Abstract: A chiral bimetallic cooperative catalysis system and use thereof in asymmetric synthesis of bedaquiline are provided. Specifically, the chiral bimetallic cooperative catalysis system is formed by a metallic lithium, sodium or potassium salt and another metal salt under the action of a suitable ligand and an additive. By means of the chiral bimetallic cooperative catalysis system, an addition reaction of 6-bromo-3-benzyl-2-methoxyquinoline (I) and 3-dimethylamino-1-naphthyl-1-propanone (II) is promoted, the selectivity is regulated, and a target product, (1R,2S)-bedaquiline, with high yield and high selectivity is obtained for the first time.

Abstract: A low-temperature continuous-flow preparation method of bedaquiline includes the following steps. (a) A first feed liquid and a second feed liquid are subjected to a first continuous flow reaction for 30-600 seconds to obtain a first reaction mixture. (b) The first reaction mixture and a third feed liquid are subjected to a second continuous flow reaction for 30-600 seconds to obtain a second reaction mixture. (c) The second reaction mixture was quenched to afford bedaquiline.

Abstract: A low-temperature continuous-flow preparation method of bedaquiline includes the following steps. (a) A first feed liquid and a second feed liquid are subjected to a first continuous flow reaction for 30-600 seconds to obtain a first reaction mixture. (b) The first reaction mixture and a third feed liquid are subjected to a second continuous flow reaction for 30-600 seconds to obtain a second reaction mixture. (c) The second reaction mixture was quenched to afford bedaquiline.

Abstract: The present disclosure provides a cutting method of a display module, including: providing a display module to be cut, the display module to be cut including a display panel and a spacing layer on the display panel, and the display panel including a region to be cut, the spacing layer being provided with a first through hole exposing the region to be cut, and the first through hole being provided therein with an encapsulation adhesive; and performing laser cutting on the display module to be cut at a position of the region to be cut so as to remove the region to be cut to form a cutting groove. In the laser cutting, at least part of the encapsulation adhesive is melted and covers a sidewall of the cutting groove.

Abstract: A method for catalytic asymmetric synthesis of a phosphorus-stereogenic (P-stereogenic) nucleoside derivative of formula (3) and a catalyst used therein. The P-stereogenic nucleoside derivative (3) can be hydrolyzed to obtain remdesivir.

Abstract: A method for catalytic asymmetric synthesis of a phosphorus-stereogenic (P-stereogenic) nucleoside derivative of formula (3) and a catalyst used therein. The P-stereogenic nucleoside derivative (3) can be hydrolyzed to obtain remdesivir. Specifically, a nucleoside and phosphoryl chloride are subjected to asymmetric reaction under the catalysis of a chiral bicyclic imidazole catalyst in the presence of a base to produce the P-stereogenic nucleoside derivative.

Abstract: A method for preparing chiral ?-secondary amino alcohol includes: adding into a solvent an acid addition salt of ?-secondary amino ketone represented by general formula (1), an alkali, a metal salt additive and a diphosphine-rhodium complex, so as to carry out a reaction in a hydrogen atmosphere and obtain a chiral ?-secondary amino alcohol compound represented by general formula (2). In general formula (2), Ar represents an aryl group with or without substituent group(s), R represents an alkyl group or an aralkyl group, and HY represents an acid. The synthesis scheme has a simple process, the metal salt additive remarkably improves the effect of a rhodium-catalyzed asymmetric hydrogenation technology, and accordingly, the reaction yield and the optical purity of a product are improved, the production process is simplified, production costs are reduced, and the synthesis scheme is highly suitable for mass industrial production.

Abstract: A method for preparing chiral ?-secondary amino alcohol includes: adding into a solvent an acid addition salt of ?-secondary amino ketone represented by general formula (1), an alkali, a metal salt additive and a diphosphine-rhodium complex, so as to carry out a reaction in a hydrogen atmosphere and obtain a chiral ?-secondary amino alcohol compound represented by general formula (2). In general formula (2), Ar represents an aryl group with or without substituent group(s), R represents an alkyl group or an aralkyl group, and HY represents an acid. The synthesis scheme has a simple process, the metal salt additive remarkably improves the effect of a rhodium-catalyzed asymmetric hydrogenation technology, and accordingly, the reaction yield and the optical purity of a product are improved, the production process is simplified, production costs are reduced, and the synthesis scheme is highly suitable for mass industrial production.

