CN117050050A - Alkynyl-sulfur ylide compound and preparation method thereof - Google Patents

Alkynyl-sulfur ylide compound and preparation method thereof Download PDF

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CN117050050A
CN117050050A CN202310869834.5A CN202310869834A CN117050050A CN 117050050 A CN117050050 A CN 117050050A CN 202310869834 A CN202310869834 A CN 202310869834A CN 117050050 A CN117050050 A CN 117050050A
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alkynyl
aryl
alkyl
heteroaryl
groups
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黄湧
陈杰安
武丰瑾
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Shenzhen Bay Laboratory Pingshan Biomedical R & D And Transformation Center
Hong Kong University of Science and Technology HKUST
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Shenzhen Bay Laboratory Pingshan Biomedical R & D And Transformation Center
Hong Kong University of Science and Technology HKUST
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C07D307/80—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The application relates to the technical field of organic chemical synthesis, in particular to an alkynyl-sulfur ylide compound and a preparation method thereof. The preparation method of the alkynyl-sulfur ylide compound provided by the application comprises the following steps: the iodine-sulfur She Li compound shown in the specification and the alkyne compound shown in the formula III are subjected to coupling reaction under the condition of a copper catalyst to obtain the alkyne-sulfur ylide compound shown in the formula I. The preparation method has the advantages that raw materials are easy to obtain, the preparation method can be directly used for preparation production without additional modification protection, the operation steps are simplified, the reaction route is shortened, the atomic utilization rate of reactants is high, the reaction rate is high, the production efficiency is obviously improved, and the designability and the application prospect of the alkynyl-sulfur ylide compound shown in the formula I can be greatly expanded.

Description

Alkynyl-sulfur ylide compound and preparation method thereof
Technical Field
The application belongs to the technical field of organic chemical synthesis, and particularly relates to an alkynyl-sulfur ylide compound and a preparation method thereof.
Background
Sulfur ylides (s-ylides) have a carbanion structure stabilized by an adjacent positive sulfur ion; sulfur ylide is a functional group that can undergo multiple transformations, and due to its poor stability, it is generally introduced at the alpha position of the ketocarbonyl group to act to stabilize the functional group. As the interest of chemists on sulfur ylide increases, it has a significant impact on the fields of medicinal chemistry, material chemistry, chemical biology, biochemistry, etc.
Currently, α -carbonyl-thio ylides are mostly alkyl-substituted and the sulfur center is mostly tetravalent. The reported synthesis of alkyl-substituted sulfur ylides utilizes S N 2 reacting thioether with halide, and performing strong alkali treatment to obtain the product; in addition, there are also alkynyl-sulfur (IV) ylides produced from unsubstituted α -carbonyl-sulfur ylides and anhydrides, but only alkynyl-sulfur ylides containing tetravalent sulfur centers can be obtained in this process, and the anhydride compounds easily absorb water, and the operational difficulty of the synthesis process is large.
Disclosure of Invention
The application aims to provide an alkynyl-sulfur ylide compound and a preparation method thereof, and aims to solve the technical problem of how to obtain alkynyl-sulfur ylide containing hexavalent sulfur center.
In order to achieve the purposes of the application, the technical scheme adopted by the application is as follows:
in a first aspect, the application provides a method for preparing an alkynyl-sulfur ylide compound, which is characterized by comprising the following steps:
the iodine-sulfur She Li compound shown in the formula II and the alkyne compound shown in the formula III are reacted in a copper catalyst
Wherein R is 1 And R is 2 Independently include C 1 -C 20 Alkyl, C 1 -C 20 Heteroalkyl, C 3 -C 20 Cycloalkyl, C 3 -C 20 Heterocycloalkyl, C 2 -C 20 Alkenyl, C 2 -C 20 Heteroalkenyl, C 3 -C 20 Cycloalkenyl group、C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl radicals, C 3 -C 20 Heterocyclic alkynyl, C 1 -C 20 Alkoxy, C 6 -C 20 Aryl, substituted (C) 6 -C 20 ) Aryl, C 3 -C 20 Heteroaryl, substituted (C) 3 -C 20 ) Heteroaryl, C 6 -C 20 Aryloxy, C 3 -C 20 Heteroaryloxy, C 6 -C 20 Aryl (C) 1 -C 20 ) Alkyl, C 3 -C 20 Heteroaryl (C) 1 -C 20 ) Any one of alkyl groups.
In the preparation method of the alkynyl-sulfur ylide compound provided by the first aspect of the application, an iodine-sulfur ylide compound reagent (shown as a formula II) and an alkyne compound (shown as a formula III) containing high-valence iodine and hexavalent sulfur are used as substrates, and a commercially available copper-based catalyst is used for carrying out a Sonogashira coupling reaction to obtain the alkynyl-sulfur ylide compound shown as a formula I. The preparation method has the advantages that raw materials are easy to obtain, and the preparation method can be directly used for preparation without additional modification protection before synthesis, so that the operation steps are simplified, the reaction route is shortened, the atomic utilization rate of reactants is high, the reaction rate is high, the production efficiency is obviously improved, and the designability and the application prospect of the alkynyl-sulfur ylide compound shown in the formula I can be greatly expanded.
In a second aspect, the application provides an alkynyl-sulfur ylide compound, wherein the molecular structural general formula of the alkynyl-sulfur ylide compound is shown as formula I:
wherein R is 1 And R is 2 Independently include C 1 -C 20 Alkyl, C 1 -C 20 Heteroalkyl, C 3 -C 20 Cycloalkyl, C 3 -C 20 Heterocycloalkyl, C 2 -C 20 Alkenyl, C 2 -C 20 Heteroalkenyl, C 3 -C 20 Cycloalkenyl, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl radicals, C 3 -C 20 Heterocyclic alkynyl, C 1 -C 20 Alkoxy, C 6 -C 20 Aryl, substituted (C) 6 -C 20 ) Aryl, C 3 -C 20 Heteroaryl, substituted (C) 3 -C 20 ) Heteroaryl, C 6 -C 20 Aryloxy, C 3 -C 20 Heteroaryloxy, C 6 -C 20 Aryl (C) 1 -C 20 ) Alkyl, C 3 -C 20 Heteroaryl (C) 1 -C 20 ) Any one of alkyl groups.
