CN109942612B - Diyne enamine compound and preparation method and application thereof - Google Patents
Diyne enamine compound and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a diyne enamine compound and a preparation method and application thereof. The general formula of the molecular structure of the diyne enamine compound is shown in the general formula (I) in the specification. The preparation method of the diyne enamine compound comprises the steps of adding secondary amine A and a gold catalyst into a reaction system containing an electrophilic reagent compound B, a pyridine ligand C and an alkynone compound D for reaction and the like. The diyne enamine compound contains a highly conjugated enamine structure skeleton, is convenient for further functionalization, and can be widely used for synthesis and preparation of a drug intermediate, particularly a polycyclic structure compound. The preparation method has the advantages of simple process, low requirement on reaction conditions, safe and controllable reaction process, high atom utilization rate and production efficiency, high efficiency, and capability of ensuring the regioselectivity and stereoselectivity of the product, and the introduction of the organometallic catalysis concept ensures that the methodology has small environmental pollution pressure.
Description
Technical Field
The invention belongs to the technical field of synthesis of enamine compounds, and particularly relates to a diyne enamine compound, a preparation method thereof and application of the diyne enamine compound.
Background
The highly conjugated enamine compound refers to an enamine compound having a highly conjugated π system in its molecular structure. The highly conjugated enamine compound is not only an extremely important medical fragment and intermediate, but also a potential bioactive molecule. The high conjugated enamine compound is used as a reaction intermediate, and is modified by a known chemical means, so that the high conjugated enamine compound is an important content for developing novel drug molecules. The existing enamine compound generally faces the difficulties in separation and synthesis due to poor stability, and the classical synthesis method usually faces higher reaction temperature, harsh reaction conditions, low yield, complex process and environment-friendliness.
The diyne enamine compound is an important one of highly conjugated enamine compounds. Due to the unique functional group property, the diyne enamine compound can be derived and converted into a plurality of chiral compounds with potential pharmaceutical activity. To date, efficient synthesis of diyne enamine compounds has not been achieved.
Therefore, a method for synthesizing the diyne enamine compound is urgently needed.
Disclosure of Invention
The invention aims to provide a preparation method of a diyne enamine compound, which aims to overcome the technical problems of harsh preparation conditions, low yield, complex process, environment friendliness, limited application range and the like of the existing high-conjugated enamine compound.
In order to achieve the above object, according to one aspect of the present invention, there is provided a diyne enamine compound.
The general molecular structure formula of the diyne enamine compound is as follows (I):
wherein, R is1、R2、R3、R4And R5Are identical or different C1-C20Alkyl radical, C1-C20Heteroalkyl group, C3-C20Cycloalkyl radical, C3-C20Heterocycloalkyl radical, C2-C20Alkenyl radical, C2-C20Heteroalkenyl, C3-C20Cycloalkenyl radical, C3-C20Heterocycloalkenyl, C2-C20Alkynyl, C2-C20Heteroalkynyl, C3-C20Cycloalkynyl group, C3-C20Heterocycloalkynyl, C1-C20Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl C1-C20Alkyl, aryl C9-C15Cycloalkyl, aryl C9-C20Hetero-atomic cycloalkyl, heteroaryl C1-C20Alkyl radical, C2-C20Alkenyl radical C1-C20Alkyl radical, C2-C20Alkynyl C1-C20Alkyl, cyano C1-C20Any of an alkyl group, an alkyloxycarbonylalkyl group, and a hydrogen atom;
the R is6、R7、R8And R9Is C1-C20Alkyl radical, C1-C20Heteroalkyl group, C3-C20Cycloalkyl radical, C3-C20Heterocycloalkyl radical, C2-C20Alkynyl, C2-C20Heteroalkynyl, C3-C20Cycloalkynyl group, C3-C20Heterocycloalkynyl, C1-C20Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl C1-C20Alkyl, heteroaryl C1-C20Alkyl radical, C2-C20Alkenyl radical C1-C20Alkyl radical, C2-C20Alkynyl C1-C20Alkyl, cyano C1-C20Any one of alkyl, alkyloxycarbonylalkyl, and halogen substituents.
As another aspect of the present invention, there is provided a method for preparing a diyne enamine compound, comprising the steps of:
providing a secondary amine A, an electrophilic compound B and an alkynone compound D represented by the following structural formulas respectively:
adding the secondary amine A and a gold catalyst into a reaction system containing the electrophilic reagent compound B, the pyridine ligand C and the alkynone compound D to react at the temperature of 25-100 ℃ to obtain a diyne enamine compound shown as the following structural general formula (I):
wherein, the compound A, B and R in the structural formula of (I)1、R2、R3、R4And R5Are identical or different C1-C20Alkyl radical, C1-C20Heteroalkyl group, C3-C20Cycloalkyl radical, C3-C20Heterocycloalkyl radical, C2-C20Alkenyl radical, C2-C20Heteroalkenyl, C3-C20Cycloalkenyl radical, C3-C20Heterocycloalkenyl, C2-C20Alkynyl, C2-C20Heteroalkynyl, C3-C20Cycloalkynyl group, C3-C20Heterocycloalkynyl, C1-C20Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl C1-C20Alkyl, aryl C9-C15Cycloalkyl, aryl C9-C20Hetero-atomic cycloalkyl, heteroaryl C1-C20Alkyl radical, C2-C20Alkenyl radical C1-C20Alkyl radical, C2-C20Alkynyl C1-C20Alkyl, cyano C1-C20Any of an alkyl group, an alkyloxycarbonylalkyl group, and a hydrogen atom;
the R is6、R7、R8And R9Is C1-C20Alkyl radical, C1-C20Heteroalkyl group, C3-C20Cycloalkyl radical, C3-C20Heterocycloalkyl radical, C2-C20Alkynyl, C2-C20Heteroalkynyl, C3-C20Cycloalkynyl group, C3-C20Heterocycloalkynyl, C1-C20Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl C1-C20Alkyl, heteroaryl C1-C20Alkyl radical, C2-C20Alkenyl radical C1-C20Alkyl radical, C2-C20Alkynyl C1-C20Alkyl, cyano C1-C20Any one of alkyl, alkyloxycarbonylalkyl, and halogen substituents.
As another aspect of the present invention, the present invention provides an application of the above-described diyne enamine compound according to the present invention or a diyne enamine compound prepared by the above-described preparation method of the diyne enamine compound according to the present invention to synthesis of a pharmaceutical intermediate or preparation of a functional material.
Compared with the prior art, the diyne enamine compound has a typical high-functional group structure, such as an electron-withdrawing group-containing structure and a polycyclic structure, so that the diyne enamine compound has the same characteristics as other diyne enamine compounds, enhances the application of the diyne enamine compound in the field of medicines, and can be widely used for synthesizing medicine intermediates.
Compared with the prior art, the preparation method of the diyne enamine compound has the following advantages:
1. commercially available metal catalysts are employed. The catalyst is commercially available, the reaction process is safe and controllable, and the operation in the preparation production process is simplified;
2. the catalyst dosage is low, and the atom economy is high;
3. the reaction is carried out by taking a simple and easily-obtained alkynyl phenyliodoacyl ketone reagent as an electrophilic reagent, attacking an enamine compound formed by alkynone and a secondary amine compound, and then forming a diyne enamine target product with high conjugation, high stereoselectivity and extremely wide range.
4. The method of the invention essentially belongs to alkynylation and enamine reaction with high atom utilization rate, and accords with atom economics;
5. the reactants are simple acetylenic ketone compounds and commercially available secondary amine compounds, the raw materials are low in price and very easy to obtain, the reactants are not required to be subjected to additional modification protection before reaction and can be directly used for preparation production, the operation steps are simplified, and the reaction route is shortened; the forward reaction rate is high, and the production efficiency is obviously improved;
6. due to the advantages of the 1 st to the 5 th, the method has the advantages of simple process, low requirement on reaction conditions, safe and controllable reaction process, high atom utilization rate and production efficiency and low environmental pollution pressure, the method obviously reduces the production cost for preparing the high-conjugated enamine compound, and greatly expands the designability and application prospect of the compound.
Due to the fact that the diyne enamine compound has a typical high-functionalization structure and the advancement of the preparation method, the diyne enamine compound can be widely used for synthesis of a drug intermediate or preparation of a functional material, can effectively reduce the economic cost of the drug intermediate, and is environment-friendly.
Detailed Description
In order to make the technical problems, technical solutions and advantageous effects to be solved by the present invention more clearly apparent, the present invention is further described in detail below with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The compounds and derivatives thereof referred to in the examples of the present invention are named according to the IUPAC (International Union of pure and applied chemistry) or CAS (chemical abstracts service, Columbus, Ohio) naming system. Accordingly, the groups of compounds specifically referred to in the examples of the present invention are illustrated and described as follows:
with respect to "hydrocarbon group", the minimum and maximum values of the carbon atom content in a hydrocarbon group are indicated by a prefix, e.g., the prefix (C)a-Cb) Alkyl represents any alkyl group containing from "a" to "b" carbon atoms. Thus, for example, (C)1-C6) Alkyl refers to alkyl groups containing one to six carbon atoms.
"alkoxy" refers to a straight or branched, monovalent, saturated aliphatic chain bonded to an oxygen atom and includes, but is not limited to, groups such as methoxy, ethoxy, propoxy, butoxy, isobutoxy, t-butoxy, and the like. (C)a-Cb) Alkoxy means any straight or branched, monovalent, saturated aliphatic chain in which an alkyl group containing "a" to "b" carbon atoms is 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" means a straight or branched, monovalent, saturated aliphatic chain attached to at least one heteroatom, such as, but not limited to, methylaminoethyl or other similar groups.
