Organometallic compounds, production and use thereof

Abstract

The present application relates to novel palladium complexes, processes for the preparation thereof, and the use thereof.

Description

[0001] Organometallic compounds, their production and use

[0002] Introduction

[0003] Numerous organometallic compounds, especially palladium compounds, are known as catalysts in chemical synthesis. Numerous palladium-catalyzed reactions, such as the Heck and Stille reaction, the Hartwig-Buchwald reaction, the Negishi coupling, the Suzuki coupling, and the Sonogashira coupling, are established in preparative organic chemistry.

[0004] Nevertheless, there is a constant need for new catalysts that meet specific requirements or have new properties in order to expand and complement the range of preparative chemistry.

[0005] WO 2017 / 093427, for example, shows a palladium-catalyzed, selective arylation process.

[0006] WO 2019 / 030304 shows the use of novel ligands for the preparation of metal complexes and their use in organometallic catalysis.

[0007] It has now been surprisingly found that such ligands can form new, previously unknown and catalytically active palladium complexes.

[0008] Brief description of the invention

[0009] 1. A compound of formula I or II where X is halogen, R1 is alkyl, perfluoroalkyl, aryl or cycloalkyl, each substituted or unsubstituted, cyano, sulfonyl -SO2-R10 with R10= C1-C5 alkyl, C5-C6 cycloalkyl, C5-C10 aryl, each unsubstituted or substituted with C1 to C4 alkyl or C1 to C4 perfluoroalkyl, silyl - Si(R20R30R40) with R20, R30 and R40, each independently of one another, being C1-C6 alkyl or C5-C10 aryl, each unsubstituted or substituted with C1 to C4 alkyl,

[0010] R2 represents alkyl or cycloalkyl, adamantyl and aryl,

[0011] R3 represents alkyl, cycloalkyl, or aryl. 2. A compound according to item 1, where X represents chlorine, bromine, iodine, or combinations thereof. 3. A compound according to one or more of the above points, wherein R1 is C1 to C9 alkyl, C4-C8 cycloalkyl, cyano, sulfonyl -SO2-R10 with R10 = C1-C5 alkyl, C5-C6 cycloalkyl, C5-C10 aryl, each unsubstituted or mono- or polysubstituted with C1 to C4 alkyl, C1 to C4 alkoxy or C1 to C4 perfluoroalkyl, silyl -Si(R20R30R40) with R20, R30 and R40, each independently of one another, is C1-C6 alkyl or C5-C10 aryl, each unsubstituted or substituted with C1 to C4 alkyl, or R1 is C5-C10 aryl, which is mono- or polysubstituted with C1 to C5 alkyl, C1 to C5 alkoxy or C1 to C5 perfluoroalkyl can be substituted. 4.A compound according to one or more of the above points, wherein R2 is C1 to C9 alkyl, C4-C9 cycloalkyl, adamantyl or C5-C10 aryl, which may be mono- or polysubstituted by C1 to C5 alkyl, C1 to C5 alkoxy or C1 to C5 perfluoroalkyl. 5. A compound according to one or more of the above points, wherein R3 is C1-C12 alkyl, C4-C8 cycloalkyl, C5-C10 aryl, which may be mono- or polysubstituted by C1 to C5 alkyl, C1 to C5 alkoxy or 6. A compound according to one or more of the above points, wherein R1 is selected from methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert.-Butyl, n-pentyl, n-Pentyl (Amyl), 2-Pentyl (sec-Pentyl), 3- Pentyl, 2-Methylbutyl, 3-Methylbutyl ( / so-Pentyl oder / so-Amyl), 3-Methyl- but-2-yl, 2-Methylbut-2-yl, 2,2-Dimethylpropyl (Neopentyl), n-hexyl, Triflu- ormethyl, Cyclobutyl, Cyclopentyl, Cyclohexyl, Menthyl, Phenyl, o-Toluyl, Naphtyl, o-Methoxyphenyl, o-Ethoxyphenyl, Di-(o-Methoxy)phenyl, p-Triflu- ormethylphenyl, Trimethylsilyl, Triisopropylsilyl, Tri-tert.-butylsilyl, Cyano, Methylsulfonyl, Toluylsulfonyl und Trifluormethylsulfonyl.

[0012] 7. A compound according to one or more of the above points, wherein R.2 is selected from methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, n-pentyl (amyl), 2-pentyl (sec-pentyl), 3-pentyl, 2-methylbutyl, 3-methylbutyl ( / so-pentyl or / so-amyl), 3-methylbut-2-yl, 2-methylbut-2-yl, 2,2-dimethylpropyl (neopentyl), n-hexyl, trifluoromethyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-adamantyl, 2-adamantyl, phenyl, o-, m-, or p-methylphenyl, naphthyl.

[0013] 8. A compound according to one or more of the above points, wherein R3 is selected from methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, n-pentyl (amyl), 2-pentyl (sec-pentyl), 3-pentyl, 2-methylbutyl, 3-methylbutyl ( / so-pentyl or / so-amyl), 3-methylbut-2-yl, 2-methylbut-2-yl, 2,2-dimethylpropyl (neopentyl), n-hexyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl.

[0014] 9. A compound according to one or more of the preceding points, wherein R2 is C1 to C9 alkyl or C4-C9 cycloalkyl and R3 is C1 to C12 alkyl or C4-C8 cycloalkyl, in particular wherein R2 and R3 are C4-C8 cycloalkyl.

[0015] 10. A compound according to item 9, wherein R2 and R3 are cyclohexyl or wherein R2 is tert-butyl and R3 is cyclohexyl.

[0016] 11. A compound according to one or more of the preceding points, wherein X is chlorine or bromine.

[0017] 12. A compound according to one or more of the above points, wherein R1 is selected from the group consisting of methyl, phenyl, o-toluyl, and o-methoxyphenyl. 13. A process for the preparation of compounds according to one or more of points 1 to 12 according to formula I, wherein a ligand of the type R1-C-(P(R2)2)(P(R3)3), wherein R1, R2, and R3 are as defined in the above points, is reacted with a palladium compound of the type PdX2 or L n(PdX2), where X is halogen as defined above, L is a neutral electron donor ligand and n = 1 or 2. 14. A process for the preparation of compounds according to one or more of points 1 to 12 according to formula II, wherein a ligand of the type R1-CH-(P(R2)2)(P(R3)3)(X), where R1, R2 and R3 are as defined in the above points, is reacted with a palladium compound of the type H2PdX4, PdX2 or L n(PdX2), where X is halogen as defined above, L is a neutral electron donor ligand, and n = 1 or 2. 15. Process according to item 13 or 14, wherein the reactants react in a solvent, in particular a polar solvent mixture, in particular containing tetrahydrofuran, dichloromethane, acetone, ethanol, ethyl acetate, or acetonitrile. 16. Process according to any one of the above items 13 to 15, wherein L is acetonitrile, dimethyl sulfoxide, dibenzylideneacetone, or 1,5-cyclooctadiene. 17. Process according to any one of the above items 13 to 16, wherein the palladium compound of type L n(PdX2) is selected from the group consisting of (CH3CN)2PdCl2, (COD)PdCl2, and (DBA)PdCl2. 18. Process according to any one of the above items 13 to 16, wherein a palladium compound of the type PdX2 is used and X is advantageously Cl or Br. 19. Process according to item 14, wherein the palladium compound of the type PdX2 is used in acidic solution, which in particular contains water. 20. Process for carrying out a coupling reaction, which comprises the following

[0018] steps - providing a reaction mixture containing at least one substrate, one coupling partner and at least one metal complex according to one of points 1 to 12; and

[0019] - reacting the substrate with the coupling partner in the presence of the metal complex or its derivative to form a coupling product.

