Novel photoreaction chiral catalyst compound and synthesis method thereof

Abstract

The invention belongs to the technical field of organic synthesis, particularly discloses a novel photoreaction chiral catalyst compound and a synthesis method thereof, and mainly relates to a compound as shown in a general formula I, a racemate, a stereoisomer, a tautomer or a salt form thereof. The preparation method is characterized in that a bifunctional complex with the effects of a photosensitizer and a chiral catalyst is successfully synthesized through design of a ligand structure and strategy planning of complex synthesis, so that the photocatalyst disclosed by the invention can realize a catalytic reaction in a high enantioselectivity manner in the absence of the photosensitizer. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a novel bifunctional catalyst compound having the effects of a photosensitizer and a chiral catalyst and a synthesis method thereof. Background Art

[0002] With the continuous development of organic synthetic chemistry, the synthesis of chiral molecules plays an increasingly important role in the fields of medicine, pesticides and materials science. Different stereoisomers of chiral molecules often show significant differences in biological activity, efficacy and toxicity. Therefore, the development of efficient chiral synthesis methods has become one of the hot topics in modern organic chemistry research.

[0003] Traditional chiral catalysts are mostly metal catalysts or organic small molecule catalysts. Although these catalysts can promote the construction of chiral centers to a certain extent, they often have problems such as low catalytic efficiency, poor selectivity, and harsh reaction conditions. At the same time, many metal catalysts are difficult to recycle and reuse after use, resulting in environmental pollution and waste of resources. Therefore, researchers began to explore new catalytic systems to improve the efficiency and environmental friendliness of chiral synthesis.

[0004] Photocatalysis is a new catalytic technology that has emerged in recent years. It uses light energy to drive chemical reactions and has the advantages of high efficiency, greenness, and renewability. Especially in asymmetric synthesis, photocatalysis can generate reactive species by exciting photosensitive substances, thereby achieving the construction of chiral centers. However, the existing photocatalytic systems still have shortcomings in terms of catalytic effect and chiral selectivity. In particular, how to effectively regulate the chiral selectivity of the reaction under photoreaction conditions has become a problem that needs to be solved urgently.

[0005] In order to solve the above problems, researchers began to focus on the development of chiral organic asymmetric catalysts for photoreactions. This type of catalyst can not only catalyze reactions efficiently under light conditions, but also improve the stereoselectivity of the reaction by designing chiral structures. At the same time, chiral organic catalysts usually have good recyclability and environmental friendliness during the synthesis process, which is in line with the sustainable development concept of modern chemistry.

[0006] In summary, the development of efficient photoreactive chiral organic asymmetric catalysts is of great significance for improving the synthesis efficiency, selectivity and environmental friendliness of chiral molecules. Therefore, this patent aims to provide a new type of photoreactive chiral organic asymmetric catalyst and its application in asymmetric synthesis to promote the further development of chiral chemistry. Summary of the invention

[0007] The purpose of the present invention is to provide a type of photocatalyst which can achieve an asymmetric photocatalytic effect without the need for a photosensitizer.

[0008] To achieve the above objectives, an embodiment of the present invention provides a photocatalyst having the structural formula:

[0009]

[0010] Among them, R m Represents H, R a or -C(=X)-NR b R c :

[0011] R a , R b and R c are the same or different and are independently selected from H, unsubstituted or optionally substituted with one, two or more R d Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylamino, C 2-20 Alkenylamino, C 3-20 Cycloalkylamino, C 3-20 Cycloalkenylamino, 3-20 membered heterocyclylamino, C 6-20 Arylamino, 5-20 membered heteroarylamino, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, carbonyl, acyl, acyloxy, etc.;

[0012] R n represents H, unsubstituted or optionally substituted with one, two or more R e Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylamino, C 2-20 Alkenylamino, C 3-20 Cycloalkylamino, C 3-20 Cycloalkenylamino, 3-20 membered heterocyclylamino, C 6-20 Arylamino, 5-20 membered heteroarylamino, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, carbonyl, acyl, acyloxy, etc.;

[0013] R and R' are the same or different and are independently unsubstituted or optionally substituted by one, two or more R f Substituted with the following groups: hydroxyl, C 1-6 Hydrocarbyl-substituted amino, carbonyl, C 1-6 Hydrocarbyl or halogen;

[0014] G represents chemical bond, C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl; provided that when G is not a chemical bond, the positions of different groups connected to G on G can be separated by 1-10 atoms, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 atoms; for example, when G is phenyl, the positions of different groups connected to it on G can be separated by 1, 2, 3, 4 or 5 carbon atoms;

[0015] Each X is the same or different and is independently selected from O or S;

[0016] Each Y is the same or different and is independently selected from O, S or NH.

[0017] Every R d , R e and R f Same or different, choose C independently 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio.

[0018] Each compound is an optically pure compound.

[0019] Optionally, the C 3-20 One, two or more carbon atoms of the cycloalkyl or 3-20 membered heterocyclic group may be optionally substituted with oxygen to form a carbonyl group.

[0020] According to an embodiment of the present invention, G represents a chemical bond, C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl; provided that when G is not a chemical bond, the positions substituted on G by different groups connected to G may be separated by 1-10 atoms, for example, by 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 atoms; for example, when G is phenyl, the positions substituted on G by different groups connected to it may be separated by 1, 2, 3, 4 or 5 carbon atoms.

[0021] According to an embodiment of the present invention, halogen represents F, Cl, Br or I.

[0022] According to an embodiment of the present invention, Y is selected from O, NH or S.