"alkenyl" refers to straight or branched chain hydrocarbons having one or more double bonds, including but not limited to, groups such as ethenyl, propenyl, and the like.
"Heteroalkenyl" means a straight or branched chain hydrocarbon with one or more double bonds attached to at least one heteroatom, including but not limited to, for example, vinylaminoethyl or other similar groups.
"alkynyl" refers to a straight or branched chain hydrocarbon with one or more triple bonds, including but not limited to, for example, ethynyl, propynyl, and the like.
"Heteroalkynyl" means a straight or branched chain hydrocarbon with one or more triple bonds attached to at least one heteroatom, including but not limited to, groups such as ethynyl, propynyl, and the like.
"aryl" refers to a cyclic aromatic hydrocarbon including, but not limited to, 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 with a heteroatom such as nitrogen, oxygen, or sulfur. If the heteroaryl group contains more than one heteroatom, these heteroatoms may be the same or 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, pyridine [3,4-b ] indolyl, pyridyl, pyrimidinyl, pyrrolyl, quinolizinyl, quinolyl, 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, groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, indanyl, tetrahydronaphthyl, and the like.
"Heterocycloalkyl" means a saturated monocyclic or polycyclic alkyl group, possibly fused to an aromatic hydrocarbon group, in which 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. Heterocycloalkyl groups include, but are not limited to, groups such as azepanyl, azetidinyl, indolinyl, morpholinyl, pyrazinyl, piperidinyl, pyrrolidinyl, tetrahydrofuryl, tetrahydroquinolinyl, tetrahydroindazolyl, tetrahydroindolyl, tetrahydroisoquinolinyl, tetrahydropyranyl, tetrahydroquinoxalinyl, tetrahydrothiopyranyl, thiazolidinyl, thiomorpholinyl, thioxanthyl, and the like.
"cycloalkenyl" refers to an unsaturated, monocyclic or polycyclic alkenyl group with one or more double bonds, possibly fused to an aromatic hydrocarbon group, including, but not limited to, cyclic ethenyl, cyclopropenyl, or other similar groups.
"Heterocycloalkenyl" means an unsaturated, monocyclic or polycyclic alkenyl radical having one or more double bonds, possibly condensed with an aromatic hydrocarbon radical, 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, monocyclic or polycyclic alkynyl group having one or more triple bonds, possibly fused to an aromatic hydrocarbon group, including, but not limited to, cycloalkynyl, cyclopropynyl, or the like.
"Heterocycloalkynyl" means an unsaturated, monocyclic or polycyclic alkynyl radical having one or more triple bonds, possibly condensed with an aromatic hydrocarbon radical, in which 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.
In one aspect, the embodiment of the present invention provides a diyne enamine compound, whose molecular structural general formula is the following (I):
wherein R in the molecular structure general formula (I)1、R2、R3、R4And R5Are identical or different C1-C20Alkyl radical, C1-C20Heteroalkyl group, C3-C20Cycloalkyl radical, C3-C20Heterocycloalkyl radical, C2-C20Alkenyl radical, C2-C20Heteroalkenyl, C3-C20Cycloalkenyl radical, C3-C20Heterocycloalkenyl, C2-C20Alkynyl, C2-C20Heteroalkynyl, C3-C20Cycloalkynyl group, C3-C20Heterocycloalkynyl, C1-C20Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl (C)1-C20) Alkyl, aryl C9-C15Cycloalkyl, aryl C9-C20Heteroatom cycloalkyl, heteroaryl (C)1-C20) Alkyl radical, C2-C20Alkenyl (C)1-C20) Alkyl radical, C2-C20Alkynyl (C)1-C20) Alkyl, cyano (C)1-C20) Any of an alkyl group, an alkyloxycarbonylalkyl group, and a hydrogen atom;
when R is1、R2、R3、R4And R5Are identical or different (C)1-C20) When it is an alkyl group, in one embodiment, the group (C)1-C20) The alkyl group may be (C)1-C10) Alkyl, (C)1-C5) Alkyl, (C)1-C4) Alkyl, (C)1-C3) Alkyl, (C)1-C2) Alkyl groups, and the like. In certain embodiments, (C)1-C20) The alkyl group may be methyl, ethyl, propyl, butyl, isobutyl, pentyl, isopentyl, and the like.
When R is1、R2、R3、R4And R5Are identical or different (C)1-C20) When it is heteroalkyl, in one embodiment, (C) is1-C20) The heteroalkyl group may be (C)1-C10) Heteroalkyl group, (C)1-C5) Heteroalkyl group, (C)1-C4) Heteroalkyl group, (C)1-C3) Heteroalkyl group, (C)1-C2) Heteroalkyl groups and the like. In certain embodiments, the heteroatom in the heteroalkyl group may be a halogen, nitrogen atom, sulfur atom, or the like.
When R is1、R2、R3、R4And R5Are identical or different (C)3-C20) Cycloalkyl, in one embodiment, the (C)3-C20) The cycloalkyl group may be (C)3-C10) Cycloalkyl group, (C)3-C5) Cycloalkyl group, (C)3-C4) Cycloalkyl groups, and the like. In certain embodiments, (C)3-C20) Cycloalkyl groups may be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.
When R is1、R2、R3、R4And R5Are identical or different (C)3-C20) When it is heterocycloalkyl, in one embodiment, (C) is3-C20) The heterocycloalkyl group may be (C)3-C10) Heterocycloalkyl group, (C)3-C10) Heterocycloalkyl group, (C)3-C5) Heterocycloalkyl group, (C)3-C4) Heterocycloalkyl, and the like. In certain embodiments, the heteroatom in the heterocycloalkyl group can be a halogen, nitrogen atom, sulfur atom, or the like.
When R is1、R2、R3、R4And R5Are identical or different (C)2-C20) Alkenyl, in one embodiment, the (C)2-C20) The alkenyl group may be (C)3-C10) Alkenyl, (C)3-C5) Alkenyl, (C)3-C4) Alkenyl, (C)2-C3) Alkenyl groups, and the like. In certain embodiments, (C)2-C20) The alkenyl group may be ethenyl, propenyl, butenyl, pentenyl, etc.
When R is1、R2、R3、R4And R5Are identical or different (C)2-C20) When it is heteroalkenyl, the group (C)2-C20) The heteroalkenyl group can be (C)2-C10) Heteroalkenyl, (C)3-C10) Heteroalkenyl, (C)3-C5) Heteroalkenyl, (C)3-C4) Heteroalkenyl, (C)2-C3) Heteroalkenyl and the like. In certain embodiments, the heteroatom in the heteroalkenyl group can be a halogen, a nitrogen atom, a sulfur atom, and the like.
When R is1、R2、R3、R4And R5Are identical or different (C)3-C20) Cycloalkenyl group of the formula (C)3-C20) Cycloalkenyl can be (C)3-C10) Cycloalkenyl group, (C)3-C5) Cycloalkenyl group, (C)3-C4) Cycloalkenyl groups, and the like. In certain embodiments, (C)3-C20) Cycloalkenyl can be cyclopropenyl, cyclobutenyl, cyclopentenyl and the like.
When R is1、R2、R3、R4And R5Are identical or different (C)3-C20) When it is heterocycloalkenyl, the compound (C)3-C20) The heterocycloalkenyl group may be (C)3-C10) Heterocycloalkenyl, (C)3-C5) Heterocycloalkenyl, (C)3-C4) Heterocycloalkenyl, and the like. In certain embodiments, the heteroatom in the heterocycloalkenyl can be a halogen, a nitrogen atom, a sulfur atom, and the like.
When R is1、R2、R3、R4And R5Are identical or different (C)2-C20) Alkynyl, the (C)2-C20) Alkynyl may be (C)2-C10) Alkynyl, (C)3-C10) Alkynyl, (C)3-C5) Alkynyl, (C)3-C4) Alkynyl, (C)2-C3) Alkynyl and the like. In certain embodiments, (C)2-C20) The alkynyl group may be an ethynyl group, propynyl group, butynyl group, pentynyl group or the like.
When R is1、R2、R3、R4And R5Are identical or different (C)2-C20) When it is heteroalkynyl, (C)2-C20) The heteroalkynyl can be (C)2-C10) Heteroalkynyl, (C)3-C10) Heteroalkynyl, (C)3-C5) Heteroalkynyl, (C)3-C4) Heteroalkynyl, (C)2-C3) Heteroalkynyl, and the like. In certain embodiments, the heteroatom in the heteroalkynyl group can be a halogen, nitrogen atom, sulfur atom, and the like.
When R is1、R2、R3、R4And R5Are identical or different (C)3-C20) Cycloalkynyl group, the (C)3-C20) The cycloalkynyl group can be (C)3-C10) Cycloalkynyl, (C)3-C5) Cycloalkynyl, (C)3-C4) Cycloalkynyl, and the like. In certain embodiments, (C)2-C20) The cycloalkynyl group may be cyclopropynyl, cyclobutynyl, cyclopentynyl, or the like.
When R is1、R2、R3、R4And R5Are identical or different (C)3-C20) When the heterocyclic ring is alkynyl, the compound (C)3-C20) The heterocycloalkynyl can be (C)3-C10) Heterocycloalkynyl, (C)3-C5) Heterocycloalkynyl, (C)3-C4) Heterocycloalkynyl, and the like. In certain embodiments, the heteroatoms in the heterocyclic alkynyl group can be halogens, nitrogen atoms, sulfur atoms, and the like.