[0020] 21. A process for carrying out a coupling reaction, which comprises the following

[0021] Steps include

[0022] - Providing a metal complex by a process according to at least one of points 13 to 19;

[0023] - providing a reaction mixture containing at least one substrate, one coupling partner and the metal complex; and

[0024] - Reacting the substrate with the coupling partner in the presence of the meta II complex or its derivative to form a coupling product.

[0025] 22. Process according to one or more of items 20 or 21, wherein the substrate is a substituted aromatic compound.

[0026] 23. The process according to item 22, wherein the substituted aromatic compound is an aromatic or heteroaromatic compound.

[0027] 24. The process according to item 22 or 23, wherein the substituted aromatic compound is substituted with a leaving group and / or an unsaturated aliphatic group or a leaving group.

[0028] 25. The process according to item 24, wherein the leaving group is selected from the group consisting of halogen, triflate, tosylate, nosylate, and mesylate, and / or the unsaturated aliphatic group is selected from the group consisting of alkene or alkyne, in particular having 2 to 12, in particular having 2 to 8, carbon atoms. 26. The process according to one or more of the preceding items, wherein the coupling partner is an organometallic compound.

[0029] 27. The process according to item 26, wherein the organometallic compound is selected from the group consisting of organic boron compounds, organolithium compounds, organozinc compounds, organolithium compounds and Grignard compounds.

[0030] 28. A process according to item 26 or 27, wherein the organometallic compound contains at least one aromatic radical.

[0031] 29. A process according to item 26 or 27, wherein the organometallic compound contains at least one unsaturated aliphatic radical.

[0032] 30. A process according to item 26 or 27, wherein the organometallic compound contains at least one saturated aliphatic radical.

[0033] 31. Process according to one or more of items 20 to 30, wherein the coupling reaction can be selected from the group consisting of

[0034] (i) catalytic hydrofunctionalization reactions of alkynes and alkenes;

[0035] (ii) catalytic hydroamination reactions of alkynes and alkenes;

[0036] (iii) catalytic OH addition reactions to alkynes and alkenes;

[0037] (iv) catalytic coupling reactions;

[0038] (v) catalytic Kumada coupling reactions, Murahashi coupling reactions, Negishi coupling reactions or Suzuki coupling reactions, in particular for the preparation of biaryls;

[0039] (vi) catalytic cross-coupling reactions, in particular CN and CO coupling reactions, such as the Hartwig-Buchwald coupling; and / or

[0040] (vii) catalytic Heck coupling reactions, in particular for the preparation of arylated olefins, and Sonogashira coupling reactions, in particular for the preparation of arylated and alkenylated alkynes.

[0041] Detailed description of the invention

[0042] It was surprisingly found that compounds of formula I or II

[0043] where

[0044] X is halogen, R1 is alkyl, perfluoroalkyl, aryl or cycloalkyl, each unsubstituted or substituted, cyano, sulfonyl -SO2-R10 with R10= C1-C5 alkyl, C5-C6 cycloalkyl, C5-C10 aryl, each unsubstituted or substituted with C1 to C4 alkyl or C1 to C4 perfluoroalkyl, silyl -Si(R20R30R40) with R20, R30 and R40, each independently of one another, being C1-C6 alkyl or C5-C10 aryl, each unsubstituted or substituted with C1 to C4 alkyl,

[0045] R2 is alkyl, cycloalkyl, adamantyl or aryl

[0046] R3 represents alkyl, cycloalkyl and aryl, by reacting a ligand of the type R1-C-(P(R2)2)(P(R3)3) or R1-CH-(P(R2)2)(P(R3)3)(X), where R1, R2 and R3 are as defined above, with a palladium compound of the type M2PdX4, PdX2 or L n (PdX2), where X is halogen as defined above, M is hydrogen (H) or sodium (Na), L is a neutral electron donor ligand and n = 1 or 2.

[0047] These new compounds surprisingly exhibit catalytic activity in various coupling reactions.

[0048] The halogen X is, in particular, chlorine, bromine, iodine, or combinations thereof, advantageously chlorine, bromine, or combinations thereof. L is a neutral electron donor ligand. In specific embodiments, L is selected from the group consisting of nitriles, sulfoxides, ketones, dienes, and diamines.

[0049] Compounds of the formula R20-CN, such as acetonitrile (CH3CN), are particularly suitable as nitriles.

[0050] Suitable sulfoxides are compounds of the formula R50-(S=O)-R60 where R50 and R60 each independently represent C1-C6 alkyl, C5-C6 cycloalkyl or C5-C10 aryl, each unsubstituted or substituted by C1 to C4 alkyl, or where R50 and R60 together comprise three to seven carbon atoms and form a four- to eight-membered, in particular five- or six-membered ring with the sulfoxide group, such as, for example, dimethyl sulfoxide (DMSO), dibutyl sulfoxide, diphenyl sulfoxide or tetrahydrothiophene-1-oxide.

[0051] Suitable ketones are compounds of the formula R70-(C=0)-R80, where R70 and R80 each independently represent C1-C6 alkyl, C1-C6 alkenyl, C5-C6 cycloalkyl, C5-C10 aryl or C7 to C12 arylidene, each unsubstituted or substituted with C1 to C4 alkyl, such as dibenzylideneacetone (DBA).

[0052] In principle, all dialkenes that complex palladium, such as 1,5-cyclooctadiene (COD) or norbornadiene (NBD), are suitable as dienes.

[0053] Suitable diamines are generally diamines that complex palladium, such as 1,2-diaminocyclohexane or N,N,N',N'-tetramethylethylenediamine, often referred to as TMEDA. R1 stands for C1 to C9 alkyl, C4-C8 cycloalkyl, cyano, sulfonyl -SO2-R10 with R10 = C1-C5 alkyl, C5-C6 cycloalkyl, C5-C10 aryl, in each case unsubstituted or mono- or polysubstituted with C1 to C4 alkyl, C1 to C4 alkoxy or C1 to C4 perfluoroalkyl, silyl -Si(R20R30R40) with R20, R30 and R40, each independently of one another, standing for C1-C6 alkyl or C5-C10 aryl, in each case unsubstituted or substituted with C1 to C4 alkyl, or R1 stands for C5-C10 aryl, which may be substituted with C1 to C5 alkyl, C1 to C5 alkoxy or C1 to C5 perfluoroalkyl.

