Procedure for the synthesis of derivatives 1,2-di (hetero) ariletanonas and 1,2,2-tri (hetero) arile

专利摘要:
Process for the synthesis of 1,2-di (hetero) arylethanones and 1,2,2-tri (hetero) arylethanones derivatives in water. The invention describes a novel process for the regioselective synthesis of 1- (hetero) arylketones α -mono- or α, α -di (hetero) arylated, through a reaction of α -allation of enolates of ketone with a aryl halide or heteroaryl, catalyzed by a palladium compound and a phosphorous compound, and in water as a reaction medium.
公开号:ES2636091A1
申请号:ES201630409
申请日:2016-04-04
公开日:2017-10-05
发明作者:Iratxe ASTARLOA MASEDA；Raúl San Martín Faces；María Teresa HERRERO CORRAL；Esther Domínguez Pérez
申请人:Euskal Herriko Unibertsitatea；
IPC主号:

专利说明:

DESCRIPTION

PROCEDURE FOR THE SYNTHESIS OF DERIVATIVES 1,2-DI (HETERO) ARILETANONAS AND 1,2,2-TRI (HETERO) ARILETANONAS IN WATER
 5
Field of the Invention
The present invention is part of the chemical and / or pharmaceutical sector. In particular, the invention relates to a process which concerns the regioselective synthesis of 1- (hetero) aryl ketones -mono- or , -di (hetero) arylated, through a reaction of α- (hetero) arylation of ketone enolates with a (hetero) aryl halide, catalyzed by a palladium compound and a phosphorus compound, and in water as a reaction medium.

Background of the invention
The synthesis of α-arylcarbonyl compounds arouses great interest, since said functional grouping is present in various natural products and pharmacologically active compounds, mainly as antioxidants and antitumor agents [Hu, Q. F .; Zhou, B .; Ye, Y. Q .; Jiang, Z. Y .; Huang, X. Z .; Li, Y. K .; Du, G .; Yang, G. Y .; Gao, X. M. J. Nat. Prod. 2013, 76, 1854-1859; Elavarasan, S .; Gopalakrishnan, M. Chem. Sci. Rev. Lett. 2014, 2, 508-514; Taillefer, M .; Monnier, F.; Tlili, A .; Danoun, G .; WO 2013182640 A1].
In addition, 1,2-diaryl- and 1,2,2-triaryletanones have been used as key ingredients and precursors of new materials, such as combustion retardants [Zhang, L .; Wu, W .; Zhong, Y .; Zhu, S .; Wang, Z .; Zou, Z. RSC Adv. 2015, 5, 87609-87615; Szyndler, M. W .; Timmons, J. C .; Yang, Z. H .; Lesser, A. J .; Emrick, T. Polymer 2014, 55, 4441-4446; Kumar, J .; Coughlin, E. B .; Emrick, T .; Ku, B. C .; Ravichandran, S .; Nagarajan, S .; Nagarajan, R .; WO 2012151154 A2; Ravichandran, S .; Nagarajan, S .; Ku, B. C .; Coughlin, B .; Emrick, T .; Kumar, J .; Nagarajan, R. Green Chem. 2012, 14, 819-824]. 25
Undoubtedly, another of the applications of these ketones is based on their use as key synthetic intermediates for the formation of compounds of greater structural complexity [Chang, M. Y. Tetrahedron 2015, 71, 9187-9195; Diaz, A .; Lopez-Romero, J. M .; Contreras-Caceres, R .; Algarra, M .; Rico, R .; Valpuesta, M. Curr. Org. Chem. 2015, 19, 1292-1300; Madhavachary, R .; Ramachary, D. B. Chem. Eur. J. 2014, 20, 16877-16881; Naveen, T .; Kancherla, R .; Maiti, D. Org. Lett. 2014, 16, 5446-5449; Look at.; Wagner, S .; Kramer, R. H .; 30 Deglmann, P .; Emrick, T. Polymer 2016, 84, 59-64; Soria-Castro, S. M .; Caminos, D. A .; Penenory, A. B. RSC Advances 2014, 4, 17490-17497; Danoun, G .; Tlili, A .; Monnier, F .; Taillefer, M. Angew. Chem., Int. Ed. 2012, 51, 12815-12819]

In contrast to the alkylation of enolates, the coupling of enolates with aryl halides has historically resulted in a difficult transformation. Initially, stoichiometric amounts of tin or zinc enolates were required, or the use of electrophilic aryl compounds of the main group (such as aryl-lead triacetates) that usually turned out to be toxic among several disadvantages. Other variants involved the use of stoichiometric amounts of metal enolates or the initial derivatization of the initial carbonyl compound, with the subsequent additional steps [Barton, D. H. R .; Donnelly, D. M. X .; Finet, J.-P .; 40 Guiry, P. J. J. Chem. Soc., PerkinTrans. 1, 1992, 11, 1365-1375; Millard, A. A .; Rathke, M. W. J. Am. Chem. Soc. 1977, 99, 4833-4835; Mino, T .; Matsuda, T .; Murahashi, M .; Yamashita, M. Organometallics, 1997, 16, 3241-3242; Marino, J. P .; Jaen, J. Am. Chem. Soc. 1982, 104, 3165-3172].

After the first practical discovery of the reaction of α-arylation of carbonyl compounds mediated by 45 palladium, which was published simultaneously by the Miura, Hartwig and Buchwald groups in 1997, there have been significant advances in this area, both in nature of the carbonyl compounds to be arylated and the arylating agents as in the bases and ligands or metal complexes employed. However, relatively high loads of both the palladium source and the ligands to be used are still necessary (1-10 mol%); In many cases these ligands are also not commercial or have a high price, and flammable or harmful organic solvents are necessary as a reaction medium. Similarly to other reactions catalyzed by palladium, the removal of traces of said metal from the final products is also problematic in the case of biologically active compounds, with additional purification steps that make the process more expensive [Magano, J .; Dunetz J. R. Chem. Rev. 2011, 111, 2177-2250; Thayer, A. Chem. Eng. News 2005, 83, 55-58; Recoverable and Recyclable Catalysts, Benaglia, M. (Ed.), John Wiley & 55 Sons, Chichester, 2009; Phillips, S .; Kauppinen, P. Plat.Metals Rev. 2010, 54, 69-70].
Progress has been made in reducing the amount of palladium catalyst to be used or in terms of the solvent used. Thus, the arylation of ketones with only 0.02-0.2 mol% palladium catalyst has been described, although at the expense of the use of non-commercial or high-cost palatecycles or complexes, strong bases (tert-butoxides and amides) metal) and organic solvents such as N, N-dimethylformamide, toluene, 1,4-60 dioxane or tetrahydrofuran [Viciu, MS; Kelly, R. A .; Stevens, E. D .; Naud, F .; Studer, M .; Nolan, S. P. Org. Lett. 2003, 5, 1479-1482; Churruca, F .; SanMartin, R .; Tellitu, I .; Dominguez, E. Tetrahedron Lett. 2006, 47, 3233-3237; Fat, G. A .; Colacot, T. J. Org. Process Res. Dev. 2008, 12, 522-529; Marelli, E .; Corpet, M .; Davies, S. R .; Nolan, S. P. Chem. Eur. J. 2014, 20, 17272-17276]. It is also worth mentioning the publication of a single example in which the use of water as a reaction solvent is described, although in this case high catalytic loads of the palladium source and of the ligand used (2.5 and 10 mol% were necessary)
respectively), the reaction having to be carried out in the presence of a surfactant [Lessi, M .; Masini, T .; Nucara, L .; Bellina, F .; Rossi, R. Adv. Synth. Catal. 2011, 353, 501-507].

In view of the above, and despite the progress achieved so far, there is still a need to provide an alternative procedure that overcomes at least the disadvantages of the above-mentioned methodologies 5, both from the point of view of the decrease in amount of catalyst to be used and its commercial availability / low cost as for the use of sustainable solvents in this context.

Surprisingly, the authors of the invention have discovered that the combination of a palladium compound 10 with a phosphorus derived ligand, a metal base, such as a phosphate and a quaternary ammonium salt, such as a tetraalkylammonium salt allows the arylation of aromatic ketones with aryl halides in water as a solvent and also using infinitesimal amounts of both the palladium source and the ligand.
 fifteen
In this sense, the authors of the present invention have found clear economic advantages with respect to the known processes, mainly, by the use of water as a solvent, this being the least contaminating reaction medium possible, easily accessible and handled, thanks to its safety and the fact of not being a flammable liquid, which does not need to take special safety measures, or for handling. And since the reactions are carried out in water, the reagents and material used do not require special anhydrous storage conditions, and the separation protocols of the products and catalysts are simplified. As a second point to note, there is the low catalytic load used of commercially available palladium and phosphine oxide ligand salts, without the need for prior formation of economically more expensive catalysts. Finally, the protocol set up allows the scaling of the process to a multigram scale, so its application at industrial scale is evident. 25


Description of the invention
In a first aspect, the invention relates to a new process, hereinafter process of the invention, for obtaining a compound of formula (I),

A1-C (O) –CH (A2) (A3)


which comprises reacting a compound of formula (II) 35

A1-C (O) -CH2-A2

with a compound of formula (III)
 40
A3-X


where
 Four. Five
A1 represents an aryl or heteroaryl group;
A2 represents a group selected from hydrogen, C1-C14 alkyl, C2-C14 alkenyl, aryl and heteroaryl;
A3 represents an aryl or heteroaryl group; Y
X represents a leaving group,
 fifty

in the presence of:

(i) a palladium compound;
(ii) a phosphorus derived ligand compound; 55
(iii) a metal base; Y
(iv) a quaternary ammonium salt,
in water

In the context of the present invention the term "aryl" should preferably be understood as a monovalent, aromatic or partially aromatic mono, bi or tricyclic monovalent hydrocarbon ring having 6, 7, 8, 9, 10, 11, 12, 13 or 14 atoms carbon, particularly a ring having 6 carbon atoms, for example a phenyl group, or a ring having 9 carbon atoms, for example an indanyl or indenyl group, or a ring having 10 carbon atoms, for example a tetralinyl, dihydronaphthyl, or naphthyl group, or a ring having 13 carbon atoms, for example a fluorenyl group, or a ring having 14 carbon atoms, for example an anthranyl group, or a phenanthryl group.