The alkynyl-sulfur ylide compounds provided in the second aspect of the application are a class of alkynyl-sulfur (VI) She Li-containing hexavalent sulfur centers. The alkynyl-sulfur ylide compound shown in the formula I has high functionality and more active chemical property, and can generate various chemical transformations, so that the alkynyl-sulfur ylide compound is more diversified in the application of synthesis of a drug intermediate and a functional material, can be used for synthesis of the drug intermediate and preparation of the functional material, can effectively reduce the economic cost of preparation of the drug intermediate and the functional material, and can be widely applied to the fields of organic synthetic chemistry, biochemistry, asymmetric catalysis, pesticides and medicine research.
Detailed Description
In order to make the technical problems, technical schemes and beneficial effects to be solved more clear, the application is further described in detail below with reference to the embodiments. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the application.
In the present application, the term "and/or" describes an association relationship of an association object, which means that three relationships may exist, for example, a and/or B may mean: a alone, a and B together, and B alone. Wherein A, B may be singular or plural. The character "/" generally indicates that the context-dependent object is an "or" relationship.
In the present application, "at least one" means one or more, and "a plurality" means two or more. "at least one of" or the like means any combination of these items, including any combination of single item(s) or plural items(s).
It should be understood that, in various embodiments of the present application, the sequence number of each process described above does not mean that the execution sequence of some or all of the steps may be executed in parallel or executed sequentially, and the execution sequence of each process should be determined by its functions and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.
The terminology used in the embodiments of the application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used in this application and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.
The weights of the relevant components mentioned in the description of the embodiments of the present application may refer not only to the specific contents of the components, but also to the proportional relationship between the weights of the components, so long as the contents of the relevant components in the description of the embodiments of the present application are scaled up or down within the scope of the disclosure of the embodiments of the present application. Specifically, the mass described in the specification of the embodiment of the application can be mass units known in the chemical industry field such as mu g, mg, g, kg.
The compounds and derivatives thereof referred to in the examples of the present application are named according to the IUPAC (International Union of pure and applied chemistry) or CAS (chemical abstract service Co., columbus, ohio) naming system. Thus, the compound groups specifically referred to in the examples of the present application are described and illustrated as follows:
with respect to "hydrocarbon groups", the minimum and maximum values of the carbon atom content in the hydrocarbon groups are represented by prefixes, for example, prefixes (C a -C b ) Alkyl means any alkyl group containing from "a" to "b" carbon atoms. Thus, for example, (C) 1 -C 6 ) Alkyl refers to alkyl groups containing one to six carbon atoms.
"alkoxy" refers to a straight or branched, monovalent, saturated aliphatic chain having an oxygen atom attached thereto and includes, but is not limited to, e.g., methoxy, ethoxy, propoxy, butoxy, isobutoxy, t-butoxy, and the like. (C) a -C b ) Alkoxy refers to any straight or branched, monovalent, saturated aliphatic chain having an alkyl group of "a" to "b" carbon atoms bonded to an oxygen atom.
"alkyl" refers to a straight or branched, monovalent, saturated aliphatic chain including, but not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, hexyl, and the like.
"heteroalkyl" refers to a straight or branched, monovalent, saturated fatty chain attached to at least one heteroatom, such as, but not limited to, methylaminoethyl or other similar group.
"alkenyl" refers to straight or branched chain hydrocarbons with one or more double bonds, including but not limited to, e.g., ethenyl, propenyl, and the like.
"heteroalkenyl" refers to a straight or branched chain hydrocarbon attached to at least one heteroatom with one or more double bonds, including but not limited to, e.g., vinylaminoethyl or other similar groups.
"alkynyl" refers to a straight or branched hydrocarbon bearing one or more triple bonds, including but not limited to, e.g., ethynyl, propynyl, and the like.
"heteroalkynyl" refers to a straight or branched chain hydrocarbon attached to at least one heteroatom with one or more triple bonds, including but not limited to, e.g., ethynyl, propynyl, and the like.
"aryl" refers to a cyclic aromatic hydrocarbon including, but not limited to, groups such as phenyl, naphthyl, anthryl, phenanthryl, and the like.
"heteroaryl" refers to a monocyclic or polycyclic or fused ring aromatic hydrocarbon in which one or more carbon atoms have been replaced by a heteroatom such as nitrogen, oxygen or sulfur. If the heteroaryl group contains more than one heteroatom, these heteroatoms may be the same or may be different. Heteroaryl groups include, but are not limited to, groups such as benzofuranyl, benzothienyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzopyranyl, furanyl, imidazolyl, indazolyl, indolizinyl, indolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxadiazolyl, oxazinyl, oxazolyl, phthalazinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridin [3,4-b ] indolyl, pyridinyl, pyrimidinyl, pyrrolyl, quinolizinyl, quinolinyl, quinoxalinyl, thiadiazolyl, thiatriazolyl, thiazolyl, thienyl, triazinyl, triazolyl, xanthenyl, and the like.
"cycloalkyl" refers to a saturated monocyclic or polycyclic alkyl group, possibly fused to an aromatic hydrocarbon group. Cycloalkyl groups include, but are not limited to, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, indanyl, tetrahydronaphthyl, and the like.
"Heterocyclyl" refers to a saturated mono-or polycyclic alkyl group, possibly fused to an aromatic hydrocarbon group, wherein at least one carbon atom has been replaced by a heteroatom such as nitrogen, oxygen or sulfur. If the heterocycloalkyl group contains more than one heteroatom, these heteroatoms may be the same or different. Heterocyclylalkyl groups include, but are not limited to, for example, azabicycloheptyl, azetidinyl, indolinyl, morpholinyl, pyrazinyl, piperidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydroquinolinyl, tetrahydroindazolyl, tetrahydroindolyl, tetrahydroisoquinolinyl, tetrahydropyranyl, tetrahydroquinoxalinyl, tetrahydrothiopyranyl, thiazolidinyl, thiomorpholinyl, thioxanthyl, thiooxalkyl, and the like.
