A method for preparing fused ring arylamines from isonitriles and cyclopropenes

Abstract

A process for the preparation of fused ring arylamines from isonitriles and cyclopropenes is disclosed, the reaction scheme being as follows:

Description

Technical Field

[0001] This application relates to the field of organic synthesis technology, and in particular to a method for preparing polycyclic aromatic amines from isonitriles and cyclopropenes. Background Technology

[0002] The synthesis of fused-ring aromatic amines is one of the most important research areas in organic synthetic chemistry, as they are the core structures of many important functional materials and bioactive molecules. Fused-ring aromatic amine compounds can be used as starting materials to prepare various materials through subsequent transformations, such as electrophilic and nucleophilic aryl substitution, aryl C-H activation, and dearomatization reactions.

[0003] The high cost and complex preparation methods of aromatic amines hinder the full realization of their application potential. Currently, most polycyclic aromatic amines are obtained from natural resources such as coal tar or petroleum, resulting in very limited structural diversity.

[0004] Currently, the synthesis of fused-ring aromatic amines is based on intramolecular reactions (such as ring isomerization), which seriously hinders the development of related fields such as medicinal chemistry and combinatorial chemistry, as well as the optimization of functional materials. Therefore, there is an urgent need to develop intermolecular methods for the efficient synthesis of multifunctionalized fused-ring aromatic amines, preferably starting with readily available starting materials. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide a process for preparing compound (III) from compounds of formula (I) and formula (II) in the presence of carbene and transition metal catalysts or their precursors.

[0006]

[0007] Its features are,

[0008] Ar 1 It can be any one of aryl, heteroaryl, or alkenyl.

[0009] R 1 R 2 and R 3 It can be independently selected from one of hydrogen, halogen, alkyl, aryl, heteroaryl, alkenyl, alkynyl or metalloid.

[0010] The substituents on the compounds of formula (I) are optionally linked to alkylene chains.

[0011] R 4 It can be any of the following: alkyl, aryl, heteroaryl, alkenyl, alkynyl, or metalloid, and is attached to a substituent on the compound of formula (I).

[0012] Ar 2 Optional aryl, heteroaryl (from Ar) 1Substituted aryl and heteroaryl), or optionally aliphatic structures (from Ar) 1 (substituted alkenyl groups).

[0013] Transition metal catalysts can be selected from groups 3-12.

[0014] Carbene can be any member containing a divalent carbon atom. Detailed Implementation

[0015] Many specific details are set forth in the following description to provide a full understanding of this specification. However, those skilled in the art will recognize that it can be implemented using other methods, components, materials, etc., without one or more of these specific details.

[0016] Unless the context otherwise requires, throughout the specification and appended claims, the word “comprising” and its variations, such as “including” and “contains”, shall be interpreted in an open and inclusive sense, meaning “including but not limited to”.

[0017] Throughout this specification, references to "one embodiment," "another embodiment," "some embodiments," or "in some embodiments" refer to specific reference features, structures, or characteristics associated with an embodiment that are included in at least one embodiment. Therefore, phrases such as "in one embodiment," "another embodiment," or "in some embodiments" appearing throughout this specification do not necessarily refer to the same embodiment. Furthermore, specific features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

[0018] It should be noted that, in this specification and the appended claims, unless otherwise expressly specified, the singular forms “a,” “an,” and “the” include plural objects. In this application, unless otherwise stated, “or” is used to mean “and / or.”

[0019] Some chemical groups mentioned in this article are preceded by abbreviations indicating the total number of carbon atoms found in the indicated chemical group. For example, C7-C 12 Alkyl refers to an alkyl group having a total of 7 to 12 carbon atoms as defined below, C4-C 12 Cycloalkyl refers to a cycloalkyl group having a total of 4 to 12 carbon atoms as defined below. The total number of carbons in the abbreviated symbol does not include carbons that may be present in substituents of the group.

[0020] The "C" used in this article m To C n "or "C m至nThe term “C1 to C4 alkyl” refers to the number of carbon atoms in an alkyl, alkenyl, or ynyl group, or the number of carbon atoms in the ring of a cycloalkyl or cycloalkenyl group. That is, the ring of an alkyl, alkenyl, ynyl, cycloalkyl, or cycloalkenyl group can contain carbon atoms from “m” to “n” (inclusive). Therefore, for example, “C1 to C4 alkyl” groups refer to all alkyl groups having 1 to 4 carbon atoms, namely CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH-, CH3CH2CH2CH2-, CH3CH2CH(CH3)-, and (CH3)3C-. If “m” and “n” are not specified for alkyl, alkenyl, ynyl, cycloalkyl, or cycloalkenyl groups, the widest range described in these definitions is assumed.