The term "heteroaryl" is preferably understood as a monovalent, mono or bicyclic aromatic ring system having 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 ring atoms (a "heteroaryl group of 5 to 14 members ”), particularly 5 or 6 or 9 or 10 atoms, and which contains one or more heteroatoms, the same or different, where said heteroatoms are oxygen, nitrogen or sulfur, and can be monocyclic, bicyclic or tricyclic, 5 and more In each case it can be benzo condensed. Particularly, the heteroaryl is selected from thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, thia-4H-pyrazolyl etc., and benzo derivatives thereof, such as, by example, benzofuranyl, benzothienyl, benzoxazolyl, bencisoxazolyl, benzimidazolyl, benzotriazolyl, indazolyl, indolyl, isoindolyl, etc .; or pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, etc., and benzo derivatives thereof, such as, for example, quinolinyl, quinazolinyl, isoquinolinyl, etc .; or azocinyl, indolizinyl, purinyl, etc., and benzo derivatives thereof; or cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, xanthenyl, or oxepinyl, etc. More particularly, heteroaryl is selected from pyridyl, benzofuranyl, bencisoxazolyl, indazolyl, quinazolinyl, thienyl, quinolinyl, benzothienyl, pyrazolyl, or furanyl. fifteen

The aryl group and the heteroaryl group may be unsubstituted or substituted. If substituted, they may have one or more substituents independently selected from C1-C6 alkyl, halogen, halo (C1-C6) alkyl, (C1-C6) alkoxide, nitro, hydroxyl and cyano.
 twenty
The term "alkyl" should be understood as a linear or branched, saturated monovalent hydrocarbon group having 1 to 14 carbon atoms, preferably 1 to 10, for example 1, 2, 3, 4, 5, or 6 carbon atoms , such as a methyl, ethyl, propyl, butyl, pentyl, hexyl, iso-propyl, iso-butyl, sec-butyl, tert-butyl, iso-pentyl group. Particularly, said group has 1, 2, 3 or 4 carbon atoms, for example a methyl, ethyl, propyl, butyl, iso-propyl, iso-butyl, sec-butyl, tert-butyl group, more particularly 1, 2 or 3 carbon atoms, for example a methyl, ethyl, n-propyl- or iso-propyl group.
When the "alkyl" group represents a substituent it contains in particular up to 6 carbon atoms and expressly indicates as C1-6 alkyl.
The term "halogen" or "halo-" should be understood as a fluorine, chlorine, bromine or iodine atom.
The term "halo-alkyl" should preferably be understood as a saturated linear or branched monovalent hydrocarbon group in which the term "alkyl" has the values defined above, and in which one or more hydrogen atoms is replaced by a halogen atom or more, these being the same or different. Particularly, said halogen atom is F. Said halo-alkyl group is, for example, -CF3, -CHF2, -CH2F, -CF2CF3, or -CH2CF3.
The term "alkoxy" should preferably be understood as a linear or branched saturated monovalent saturated hydrocarbon group of the formula -O- (alkyl), in which the term "alkyl" has the values defined above, for example a methoxy, ethoxy group , n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, tert-butoxy, sec-butoxy, pentoxy, iso-pentoxy, or n-hexoxy.

The term "alkenyl" should be understood as a linear or branched monovalent hydrocarbon group having 1 to 14 carbon atoms, which contains one or more double bonds, and which preferably has 2 to 10 carbon atoms, for example 2, 3 , 4, 5 or 6 carbon atoms, particularly 2 or 3 carbon atoms, it being understood that in the case in which said alkenyl group contains more than one double bond, then double bonds can be isolated or conjugated to each other. Said alkenyl group is, for example, a vinyl group, or allyl. In the context of the present invention, an alkenyl group may have one or more triple bonds in place of, or in addition to, the double bond (s).

The leaving group X in the compound of formula (III) may in principle be any leaving group known to a person skilled in the art. In a particular embodiment X represents a halide such as F, Cl, Br or I.
 fifty
In a particular embodiment of the process of the invention the palladium compound is a palladium salt. In a particular embodiment, the palladium salt is selected from Pd (II) acetate, Pd (II) trifluuroacetate, dichloro (1,5-cyclooctadiene) palladium (II), Pd (II) chloride and mixtures thereof, being a preferable salt Pd (II) acetate.

The amount of palladium used in the procedure can vary within a wide range. The amount of palladium in each particular case can easily be determined by the person skilled in the art. In a particular embodiment of the invention the amount is 0.001 to 0.1 mole% relative to the moles of the compound of the starting formula (II), preferably 0.01% to 0.09 mole%, for example: 0 , 02%, 0.04%, 0.06% or 0.08% molar.
 60
In a particular embodiment of the process of the invention the phosphorus derivative ligand compound is selected from phosphine derivatives, phosphine oxide derivatives and mixtures thereof.

In a particular embodiment, a phosphine derivative having the formula PR1R2R3 is used, where R1, R2, R3, the same or different from each other, represent hydrogen, C1-C6 alkyl or aryl. 65
In another particular embodiment, a phosphine oxide derivative having the formula OPR1R2R3 is used,
where R1, R2, R3, the same or different from each other, represent hydrogen, C1-C6 alkyl or aryl.
Commercially available phosphorus derivatives are preferably used, whereby the groups R1, R2, R3, when they are C1-C6 alkyl or aryl, are generally phenyl, or alkyl of 1 to 4 carbon atoms

In a preferred embodiment the phosphorous derivative ligand compound is selected from triphenylphosphine (PPh3), diphenylphosphine oxide (PPh2 (O) H), triphenylphosphine oxide (PPh3 (O)), di (tert-butyl) phosphine oxide (PtBu2 (O) H) and mixtures thereof. In a more preferred embodiment diphenylphosphine oxide (PPh2 (O) H) is used.


The reaction can be carried out using different combinations of palladium compound and phosphorus derived ligand compound. In a particular embodiment, the combination of Pd (OAc) 2 (palladium (II) acetate) and triphenylphosphine oxide (PPh3 (O)) is used. In another particular embodiment the combination of palladium (II) acetate and triphenylphosphine (PPh3) is used. In another particular embodiment, palladium (II) chloride (PdCl2) and diphenylphosphine oxide (PPh2 (O) H) are used. In another particular embodiment, Pd (OAc) 2 (palladium (II) acetate) and di (tert-butyl) phosphine oxide (PtBu2 (O) H) are used. In a preferred embodiment, the combination of 15 Pd (OAc) 2 (palladium (II) acetate) and diphenylphosphine oxide (PPh2 (O) H) is used, in equivalent and sub-stoichiometric amounts, relative to the moles of the compound of formula ( II), and between 0.02 and 0.05% molar.

The amount of phosphorous derivative ligand compound that is employed can be determined by a person skilled in the art in a conventional manner. In a particular embodiment, the amount is 0.001% to 0.1 mole% relative to the moles of the compound of the starting formula (II), preferably 0.01% to 0.09%, for example: 0.02%, 0 , 04%, 0.06% or 0.08% molar.

In a particular embodiment of the process of the invention the metal base is a base of an alkali metal or alkaline earth metal, such as Li, Na, K, Rb, Cs, Fr, Be, Mg, Ca, Sr, Ba or Ra, preferably an alkali metal such as Li, Na, K, Rb, or Cs.
In a particular embodiment of the process of the invention the metal base is selected from the group of carbonates, phosphates and mixtures thereof.
In a preferred embodiment the metal base is cesium carbonate. In another preferred embodiment, the metal base 30 is potassium phosphate.
The amount of metal base used is typically from 50% to 500% molar with respect to the moles of the compound (II), in particular from 100% to 300% molar, although the expert can easily determine the amount in each particular case. In a more particular embodiment the amount is 125%, 150%, 175%, 200%, 225%, 250% or 275% for example. In a preferred embodiment, 130 mol% potassium phosphate is used. 35

In a particular embodiment of the process of the invention, the quaternary ammonium salt is a tetraalkylammonium salt, preferably a tetraalkylammonium halide, more preferably tetrabutyl ammonium bromide.
 40
The amount of quaternary ammonium salt used is from 1% to 5% mole relative to the moles of the compound (II), in particular of for example 1.5%, 3%, 4% or 4.5%. In a preferred embodiment, 5% molar is used, for example 5% molar tetrabutylammonium bromide.

The volume of the solvent used and the temperature of the reaction influence the results obtained. In each particular case, the expert can determine these parameters in a conventional manner.
Typically the reaction is carried out using between 0.1 and 5 mL of water per mmol of the compound of formula (II), in particular 0.2 and 2 mL for example 0.50 mL, 1 mL, or 1.50 mL. The process of the invention is generally carried out by typically heating at a temperature between 100 and 170 ° C, for example 130 ° C, 140 ° C, 150 ° C or 160 ° C, depending on the particular case. fifty

The reaction times vary depending on the compound of formula (II) and starting formula (III), and in principle they are variable, but in any case, they are generally less than 48 hours. In a particular embodiment the reaction time is at least 24 hours. However, in each particular case the expert can determine the necessary reaction time in a conventional manner. 55

In the present invention the phosphorus derivative compound acts as a ligand, coordinating the palladium species present in the reaction medium. Without wishing to limit themselves to a particular particular theory, the inventors believe that it may be possible for said phosphorus derivative to participate in the formation of short-lived reaction intermediates whose structure is still undiluted, acting as an active catalytic system in water. 60

The compounds of formula (I) obtained are purified by methods well known in the state of the art.

In a particular embodiment of the process of the invention the residue A1 is a phenyl, naphthyl, phenanthryl, pyridyl, thienyl, optionally substituted with one or more substituents, selected from methoxy, chloro, methyl, fluoro, trifluoromethyl and bromine. In a particular embodiment, the rest has 1, 2, 3 or 4 substituents.

In a particular embodiment of the process of the invention the residue A2 is an aryl. In another particular embodiment, the aryl is a phenyl, optionally substituted with one or more substituents selected from methoxy, chloro, methyl, fluoro, trifluoromethyl and bromine. In a particular embodiment the moiety has 1, 2, 3 or 4 substituents. 5

In a particular embodiment of the process of the invention the residue A3 is an aryl. In another particular embodiment the aryl is phenyl or a naphthyl, optionally substituted with one or more substituents selected from methoxy, chloro, methyl, fluoro, trifluoromethyl and bromine. In a particular embodiment, the rest has 1, 2, 3 or 4 substituents. 10