[0054] In particular, R1 is selected from methyl, ethyl, propyl, isopropyl, n-butyl, see. -Butyl, tert. -Butyl, n-pentyl, n-pentyl (amyl), 2-pentyl (sec-pentyl), 3-pentyl, 2-methylbutyl, 3-methylbutyl ( / so-pentyl or / so-amyl), 3-methylbut-2-yl, 2-methylbut-2-yl, 2,2-dimethylpropyl (neopentyl), n-hexyl, trifluoromethyl, cyclobutyl, cyclopentyl, cyclohexyl, menthyl, phenyl, o-toluyl, naphtyl, o-methoxyphenyl, o-ethoxyphenyl, di-(o-methoxy)phenyl, p-trifluoromethylphenyl, trimethylsilyl, triisopropylsilyl, tri-tert. -butylsilyl, cyano, methylsulfonyl, toluylsulfonyl and trifluoromethylsulfonyl; or

[0055] R.1 is selected from the group consisting of methyl, phenyl, o-toluyl and o-methoxyphenyl.

[0056] R.2 represents C1 to C9 alkyl, C4-C9 cycloalkyl, adamantyl or C5-C10 aryl, which may be substituted by C1 to C5 alkyl, C1 to C5 alkoxy or C1 to C5 trifluoroalkyl or perfluoroalkyl.

[0057] In particular, R.2 is selected from methyl, ethyl, propyl, isopropyl, n-butyl, see. -Butyl, tert. -Butyl, n-pentyl, n-pentyl (amyl), 2-pentyl (sec-pentyl), 3-pentyl, 2-methylbutyl, 3-methylbutyl ( / so-pentyl or / so-amyl), 3-methylbut-2-yl, 2-methylbut-2-yl, 2,2-dimethylpropyl (neopentyl), n-hexyl, trifluoromethyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-adamantyl, 2-adamantyl, phenyl, o-, m-, or p-methylphenyl, naphthyl; or

[0058] R2 is selected from methyl, isopropyl, tert-butyl, phenyl and cyclohexyl; or

[0059] R2 is selected from tert-butyl, isopropyl and cyclohexyl.

[0060] R3 represents C1-C12 alkyl, C4-C8 cycloalkyl and C5-C10 aryl, which may be substituted by C1 to C5 alkyl, C1 to C5 alkoxy or.

[0061] In particular, R3 is selected from methyl, ethyl, propyl, isopropyl, n-butyl, see. -Butyl, tert. -Butyl, n-pentyl, n-pentyl (amyl), 2-pentyl (sec-pentyl), 3-pentyl, 2-methylbutyl, 3-methylbutyl ( / so-pentyl or / so-amyl), 3-methylbut-2-yl, 2-methylbut-2-yl, 2,2-dimethylpropyl (neopentyl), n-hexyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl; or

[0062] R3 is selected from phenyl and cyclohexyl. In a specific embodiment, R2 is C1 to C9 alkyl or C4-C9 cycloalkyl, such as 1-adamantyl or 2-adamantyl, and R3 is C1 to C12 alkyl or C4-C8 cycloalkyl.

[0063] In a further embodiment, R.2 and R3 are C4-C9 cycloalkyl.

[0064] In each of these embodiments, R1 can be C1 to C9 alkyl, in particular C1 to C4 alkyl, C4-C8 cycloalkyl or C5-C10 aryl, in particular C1-C3 alkyl or C5-C6 aryl, which can be substituted by C1 to C5 alkyl or C1 to C5 alkoxy, in particular C1 to C3 alkyl or C1 to C3 alkoxy. In these cases, X is selected from the group consisting of Cl, Br, I and combinations thereof, in particular Cl, Br and combinations thereof.

[0065] In further specific embodiments, R2 and R3 are cyclohexyl, or R2 is tert-butyl or isopropyl and R3 is cyclohexyl. In each of these embodiments, R1 can be selected from the group consisting of methyl, isopropyl, phenyl, o-tolyl, and o-methoxyphenyl. In these cases, X is selected from the group consisting of Cl, Br, I, and combinations thereof, in particular Cl, Br, and combinations thereof.

[0066] In a further embodiment, R1 is selected from the group consisting of methyl, isopropyl, phenyl, o-tolyl and o-methoxyphenyl, R2 is selected from iso-propyl, tert-butyl, phenyl and cyclohexyl, R3 is selected from phenyl and cyclohexyl and X is selected from the group consisting of Cl, Br, I and combinations thereof.

[0067] Specific combinations are listed in the following Tables 1 to 7.

[0068] Table 1 Table 2 shows the 35 compounds 2.01 to 2.35 of formula I and the 35 compounds 2.36 to 2.70 of formula II, where R1 and R2 have the meanings defined in Table 1, R3 is phenyl and X is CI.

[0069] Table 3 shows the 35 compounds 3.01 to 3.35 of formula I and the 35 compounds 3.36 to 3.70 of formula II, where R1 and R2 have the meanings defined in Table 1, R3 is cyclohexyl and X is CI.

[0070] Table 4 shows the 35 compounds 4.01 to 4.35 of formula I and the 35 compounds 4.36 to 4.70 of formula II, where R1 and R2 have the meanings defined in Table 1, R3 is phenyl and X is Br.

[0071] Table 5 shows the 35 compounds 3.01 to 3.35 of formula I and the 35 compounds 3.36 to 3.70 of formula II, where R1 and R2 have the meanings defined in Table 1, R3 is cyclohexyl and X is Br.

[0072] Table 6 shows the 35 compounds 6.01 to 6.35 of formula I and the 35 compounds 6.36 to 6.70 of formula II, where R1 and R2 have the meanings defined in Table 1, R3 is phenyl and XI.

[0073] Table 7 shows the 35 compounds 7.01 to 7.35 of formula I and the 35 compounds 7.36 to 7.70 of formula II, where R1 and R2 have the meanings defined in Table 1, R3 is cyclohexyl and XI.

[0074] The compounds of formula I can be obtained by a process wherein a ligand of the type R1-C-(P(R2)2)(P(R3)3), where R1, R2 and R3 are as defined above, is reacted with a palladium compound of the type PdX2 or L n (PdX2), where X is halogen as defined above, L is a neutral electron donor ligand and n = 1 or 2.

[0075] The ligand used of the type R1-C-(P(R2)2)(P(R3)3) has the structure of formula III.

[0076] Formula III

[0077] The substituents R1, R2 and R3 are as defined above. In particular, the

[0078] Substituents R1, R2 and R3 are as defined in Table 8 below.

[0079] The palladium compounds of the type PdX2 are the well-known palladium halides PdCl2, PdBr2 and Pdl2, in particular palladium chloride PdCl2.

[0080] Palladium compounds of type L have also proven to be suitable as starting materials for the preparation of compounds of formulas I and II. n (PdX2), where L is a neutral electron donor ligand and n = 1 or 2. If the neutral electron donor ligand is a monodentate ligand, n = 2; for a bidentate ligand, n = 1.

[0081] In specific embodiments, L is selected from the group consisting of acetonitrile (CH3CN), dimethyl sulfoxide (DMSO), dibenzylideneacetone (DBA) and 1,5-cyclooctadiene (COD), norbornadiene (NBD)

[0082] Compounds such as (CH3CN)2PdCl2, (COD)PdCl2 or (DBA)PdCl2 are well suited.

[0083] To prepare the compound of formula II, a ligand of the type R.1-CH- (P(R2)2)(P(R3)3)(X) of formula IV can be used:

[0084] Formula IV

[0085] This can be obtained by acid treatment of a ligand of the type R.1-C-(P(R2)2)(P(R3)3) of formula III. For this purpose, the ligand is suspended in a suitable solvent, such as dichloromethane, and treated with a suitable acid, such as concentrated hydrochloric acid or HBF4.