[0021] Therefore, the following terms used in the specification and appended claims, unless otherwise stated, shall have the following meanings:

[0022] The term "alkyl" as used herein, alone or as part of a group, refers to any unbranched or branched, substituted or unsubstituted saturated hydrocarbon group. The alkyl moiety can be branched or straight-chain. An alkyl group can have 1 to 20 carbon atoms (wherever it appears herein, a numerical range such as "1 to 20" refers to every integer within a given range; for example, "1 to 20 carbon atoms" means that an alkyl group can consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 20 carbon atoms, although this definition also covers the occurrence of the term "alkyl" where no numerical range is specified). An alkyl group can also be a medium-sized alkyl group having 1 to 10 carbon atoms. An alkyl group can also be a lower alkyl group having 1 to 5 carbon atoms. An alkyl group can be referred to as "C1-C4 alkyl" or similar names. By way of example only, "C1-C4 alkyl" means that there are 1-4 carbon atoms in the alkyl chain, i.e., the alkyl chain is selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and tert-butyl.

[0023] Alkyl groups can be substituted or unsubstituted. When substituted, the substituent is one or more independently selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroaryloxy, heterocyclic, heterocyclic, heteroalicyclic, hydroxyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryloxy, acyl, thiol, substituted or unsubstituted thioalkoxy, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, acylalkyl, acylamino, acyloxy, aminoacyl Aminoacyloxy, oxyacylamino, ketone, thioketone, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, C-acylamino, N-acylamino, S-sulfinylamino, N-sulfinylamino, C-carboxyl, O-carboxyl, isocyanate, cyanothio, isocyanothio, nitro, silyl, trihalomethanesulfonyl, and substituted or unsubstituted amino groups, including monosubstituted -SO2-alkyl, -SO2-substituted alkyl, -SO2-aryl, and -SO2-heteroaryl.

[0024] Typical alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, and hexyl. When a substituent is described as "optional," the substituent can be replaced by one or more of the above-mentioned substituents.

[0025] The term "alkenyl" as used alone or as part of a group herein refers to a straight-chain or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, containing at least one double bond, having 2 to 12 carbon atoms, preferably 2 to 8 carbon atoms, and connected to the rest of the molecule by single bonds, such as vinyl, propenyl, butenyl, pentenyl, pent-1,4-dienyl, cyclohexenyl, etc.

[0026] The term "alkynyl" as used alone or as part of a group herein refers to a straight-chain or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, containing at least one triple bond, having 2 to 12 carbon atoms, preferably 2 to 8 carbon atoms, and connected to the rest of the molecule by single bonds, such as ethynyl, propynyl, butynyl, pentynyl, and hexynyl.

[0027] The term "aryl" as used alone or as part of a group in this document refers to a carbocyclic aromatic ring or ring system. Aryl groups can be unsubstituted or substituted. Furthermore, the term "aryl" includes fused-ring systems, wherein there are at least two aryl rings, or at least one aryl group and at least one C2C2 ring. 3-8 - Cycloalkyl groups share at least one chemical bond. Some examples of "aryl" rings include optionally substituted phenyl, naphthyl, phenanthryl, anthracene, tetrahydronaphthyl, fluorenyl, indene, and dihydroindene.

[0028] The term "aryl" refers to an aromatic group, including, for example, a benzene-type group, linked by a cyclic carbon atom and optionally carrying one or more substituents selected from: heterocyclic, heteroaryl, halogen, hydroxyl, amino, cyano, nitro, alkylamide, acyl, C 1-6 -alkoxy group, C 1-6 -alkyl, C 1-6 -hydroxyalkyl, C 1-6 -aminoalkyl, C 1-6 -alkylamino, alkylsulfinyl, alkylsulfinyl, alkylsulfonyl, aminosulfonyl, or trifluoromethyl. The aryl group may optionally be substituted at the para, ortho, and / or meta positions.

[0029] The term “heteroaryl” as used alone or as part of a group in this article refers to a heterocyclic aromatic group in which one or more carbon atoms of an aromatic ring are replaced by one or more heteroatoms such as nitrogen, sulfur, and oxygen.

[0030] Furthermore, in this document, the term "heteroaryl" includes fused ring systems in which at least one aromatic ring and at least one heteroaryl ring, at least two heteroaryl rings, at least one heteroaryl ring and at least one heterocyclic ring, or at least one heteroaryl ring and at least one cycloalkyl ring share at least one chemical bond.