[0023] According to an embodiment of the present invention, R n represents H, unsubstituted or optionally substituted with one, two or more R e Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylamino, C 2-20 Alkenylamino, C 3-20 Cycloalkylamino, C 3-20 Cycloalkenylamino, 3-20 membered heterocyclylamino, C 6-20 Arylamino, 5-20 membered heteroarylamino, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, carbonyl, acyl, acyloxy, etc.;

[0024] According to an embodiment of the present invention, R m Represents H, R a or -C(=X)-NR b R c , R a , R b and R c are the same or different and are independently selected from H, unsubstituted or optionally substituted with one, two or more R d Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylamino, C 2-20 Alkenylamino, C 3-20 Cycloalkylamino, C 3-20 Cycloalkenylamino, 3-20 membered heterocyclylamino, C 6-20 Arylamino, 5-20 membered heteroarylamino, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20Arylthio, 5-20 membered heteroarylthio, carbonyl, acyl, acyloxy, etc.;

[0025] According to an embodiment of the present invention, R and R′ are the same or different and are independently unsubstituted or optionally substituted by one, two or more R f Substituted with the following groups: hydroxyl, C 1-6 Hydrocarbyl-substituted amino, carbonyl, C 1-6 Hydrocarbon or halogen.

[0026] According to an embodiment of the present invention, the compound represented by formula I can be selected from the compounds represented by the following formulas II, III and IV:

[0027]

[0028] According to an embodiment of the present invention, R 1 , R 2 are the same or different and are independently selected from H, unsubstituted or optionally substituted with one, two or more R h Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylamino, C 2-20 Alkenylamino, C 3-20 Cycloalkylamino, C 3-20 Cycloalkenylamino, 3-20 membered heterocyclylamino, C 6-20 Arylamino, 5-20 membered heteroarylamino, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, R e C(=O)-、R e OC (=O), etc., R 1 and R 2 In addition to being substituted individually, they can also jointly form a polycyclic structure.

[0029] According to an embodiment of the present invention, R 3 , R 4 and R5 are the same or different and are independently selected from H, unsubstituted or optionally substituted with one, two or more R i Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylamino, C 2-20 Alkenylamino, C 3-20 Cycloalkylamino, C 3-20 Cycloalkenylamino, 3-20 membered heterocyclylamino, C 6-20 Arylamino, 5-20 membered heteroarylamino, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, substituted acyl, substituted acyloxy, etc.;

[0030] According to an embodiment of the present invention, R and R′, R e and Y are independently selected from the definitions given above;

[0031] According to an embodiment of the present invention, n1 and n2 are the same or different and are independently selected from integers of 0 and above:

[0032] According to an embodiment of the present invention, R h and R i Same or different, choose C independently 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio;

[0033] According to an embodiment of the present invention, each compound is an optically pure compound.

[0034] According to an embodiment of the present invention, the compound may be selected from the compounds shown in the following formulas V, VI and VII:

[0035]

[0036] According to an embodiment of the present invention, R 6 , R 7 and R 8 are the same or different and are independently selected from H, unsubstituted or optionally substituted with one, two or more R j Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylamino, C 2-20 Alkenylamino, C 3-20 Cycloalkylamino, C 3-20 Cycloalkenylamino, 3-20 membered heterocyclylamino, C 6-20 Arylamino, 5-20 membered heteroarylamino, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, etc.;

[0037] According to an embodiment of the present invention, R j Independently choose C 1-20 Alkyl, C 2-20Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio;

[0038] According to an embodiment of the present invention, R 1 , R 2 , R, R', Y, n1 and n2 are independently selected from the definitions given above:

[0039] According to an embodiment of the present invention, each X is independently selected from O or S;

[0040] According to an embodiment of the present invention, each compound is an optically pure compound.

[0041] According to an embodiment of the present invention, the compound represented by formula I can be selected from the following compounds, but is not limited to the following compounds:

[0042]

[0043] An embodiment of the present invention further provides a method for preparing the above-mentioned photocatalyst, comprising the following steps:

[0044]

[0045] Among them, R n , R m , R, R′, X, Y, G, R 12 Has the definition given above.

[0046] In the above preparation method, the condensing agent includes HATU, HOBT, EDCI, DCC, etc., preferably HATU, HOBT and EDCI.

[0047] In the above preparation method, the reaction temperature is -60 to 30° C., preferably 25° C. The reaction time is 1 to 72 hours, preferably 48 hours.

[0048] In the above preparation method, the solvent used includes but is not limited to benzene, toluene, chlorobenzene, chloroform, n-hexane, n-heptane, cyclohexane, dichloromethane, carbon tetrachloride, 1,2-dichloroethane, 1,1,2-trichloroethane, 1,1,2,2-tetrachloroethane, 1,4-dioxane, methyl tert-butyl ether, ethyl acetate, propyl acetate, butyl acetate, methanol, ethanol, acetone, tetrahydrofuran, ether, acetonitrile, anisole, N,N-dimethylformamide, dimethyl sulfoxide or a mixed solvent composed of these solvents, preferably 1,2-dichloroethane. The most preferred is dichloromethane.

[0049] The compound provided by the present invention combines a photosensitizer with a chiral catalyst, so that the light absorption range of the photosensitizer is within visible light or ultraviolet light, so as to meet the basic requirements of visible light catalysis. Based on the development concept of sustainable chemistry, it has the beneficial effects of safety, mildness, high efficiency and economy.

[0050] Beneficial Effects

[0051] The present invention is a novel bifunctional catalyst compound having the effects of both photosensitizer and chiral catalyst, which can achieve the effect of asymmetric photocatalysis without the cooperation of photosensitizer. In addition, the preparation method of the photocatalyst also has the advantages of cheap and easy-to-obtain raw materials and simple operation.

[0052] Definition and explanation of terms

[0053] Unless otherwise specified, the definitions of groups and terms recorded in the specification and claims of this application, including their definitions as examples, exemplary definitions, preferred definitions, definitions recorded in tables, definitions of specific compounds in examples, etc., can be arbitrarily combined and combined with each other. The definitions of groups and compound structures after such combinations and combinations should be understood to be within the scope of the specification and / or claims of this application.

