Method for preparing fused ring arylamine by taking isocyanide and cyclopropene as raw materials

Abstract

The invention discloses a method for preparing fused ring arylamine from isonitrile and cyclopropene. The reaction formula is as follows: # imgabs0 #.

Description

Technical Field

[0001] The present application relates to the technical field of organic synthesis, and in particular to a method for preparing condensed ring aromatic amines using isonitrile and cyclopropene as raw materials. Background Art

[0002] The synthesis of polycyclic aromatic amines is one of the most important research topics in organic synthetic chemistry. They are the core structures of many important functional materials and bioactive molecules. Polycyclic aromatic amine compounds can be used as starting materials to prepare various materials through subsequent transformations, such as electrophilic and nucleophilic aromatic substitution, aromatic hydrocarbon activation, and dearomatization reactions.

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

[0004] At present, the synthesis of polycyclic aromatic amines is based on intramolecular reactions (such as cycloisomerization), which seriously affects the development of related fields such as medicinal chemistry and combinatorial chemistry and the optimization of functional materials. Therefore, it is urgent to develop intermolecular methods to efficiently synthesize polycyclic aromatic amines with multiple functional groups, preferably starting from readily available raw materials. Summary of the invention

[0005] In view of the deficiencies of the prior art, the object of the present invention is to provide a process for preparing a compound of formula (III) from a compound of formula (I) and a compound of formula (II) in the presence of a carbene and a transition metal catalyst or a precursor thereof.

[0006]

[0007] It is characterized in that

[0008] Ar 1 is one of optionally aryl, heteroaryl and alkenyl,

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

[0010] The substituents on the compounds of formula (I) are optionally linked via an alkylene chain.

[0011] R 4 is one of an optional alkyl, aryl, heteroaryl, alkenyl, alkynyl or metalloid, and is linked 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).

[0013] The transition metal catalyst is optionally from Groups 3-12.

[0014] The carbene optionally contains any member of a divalent carbon atom. DETAILED DESCRIPTION

[0015] In the following description, many specific details are set forth to provide a thorough understanding of the specification. However, one skilled in the relevant art will recognize that other methods, components, materials, etc. can be used to implement the invention without one or more of these specific details.

[0016] Unless the context requires otherwise, throughout the specification and the appended claims, the word "comprise" and variations such as "include" and "comprising" are to be interpreted in an open, inclusive sense, i.e., "including, but not limited to."

[0017] References throughout this specification to "one embodiment", or "an embodiment", or "in another embodiment", or "some embodiments", or "in certain embodiments" mean that a particular referenced feature, structure, or characteristic associated with an embodiment is included in at least one embodiment. Therefore, phrases such as "in one embodiment", or "in an embodiment", or "in another embodiment", or "in certain embodiments" that appear throughout this specification do not necessarily all refer to the same embodiment. Furthermore, particular 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, the singular forms "a", "an", and "the" include plural referents unless the content clearly dictates otherwise. In this application, "or" is used to mean "and / or" unless otherwise stated.

[0019] Certain chemical groups described herein are preceded by a shorthand notation indicating the total number of carbon atoms found in the chemical group shown. For example, C7-C 12 Alkyl refers to an alkyl group as defined below having a total of 7 to 12 carbon atoms, C4-C 12 Cycloalkyl refers to a cycloalkyl group as defined below having a total of 4 to 12 carbon atoms. The total number of carbons in the shorthand notation does not include carbons that may be present in substituents of the group.

[0020] The “C m To C n ” or “C m至n”, where “m” and “n” are integers referring to the number of carbon atoms in an alkyl, alkenyl, or alkynyl group or in the ring of a cycloalkyl or cycloalkenyl group. That is, the ring of an alkyl, alkenyl, alkynyl, cycloalkyl, or cycloalkenyl group can contain from “m” to “n” (inclusive) carbon atoms. Thus, for example, a “C1 to C4 alkyl” group refers to all alkyl groups having 1 to 4 carbons, i.e., CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH-, CH3CH2CH2CH2-, CH3CH2CH(CH3)-, and (CH3)3C-. If “m” and “n” are not specified for an alkyl, alkenyl, alkynyl, cycloalkyl, or cycloalkenyl group, the broadest range described in these definitions is assumed.