[0086] The reaction is then carried out with a palladium compound. Palladium compounds of the PdX2 type are the well-known palladium halides PdCl2, PdBr2, and Pd12, in particular palladium chloride PdCl2.

[0087] In strongly acidic, aqueous solutions, these compounds usually occur in the form of the corresponding acid H2PdX4, i.e., in the case of palladium chloride, in the form of the compound H2PdCl4. These acidic solutions, usually produced industrially, contain palladium halides, especially palladium chloride or H2PdX4 or H2PdCl4, and are well-suited as starting materials for the preparation of the compounds of formula II. The order of addition of the starting materials is uncritical in this procedure and leads to the same product in comparable purities and yields.

[0088] When using such an acidic solution of PdX2, in particular PdCl and / or PdBr2, the ligand according to formula III can also be used; a ligand according to formula IV is then not required.

[0089] In a further embodiment, a compound of formula II can be obtained by first preparing a compound of formula I and then treating it with acid. For this purpose, the ligand is suspended in a suitable solvent, such as dichloromethane, and mixed with, for example, concentrated hydrochloric acid. Conversely, a compound of formula II can also be converted into a compound of formula I by treatment with a base. Various alkali metal carbonates, alkali metal alcoholates and HMDS bases (hexamethylenedisilazides) such as sodium or potassium ethanolate, sodium or potassium carbonate and sodium or potassium hexamethyldisilazide (Na-HMDS or K-HMDS) are generally suitable for this purpose; in practice, potassium tert-butoxide and sodium carbonate have proven suitable. The reaction can be carried out in a solvent or mechanochemically.For example, alcohols such as ethanol or isopropanol, ethers such as tetrahydrofuran or aromatic solvents such as toluene can be used as solvents.

[0090] Palladium compounds of type L have also proven to be suitable as starting materials for the preparation of compounds of formulas I and II. n (PdX2), where L is a neutral electron donor ligand and n = 1 or 2. If the neutral electron donor ligand is a monodentate ligand, n = 2; for a bidentate ligand, n = 1.

[0091] In specific embodiments, L is selected from the group consisting of acetonitrile (CH3CN), dimethyl sulfoxide (DMSO), dibenzylideneacetone (DBA) and 1,5-cyclooctadiene (COD).

[0092] Compounds such as (CH3CN)2PdCl2, (COD)PdCl2 or (DBA)PdCl2 are well suited.

[0093] The reaction of the ligand of formula III or formula IV with a palladium compound to form the compounds of formula I or II can be carried out at temperatures from 0°C to 100°C, in particular from 10°C to 50°C, advantageously from 15°C to 30°C, or the respective room temperature. The reaction times are from 2 hours to 72 hours, in particular from 2 hours to 12 hours, or from 2 hours to 8 hours, or from 2 to 4 hours.

[0094] The reaction can be carried out in a solvent. Polar solvents, usually polar, aprotic solvents, are particularly suitable, although in some cases good results have been achieved with ethanol. It may be advantageous to select water-miscible solvents. When using an acidic palladium halide solution, especially acidic palladium chloride solution, a water-soluble solvent is required.

[0095] Tetrahydrofuran, dichloromethane, acetone, ethanol, ethyl acetate and acetonitrile have proven particularly suitable solvents.

[0096] The palladium complexes of formula I and formula II described above can be used in homogeneous catalysis, in particular in coupling reactions, where the coupling reaction can be selected from the group consisting of

[0097] (i) catalytic hydrofunctionalization reactions of alkynes and alkenes;

[0098] (ii) catalytic hydroamination reactions of alkynes and alkenes;

[0099] (iii) catalytic OH addition reactions to alkynes and alkenes;

[0100] (iv) catalytic coupling reactions;

[0101] (v) catalytic Kumada coupling reactions, Murahashi coupling reactions, Negishi coupling reactions or Suzuki coupling reactions, in particular for the preparation of biaryls;

[0102] (vi) catalytic cross-coupling reactions, in particular CN and CO coupling reactions; and / or

[0103] (vii) catalytic Heck coupling reactions, in particular for the preparation of arylated olefins, and Sonogashira coupling reactions, in particular for the preparation of arylated and alkenylated alkynes.

[0104] Furthermore, the patent application relates to a process for carrying out a coupling reaction comprising the steps

[0105] - Providing a reaction mixture containing at least substrate, coupling partner and at least one of the palladium complexes of formula I and formula II; and

[0106] - Reacting the substrate with the coupling partner in the presence of the metal complex or its derivative to form a coupling product.

[0107] In another embodiment, a method for carrying out a coupling reaction is carried out, which comprises the following steps - providing a metal complex according to a method as described above;

[0108] - providing a reaction mixture containing at least one substrate, one coupling partner and the metal complex; and

[0109] - reacting the substrate with the coupling partner in the presence of the metal complex or its derivative to form a coupling product.

[0110] The substrate may be a substituted unsaturated or substituted aromatic compound, in particular the substituted aromatic compound may be an aromatic or heteroaromatic compound.

[0111] This can be substituted, inter alia, with a leaving group or an unsaturated aliphatic group or a leaving group, it being advantageous if the leaving group is selected from the group consisting of halogen, triflate, tosylate, nosylate and mesylate and / or the unsaturated aliphatic group is selected from the group consisting of alkene or alkyne, in particular having 2 to 12, in particular 2 to 8 carbon atoms.

[0112] The coupling partner can comprise an organometallic compound, which can in particular be selected from the group consisting of organic boron compounds, organic lithium compounds, organic zinc compounds, organic lithium compounds and Grignard compounds, wherein advantageously the organometallic compound comprises at least one aromatic radical or wherein the organometallic compound comprises at least one unsaturated aliphatic radical, or wherein the organometallic compound comprises at least one saturated aliphatic radical.

[0113] The subject of the patent application is also such a process, wherein the coupling reaction is selected from the group consisting of

[0114] (i) catalytic hydrofunctionalization reactions of alkynes and alkenes;

[0115] (ii) catalytic hydroamination reactions of alkynes and alkenes;

[0116] (iii) catalytic OH addition reactions to alkynes and alkenes;

[0117] (iv) catalytic coupling reactions; (v) catalytic Kumada coupling reactions, Murahashi coupling reactions, Negishi coupling reactions or Suzuki coupling reactions, in particular for the preparation of biaryls;

[0118] (vi) catalytic cross-coupling reactions, in particular CN and CO coupling reactions; and / or

[0119] (vii) catalytic Heck coupling reactions, in particular for the preparation of arylated olefins, and Sonogashira coupling reactions, in particular for the preparation of arylated and alkenylated alkynes.

[0120] The invention is further illustrated by the following examples. These represent examples of the preparation of palladium complexes, their preparation, and their use in catalysis and are in no way to be understood as limiting the scope of the invention.

[0121] Examples

[0122] Example 1 : Isolation of keYPhos-PdCl2

[0123] Under protective gas, keYPhos (1.00 g, 1.98 mmol, 1.05 eq.) and Pd(CH3CN)2Cl2 (0.49 g, 1.89 mmol, 1.00 eq.) were suspended in dry THF (30 mL). The reddish suspension was stirred for two days under protective gas at room temperature. The solid was filtered under protective gas and washed three times with 10 mL of THF each time. The product was dried in vacuo and obtained as a yellowish solid (1.24 g, 1.81 mmol, 96%).