[0031] The term "heteroaryl" should be understood to refer to aromatic C atoms containing one oxygen or sulfur atom or at most four nitrogen atoms, or a combination of one oxygen or sulfur atom and at most two nitrogen atoms. 3-8 Cyclic groups, and their substituted and benzo[a] and pyridin[b] fused derivatives, are linked, for example, by a cyclic carbon atom. Heteroaryl groups may have one or more substituents selected from halogens, hydroxyl groups, amino groups, cyano groups, nitro groups, alkylamide groups, acyl groups, and C[a] groups. 1-6 -alkoxy group, C 1-6 -alkyl, C 1-6 -hydroxyalkyl, C 1-6 -aminoalkyl, C 1-6 -alkylamino, alkylsulfinyl, alkylsulfinyl, alkylsulfonyl, or trifluoromethyl. In some embodiments, the heteroaryl group can be a five- or six-membered aromatic heterocyclic system with 0, 1, or 2 substituents, which may be the same as or different from each other, selected from the list above.

[0032] Representative examples of heteroaryl groups include, but are not limited to, unsubstituted and monosubstituted or disubstituted derivatives of furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, indole, oxazole, benzoxazole, isoxazole, benzoisoxazole, thiazole, benzothiazole, isothiazole, imidazole, benzimidazole, pyrazole, indazole, tetrazolium, quinoline, isoquinoline, pyridazine, pyrimidine, purine and pyrazine, furazine, 1,2,3-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, borazine, triazole, benzotriazole, pteridine, benzoxazole, oxadiazole, benzopyrazole, quinazine, cinnamon, phthalazine, quinazoline, and quinoxaline. In some embodiments, the substituent is halogen, hydroxyl, cyano, or OC. 1-6 -alkyl, C 1-6 -alkyl, hydroxy-C 1-6 -alkyl and amino-C 1-6 -alkyl.

[0033] As used herein, the terms “optional,” “optional,” or “optionally” mean that the event in the following description may or may not occur, and the description includes both the possibility that the event or situation occurs and the possibility that it does not occur.

[0034] Unless otherwise stated, when a substituent is considered "optional," it means that the substituent is a group that can be replaced by one or more groups selected individually and independently from morpholino esters, cycloalkyl, aryl, heteroaryl, heterocyclic, heterocyclocyclic, hydroxyl, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, C-carbamoyl S-sulfonamide, N-sulfonamide, C-carboxyl, O-carboxyl, isocyanate, cyanothio, isocyanothio, nitro, silyl, trihalomethanesulfonyl, and amino, including mono- and di-substituted amino groups, and their protected derivatives.

[0035] For example, "optional aryl" means that the aryl group may or may not be substituted, and the description includes substituted aryl groups and unsubstituted aryl groups.

[0036] As used in this article, the term "transition metal" refers to any element in the d-block of the periodic table. This corresponds to Groups 3 (IIIB) through 12 (IIB) of the periodic table.

[0037] In chemistry, the term "ligand" typically refers to the bond between an atom, ion, or molecule and a central metal, generally involving the formal donation of one or more electrons. The bonding between a metal and a ligand ranges from covalent to ionic.

[0038] As used in this article, the term "carbene" refers to an organic molecule containing a carbon atom with six valence electrons and having the general formula RRC:

[0039] The term "alkylene" or "alkylene chain" as used alone or as part of a group in this document refers to a straight-chain or branched divalent hydrocarbon chain that connects the remainder of a molecule to a group consisting only of carbon and hydrogen, without unsaturated bonds, and having 1-12 carbon atoms, such as methylene, ethylene, propylene, n-butylene, etc. The alkylene chain is connected to the remainder of the molecule and to the group via single bonds. The connection points between the alkylene chain and the remainder of the molecule and to the group can be one carbon or any two carbons within the chain.

[0040] The term "alkenyl subchain" or "alkenyl subchain" as used alone or as part of a group refers to a straight-chain or branched divalent hydrocarbon chain, such as vinylene, allylene, n-butenyl, etc., that links the remainder of a molecule to a group consisting only of carbon and hydrogen, contains at least one double bond, and has 2 to 12 carbon atoms. The alkenyl subchain is attached to the remainder of the molecule by a single bond and to the group by either a double or single bond. The connection point between the alkenyl subchain and the remainder of the molecule, and to the group, can be one carbon or any two carbons within the chain.

[0041] The term "ynynyl" or "ynynyl chain," used alone or as part of a group, refers to a straight-chain or branched divalent hydrocarbon chain that connects the remainder of a molecule to a group consisting only of carbon and hydrogen, containing at least one triple bond, and having 2 to 12 carbon atoms, such as propynylene, n-butynylene, etc. The ynynyl chain is connected to the remainder of the molecule by a single bond and to the group by a double or single bond. The connection point between the ynynyl chain and the remainder of the molecule, and to the group, can be one carbon or any two carbons within the chain.

[0042] As used herein, the term "amine" refers to a compound containing an amino group. The term "amino" as used herein, alone or as part of a group, refers to a substituted N-group.