Abstract: The invention relates to an asymmetric hydrogenation method for ketone compounds, comprising the step of: under hydrogen atmosphere, in the presence of an in situ catalyst derived from a chiral ligand and a ruthenium salt, adding a ketone compound and a base into a second solvent to carry out an asymmetric hydrogenation for the ketone compound. The invention can obtain a conversion of 100% and a highest asymmetric inducement effect of 99.7% for the ketone compound. The invention has the advantages including simple procedure, high conversion and selectivity, good atom economy and good prospect of industrial application.

Abstract: The present invention relates to a 2,2?,6,6?-tetrasubstituted aminophosphine ligand and its synthesis method. The structure of the ligand is shown as below. Its synthesis method comprises: Step (1) coupling 2,6-dinitrochlorobenzene as the starting material to obtain 2,2?,6,6?-tetranitrobiphenyl; Step (2): hydrogenating the 2,2?,6,6?-tetranitrobiphenyl with Pd/C to obtain 2,2?,6,6?-tetraminobiphenyl; Step (3): reacting the 2,2?,6,6?-tetraminobiphenyl with a phosphine halide to obtain the 2,2?,6,6?-tetrasubstituted aminophosphine ligand. The ligand of the present invention is an achiral compound, and its preparation method is simple. The ligand can be converted to a chiral bimetallic catalyst with single configuration eventually through introduction of external chirality. Moreover, the ligand can be used in various asymmetric reaction catalyzed by metals with high reactivity and stereoselectivity.

Abstract: The invention affords C2-symmetrical ruthenocene diphosphine ligands with surface chirality and their manufacture. The present invention uses (S)-(S)-1,1?-2(diphenylphosphino)-2,2?-2[(S)-4-isopropyloxazolinyl] ruthenocene as raw material and the product is prepared through two or three steps of reaction. At the action of trifluoroacetic acid, (S)-(S)-1,1?-2(diphenylphosphino)-2,2?-2[(S)-4-isopropyloxazolinyl] ruthenocene first removes oxazoline and gets ester amides compound which then carries out ester exchange or reduction alkylation and gets the product of ruthenocene diphosphine ligand with surface chirality. The ligands prepared with the structure as follows from the invention can be used in all kinds of metallic catalysis asymmetric reaction and has good reaction activity and stereoselectivity, wherein R is methyl or ethyl, R1 is linear or branched alkyl, cycloalkyl, alkoxy, aryl, aralkyl and alkyl amino.

Abstract: The invention relates to an asymmetric hydrogenation method for ketone compounds, comprising the step of: under hydrogen atmosphere, in the presence of an in situ catalyst derived from a chiral ligand and a ruthenium salt, adding a ketone compound and a base into a second solvent to carry out an asymmetric hydrogenation for the ketone compound. The invention can obtain a conversion of 100% and a highest asymmetric inducement effect of 99.7% for the ketone compound. The invention has the advantages including simple procedure, high conversion and selectivity, good atom economy and good prospect of industrial application.

Abstract: The invention affords C2-symmetrical ruthenocene diphosphine ligands with surface chirality and their manufacture. The present invention uses (S)—(S)-1,1?-2(diphenylphosphino)-2,2?-2[(S)-4-isopropyloxazolinyl]ruthenocene as raw material and the product is prepared through two or three steps of reaction. At the action of trifluoroacetic acid, (S)—(S)-1,1?-2(diphenylphosphino)-2,2?-2[(S)-4-isopropyloxazolinyl]ruthenocene first removes oxazoline and gets ester amides compound which then carries out ester exchange or reduction alkylation and gets the product of ruthenocene diphosphine ligand with surface chirality. The ligands prepared with the structure as follows from the invention can be used in all kinds of metallic catalysis asymmetric reaction and has good reaction activity and stereoselectivity, wherein R is methyl or ethyl, R1 is linear or branched alkyl, cycloalkyl, alkoxy, aryl, aralkyl and alkyl amino.