In another particular embodiment of the process of the invention the compound of general formula (I) obtained is selected from the group consisting of:
[1] 1,2,2-triphenylethan-1-one
[2] 1,2-diphenyl-2- (m-tolyl) ethan-1-one 15
[3] 2- (4-methoxyphenyl) -1,2-diphenylethan-1-one
[4] 2- (3-methoxyphenyl) -1,2-diphenylethan-1-one
[5] 2- (3,4-dimethoxyphenyl) -1,2-diphenylethan-1-one
[6] 2- (3,5-Dimethoxyphenyl) -1,2-diphenylethan-1-one
[7] 2- (2-fluorophenyl) -1,2-diphenylethan-1-one 20
[8] 2- (naphthalen-1-yl) -1,2-diphenylethan-1-one
[9] 2,2-bis (3-methoxyphenyl) -1-phenylethan-1-one
[10] 2,2-bis (4-methoxyphenyl) -1-phenylethan-1-one
[11] 2,2-bis (3,5-dimethoxyphenyl) -1-phenylethan-1-one
[12] 2,2-bis (3,4-dimethoxyphenyl) -1-phenylethan-1-one 25
[13] 2- (2-fluorophenyl) -1-phenylettan-1-one
[14] 2- (4-acetylphenyl) -1- (4-bromophenyl) ethan-1-one
[15] 1- (4-chlorophenyl) -2,2-bis (3-methoxyphenyl) ethan-1-one
[16] 1- (naphthalen-2-yl) -2,2-diphenylethan-1-one
[17] 1- (naphthalen-1-yl) -2,2-diphenylethan-1-one 30
[18] 2,2-bis (3,4-dimethoxyphenyl) -1- (m-tolyl) ethan-1-one
[19] 2,2-bis (3-methoxyphenyl) -1- (4-methoxyphenyl) ethan-1-one
[20] 1- (4-methoxyphenyl) -2,2-diphenylethan-1-one
[21] 1- (3-methoxyphenyl) -2,2-diphenylethan-1-one
[22] 1- (3,5-bis (trifluoromethyl) phenyl) -2,2-diphenylethan-1-one 35
[23] 1- (2-Chlorophenyl) -2,2-diphenylethan-1-one
[24] 1- (3,4-dimethoxyphenyl) -2,2-diphenylethan-1-one
[25] 2-phenyl-1- (pyridin-3-yl) ethan-1-one
[26] 2- (3-Methoxyphenyl) -1- (pyridin-3-yl) ethan-1-one
[27] 2-phenyl-1- (thiophene-2-yl) ethan-1-one 40
[28] 2- (3-methoxyphenyl) -1- (thiophene-2-yl) ethan-1-one
[29] 1- (naphthalen-2-yl) -2- (4- (trifluoromethyl) phenyl) ethan-1-one
[30] 2,2-bis (3-methoxyphenyl) -1- (naphthalen-2-yl) ethan-1-one
[31] 2,2-bis (4-fluorophenyl) -1- (naphthalen-2-yl) ethan-1-one
[32] 2,2-bis (4-methoxyphenyl) -1- (naphthalen-1-yl) ethan-1-one 45
[33] 1- (fenantren-9-yl) -2,2-diphenylethan-1-one
[34] 1- (fenantren-9-yl) -2,2-di-p-toliletan-1-one
[35] 2- (fenantren-9-il) -1-phenylettan-1-one
[36] 1-phenyl-2- (o-tolyl) ethan-1-one
[37] 2- (2-ethylphenyl) -1-phenylettan-1-one 50


The process of the present invention allows to obtain compounds of general formula (I), in an alternative way to the prior art methods, using a palladium compound such as a palladium salt and a phosphorus derived ligand such as an oxide of phosphine and a tetraalkylammonium salt, all of them being advantageously commercially available, easily accessible and economical. The process of the invention is also carried out in water as the only solvent, which is economical and safe, and does not need any precaution in handling.

The use of palladium salts together with these phosphorus ligands as palladium catalysts are an advantageous and attractive alternative to other catalysts used in prior art processes, in view of their industrial application, due to their low price and low toxicity in infinitesimal amounts used. In addition, they are commercially available compounds, and there is no need for prior formation of economically more expensive catalysts.
 65
Following this line, water is a desirable solvent for any reaction, according to easy criteria
Access, low cost, safety and sustainability. It is a very convenient reagent, based on the fact that it is not a flammable liquid, which makes it unnecessary to take special safety measures, nor for handling and storage.

Similarly, as regards the compounds of formula (II) and (III) involved, these are easily accessible, and inexpensive. In this sense they can be obtained commercially or can be synthesized in a simple way by conventional procedures known to an expert.

Consequently, the process of the invention is an economical and also advantageous procedure in terms of occupational safety, since it is carried out with water as the sole solvent. Finally, it should be noted that, in addition to the aforementioned operational and environmental benefits, the process of the invention is highly effective and compatible with several functional groups present in the starting substrates, such as alkyl, alkoxide or halogen groups, among others.

The following are examples to illustrate the process of the invention that should not be considered in any case as limiting the scope thereof.

Examples

 twenty

Example 1: Preparation of 1,2,2-triphenylethan-1-one


 25
1.1. Preparation of 1,2,2-triphenylethane-1-one using Pd (OAc) 2 and diphenylphosphine oxide in the presence of water (0.5M).

1,2-Diphenylethan-1-one (80 mg, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (113.8 mg, 0.52 mmol) were mixed in a threaded tube ), TBAB (tetrabutylammonium bromide) (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. It was allowed to cool to room temperature, and H2O (5 mL) was added for dilution. This aqueous phase was then extracted with ethyl acetate (AcOEt) (3 x 6 ml). The combined organic phases were washed with a saturated solution of NaCl in water (1 x 15 ml), dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The residue thus obtained was purified by flash chromatography (AcOEt / Hexane 1: 9) to provide 1,2,2-triphenylethan-1-one as an off-white solid (105.7 mg, 97%). 1 H-NMR (δ, ppm) 8.06-8.02 (m, 2H), 7.55-7.50 (m, 1H), 7.45-7.40 (m, 2H), 7.37 -7.25 (m, 10H), 6.07 (s, 1H); NMR-13C (δ, ppm) 198.2, 139.1, 136.8, 133.0, 129.1, 128.9, 128.7, 128.6, 127.1, 59.4; MS (m / z) (%) 270 (M +), 239, 167, 105 (100). 40
EMAR (ESI, MNa +) Calculated for C20H16ONa 295,1093; found, 295,1087.

1.2. Preparation of 1,2,2-triphenylethan-1-one using PdCl2 and diphenylphosphine oxide in the presence of water (0.5M).
 Four. Five
1,2-Diphenylethan-1-one (80 mg, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (113.8 mg, 0.52 mmol) were mixed in a threaded tube ), TBAB (6.7 mg, 0.02 mmol), palladium (II) chloride (0.007 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL , 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1,2,2-triphenylethan-1-one was obtained as a yellow solid (6.5 mg, 6%).

1.3. Preparation of 1,2,2-triphenylethan-1-one using Pd (OAc) 2 and di-tert-butylphosphine oxide in the presence of water (0.5M).
 55
1,2-Diphenylethan-1-one (80 mg, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (113.8 mg, 0.52 mmol) were mixed in a threaded tube ), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and di-tert-butylphosphine oxide (0.006 mg, 0.00004 mmol) in water ( 0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours.
maintaining vigorous agitation at all times. After the preparation and purification steps described in Example 1.1, 1,2,2-triphenylethan-1-one was obtained as a yellow solid (92.6 mg, 85%).

1.4. Preparation of 1,2,2-triphenylethan-1-one using Pd (OAc) 2 and triphenylphosphine in the presence of water (0.5M).
 5
1,2-Diphenylethan-1-one (80 mg, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (113.8 mg, 0.52 mmol) were mixed in a threaded tube ), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and triphenylphosphine (0.01 mg, 0.00004 mmol) in water (0.8 mL , 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the manufacturing and purification steps described in Example 1.1, 1,2,2-triphenylethan-1-one was obtained as a yellow solid (72.9 mg, 67%).



1.5. Preparation of 1,2,2-triphenylethan-1-one using Pd (OAc) 2 and diphenylphosphine oxide in the presence of water (0.25M).

1,2-Diphenylethan-1-one (80 mg, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (113.8 mg, 0.52 mmol) were mixed in a threaded tube ), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (1.6 mL , 0.25 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1,2,2-triphenylethan-1-one was obtained as a yellow solid (18.5 mg, 17%).

1.6. Preparation of 1,2,2-triphenylethan-1-one using Pd (OAc) 2 and diphenylphosphine oxide in the presence of water (2M).

1,2-Diphenylethan-1-one (80 mg, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (113.8 mg, 0.52 mmol) were mixed in a threaded tube ), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.2 mL , 2 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1,2,2-triphenylethan-1-one was obtained as a yellow solid (55.5 mg, 51%).

1.7. Preparation of 1,2,2-triphenylethan-1-one using Pd (OAc) 2 and diphenylphosphine oxide in the presence of water 35 (0.5M) and TBAB (50 mol%)

1,2-Diphenylethan-1-one (80 mg, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (113.8 mg, 0.52 mmol) were mixed in a threaded tube ), TBAB (67 mg, 0.2 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL, 0 ,5M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1,2,2-triphenylethan-1-one was obtained as a yellow solid (65.3 mg, 60%).

1.8. Preparation of 1,2,2-triphenylethan-1-one using Pd (OAc) 2 and diphenylphosphine oxide in the presence of water (0.5M) and potassium phosphate (1 equivalent)

1,2-Diphenylethan-1-one (80 mg, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (87.5 mg, 0.4 mmol) were mixed in a threaded tube ), TBAB (6.7 mg, 0.2 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL , 0.5 M). Then, 50 after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1,2,2-triphenylethan-1-one was obtained as a yellow solid (74.0 mg, 68%).

1.9. Preparation of 1,2,2-triphenylethane-1-one using Pd (OAc) 2 and diphenylphosphine oxide in the presence of water 55 (0.5M) and cesium carbonate (1.3 equivalents)

1,2-diphenylethan-1-one (80 mg, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), cesium carbonate (171.1 mg, 0.52) were mixed in a threaded tube mmol), TBAB (67 mg, 0.2 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1,2,2-triphenylethan-1-one was obtained as a yellow solid (43.5 mg, 40%).

1.10. Preparation of 1,2,2-triphenylethane-1-one using Pd (OAc) 2 and diphenylphosphine oxide in the presence of water 65 (0.5M) and bromine benzene (1.1 equivalents)

In a threaded tube, 1,2-diphenylethan-1-one (80 mg, 0.4 mmol), bromobenzene (47 µL, 0.44 mmol), potassium phosphate (113.8 mg, 0.52 mmol) were mixed, TBAB (67 mg, 0.2 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring at all times. After the preparation and purification steps described in Example 1.1, 1,2,2-triphenylethan-1-one was obtained as a yellow solid (77.3 mg, 71%).


1.11 Preparation of 1,2,2-triphenylethan-1-one using Pd (OAc) 2 and triphenylphosphine oxide in the presence of 10 water (0.5M).

1,2-Diphenylethan-1-one (80 mg, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (113.8mg, 0.52 mmol) were mixed in a threaded tube , TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and triphenylphosphine oxide (0.01 mg, 0.00004 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1,2,2-triphenylethan-1-one was obtained as a yellow solid (64.2 mg, 59%).

1.12. Preparation of 1,2,2-triphenylethan-1-one using Pd (OAc) 2 and diphenylphosphine oxide in the presence of water (0.5M) and iodobenzene (3 equivalents)

In a threaded tube, 1,2-diphenylethan-1-one (80 mg, 0.4 mmol), iodobenzene (0.14 mL, 1.2 mmol), potassium phosphate (113.8 mg, 0.52 mmol) were mixed , TBAB (6.7 mg, 0.02 mmol), palladium acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1,2,2-triphenylethan-1-one was obtained as a yellow solid (79.5 mg, 73%).