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

[0022] The term "alkyl" 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. The alkyl group can have 1 to 20 carbon atoms (whenever it appears in this article, a numerical range such as "1 to 20" refers to each integer in a given range; for example, "1 to 20 carbon atoms" means that the alkyl group can be composed 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). The alkyl group can also be a medium-sized alkyl group with 1 to 10 carbon atoms. The alkyl group can also be a low alkyl group with 1 to 5 carbon atoms. The alkyl group can be referred to as "C1-C4 alkyl" or similar names. As an example only, "C1-C4 alkyl" means that there are 1-4 carbon atoms in the alkyl chain, that is, the alkyl chain is selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl.

[0023] The alkyl group may be substituted or unsubstituted. When substituted, the substituents are 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, heterocyclyl, heterocyclyloxy, heteroalicyclic, hydroxy, substituted or unsubstituted alkoxy, substituted or unsubstituted aryloxy, acyl, thiol, substituted or unsubstituted thioalkoxy, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, acylalkyl, acylamino, acyloxy, aminoacyl, alkylthio ... , aminoacyloxy, oxyacylamino, keto, thioketo, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, C-acylamino, N-acylamino, S-sulfonylamino, N-sulfonylamino, C-carboxyl, O-carboxyl, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethanesulfonyl and substituted or unsubstituted amino, 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, hexyl, etc. When a substituent is described as "optionally", the substituent may be substituted with one or more of the above substituents.

[0025] The term "alkenyl" as used herein alone or as part of a group refers to a straight or branched hydrocarbon chain radical consisting solely 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 a single bond, such as ethenyl, propenyl, butenyl, pentenyl, penta-1,4-dienyl, cyclohexenyl, and the like.

[0026] The term "alkynyl" as used herein alone or as part of a group refers to a straight or branched hydrocarbon chain radical consisting solely 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 a single bond, such as ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.

[0027] The term "aryl" as used herein alone or as part of a group refers to a carbocyclic aromatic ring or ring system. The aryl group may be unsubstituted or substituted. In addition, the term "aryl" includes fused ring systems in which at least two aryl rings, or at least one aryl and at least one C 3-8 -Cycloalkyl groups share at least one chemical bond.Some examples of "aryl" rings include optionally substituted phenyl, naphthyl, phenanthrenyl, anthracenyl, tetrahydronaphthyl, fluorenyl, indenyl, and indanyl.

[0028] The term "aryl" relates to aromatic groups, including for example benzyl groups, attached via a ring-forming carbon atom, and optionally bearing one or more substituents selected from the group consisting of heterocyclyl, heteroaryl, halogen, hydroxy, amino, cyano, nitro, alkylamido, acyl, C 1-6 -alkoxy, C 1-6 -alkyl, C 1-6 -Hydroxyalkyl, C 1-6 -aminoalkyl, C 1-6 -alkylamino, alkylsulfinyl, alkylsulfinyl, alkylsulfonyl, sulfamoyl or trifluoromethyl. The aryl group may optionally be substituted in the para-, ortho- and / or meta-position.

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

[0030] Additionally, as used herein, the term "heteroaryl" includes fused ring systems wherein at least one aromatic ring and at least one heteroaromatic ring, at least two heteroaromatic rings, at least one heteroaromatic ring and at least one heterocyclyl ring, or at least one heteroaromatic ring and at least one cycloalkyl ring share at least one chemical bond.