Abstract: The present invention relates to a 2,2?,6,6?-tetrasubstituted aminophosphine ligand and its synthesis method. The structure of the ligand is shown as below. Its synthesis method comprises: Step (1) coupling 2,6-dinitrochlorobenzene as the starting material to obtain 2,2?,6,6?-tetranitrobiphenyl; Step (2): hydrogenating the 2,2?,6,6?-tetranitrobiphenyl with Pd/C to obtain 2,2?,6,6?-tetraminobiphenyl; Step (3): reacting the 2,2?,6,6?-tetraminobiphenyl with a phosphine halide to obtain the 2,2?,6,6?-tetrasubstituted aminophosphine ligand. The ligand of the present invention is an achiral compound, and its preparation method is simple. The ligand can be converted to a chiral bimetallic catalyst with single configuration eventually through introduction of external chirality. Moreover, the ligand can be used in various asymmetric reaction catalyzed by metals with high reactivity and stereoselectivity.

Abstract: The present invention relates to a method for preparing 2,2?,6,6?-tetraoxazolinyl biphenyl ligand in chemical industry field. In the present invention, compound (III) is reacted with an activator that can activate the hydroxyl group selected from the group consisting of alkyl halosulfonium compound, aryl halosulfonium compound, phosphoryl chloride, phosphorus pentachloride, thionyl chloride and triphenyl phosphine, in the presence of alkali(s), to give the target product (IV), 2,2?,6,6?-tetraoxazolinyl biphenyl ligand. The ligand of the present invention can be used in various asymmetric reactions catalyzed by metals, with high reactivity and stereoselectivity, and thus represents a good application outlook.

Abstract: The present invention relates to a 5,5?-position linked 1,1?-biphenyl axis chiral ligand in chemical industry field. The present invention incorporates both the central chirality of oxazoline and the axial chirality of diphenyls. Such ligand can be used in various asymmetric reactions catalyzed by metal with high reactivity and stereoselectivity, and thus represents a good application outlook. The ligand of the present invention has the formula of: wherein: n=5, 6, 7, 8, 9, 10, 11 or 12; R1=hydrogen, alkyl, substituted or unsubstituted aryl, substituted or unsubstituted benzyl; R2=hydrogen, alkyl, substituted or unsubstituted aryl, substituted or unsubstituted benzyl; R3=hydrogen, alkyl, substituted or unsubstituted aryl, substituted or unsubstituted benzyl; R4=hydrogen, alkyl, substituted or unsubstituted aryl, substituted or unsubstituted benzyl.

Abstract: The present invention relates to a 5,5?-position linked 1,1?-biphenyl axis chiral ligand in chemical industry field. The present invention incorporates both the central chirality of oxazoline and the axial chirality of diphenyls. Such ligand can be used in various asymmetric reactions catalyzed by metal with high reactivity and stereoselectivity, and thus represents a good application outlook. The ligand of the present invention has the formula of: wherein: n=5, 6, 7, 8, 9, 10, 11 or 12; R1=hydrogen, alkyl, substituted or unsubstituted aryl, substituted or unsubstituted benzyl; R2=hydrogen, alkyl, substituted or unsubstituted aryl, substituted or unsubstituted benzyl; R3=hydrogen, alkyl, substituted or unsubstituted aryl, substituted or unsubstituted benzyl; R4=hydrogen, alkyl, substituted or unsubstituted aryl, substituted or unsubstituted benzyl.

Abstract: The present invention relates to a method for preparing 2,2?,6,6?-tetraoxazolinyl biphenyl ligand in chemical industry field. In the present invention, compound (III) is reacted with an activator that can activate the hydroxyl group selected from the group consisting of alkyl halosulfonium compound, aryl halosulfonium compound, phosphoryl chloride, phosphorus pentachloride, thionyl chloride and triphenyl phosphine, in the presence of alkali(s), to give the target product (IV), 2,2?,6,6?-tetraoxazolinyl biphenyl ligand. The ligand of the present invention can be used in various asymmetric reactions catalyzed by metals, with high reactivity and stereoselectivity, and thus represents a good application outlook.