[0043] Metalloids, or half-metals, are a term used in chemistry to classify chemical elements. Almost every element in the periodic table can be called a metal or non-metal based on its general physical and chemical properties. However, a few elements are referred to as metalloids. The term has no strict definition, but the following properties are generally considered characteristic of metalloids: (1) metalloids often form amphoteric oxides; and (2) metalloids typically behave as semiconductors (B, Si, Ge).

[0044] The following elements are generally considered to be metalloids: boron (B), silicon (Si), germanium (Ge), arsenic (As), antimony (Sb), tellurium (Te), and polonium (Po).

[0045] On the one hand, this application relates to a method for preparing compound (III) from compounds of formula (I) and formula (II) in the presence of N-heterocyclic carbene and a transition metal catalyst or a precursor thereof.

[0046]

[0047] Its features are,

[0048] Ar 1 It can be any one of aryl, heteroaryl, or alkenyl.

[0049] R 1 R 2 and R 3 It can be independently selected from one of hydrogen, halogen, alkyl, aryl, heteroaryl, alkenyl, ynyl, or metalloid.

[0050] The substituents on the compounds of formula (I) are optionally linked to alkylene chains.

[0051] R 4 It can be any one of alkyl, aryl, heteroaryl, alkenyl, alkynyl or metalloid, and can be optionally linked to a substituent on a compound of formula (I).

[0052] Ar 2 It is either a selective aryl or a heteroaryl (from Ar) 1 Substituted aryl and heteroaryl), or optionally aliphatic structures (from Ar) 1 (substituted alkenyl groups).

[0053] Transition metal catalysts can be selected from groups 3-12.

[0054] The carbene may be substituted by one or more heteroatoms. When using cyclic carbenes, the ring size may be arbitrarily chosen to be a 4- to 12-membered ring.

[0055] In some embodiments of this application, Ar 1 It can be optionally substituted with phenyl, naphthyl, phenanthryl, anthraceneyl, tetrahydronaphthyl, fluorenyl, alkenyl, indene, or dihydroindene.

[0056] In some embodiments of this application, the compound of formula (I) may optionally contain cyclopropylene and its substituted derivatives.

[0057] In some embodiments of this application, R 1 R 2 and R 3 It can be independently selected from hydrogen, halogen, alkyl, aryl, heteroaryl, alkenyl, alkynyl or metalloid.

[0058] In some embodiments of this application, the substituents on the compound of formula (I) are optionally linked by alkylene chains.

[0059] In some embodiments of this application, R 4 It can be an alkyl, aryl, heteroaryl, alkenyl, ynyl, or metalloid that is optionally substituted.

[0060] In some embodiments of this application, the compound of formula (II) is selected from isocyanates, such as phenyl isocyanates, furanyl isocyanates, tert-butyl isocyanates and their substituted derivatives.

[0061] The transition metal catalysts of the present invention may include any catalytic transition metal and / or catalyst precursor, which, when introduced into the reaction vessel, can be converted in situ to an active form if desired, as well as the active form of the catalyst participating in the reaction. In some embodiments of this application, the transition metals are optionally from groups 3-12.

[0062] Exemplary transition metals that can be used in this application include, but are not limited to, scandium (SC), titanium (Ti), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), yttrium (Y), zirconium (Zr), niobium (Nb), molybdenum (Mo), technetium (TC), ruthenium (Ru), rhodium (Rh), palladium (PD), silver (Ag), cadmium (CD), hafnium (HF), tantalum (Ta), tungsten (W), rhenium (Re), osmium (OS), iridium (IR), platinum (Pt), gold (Au), mercury (Hg), du (Db), styrene (SG), boron (BH), potassium (Hs), metal (Mt), darmstein (DS), roentgen (Rg), and umbium (Uub).

[0063] In some embodiments of this application, the transition metal is selected from Group 10.

[0064] In some embodiments of this application, the transition metal is selected from nickel (Ni), palladium (Pd), and platinum (Pt). In some embodiments of this application, the transition metal is nickel (Ni).

[0065] In some embodiments of this application, the ligands on the transition metal catalyst are selected from carbene, heterocyclic carbene (NHCs), biscarbene, bisheterocyclic carbene, phosphine, amine, imine, arsine and their hybrids, compositions and derivatives.

[0066] In some embodiments of this application, the ligand or metal carries a weak or non-nucleophilic stable ion, including but not limited to halogens, borates, sulfonates, and phosphonates.

[0067] Ligands can be added to the reaction mixture in the form of metal complexes or as standalone reagents. If the ligand is chiral, it can be added in the form of a racemic mixture or an optically pure stereoisomer.

[0068] In some embodiments of this application, the carbene is IPr (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-yl group; CAS: 244187-81-3).

[0069] In some embodiments of this application, the transition metal catalyst is NiCl2DME, or a dimer, trimer, or higher oligomer thereof, optionally used in conjunction with NaBArF, wherein NaBArF is used in stoichiometric or catalytic amounts.