[0031] The term "heteroaryl" is understood to refer to an aromatic C 2-amino group containing one oxygen or sulfur atom or up to four nitrogen atoms, or a combination of one oxygen or sulfur atom and up to two nitrogen atoms. 3-8 Cyclic groups, and their substituted and benzo and pyrido fused derivatives, for example, linked via a ring-forming carbon atom. The heteroaryl group may carry one or more substituents selected from halogen, hydroxy, amino, cyano, nitro, alkylamido, acyl, C 1-6 -alkoxy, 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-membered and six-membered aromatic heterocyclic ring system with 0, 1 or 2 substituents, which can be the same or different from each other, selected from the above list.

[0032] Representative examples of heteroaryl include, but are not limited to, unsubstituted and mono- or di-substituted derivatives of furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, indole, oxazole, benzoxazole, isoxazole, benzisoxazole, thiazole, benzothiazole, isothiazole, imidazole, benzimidazole, pyrazole, indazole, tetrazole, quinoline, isoquinoline, pyridazine, pyrimidine, purine, and pyrazine, furazan, 1,2,3-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, borazine, triazole, benzotriazole, pteridine, benzoxazole, oxadiazole, benzopyrazole, quinolizine, cinnoline, phthalazine, quinazoline, and quinoxaline. In some embodiments, the substituents are halogen, hydroxy, cyano, 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 subsequently described event of circumstances may or may not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.

[0034] Unless otherwise indicated, when a substituent is considered to be "optional", it means that the substituent is a group that may be substituted by one or more groups individually and independently selected from morpholinoalkanoate, cycloalkyl, aryl, heteroaryl, heterocyclyl, heteroalicyclic, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-carbamyl, S-sulfonylamino, N-sulfonylamino, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethanesulfonyl and amino, including mono- and di-substituted amino, and protected derivatives thereof.

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

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

[0037] The term "ligand" in chemistry usually refers to an atom, ion, or molecule that binds to a central metal, generally involving the formal donation of one or more electrons. The bonding between metal and ligand can range from covalent to ionic.

[0038] As used herein, 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 herein alone or as part of a group refers to a straight or branched divalent hydrocarbon chain that connects the rest of the molecule to a group consisting of only carbon and hydrogen, containing no unsaturated bonds, and having 1 to 12 carbon atoms, such as methylene, ethylene, propylene, n-butylene, etc. The alkylene chain is connected to the rest of the molecule by a single bond and to the group by a single bond. The points of attachment of the alkylene chain to the rest of the molecule and to the group can be through one carbon or any two carbons within the chain.

[0040] The term "alkenylene" or "alkenylene chain", as used herein alone or as part of a group, refers to a straight or branched divalent hydrocarbon chain that connects the rest of the molecule to a radical consisting solely of carbon and hydrogen, containing at least one double bond and having from 2 to 12 carbon atoms, such as vinylene, propenylene, n-butenyl, etc. The alkenylene chain is connected to the rest of the molecule by a single bond and to the radical by a double bond or a single bond. The points of attachment of the alkenylene chain to the rest of the molecule and to the radical can be through one carbon or any two carbons within the chain.

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

[0042] The term "amine" as used herein 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 semimetals, are terms used in chemistry to classify chemical elements. Almost every element in the periodic table can be called a metal or a nonmetal, depending on their general physical and chemical properties. However, a few elements are called metalloids. There is no strict definition of the term, but the following properties are generally considered to be characteristic of metalloids: (1) metalloids often form amphoteric oxides; and (2) metalloids often 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] In one aspect, the present application relates to a method for preparing a compound of formula (III) from a compound of formula (I) and a compound of formula (II) in the presence of an N-heterocyclic carbene and a transition metal catalyst or a precursor thereof,

[0046]

[0047] It is characterized in that

[0048] Ar 1 is one of optionally aryl, heteroaryl and alkenyl,

[0049] R 1 , R 2 and R 3 independently selected from hydrogen, halogen, alkyl, aryl, heteroaryl, alkenyl, alkynyl or metalloid,

[0050] The substituents on the compounds of formula (I) are optionally linked via an alkylene chain.