1.13. Preparation of 1,2,2-triphenylethan-1-one using Pd (OAc) 2 and diphenylphosphine oxide in the presence of water (0.5M) and acetophenone

Acetophenone (49 µL, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (262.3 mg, 1.2 mmol), TBAB (6.7 mg were mixed in a threaded tube , 0.02 mmol), palladium acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1,2,2-triphenylethan-1-one was obtained as a yellow solid (92.5 mg, 85%).

1.14. Preparation of 1,2,2-triphenylethan-1-one using Pd (OAc) 2 and diphenylphosphine oxide from 40 grams deoxybenzoine

1,2-Diphenylethan-1-one (1.04 g, 5.2 mmol), bromobenzene (1.69 mL, 15.6 mmol), potassium phosphate (1.479 g, 6.76 mmol) were mixed in a threaded tube ), TBAB (87.1 mg, 0.26 mmol), palladium (II) acetate (0.12 mg, 0.00052 mmol) and diphenylphosphine oxide (0.11 mg, 0.00052 mmol) in water ( 10.4 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1,2,2-triphenylethan-1-one was obtained as a yellow solid (1.30 g, 92%)

 fifty
Example 2: Preparation of 1,2-diphenyl-2- (m-tolyl) ethan-1-one



1,2-diphenylethan-1-one (80 mg, 0.4 mmol), 3-iodotoluene (0.16 mL, 1.2 mmol), potassium phosphate (262.3 mg, 1) were mixed in a threaded tube , 2 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0 , 8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1,2-
diphenyl-2- (m-tolyl) ethan-1-one as a yellow solid (85.9 mg, 75%). 1H NMR (δ, ppm) 8.05 (d, J = 7.4 Hz, 2H), 7.60-7.49 (m, 1H), 7.44 (t, J = 7.4 Hz, 2H), 7.40-7.20 (m, 6H), 7.19-7.04 (m, 4H), 6.05 (s, 1H), 2.35 (s, 3H). NMR-13C (δ, ppm) 198.2, 139.1, 138.9, 138.3, 136.8, 135.0, 132.9, 130.0, 129.8, 129.7, 129, 1, 128.9, 128.6, 128.5, 127.9, 127.0, 126.1, 59.4, 21.4. MS (m / z) (%) 286 (M +), 239, 181, 165, 105 (100);
EMAR (ESI, MH +) Calculated for C21H19O 287.1436; found, 287.1441 5


Example 3: Preparation of 2- (4-methoxyphenyl) -1,2-diphenylethan-1-one

 10

In a threaded tube, 1,2-diphenylethane-1-one (80 mg, 0.4 mmol), para-bromoanisole (0.15 mL, 1.2 mmol), potassium phosphate (113.8 mg, 0, 52 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water ( 0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring at all times. After the preparation and purification steps described in Example 1.1, la2- (4-methoxyphenyl) -1,2-diphenylethane-1-one was obtained as a colorless oil (104.9 mg, 95%). 1 H NMR (δ, ppm) 8.01 (d, J = 7.6 Hz, 2H), 7.51 (t, J = 7.4 Hz, 1H), 7.41 (t, J = 7, 6 Hz, 2H), 7.38-7.24 (m, 7H), 6.87 (d, J = 8.3 Hz, 2H), 6.00 (s, 1H), 3.78 (s, 3H) . NMR-13C (δ, ppm) 198.5, 158.7, 139.5, 136.9, 132.9, 131.2, 130.2, 129.1, 128.9, 128.7, 128, 6, 127.1, 114.2, 58.6, 55.2. MS (m / z) (%) 302 (M +), 285, 197 (100), 182, 105; twenty
EMAR (ESI, MH +) Calculated for C21H19O2 303.1385; Found, 303.1385

Example 4: Preparation of 2- (3-methoxyphenyl) -1,2-diphenylethan-1-one

 25

1,2-Diphenylethan-1-one (80 mg, 0.4 mmol), 3-bromoanisole (0.16 mL, 1.2 mmol), potassium phosphate (262.3 mg, 1.2 mmol) were mixed in a threaded tube ), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL , 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring at all times. After the preparation and purification steps described in Example 1.1, 2- (3-methoxyphenyl) -1,2-diphenylethane-1-one was obtained as a colorless oil (99.2 mg, 82%). 1 H NMR (δ, ppm) 8.03 (d, J = 7.3 Hz, 2H), 7.52 (t, J = 7.3 Hz, 1H), 7.42 (t, J = 7, 5 Hz, 2H), 7.37-7.20 (m, 6H), 6.95-6.74 (m, 3H), 6.03 (s, 1H), 3.77 (s, 3H). NMR-13C (δ, ppm) 197.9, 159.8, 140.4, 138.9, 136.8, 132.9, 129.6, 129.1, 128.9, 128.6, 128, 5, 127.1, 121.5, 115.0, 112.3, 59.3, 55.1. MS (m / z) (%) 302 (M +), 197, 182, 165, 153, 105 (100); 35
EMAR (ESI, MH +) Calculated for C21H19O2 303.1385; Found, 303.1379

Example 5: Preparation of 2- (3,4-dimethoxyphenyl) -1,2-diphenylethan-1-one

 40
In a threaded tube, 1,2-diphenylethan-1-one (80 mg, 0.4 mmol), 4-bromoveratrol (0.18 mL, 1.2 mmol), potassium phosphate (262.3 mg, 1, 2 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0, 8 mL, 0.5 M). Then after
close the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 2- (3,4-dimethoxyphenyl) -1,2-diphenylethane-1-one was obtained as a yellow solid (102.4 mg, 77%). 1H NMR (δ, ppm) 7.98 (d, J = 7.4 Hz, 2H), 7.43 (t, J = 7.3 Hz, 1H), 7.34 (t, J = 7, 4 Hz, 2H), 6.99-6.90 (m, 3H), 6.79 (d, J = 12.5 Hz, 2H), 6.65 (d, J = 8.5 Hz, 3H) , 5.97 (s, 1 H), 3.77 (s, 6 H). NMR-13C (δ, ppm) 198.4, 149.2, 148.2, 139.4, 136.9, 133.1, 131.4, 129.0, 5 128.9, 128.7, 128 , 6, 127.1, 121.4, 112.3, 111.3, 58.9, 55.9, 55.8. MS (m / z) (%) 332 (M +), 227 (100), 196, 105;
EMAR (ESI, MH +) Calculated for C22H21O3 333.1491; found, 333.1497.

Example 6: Preparation of 2- (3,5-dimethoxyphenyl) -1,2-diphenylethan-1-one
 10


1,2-diphenylethan-1-one (80 mg, 0.4 mmol), 1-bromo-3,5-dimethoxybenzene (268.5 mg, 1.2 mmol), potassium phosphate (262.3 were mixed in a threaded tube mg, 1.2 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 2- (3,5-dimethoxyphenyl) -1,2-diphenylethane-1-one was obtained as an orange oil (99.7 mg, 75%). 1 H-NMR (δ, ppm) 8.05 (d, J = 8.6 Hz, 1H), 7.53-7.23 (m, 6H), 6.71 (d, J = 2.2 Hz, 2H), 6.51 (d, J = 2.2 Hz, 1H), 6.43-6.40 (m, 3H), 6.01 (s, 1H), 3.76 (s, 6H). NMR-13C (δ, ppm) 197.9, 161.0, 141.1, 138.8, 136.9, 133.1, 129.2, 128.9, 128.7, 127.2, 20 107 , 5, 105.5, 98.9, 59.5, 55.3. MS (m / z) (%) 332 (M +), 227, 196, 165, 152, 105 (100);
EMAR (ESI, MH +) Calculated for C22H21O3 333.1491; found, 333.1498

Example 7: Preparation of 2- (2-fluorophenyl) -1,2-diphenylethan-1-one
 25


In a threaded tube, 1,2-diphenylethan-1-one (80 mg, 0.4 mmol), 1-bromo-2-fluorobenzene (0.13 mL, 1.2 mmol), potassium phosphate (113.8 mg, 0.52 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, la2- (2-fluorophenyl) -1,2-diphenylethane-1-one was obtained as a yellow solid (40.6 mg, 35%). 1 H NMR (δ, ppm) 8.01 (d, J = 7.8 Hz, 2H), 7.54-7.04 (m, 12H), 6.31 (s, 1H). NMR-13C (δ, ppm) 197.3, 161.8, 137.1, 136.3, 133.1, 130.6, 129.4, 129.0, 128.9, 128.8, 128, 6, 127.5, 126.7, 124.2, 115.4, 52.0. MS (m / z) (%) 290 (M +), 257, 239, 183, 165, 35 157, 146, 133, 105 (100);
EMAR (EI, M +) Calculated for C20H15FO 290,1107; found, 290,1108

Example 8: Preparation of 2- (naphthalen-1-yl) -1,2-diphenylethan-1-one
 40


In a threaded tube, 1,2-diphenylethane-1-one (80 mg, 0.4 mmol), 1-bromonaphthalene (0.17 mL, 1.2 mmol), potassium phosphate (262.3 mg, 1, 2 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water ( 0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining at all times
vigorous agitation After the preparation and purification steps described in Example 1.1, la2- (naphthalen-1-yl) -1,2-diphenylethan-1-one was obtained as a yellow solid (98.0 mg, 76%). 1H NMR (δ, ppm) 8.07-8.01 (m, 3H), 7.93-7.89 (m, 1H), 7.81 (d, J = 8.2 Hz, 1H), 7.54-7.49 (m, 3H), 7.44-7.23 (m, 9H), 6.78 (s, 1H). NMR-13C (δ, ppm) 198.2, 138.0, 136.5, 135.0, 134.2, 133.0, 131.2, 129.5, 129.0, 128.8, 128, 6, 128.6, 128.0, 127.2, 127.0, 126.6, 125.7, 125.4, 123.1, 55.9. MS (m / z) (%) 322 (M +), 289, 217 (100), 163, 105; 5
EMAR (EI, M +) Calculated for C24H18O 322.1358; Found, 322.1356

Example 9: Preparation of 2,2-bis (3-methoxyphenyl) -1-phenylethan-1-one

 10

In a threaded tube, acetophenone (49 µL, 0.4 mmol), 3-bromoanisole (0.16 mL, 1.2 mmol), potassium phosphate (262.3 mg, 1.2 mmol), TBAB (6, 7 mg, 0.02 mmol), palladium acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the manufacturing and purification steps described in Example 1.1, 2,2-bis (3-methoxyphenyl) -1-phenylethane-1-one was obtained as an orange solid (122.3 mg, 92%). 1H NMR (δ, ppm) 8.02 (d, J = 7.4 Hz, 2H), 7.52 (t, J = 7.3 Hz, 1H), 7.41 (t, J = 7, 6 Hz, 2H), 7.25 (t, J = 7.9 Hz, 2H), 6.95-6.76 (m, 6H), 5.99 (s, 1H), 3.76 (s, 6H). NMR-13C (δ, ppm) 197.8, 159.8, 140.3, 136.8, 132.9, 129.6, 128.9, 128.6, 121.5, 115.1, 112, 4, 59.3, 55.1. MS (m / z) (%) 332 (M +), 227, 196, 105 (100); twenty
EMAR (EI, M +) Calculated for C22H20O3 332.1412; Found, 332.1409