"cycloalkenyl" refers to an unsaturated, mono-or polycyclic alkenyl group with one or more double bonds, possibly fused to an aromatic hydrocarbon group, including but not limited to a cycloethenyl group, a cyclopropenyl group, or other similar groups.
"heterocycloalkenyl" refers to an unsaturated, monocyclic or polycyclic alkenyl group having one or more double bonds, possibly fused to an aromatic hydrocarbon group, in which at least one carbon atom is replaced by a heteroatom such as nitrogen, oxygen or sulfur. If the heterocycloalkyl group contains more than one heteroatom, these heteroatoms may be the same or different.
"cycloalkynyl" refers to an unsaturated, mono-or polycyclic alkynyl group with one or more triple bonds, possibly fused to an aromatic hydrocarbon group, including but not limited to cycloalkynyl, cyclopropynyl, or other like groups.
"heterocycloalkynyl" refers to an unsaturated, mono-or polycyclic alkynyl group with one or more triple bonds, possibly fused to an aromatic hydrocarbon group, in which at least one carbon atom is replaced with a heteroatom such as nitrogen, oxygen or sulfur. If the heterocycloalkyl group contains more than one heteroatom, these heteroatoms may be the same or different.
In a first aspect, an embodiment of the present application provides a method for preparing an alkynyl-thio ylide compound, including the steps of:
performing a coupling reaction on an iodine-sulfur She Li de compound shown in a formula II and an alkyne compound shown in a formula III under the condition of a copper catalyst to obtain an alkynyl-sulfur ylide compound shown in a formula I;
wherein R is 1 And R is 2 Independently include C 1 -C 20 Alkyl, C 1 -C 20 Heteroalkyl, C 3 -C 20 Cycloalkyl, C 3 -C 20 Heterocycloalkyl, C 2 -C 20 Alkenyl, C 2 -C 20 Heteroalkenyl, C 3 -C 20 Cycloalkenyl, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl radicals, C 3 -C 20 Heterocyclic alkynyl, C 1 -C 20 Alkoxy, C 6 -C 20 Aryl, substituted (C) 6 -C 20 ) Aryl, C 3 -C 20 Heteroaryl, substituted (C) 3 -C 20 ) Heteroaryl, C 6 -C 20 Aryloxy, C 3 -C 20 Heteroaryloxy, C 6 -C 20 Aryl (C) 1 -C 20 ) Alkyl, C 3 -C 20 Heteroaryl (C) 1 -C 20 ) Any one of alkyl groups.
The preparation method of the alkynyl-sulfur (VI) ylide compound provided by the application is a novel C sp -C sp2 The bond construction method has the following advantages: (1) The application adopts a commercially available copper catalyst system to realize the synthesis of the alkynyl-sulfur (VI) ylide compound of hexavalent (expressed by VI) sulfur, the copper metal is used for catalyzing the coupling reaction, the atomic utilization rate of reactants is high, the reaction efficiency is high, the improvement of the product generation yield is facilitated, and the reaction process is safe and controllable. (2) According to the preparation method disclosed by the application, the high-valence iodine-sulfur (VI) ylide compound reagent (shown in formula II) and the alkyne compound (shown in formula III) are used as substrates, the substrate raw materials are easy to obtain, and the substrate reactants can be directly used for preparation production without additional modification protection before reaction, so that the operation steps are simplified, the reaction route is shortened, the production efficiency is obviously improved, and the alkyne-sulfur ylide compound with potential application can be efficiently and greenly prepared. (3) The preparation method provided by the application greatly expands the designability and application prospect of the alkynyl-sulfur ylide compound shown in the formula I, and the alkynyl-sulfur ylide compound obtained by the method has high functional group, so that the alkynyl-sulfur ylide compound is more diversified in the synthesis of a drug intermediate and the application of a functional material, can be widely used for the synthesis of the drug intermediate and the preparation of the functional material, and can effectively reduce the economic cost of the preparation of the drug intermediate and the functional material. Therefore, the catalyst can be widely used in the fields of organic synthetic chemistry, biochemistry, asymmetric catalysis, pesticides and medicine research.
In the raw material iodine-sulfur ylide compound shown in the formula II, iodine is trivalent iodine with high valence, and is connected with benzene (Ph) group and hexafluorophosphate (PF) 6 ) A sulfur ylide structure of a base and hexavalent sulfur; wherein R is 1 R in alkynyl-sulfur ylide compound shown in corresponding product formula I 1 . In the alkyne compound shown in the formula III as raw material, R 2 R in alkynyl-sulfur ylide compound shown in corresponding product formula I 2 . The iodine-sulfur She Li compound shown in the formula II and the alkyne compound shown in the formula III can be prepared by self by referring to the existing preparation method, and can also be directly obtained in a commercial way.
Wherein R is 1 And R is 2 Independently include C 1 -C 20 Alkyl, C 1 -C 20 Heteroalkyl, C 3 -C 20 Cycloalkyl, C 3 -C 20 Heterocycloalkyl, C 2 -C 20 Alkenyl, C 2 -C 20 Heteroalkenyl, C 3 -C 20 Cycloalkenyl, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl radicals, C 3 -C 20 Heterocyclic alkynyl, C 1 -C 20 Alkoxy, C 6 -C 20 Aryl, substituted (C) 6 -C 20 ) Aryl, C 3 -C 20 Heteroaryl, substituted (C) 3 -C 20 ) Heteroaryl, C 6 -C 20 Aryloxy, C 3 -C 20 Heteroaryloxy, C 6 -C 20 Aryl (C) 1 -C 20 ) Alkyl, C 3 -C 20 Heteroaryl (C) 1 -C 20 ) Any one of alkyl groups.