[0124] X H NMR (400 MHz, CD2Cl2) δ = 1.10 - 1.54 (m, 15H, CH2,PCy3 , H4 + PCy2 , H3 + H4), 1.55 - 2.18 (m, 30H, CH, PCy2, Hl + CH2, PCy3 , H2 + H3 + H4, PCy2 , H2 + H3 + H4+ CH3), 2.31 (d, 3 J HH = 12.0 Hz, 5H, CH2, PCy2, H2 + PCy3, H3,) , 2.47 - 2.83 (m, 8H, CH 2, PCy3, H2 + PCy2, H2 +CH, PCy3, H1 + PCy2, H1) Ppm .1

[0125] 13 C{ 1H} NMR (101 MHz, CD2Cl2) δ = 14.2 (dd, 1 J CP = 41.1 Hz, 1 J CP = 5.1 Hz, P- C--P), 21.2 (CH3), 26.0 (d, 4 J CP = 1.9 Hz, CH 2, pcy2, c4 ), 26.1 (d, 4 J CP = 1.7 Hz, CH 2, PCy3, C4 ), 26.3 (d, 4 J CP = 2.0 Hz, CH 2, PCy3, C4 ), 27.3 - 28.0 (m, CH 2 , PCy2, C3 ), 28.3 (d, 3 J CP = 17.1 Hz, CH 2, PCy2, C3 ), 28.5 (d, 2 J CP = 3.6 Hz, CH 2, pcy3, c3 ), 29.7 (d, 2 J CP = 4.2 Hz, CH 2, PCy3, C2 ), 29.7 (d, 2 J CP = 2.7 Hz, CH 2 pcy2, C2 ), 31.2 (d, 3 J CP = 7.9 Hz, CH 2, PCy2, C2 ), 31.8 (d, 2 J CP = 4.4 Hz, CH 2, PCy2, C2 ), 32.1 (d, 2 J CP = 3.9 Hz, CH2, PCy2, C2 ), 36.3 (d, 1 J CP = 39.2 Hz, CH, PCy3, C1 ), 37.3 (d, 1 J CP = 20.3 Hz, CH, PCy2, C1 ), 39.9 (d, 1 J CP = 15.0 Hz, CH, PCy2, c 1 ) ppm.

[0126] 31 P{ 1 H} NMR (162 MHz, CD2Cl2) δ = 37.1 (PCy3), 48.6 (PCy2) ppm.

[0127] CHNS: Calculated: C: 56.46, H: 8.53. Measured: C: 56.67, H: 8.72. IR: v = 2929 (vs), 2847 (s), 1444 (s), 885 (m), 849 (vs), 838 (vs), 569 (w), 465 (m) cm -1 .

[0128] Example 2 : Alternative synthesis routes of keYPhos-PdCI2

[0129] Scheme 1: Possible synthesis routes of an L-PdCI2 complex.

[0130] In addition to the isolation described in the previous chapter, the following synthesis methods were also successfully carried out using PdC:

[0131] Experiment 1: 0.5 g (2.82 mmol, 1 eq.) of PdCl2 was suspended in 20 ml of dry acetonitrile and stirred overnight at room temperature under protective gas. The solvent was removed under vacuum and transferred to the vial in the glove box.

[0132] 1.6 g (3.10 mmol, 1.1 eq.) of keYPhos were added, and the solids were suspended outside the glove box in 20 ml of dry tetrahydrofuran. The mixture was stirred overnight, and the yellowish solid was filtered and washed twice with 10 ml of THF each. The solid was dried in vacuo.

[0133] 1.7 g (2.52 mmol, 89 %) of a yellow-greenish powder were obtained.

[0134] Experiment 2: With slight yield losses, it is also possible to stir PdCl2 in a 1:1 solvent mixture of acetonitrile and THF overnight. However, additional purification steps are necessary to obtain a pure product.

[0135] Experiment 3 It is also possible to obtain the palladium complex mechanochemically without solvent addition in a mixture of ligand and PdCl2.

[0136] Example 3: Synthesis of trYPhos·PdCl2

[0137] Under protective gas, trYPhos (1.00 g, 2.20 mmol, 1.05 eq.) and (COD)PdCl2 (600 mg, 2.10 mmol, 1.00 eq.) were suspended in dry THF (25 mL); the reaction solution turned dark yellow. After stirring overnight, the solid was allowed to settle, and the solution was removed with a filter cannula. The remaining solid was washed twice with 25 mL of THF and 25 mL of pentane each. The solid was dried under vacuum to obtain the product as a yellow-brownish solid (1.01 g, 1.60 mmol, 76%). IR: v=2927 (m), 2847 (m), 1640 (s), 1581 (s),1332 (m), 1190 (m), 897 (w), 881 (s), 760 (s), 697 (s), 562 (w), 553 (m), 524 (s), 508 (w)cm-l.

[0138] X H NMR (400 MHz, CD2Cl2) δ = 1.22 - 1.45 (m, 9H, CH 2, Cy, H3 + H4 ), 1.61 (d, 3 J HP = 16.7 Hz, 9H, CH 3, tBu ), 1.74 (d, 3 J HP = 15.7 Hz, 9H, CH 3, tBu ), 1.66 - 1.91 (m, 6H, CH 2, cy, H2 + H4 ), 1.90 - 2.01 (m, 6H, CH2, Cy ,H3 ), 2.06 (dd, 3 J HP = 15.0 Hz, 3 J HP = 12.8 Hz, 3H, CH3, Me), 2.31 - 2.54 (m, 6H, CH2,Cy, H 1 + H2), 2.87 (s, 3H, CH2, Cy , H2) .

[0139] 13 C{ 1 H} NMR (101 MHz, CD2Cl2): δ = 20.0 (dd, L / CP = 30.2 Hz, 1 J CP = 12.7 Hz, P-C-P), 24.9 (s, CH3, Me), 25.6 (s, CH 2, pcy3, c4 ), 27.5 (d, 2 J CP = 11.6 Hz, CH2, P c y 3, c2), 27.6 (d, 2 J CP = 11.3 Hz, CH 2, pcy3, C2 ), 29.2 (s, CH 2, pcy3, c3 ), 30.3 (d, 3 J CP = 3.4 Hz, CH 2, pcy3, cs ), 31.4 (d, 2 J CP = 4.2 Hz, CH3, tBu ), 33.2 (d, 2 J CP = 2.4 Hz, CH 3, tBu ), 39.1 - 40.2 (m, CH, PC y3, ci), 40.1 (d, 1 J CP = 2.9 Hz, C, tBu ), 41.3 (d, 1 J CP = 13.1 Hz, C, tBu ) ppm.

[0140] 31 P{ 1H} NMR (162 MHz, CD2Cl2): δ = 38.7 (d, 2 J PP = 4.7 Hz, PCy2), 83.2 (d, 2 J PP = 4.7 Hz, PCy3), ppm.

[0141] CHNS: Calculated: C: 53.33, H: 8.57. Measured: C: 53.24, H: 8.73. IR: v = 2933 (s), 2850 (m), 1489 (w), 1447 (m), 1396 (m), 1370 (m), 1325 (w), 1296 (w), 1172 (s), 1124 (w), 1004 (m), 918 (f), 893 (m), 849 (m), 814 (vs), 802 (vs), 747 (f), 619 (m), 596 (f), 541 (m), 508 (m) cm -1 .