[0054] Unless otherwise stated, the numerical ranges recorded in this specification and claims are equivalent to recording at least each specific integer value therein. For example, the numerical range "1-10" is equivalent to recording each integer value in the numerical range "1-10", namely 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. In addition, when certain numerical ranges are defined as "numbers", it should be understood that the two endpoints of the range, each integer in the range, and each decimal in the range are recorded. For example, "a number from 0 to 10" should be understood as not only recording each integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, but also at least recording the sum of each integer therein and 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, respectively.

[0055] It should be understood that herein, when describing one, two or more, "more" should refer to an integer greater than 2, for example, greater than or equal to 3, for example 3, 4, 5, 6, 7, 8, 9 or 10.

[0056] The term "halogen" refers to chlorine, chlorine, bromine and iodine.

[0057] The term "C 1-20 "Alkyl" is understood to mean a straight-chain or branched saturated monovalent hydrocarbon group having 1 to 20 carbon atoms. For example, "C 1-10 "Alkyl" means straight chain and branched chain alkyl groups having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. 1-8 The term “alkyl” refers to straight-chain and branched alkyl groups having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms. The alkyl group is, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl or 1,2-dimethylbutyl or the like or isomers thereof.

[0058] The term "C 2-20 "Alkenyl" is understood to mean preferably a linear or branched monovalent hydrocarbon radical containing one or more double bonds and having 2 to 20 carbon atoms, preferably "C 2-8 "C 2-8 "Alkenyl" is understood to mean preferably a linear or branched monovalent hydrocarbon radical which contains one or more double bonds and has 2, 3, 4, 5, 6, 7 or 8 carbon atoms, in particular 2 or 3 carbon atoms ("C 2-3"alkenyl"), it being understood that, in the case where the alkenyl contains more than one double bond, the double bonds may be separated from one another or conjugated. The alkenyl is, for example, vinyl, allyl, (E)-2-methylvinyl, (Z)-2-methylvinyl, (E)-but-2-enyl, (Z)-but-2-enyl, (E)-but-1-enyl, (Z)-but-1-enyl, pent-4-enyl, (E)-pent-3-enyl, (Z)-pent-3-enyl, -enyl, (E)-pent-2-enyl, (Z)-pent-2-enyl, (E)-pent-1-enyl, (Z)-pent-1-enyl, hex-5-enyl, (E)-hex-4-enyl, (Z)-hex-4-enyl, (E)-hex-3-enyl, (Z)-hex-3-enyl, (E)-hex-2-enyl, (Z)-hex-2-enyl, (E)-hex-1-enyl, (Z)-hex-1-enyl, isopropenyl, 2-hexenyl, (E)-pent-2-enyl, (Z)-pent-2-enyl, (E)-pent-1-enyl, (Z)-pent ...1-enyl, (Z)-pent-1-enyl, isopropenyl, 2-hexenyl, (E)-pent-2-enyl, (Z)-pent-1-enyl, (Z)-pent-1-enyl, isopropenyl, 2-hexenyl, (E)-pent-2-enyl, (Z)-pent-1- -methylprop-2-enyl, 1-methylprop-2-enyl, 2-methylprop-1-enyl, (E)-1-methylprop-1-enyl, (Z)-1-methylprop-1-enyl, 3-methylbut-3-enyl, 2-methylbut-3-enyl, 1-methylbut-3-enyl, 3-methylbut-2-enyl, (E)-2-methylbut-2-enyl, (Z)-2-methylbut-2-enyl, (E)-1-methylbut-2-enyl 1-ethylprop-1-enyl, 1-propylvinyl, and 1-isopropylvinyl.

[0059] The term "C 3-20 "Cycloalkyl" is understood to mean a saturated monovalent monocyclic, bicyclic (eg bridged, spiro) hydrocarbon ring or tricyclic alkane having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. 3-10 The cycloalkyl group may be a monocyclic hydrocarbon group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl or cyclodecyl, or a bicyclic hydrocarbon group such as borneol, indolyl, hexahydroindolyl, tetrahydronaphthyl, decahydronaphthyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.1]heptenyl, 6,6-dimethylbicyclo[3.1.1]heptyl, 2,6,6-trimethylbicyclo[3.1.1]heptyl, bicyclo[2.2.2]octyl, 2,7-diazaspiro[3,5]nonanyl, 2,6-diazaspiro[3,4]octanyl, or a tricyclic hydrocarbon group such as adamantyl.

[0060] The term "C 5-20"Cycloalkenyl" is understood to mean a conjugated or non-conjugated monovalent monocyclic or bicyclic hydrocarbon ring with a degree of unsaturation of 1, 2 or 3, having 5 to 20 carbon atoms, preferably "C 5-10 The term "C 5-10 "Cycloalkenyl" is understood to mean an unsaturated, monovalent monocyclic or bicyclic hydrocarbon ring having 5, 6, 7, 8, 9 or 10 carbon atoms. 5-10 The cycloalkenyl group may be a monocyclic hydrocarbon group, such as 3-cyclopentenyl, 1-cyclohexenyl, 2-cyclohexenyl, 2,4-cyclopentadienyl, 2,5-cyclohexadienyl or 1,3,5-cycloheptatrienyl or 1,3,6-cycloheptatrienyl, or a bicyclic hydrocarbon group such as hexahydronaphthalene ring or octahydronaphthalene ring. Unless otherwise specified, the term "C 5-20 The term "cycloalkenyl" includes all possible isomeric forms thereof, such as positional isomers or configurational isomers thereof.