Specifically, R 1 And R is 2 May include the same or different C 1 -C 20 Alkyl, C 1 -C 20 Heteroalkyl, C 3 -C 20 Cycloalkyl, C 3 -C 20 Heterocycloalkyl, C 2 -C 20 Alkenyl, C 2 -C 20 Heteroalkenyl, C 3 -C 20 Cycloalkenyl, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl radicals, C 3 -C 20 Heterocyclic alkynyl, C 1 -C 20 Alkoxy, C 6 -C 20 Aryl, substituted (C) 6 -C 20 ) Aryl, C 3 -C 20 Heteroaryl, substituted (C) 3 -C 20 ) Heteroaryl, C 6 -C 20 Aryloxy, C 3 -C 20 Heteroaryloxy, C 6 -C 20 Aryl (C) 1 -C 20 ) Alkyl, C 3 -C 20 Heteroaryl (C) 1 -C 20 ) Any one of alkyl groups.
When R is 1 And R is 2 Comprising identical or non-identical C 1 -C 20 When alkyl, in some embodiments, C 1 -C 20 The alkyl group may be (C 1 -C 10 ) Alkyl, (C) 1 -C 5 ) Alkyl, (C) 1 -C 4 ) Alkyl, (C) 1 -C 3 ) Alkyl, (C) 1 -C 2 ) Alkyl groups, and the like. In some embodiments, (C) 1 -C 20 ) The alkyl group may specifically be methyl, ethyl, propyl, butyl, isobutyl, pentyl, isopentyl, and the like.
When R is 1 And R is 2 Comprising identical or non-identical (C 1 -C 20 ) In the case of heteroalkyl groups, in one embodiment, (C 1 -C 20 ) The heteroalkyl group may be (C) 1 -C 10 ) Heteroalkyl (C) 1 -C 5 ) Heteroalkyl (C) 1 -C 4 ) Heteroalkyl (C) 1 -C 3 ) Heteroalkyl (C) 1 -C 2 ) Heteroalkyl groups, and the like. In some embodiments, the heteroatom may be a halogen, nitrogen atom, sulfur atom, or the like.
When R is 1 And R is 2 Comprising identical or non-identical (C 3 -C 20 ) In the case of cycloalkyl, in one embodiment, (C 3 -C 20 ) Cycloalkyl groups may be (C) 3 -C 10 ) Cycloalkyl, (C) 3 -C 5 ) Cycloalkyl, (C) 3 -C 4 ) Cycloalkyl groups, and the like. In one embodiment, (C) 3 -C 20 ) Cycloalkyl groups may be cyclopropyl, cyclobutyl, cyclopentyl, and the like.
When R is 1 And R is 2 Comprising identical or non-identical (C 3 -C 20 ) When heterocycloalkyl, (C) in one embodiment 3 -C 20 ) Heterocyclylalkyl can be (C) 3 -C 10 ) Heterocycloalkyl, (C) 3 -C 10 ) Heterocycloalkyl, (C) 3 -C 5 ) Heterocycloalkyl, (C) 3 -C 4 ) Heterocycloalkyl, and the like. In one embodiment, the heteroatom may be halogen, nitrogen, sulfur, or the like.
When R is 1 And R is 2 Comprising identical or non-identical (C 2 -C 20 ) Alkenyl groups, in one embodiment, (C 2 -C 20 ) Alkenyl groups may be (C) 3 -C 10 ) Alkenyl group (C) 3 -C 5 ) Alkenyl group (C) 3 -C 4 ) Alkenyl group (C) 2 -C 3 ) Alkenyl groups, and the like. In some embodiments, (C) 2 -C 20 ) Alkenyl groups may be ethenyl, propenyl, butenyl, pentenyl, and the like.
When R is 1 And R is 2 Comprising identical or non-identical (C 2 -C 20 ) In the case of heteroalkenyl groups, in one embodiment, (C 2 -C 20 ) The heteroalkenyl group may be (C) 2 -C 10 ) Heteroalkenyl, (C) 3 -C 10 ) Heteroalkenyl, (C) 3 -C 5 ) Heteroalkenyl, (C) 3 -C 4 ) Heteroalkenyl, (C) 2 -C 3 ) Heteroalkenyl groups, and the like. In some embodiments, the heteroatom may be a halogen, nitrogen atom, sulfur atom, or the like.
When R is 1 And R is 2 Comprising identical or non-identical (C 3 -C 20 ) In the case of cycloalkenyl, (C) 3 -C 20 ) Cycloalkenyl groups may be (C 3 -C 10 ) Cycloalkenyl, (C) 3 -C 5 ) Cycloalkenyl, (C) 3 -C 4 ) Cycloalkenyl groups, and the like. In some embodiments, (C) 3 -C 20 ) The cycloalkenyl group may be cyclopropenyl, cyclobutenyl, cyclopentenyl, and the like.
When R is 1 And R is 2 Comprising identical or non-identical (C 3 -C 20 ) In one embodiment, (C) 3 -C 20 ) The heterocycloalkenyl group may be (C 3 -C 10 ) Heterocycloalkenyl, (C) 3 -C 5 ) Heterocycloalkenyl, (C) 3 -C 4 ) Heterocycloalkenyl, and the like. In some embodimentsThe heteroatom may be, for example, halogen, nitrogen, sulfur, etc.
When R is 1 And R is 2 Comprising identical or non-identical (C 2 -C 20 ) Alkynyl groups, in one embodiment, (C) 2 -C 20 ) Alkynyl groups may be (C) 2 -C 10 ) Alkynyl, (C) 3 -C 10 ) Alkynyl, (C) 3 -C 5 ) Alkynyl, (C) 3 -C 4 ) Alkynyl, (C) 2 -C 3 ) Alkynyl groups, and the like. In some embodiments, (C) 2 -C 20 ) Alkynyl groups may be ethynyl, propynyl, butynyl, pentynyl, and the like.