Example 10: Preparation of 2,2-bis (4-methoxyphenyl) -1-phenylethan-1-one

 25

Acetophenone (49 µL, 0.4 mmol), 4-bromoanisole (0.15 mL, 1.2 mmol), potassium phosphate (262.3 mg, 1.2 mmol), TBAB (6, were mixed in a threaded tube 7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 2,2-bis (4-methoxyphenyl) -1-phenylethane-1-one was obtained as a yellow solid (99.7 mg, 75%). 1 H-NMR (δ, ppm) 8.03-8.00 (m, 2H), 7.54-7.49 (m, 1H), 7.43-7.39 (m, 2H), 7.21 -7.18 (m, 4H), 6.88-6.86 (m, 4H), 5.95 (s, 1H), 3.78 (s, 6H). NMR-13C (δ, ppm) 199.0, 158.8, 137.2, 132.8, 131.4, 130.0, 128.8, 128.5, 114.0, 57.7, 55, one. MS (m / z) (%) 332 (M +), 227 (100), 142, 105; 35
EMAR (EI, M +) Calculated for C22H20O3 332.1412; Found, 332.1413

Example 11: Preparation of 2,2-bis (3,5-dimethoxyphenyl) -1-phenylethan-1-one

 40

Acetophenone (49 µL, 0.4 mmol), 1-bromo-3,5-dimethoxybenzene (268.5 mg, 1.2 mmol), potassium phosphate (262.3 mg, 1.2 mmol) were mixed in a threaded tube ), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0, 8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 2,2-5 bis (3,5-dimethoxyphenyl) -1-phenylethane-1-one was obtained as an orange oil (109.9 mg, 70%). 1H NMR (δ, ppm) 8.00 (d, J = 7.1 Hz, 2H), 7.52 (t, J = 7.3 Hz, 1H), 7.41 (t, J = 7, 5 Hz, 2H), 6.44 (d, J = 2.2 Hz, 4H), 6.36 (t, J = 2.2 Hz, 2H), 5.87 (s, 1H), 3.74 (s, 12H). NMR-13C (δ, ppm) 198.6, 149.0, 148.1, 136.9, 132.9, 131.6, 128.8, 128.5, 121.2, 112.1, 111, 1, 58.4, 55.8, 55.8. MS (m / z) (%) 392 (M +), 287, 165 (100), 105;
EMAR (ESI, MH +) Calculated for C24H25O5 393.1702; found, 393.1699 10

Example 12: Preparation of 2,2-bis (3,4-dimethoxyphenyl) -1-phenylethan-1-one


 fifteen
In a threaded tube, acetophenone (49 µL, 0.4 mmol), 4-bromoveratrol (0.18 mL, 1.2 mmol), potassium phosphate (113.8 mg, 0.52 mmol), TBAB (6, 7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 2,2-bis (3,4-20 dimethoxyphenyl) -1-phenylethane-1-one was obtained as an orange oil (108.3 mg, 69%). 1 H-NMR (δ, ppm) 8.00 (d, J = 8.1 Hz, 2H), 7.51 (t, J = 7.3 Hz, 1H), 7.41 (t, J = 7, 6 Hz, 2H), 6.80 (m, 6H), 5.93 (s, 1H), 3.84 (s, 6H), 3.81 (s, 6H). NMR-13C (δ, ppm) 198.3, 148.7, 147.8, 136.5, 132.7, 131.3, 128.5, 128.3, 120.9, 111.8, 110, 8, 58.0, 55.6. MS (m / z) (%) 392 (M +), 287 (100), 105;
EMAR (EI, M +) Calculated for C24H24O5 392.1624; found, 392.1626 25

Example 13: Preparation of 2- (2-fluorophenyl) -1-phenylettan-1-one


 30
Acetophenone (49 µL, 0.4 mmol), 1-bromo-2-fluorobenzene (0.13 mL, 1.2 mmol), potassium phosphate (262.3 mg, 1.2 mmol) were mixed in a threaded tube, TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL, 0 ,5M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, la2- (2-35 fluorophenyl) -1-phenylethane-1-one was obtained as a yellow solid (59.1 mg, 78%). 1 H NMR (δ, ppm) 8.04 (d, J = 7.3 Hz, 2H), 7.60-7.56 (m, 1H), 7.50-7.45 (m, 2H), 7.30-7.22 (m, 2H), 7.13-7.06 (m, 2H), 4.33 (s, 2H). NMR-13C (δ, ppm) 196.3, 162.6, 136.4, 133.3, 131.7, 129.0, 128.7, 128.4, 124.2, 122.0, 115, 3, 38.6. MS (m / z) (%) 214 (M +), 183, 109, 105 (100);
EMAR (EI, M +) Calculated for C14H11FO 214.0794; found, 214, 0791 40


Example 14: Preparation of 2- (4-acetylphenyl) -1- (4-bromophenyl) ethan-1-one

 Four. Five

In a threaded tube 4'-bromoacetophenone (80.4 mg, 0.4 mmol), 4'-bromoacetophenone (241.2 mg, 1.2 mmol), potassium phosphate (262.3 mg, 1.2 mmol) were mixed ), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL , 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, la2- (4-acetylphenyl) -1- (4-bromophenyl) ethan-1-one was obtained as an off-white solid (31.7 mg, 25%). 1 H NMR (δ, ppm) 7.93 (d, J = 8.2 Hz, 2H), 7.86 (d, J = 8.6 Hz, 2H), 7.61 (d, J = 8, 6 Hz, 2H), 7.34 (d, J = 8.2 Hz, 2H), 4.31 (s, 2H), 2.58 (s, 3H). NMR-13C (δ, ppm) 197.6, 195.7, 139.5, 135.9, 135.0, 132.0, 130.0, 129.7, 128.7, 46.2. MS (m / z) (%) 318 (M + 1), 182 (100), 165, 105;
EMAR (EI, M +) Calculated for C16H13BrO2 316.0099; found, 316.0101 10

Example 15: Preparation of 1- (4-chlorophenyl) -2,2-bis (3-methoxyphenyl) ethan-1-one


 fifteen
In a threaded tube, 4'-chloroacetophenone (54 µL, 0.4 mmol), 3-bromoanisole (0.16 mL, 1.2 mmol), potassium phosphate (262.3 mg, 1.2 mmol), TBAB were mixed (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL, 0, 5M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, la1- (4-20 chlorophenyl) -2,2-bis (3-methoxyphenyl) ethan-1-one was obtained as a yellow oil (92.4 mg, 63% ). 1H NMR (δ, ppm) 7.94 (d, J = 8.7 Hz, 2H), 7.37 (d, J = 8.7 Hz, 2H), 7.28-7.22 (m, 2H), 6.87-6.80 (m, 6H), 5.90 (s, 1H), 3.76 (s, 6H). NMR-13C (δ, ppm) 196.7, 159.9, 140.0, 139.5, 135.1, 130.4, 129.8, 128.9, 121.5, 115.2, 112, 5, 59.5, 55.2. MS (m / z) (%) 366 (M +), 227 (100), 212, 196, 181, 169, 152, 139, 111;
EMAR (ESI, MH +) Calculated for C22H20ClO3 367.1101; found, 367,1098. 25

Example 16: Preparation of 1- (naphthalen-2-yl) -2,2-diphenylethan-1-one


 30
In a threaded tube 1- (naphthalen-2-yl) ethan-1-one (69.5 mg, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (262, 3 mg, 1.2 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1-35 (naphthalen-2-yl) -2,2-diphenylethane-1-one was obtained as a yellow solid (82.5 mg, 64%). 1H NMR (δ, ppm) 8.54 (d, J = 1.6 Hz, 1H), 8.06 (dd, J = 8.7, 1.8 Hz, 1H), 7.85-7, 82 (m, 3H), 7.56-7.52 (m, 2H), 7.34-7.24 (m, 10H), 6.21 (s, 1H). NMR-13C (δ, ppm) 198.3, 139.3, 135.6, 134.3, 132.6, 130.8, 129.8, 129.3, 128.9, 128.7, 128, 6, 127.8, 127.3, 126.8, 124.7, 59.6. MS (m / z) (%) 322 (M +), 215, 165, 155 (100), 139, 127, 115;
EMAR (ESI, MNa +) Calculated for C24H18NaO 345,1255; found, 345,1259 40

Example 17: Preparation of 1- (naphthalen-1-yl) -2,2-diphenylethan-1-one


 Four. Five
In a threaded tube, 1- (naphthalen-1-yl) ethan-1-one (62 µL, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (113.8 mg) were mixed , 0.52 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, la1- (naphthalen-1-yl) -2,2-diphenylethan-1-one was obtained as an orange oil (95.4 mg, 74%). 1H NMR (δ, ppm) δ 1H NMR (δ, ppm) 8.56 (s, 1H), 8.08 (dd, J = 8.7, 1.8 Hz, 1H), 7.95- 7.81 (m, 3H), 7.61-7.50 (m, 2H), 7.36-7.24 (m, 10H), 6.23 (s, 1H). NMR-13C (δ, ppm) 198.1, 139.1, 135.4, 134.1, 132.4, 130.6, 129.6, 129.1, 128.7, 128.5, 128, 4, 127.6, 127.1, 126.6, 124.5, 59.4. MS (m / z) (%) 322 (M +), 215, 165, 155 (100), 139, 127, 115;
EMAR (ESI, MNa +) Calculated for C24H18NaO 345,1255; found, 345,1256 10

Example 18: Preparation of 2,2-bis (3,4-dimethoxyphenyl) -1- (m-tolyl) ethan-1-one


 fifteen
In a threaded tube 3'-methylacetophenone (55 µL, 0.4 mmol), 4-bromoveratrol (0.18 mL, 1.2 mmol), potassium phosphate (262.3 mg, 1.2 mmol), TBAB were mixed (6.7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 2,2-20 bis (3,4-dimethoxyphenyl) -1- (m-tolyl) ethan-1-one was obtained as an orange solid (55.2 mg , 3. 4%). 1 H NMR (δ, ppm) 7.82-7.78 (m, 2H), 7.37-7.27 (m, 2H), 6.83-6.76 (m, 6H), 5.92 (s, 1H), 3.93 (s, 3H), 3.84 (s, 6H), 3.81 (s, 3H). NMR-13C (δ, ppm) 198.9, 149.1, 148.2, 138.4, 137.0, 133.8, 131.8, 129.3, 128.5, 126.1, 121, 3, 112.2, 111.2, 58.3, 55.9, 55.8, 21.4. MS (m / z) (%) 407 (M + 1), 287 (100), 271, 257, 165, 119;
EMAR (ESI, MH +) Calculated for C25H27O5 407.1858; found, 407.1860 25