[0061] Unless otherwise defined, the term "3-20 membered heterocyclyl" refers to a saturated or unsaturated non-aromatic ring or ring system, for example, a 4-, 5-, 6- or 7-membered monocyclic ring, a 7-, 8-, 9- or 10-membered bicyclic ring (such as a fused ring, a bridged ring, a spirocyclic ring) or a 10-membered tricyclic ring system, and contains at least one, for example 1, 2, 3, 4, 5 or more heteroatoms selected from O, S and N, wherein N and S may also be optionally oxidized to various oxidation states to form nitrogen oxides, -S(O)- or -S(O)2- states. Preferably, the heterocyclyl may be selected from "3-10 membered heterocyclyl". The heterocyclyl may be connected to the rest of the molecule via any one of the carbon atoms or a nitrogen atom (if present). The heterocyclyl may include fused or bridged rings and spirocyclic rings. In particular, the heterocyclic group may include, but is not limited to, a 4-membered ring, such as azetidinyl, oxetanyl; a 5-membered ring, such as tetrahydrofuranyl, dioxolyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, pyrrolinyl; or a 6-membered ring, such as tetrahydropyranyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl or trithianyl; or a 7-membered ring, such as diazepanyl. Optionally, the heterocyclic group may be benzo-fused. The heterocyclic group may be bicyclic, such as, but not limited to, a 5,5-membered ring, such as a hexahydrocyclopenta [c] pyrrole-2 (1H) -yl ring, or a 5,6-membered bicyclic ring, such as a hexahydropyrrolo [1,2-a] pyrazine-2 (1H) -yl ring. The heterocyclic group may be partially unsaturated, i.e., it may contain one or more double bonds, such as but not limited to dihydrofuranyl, dihydropyranyl, 2,5-dihydro-1H-pyrrolyl, 4H-[1,3,4]thiadiazinyl, 4,5-dihydrooxazolyl or 4H-[1,4]thiazinyl, or it may be benzo-fused, such as but not limited to dihydroisoquinolinyl. When the 3-10 membered heterocyclic group is connected to other groups to form the compound of the present invention, it may be a carbon atom on the 3-10 membered heterocyclic group connected to other groups, or it may be a heterocyclic atom on the 3-10 membered heterocyclic group ring connected to other groups. For example, when the 3-10 membered heterocyclic group is selected from piperazinyl, it may be a nitrogen atom on the piperazinyl group connected to other groups. Or when the 3-10 membered heterocyclic group is selected from piperidinyl, it may be a nitrogen atom on the piperidinyl ring and a carbon atom on the para position thereof connected to other groups.

[0062] The term "C 6-20 The term "aryl" is understood to mean preferably a monovalent aromatic or partially aromatic monocyclic or bicyclic (e.g. fused, bridged, spiro) hydrocarbon ring having 6 to 20 carbon atoms, which may be a single aromatic ring or a polyaromatic ring fused together, in particular a ring having 6 carbon atoms ("C6 aryl"), such as phenyl; or biphenyl, or a ring having 9 carbon atoms ("C9 aryl"), such as indanyl or indenyl, or a ring having 10 carbon atoms ("C 10 aryl”), such as naphthyl. When the C6-10 When the aryl group is substituted, it may be monosubstituted or polysubstituted. Also, there is no limitation on the substitution site, for example, it may be substituted at the ortho, para or meta position.

[0063] The term "5-20 membered heteroaryl" is understood to include monovalent monocyclic, bicyclic (e.g. fused, bridged, spiro) or tricyclic aromatic ring systems having 5 to 10 ring atoms and containing 1 to 5 heteroatoms independently selected from N, O and S, preferably 1 to 3 heteroatoms each independently selected from N, O and S and, in each case, may additionally be benzo-fused. "Heteroaryl" also refers to a group in which a heteroaromatic ring is fused to one or more aryl, alicyclic or heterocyclyl rings, wherein the radical or point of attachment is on the heteroaromatic ring. Non-limiting examples include 1-, 2-, 3-, 5-, 6-, 7-, or 8-indolizinyl, 1-, 3-, 4-, 5-, 6-, or 7-isoindolyl, 2-, 3-, 4-, 5-, 6-, or 7-indolyl, 2-, 3-, 4-, 5-, 6-, or 7-indazolyl, 2-, 4-, 5-, 6-, 7-, or 8-purinyl, 1-, 2-, 3-, 4-, 6-, 7-, 8-, or 9-quinolizinyl, 2-, 3-, 4-, 5-, 6-, 7-, or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7-, or 8-isoquinolyl, 1-, 4-, 5-, 6-, 7-, or 8-indolyl, 7- or 8-phthalazinyl, 2-, 3-, 4-, 5-, or 6-naphthyridinyl, 2-, 3-, 5-, 6-, 7-, or 8-quinazolinyl, 3-, 4-, 5-, 6-, 7-, or 8-cinnolinyl, 2-, 4-, 6-, or 7-pteridinyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, or 8-4aH carbazolyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, or 8-carbazolyl carbazolyl, 1-, 3-, 4-, 5-, 6-, 7-, 8-, or 9-carbolinyl, 1-, 2-, 3-, 4-, 6-, 7-, 8- , 9- or 10-phenanthridinyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-acridinyl, 1-, 2-, 4-, 5-, 6-, 7-, 8- or 9-piperidinyl, 2-, 3-, 4-, 5-, 6-, 8-, 9- or 10-phenanthrolinyl, 1-, 2-, 3-, 4-, 6-, 7-, 8- or 9-phenazinyl, 1-, 2-, 3-, 4-, 6-, 7-, 8-, 9- or 10-phenothiazinyl, 1-, 2-, 3-, 4-, 6-, 7-, 8-, 9- or 10-phenanthridinyl, , 4-, 5-, 6-, 7-, 8-, 9- or 10-benzoisoquinolyl, 2-, 3-, 4- or thieno[2,3-b]furanyl, 2-, 3-, 5-, 6-, 7-, 8-, 9-, 10- or 11-7H-pyrazino[2,3-c]carbazolyl, 2-, 3-, 5-, 6- or 7-2H-furo[3,2-b]pyranyl, 2-, 3-, 4-, 5-, 7- or 8-5H-pyrido[2,3-d]-o-oxazinyl, 1-, 3- or 5-1H-pyrazolo[4,3-d]oxazolyl, 2-, 4- or 54H-imidazo[4,5-d]thiazolyl, 3-, 5- or 8-pyrazino[2,3-d]pyridazinyl, 2-, 3-, 5- or 6-imidazo[2,1-b]thiazolyl, 1-, 3-, 6-, 7-, 8- or 9-furo[3,4-c]cinnolinyl, 1-, 2-, 3-, 4-, 5-, 6-, 8-, 9-, 10 or 11-4H-pyrido[2,3-c]carbazolyl, 2-, 3-, 6- or 7-imidazo[1,2-b][1,2,4]triazinyl, 7-benzo[b]thienyl, 2-, 4-, 5-, 1-, 2-, 3-, 5-, 6-, 7-, 8-, 9-, 10-, or 11-1H-pyrrolo[1,2-b][2]benzazepinyl. Typical fused heteroaryl groups include, but are not limited to, 2-, 3-, 4-, 5-, 6-, 7-, or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7-, or 8-isoquinolyl, 2-, 3-, 4-, 5-, 6-, or 7-indolyl, 2-, 3-, 4-, 5-, 6-, or 7-benzo[b]thienyl, 2-, 4-, 5-, 6-, or 7-benzoxazolyl, 2-, 4-, 5-, 6-, or 7-benzimidazolyl, and 2-, 4-, 5-, 6-, or 7-benzothiazolyl. When the 5-10 membered heteroaryl group is connected to other groups to form the compound of the present invention, the carbon atoms on the 5-10 membered heteroaryl ring may be connected to other groups, or the heteroatoms on the 5-10 membered heteroaryl ring may be connected to other groups. When the 5-10 membered heteroaryl group is substituted, it may be monosubstituted or polysubstituted. Furthermore, there is no limitation on the substitution site, for example, the hydrogen bonded to the carbon atom on the heteroaryl ring may be substituted, or the hydrogen bonded to the heteroatom on the heteroaryl ring may be substituted.