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

[0052] Ar 2 is an optional aryl, heteroaryl (from Ar 1 substituted aryl and heteroaryl), or optionally aliphatic structures (from Ar 1 substituted alkenyl).

[0053] The transition metal catalyst is optionally from Groups 3-12.

[0054] The carbene is optionally substituted with one or more heteroatoms. When a cyclic carbene is used, the ring size is optionally 4-12 members.

[0055] In some embodiments of the present application, Ar 1 is optionally substituted phenyl, naphthyl, phenanthrenyl, anthracenyl, tetrahydronaphthyl, fluorenyl, alkenyl, indenyl or indanyl.

[0056] In some embodiments of the present application, the compound of formula (I) is optionally cyclopropene and its substituted derivatives.

[0057] In some embodiments of the present application, R 1 , R 2 and R 3 Independently selected are hydrogen, halogen, alkyl, aryl, heteroaryl, alkenyl, alkynyl or metalloid.

[0058] In some embodiments of the present application, the substituents on the compound of formula (I) are optionally connected by an alkylene chain.

[0059] In some embodiments of the present application, R 4 is optionally substituted alkyl, aryl, heteroaryl, alkenyl, alkynyl or metalloid.

[0060] In some embodiments of the present application, the compound of formula (II) is selected from isocyanides, such as phenyl isocyanide, furyl isocyanide, tert-butyl isocyanide and substituted derivatives thereof.

[0061] The transition metal catalyst of the present invention may include any catalytic transition metal and / or catalyst precursor, when it is introduced into the reaction vessel, and if necessary, it can be converted into an active form in situ, as well as an active form of the catalyst participating in the reaction. In some embodiments of the present application, the transition metal is optionally Groups 3-12.

[0062] Exemplary transition metals that can be used in the present 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), dub (Db), phosphine (SG), boron (BH), potassium (Hs), metal (Mt), darmstein (DS), roentgen (Rg) and unubiium (Uub).

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

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

[0065] In some embodiments of the present application, the ligand on the transition metal catalyst is selected from carbene, heterocyclic carbene (NHCs), dicarbene, diheterocyclic carbene, phosphine, amine, imine, arsine and hybrids, combinations and derivatives thereof.

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

[0067] The ligand may be added to the reaction mixture in the form of a metal complex or as a separate reagent. The ligand, if chiral, may be added as a racemic mixture or as an optically pure stereoisomer.

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

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

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

[0071] In some embodiments of the present application, a transition metal catalyst is provided in a catalytic amount in the reaction. In a specific embodiment, the catalytic amount is less than 10 mol% relative to an equivalent reagent, and the equivalent reagent 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 the present application, the reaction can be carried out in an optional solvent, which 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 the present application include, but are not limited to, benzene, toluene, xylene, etc. Exemplary aliphatic hydrocarbons that can be used in the present application include, but are not limited to, pentane, hexane, heptane, octane, etc. Exemplary alicyclic hydrocarbons that can be used in the present application include, but are not limited to, cyclohexane, cyclohexanone, methylcyclohexanone, etc. Exemplary alcohols that can be used in the present application include, but are not limited to, methanol, ethanol, isopropanol, etc. Exemplary ethers that can be used in the present application include, but are not limited to, diethyl ether, methyl ethyl ether, propyl ether, propylene oxide, etc. Exemplary esters that can be used in the present application include, but are not limited to, methyl formate, ethyl formate, butyl formate, pentyl formate, methyl acetate, ethyl acetate, propyl acetate, benzyl phenylacetate, etc. Exemplary ketones that can be used in the present application include, but are not limited to, acetone, methyl butyl ketone, methyl isobutyl ketone, etc. Exemplary nitriles that can be used in the present application include, but are not limited to, acetonitrile, propionitrile, acrylonitrile, etc. Exemplary diol derivatives that can be used in the present 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 the present application, the solvent is an aromatic hydrocarbon. In some embodiments of the present application, the solvent is selected from benzene, toluene and xylene.