Example 19: Preparation of 2,2-bis (3-methoxyphenyl) -1- (4-methoxyphenyl) ethan-1-one


 30
In a threaded tube 4-methoxyacetophenone (60.7 mg, 0.4 mmol), 3-bromoanisole (0.16 mL, 1.2 mmol), potassium phosphate (113.8 mg, 0.52 mmol) were mixed, TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0.8 mL , 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 2,2-35 bis (3-methoxyphenyl) -1- (4-methoxyphenyl) ethan-1-one was obtained as an orange oil (44.9 mg, 31 %). 1 H-NMR (δ, ppm) 8.05 (d, J = 9.0, 2H), 7.24 (d, J = 9.0, 2H), 6.95-6.83 (m, 8H) , 5.93 (s, 1H), 3.84 (s, 3H), 3.75 (s, 6H). NMR-13C (δ, ppm) 196.5, 163.5, 159.9, 140.8, 131.4, 129.9, 129.7, 121.7, 115.2, 113.9, 112, 5, 59.2, 55.6, 55.3.
MS (m / z) (%) 362 (M +), 243, 227, 196, 181, 135 (100), 107;
EMAR (ESI, MH +) Calculated for C23H23O4 363.1596; found, 363.1593. 40

Example 20: Preparation of 1- (4-methoxyphenyl) -2,2-diphenylethan-1-one



In a threaded tube 4-methoxycetophenone (60.7 mg, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (262.3 mg, 1.2 mmol), TBAB ( 6.7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0.8 mL, 0 ,5M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the processing and purification steps described in Example 1.1, the whitish solid 1- (4-methoxyphenyl) -2,2-diphenylethan-1-one (66.5 mg, 55%) was obtained. 1 H-NMR (δ, ppm) 8.07-7.99 (m, 2H), 7.39-7.22 (m, 10H), 6.96-6.84 (m, 2H), 6.04 (s, 1H), 3.83 (s, 3H). NMR-13C (δ, ppm) 196.7, 163.4, 139.4, 131.3, 129.8, 129.2, 128.7, 127.1, 113.8, 59.1, 55.5. MS (m / z) (%) 302 (M +), 165, 152, 135 (100), 128, 115, 107;
EMAR (EI, M +) Calculated for C21H18O2 302,1307; found, 302,1308 10

Example 21: Preparation of 1- (3-methoxyphenyl) -2,2-diphenylethan-1-one


 fifteen
In a threaded tube, 3-acetylannisol (57 µL, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (262.3 mg, 1.2 mmol), TBAB (6, 7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1- (3-methoxyphenyl) -20 2,2-diphenylethane-1-one was obtained as an off-white solid (83.4 mg, 69%). 1 H-NMR (δ, ppm) 7.60-7.54 (m, 2H), 7.39-7.18 (m, 11H), 7.07 (ddd, J = 8.2, 2.6, 0.9 Hz, 1H), 6.03 (s, 1H), 3.81 (s, 3H). NMR-13C (δ, ppm) 198.0, 159.8, 139.1, 138.2, 129.6, 129.1, 128.7, 127.2, 121.6, 119.5, 113, 3, 59.6, 55.4. MS (m / z) (%) 302 (M +), 239, 165, 152, 135 (100), 128, 115, 107;
EMAR (ESI, MNa +) Calculated for C21H18NaO2 325,1204; found, 325,1202. 25

Example 22: Preparation of 1- (3,5-bis (trifluoromethyl) phenyl) -2,2-diphenylethan-1-one


 30
In a threaded tube, 3', 5'-bis (trifuoromethyl) acetophenone (74 µL, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (113.8 mg, 0, 52 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0, 8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, the yellow solid 1- (3,5-bis (trifluoromethyl) phenyl) -2,2-diphenylethan-1-one (142.1 mg, 87%) was obtained. . 1H NMR (δ, ppm) 8.32 (s, 2H), 7.91 (s, 1H), 7.27-7.17 (m, 10H), 5.89 (s, 1H). NMR-13C (δ, ppm) 195.4, 138.2, 137.7, 132.3, 129.1, 129.0, 127.7, 124.6, 121.0, 60.0. MS (m / z) (%) 408 (M +), 389, 301, 241, 213, 194, 167 (100), 152, 139, 128, 115;
EMAR (EI, M +) Calculated for C22H14F6O 408.0949; Found, 408.0947
 40
Example 23: Preparation of 1- (2-chlorophenyl) -2,2-diphenylethan-1-one



In a threaded tube, 2'-chloroacetophenone (54 µL, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (113.8 mg, 0.52 mmol), TBAB ( 6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL, 0.5 M). Then after
close the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1- (2-chlorophenyl) -2,2-diphenylethane-1-one was obtained as a light yellow solid (76.0 mg, 62%). 1 H NMR (δ, ppm) 7.44-7.12 (m, 14H), 5.92 (s, 1H). NMR-13C (δ, ppm) 201.6, 139.9, 138.1, 131.6, 130.9, 130.5, 129.6, 129.4, 128.8, 127.5, 126, 9, 63.2. MS (m / z) (%) 306 (M +), 281, 239, 207, 181, 167, 152, 139 (100), 111; 5
EMAR (ESI, MH +) Calculated for C20H16ClO 307.0890; Found, 307.0888

Example 24: Preparation of 1- (3,4-dimethoxyphenyl) -2,2-diphenylethan-1-one

 10

In a threaded tube, 3,4-dimethoxyacetophenone (73.6 mg, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (262.3 mg, 1.2 mmol) were mixed, TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0.8 mL , 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring at all times. After the preparation and purification steps described in Example 1.1, 1- (3,4-dimethoxyphenyl) -2,2-diphenylethane-1-one was obtained as an off-white solid (67.8 mg, 51%). 1 H NMR (δ, ppm) 7.66 (dd, J = 8.4, 2.0 Hz, 1H), 7.60 (d, J = 2.0 Hz, 1H), 7.37-7, 20 (m, 10H), 6.83 (d, J = 8.4 Hz, 1H), 6.03 (s, 1H), 3.90 (s, 3H), 3.88 (s, 3H). NMR-13C (δ, ppm) 196.8, 153.2, 149.0, 139.4, 129.9, 129.1, 128.7, 127.1, 123.7, 111.2, 110.0, 59.0, 56.0, 55.9. MS (m / z) (%) 331 (M +), 207, 165 (100), 137, 122, 115; twenty
EMAR (EI, M +) Calculated for C22H20O3 332.1412; Found, 332.1411

Example 25: Preparation of 2-phenyl-1- (pyridin-3-yl) ethan-1-one

 25

In a threaded tube 1- (pyridin-3-yl) ethan-1-one (45 µL, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (113.8 mg, 0.52 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring at all times. After the preparation and purification steps described in Example 1.1, 2-phenyl-1- (pyridin-3-yl) ethan-1-one was obtained as a white solid (51.2 mg, 65%). 1H-NMR (δ, ppm) 9.29-9.13 (d, J = 1.7 Hz, 1H), 8.75 (dd, J = 4.8, 1.7 Hz, 1H), 8, 28-8.22 (m, 1H), 7.39-7.23 (m, 6H), 4.29 (s, 2H). NMR-13C (δ, ppm) 196.4, 153.5, 150.1, 135.9, 133.6, 131.8, 129.4, 128.8, 127.2, 123.7, 45, 8. MS (m / z) (%) 197 (M +), 167, 139, 115, 106 (100); 35
EMAR (ESI, MH +) Calculated for C13H12NO 198.0919; found, 198.0915

Example 26: Preparation of 2- (3-methoxyphenyl) -1- (pyridin-3-yl) ethan-1-one

 40
In a threaded tube 1- (pyridin-3-yl) ethan-1-one (45 µL, 0.4 mmol), 3-bromoanisole (0.16 mL, 1.2 mmol), potassium phosphate (113, 8 mg, 0.52 mmol), TBAB (6.7 mg, 0.02 mmol), palladium acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 2- (3-45 methoxyphenyl) -1- (pyridin-3-yl) ethan-1-one was obtained as an orange oil (55.4 mg, 61% ). 1H NMR (δ, ppm) 9.22 (d, J = 1.4 Hz, 1H), 8.76 (d, J = 4.8 Hz, 1H), 8.25 (d, J = 8, 0 Hz, 1H), 7.40 (dd, J = 8.0, 4.8 Hz, 1H), 7.29-7.23 (m, 1H), 6.86-6.82 (m, 3H ), 4.26 (s, 2H), 3.78 (s, 3H). NMR-13C (δ, ppm) 196.2, 159.9, 153.5, 149.8, 136.0, 134.6, 131.6, 129.9, 123.3, 121.6, 115, 0, 112.7, 55.3, 46.0. MS (m / z) (%) 227 (M +), 199, 154, 121, 106 (100);
EMAR (ESI, MH +) Calculated for C14H14NO2 228,1025; found, 228.1024 50

Example 27: Preparation of 2-phenyl-1- (thiophen-2-yl) ethan-1-one


 5
1- (Thiophen-2-yl) ethan-1-one (44 µL, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (113.8 mg) were mixed in a threaded tube , 0.52 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 2-phenyl-1- (thiophene-2-yl) ethan-1-one was obtained as an orange oil (32.3 mg, 40%). 1 H NMR (δ, ppm) 7.79 (dd, J = 3.8, 1.1 Hz, 1H), 7.66 (dd, J = 5.0, 1.1 Hz, 1H), 7, 37-7.33 (m, 5H), 7.14 (dd, J = 5.0, 3.8 Hz, 1H), 4.22 (s, 2H). NMR-13C (δ, ppm) 190.4, 143.9, 134.3, 134.0, 132.6, 129.4, 129.0, 128.7, 128.2, 127.3, 127, 0, 46.4. MS (m / z) (%) 202 (M +), 197, 167, 139, 115, 106 (100);
EMAR (ESI, MH +) Calculated for C12H11OS 203.0531; found, 203.0528 15