[0064] Unless otherwise specified, a heterocyclic group, a heteroaryl group or a heteroarylene group includes all possible isomeric forms thereof, such as positional isomers thereof. Thus, for some illustrative non-limiting examples, forms substituted or bonded to other groups at one, two or more positions of the 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-position, etc. (if present) may include pyridin-2-yl, pyridin-2-ylene, pyridin-3-yl, pyridin-3-ylene, pyridin-4-ylene and pyridin-4-ylene; thienyl or thienylene group includes thien-2-yl, thien-2-ylene, thien-3-yl and thien-3-ylene; pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl.

[0065] The term "oxo" refers to a substituent in which a carbon atom, a nitrogen atom or a sulfur atom is oxidized to form an oxy group (=O).

[0066] Unless otherwise stated, the definitions of terms herein also apply to groups containing the term, e.g. 1-20 The definition of alkyl also applies to C 1-20 Alkyloxy and other terms.

[0067] Those skilled in the art will appreciate that the compounds of formula (I) may exist in the form of various acceptable salts. If these compounds have a basic center, they may form acid addition salts; if these compounds have an acidic center, they may form a base addition salt; if these compounds contain both an acidic center (e.g., a carboxyl group) and a basic center (e.g., an amino group), they may also form an internal salt.

[0068] The compounds of the present invention may exist in the form of solvates (e.g. hydrates), wherein the compounds of the present invention contain polar solvents as structural elements of the crystal lattice of the compounds, in particular water, methanol or ethanol. The amount of polar solvents, in particular water, may exist in a stoichiometric or non-stoichiometric ratio.

[0069] The compounds of the present invention may exist in the form of stereoisomers, which may be enantiomers and cis-trans isomers, or enantiomers and diastereomers. DETAILED DESCRIPTION

[0070] In order to make the specific technology of the present invention clearer, the present invention is further explained in conjunction with the following examples. The following examples are only examples, and the protection content of the present invention is further described, but not limited. All reactions made based on the given examples are within the scope of protection, specifically with the attached claims as the scope of protection. Except for the following specific description, the raw materials and reagents used in the examples can be purchased or have been invented, and the present invention has no special restrictions.

[0071] Analytical methods

[0072] The spectrometer was used to analyze the solvents at room temperature. 1 H nuclear magnetic resonance (NMR) spectra, unless otherwise indicated. In all cases, NMR data are consistent with the proposed structure. Characteristic chemical shifts (δ) are given in parts per million using conventional abbreviations for designating major peaks: for example, s, singlet; d, doublet; t, triplet; q, quartet; dd, doublet of doublets; br, broad. Mass spectra were recorded using an Agilent 1290 Infinity / 6460 triple Quad LCMS. When thin layer chromatography (TLC) was used, it refers to silica gel TLC.

[0073] Example 1: Preparation of Compound 1

[0074]

[0075] At room temperature, DIPEA (1.03 g, 8 mmol) and HATU (1.14 g, 3 mmol) were added to a DCM solution of rhodamine B (910.3 mg, 1.9 mmol). After 1 h, 1a (429 mg, 2 mmol) was added to the solution. The reaction was continued at room temperature for 12 h. After the reaction was completed, saturated sodium bicarbonate solution (3 × 20 mL) and saturated sodium chloride solution (3 × 20 mL) were added to extract and wash, and dried over anhydrous sodium sulfate. Filtered and dried by spin drying. Column separation PE: EA = 4: 1.