When R is 1 And R is 2 Comprising identical or non-identical (C 2 -C 20 ) In the case of heteroalkynyl, (C) 2 -C 20 ) The heteroalkynyl group may be (C) 2 -C 10 ) Heteroalkynyl, (C) 3 -C 10 ) Heteroalkynyl, (C) 3 -C 5 ) Heteroalkynyl, (C) 3 -C 4 ) Heteroalkynyl, (C) 2 -C 3 ) Heteroalkynyl, and the like. In some embodiments, the heteroatom may be a halogen, nitrogen atom, sulfur atom, or the like.
When R is 1 And R is 2 Comprising identical or non-identical (C 3 -C 20 ) In the case of cycloalkynyl, in one embodiment, (C 3 -C 20 ) The cycloalkynyl group may be (C) 3 -C 10 ) Cycloalkynyl, (C) 3 -C 5 ) Cycloalkynyl, (C) 3 -C 4 ) Cycloalkynyl, and the like. In some embodiments, (C) 2 -C 20 ) The cycloalkynyl group may be cyclopropynyl group, cyclobutynyl group, cyclopentynyl group or the like.
When R is 1 And R is 2 Comprising identical or non-identical (C 3 -C 20 ) In one embodiment, (C) 3 -C 20 ) The heterocycloalkynyl group may be (C) 3 -C 10 ) Heterocycloalkynyl, (C) 3 -C 5 ) Heterocycloalkynyl, (C) 3 -C 4 ) Heterocycloalkynyl, and the like. In some embodiments, the heteroatom may be a halogen, nitrogen atom, sulfur atom, or the like.
When R is 1 And R is 2 Comprising phasesIdentical or different (C 1 -C 20 ) In the case of alkoxy groups, in one embodiment, (C 1 -C 20 ) Alkoxy groups may be (C) 1 -C 10 ) Alkoxy, (C) 1 -C 8 ) Alkoxy, (C) 1 -C 6 ) Alkoxy, (C) 1 -C 4 ) Alkoxy, (C) 1 -C 3 ) Alkoxy, (C) 1 -C 2 ) An alkoxy group. In some embodiments, (C) 1 -C 20 ) Alkoxy groups may be, but are not limited to, methyl, ethyl, propyl, etc.
When R is 1 And R is 2 Comprising identical or non-identical (C 6 -C 20 ) When aryl, the aryl may be, but is not limited to, monocyclic aryl, polycyclic aryl, fused ring aryl. In one embodiment, the aryl is a monocyclic aryl. In some embodiments, the aryl is phenyl.
When R is 1 And R is 2 Comprising identical or different substituents (C 6 -C 20 ) When aryl, the substituted aryl may be, but is not limited to, ortho, meta, para substituted phenyl, singly or multiply. Substituents include, but are not limited to, C 1 -C 10 Alkyl, substituted C 1 -C 10 Alkyl, halogen, C 1 -C 10 An alkylamino group, a nitro group. Where the substituents are alkyl groups, alkyl groups such as, but not limited to, methyl, ethyl, propyl, butyl, isobutyl; when the substituent is a substituted alkyl group, the substituted alkyl group is such as, but not limited to, trifluoromethyl, trichloromethyl, trifluoroethyl, trichloroethyl; when the substituent is halogen, halogen such as, but not limited to, fluorine, chlorine, bromine, iodine; when the substituent is an alkoxy group, the alkoxy group is, for example, but not limited to, a methyloxy group, an ethyloxy group, a propyloxy group. In one embodiment, the substituted aryl group may also be cyano (C 1 -C 10 ) Alkyl (C) 3 -C 8 ) Aryl, substituted (C) 3 -C 8 ) Aryl groups.
When R is 1 And R is 2 Comprising identical or non-identical C 3 -C 20 In the case of heteroaryl groups, in one embodiment, the heteroaryl group may be (C 3 -C 10 ) Heteroaryl, furan, thiophene.
When R is 1 And R is 2 Comprising identical or different substituents C 3 -C 20 In the case of heteroaryl groups, in one embodiment, the substituted heteroaryl groups may be substituted (C 3 -C 10 ) Heteroaryl, alkoxy substituted furans, (C) 3 -C 8 ) Heteroaryl substituted furans, fatty chain substituted thiophenes. Substituents include, but are not limited to, C 1 -C 10 Alkyl, substituted C 1 -C 10 Alkyl, halogen, C 1 -C 10 An alkylamino group, a nitro group. Where the substituents are alkyl groups, alkyl groups such as, but not limited to, methyl, ethyl, propyl, butyl, isobutyl; when the substituent is a substituted alkyl group, the substituted alkyl group is such as, but not limited to, trifluoromethyl, trichloromethyl, trifluoroethyl, trichloroethyl; when the substituent is halogen, halogen such as, but not limited to, fluorine, chlorine, bromine, iodine; when the substituent is an alkoxy group, the alkoxy group is, for example, but not limited to, a methyloxy group, an ethyloxy group, a propyloxy group.
When R is 1 And R is 2 Comprising identical or non-identical C 6 -C 20 When aryloxy, in one embodiment, the aryloxy may be phenoxy, naphthoxy, anthracenoxy, phenanthroxy.
When R is 1 And R is 2 Comprising identical or non-identical C 6 -C 20 Aryl (C) 1 -C 20 ) In the case of alkyl, in one embodiment, the aryl group (C 1 -C 20 ) The alkyl group may be aryl (C) 1 -C 10 ) Alkyl, phenyl (C) 1 -C 10 ) Alkyl, phenyl (C) 1 -C 5 ) Alkyl, phenyl (C) 1 -C 4 ) Alkyl, phenyl (C) 1 -C 3 ) Alkyl, phenyl (C) 1 -C 2 ) Alkyl groups, and the like. In some embodiments, aryl (C 1 -C 20 ) The alkyl group may be phenylmethyl, phenylethyl, phenylpropyl, phenylbutyl, phenylisobutyl, phenylpentyl, phenylisopentyl, phenylneopentyl.