[0142] Example 4: Synthesis of pinkYPhos-PdCl2

[0143] Under protective gas, pinkYPhos (1.0 g, 1.72 mmol, 1.1 eq.) and Pd(CH3CN)2Cl2 (0.4 g, 1.56 mmol, 1.0 eq.) were suspended in THF (30 mL), and the orange suspension was stirred for 72 h. The resulting yellow suspension was filtered through a protective gas frit and washed twice with 20 mL of THF each time. The solid was dried in vacuo, and the product was obtained as a yellowish solid (0.9 g, 1.18 mmol, 76%).

[0144] X H NMR (400 MHz, CD2Cl2) δ = 0.46 - 2.41 (m, 50H, CH + CH 2, PCy3 + pcy2 ), 2.48 (s, 3H, CH3), 2.55 - 3.87 (m, 5H, CH + CH 2, Pcy3 + pcy2 ), 7.00 - 7.14 (m, 1H), 7.14 - 7.32 (m, 2H), 8.62 - 9.27 (m, 1H, CH, Ar, ortho ) ppm. 31 P{ 1 H} NMR (162 MHz, CD2Cl2): δ = 38.2 (d, 2 J PP = 5.7 Hz, Cy2), 57.4 (Cy3) (isomer: 40.0 (PCy3), 51.8 (PCy3)). Due to isomers, the signals in 13 C{ 1 H}- NMR could not be evaluated.

[0145] CHNS: Calculated: C: 60.03, H: 8.20. Measured: C: 60.04, H: 8.27.

[0146] IR: v = 2932 (s), 2917 (vs), 2853 (m), 1445 (m), 1174 (w), 1005 (w), 964 (w), 933 (w), 893 (w), 865 (w), 854 (w), 773 (w), 756 (w), 732 (w), 550 (w), 530 8w), 516 (w) cm -1 .

[0147] Example 5: Synthesis of oxYPhos-PdCl2 Under protective gas, oxYPhos (550 mg, 0.92 mmol, 1.0 eq.) was suspended with Pd(CH3CN)2Cl2 (239 mg, 0.92 mmol, 1.0 eq.) in 10 mL of dry THF. The yellowish suspension was stirred overnight. The solid was filtered and washed with 10 mL of THF. The solid was dried in vacuo, yielding the product as a dark yellow solid (477 mg, 0.62 mmol, 67%).

[0148] X H NMR (400 MHz, CD2Cl2) δ = 0.77 - 3.48 (m, 55H, CH, PCy3 + PCy2 + CH2, PCy3 + pc y2 ), 3.81 (s, 3H, OCH3), 6.76 (d, J = 8.2 Hz, 1H, CH, Ar , meta), 7.01 (t, J = 7.6 Hz, 1H, CH, Ar, meta), 7.32 (td, J = 7.8, 1.8 Hz, 1H, CH, Ar, para), 8.86 (d, 3 J HH = 7.7 Hz, 1H, CH, Ar, ortho) ppm.

[0149] 13 C{ 1 H} NMR (101 MHz, CD2Cl2) : δ = 25.8 - 26.1 (m, CH, CH 2, pcy3, c4 ), 26.1 -

[0150] 26.3 (m, CH 2, pcy3, c3 ), 27.4 - 28.0 (m, CH2, PCy3, C2 + C3 + PCy2, C3), 28.1 (d, 3 J CP= 16.1 Hz, CH 2, PCy2, C3 ), 29.1 — 31.5 (vbr, CH 2, pcy3, c2 )30.6 (CH 2, pcy2, c2 ), 30.8 (d, 2 J CP = 7.5 Hz, CH 2, PCy2, C2 ), 31.2 (d, 2 J CP = 2.4 Hz, CH 2, PCy2, C2 ), 32.1 (CH 2, PCy2, C2 ), 36.8 - 39.2 (vbr, CH , PCy2, C 1 ), 39.5 (d, 1 J PP = 15.5 Hz, CH , PCy2, C 1 ), 39.6 (d, 1 J PP = 21.5 Hz, CH , PCy2, C1 ), 55.5 (s, OCH3), 109.9 (CH, Ar, meta ), 122.2 (CH, Ar, ipso),

[0151] 122.3 (CH, Ar, meta ), 130.7 (CH, Ar, pa ra ), 142.5 (CH, Ar, ortho ), 158.5 (CH, Ar, ortho) ppm.

[0152] 31 P{ 1 H} NMR (162 MHz, CD2Cl2): δ = 36.4 (d, 2 J PP = 7.6 Hz, PCy3), 54.1 (PCy2) ppm.

[0153] IR: v = 2980 (m), 2971 (m), 2945 (m), 2915 (vs), 2868 (w), 2848 (s), 1478 (w), 1467 (w), 1443 (m), 1429 (w), 1238 (vs), 1210 (w), 1171 (w), 1115 (w), 1034 (w), 1007 (m), 979 (s), 900 (s), 884 (m), 847 (m), 745 (s), 736 (m), 542 (m), 516 (w) cm -1 .

[0154] Example 6 : Isolation of joYPhos-PdCl2

[0155] Under protective gas, iYPhos (1.00 g, 1.76 mmol, 1.10 eq.) and Pd(CH3CN)2Cl2 (0.42 g, 1.60 mmol, 1.00 eq.) were suspended in dry THF (50 ml). The orange suspension was stirred for 48 h, the crude product was filtered through a protective gas frit and washed with 40 ml of THF. The yellow solid was dried in vacuo, and the product was isolated as a yellowish powder (1.04 g, 1.39 mmol, 87%).

[0156] 1 H NMR (400 MHz, CD2Cl2) δ = 0.60 - 2.88 (m, 55H, CH,PCy3 + PCy2 + CH2, PCy3 + pcy2 ), 7.12 (d, 3 J HH = 7.9 Hz, 1H, CH, ortho ), 7.22 (t, 3 JHH = 7.5 Hz, 1H, CH, meta ), 7.32 (t, 3 J HH = 7.4 Hz, 1H, CH, pa ra ), 7.40 (t, 3 J HH = 7.7 Hz, 1H, CH, meta ), 8.91 (d, 3 J HH = 7.7 Hz, 1H, CH, ortho ) ppm.

[0157] 13 C{ 1 H} NMR (101 MHz, CD2Cl2): δ = 26.1 (s, CH2, PCy2, C4 + PCy3, C4), 27.4 (d, 3 J CP = 11.6 Hz, CH 2, PCy3, C3 ), 27.7 (d, 3 J CP = 12.1 Hz, CH 2, PCy2, C3 ), 28.0 (S, CH2, PCy2, C3 ), 28.1 (d, 3 J CP = 23.6 Hz, CH2, PCy2, C3 ), 28.5 (d, 2 J CP = 16.5 Hz, CH2, PCy2, C2), 30.8 (s, CH2, PCy2, C3 ), 32.0 (d, 2 J CP = 8.0 Hz, CH2, pcy2, c2 ), 32.3 - 32.1 (m, CH2, PCy2, C2 ), 39.8 (d, 1 J CP = 21.8 Hz, CH, PCy2, C1 ), 41.0 (d, 1 J CP = 13.0 Hz, CH, PCy2, Cl), 127.7 (s, CH, Ph, meta ), 129.0 (s, CH, Ph , para ), 130.3 (s, CH,Ph , meta ), 132.4 (s, CH, Ph, ortho ), 133.9 (S, CH, ph, ipso ), 141.2 (t, 3 JCP = 5.2 Hz, CH, ph, ortho ) -

[0158] 31 P{ 1 H} NMR (162 MHz, CD2Cl2): δ = 35.3 (d, 2 J PP = 3.9 Hz, PCy3), 53.7 (d, 2 J PP = 4.0 Hz, PCy2) ppm.