When R is1、R2、R3、R4And R5Are identical or different (C)1-C20) Alkoxy, in one embodiment, the (C)1-C20) The alkoxy group may be (C)1-C10) Alkane (I) and its preparation methodOxy, (C)1-C8) Alkoxy group, (C)1-C6) Alkoxy group, (C)1-C4) Alkoxy group, (C)1-C3) Alkoxy group, (C)1-C2) An alkoxy group. In certain embodiments, this (C)1-C20) Alkoxy groups may be, but are not limited to, methyloxy, ethyloxy, propyloxy, and the like.
When R is1、R2、R3、R4And R5When the aryl groups are the same or different, the aryl groups may be, but are not limited to, monocyclic aryl groups, polycyclic aryl groups, and fused ring aryl groups. In one embodiment, the aryl group is a monocyclic aryl group. In certain embodiments, aryl is phenyl, substituted phenyl, and the like, respectively.
When R is1、R2、R3、R4And R5When the aryl group is the same or different, the substituted aryl group may be, but is not limited to, a phenyl group substituted by one or more of ortho, meta, and para. Substituents include, but are not limited to, alkyl, substituted alkyl, halogen, alkoxyamino, nitro, -NR5R6、-NR5-CO-NR6、-OCONR5、-PR5R6、-SOR5、-SO2-R5、-SiR5R6R7、-BR5R6Wherein R is5、R6、R7Which may be the same or different is as R above1、R2The groups shown. Wherein, when the substituent is an alkyl group, the alkyl group is exemplified by, but not limited to, methyl, ethyl, propyl, butyl, isobutyl; when the substituent is a substituted alkyl group, such as, but not limited to, trifluoromethyl, trichloromethyl, trifluoroethyl, trichloroethyl; when the substituent is 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, methyloxy, ethyloxy, propyloxy. The substituted aryl group may also be cyano (C)1-C10) Alkyl radical (C)3-C8) Aryl, substituted (C)3-C8) And (4) an aryl group.
When R is1、R2、R3、R4And R5When the same or different heteroaryl groups are present, the heteroaryl group may be (C)3-C8) Heteroaryl, furan, thiophene.
When R is1、R2、R3、R4And R5In the case of identical or different substituted hetaryl, the substituted hetaryl may be substituted (C)3-C8) Heteroaryl, alkoxy substituted furan, (C)3-C8) Heteroaryl substituted furans, aliphatic chain substituted thiophenes.
When R is1、R2、R3、R4And R5When identical or different aryloxy groups are present, the aryloxy group may be a phenoxy, naphthoxy, anthracenoxy or phenanthrenoxy group.
When R is1、R2、R3、R4And R5Are identical or different aryl radicals (C)1-C20) When it is an alkyl group, the aryl group (C)1-C20) The alkyl group may be aryl (C)1-C10) Alkyl, phenyl (C)1-C10) Alkyl, phenyl (C)1-C5) Alkyl, phenyl (C)1-C4) Alkyl, phenyl (C)1-C3) Alkyl, phenyl (C)1-C2) Alkyl groups, and the like. In certain embodiments, aryl (C)1-C20) The alkyl group may be phenylmethyl, phenylethyl, phenylpropyl, phenylbutyl, phenylisobutyl, phenylpentyl, phenylisopentyl, phenylneopentyl.
When R is1、R2、R3、R4And R5Are identical or different heteroaryl (C)1-C20) When it is alkyl, the heteroaryl group (C)1-C20) The alkyl group may be heteroaryl (C)1-C10) Alkyl, heteroaryl (C)1-C10) Alkyl, heteroaryl (C)1-C5) Alkyl, heteroaryl (C)1-C4) Alkyl, heteroaryl (C)1-C3) Alkyl, heteroaryl (C)1-C2) Alkyl groups, and the like. Wherein the heteroaryl group mayIs (C)3-C8) Heteroaryl, furan, pyridine, and the like.
When R is1、R2、R3、R4And R5Are identical or different (C)2-C20) Alkenyl (C)1-C20) When it is an alkyl group, the (C)2-C20) Alkenyl (C)1-C20) The alkyl group may be (C)2-C10) Alkenyl (C)1-C10)、(C2-C5) Alkenyl (C)1-C3). In certain embodiments, the (C)2-C20) Alkenyl (C)1-C20) The alkyl group may be 2-butenyl, 2-pentenyl, 3-hexenyl, 3-heptenyl, etc.
When R is1、R2、R3、R4And R5Are identical or different (C)2-C20) Alkynyl (C)1-C20) When it is an alkyl group, in one embodiment, the group (C)2-C20) Alkynyl (C)1-C20) The alkyl group may be (C)2-C10) Alkynyl (C)1-C10) Alkyl, (C)2-C5) Alkynyl (C)1-C3) An alkyl group. In certain embodiments, the (C)2-C20) Alkynyl (C)1-C20) The alkyl group may be 2-butynyl, 2-pentynyl, 3-hexynyl, 3-heptynyl, etc.
When R is1、R2、R3、R4And R5Are identical or different cyano groups (C)1-C20) Alkyl, in one embodiment, the cyano (C)1-C20) The alkyl group may be cyano (C)1-C10) Alkyl, cyano (C)1-C5) Alkyl, cyano (C)1-C4) Alkyl, cyano (C)1-C3) Alkyl, cyano (C)1-C2) Alkyl groups, and the like. In certain embodiments, cyano (C)1-C20) The alkyl group may be cyanomethyl, cyanoethyl, cyanopropyl, cyanobutyl, cyanopentyl, or the like.
When R is1、R2、R3、R4And R5When the alkyl groups are the same or different alkyl oxycarbonylalkyl groups, in one embodiment, the alkyl oxycarbonylalkyl groups may be (C)1-C10) Alkyloxycarbonyl (C)1-C10) Alkyl, (C)1-C5) Alkyloxycarbonyl (C)1-C5) Alkyl, (C)1-C4) Alkyloxycarbonyl (C)1-C4) Alkyl, (C)1-C3) Alkyloxycarbonyl (C)1-C3) Alkyl, (C)1-C2) Alkyloxycarbonyl (C)1-C2) Alkyl groups, and the like. In certain embodiments, the alkyloxycarbonylalkyl group can be an ethoxycarbonylethyl group, ethoxycarbonylmethyl group, methoxycarbonylethyl group, methoxycarbonylmethyl group, propoxycarbonylpropyl group, propoxycarbonylethyl group, propoxycarbonylmethyl group, and the like.
Based on the above examples, R in the above general molecular structural formula (I)1、R2、R3、R4And R5Are the same or different C1-C20Alkyl radical, C1-C20Heteroalkyl, sulfonic acid (C)1-C20) Heteroalkyl group, C1-C20Perfluoroalkyl, alkyloxycarbonylalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl (C)1-C20) Alkyl, heteroaryl (C)1-C20) Alkyl, cyano, isocyano, sulfonic acid (C)1-C20) Any one of alkyl, nitro, fluoro, bromo, chloro, and iodo.
When R is6、R7、R8And R9Are identical or different (C)1-C20) When it is an alkyl group, in one embodiment, the group (C)1-C20) The alkyl group may be (C)1-C10) Alkyl, (C)1-C5) Alkyl, (C)1-C4) Alkyl, (C)1-C3) Alkyl, (C)1-C2) Alkyl groups, and the like. In certain embodiments, (C)1-C20) The alkyl group can be methyl, ethyl, propyl, butyl, isobutylPentyl, isopentyl, and the like.
When R is6、R7、R8And R9Are identical or different (C)1-C20) When it is heteroalkyl, in one embodiment, (C) is1-C20) The heteroalkyl group may be (C)1-C10) Heteroalkyl group, (C)1-C5) Heteroalkyl group, (C)1-C4) Heteroalkyl group, (C)1-C3) Heteroalkyl group, (C)1-C2) Heteroalkyl groups and the like. In certain embodiments, the heteroatom in the heteroalkyl group may be a halogen, nitrogen atom, sulfur atom, or the like.
When R is6、R7、R8And R9Are identical or different (C)3-C20) Cycloalkyl, in one embodiment, the (C)3-C20) The cycloalkyl group may be (C)3-C10) Cycloalkyl group, (C)3-C5) Cycloalkyl group, (C)3-C4) Cycloalkyl groups, and the like. In certain embodiments, (C)3-C20) Cycloalkyl groups may be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.
When R is6、R7、R8And R9Are identical or different (C)3-C20) When it is heterocycloalkyl, in one embodiment, (C) is3-C20) The heterocycloalkyl group may be (C)3-C10) Heterocycloalkyl group, (C)3-C10) Heterocycloalkyl group, (C)3-C5) Heterocycloalkyl group, (C)3-C4) Heterocycloalkyl, and the like. In certain embodiments, the heteroatom in the heterocycloalkyl group can be a halogen, nitrogen atom, sulfur atom, or the like.
When R is6、R7、R8And R9Are identical or different (C)2-C20) When it is heteroalkenyl, the group (C)2-C20) The heteroalkenyl group can be (C)2-C10) Heteroalkenyl, (C)3-C10) Heteroalkenyl, (C)3-C5) Heteroalkenyl, (C)3-C4) Heteroalkenyl, (C)2-C3) Heteroalkenyl and the like. In some embodiments, theThe heteroatom in the heteroalkenyl group may be a halogen atom, a nitrogen atom, a sulfur atom, or the like.
When R is6、R7、R8And R9Are identical or different (C)2-C20) Alkynyl, the (C)2-C20) Alkynyl may be (C)2-C10) Alkynyl, (C)3-C10) Alkynyl, (C)3-C5) Alkynyl, (C)3-C4) Alkynyl, (C)2-C3) Alkynyl and the like. In certain embodiments, (C)2-C20) The alkynyl group may be an ethynyl group, propynyl group, butynyl group, pentynyl group or the like.