When R is 1 And R is 2 Comprising identical or non-identical C 3 -C 20 Heteroaryl (C) 1 -C 20 ) In the case of alkyl groups, in aIn an embodiment, the heteroaryl (C 1 -C 20 ) The alkyl group may be heteroaryl (C) 1 -C 10 ) Alkyl, heteroaryl (C) 1 -C 10 ) Alkyl, heteroaryl (C) 1 -C 5 ) Alkyl, heteroaryl (C) 1 -C 4 ) Alkyl, heteroaryl (C) 1 -C 3 ) Alkyl, heteroaryl (C) 1 -C 2 ) Alkyl groups, and the like. Wherein the heteroaryl group may be (C 3 -C 8 ) Heteroaryl, furan, pyridine, and the like.
In some embodiments, R 1 And R is 2 C being identical or different 1 -C 10 Alkyl, C 1 -C 10 Heteroalkyl, C 3 -C 10 Cycloalkyl, C 3 -C 10 Heterocycloalkyl, C 2 -C 10 Alkenyl, C 2 -C 10 Heteroalkenyl, C 3 -C 10 Cycloalkenyl, C 3 -C 10 Heterocycloalkenyl, C 2 -C 10 Alkynyl, C 2 -C 10 Heteroalkynyl, C 3 -C 10 Cycloalkynyl radicals, C 3 -C 10 Heterocyclic alkynyl, C 1 -C 10 Alkoxy, C 6 -C 20 Aryl, C 3 -C 20 Any of the heteroaryl groups.
In some embodiments, R 1 And R is 2 In (C) substituted (C) 6 -C 20 ) Aryl, C 3 -C 20 Heteroaryl, substituted (C) 3 -C 20 ) Heteroaryl groups, the substituents being independently selected from halogen atoms, C 1 -C 5 Alkyl, C 1 -C 5 At least one of an alkoxy group, a phenyl group, a phenoxy group, a nitro group, and an acyl group.
In some embodiments, R 1 Comprises C 1 -C 10 Alkyl and C 6 -C 16 Any one of aryl groups; r is R 2 Comprises C 6 -C 16 Aryl and C 3 -C 16 Heteroaryl groups.
In some embodiments, the copper-based catalyst comprises Cu (MeCN) 4 PF 6 And at least one of L-Cu-X; wherein X is a halogen atom and L is a diimine-containing ligand, e.gPhenanthroline and bipyridine and their derivative ligands. For example, the copper-based catalyst may be at least one of cuprous chloride/bipyridine ligand, cuprous iodide/bipyridine ligand catalyst, and copper tetraacetonitrile hexafluorophosphate. In a specific experiment, the tetra-acetonitrile copper hexafluorophosphate catalyst can catalyze the reaction more efficiently.
In some embodiments, the reaction system of the coupling reaction is added with an alkali reagent, wherein the alkali reagent comprises at least one of lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, triethylamine, diisopropylethylamine, lithium bis (trimethylsilyl) amide, sodium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide, lithium bis (isopropylamide), n-butyllithium, tert-butyllithium, methyllithium, sodium methoxide, sodium ethoxide, and sodium ethylthiolate.
According to the iodine-sulfur She Li de compound shown in the formula II and the alkyne compound shown in the formula III, the alkyne compound forms a copper alkyne active species with a copper catalyst under the action of alkali, so that the iodine-sulfur ylide compound reaction is further improved. Therefore, the atomic utilization rate of the reactant is effectively improved, the limitation of the substrate is widened, the target product precursor with high enantioselectivity and extremely wide range is efficiently and greenly prepared, and the alkynyl-sulfur (VI) She Li German compound with potential application value is obtained through a simple reduction reaction.
The above equation is as follows:
in the chemical reaction formula, the copper catalyst and the alkali reagent act synergistically, so that the catalytic system has low toxicity, the atomic utilization rate and the reaction efficiency are improved, and the byproducts are few; meanwhile, the reaction process is safe and controllable, and the operation in the preparation and production processes is simplified. The base reagent reacts with the alkyne compound to deprotonate the alkyne to form activated copper alkyne. Under the condition that the contents of the three are in a certain range and in proportion, the reaction has high catalytic efficiency, and the target product with nearly equivalent yield is obtained.
In order to allow the synergistic catalytic system to perform a more efficient catalytic action, in one embodiment, the molar ratio of copper-based catalyst to alkaline reagent is (0.1-20): 0.1-20. Under the condition, the reaction has high catalytic efficiency under the synergistic action of the copper catalyst and the alkali reagent, and is beneficial to improving the yield of reaction products. Preferably, the molar ratio of the copper-based catalyst to the alkali agent is (0.2-20): (1-10), in which case it is advantageous to obtain a near equivalent yield of the desired product.
In one embodiment, the molar ratio of the copper-based catalyst, the alkaline reagent, and the iodine-sulfur ylide compound of formula II is (0.1-20): 0.2-40. In this case, the reaction has high catalytic efficiency, which is advantageous in improving the yield of the reaction product. In some embodiments, the addition amount of the copper-based catalyst and the alkali agent in the reaction system is controlled and the molar ratio of the iodine-sulfur ylide compound shown in the formula II is (0.2-20): 2 (1-10).
Furthermore, the reaction system can be smoothly carried out at a lower temperature, and the reaction temperature ranges from 0 ℃ to 25 ℃. In order to further increase the reaction efficiency and increase the yield of the reaction product, in one embodiment, the reaction temperature of the reaction system is 0 ℃. In another embodiment, the reaction temperature of the reaction system is 0℃to 10 ℃. In another embodiment, the reaction temperature of the reaction system is 0℃to 20 ℃. In another embodiment, the reaction temperature of the reaction system is 10℃to 25 ℃. The reaction time in the environment of each preferred reaction temperature should be such that the above reactants react sufficiently, e.g., the reaction time may be 1 to 5 hours, or longer.