Example 28: Preparation of 2- (3-methoxyphenyl) -1- (thiophen-2-yl) ethan-1-one


 twenty
In a threaded tube 1- (thiophen-2-yl) ethan-1-one (44 µL, 0.4 mmol), 3-bromoanisole (0.16 mL, 1.2 mmol), potassium phosphate (113, 8 mg, 0.52 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 2- (3-25 methoxyphenyl) -1- (thiophene-2-yl) ethan-1-one was obtained as a yellow solid (23.2 mg, 25% ). 1 H NMR (δ, ppm) 7.77 (dd, J = 3.8, 1.1 Hz, 1H), 7.63 (dd, J = 5.0, 1.1 Hz, 1H), 7, 26 (t, J = 3.9 Hz, 1H), 7.12 (dd, J = 5.0, 3.9 Hz, 1H), 6.88 (m, 2H), 6.80 (dd, J = 8.2, 2.5 Hz, 1H), 4.16 (s, 2H), 3.79 (s, 3H). NMR-13C (δ, ppm) 190.3, 159.8, 143.8, 135.8, 134.0, 132.7, 129.7, 128.2, 121.7, 115.0, 112, 6, 55.2, 46.5. MS (m / z) (%) 232 (M +), 121, 111 (100);
EMAR (ESI, MH +) Calculated for C13H13O2S 233.0636; found, 233.0636 30

Example 29: Preparation of 1- (naphthalen-2-yl) -2- (4- (trifluoromethyl) phenyl) ethan-1-one


 35
In a threaded tube 1- (naphthalen-2-yl) ethan-1-one (69.5 mg, 0.4 mmol), 1-bromo-4- (trifluoromethyl) benzene (0.17 mL, 1, 2 mmol), potassium phosphate (262.3 mg, 1.2 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1- (naphthalen-2-yl) -2- (4- (trifluoromethyl) phenyl) ethan-1-one was obtained as a white solid (50.2 mg, 40%) 1H NMR (δ, ppm) 8.55 (s, 1H), 8.06 (dd, J = 8.7, 1.8 Hz, 1H), 7.99 (d, J = 7.7 Hz, 1H), 7.95-7.86 (m, 2H), 7.66-7.54 (m, 4H), 7.44 (d, J = 8.3 Hz, 2H), 4.49 (s , 2H). NMR-13C (δ, ppm) 196.6, 138.6, 135.7, 133.7, 132.5, 130.3, 130.0, 129.6, 128.8, 128.7, 127, 8, 126.9, 125.6, 124.0, 45.1. MS (m / z) (%) 314 (M +), 215, 155 (100), 139, 127; EMAR (ESI, MH +) Calculated for C19H14F3O 315.0997; found, 315.0994. Four. Five

Example 30: Preparation of 2,2-bis (3-methoxyphenyl) -1- (naphthalen-2-yl) ethan-1-one



In a threaded tube 1- (naphthalen-2-yl) ethan-1-one (69.5 mg, 0.4 mmol), 3-bromoanisole (0.16 mL, 1.2 mmol), potassium phosphate ( 262.3 mg, 1.2 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0 .0002 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. Following the manufacturing and purification steps described in Example 1.1, 2,2-bis (3-methoxyphenyl) -1- (naphthalen-2-yl) ethan-1-one was obtained as a yellow oil (55.0 mg, 36 %). 1H NMR (δ, ppm) 8.55 (d, J = 1.8 Hz, 1H), 8.07 (dd, J = 8.6, 1.8 Hz, 1H), 7.95-7, 82 (m, 3H), 7.56 (dddd, J = 17.4, 8.2, 6.9, 1.4 Hz, 2H), 7.30 - 7.21 (m, 2H), 6, 97-6.88 (m, 4H), 6.81 (ddd, J = 8.2, 2.7, 1.0 Hz, 2H), 6.15 (s, 1H), 3.77 (s, 6H). NMR-13C (δ, 10 ppm) 197.9, 159.9, 140.5, 135.5, 134.2, 132.5, 130.6, 129.7, 129.7, 128.5, 128 , 5, 127.7, 126.7, 124.6, 121.6, 115.2, 112.4, 59.4, 55.2. MS (m / z) (%) 381 (M +), 253, 242, 155, 135 (100), 107; EMAR (EI, M +) Calculated for C26H22O3 382.1569; found, 382.1570.

Example 31: Preparation of 2,2-bis (4-fluorophenyl) -1- (naphthalen-2-yl) ethan-1-one 15



In a threaded tube 1- (naphthalen-2-yl) ethan-1-one (69.5 mg, 0.4 mmol), 1-bromo-4-fluorobenzene (0.13 mL, 1.2 mmol) were mixed , potassium phosphate (262.3 mg, 1.2 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate 20 (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0 , 04 mg, 0.0002 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. Following the manufacturing and purification steps described in Example 1.1, 2,2-bis (4-fluorophenyl) -1- (naphthalen-2-yl) ethan-1-one was obtained as a colorless oil (84.6 mg, 59 %). 1H NMR (δ, ppm) 8.51 (d, J = 1.8 Hz, 1H), 8.03 (dd, J = 8.7, 1.8 Hz, 1H), 7.95-7, 83 (m, 3H), 7.64-7.52 (m, 25 2H), 7.31-7.24 (m, 4H), 7.10-6.98 (m, 4H), 6.17 (s, 1H). NMR-13C (δ, ppm) 197.9, 163.6, 160.4, 135.6, 134.8, 133.8, 132.4, 130.7, 130.7, 130.6, 129, 7, 128.8, 128.6, 127.7, 126.9, 124.4, 115.9, 115.6, 57.6. MS (m / z) (%) 259 (M +), 233, 201, 183, 155 (100), 127, 101; EMAR (ESI, MH +) Calculated for C24H17F2O 359,1247; found, 359,1249.
 30
Example 32: Preparation of 2,2-bis (4-methoxyphenyl) -1- (naphthalen-1-yl) ethan-1-one



In a threaded tube 1- (naphthalen-1-yl) ethan-1-one (62 µL, 0.4 mmol), para-bromoanisole (0.15 mL, 1.2 35 mmol), potassium phosphate (113) were mixed , 8 mg, 0.52 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol ) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. Following the manufacturing and purification steps described in Example 1.1, 2,2-bis (4-methoxyphenyl) -1- (naphthalen-1-yl) ethan-1-one was obtained as a white solid (64.2 mg, 42 %). 1 H-NMR (δ, ppm) 40 8.58-8.48 (m, 1H), 7.98-7.81 (m, 3H), 7.60-7.38 (m, 3H), 7, 34-7.26 (m, 4H), 6.93-6.83 (m, 4H), 5.96 (s, 1H), 3.78 (s, 6H). NMR-13C (δ, ppm) 202.73, 158.67, 136.61, 133.94, 132.51, 131.59, 130.54, 130.07, 128.40,
127.89, 127.59, 126.43, 125.82, 124.35, 114.15, 60.94, 55.24. MS (m / z) (%) 382 (M +), 227, 196, 181, 169, 155 (100), 127; EMAR (EI, M +) Calculated for C26H22O3 382.1569; found, 382.1566.

Example 33: Preparation of 1- (phenanthren-9-yl) -2,2-diphenylethan-1-one
 5


In a threaded tube, 1- (phenanthren-9-yl) ethan-1-one (88.1 mg, 0.4 mmol), bromobenzene (0.13 mL, 1.2 mmol), potassium phosphate (262, 3 mg, 1.2 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1- (phenanthren-9-yl) -2,2-diphenylethane-1-one was obtained as a yellow solid (84.9 mg, 57%). 1H NMR (δ, ppm) 8.74-8.61 (m, 2H), 8.49 (dd, J = 8.1, 1.6 Hz, 1H), 8.18 (s, 1H), 7.88 (dd, J = 7.9, 1.4 Hz, 1H), 7.80-7.56 (m, 4H), 7.50-7.25 (m, 10H), 6.18 ( s, 1H). NMR-13C (δ, ppm) 202.1, 139.1, 135.9, 131.8, 130.8, 129.9, 129.9, 129.5, 129.2, 15 128.9, 128 , 8, 128.6, 127.6, 127.3, 127.2, 127.1, 126.6, 122.8, 122.7, 62.6. MS (m / z) (%) 370 (M +), 339, 267, 205 (100), 177, 165, 151; EMAR (EI, M +) Calculated for C28H20O 372.1514; found, 372.1515.

Example 34: Preparation of 1- (phenanthren-9-yl) -2,2-di-p-tolyletan-1-one
 twenty


In a threaded tube 1- (phenanthren-9-yl) ethan-1-one (88.1 mg, 0.4 mmol), 4-bromotoluene (0.15 mL, 1.2 mmol), potassium phosphate ( 262.3 mg, 1.2 mmol), TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and diphenylphosphine oxide (0.04 mg, 0 .0002 mmol) in water (0.8 mL, 0.5 M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 1- (phenanthren-9-yl) -2,2-di-p-tolyletan-1-one was obtained as a yellow solid (88.1 mg, 55%) . 1H NMR (δ, ppm) 8.74-8.60 (m, 2H), 8.51 (dd, J = 8.2, 1.6 Hz, 1H), 8.19 (s, 1H), 7.89 (dd, J = 7.9, 1.4 Hz, 1H), 7.78-7.58 (m, 4H), 7.36 (d, J = 8.1 Hz, 4H), 7.19 (d , J = 8.1 Hz, 4H), 6.12 (s, 1H), 2.35 (s, 6H). NMR-13C (δ, ppm) 202.5, 136.8, 136.3, 30 136.1, 131.8, 130.8, 130.2, 129.9, 129.5, 129.4, 129 , 0, 128.8, 128.7, 127.5, 127.1, 127.0, 126.7, 122.8, 122.7, 61.9, 21.1. MS (m / z) (%) 400 (M +), 355, 279, 205 (100), 177, 151; EMAR (EI, M +) Calculated for C30H24O 400.1817; found, 400.1820.

Example 35: Preparation of 2- (phenanthren-9-yl) -1-phenylettan-1-one 35



Acetophenone (49 µL, 0.4 mmol), 9-bromophenanthrene (321.4 mg, 1.2 mmol), potassium phosphate (262.3 mg, 1.2 mmol), TBAB (6, were mixed in a threaded tube 7 mg, 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 40 mmol) and diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0.8 mL, 0, 5M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 2- (phenanthren-9-yl) -1-phenylettan-1-one was obtained as a yellow solid (40.3 mg, 34%). 1H NMR (δ, ppm) 8.76 (d, J = 8.1, 1H), 8.68 (d, J = 8.2 Hz, 1H), 8.16 - 8.08 (m, 2H ), 7.90 (dd, J = 8.0, 1.5 Hz, 1H), 7.82 (dd, J = 7.7, 1.6 Hz, 1H), 7.70 - 45 7.45 (m, 8H), 4.77 (s, 2H). NMR-13C (δ, ppm) 197.7, 136.7, 133.3, 131.6, 131.2, 130.8, 130.2, 129.9, 128.9,
128.8, 128.5, 128.3, 126.8, 126.7, 126.6, 126.5, 124.5, 123.3, 122.5, 43.5. MS (m / z) (%) 296 (M +), 263, 191, 165, 105 (100), 127, 101; EMAR (ESI, MH +) Calculated for C22H17O 297,1279; found, 297.1276.