[0070] In some embodiments of this application, the transition metal catalyst and carbene are used in the form of a separate complex [(carbene)NiX2]L, optionally used with NaBArF, wherein L is a solvent molecule or an isocyanate of formula (II), the carbene is IPr (IPr = 1,3-bis(2,6-di-isopropylphenyl)imidazol-2-yl group; CAS: 244187-81-3), and X is a halogen or other similar group.

[0071] In some embodiments of this application, a transition metal catalyst is provided in a catalytic amount during the reaction. In specific embodiments, this catalytic amount is less than 10 mol% relative to an equivalence reagent, which may be a compound of formula (I) or a compound of formula (II), depending on which reagent is in stoichiometric excess.

[0072] In some embodiments of this application, the reaction may be carried out using any solvent. The solvent is selected from aromatic hydrocarbons, aliphatic hydrocarbons, alicyclic hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, ketones, nitriles, and diol derivatives.

[0073] Exemplary aromatic hydrocarbons that can be used in this application include, but are not limited to, benzene, toluene, xylene, etc. Exemplary aliphatic hydrocarbons that can be used in this application include, but are not limited to, pentane, hexane, heptane, octane, etc. Exemplary alicyclic hydrocarbons that can be used in this application include, but are not limited to, cyclohexane, cyclohexanone, methylcyclohexanone, etc. Exemplary alcohols that can be used in this application include, but are not limited to, methanol, ethanol, isopropanol, etc. Exemplary ethers that can be used in this application include, but are not limited to, diethyl ether, methyl ethyl ether, propyl ether, propylene oxide, etc. Exemplary esters that can be used in this application include, but are not limited to, methyl formate, ethyl formate, butyl formate, amyl formate, methyl acetate, ethyl acetate, propyl acetate, benzyl phenylacetate, etc. Exemplary ketones that can be used in this application include, but are not limited to, acetone, methyl butanone, methyl isobutyl ketone, etc. Exemplary nitriles that can be used in this application include, but are not limited to, acetonitrile, propionitrile, acrylonitrile, etc. Exemplary glycol derivatives that can be used in this application include, but are not limited to, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, etc.

[0074] In some embodiments of this application, the solvent is an aromatic hydrocarbon. In some embodiments of this application, the solvent is selected from benzene, toluene, and xylene.

[0075] Alternatively, the reaction can be carried out under solvent-free conditions. Ionic liquids such as imidazole salts can also be used as reaction media.

[0076] In some embodiments of this application, the method may optionally be carried out in a buffer solution to minimize problems related to isomerization, oligomerization, and polymerization. Examples of buffers that can be used in this application include, but are not limited to, ammonium salts, phosphorus buffers, and carbonates. Detailed Implementation

[0078] The reaction is sensitive to oxygen and moisture; the substrate should be dried and degassed before use (usually overnight on CaH2 or CaCl2 powder). Unless otherwise specified, all reactions are carried out under an oxygen-free atmosphere of nitrogen or argon, with strict removal of moisture from reagents and glassware. NiBr2DME, purchased from Acros or IL, is stored under a nitrogen atmosphere and is ready for use without further purification. IPr and NaBArF are purchased from Aldrich or Strem. Isocyanates are filtered through a short silica gel column and dried before use to remove any potential stabilizers. Substituted cyclopropenes are prepared according to standard methods. Toluene is distilled with sodium before use.

[0079] Thin-layer chromatography (TLC) was performed using EM Science silica gel 60 F254 plates. The developed chromatograms were analyzed using UV light (254 nm) and ethanol phosphomolybdic acid (PMA) or potassium permanganate (KMnO4). Liquid chromatography was performed using forced flow (fast chromatography) with a specified solvent system on silica gel (230–400 mesh). 1 H and 13 C10 NMR spectra were recorded in CDCl3 on a Bruker 400MHz or 300MHz spectrometer. 1 Chemical shifts in the 1H NMR spectra are expressed in ppm on the δ scale with an internal standard of residual chloroform (7.27 ppm). The data are reported as follows: chemical shifts, multiplicity (s = singlet, d = doublet, t = triplet, q = quadruplet, m = multit, br = broad), coupling constants in Hertz (Hz), and integrals. 13 The chemical shifts in the C NMR spectra are reported in ppm on the δ scale from the central peak of CDCl3 (77.16 ppm).

[0080] In this case, the general formula [(NHC)NiX2](NaBArF) is used as an example. n The catalyst [(IPr)NiBr2] / (NaBArF)2 can be produced by, but is not limited to, the following method: IPr, NiBr2DME, and NaBArF are stirred in toluene at 80°C for 3-5 minutes in a ratio of 1:1:2.