[0159] CHNS: Calculated: C: 59.72, H: 8.13. Measured: C: 60.08, H: 8.10.

[0160] IR: v = 2918 (vs), 2851 (s), 1446 (s), 1174 (m), 1000 (s), 950 (m), 918 (m), 892 (w), 857 8m), 851 (m), 707 (s), 538 (s), 529 (s), 512 (m) cm' 1 .

[0161] Example 7: Isolation of joYPhos-PdBrz joYPhos (500 mg, 0.88 mmol, 1.1 eq.) and (cod)Pdßr2 (300 mg, 0.80 mmol,

[0162] 1.0 eq.) was suspended in THF (25 ml). The orange suspension was stirred overnight, and the crude product was filtered through a Schlenk frit. The solid was washed twice with 10 ml of THF and dried in vacuo. The product was obtained as a yellowish powder (550 mg, 0.66 mmol, 82%).

[0163] X H NMR (400 MHz, CD2Cl2) δ = 0.56 - 3.16 (m, 55H, CH, PCy3 + PCy2 + CH2, PCy3 + pcy2), 7.15 (d, 3 J HH = 7.9 Hz, 1H, CH, ortho), 7.23 (t, 3 J HH = 7.5 Hz, 1H, CH, meta ), 7.33 (t, 3 J HH = 7.4 Hz, 1H, CH, para ), 7.40 (t, 3 J HH = 7.7 Hz, 1H, CH, meta ), 8.96 (d, 3 J HH = 7.7 Hz, 1H, CH, ortho ) ppm.

[0164] 13 C{ 1 H} NMR (101 MHz, CD2Cl2) : δ = 25.8 - 26.1 (m, CH2, PCy2, C4 + PCy3, C4), 27.1 - 27.4 (m, CH 2, PCy3, C3 ), 27.6 (d, 3 J CP = 12.3 Hz, CH 2, pcy2, c3 ), 27.9 (d,3 J CP =

[0165] 4.9 Hz, CH 2, pcy2, c3 ), 28.0 ( CH 2, PCy2, C3 ), 28.3 (d, 2 J CP = 16.4 Hz, CH 2, PCy2, C3 ),

[0166] 30.9 (CH 2, pcy2, C2 ), 32.08 (d, 2 J CP = 13.6 Hz, CH 2, PCy2, C2 ), 32.09 (CH 2, PCy2, C2 ), 32.4 (d, 2 J CP = 2.9 Hz, CH 2, PCy2, C2) , 40.0 (d, 1 J CP = 21.7 Hz, CH, PCy2, C1 ), 41.3 (d, 1 J CP = 13.0 Hz, CH, Pcy2, C1) ,2127.6 (t, 4 J CP = 2.1 Hz, CH, Ph, meta ), 128.9 (t, 5 J CP = 2.5 Hz, CH, Ph, para ), 130.2 (CH, Ph, meta ), 132.5 (t, 3 J C P = 3.8 HZ, CH, Ph, ortho ), 133.5 (CH, Ph, ipso), 141.7 (t, 3 J CP = 5.1 Hz, CH, Ph, ortho ).

[0167] 31 P{ 1 H} NMR (162 MHz, CD2Cl2): δ = 35.2 (d, 2 J PP = 3.9 Hz, PCy3), 59.2 (d, 2 J PP = 3.9 Hz, PCy2) ppm.

[0168] Example 8: Isolation of joYPhos-HPdCH joYPhos'HPdCI3 can be synthesized from both joYPhos-H and joYPhos-PdCI2:

[0169] Scheme 2: Possible synthesis routes of joYPhos-HPdCI3.

[0170] The synthesis route starting from joyPhos-PdCI2 is described below.

[0171] joYPhos-PdCl2 (0.2 g, 0.27 mmol, 1.0 eq.) was suspended in dry dichloromethane (10 mL) and treated with concentrated hydrochloric acid (0.1 mL, 37% in water, 1.35 mmol, 5.0 eq.). The orange solution was stirred overnight, and the solvent was removed in vacuo. Dry THF (20 mL) was added, and the mixture was stirred for one hour. The precipitated solid was filtered through a Schlenk frit and washed with dry THF (10 mL). The solid was dried in vacuo, and the product was obtained as a yellowish powder (130 mg, 0.17 mmol, 62%).

[0172] 1 H NMR (400 MHz, CD2Cl2) δ = -0.12 - 0.24 (m, 1H, CH 2, PCy2, H3 ), 0.96 - 2.01 (m, 45H, CH 2, pcy3 + pcy2 ), 2.03 - 2.32 (m, 7H, CH2, pcy3, H2 + pcy2, H2), 2.33 - 2.52 (m, 1H, CH, PCy2, H 1 ) , 2.63 - 2.75 (m, 1H, CH, PCy2, H 1 ), 2.75 - 2.84 (m, 1H, CH2, PCy2, H2 ), 3.06 - 3.17 (m, 1H, CH2, PCy2, H2 ), 3.21 - 4.67 (m, 2H, CH, PCy3, H 1 ), 4.39 (dd, 1H, 1 J CP = 15.6 Hz, 3 J CP = 12.3 Hz, CH, PCy 3, HI), 7.22 (d, 1H, 4 J CP = 7.7 Hz, CH, ortho), 7.37 (t, 1H, 5 J CP = 7.6 Hz, CH, meta ), 7.45 (t, 1H, 6 J CP = 7.5 HZ, CH, pa ra ), 7.52 (t, 1H, 5 J CP = 7.6 Hz, CH, meta ), 8.55 (d, 1H, 4 J CP = 7.9 Hz, CH, ortho ) ppm. 13 C{ 1 H} NMR (101 MHz, CD2Cl2): δ = 26.3 (d, J=1.8 Hz, CH2, pc y 3, c4), 26.6 - 27.1 (m, CH2,PCy2, C4 + PCy3, C3), 27.3 (d, 3 J CP= 11.8 Hz, CH2, pcy3, C3 ), 28.1 (d, 3 J CP = 15.6 Hz, CH2, PCy2, C3 ), 28.26 (d, 3 J CP = 2.3 Hz, CH2, pcy2, c3 ), 28.34 (d, 3 J CP = 1-9 Hz, CH2, PCy2, C3 ), 28.9 (d, 3 J CP = 16.2 Hz, CH2, PCy2, C3 ), 30.5 (d, 2 J CP = 8.7 Hz, CH2, PCy2, C2 ), 30.8 (d, 2 J CP = 4.9 Hz, CH 2, PCy3, C2 ), 31.4 (CH2, pcy3, C2 ), 32.0 (d, 2 J CP = 8.7 Hz, CH2, PCy2, C2 ), 32.8 (d, 2 J CP = 3.8 Hz, CH2, pcy2, C2 ), 34.3 (d, 1 J CP = 6.2 Hz, CH2, PCy2, C2 ), 34.4 - 35.1 (m, CH, PCy3, C1 ), 38.4 (d, 1 J CP = 16.5 Hz, CH, PCy2, C1 ), 41.1 (dd, 1 J CP = 17.7 Hz, 3 J CP = 2.3 Hz, CH, PCy2, C1 ), 127.4 (dd, 2 J CP = 5.5 Hz, 4 J CP = 3.8 Hz, CH, Ph , ipso ), 129.1 (CH, Ph , meta ), 129.5 (d,4 J CP = 2.5 Hz, CH, Ph, meta ), 130.2 (t, 5 J CP = 1.9 Hz, CH, Ph, para ), 132.3 (dd, 3 J CP = 6.7 Hz, 5 J CP = 4.1 Hz, CH, Ph , ortho), 134.0 (d, 3 J CP = 2.7 Hz, CH, ph, ortho ppm.