[0075] Alternatively, the reaction can be carried out without solvent. Ionic liquids such as imidazolium salts can also be used as reaction media.

[0076] In some embodiments of the present application, the method can be carried out in an optional buffer to minimize problems associated with isomerization, oligomerization and polymerization. Examples of buffers that can be used in the present application include, but are not limited to, ammonium salts, phosphate buffers, and carbonates. DETAILED DESCRIPTION

[0078] The reaction is sensitive to oxygen and moisture, and the substrate should be dried and degassed before use (usually overnight on CaH2 or CaCl2 powder). Unless otherwise stated, all reactions were carried out in an oxygen-free atmosphere of nitrogen or argon, and moisture was strictly excluded from reagents and glassware. NiBr2DME was purchased from Acros or IL, stored under a nitrogen atmosphere, and used without further purification. IPr and NaBArF were purchased from Aldrich or Strem. The isonitrile was filtered through a short column of silica gel and dried before use to remove possible stabilizers. Substituted cyclopropenes were prepared according to conventional methods. Toluene was distilled over sodium before use.

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

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

[0081] [(NHC)NiBr2] / (NaBArF)2 catalysts can also be generated 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 common hydride or hydrogen source, optionally with an activator and a buffer, including but not limited to Lewis acid additives, protic acids and or nucleophiles; or 4) other common organometallic transformations and manipulation techniques, such as hydride addition or elimination steps and substitutions, etc.

[0082] The experimental results show that the outcome of the coupling reaction is sensitive to the structure of the carbene catalyst, the counterion used and possibly the method of preparation.

[0083] General procedure for catalyst generation: NHC (0.05 mmol, 10 mol%), NiBr2DME (0.05 mmol, 10 mol%) and NaBArF (0.10 mmol, 20 mol%) were added to a dried test tube equipped with a stirring bar in a glove box. The catalyst mixture was dissolved in degassed toluene (1 ml) under nitrogen and stirred at 80° C. for 3-5 minutes.

[0084] The general procedure for the synthesis of condensed ring aromatic amines is as follows: 1 ml of toluene solution of compounds (I) and (II) (0.5 mmol, 100 mol% and 1 mmol, 200 mol%) is added to a mixture of [NHC-NiBr2](NaBArF2 at 80 degrees Celsius, 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 in the open air at room temperature for 30 minutes. The mixture is then filtered through a silica gel short column and rinsed with 20% ethyl acetate / hexane (50 ml). The solvent is removed under reduced pressure and the product is obtained by silica gel chromatography.