In the above reaction system, a certain amount of solvent may be optionally added. The solvent includes, but is not limited to, diethyl ether, tetrahydrofuran, methylene chloride, toluene. In one embodiment, the solvent may be added in a molar ratio of solvent to catalyst such that (1000-1000000): 1.
in a second aspect, an embodiment of the present application provides an alkynyl-sulfur ylide compound, where the molecular structural general formula of the alkynyl-sulfur ylide compound is shown in formula I:
wherein R is 1 And R is 2 Independently include C 1 -C 20 Alkyl, C 1 -C 20 Heteroalkyl, C 3 -C 20 Cycloalkyl, C 3 -C 20 Heterocycloalkyl, C 2 -C 20 Alkenyl, C 2 -C 20 Heteroalkenyl, C 3 -C 20 Cycloalkenyl, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl radicals, C 3 -C 20 Heterocyclic alkynyl, C 1 -C 20 Alkoxy, C 6 -C 20 Aryl, substituted (C) 6 -C 20 ) Aryl, C 3 -C 20 Heteroaryl, substituted (C) 3 -C 20 ) Heteroaryl, C 6 -C 20 Aryloxy, C 3 -C 20 Heteroaryloxy, C 6 -C 20 Aryl (C) 1 -C 20 ) Alkyl, C 3 -C 20 Heteroaryl (C) 1 -C 20 ) Any one of alkyl groups.
The alkynyl-sulfur ylide compound shown in the formula I provided by the application is an alkynyl-sulfur (VI) She Li German compound containing hexavalent sulfur center. The alkynyl-sulfur ylide compound shown in the formula I has high functionality and more active chemical property, and can generate various chemical transformations, so that the alkynyl-sulfur ylide compound is more diversified in the application of synthesis of a drug intermediate and a functional material, can be used for synthesis of the drug intermediate and preparation of the functional material, can effectively reduce the economic cost of preparation of the drug intermediate and the functional material, and can be widely applied to the fields of organic synthetic chemistry, biochemistry, asymmetric catalysis, pesticides and medicine research.
In one embodiment, R 1 And R is 2 For specific choices see above.
In one embodiment, R 1 Comprises C 1 -C 10 Alkyl and C 6 -C 16 Any one of aryl groups. R is R 2 Comprises C 6 -C 16 Aryl and C 3 -C 16 Any one of heteroaryl groups.
In one embodiment, R 1 Is C 4 -C 10 Tertiary alkyl or C 6 -C 10 Aryl, R 2 Is C 6 -C 10 Aryl or C 3 -C 10 Heteroaryl groups.
In one embodiment, the alkynyl-thio-ylide compound includes at least one of:
the following description is made with reference to specific embodiments.
Example 1
This example provides a 4- (dimethyloxo) -6-sulfolobus) -2, 2-dimethyl-6-thiophene-5-alkyne-3-one and a method for preparing the same. The structural formula of the 4- (dimethyloxo) -6-sulfosubunit) -2, 2-dimethyl-6-thiophene 5-alkyne-3-ketone is shown as the following molecular structural formula I1.
The preparation method comprises the following steps:
copper catalyst Cu (MeCN) was added in 10ml tubes 4 PF 6 (0.01 mmol,0.1 equivalent), R in formula II 1 To the tert-butyl corresponding iodine-sulfur ylide reagent (0.2 mmol,1.0 equiv.) was dissolved in 1.0mL of pretreated dichloromethane, sealed with a rubber stopper, then replaced with gas under argon atmosphere (3 times), triethylamine (Et) was added 3 N) (28. Mu.L, 1.0 equiv.) and R in formula III 2 2-acetylenic thiophene (21 μl,1.0 equiv.) corresponding to thienyl was replaced with gas again under argon atmosphere (3 times). Sealing film for test tubeAfter which stirring is carried out at 0℃for 1 hour. The mixture was directly separated and purified using neutral alumina column chromatography (dichloromethane and acetone as eluent) to give the target product I1 as a white solid in 89% yield.
And (3) relevant characterization analysis, wherein the result is as follows: 1 H NMR(400MHz,Acetone-d 6 )δ7.42(dd,J＝5.3,1.2Hz,1H),7.12(dd,J＝3.6,1.2Hz,1H),7.04(dd,J＝5.2,3.6Hz,1H),3.64(s,6H),1.26(s,9H). 13 C NMR(101MHz,Acetone-d 6 )δ196.66,129.32,126.62,125.99,124.85,90.43,87.89,76.91,41.35,40.10,25.68.HRMS(ESI-TOF)calculated for C 14 H 18 O 2 S 2 (M+Na + ) 365.0640, found 365.0646. This result further demonstrates that the product molecular structure is as described above for molecular structure I1.
Example 2
This example provides a 6-benzofuran-2-yl-4-dimethyloxo-L6-sulfonylidene-2, 2-dimethylhex-5-yn-3-one and a method of making the same. The structural formula of the 6-benzofuran-2-yl-4-dimethyloxo-L6-sulfonyl subunit-2, 2-dimethylhex-5-yn-3-one is shown as the following molecular structural formula I2:
the preparation was described with reference to example 1 for the preparation of 4- (dimethyloxo) -6-sulpho) -2, 2-dimethyl-6-thiophen-5-yn-3-one, except that 2-ethynylbenzofuran was used instead of 2-ethynylthiophene. The reaction solution is directly separated and purified by neutral alumina column chromatography (dichloromethane and acetone are used as eluent) to obtain the target product, which is white solid with the yield of 55 percent.
The characterization data analysis of the prepared product I2 is carried out, and the result is that 1 H NMR(400MHz,Acetone-d 6 )δ7.60(ddd,J＝7.7,1.4,0.7Hz,1H),7.47(dq,J＝8.3,0.9Hz,1H),7.34(ddd,J＝8.4,7.2,1.3Hz,1H),7.25(td,J＝7.5,1.0Hz,1H),6.98(d,J＝1.0Hz,1H),3.69(s,6H),1.29(s,9H). 13 C NMR(101MHz,Acetone-d 6 )δ197.07,154.05,140.20,127.72,124.46,122.48,120.28,110.11,109.02,90.83,88.74,76.88,41.60,40.16,25.68.HRMS(ESI-TOF)calculated for C 18 H 20 O 3 S(M+Na + ) 339.1025, found:339.1031. This result further confirms that the product molecular structure is as described above for molecular structure I2.