When R is6、R7、R8And R9Are identical or different (C)3-C20) Cycloalkynyl group, the (C)3-C20) The cycloalkynyl group can be (C)3-C10) Cycloalkynyl, (C)3-C5) Cycloalkynyl, (C)3-C4) Cycloalkynyl, and the like. In certain embodiments, (C)2-C20) The cycloalkynyl group may be cyclopropynyl, cyclobutynyl, cyclopentynyl, or the like.
When R is6、R7、R8And R9Are identical or different (C)1-C20) Alkoxy, in one embodiment, the (C)1-C20) The alkoxy group may be (C)1-C10) Alkoxy group, (C)1-C8) Alkoxy group, (C)1-C6) Alkoxy group, (C)1-C4) Alkoxy group, (C)1-C3) Alkoxy group, (C)1-C2) An alkoxy group. In certain embodiments, this (C)1-C20) Alkoxy groups may be, but are not limited to, methyloxy, ethyloxy, propyloxy, and the like.
When R is6、R7、R8And R9When the aryl groups are the same or different, the aryl groups may be, but are not limited to, monocyclic aryl groups, polycyclic aryl groups, and fused ring aryl groups. In one embodiment, the aryl group is a monocyclic aryl group. In certain embodiments, aryl is phenyl, substituted phenyl, and the like, respectively.
When R is6、R7、R8And R9When the aryl group is the same or different, the substituted aryl group may be, but is not limited to, a phenyl group substituted by one or more of ortho, meta, and para. Substituents include, but are not limited to, alkyl, substituted alkyl, halo, alkoxyamino, nitro, substituted amino, substituted boryl, substituted phosphino, substituted silyl, substituted thio, and the like. Wherein, when the substituent is an alkyl group, the alkyl group is exemplified by, but not limited to, methyl, ethyl, propyl, butyl, isobutyl; when the substituent is a substituted alkyl group, such as, but not limited to, trifluoromethyl, trichloromethyl, trifluoroethyl, trichloroethyl; when the substituent is 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, methyloxy, ethyloxy, propyloxy. The substituted aryl group may also be cyano (C)1-C10) Alkyl radical (C)3-C8) Aryl, substituted (C)3-C8) And (4) an aryl group.
When R is6、R7、R8And R9When the same or different heteroaryl groups are present, the heteroaryl group may be (C)3-C8) Heteroaryl, furan, thiophene.
When R is6、R7、R8And R9In the case of identical or different substituted hetaryl, the substituted hetaryl may be substituted (C)3-C8) Heteroaryl, alkoxy substituted furan, (C)3-C8) Heteroaryl substituted furans, aliphatic chain substituted thiophenes.
When R is6、R7、R8And R9When identical or different aryloxy groups are present, the aryloxy group may be a phenoxy, naphthoxy, anthracenoxy or phenanthrenoxy group.
When R is6、R7、R8And R9Are identical or different aryl radicals (C)1-C20) When it is an alkyl group, the aryl group (C)1-C20) The alkyl group may be aryl (C)1-C10) Alkyl, phenyl (C)1-C10) Alkyl, phenyl (C)C1-C5) Alkyl, phenyl (C)1-C4) Alkyl, phenyl (C)1-C3) Alkyl, phenyl (C)1-C2) Alkyl groups, and the like. In certain embodiments, aryl (C)1-C20) The alkyl group may be phenylmethyl, phenylethyl, phenylpropyl, phenylbutyl, phenylisobutyl, phenylpentyl, phenylisopentyl, phenylneopentyl.
When R is6、R7、R8And R9Are identical or different heteroaryl (C)1-C20) When it is alkyl, the heteroaryl group (C)1-C20) The alkyl group may be heteroaryl (C)1-C10) Alkyl, heteroaryl (C)1-C10) Alkyl, heteroaryl (C)1-C5) Alkyl, heteroaryl (C)1-C4) Alkyl, heteroaryl (C)1-C3) Alkyl, heteroaryl (C)1-C2) Alkyl groups, and the like. Wherein the heteroaryl group may be (C)3-C8) Heteroaryl, furan, pyridine, and the like.
When R is6、R7、R8And R9Are identical or different (C)2-C20) Alkenyl (C)1-C20) When it is an alkyl group, the (C)2-C20) Alkenyl (C)1-C20) The alkyl group may be (C)2-C10) Alkenyl (C)1-C10)、(C2-C5) Alkenyl (C)1-C3). In certain embodiments, the (C)2-C20) Alkenyl (C)1-C20) The alkyl group may be 2-butenyl, 2-pentenyl, 3-hexenyl, 3-heptenyl, etc.
When R is6、R7、R8And R9Are identical or different (C)2-C20) Alkynyl (C)1-C20) When it is an alkyl group, in one embodiment, the group (C)2-C20) Alkynyl (C)1-C20) The alkyl group may be (C)2-C10) Alkynyl (C)1-C10) Alkyl, (C)2-C5) Alkynyl (C)1-C3) An alkyl group. In some toolsIn the embodiment, the (C)2-C20) Alkynyl (C)1-C20) The alkyl group may be 2-butynyl, 2-pentynyl, 3-hexynyl, 3-heptynyl, etc.
When R is6、R7、R8And R9When the alkyl groups are the same or different alkyl oxycarbonylalkyl groups, in one embodiment, the alkyl oxycarbonylalkyl groups may be (C)1-C10) Alkyloxycarbonyl (C)1-C10) Alkyl, (C)1-C5) Alkyloxycarbonyl (C)1-C5) Alkyl, (C)1-C4) Alkyloxycarbonyl (C)1-C4) Alkyl, (C)1-C3) Alkyloxycarbonyl (C)1-C3) Alkyl, (C)1-C2) Alkyloxycarbonyl (C)1-C2) Alkyl groups, and the like. In certain embodiments, the alkyloxycarbonylalkyl group can be an ethoxycarbonylethyl group, ethoxycarbonylmethyl group, methoxycarbonylethyl group, methoxycarbonylmethyl group, propoxycarbonylpropyl group, propoxycarbonylethyl group, propoxycarbonylmethyl group, and the like.
Therefore, the diyne enamine compound with the molecular structure general formula (I) in each embodiment can be widely applied to the synthesis of pharmaceutical intermediates, particularly heterocyclic compounds.
On the other hand, on the basis of the diyne enamine compound of the embodiment of the invention described above, the embodiment of the invention also provides a preparation method of the diyne enamine compound of the molecular structure general formula (I).
The method comprises the following steps:
s01: providing a secondary amine A, an electrophilic compound B and an alkynone compound D represented by the following structural formulas respectively:
s02: adding the secondary amine A and a gold catalyst into a reaction system containing the electrophilic reagent compound B, the pyridine ligand C and the alkynone compound D to react at the temperature of 25-100 ℃ to obtain a diyne enamine compound shown as the following structural general formula (I):
specifically, in step S01, R in the molecular structural formula of the secondary amine compound a6、R7The group is represented by the general formula (I) of the molecular structure of the dialkyne enamine compound in the embodiment of the invention6、R7The groups represented are the same. R in molecular structural formula of electrophilic reagent compound B8The group is as R in the structural general formula (I) of the diyne enamine compound8The groups represented are the same. R in the molecular structural formula of alkynone compound C1、R2、R3、R4、R5、R9The group is as R in the structural general formula (I) of the diyne enamine compound1、R2、R3、R4、R5、R9The groups represented are the same. For economy of disclosure, further description is omitted here.
In addition, the secondary amine compound a, the electrophile compound B, and the alkynone compound C in step S01 can be prepared according to a conventional method in the art, and can be obtained directly from the market.
In step S02, it can be seen from the structural formulas of the substrate secondary amine compound a, the electrophilic reagent compound B and the alkynone compound C that the secondary amine compound a has nucleophilicity, the electrophilic reagent compound B has electrophilic character, and the alkynone compound C has carbonyl carbon atom with carbon positive. The alkynylation and enamine reaction formula is as follows:
in the chemical reaction formula, the gold catalyst plays a role in activating the electrophilic reagent compound B, and the pyridine ligand plays a role in coordinating with the gold catalyst, so that the gold catalyst is more electron-deficient, the activation effect is enhanced, the atom utilization rate and the reaction efficiency are improved, and byproducts are few. Meanwhile, the reaction process is safe and controllable, and the operation in the preparation production process is simplified.
In order to make the synergistic catalytic system exert more effective catalytic action, in one embodiment, the molar ratio of the gold catalyst to the pyridine ligand C is (0.1-20) to (0-20), preferably (0.1-20): 20.
in a specific embodiment, the molar ratio of the gold catalyst to the pyridine ligand C is 1: 10.
in one embodiment, the mole ratio of the gold catalyst, the pyridine ligand C, the secondary amine A, the electrophilic reagent compound B and the alkynone compound D is (0.1-20): (0-20): (1-120): (1-120): (1-100).