[0076] Compound 1: light pink solid, 582 mg, yield 48%. 1 H NMR (400MHz, CDCl3) δ7.92-7.83 (m, 1H), 7.49-7.38 (m, 2H), 7.05 (s, 1H), 6.50-6.18 (m, 6H), 4.57 (s, 1H), 3.45-3.22 ( m, 9H), 2.45 (s, 1H), 2.13-1.94 (m, 2H), 1.53-1.42 (m, 2H), 1.35 (s, 10H), 1.16 (dt, J=13.7, 7.0Hz, 14H).HRMS (ESI) m / z calcd for C 39 H 50 N4O4, [M+H] + 639.3905, found 639.3905.

[0077] Example 2: Preparation of Compound 2

[0078] Step 2.1

[0079] Preparation of intermediate 1

[0080]

[0081] At room temperature, DIPEA (1.03 g, 8 mmol) and HATU (1.14 g, 3 mmol) were added to a DCM solution of rhodamine B (910.6 mg, 1.9 mmol). After 1 h, 2a (401.1 mg, 2 mmol) was added to the solution. The reaction was continued at room temperature for 12 h. After the reaction was completed, saturated sodium bicarbonate solution (3×20 mL) and saturated sodium chloride solution (3x20 mL) were added to extract and wash, and dried over anhydrous sodium sulfate. Filtered and dried by spin drying. Column separation PE:EA=4:1.

[0082] Intermediate 1: light pink solid, 833 mg, yield 70%. 1 H NMR (400MHz, CDCl3) δ7.85 (dd, J=6.0, 2.8Hz, 1H), 7.49-7.35 (m, 2H), 7.01 (dd, J=5.8, 2.7Hz, 1H ), 6.49 (dd, J=13.8, 8.8Hz, 2H), 6.42-6.33 (m, 2H), 6.26 (d, J=9.0Hz, 2H), 3.96 (d, J=12.6Hz, 1H ), 3.54 (s, 2H), 3.33 (dd, J=7.2Hz, 8H), 2.91 (s, 1H), 2.60-2.46 (m, 1H), 2.44-2.28 (m, 1H), 1.70 (s, 1H), 1.51 (dt, J=13.6, 3.2Hz, 1H), 1.23 (s, 11H), 1.16 (td, J=7.1, 3.3Hz, 12H).HRMS (ESI) m / z calcd forC 38 H 48 N4O4, [M+H] + 625.3748, found 625.3746.

[0083] Step 2.2

[0084] Preparation of compound 2

[0085]

[0086] At room temperature, the intermediate 1 was dissolved in a certain amount of ethyl acetate, and a sufficient amount of 4M HCl solution was added, and stirred for 2 h. After the reaction was completed, the mixture was spin-dried.

[0087] Compound 2: light pink solid, 566 mg, yield 68%. 1H NMR (400MHz, D2O) δ7.94-7.88 (m, 1H), 7.66-7.56 (m, 4H), 7.20 (ddd, J=8.7, 3.5, 2.3Hz, 2H), 7.14-7.05 (m, 3H ), 3.67-3.58 (m, 8H), 3.54 (d, J = 11.8Hz, 1H), 3.40 (ddd, J = 15.3, 11.1, 4.2Hz, 1H), 3.15 (d, J = 12.7Hz, 1H), 2.8 3(td, J=12.7, 3.2Hz, 1H), 2.72 (dd, J=12.2, 4.1Hz, 1H), 2.14 (q, J=11.1Hz, 1H), 2.00 (d, J=0.8Hz, 2H), 1.83-1 .73 (m, 1H), 1.35 (q, J=13.0Hz, 1H), 1.21 (td, J=10.9, 10.0, 5.7Hz, 1H), 1.07 (q, J=7.0Hz, 12H).HRMS (ESI) m / z calcd for C 33 H 40 N4O2, [M+H] + 525.3224, found 525.3217.

[0088] Example 3: Preparation of Compound 3

[0089] Step 3.1

[0090] Preparation of intermediate 2

[0091]

[0092] At room temperature, DIPEA (1.03 g, 8 mmol) and HATU (1.14 g, 3 mmol) were added to a DCM solution of rhodamine B (910.1 mg, 1.9 mmol). After 1 h, 3a (402.5 mg, 2 mmol) was added to the solution. The reaction was continued at room temperature for 12 h. After the reaction was completed, saturated sodium bicarbonate solution (3×20 mL) and saturated sodium chloride solution (3×20 mL) were added to extract and wash, and dried over anhydrous sodium sulfate. Filtered and dried by suction. Column separation PE:EA=4:1.

[0093] Intermediate 2: light pink solid, 726 mg, yield 61%. 1H NMR (400MHz, CDCl3) δ7.87 (dd, J=5.7, 3.1Hz, 1H), 7.40 (dd, J=5.7, 3.1Hz, 2H), 7.04 (dd, J=5.8, 3.0Hz, 1H) , 6.47 (d, J=8.8Hz, 1H), 6.40-6.29 (m, 3H), 6.26 (dd, J=9.0, 2.4Hz, 2H), 3.55-3.43 (m, 1H), 3.40-3.25 (m, 9 H), 3.21-3.11 (m, 2H), 2.97 (dd, J=13.7, 4.9Hz, 1H), 2.14-2.03 (m, 1H), 1.82 (dd, J=12.8, 6.6Hz, 1H), 1.68 (dt, J=15.0, 7.7Hz, 1H), 1.43 (dt, J=12.0, 4.8Hz, 1H), 1.31 (s, 9H), 1.14 (q, J=7.2Hz, 12H).HRMS (ESI) m / z calcd for C 38 H 48 N4O4, [M+Na] + 647.3568, found 647.3563.

