solvent. A hydrogenation reaction occurs in this homogeneous catalytic system, yielding axially chiral diaryl nitrophenol compounds in high yield (99%) and with high ee values ​​(>99%). This reaction has the advantages of high efficiency, mild conditions, and environmental friendliness. The obtained chiral N-tert-butylsulfonamide can be deprotected with a sulfonyl protecting group to obtain the corresponding chiral primary amine.