Example 36: Preparation of 1-phenyl-2- (o-tolyl) ethan-1-one
 5



Acetophenone (49 µL, 0.4 mmol), ortho-bromotoluene (0.15 mL, 1.2 mmol), potassium phosphate (113.8 mg, 0.52 mmol), TBAB (6.7 mg were mixed in a threaded tube , 0.02 mmol), palladium (II) acetate (0.045 mg, 0.0002 mmol) and 10 diphenylphosphine oxide (0.04 mg, 0.0002 mmol) in water (0.8 mL, 0.5 M ). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 24 hours while maintaining vigorous stirring. Following the manufacturing and purification steps described in Example 1.1, 1-phenyl-2- (o-tolyl) ethan-1-one was obtained as a yellow solid (43.7 mg, 52%). 1 H NMR (δ, ppm) 8.05 (dd, J = 8.3, 1.4 Hz, 2H), 7.59 (ddt, J = 8.3, 6.6, 1.4 Hz, 1H ), 7.50 (ddt, J = 8.3, 6.6, 1.4 Hz, 2H), 7.24-7.12 (m, 4H), 4.32 (s, 2H), 2, 28 (s, 3H). NMR-13C (δ, ppm) 197.5, 136.9, 136.9, 133.5, 133.2, 130.4, 130.3, 128.7, 128.4, 127.2, 126 , 1, 43.5, 19.8. MS (m / z) (%) 210 (M +), 165, 105 (100); EMAR (ESI, MH +) Calculated for C15H15O 211,1123; found, 211,1122.

Example 37: Preparation of 2- (2-ethylphenyl) -1-phenylettan-1-one
 twenty


Acetophenone (49 µL, 0.4 mmol), 1-bromo-2-ethylbenzene (0.17 mL, 1.2 mmol), potassium phosphate (262.3 mg, 1.2 mmol) were mixed in a threaded tube, TBAB (6.7 mg, 0.02 mmol), palladium (II) acetate (0.009 mg, 0.00004 mmol) and diphenylphosphine oxide (0.008 mg, 0.00004 mmol) in water (0.8 mL, 0 ,5M). Then, after closing the tube, the reaction mixture was heated at 160 ° C for 48 hours while maintaining vigorous stirring. After the preparation and purification steps described in Example 1.1, 2- (2-ethylphenyl) -1-phenylettan-1-one was obtained as a yellow oil (52.9 mg, 59%). 1 H-NMR (δ, ppm) 8.08-7.99 (m, 2H), 7.64-7.54 (m, 1H), 7.53-7.44 (m, 2H), 7.27 - 7.24 (m, 2H), 7.23-7.10 (m, 2H), 4.35 (s, 2H), 2.62 (q, J = 7.5 Hz, 2H), 1, 21 (t, J = 7.5 Hz, 3H). NMR-13C (δ, ppm) 197.8, 142.5, 136.9, 133.1, 132.7, 130.6, 128.7, 128.5, 128.3, 127.4, 30 126 , 0, 42.9, 25.9, 14.7.EM (m / z) (%) 224 (M +), 178, 165, 115, 105 (100); EMAR (ESI, MH +) Calculated for C16H17O 225,1279; found, 225,1276.


 35

权利要求:
Claims (21)
[1]


1. A process comprising reacting a compound of formula (II) 5
A1-C (O) -CH2-A2
with a compound of formula (III)
 10
A3-X
to obtain a compound of formula (I):
A1-C (O) –CH (A2) (A3) 15

where
A1 represents an aryl or heteroaryl group;
A2 represents a group selected from hydrogen, C1-C14 alkyl, C2-C14 alkenyl, aryl and heteroaryl; twenty
A3 represents an aryl or heteroaryl group; Y
X represents a leaving group,
in the presence of:
(i) a palladium compound; 25
(ii) a phosphorus derived ligand compound;
(iii) a metal base; Y
(iv) a quaternary ammonium salt,
in water
 30
[2]
2. A process according to claim 1, wherein the palladium compound is a palladium salt.

[3]
3. A process according to claim 2 wherein the palladium salt is selected from Pd (II) acetate, Pd (II) trifluuroacetate, dichloro (1,5-cyclooctadiene) palladium (II), Pd (II chloride) ) and their mixtures,
 35
[4]
4. A process according to claim 3 wherein the palladium salt is Pd (II) acetate.

[5]
5. A process according to claim 2-4, wherein the amount of palladium used is 0.001% to 0.1 mol% relative to the moles of the compound of formula (II).
 40
[6]
6. A process according to any one of the preceding claims, wherein the phosphorus derivative ligand compound is selected from phosphine derivatives, phosphine oxide derivatives and mixtures thereof.

[7]
7. A process according to claim 6, wherein the phosphine derivative has the formula PR1R2R3, wherein R1, R2, R3 the same or different, represent hydrogen, C1-C6 alkyl or aryl. Four. Five

[8]
8. The method according to claim 6, wherein the phosphine oxide derivative has the formula OPR1R2R3, wherein R1, R2, R3 the same or different, represent hydrogen, C1-C6 alkyl or aryl.

[9]
9. The method according to any one of the preceding claims 6 to 8, wherein the phosphatic derivative ligano compound 50 is selected from triphenylphosphine (PPh3), diphenylphosphine oxide (PPh2 (O) H), triphenylphosphine oxide (PPh3 (O) ), di (tert-butyl) phosphine oxide (PtBu2 (O) H) and mixtures thereof.

[10]
10. The method according to any one of the preceding claims 6 to 9, wherein the amount of phosphorus derivative ligand compound used is 0.001% to 0.1 mole% relative to the moles of the compound of formula (II).

[11]
11. A method according to any one of the preceding claims wherein the metal base is a base of an alkali metal or alkaline earth metal, preferably an alkali metal.
 60
[12]
12. The method according to claim 11, wherein the metal base is selected from the group of carbonates, phosphates and mixtures thereof.

[13]
13. The method according to one of claims 11 or 12, wherein the metal base is cesium carbonate or potassium phosphate. 65

[14]
14. A method according to one of claims 11 to 13 wherein the amount of metal base used is 50% to 500% mole relative to the moles of the compound of formula (II).

[15]
15. The method according to any one of the preceding claims, wherein the quaternary ammonium salt is a tetraalkylammonium salt, preferably a tetraalkylammonium halide. 5

[16]
16. The method of claim 15, wherein the quaternary ammonium salt is tetrabutyl ammonium bromide.

[17]
17. The method according to one of claims 15 or 16, wherein the amount of quaternary ammonium salt 10 used is from 1% to 5% mole relative to the moles of the compound of formula (II).

[18]
18. The method according to one of claims 2 to 17, wherein the A1 moiety is a phenyl, naphthyl, phenanthryl, pyridyl, thienyl, optionally substituted with one or more substituents selected from methoxy, chlorine, methyl, fluoro, trifluoromethyl and bromine . fifteen

[19]
19. The method according to one of claims 2 to 17, wherein the A2 moiety is a phenyl, optionally substituted with one or more substituents selected from methoxy, chloro, methyl, fluoro, trifluoromethyl and bromine.

[20]
20. The method according to one of claims 2 to 17, wherein the A3 moiety is a phenyl or a naphthyl, optionally substituted with one or more substituents selected from methoxy, chlorine, methyl, fluoro, trifluoromethyl and bromine.

[21]
21. The method according to any one of the preceding claims, wherein the compound of the general formula (I) obtained is selected from the group consisting of:
[1] 1,2,2-triphenylethan-1-one
[2] 1,2-diphenyl-2- (m-tolyl) ethan-1-one
[3] 2- (4-methoxyphenyl) -1,2-diphenylethan-1-one
[4] 2- (3-methoxyphenyl) -1,2-diphenylethan-1-one
[5] 2- (3,4-dimethoxyphenyl) -1,2-diphenylethan-1-one 30
[6] 2- (3,5-Dimethoxyphenyl) -1,2-diphenylethan-1-one
[7] 2- (2-fluorophenyl) -1,2-diphenylethan-1-one
[8] 2- (naphthalen-1-yl) -1,2-diphenylethan-1-one
[9] 2,2-bis (3-methoxyphenyl) -1-phenylethan-1-one
[10] 2,2-bis (4-methoxyphenyl) -1-phenylethan-1-one 35
[11] 2,2-bis (3,5-dimethoxyphenyl) -1-phenylethan-1-one
[12] 2,2-bis (3,4-dimethoxyphenyl) -1-phenylethan-1-one
[13] 2- (2-fluorophenyl) -1-phenylettan-1-one
[14] 2- (4-acetylphenyl) -1- (4-bromophenyl) ethan-1-one
[15] 1- (4-Chlorophenyl) -2,2-bis (3-methoxyphenyl) ethan-1-one 40
[16] 1- (naphthalen-2-yl) -2,2-diphenylethan-1-one
[17] 1- (naphthalen-1-yl) -2,2-diphenylethan-1-one
[18] 2,2-bis (3,4-dimethoxyphenyl) -1- (m-tolyl) ethan-1-one
[19] 2,2-bis (3-methoxyphenyl) -1- (4-methoxyphenyl) ethan-1-one
[20] 1- (4-methoxyphenyl) -2,2-diphenylethan-1-one 45
[21] 1- (3-methoxyphenyl) -2,2-diphenylethan-1-one
[22] 1- (3,5-bis (trifluoromethyl) phenyl) -2,2-diphenylethan-1-one
[23] 1- (2-Chlorophenyl) -2,2-diphenylethan-1-one
[24] 1- (3,4-dimethoxyphenyl) -2,2-diphenylethan-1-one
[25] 2-phenyl-1- (pyridin-3-yl) ethan-1-one 50
[26] 2- (3-Methoxyphenyl) -1- (pyridin-3-yl) ethan-1-one
[27] 2-phenyl-1- (thiophene-2-yl) ethan-1-one
[28] 2- (3-methoxyphenyl) -1- (thiophene-2-yl) ethan-1-one
[29] 1- (naphthalen-2-yl) -2- (4- (trifluoromethyl) phenyl) ethan-1-one
[30] 2,2-bis (3-methoxyphenyl) -1- (naphthalen-2-yl) ethan-1-one 55
[31] 2,2-bis (4-fluorophenyl) -1- (naphthalen-2-yl) ethan-1-one
[32] 2,2-bis (4-methoxyphenyl) -1- (naphthalen-1-yl) ethan-1-one
[33] 1- (fenantren-9-yl) -2,2-diphenylethan-1-one
[34] 1- (fenantren-9-yl) -2,2-di-p-toliletan-1-one
[35] 2- (phenanthren-9-yl) -1-phenyletan-1-one 60
[36] 1-phenyl-2- (o-tolyl) ethan-1-one
[37] 2- (2-ethylphenyl) -1-phenylettan-1-one

  65

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引用文献:

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公开号 | 申请日 | 公开日 | 申请人 | 专利标题

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US6072073A|1998-08-21|2000-06-06|Yale University|Carbonyl arylations and vinylations using transition metal catalysts|

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