[0094] Step 3.2

[0095] Preparation of compound 3

[0096]

[0097] At room temperature, the intermediate 2 was dissolved in a certain amount of ethyl acetate, and a sufficient amount of 4M HCl solution was added, and stirred for 2 h. After the reaction was completed, the mixture was spin-dried.

[0098] Compound 3: light pink solid, 726 mg, yield 61%. 1 H NMR (400MHz, D2O) δ7.98-7.91 (m, 1H), 7.67-7.60 (m, 2H), 7.58 (dd, J=5.1, 2.3H z, 1H), 7.28-7.09 (m, 5H), 7.01 (d, J=8.6Hz, 1H), 3.68-3.57 (m, 9H), 3A0-3.23 (m , 2H), 3.14 (ddd, J=12.0, 8.9, 5.6Hz, 2H), 2.00 (s, 1H), 1.87 (tt, J=8.9, 4.7Hz, 1 H), 1.76-1.59 (m, 2H), 1.38-1.29 (m, 1H), 1.07 (t, J=7.1Hz, 12H).HRMS (ESI) m / z calcd for C 33 H 40N4O2, [M+Na] + 547.3049, found 547.3032.

[0099] Example 4: Preparation of Compound 4

[0100] Step 4.1

[0101] Preparation of intermediate 3

[0102]

[0103] Under ice-water bath, 4a (345.2 mg, 3 mmol) was dissolved in 20 mL of DCM solution and stirred to dissolve, then 4b (543 mg, 2 mmol) dissolved in DCM solution was added dropwise to the above solution. After 1 h of dropwise addition, the reaction was warmed to room temperature and stirred for 2 h. After the reaction was completed, the mixture was dried by spin drying. DCM: CH3OH = 16:1 was separated by column.

[0104] Intermediate 3: pale yellow solid, 508 mg, yield 66%. 1 H NMR (400MHz, CDCl3) δ8.01 (d, J=1.5Hz, 2H), 7.57 (s, 1H), 6.42 (s, 1H), 3.38 (s, 1H), 2.68 (s ,1H),2.04(s,1H),1.95(d,,J=10.8Hz,1H),1.77(s,2H),1.36-1.12(m,6H).HRMS(ESI)m / z calcd for C 1s H 17 F6N3S, [M+H] + 386.1120, found 386.1114.

[0105] Step 4.2

[0106] Preparation of compound 4

[0107]

[0108] At room temperature, DIPEA (423 mg, 3.12 mmol) and HATU (448.2 mg, 1.173 mmol) were added to a DCM solution of rhodamine B (354.6 mg, 0.74 mmol). After 1 h, intermediate 3 (298.3 mg, 0.78 mmol) was added to the solution. The reaction was allowed to proceed at room temperature for 12 h. After the reaction was completed, saturated sodium bicarbonate solution (3x20 mL) and saturated sodium chloride solution (3×20 mL) were added for extraction and washing, and dried over anhydrous sodium sulfate. Filtered and dried by spin drying. Column separation PE:EA=10:1, 0.5% TEA.

[0109] Compound 4: light pink solid, 397 mg, yield 66%. 1 H NMR (400MHz, CDCl3) δ9.50 (s, 1H), 8.33 (s, 2H), 7.89 (dd, J=5.7, 3.1Hz, 1H), 7.57 (s, 1H), 7.50 (dd, J=5.6, 3.1 Hz, 2H), 7.12 (dd, J=5.6, 3.0Hz, 1H), 6.54 (dd, J=9.0, 2.6Hz, 1H), 6.47-6.33 (m, 4H), 6.28 (dd, J=8.9, 2.6Hz, 1 H), 5.10 (d, J=11.2Hz, 1H), 4.75 (qd, J=11.0, 3.5Hz, 1H), 3.43-3.26 (m, 8H), 2.66 (td,, J=11.3, 3.5Hz, 1H), 2. 06-1.84 (m, 2H), 1.66 (d, J=13.0Hz, 1H), 1.57 (s, 1H), 1.41-1.24 (m, 3H), 1.18 (q, J=7.3Hz, 13H).HRMS (ESI) m / z calcd for C 43 H 45 F6N5O2S, [M+H] + 810.3271, found 810.3271.

[0110] Example 5: Preparation of Compound 5

[0111] Step 5.1

[0112] Preparation of intermediate 4

[0113]

[0114] Under ice-water bath, 5a (867 mg, 7.5 mmol) was dissolved in 75 mL of DCM solution and stirred to dissolve, then 5b (1.37 g, 5 mmol) dissolved in DCM solution was added dropwise to the above solution. After 1 h of dropwise addition, the reaction was warmed to room temperature and stirred for 2 h. After the reaction was completed, the mixture was dried by spin drying. Column separation DCM: CH3OH = 16:1.

[0115] Same as step 4.1

[0116] Step 5.2

[0117] Preparation of compound 5

[0118]

[0119] At room temperature, DIPEA (361 mg, 0.7 mmol), HOBt (113 mg, 0.84 mmol), EDCI (160 mg, 0.84 mmol) were added to a DCM solution of Eosin Y (477 mg, 0.735 mmol). After 1 h, intermediate 4 (267 mg, 0.7 mmol) was added to the solution. The reaction was carried out at room temperature for 12 h. After the reaction was completed, saturated sodium bicarbonate solution (3×20 mL) and saturated sodium chloride solution (3×20 mL) were added to extract and wash, and dried over anhydrous sodium sulfate. Filtered and dried by spin drying. Column separation.