[0081] [(NHC)NiBr2] / (NaBArF)2 catalysts can also be produced by other methods, including but not limited to mixing a Ni source with 1) an imidazolium salt or ionic liquid, typically with or without a base; or 2) an alkyl, aryl, benzyl, vinyl, alkenyl, or alkynyl X; or 3) a conventional hydride or hydrogen source, optionally with activators and buffers, including but not limited to Lewis acid additives, protic acids, and / or nucleophiles; or 4) other common organometallic conversion and manipulation techniques, such as hydride addition or elimination steps and substitution.

[0082] Experimental results show that the outcome of the coupling reaction is highly sensitive to the structure of the carbene catalyst, the antiion used, and the possible preparation method.

[0083] The general procedure for catalyst preparation is as follows: NHC (0.05 mmol, 10 mol%), NiBr2DME (0.05 mmol, 10 mol%), and NaBArF (0.10 mmol, 20 mol%) are added to a dried test tube equipped with a stir bar in a glove box. The catalyst mixture is dissolved in degassed toluene (1 ml) under nitrogen atmosphere and stirred at 80 °C for 3–5 minutes.

[0084] The general procedure for the synthesis of fused-ring aromatic amines is as follows: A 1 mL toluene solution of compounds (I) and (II) (0.5 mmol, 100 mol% and 1 mmol, 200 mol%, respectively) is added to a mixture of [NHC-NiBr2](NaBArF)2 at 80°C, and the mixture is stirred overnight (~12 hours). The mixture is then cooled, diluted with n-hexane / ethyl acetate (6 mL, 10:1), and stirred at room temperature for 30 minutes. The mixture is then filtered through a short silica gel column and washed with 20% ethyl acetate / hexane (50 mL). The solvent is removed under reduced pressure, and the product is purified by silica gel chromatography.

[0085] Following the general procedure described above, the following compounds were synthesized from the corresponding starting materials, and their characterization data are provided.

[0086] Example 1

[0087]

[0088] Yield 89%, purified with 5% EA / Hex 1H NMR (400MHz, CDCl3) δ: 8.17-8.10 (m, 1H), 8.05-7.98 (m, 1H), 7.63-7.52 (m, 2H), 7.35-7.28 (m, 1H), 7.24-7.21 (m, 2H), 7.03 (dd, J =0.8, 6.8 Hz, 1H), 6.10 (d, J = 7.6 Hz, 1H), 5.61 (br, 1H), 3.14 (hept, J = 6.8 Hz, 2H), 2.58 (s, 3H), 1.18 (d, J = 6.8 Hz, 6H), 1.09 (d, J = 6.8 Hz, 6H); 13 C NMR (100MHz, CDCl3) δ: 146.9, 142.0, 136.1, 133.4, 127.2, 126.9, 125.8, 125.2, 124.8, 124.1, 124.0, 120.8, 107.2, 28.3, 24.9, 23.3, 19.1.

[0089] HRMS (EI-MS): Calculated value C 23 H 28 N: 318.2216 (M+H), Measured value: 318.2216

[0090] Example 2

[0091]

[0092] Yield 81%, purified with 10% EA / Hex

[0093] 1 H NMR (400MHz, CDCl3) δ: 7.95 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.44 (dt, J = 1.2, 8.0 Hz, 1H), 7.37 (dt, J = 1.2, 7.2 Hz, 1H), 7.35-7.30 (m, 1H), 7.29-7.22 (m, 2H), 6.97 (d, J = 8.0 Hz, 1H), 6.04 (dd, J = 1.2, 8.0 Hz, 1H), 5.70-5.60 (br, 1H), 3.23 (hept, J = 6.8 Hz, 2H), 2.48 (s, 3H), 1.20 (d, J = 6.8 Hz, 6H), 1.13 (d, J = 6.8 Hz, 6H); 13C NMR (100MHz, CDCl3) δ: 156.0, 155.6, 147.0, 142.5, 135.3, 129.1, 127.4, 125.6, 124.7, 124.1, 122.7, 120.5, 111.6, 111.3, 110.3, 106.1, 28.5, 24.8, 23.3, 14.7.

[0094] HRMS (EI-MS): Calculated value C 25 H 28 NO:358.2165 (M+H), measured value: 358.2158.

[0095] Example 3

[0096]

[0097] 95% yield, purified with 5% EA / Hex

[0098] 1 H NMR (400MHz, CDCl3) δ: 8.14 (dd, J = 1.2, 8.4 Hz, 1H), 8.00 (dd, J = 1.2, 8.4Hz, 1H), 7.59-7.53 (m, 1H), 7.50-7.40 (m, 5H), 7.38-7.31 (m, 2H), 7.30-7.24 (m, 2H), 7.16-7.12 (m, 1H), 6.24 (d, J = 7.6 Hz, 1H), 5.77 (br, 1H), 3.19 (hept, J = 6.8 Hz, 2H), 1.21 (d, J = 6.8 Hz, 6H), 1.13 (d, J = 6.8 Hz, 6H); 13 C NMR (100MHz, CDCl3) δ: 147.1, 143.0, 141.5, 135.6, 132.5, 130.6, 130.5, 128.3, 127. 9, 127.3, 127.1, 126.7, 126.1, 125.0, 124.2, 123.4, 120.4, 106.9, 28.4, 25.0, 23.4.