[0085] According to the above general procedure, 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 , 6.8Hz, 1H), 6.10 (d, J = 7.6Hz, 1H), 5.61 (br, 1H), 3.14 (hept, J = 6.8Hz, 2H), 2.58 (s, 3H), 1.18 (d, J = 6.8Hz, 6H), 1.09 (d, J = 6.8Hz, 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), Found: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=8.0Hz, 1H), 7.63 (d, J=8.0Hz, 1H), 7.44 (dt, J= 1.2, 8.0Hz, 1H), 7.37 (dt, J=1.2, 7.2Hz, 1H), 7.35-7.30 (m, 1H), 7.29-7.22 (m, 2 H), 6.97 (d, J=8.0Hz, 1H), 6.04 (dd, J=1.2, 8.0Hz, 1H), 5.70-5.60 (br, 1H), 3.23 (hept, J=6.8Hz, 2H), 2.48 (s, 3H), 1.20 (d, J=6.8Hz, 6H), 1.13 (d, J=6.8Hz, 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), found: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, 8.4Hz, 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 = 7.6Hz, 1H), 5.77 (br, 1H), 3.19 (hept, J = 6.8Hz, 2H), 1.21 (d, J = 6.8Hz, 6H), 1.13 (d, J = 6.8Hz, 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), found: 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, 8.4Hz, 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=8.0Hz, 1H), 7.22-7.12 (m, 2H), 7.08-7.02 (m, 1H) 7.00 (d, J=7.6Hz, 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), found: 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 22 N: 276.1747 (M+H), found: 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 = 6.8Hz, 6H), 1.16 (d, J = 6.8Hz, 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), found: 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, 8.5Hz, 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=8.0Hz, 1H), 6.12 (d, J=7.5Hz, 1H), 5.57 (br, 1H), 3.20-3.08 (m, 4H), 3.00 (t, J=6.5Hz, 2H), 2.05 (hept, J=6.8Hz, 2H), 1.18 (d, J=6.8Hz, 6H), 1.09 (d, J=6Hz, 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), found: 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=8.0Hz, 1H), 5.92 (d, J=8.4Hz, 1H), 4.81 (br, 1H), 3.07 (hept, J=6.8Hz, 2H), 2.65 (t, J=6.4Hz, 4H), 2.13 (s, 3H), 1.98-1.80 (m, 4H), 1.14 (t, J=6.8Hz, 6H), 1.13 (t, J=6.8Hz, 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 32N: 322.2529 (M+H), found: 322.2520.

[0125] The entire contents of all of the above-mentioned U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications, and non-patent publications mentioned in this specification and / or listed in the Application Data Sheet are incorporated into this specification by reference.

[0126] It can be seen from the above that although the specific embodiments of the present application are only for illustration purposes, various modifications can be made without departing from the spirit and scope of the present application. Therefore, the present application is not limited except for the attached claims.

Claims

1. A process for reacting a cyclopropene of formula (I) with an isonitrile of formula (II) in the presence of a transition metal catalyst to produce a condensed ring aromatic amine of formula (III), wherein the reaction formula is as follows: It is characterized in that Ar 1 One of aryl, heteroaryl and alkenyl is selected, R 1 , R 2 and R 3 It is selected from one of hydrogen, halogen, alkyl, aryl, heteroaryl, alkenyl, alkynyl or metalloid. The substituents on the compounds of formula (I) are optionally linked via an alkylene chain. R 4 It is optionally one of an alkyl group, an aryl group, a heteroaryl group, an alkenyl group, an alkynyl group or a metalloid group, and is optionally connected to a substituent on the compound of formula (I). Ar 2 is an optional aryl, heteroaryl (from Ar 1 substituted aryl and heteroaryl), or an optionally substituted aliphatic structure (from Ar 1 substituted alkenyl). The transition metal catalyst is optionally from Groups 3-12. The carbene optionally contains any member of a divalent carbon atom.

2. The method according to claim 1, wherein the compound of formula (I) is an optionally substituted cyclopropene, such as 3-methyl-3-phenylcyclopropene, and substituted derivatives thereof.

3. The process according to claim 1, wherein the compound of formula (II) is optionally isonitrile, such as tert-butyl isonitrile, and substituted derivatives thereof.

4. The method according to claim 1, wherein the ligand on the transition metal catalyst is selected from one of carbene, heterocyclic carbene, dicarbene, diheterocyclic carbene, phosphine, amine, imine, arsine and derivatives thereof.

5. The method of claim 1, wherein the catalyst carries a weak or non-nucleophilic stabilizing ion.

6. The method according to claim 1, wherein the transition metal catalyst is produced by [(NHC)NiBr2]L / (NaBArF)2, etc., wherein L is a solvent molecule such as toluene, THF, DME or an isocyanate having formula (II).

7. The method according to claim 1, wherein the method is carried out in a solvent, and the solvent is optionally aromatic hydrocarbons, aliphatic hydrocarbons, alicyclic hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, ketones, nitriles and diol derivatives, and ionic liquids such as imidazolium salts.

8. The method of claim 1, wherein the method is performed in a buffer.

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