[0120] Compound 5: light orange solid, 263 mg, yield 38%. 1 H NMR (400MHz, CDCl3) δ9.14 (s, 1H), 8.23 ​​(s, 2H), 8.00-7.93 (m, 1H), 7.70-7.63 (m, 2H) ,7.59(s,1H),7.41(s,1H),7.12-7.05(m,1H),6.74(s,1H),6.68(s,1H),6.33(s,1H) , 5.71 (d,, J=11.1Hz, 1H), 4.77 (s, 1H), 2.65 (t, J=10.8Hz, 1H), 1.96 (d, J=13.1Hz, 1H ), 1.73 (d, J=6.8Hz, 1H), 1.47-1.39 (m, 2H), 0.88 (q, J=4.9, 3.6Hz, 4H).HRMS (ESI) m / z calcd for C 35 H 23 Br4F6N3O4S, [M+H] + 1011.8120, found 1011.8120.

Claims

1. A novel photoreaction chiral catalyst compound having a structure as shown in Formula I: in, R m Represents H, R a or -C(=X)-NR b R c : R a , R b and R e are the same or different and are independently selected from H, unsubstituted or optionally substituted with one, two or more R d Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylamino, C 2-20 Alkenylamino, C 3-20 Cycloalkylamino, C 3-20 Cycloalkenylamino, 3-20 membered heterocyclylamino, C 6-20 Arylamino, 5-20 membered heteroarylamino, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, R e C(=O)-、R c OC(=O)-etc.; R n represents H, unsubstituted or optionally substituted with one, two or more R f Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylamino, C 2-20 Alkenylamino, C 3-20 Cycloalkylamino, C 3-20 Cycloalkenylamino, 3-20 membered heterocyclylamino, C 6-20 Arylamino, 5-20 membered heteroarylamino, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, R e C(=O)-、R e OC(=O)-etc.; R and R' are the same or different and are independently unsubstituted or optionally substituted by one, two or more Rg: hydroxyl, C 1-6 Hydrocarbon mono- or poly-substituted amino, carboxyl, ester, cyano, C 1-6 Hydrocarbyl or halogen; G represents chemical bond, C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl; provided that when G is not a chemical bond, the positions of different groups connected to G on G can be separated by 1-10 atoms, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 atoms; for example, when G is phenyl, the positions of different groups connected to it on G can be separated by 1, 2, 3, 4 or 5 carbon atoms; Each Y is independently selected from O, S or NH; Every R d , R e , R f and R g Same or different, choose C independently 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio; Each compound is an optically pure compound.

2. According to claim 1, the bifunctional catalyst having the effects of both a photosensitizer and a chiral catalyst is prepared by preparing the compound shown in formula I, which is divided into the following three general structural formulas: R 1 , R 2 are the same or different and are independently selected from H, unsubstituted or optionally substituted with one, two or more R h Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylamino, C 2-20 Alkenylamino, C 3-20 Cycloalkylamino, C 3-20 Cycloalkenylamino, 3-20 membered heterocyclylamino, C 6-20 Arylamino, 5-20 membered heteroarylamino, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, R e C(=O)-、R e OC (=O), etc., R 1 and R 2 In addition to being substituted individually, they can also jointly form a polycyclic structure. R 3 , R 4 and R 5 are the same or different and are independently selected from H, unsubstituted or optionally substituted with one, two or more R i Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylamino, C 2-20 Alkenylamino, C 3-20 Cycloalkylamino, C 3-20 Cycloalkenylamino, 3-20 membered heterocyclylamino, C 6-20 Arylamino, 5-20 membered heteroarylamino, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, substituted acyl, substituted acyloxy, etc.; R and R′, R e and Y are independently selected from the definitions in claim 1; n 1 and n 2 The same or different, independently selected from integers 0 and above: Every R h and R i Same or different, choose C independently 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio; Each compound is an optically pure compound.

3. According to claim 1, the bifunctional catalyst having the functions of both a photosensitizer and a chiral catalyst, the compounds are classified into the following three structural formulas: in, R 6 , R 7 and R 8 are the same or different and are independently selected from H, unsubstituted or optionally substituted with one, two or more R j Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylamino, C 2-20 Alkenylamino, C 3-20 Cycloalkylamino, C 3-20 Cycloalkenylamino, 3-20 membered heterocyclylamino, C 6-20 Arylamino, 5-20 membered heteroarylamino, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, etc.; Every R j Independently choose C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio; R 1 , R 2 , R, R′, Y, n 1 and n 2 Selected independently from the definitions given above; Each X is independently selected from O or S; Each compound is an optically pure compound.

4. The bifunctional catalyst having both the effects of a photosensitizer and a chiral catalyst according to claims 1-3, the structure of the catalyst compound is exemplified as follows:

5. A method for preparing a bifunctional catalyst having both the effects of a photosensitizer and a chiral catalyst according to claims 1-4, It is characterized in that The following steps are involved: S1 Under argon protection, the photosensitizer, organic base and condensation agent are dissolved in an organic solvent and stirred thoroughly for 1 hour; S2: Under argon atmosphere, a compound containing an amino group is dissolved in an organic solvent, added to the above reaction solvent, reacted for 12 hours, and the final product is obtained after post-treatment and purification.

6. The photosensitizer according to claims 1-5, It is characterized in that The photosensitizer has the following molecular structure formula: wherein R and R′ are the same or different and are independently unsubstituted or optionally substituted by one, two or more R o Substituted with the following groups: hydroxyl, C 1-6 Hydrocarbyl-substituted amino, carbonyl, C 1-6 Hydrocarbyl or halogen; R 12 Represents H or C 1-20 Alkyl, etc.: Y represents O, S or NH.

7. The organic base according to claim 5, wherein the organic base is preferably DIPEA.

8. The condensing agent according to claim 5, wherein the condensing agent is preferably HATU, HOBT and EDCI.

9. A photocatalytic system, It is characterized in that Comprising the photocatalyst as described in claims 1-4.

10. Use of the bifunctional photocatalyst according to claims 1 to 4 or the photocatalytic system according to claim 9 in a photocatalytic asymmetric reaction.

Images