[0099] HRMS (EI-MS): Calculated value C 28 H 30 N: 380.2373 (M+H), measured value: 380.2376.

[0100] Example 4

[0101]

[0102] Yield 60%, purified with 5% EA / Hex

[0103] 1 H NMR (400MHz, CDCl3) δ: 8.05 (dd, J = 1.6, 8.4 Hz, 1H), 7.97 (dd, J = 1.2, 8.0Hz, 1H), 7.54-7.41 (m, 7H), 7.41-7.35 (m, 1H), 7.27 (d, J = 8.0 Hz, 1H), 7.22-7.12 (m, 2H), 7.08-7.02 (m, 1H) 7.00 (d, J = 7.6 Hz, 1H), 6.06 (br, 1H), 1.52 (s, 9H); 13 C NMR (100MHz, CDCl3) δ: 142.2, 141.7, 141.2, 140.9, 133.0, 132.7, 130.4, 128.4, 127.6, 1 27.2, 127.1, 127.0, 126.9, 126.3, 126.2, 125.5, 124.7, 123.2, 121.3, 112.1, 35.0, 30.8.

[0104] HRMS (EI-MS): Calculated value C 26 H 26 N: 352.2060 (M+H), measured value: 352.2058.

[0105] Example 5

[0106]

[0107] Yield 28%, purified with 5% EA / Hex

[0108] 1 H NMR (500MHz, CDCl3) δ: 7.93-7.85 (m, 2H), 7.50-7.40 (m, 5H), 7.41-7.35 (m, 2H), 7.30-7.25 (m, 1H), 7.02-6.95 (m, 1H), 1.51 (s, 9H); 13 C NMR (125MHz, CDCl3) δ: 141.5, 141.2, 132.7, 130.5, 130.1, 128.3, 127.4, 126.9, 126.6, 125.7, 125.4, 124.7, 120.7, 109.4, 51.9, 30.1;

[0109] HRMS (EI-MS): Calculated value C 20 H 22N: 276.1747 (M+H), measured value: 276.1740.

[0110] Example 6

[0111]

[0112] Yield 81%, purified with 5% EA / Hex

[0113] 1 H NMR (500MHz, CDCl3) δ: 8.20-8.10 (m, 2H), 7.67-7.52 (m, 2H), 7.42-7.36 (m, 1H), 7.35-7.30 (m, 2H), 6.15-6.08 (m, 1H), 5.98-5.82 (m, 1H), 5.72-5.66 (m, 1H),5.02-4.94 (m, 1H), 4.94-4.84 (m, 1H), 3.45-3.40 (m, 2H), 3.29-3.18 (m, 2H),2.60-2.55 (m, 3H), 1.25 (d, J = 6.8 Hz, 6H), 1.16 (d, J = 6.8 Hz, 6H); 13 C NMR (125MHz, CDCl3) δ: 146.9, 141.5, 136.9, 135.9, 135.5, 134.0, 126.9, 126.0, 125 .0, 124.2, 124.0, 122.9, 121.4, 120.5, 115.1, 110.1, 39.0, 28.3, 24.9; 23.4, 13.9.

[0114] HRMS (EI-MS): Calculated value C 26 H 32 N: 358.2529 (M+H), measured value: 358.2521.

[0115] Example 7

[0116]

[0117] Yield 62%, purified with 5% EA / Hex

[0118] 1H NMR (500MHz, CdCl3) δ: 7.93 (dd, J = 1.0, 8.5 Hz, 1H), 7.44 (dd, J = 7.0, 8.5Hz, 1H) 7.35-7.27 (m, 2H) 7.27-7.23 (m, 2H), 6.94 (d, J = 8.0 Hz, 1H), 1.09 (d, J = 6 Hz, 6H). 13 C NMR (125MHz, CDCl3) δ: 130.8, 126.9, 126.2, 124.7, 124.4, 124.3, 123.7, 118.2, 107.2, 31.9, 31.0, 28.3, 24.9, 23.5, 23.3.

[0119] HRMS (EI-MS): Calculated value C 25 H 30 N: 344.2373 (M+H), measured value: 344.2368.