In an embodiment, the pyridine ligand C may be 2, 2-bipyridine or one of substituted 2, 2-bipyridines, or may not be added. In specific experiments, the pyridine ligands listed as preferred can catalyze the reaction, but the reaction efficiency is different, and the reaction rate is slower when no pyridine ligand is added. As in the specific example, the pyridine ligand may be compound C:
r in the general structural formula C10、R11、R12、R13、R14、R15、R16、R17Are identical or different C1-C20Alkyl radical, C1-C20Heteroalkyl group, C3-C20Cycloalkyl radical, C3-C20Heterocycloalkyl radical, C2-C20Alkenyl radical, C2-C20Heteroalkenyl, C1-C20Perfluoroalkyl radical, C3-C20Cycloalkenyl radical, C3-C20Heterocycloalkenyl, C2-C20Alkynyl, C2-C20Heteroalkynyl, C3-C20CycloalkynesBase, C3-C20Heterocycloalkynyl, C1-C20Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl (C)1-C20) Alkyl, heteroaryl (C)1-C20) Alkyl radical, C2-C20Alkenyl (C)1-C20) Alkyl radical, C2-C20Alkynyl (C)1-C20) Alkyl, cyano (C)1-C20) Any one of an alkyl group, an alkyloxycarbonylalkyl group, and a hydrogen atom.
The gold catalyst is at least one of the following compounds:
under the action of the pyridine ligand C and the gold catalyst, the reaction system can be smoothly carried out even at room temperature, and the reaction temperature range is 25-100 ℃.
In order to further improve the reaction efficiency, in one embodiment, the reaction temperature of the reaction system is 40 to 90 ℃.
In another embodiment, the reaction temperature of the reaction system is 50 to 90 ℃. At the temperature, the time required by the reaction is shortened from the original 6-72 hours to 6-48 hours, and the yield is improved from the original 68% to 88%.
The reaction time in the environment of the temperature of each preferable reaction should be sufficient for the above reactants to react, for example, the reaction time may be 6 to 48 hours, or longer.
In the above reaction system, a certain amount of solvent is optionally added. Such solvents include, but are not limited to, diethyl ether, tetrahydrofuran, dichloromethane, toluene. Alternative solvents will be readily selected by those of ordinary skill in the art based on the reactions and disclosures set forth herein.
In one embodiment, the solvent is added in a molar ratio of solvent to catalyst such that (100-: 1.
therefore, the preparation method of the diyne enamine compound uses the combined action of the gold catalyst and the bipyridine ligand, so that the catalytic system has low toxicity, high atom utilization rate and production efficiency, safe and controllable reaction process, and simplified operation in the preparation production process. Meanwhile, the toxicity of the reaction residues is reduced to the minimum, the pollution to the environment in the production process is reduced, and the steps and the operation for removing the residues after the reaction are simplified. In addition, reactant raw materials are very easy to obtain, and the reactants can be directly used for preparation production without additional modification before reaction, so that the operation steps are simplified, and the reaction route is shortened; obviously reduces the production cost. Secondly, the method can also flexibly adjust the proportion and the addition amount of the gold catalyst, the bipyridine ligand and the reactant, further improve the atom utilization rate and the production efficiency, and reduce the production of byproducts.
In another aspect, based on the diyne enamine compound and the preparation method thereof, the embodiment of the invention provides an application range of the diyne enamine compound. In one embodiment, the application of the high stereoselectivity diyne enamine compound in the synthesis of a drug intermediate or the preparation of a functional material is provided. For example, the high stereoselectivity diyne enamine compound can be converted into a fluorine atom-containing drug intermediate or a functional material with a polyaromatic ring structure through a simple reaction. Thus, since the diyne enamine compound has a typical high-functionalization structure as described above and the advancement of the above preparation method, it can be widely used for the synthesis of pharmaceutical intermediates, and can effectively reduce the economic cost of pharmaceutical intermediates and provide its environmental friendliness.
The present invention will now be described in further detail with reference to examples.
Example 1
This example provides trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine and a process for its preparation.
The structural formula of the trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-ene-1, 5-diyne-3) pyrrolidine is shown as the following molecular structural formula I1:
the preparation method comprises the following steps:
1-phenyl-4-triisopropylsilyl-butane-3-yn-2-one (0.1mmol,1.0eq), bipyridine (0.02mmol,0.2eq), triisopropylsilyl-alkynyliodoxolone (0.12mmol,1.2eq), and 2mL of anhydrous ether were added to a dry 10mL sealed tube, followed by addition of aurous chloride (0.01mmol,0.1eq) and pyrrolidine (0.12mmol,1.2eq), and the reaction was allowed to stand at 50 ℃ for 10 h.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 88%, and the trans-product is: the cis product is >20: 1.
The result of the correlation characterization analysis is as follows:1H NMR(400MHz,CDCl3)δ7.63–7.61(m,2H),7.21–7.17(m,2H),7.10–7.06(m,1H),3.74–3.70(m,4H),1.90–1.86(m,4H),1.07–1.06(m,18H,3H,3H),0.95(s,18H)；13C NMR(101MHz,CDCl3)δ140.36,136.38,129.85,127.41,125.60,109.39,102.62,101.09,100.20,97.96,51.58,25.82,18.93,18.66,11.87,11.33；HRMS(ESI-TOF)[M+H]calculated for[C34H56NSi2]+534.3951, found 534.3946. this result further confirms the molecular structure of the product as described above under molecular structure I1.
Example 2
This example provides trans-1- (4-m-methylbenzene) -1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine and a process for its preparation.
The structural formula of the trans-1- (4-m-methylphenyl-1, 6-bis (triisopropylsilyl) hexyl-3-ene-1, 5-diyne-3) pyrrolidine is shown as the following molecular structural formula I2:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1- (3-methyl-phenyl) -4-triisopropylsilyl-butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 86%, and the trans-product is: cis-product 10.2: 1.
the product I2 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(400MHz,CDCl3)δ7.45–7.43(m,2H),7.09(dd,J＝7.6,7.6Hz,1H),6.90(d,J＝7.6Hz,1H),3.72–3.69(m,4H),2.28(s,3H),1.89–1.86(m,4H),1.14–1.08(m,18H,3H,3H),0.96(s,18H)；13C NMR(major isomer)(101MHz,CDCl3)δ140.18,136.59,136.21,130.63,127.34,126.89,126.40,109.49,102.65,101.21,100.07,97.93,51.58,25.83,21.55,18.93,18.65,11.87,11.32；HRMS(ESI-TOF)[M+H]calculated for[C35H58NSi2]+548.4108, found 548.4102. this result further confirms the molecular structure of the product as described above under molecular structure I2.
Example 3
This example provides trans-1- (4-p-methylphenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine and a process for its preparation.
The structural formula of trans-1- (4-p-methylphenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine is shown as molecular structural formula I3:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1- (4-methyl-phenyl) -4-triisopropylsilyl-butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 82%, and a trans-product: cis-product 9.1: 1.
the product I3 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(400MHz,CDCl3)δ7.50(d,J＝8.0Hz,2H),7.00(d,J＝8.0Hz,2H),3.72–3.68(m,4H),2.28(s,3H),1.89–1.85(m,4H),1.12–1.07(m,18H,3H,3H),0.95(s,18H)；13C NMR(major isomer)(101MHz,CDCl3)δ137.39,136.13,135.11,129.68,128.14,109.44,102.75,101.20,100.06,97.87,51.53,25.81,21.22,18.93,18.63,11.86,11.33；HRMS(ESI-TOF)[M+H]calculated for[C35H58NSi2]+548.4108, found 548.4098. this result further confirms the molecular structure of the product as described above under molecular structure I3.
Example 4
This example provides trans-1- (4-p-tert-butylphenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine and a method for producing the same.
The structural formula of trans-1- (4-p-tert-butylphenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine is represented by the following molecular structural formula I4:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1- (4-tert-butyl-phenyl) -4-triisopropylsilyl-butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid with the yield of 78 percent and a trans-product: cis-product 19.4: 1.
the product I4 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(500MHz,CDCl3)δ7.54(d,J＝8.4Hz,2H),7.21(d,J＝8.4Hz,2H),3.71–3.69(m,4H),1.89–1.86(m,4H),1.29(s,9H),1.12–1.07(m,18H,3H,3H),0.95(s,18H)；13C NMR(major isomer)(126MHz,CDCl3)δ148.34,137.32,136.31,129.49,124.35,109.47,102.96,101.59,99.90,98.00,51.54,34.51,31.54,25.81,18.96,18.71,11.95,11.42；HRMS(ESI-TOF)[M+H]calculated for[C38H64NSi2]+590.4572, found 590.4571. this result further confirms the molecular structure of the product as described above under molecular structure I4.
Example 5
This example provides trans-1- (4-p-methoxyphenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine and a method for its preparation.
The structural formula of trans-1- (4-p-methoxyphenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine is shown as the following molecular structural formula I5:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1- (4-methoxy-phenyl) -4-triisopropylsilyl-butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid with the yield of 75 percent and a trans-product: cis product >20: 1.
the product I5 prepared was subjected to characterization data analysis, which resulted in:1H NMR(400MHz,CDCl3)δ7.54(d,J＝8.8Hz,2H),6.76(d,J＝8.8Hz,2H),3.78(s,3H),3.72–3.68(m,4H),1.89–1.86(m,4H),1.09–1.07(m,18H,3H,3H),0.97(s,18H)；13C NMR(101MHz,CDCl3)δ157.85,135.82,133.00,130.91,112.99,109.56,102.83,100.98,99.96,97.97,55.41,51.50,25.80,18.92,18.67,11.86,11.35；HRMS[M+H]calculated for[C35H58NOSi2]+564.4051, found 564.4056. this result further confirms the molecular structure of the product as described above under molecular structure I5.
Example 6
This example provides trans-1- (4-m-methoxyphenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine and a method for its preparation.