Example 3
This example provides a 2-dimethyl-6-sulfonylidene-1, 4-diphenyl-but-3-yn-1-one and a method for preparing the same. The structural formula of the 2-dimethyl-6-sulfonyl subunit-1, 4-diphenyl but-3-alkyne-1-ketone is shown as the following molecular structural formula I3:
the preparation is described with reference to example 1 for the preparation of 4- (dimethyloxo) -6-sulpho-subunit) -2, 2-dimethyl-6-thiophen-5-yn-3-one, with the difference that R is in the corresponding iodo-thioylide reagent of formula II 1 Phenyl is adopted, and phenylacetylene is adopted to replace 2-ethynyl thiophene. The reaction solution is directly separated and purified by neutral alumina column chromatography (dichloromethane and acetone are used as eluent) to obtain the target product, which is white solid with the yield of 78 percent.
The prepared product I3 is subjected to characterization data analysis, and the result is as follows: 1 H NMR(400MHz,CDCl 3 )δ8.11–8.05(m,2H),7.49–7.38(m,3H),7.31–7.27(m,4H),7.26–7.18(m,1H),3.69(s,6H). 13 C NMR(101MHz,CDCl 3 )δ185.13,138.18,130.28,129.19,127.74,127.68,127.12,126.33,123.88,96.06,82.37,78.31,41.36.HRMS(ESI-TOF)calculated for C 18 H 16 O 2 S(M+H + ) 297.0944, found:297.0948. This result further confirms that the product molecular structure is as described above for molecular structure I3.
The foregoing description of the preferred embodiments of the application is not intended to be limiting, but rather is intended to cover all modifications, equivalents, and alternatives falling within the spirit and principles of the application.

Claims (10)

1. The preparation method of the alkynyl-sulfur ylide compound is characterized by comprising the following steps of:
performing a coupling reaction on an iodine-sulfur She Li de compound shown in a formula II and an alkyne compound shown in a formula III under the condition of a copper catalyst to obtain an alkynyl-sulfur ylide compound shown in a formula I;
wherein R is 1 And R is 2 Independently include C 1 -C 20 Alkyl, C 1 -C 20 Heteroalkyl, C 3 -C 20 Cycloalkyl, C 3 -C 20 Heterocycloalkyl, C 2 -C 20 Alkenyl, C 2 -C 20 Heteroalkenyl, C 3 -C 20 Cycloalkenyl, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl radicals, C 3 -C 20 Heterocyclic alkynyl, C 1 -C 20 Alkoxy, C 6 -C 20 Aryl, substituted (C) 6 -C 20 ) Aryl, C 3 -C 20 Heteroaryl, substituted (C) 3 -C 20 ) Heteroaryl, C 6 -C 20 Aryloxy, C 3 -C 20 Heteroaryloxy, C 6 -C 20 Aryl (C) 1 -C 20 ) Alkyl, C 3 -C 20 Heteroaryl (C) 1 -C 20 ) Any one of alkyl groups.
2. The process of claim 1, wherein R is 1 Comprises C 1 -C 10 Alkyl and C 6 -C 16 Any one of aryl groups; and/or the number of the groups of groups,
R 2 comprises C 6 -C 16 Aryl and C 3 -C 16 Heteroaryl groups.
3. The method of claim 1, whereinThe copper-based catalyst comprises Cu (MeCN) 4 PF 6 And at least one of L-Cu-X; wherein X is a halogen atom, and L is a diimine-containing ligand.
4. The preparation method according to claim 1, wherein an alkali reagent is added to the reaction system of the coupling reaction, and the alkali reagent comprises at least one of lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium hydrogen phosphate, potassium dihydrogen phosphate, triethylamine, diisopropylethylamine, lithium bis (trimethylsilyl) amide, sodium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide, lithium diisopropylamide, n-butyllithium, t-butyllithium, methyllithium, sodium methoxide, sodium ethoxide, and sodium ethylthiolate.
5. The process according to any one of claims 1 to 4, wherein the temperature of the coupling reaction is 0 to 25 ℃.
6. The alkynyl-sulfur ylide compound is characterized in that the molecular structural general formula of the alkynyl-sulfur ylide compound is shown as formula I:
wherein R is 1 And R is 2 Independently include C 1 -C 20 Alkyl, C 1 -C 20 Heteroalkyl, C 3 -C 20 Cycloalkyl, C 3 -C 20 Heterocycloalkyl, C 2 -C 20 Alkenyl, C 2 -C 20 Heteroalkenyl, C 3 -C 20 Cycloalkenyl, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl radicals, C 3 -C 20 Heterocyclic alkynyl, C 1 -C 20 Alkoxy, C 6 -C 20 Aryl, substituted (C) 6 -C 20 ) Aryl, C 3 -C 20 Heteroaryl, substituted (C) 3 -C 20 ) Heteroaryl, C 6 -C 20 Aryloxy, C 3 -C 20 Heteroaryloxy, C 6 -C 20 Aryl (C) 1 -C 20 ) Alkyl, C 3 -C 20 Heteroaryl (C) 1 -C 20 ) Any one of alkyl groups.
7. The alkynyl-thioylide compound according to claim 6, wherein R 1 Comprises C 1 -C 10 Alkyl and C 6 -C 16 Any one of aryl groups.
8. The alkynyl-thioylide compound according to claim 6, wherein R 2 Comprises C 6 -C 16 Aryl and C 3 -C 16 Any one of heteroaryl groups.
9. The alkynyl-thioylide compound according to claim 6, wherein R 1 Is C 4 -C 10 Tertiary alkyl or C 6 -C 10 Aryl, R 2 Is C 6 -C 10 Aryl or C 3 -C 10 Heteroaryl groups.
10. The alkynyl-sulfur ylide compound of any of claims 6-9, wherein the alkynyl-sulfur ylide compound comprises at least one of:
CN202310869834.5A 2023-07-14 2023-07-14 Alkynyl-sulfur ylide compound and preparation method thereof Pending CN117050050A (en)

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