[0120] Example 8

[0121]

[0122] Yield 65%, purified with 5% EA / Hex

[0123] 1 H NMR (400MHz, CDCl3) δ: 7.30-7.16 (m, 3H), 6.73 (d, J = 8.0 Hz, 1H), 5.92 (d, J = 8.4 Hz, 1H), 4.81 (br, 1H), 3.07 (hept, J = 6.8 Hz, 2H), 2.65 (t, J = 6.4 Hz, 4H), 2.13 (s, 3H), 1.98-1.80 (m, 4H), 1.14 (t, J = 6.8 Hz, 6H), 1.13 (t, J = 6.8 Hz, 6H); 13 C NMR (100MHz, CDCl3) δ: 147.1, 143.8, 136.4, 136.0, 127.2, 126.8, 125.5, 123.8, 121.2, 108.7, 28.3, 27.6, 25.0, 24.8, 23.1, 22

[0124] HRMS (EI-MS): Calculated value C 23 H 32 N: 322.2529 (M+H), measured value: 322.2520.

[0125] All contents of the aforementioned U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications mentioned in and / or listed in the application data sheets are incorporated herein by reference.

[0126] As can be seen from the foregoing, although the specific embodiments of this application are provided for illustrative purposes only, various modifications can be made without departing from the spirit and scope of this application. Therefore, this application is not limited except for the appended claims.

Claims

1. A method for preparing polycyclic aromatic amines from isonitriles and cyclopropenes, characterized in that, In the presence of a transition metal catalyst, compound (I) reacts with compound (II) to form compound (III), as shown in the following reaction formula: ； The transition metal catalyst is [(NHC)NiBr2] / (NaBArF)2; the compound of formula (I) is... The compound of formula (II) is The compound of formula (III) is .

2. A method for preparing polycyclic aromatic amines from isonitriles and cyclopropenes, characterized in that, In the presence of a transition metal catalyst, compound (I) reacts with compound (II) to form compound (III), as shown in the following reaction formula: ； The transition metal catalyst is [(NHC)NiBr2] / (NaBArF)2; the compound of formula (I) is... The compound of formula (II) is ; The compound of formula (III) is .

3. A method for preparing polycyclic aromatic amines from isonitriles and cyclopropenes, characterized in that, In the presence of a transition metal catalyst, compound (I) reacts with compound (II) to form compound (III), as shown in the following reaction formula: ； The transition metal catalyst is [(NHC)NiBr2] / (NaBArF)2; the compound of formula (I) is... The compound of formula (II) is The compound of formula (III) is .

4. A method for preparing polycyclic aromatic amines from isonitriles and cyclopropenes, characterized in that, In the presence of a transition metal catalyst, compound (I) reacts with compound (II) to form compound (III), as shown in the following reaction formula: ； The transition metal catalyst is [(NHC)NiBr2] / (NaBArF)2; the compound of formula (I) is... The compound of formula (II) is ; The compound of formula (III) is .

5. A method for preparing polycyclic aromatic amines from isonitriles and cyclopropenes, characterized in that, In the presence of a transition metal catalyst, compound (I) reacts with compound (II) to form compound (III), as shown in the following reaction formula: ； The transition metal catalyst is [(NHC)NiBr2] / (NaBArF)2; the compound of formula (I) is... The compound of formula (II) is The compound of formula (III) is .

6. A method for preparing polycyclic aromatic amines from isonitriles and cyclopropenes, characterized in that, In the presence of a transition metal catalyst, compound (I) reacts with compound (II) to form compound (III), as shown in the following reaction formula: The transition metal catalyst is [(NHC)NiBr2] / (NaBArF)2; the compound of formula (I) is... The compound of formula (II) is The compound of formula (III) is .

7. A method for preparing polycyclic aromatic amines from isonitriles and cyclopropenes, characterized in that, In the presence of a transition metal catalyst, compound (I) reacts with compound (II) to form compound (III), as shown in the following reaction formula: ； The transition metal catalyst is [(NHC)NiBr2] / (NaBArF)2; the compound of formula (I) is... The compound of formula (II) is The compound of formula (III) is .

8. A method for preparing polycyclic aromatic amines from isonitriles and cyclopropenes, characterized in that, In the presence of a transition metal catalyst, compound (I) reacts with compound (II) to form compound (III), as shown in the following reaction formula: ； The transition metal catalyst is [(NHC)NiBr2] / (NaBArF)2; the compound of formula (I) is... The compound of formula (II) is The compound of formula (III) is .

9. The method according to any one of claims 1 to 8, characterized in that, The method is carried out in a solvent selected from aromatic hydrocarbons, aliphatic hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, ketones, nitriles, and ionic liquids, wherein the ionic liquid is an imidazolium salt.

10. The method according to any one of claims 1 to 8, characterized in that, The method is carried out in a solvent selected from alicyclic hydrocarbons.

11. The method according to any one of claims 1 to 8, characterized in that, The method is performed in a buffer solution.

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