The structural formula of trans-1- (4-m-methoxyphenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine is shown as the following molecular structural formula I6:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1- (3-methoxy-phenyl) -4-triisopropylsilyl-butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 71 percent, and the trans-product is: cis-product 9.8: 1.
the product I6 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(500MHz,CDCl3)δ7.23(d,J＝8.0Hz,1H),7.16(dd,J＝2.0,2.0Hz,1H),7.09(dd,J＝8.0,8.0Hz,1H),6.66(dd,J＝8.0,2.0Hz,1H),3.77(s,3H),3.73–3.70(m,4H),1.89–1.87(m,4H),1.11–1.06(m,18H,3H,3H),0.96(s,18H)；13C NMR(major isomer)(126MHz,CDCl3)δ159.11,141.85,136.58,128.23,122.79,114.91,112.11,109.38,102.58,101.09,100.47,98.06,55.20,51.58,25.81,18.95,18.67,11.92,11.39；HRMS[M+H]calculated for[C35H58NOSi2]+564.4051, found 564.4050. this result further confirms the molecular structure of the product as described above under molecular structure I6.
Example 7
This example provides a trans-1- (4-p-nitrophenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine and a method for its preparation.
The structural formula of the trans-1- (4-p-nitrophenyl-1, 6-bis (triisopropylsilyl) hexyl-3-ene-1, 5-diyne-3) pyrrolidine is shown as the following molecular structural formula I7:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1- (4-nitro-phenyl) -4-triisopropylsilyl-butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 63 percent, and the trans-product is: cis product >20: 1.
the product I7 prepared was subjected to characterization data analysis, which resulted in:1H NMR(400MHz,CDCl3)δ8.04(d,J＝8.9Hz,2H),7.81(d,J＝8.9Hz,2H),3.79–3.75(m,4H),1.94–1.90(m,4H),1.09–1.07(m,18H,3H),0.99–0.93(m,18H,3H)；13C NMR(101MHz,CDCl3)δ148.06,144.81,138.14,129.56,122.85,107.62,102.49,101.59,98.81,97.96,51.99,25.80,18.92,18.64,11.83,11.29；HRMS(ESI-TOF)[M+H]calculated for[C34H55N2O2Si2]+578.3797, found 578.3797. this result further confirms the molecular structure of the product as described above under molecular structure I7.
Example 8
This example provides trans-1- (4-m-fluorophenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine and a process for its preparation.
The structural formula of the trans-1- (4-m-fluorophenyl-1, 6-bis (triisopropylsilyl) hexyl-3-ene-1, 5-diyne-3) pyrrolidine is shown as the following molecular structural formula I8:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1- (3-fluoro-phenyl) -4-triisopropylsilyl-butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 66%, and the trans-product is: cis-product 14.7: 1.
the product I8 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(500MHz,CDCl3)δ7.41(d,J＝8.3Hz,1H),7.34(ddd,J＝10.9,2.4,2.4Hz,1H),7.16–7.12(m,1H),6.78(ddd,J＝8.5,8.5,2.4Hz,1H),3.74–3.71(m,4H),1.90–1.87(m,4H),1.12–1.08(m,18H,3H),0.98–0.96(m,18H,3H)；13C NMR(major isomer)(126MHz,CDCl3)δ162.41(d,J＝243.2Hz),142.91(d,J＝8.1Hz),136.71,128.59(d,J＝8.6Hz),125.50(d,J＝2.6Hz),116.62(d,J＝22.0Hz),112.26(d,J＝21.2Hz),108.93,102.25,101.07,99.66,98.27,51.63,25.81,18.92,18.65,11.91,11.36；19F NMR(major isomer)(376MHz,CDCl3)δ-115.48；HRMS(ESI-TOF)[M+H]calculated for[C34H55FNSi2]+552.3852, found 552.3850. this result further confirms the molecular structure of the product as described above under molecular structure I8.
Example 9
This example provides trans-1- (4-m-chlorophenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine and a process for its preparation.
The structural formula of the trans-1- (4-m-chlorophenyl-1, 6-bis (triisopropylsilyl) hexyl-3-ene-1, 5-diyne-3) pyrrolidine is shown as the following molecular structural formula I9:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1- (3-chloro-phenyl) -4-triisopropylsilyl-butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 84%, and the trans-product is: cis-product 18.0: 1.
the product I9 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(300MHz,CDCl3)δ7.62(dd,J＝2.0,2.0Hz,1H),7.52(ddd,J＝8.0,2.0,2.0Hz,1H),7.15–7.03(m,2H),3.75–3.70(m,4H),1.91–1.87(m,4H),1.08–1.07(m,18H,3H),0.98–0.96(m,18H,3H)；13C NMR(major isomer)(75MHz,CDCl3)δ142.47,136.65,133.10,129.86,128.58,127.84,125.43,108.78,102.02,100.97,98.99,98.11,51.63,25.81,18.91,18.65,11.83,11.25；HRMS(ESI-TOF)[M+H]calculated for[C34H55ClNSi2]+568.3556, found 568.3552. this result further confirms the molecular structure of the product as described above under molecular structure I9.
Example 10
This example provides a trans-1- (4-m-bromophenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine and a method for its preparation.
The structural formula of the trans-1- (4-m-bromophenyl-1, 6-bis (triisopropylsilyl) hexyl-3-ene-1, 5-diyne-3) pyrrolidine is shown as the following molecular structural formula I10:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1- (3-bromo-phenyl) -4-triisopropylsilyl-butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 84%, and the trans-product is: cis-product 14.9: 1.
the product I10 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(500MHz,CDCl3)δ7.76(dd,J＝1.5,1.5Hz,1H),7.56(ddd,J＝7.8,1.5,1.5Hz,1H),7.22–7.19(m,1H),7.06(dd,J＝7.9,7.9Hz,1H),3.73–3.71(m,4H),1.90–1.87(m,4H),1.09–1.07(m,18H,3H),0.99–0.96(m,18H,3H)；13C NMR(major isomer)(126MHz,CDCl3)δ142.96,136.66,132.83,128.90,128.42,128.39,121.53,108.91,102.13,101.08,99.18,98.26,51.62,25.81,18.93,18.70,11.91,11.36；HRMS(ESI-TOF)[M+H]calculated for[C34H55BrNSi2]+612.3051, found 612.3064. this result further confirms the molecular structure of the product as described above under molecular structure I10.
Example 11
This example provides trans-1- (4-p-fluorophenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine and a process for its preparation.
The structural formula of the trans-1- (4-p-fluorophenyl-1, 6-bis (triisopropylsilyl) hexyl-3-ene-1, 5-diyne-3) pyrrolidine is shown as the following molecular structural formula I11:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1- (4-fluoro-phenyl) -4-triisopropylsilyl-butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 76%, and the trans-product is: cis-product 12.0: 1.
the product I11 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(500MHz,CDCl3)δ7.55(dd,J＝8.8,5.6Hz,1H),6.88(dd,J＝8.8,8.8Hz,1H),3.73–3.70(m,4H),1.89–1.87(m,4H),1.08–1.07(m,18H,3H),0.96–0.95(m,18H,3H)；13C NMR(major isomer)(126MHz,CDCl3)δ161.37(d,J＝244.2Hz),136.71(d,J＝3.2Hz),136.27,131.47(d,J＝7.9Hz),114.19(d,J＝21.3Hz),109.40,102.56,100.47,99.93,98.19,51.53,25.80,18.92,18.64,11.91,11.37；19F NMR(major isomer)(376MHz,CDCl3)δ-117.93；HRMS(ESI-TOF)[M+H]calculated for[C34H55FNSi2]+552.3852, found 552.3851. this result further confirms the molecular structure of the product as described above under molecular structure I11.
Example 12
This example provides trans-1- (4- (furyl-2) -1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine and a process for its preparation.
The structural formula of the trans-1- (4- (furyl-2) -1, 6-bis (triisopropylsilyl) hexyl-3-ene-1, 5-diyne-3) pyrrolidine is shown as the following molecular structural formula I12:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1- (2-furyl) -4-triisopropylsilyl-butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 73%, and a trans-product: cis-product 12.8: 1.
the product I12 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(500MHz,CDCl3)δ7.25(dd,J＝1.9,0.9Hz,1H),6.40(dd,J＝3.3,0.9Hz,1H),6.32(dd,J＝3.3,1.9Hz,1H),3.73–3.70(m,4H),1.88–1.85(m,4H),1.09–1.08(m,18H,3H,3H),1.06(s,18H)；13C NMR(major isomer)(126MHz,CDCl3)δ153.71,140.00,135.53,110.90,106.95,106.74,102.06,101.65,97.49,91.61,51.71,25.79,18.92,18.75,11.88,11.50；HRMS(ESI-TOF)[M+H]calculated for[C32H54NOSi2]+524.3738, found 524.3738. this result further confirms the molecular structure of the product as described above under molecular structure I12.
Example 13
This example provides trans-1- (4- (naphthyl-1) -1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine and a process for its preparation.
The structural formula of the trans-1- (4- (naphthyl-1) -1, 6-bis (triisopropylsilyl) hexyl-3-ene-1, 5-diyne-3) pyrrolidine is shown as the following molecular structural formula I13:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1- (1-naphthyl) -4-triisopropylsilyl-butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid with the yield of 61 percent and a trans-product: cis-product 15.6: 1.
the product I13 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(400MHz,CDCl3)δ8.26(dd,J＝7.7,1.8Hz,1H),7.76(dd,J＝7.2,2.1Hz,1H),7.67(d,J＝8.3Hz,1H),7.52(dd,J＝7.1,1.3Hz,1H),7.42–7.32(m,3H),3.86–3.83(m,4H),1.95–1.92(m,4H),0.97–0.94(m,18H,3H),0.68–0.65(m,18H,3H)；13C NMR(major isomer)(101MHz,CDCl3)δ139.05,137.51,134.14,132.79,128.85,127.94,126.96,126.88,125.55,125.22,125.15,109.79,102.27,100.58,97.65,97.57,51.41,25.82,18.82,18.38,11.77,10.98；HRMS(ESI-TOF)[M+H]calculated for[C38H58NSi2]+584.4102, found 584.4100. this result further confirms the molecular structure of the product as described above under molecular structure I13.
Example 14
This example provides trans-1- (4- (naphthyl-2) -1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine and a process for its preparation.
The structural formula of the trans-1- (4- (naphthyl-2) -1, 6-bis (triisopropylsilyl) hexyl-3-ene-1, 5-diyne-3) pyrrolidine is shown as the following molecular structural formula I14:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1- (2-naphthyl) -4-triisopropylsilyl-butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid with the yield of 61 percent and a trans-product: cis-product 15.6: 1.
the product I14 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(500MHz,CDCl3)δ8.05(d,J＝1.8Hz,1H),7.81(dd,J＝8.6,1.8Hz,1H),7.75–7.65(m,3H),7.40–7.33(m,2H),3.78–3.76(m,4H),1.92–1.90(m,4H),1.10–1.09(m,18H,3H),0.87–0.85(m,18H,3H)；13C NMR(major isomer)(126MHz,CDCl3)δ138.15,136.64,133.50,132.27,128.67,128.39,128.00,127.45,126.67,125.37,124.98,109.48,102.77,101.02,100.31,98.18,51.64,25.85,18.97,18.58,11.95,11.31；HRMS(ESI-TOF)[M+H]calculated for[C38H58NSi2]+584.4102, found 584.4107. this result further confirms the molecular structure of the product as described above under molecular structure I14.
Example 15
This example provides trans-1- (4-phenyl-6-triisopropylsilyl-1-trimethylsilyl-hexyl-3-en-1, 5-diyne-3) pyrrolidine and a process for its preparation.
The structural formula of the trans-1- (4-phenyl-6-triisopropylsilyl-1-trimethylsilyl-hexyl-3-ene-1, 5-diyne-3) pyrrolidine is shown as the following molecular structural formula I15:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1-phenyl-4-trimethylsilyl-butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 82%, and a trans-product: cis-product 2.0: 1.
the product I15 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(400MHz,CDCl3)δ7.68–7.62(m,2H),7.24–7.20(m,2H),7.14–7.10(m,1H),3.71–3.68(m,4H),1.89–1.86(m,4H),1.08–1.06(m,18H,3H),0.07(s,9H)；13C NMR(major isomer)(101MHz,CDCl3)δ140.03,136.11,129.64,127.21,125.64,109.18,103.35,101.34,101.03,98.04,51.44,25.76,18.92,11.85,-0.44；HRMS(ESI-TOF)[M+H]calculated for[C28H44NSi2]+450.3007, found 450.3005. this result further confirms the molecular structure of the product as described above under molecular structure I15.
Example 16
This example provides trans-1- (4-phenyl-6-triisopropylsilyl-1-triethylsilyl-hexyl-3-en-1, 5-diyne-3) pyrrolidine and a process for its preparation.
The structural formula of the trans-1- (4-phenyl-6-triisopropylsilyl-1-triethylsilyl-hexyl-3-ene-1, 5-diyne-3) pyrrolidine is shown as the following molecular structural formula I16:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1-phenyl-4-triethylsilyl-butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 85%, and the trans-product is: cis-product 4.7: 1.
the product I16 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(400MHz,CDCl3)δ7.67–7.64(m,2H),7.24–7.19(m,2H),7.12–7.08(m,1H),3.74–3.70(m,4H),1.90–1.87(m,4H),1.11–1.09(m,18H,3H),0.88(t,J＝7.9Hz,9H),0.51(q,J＝7.9Hz,6H)；13C NMR(major isomer)(101MHz,CDCl3)δ140.18,136.24,129.72,127.26,125.63,109.28,101.99,101.25,97.98,90.96,51.47,25.78,18.92,11.86,7.49,4.26；HRMS(ESI-TOF)[M+H]calculated for[C31H50NSi2]+492.3476, found 492.3476. this result further confirms the molecular structure of the product as described above under molecular structure I16.
Example 17
This example provides trans-1- (7, 7-dimethyl-3-phenyl-1-triisopropylsilyl-octane-3-ene-1, 5-diyne-4) pyrrolidine and a method for its preparation.
The structural formula of the trans-1- (7, 7-dimethyl-3-phenyl-1-triisopropylsilyl-octane-3-ene-1, 5-diyne-4) pyrrolidine is shown as the following molecular structural formula I17:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1-phenyl-4-tert-butyl-butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 74%, and the trans-product is: cis-product ═ 3.2: 1.
the product I17 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(400MHz,CDCl3)δ7.69–7.61(m,2H),7.23–7.19(m,2H),7.11–7.06(m,1H),3.71–3.68(m,4H),1.88–1.85(m,4H),1.11(s,9H),1.09–1.08(m,18H,3H)；13C NMR(major isomer)(101MHz,CDCl3)δ140.63,137.08,129.57,127.11,125.20,109.61,106.31,98.76,96.46,76.18,51.41,30.31,28.33,25.77,18.94,11.89；HRMS(ESI-TOF)[M+H]calculated for[C29H44NSi]+434.3238, found 434.3237. this result further confirms the molecular structure of the product as described above under molecular structure I17.
Example 18
This example provides trans-3- (4-phenyl-1- (3-pyridyl) -6-triisopropylsilyl-hex-3-ene-1, 5-diyne-1) pyrrolidine and a method for its preparation.
The structural formula of the trans-3- (4-phenyl-1- (3-pyridyl) -6-triisopropylsilyl-hexane-3-ene-1, 5-diyne-1) pyrrolidine is shown as the following molecular structural formula I18:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1-phenyl-4- (3-pyridyl) -butan-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 77%, and the trans-product is: cis-product ═ 2.2: 1.
the product I18 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(400MHz,CDCl3)δ8.46(dd,J＝4.9,2.0Hz,1H),8.42(d,J＝2.0Hz,1H),7.69–7.66(m,2H),7.45–7.38(m,2H),7.30–7.26(m,2H),7.19–7.17(m,1H),3.80–3.76(m,4H),1.94–1.91(m,4H),1.09–1.07(m,18H,3H)；13C NMR(major isomer)(101MHz,CDCl3)δ151.88,148.72,140.30,138.05,135.70,129.77,127.45,126.05,123.10,120.07,108.98,101.93,98.66,93.31,89.94,51.49,25.78,18.91,11.84；HRMS(ESI-TOF)[M+H]calculated for[C30H39N2Si]+455.2877, found 455.2876. this result further confirms the molecular structure of the product as described above under molecular structure I18.
Example 19
This example provides trans-1- (1, 4-diphenyl-6-triisopropylsilyl-hex-3-ene-1, 5-diyne-3) pyrrolidine and a method for its preparation.
The structural formula of the trans-1- (1, 4-diphenyl-6-triisopropylsilyl-hexane-3-ene-1, 5-diyne-3) pyrrolidine is shown as the following molecular structural formula I19:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that 1, 4-diphenyl-butane-3-yn-2-one (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butane-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 85%, and the trans-product is: cis-product 2.8: 1.
the product I19 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(400MHz,CDCl3)δ7.74–7.71(m,2H),7.31–7.26(m,6H),7.22–7.21(m,2H),3.81–3.78(m,4H),1.94–1.91(m,4H),1.10–1.09(m,18H,3H)；13C NMR(major isomer)(101MHz,CDCl3)δ140.44,136.49,131.89,131.32,129.71,128.40,127.36,125.68,122.88,109.35,100.84,97.93,96.94,86.67,51.52,25.81,18.94,11.88；HRMS(ESI-TOF)[M+H]calculated for[C31H40NSi]+454.2925, found 454.2926. this result further confirms the molecular structure of the product as described above under molecular structure I19.
Example 20
This example provides trans-1- (4- (4-phenyl- (3-pyrrolidinyl-1) -6-triisopropylsilyl-hex-3-ene-1, 5-diyne-1) phenyl) pentan-1-one and a method for its preparation.
The structural formula of the trans-1- (4- (4-phenyl- (3-pyrrolidinyl-1) -6-triisopropylsilyl-hexane-3-ene-1, 5-diyne-1) phenyl) pentane-1-ketone is shown as the following molecular structural formula I20:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that the corresponding alkynone (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 62%, and the trans-product is: cis-product 2.8: 1.
the product I20 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(400MHz,CDCl3)δ7.83(d,J＝8.2Hz,2H),7.70–7.68(m,2H),7.30–7.27(m,2H),7.24(d,J＝8.2Hz,2H),7.20–7.16(m,1H),3.80–3.77(m,4H),2.91(t,J＝7.4Hz,2H),1.95–1.91(m,4H),1.73–1.65(m,2H),1.45–1.36(m,2H),1.10–1.07(m,18H,3H),0.94(t,J＝7.4Hz,3H)；13C NMR(major isomer)(101MHz,CDCl3)δ199.79,140.34,136.32,135.92,131.92,131.33,129.79,128.08,127.44,125.98,109.07,102.08,98.82,96.05,89.92,51.51,38.49,26.59,25.81,22.59,18.93,14.06,11.86；HRMS(ESI-TOF)[M+H]calculated for[C36H48NOSi]+538.3500, found 538.3503. this result further confirms the molecular structure of the product as described above under molecular structure I20.
Example 21
This example provides a trans-1- (9-chloro-3-phenyl-1-triisopropylsilyl-nonane-3-en-1, 5-diyne-4) -pyrrolidine and a process for its preparation.
The structural formula of the trans-1- (9-chloro-3-phenyl-1-triisopropylsilyl-nonane-3-ene-1, 5-diyne-4) -pyrrolidine is shown as the following molecular structural formula I21:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that the corresponding alkynone (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid, wherein the yield is 55%, and the trans-product is: cis-product 2.5: 1.
the product I21 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(400MHz,CDCl3)δ7.63–7.56(m,2H),7.25–7.21(m,2H),7.14–7.09(m,1H),3.71–3.68(m,4H),3.36(t,J＝6.5Hz,2H),2.42(t,J＝6.5Hz,2H),1.89–1.85(m,4H),1.80(tt,J＝6.5,6.5Hz,2H),1.08–1.06(m,18H,3H)；13C NMR(major isomer)(101MHz,CDCl3)δ140.71,136.60,129.66,127.36,125.52,109.38,99.53,96.93,96.12,78.42,51.46,43.61,30.87,25.76,18.93,17.03,11.87；HRMS(ESI-TOF)[M+H]calculated for[C28H41ClNSi]+454.2691, found 454.2699. this result further confirms the molecular structure of the product as described above under molecular structure I21.
Example 22
This example provides a trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) azacyclobutane and a method of making the same.
The structural formula of the trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-ene-1, 5-diyne-3) azetidine is shown as the following molecular structural formula I22:
the procedure is as described for the preparation of trans-1- (4-phenyl-1, 6-bis (triisopropylsilyl) hexyl-3-en-1, 5-diyne-3) pyrrolidine as in example 1, except that the corresponding alkynone (0.1mmol) is used instead of 1-phenyl-4-triisopropylsilyl-butan-3-yn-2-one.
After the reaction is finished, spin-drying the filtrate, and performing column chromatography separation to obtain a target product which is a bright yellow oily liquid with the yield of 75 percent and a trans-product: cis-product 4.2: 1.
the product I22 prepared was subjected to characterization data analysis, which resulted in:1H NMR(major isomer)(400MHz,CDCl3)δ7.70–7.68(m,2H),7.23–7.19(m,2H),7.13–7.09(m,1H),4.23(t,J＝7.5Hz,4H),2.24(p,J＝7.5Hz,2H),1.10–1.07(m,18H,3H),1.01–1.00(m,18H,3H)；13C NMR(major isomer)(126MHz,CDCl3)δ139.19,138.71,129.07,127.48,125.83,107.37,102.05,101.56,100.43,99.04,54.54,18.91,18.67,16.77,11.86,11.39；HRMS(ESI-TOF)[M+H]calculated for[C33H54NSi2]+520.3789, found 520.3786. this result further confirms the molecular structure of the product as described above under molecular structure I22.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (3)
1. A preparation method of a diyne enamine compound at least comprises the following steps:
providing a secondary amine A, an electrophilic compound B and an alkynone compound D represented by the following structural formulas respectively:
A、
B、
D、
adding a gold catalyst and the secondary amine A into a reaction system containing the electrophilic reagent compound B, the pyridine ligand C and the alkynone compound D, and reacting at the temperature of 25-100 ℃ to obtain a diyne enamine compound shown as the following structural general formula (I):
wherein, the compound A, B, D and R in the structural formula of (I)1、R2、R3、R4And R5Are identical or different C1-C20Alkyl radical, C1-C20Heteroalkyl group, C3-C20Cycloalkyl radical, C3-C20Heterocycloalkyl radical, C2-C20Alkenyl radical, C2-C20Heteroalkenyl, C3-C20Cycloalkenyl radical, C3-C20Heterocycloalkenyl, C2-C20Alkynyl, C2-C20Heteroalkynyl, C3-C20Cycloalkynyl group, C3-C20Heterocycloalkynyl, C1-C20Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl C1-C20Alkyl, aryl C9-C15Cycloalkyl, aryl C9-C20Hetero-atomic cycloalkyl, heteroaryl C1-C20Alkyl radical, C2-C20Alkenyl radical C1-C20Alkyl radical, C2-C20Alkynyl C1-C20Alkyl, cyano C1-C20Any of an alkyl group, an alkyloxycarbonylalkyl group, and a hydrogen atom;
the R is6、R7Is C1-C20Alkyl radical, C1-C20Heteroalkyl group, C3-C20Cycloalkyl radical, C3-C20Heterocycloalkyl radical, C2-C20Alkynyl, C2-C20Heteroalkynyl, C3-C20Cycloalkynyl group, C3-C20Heterocycloalkynyl, C1-C20Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl C1-C20Alkyl, heteroaryl C1-C20Alkyl radical, C2-C20Alkenyl radical C1-C20Alkyl radical, C2-C20Alkynyl C1-C20Alkyl, cyano C1-C20Any one of alkyl, alkyloxycarbonylalkyl, halogen substituent, or, the R6、R7Forming pyrrolidine or azacyclobutane with N;
the R is8And R9Is C1-C20Alkyl radical, C1-C20Heteroalkyl group, C3-C20Cycloalkyl radical, C3-C20Heterocycloalkyl radical, C2-C20Alkynyl, C2-C20Heteroalkynyl, C3-C20Cycloalkynyl group, C3-C20Heterocycloalkynyl, C1-C20Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl C1-C20Alkyl, heteroaryl C1-C20Alkyl radical, C2-C20Alkenyl radical C1-C20Alkyl radical, C2-C20Alkynyl C1-C20Alkyl, cyano C1-C20Any one of an alkyl group, an alkyloxycarbonylalkyl group, a halogen substituent, a triisopropylsilyl group, and a triethylsilyl group;
the molar ratio of the gold catalyst to the pyridine ligand C to the alkynone compound D is (0.1-20) to (0-20) to (1-100);
the pyridine ligand C is a heterocyclic compound with the following molecular structure general formula:
C：
R10、R11、R12、R13、R14、R15、R16、R17are identical or different C1-C20Alkyl radical, C1-C20Heteroalkyl group, C3-C20Cycloalkyl radical, C3-C20Heterocycloalkyl radical, C2-C20Alkenyl radical, C2-C20Heteroalkenyl, C1-C20Perfluoroalkyl radical, C3-C20Cycloalkenyl radical, C3-C20Heterocycloalkenyl, C2-C20Alkynyl, C2-C20Heteroalkynyl, C3-C20Cycloalkynyl group, C3-C20Heterocycloalkynyl, C1-C20Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl C1-C20Alkyl, heteroaryl C1-C20Alkyl radical, C2-C20Alkenyl radical C1-C20Alkyl radical, C2-C20Alkynyl C1-C20Alkyl, cyano C1-C20Any of an alkyl group, an alkyloxycarbonylalkyl group, and a hydrogen atom;
the gold catalyst is at least one of the following compounds:
wherein, the aryl is phenyl, naphthyl, anthryl and phenanthryl;
the heteroaryl group means a monocyclic or polycyclic or fused-ring aromatic hydrocarbon in which one or more carbon atoms have been substituted by nitrogen, oxygen or sulfur.
2. The method of claim 1, wherein: the R is1、R2、R3、R4And R5Are identical or different C1-C20Alkyl radical, C1-C20Heteroalkyl group, C3-C20Cycloalkyl radical, C3-C20Cycloalkenyl radical, C3-C20Heterocycloalkenyl, C2-C20Alkynyl, C2-C20Heteroalkynyl, C1-C20Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl C1-C20Alkyl, aryl C9-C15Cycloalkyl, aryl C9-C20Hetero-atomic cycloalkyl, heteroaryl C1-C20Alkyl radical, C2-C20Alkenyl radical C1-C20Alkyl radical, C2-C20Alkynyl C1-C20Any of an alkyl group, an alkyloxycarbonylalkyl group, and a hydrogen atom;
the R is6、R7、R8And R9Is C1-C20Alkyl radical, C1-C20Heteroalkyl group, C3-C20Cycloalkyl radical, C3-C20Heterocycloalkyl radical, C2-C20Alkynyl, C3-C20Cycloalkynyl group, C3-C20Heterocycloalkynyl, C1-C20Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl C1-C20Alkyl, heteroaryl C1-C20Alkyl radical, C2-C20Alkenyl radical C1-C20Alkyl radical, C2-C20Alkynyl C1-C20Alkyl, cyano C1-C20Any one of alkyl, alkyloxycarbonylalkyl, and halogen substituents.
3. The method of claim 2, wherein: the R is1、R2、R3、R4And R5Is C1-C5Alkyl radical, C3-C20Cycloalkyl, phenyl C9-C15Cycloalkyl, phenyl C9-C20Heteroatom cycloalkyl, halogen substituted phenyl, alkoxy substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl C1-C20Alkyl, heteroaryl C1-C20Any of alkyl groups;
the R is6、R7、R8And R9Is C1-C6Alkyl radical, C1-C10Heteroalkyl group, C3-C8Cycloalkyl radical, C3-C8Heterocycloalkyl radical, C2-C6Alkynyl, C1-C6Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl C1-C6Alkyl radical, C2-C6Alkynyl C1-C4Any one of alkyl, alkyloxycarbonylalkyl, and halogen substituents.
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| Pd-Catalyzed, Ligand-Enabled Stereoselective 1,2-Iodine(III) Shift/1,1-Carboxyalkynylation of Alkynylbenziodoxoles;Junliang Wu等;《Chem. Eur. J.》;20170106;第23卷;第1521-1525页 * |
| Reactions of (tert-Butyldimethylsilyl)alkynes with IPy2BF4: Selective Synthesis of Novel Head-to-Head Dimers;Isidro Llorente等;《J. Am. Chem. Soc.》;19970723;第119卷;第6933-6934页 * |
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