[0173] 31 P{ 1 H} NMR (162 MHz, CD2Cl2): δ = 31.4 (d, 2 J PP = 14.5 Hz, PCy3), 38.5 (d, 2 JPP = 14.5 Hz, PC 2) ppm.

[0174] By adding base (KOtBu), the complex can be converted into the corresponding joYPhos-PdCh complex.

[0175] Examples of the synthesis of compounds of formula II from H2PdX4, here: acidic, aqueous palladium chloride solution / H2PdCl4

[0176] Example 8a: ioYPhos HPdCI3: Palladium chloride solution

[0177] 0.47 g of palladium chloride solution (20% Pd; 0.88 mmol; 1.0 eq) was placed in 15 mL of degassed acetone, and the container was rinsed with 5 mL of acetone.

[0178] 0.50 g of joYPhos (0.88 mmol; 1.0 eq) was added, and the container was rinsed with 5 mL of acetone. After addition, the reaction mixture became lighter in color. The orange suspension was stirred at room temperature for 4 hours. The light orange suspension was filtered, and the light yellow solid was washed with 10 mL of acetone. The product was dried in vacuo at 40 °C. 0.57 g of yellow, amorphous product was obtained (0.73 mmol; 83%). Analytical data correspond to the product from the two-step synthesis.

[0179] Example 8b: Ligand presented

[0180] 0.50 g of joYPhos (0.88 mmol; 1.0 eq) was initially dissolved in 15 mL of degassed acetone, and the container was rinsed with 5 mL of acetone. 0.47 g of palladium chloride solution (20% Pd; 0.88 mmol; 1.0 eq) was added dropwise, and the container was rinsed with 5 mL of acetone. The orange suspension was stirred at room temperature for 4 hours. The light orange suspension was filtered, and the light yellow solid was washed with 10 mL of acetone. The product was dried under vacuum at 40 °C. 0.60 g of yellow, amorphous product was obtained (0.77 mmol; 87%). Analytical data correspond to the product from the two-step synthesis.

[0181] Example I 8c: Solvent ethanol instead of acetone

[0182] 0.47 g of palladium chloride solution (20% Pd; 0.88 mmol; 1.0 eq) was placed in 15 mL of degassed ethanol, and the container was rinsed with 5 mL of ethanol.

[0183] 0.50 g of joYPhos (0.88 mmol; 1.0 eq) was added, and the container was rinsed with 5 mL of ethanol. After addition, the reaction mixture became lighter in color. The orange suspension was stirred at room temperature for 4 hours. The light orange suspension was filtered, and the light yellow solid was washed with 10 mL of ethanol. The product was dried in vacuo at 40 °C. 0.61 g of yellow, amorphous product was obtained (0.78 mmol; 89%). Analytical data correspond to the product from the two-step synthesis.

[0184] Example 8d: trYPhos HPdCI3: Palladium chloride solution

[0185] 0.59 g of palladium chloride solution (20% Pd; 1.10 mmol; 1.0 eq) was placed in 15 mL of degassed acetone, and the container was rinsed with 5 mL of acetone.

[0186] 0.50 g of trYPhos (1.10 mmol; 1.0 eq) was added, and the container was rinsed with 5 mL of acetone. After addition, the reaction mixture became lighter in color. The orange-red suspension was stirred at room temperature for 2 hours. The suspension was filtered, and the orange solid was washed with 10 mL of acetone. The product was dried in vacuo at 40 °C. 0.42 g of light red, amorphous product was obtained (0.63 mmol; 57.29%). Analytical data correspond to the product from the two-step synthesis.

[0187] Example 8e: Ligand initially introduced: 0.50 g of trYPhos (1.10 mmol; 1.0 eq) was initially introduced into 10 mL of degassed acetone, and the container was rinsed with 5 mL of acetone. 0.59 g of palladium chloride solution (20% Pd; 1.10 mmol; 1.0 eq) was filled into a dropping funnel with 5 mL of acetone and slowly added dropwise. The dropping funnel was rinsed with 5 mL of acetone. After addition, the reaction mixture became lighter in color. The orange-red suspension was stirred at room temperature for 2 hours. The suspension was filtered, and the orange solid was washed with 10 mL of acetone. The product was dried under vacuum at 40 °C. 0.42 g of bright red, amorphous product was obtained (0.63 mmol; 57.29%). Analytical data correspond to the product from the two-step synthesis.

[0188] Example 8f keYPhos HPdCI3: Palladium chloride solution

[0189] MIE21040:

[0190] 0.59 g of palladium chloride solution (20% Pd; 1.10 mmol; 1.0 eq) was placed in 15 mL of degassed acetone, and the container was rinsed with 5 mL of acetone.

[0191] 0.50 g of trYPhos (1.10 mmol; 1.0 eq) was added, and the container was rinsed with 5 mL of acetone. After addition, the reaction mixture became lighter in color. The orange suspension was stirred at room temperature for 2 hours. The suspension was filtered, and the light orange solid was washed with 10 mL of acetone. The product was dried in vacuo at 40 °C. 0.54 g of light orange, amorphous product was obtained (0.75 mmol; 76%). Analytical data correspond to the product from the two-step synthesis. Application in catalysis

[0192] Buchwald-Hartwig Amination - General Implementation

[0193] R'NH20.5 mol % [Pd] + or

[0194] KOffiu

[0195] RR"NH RT 1 hour

[0196] In the glove box, a 6 mL vial was filled with the precatalyst (0.005 mmol, 0.005 eq.) and potassium tert-butoxide (1.5 mmol, 1.5 eq.) and sealed with a septum cap. The vial was removed from the glove box, and another vial was prepared with a standard solution. For this purpose, 1.0 mmol (1.0 eq.) of a haloaryl was filled with 1.1 mmol (1.1 eq.) of a primary or secondary amine and the GC standard tetradecane (1.0 mmol, 1.0 eq.) and made up to a volume of 3 mL with dry THF. [For L-PdCl2 complexes only: 0.61 μl (0.005 mmol, 0.005 eq.) of 1,5-cyclooctadiene in 1 mL of dry THF was first added to the precatalyst vessel, and the mixture was stirred for 5 minutes.] The standard solution was added to the catalyst mixture, and the catalytic reaction was stirred for 1 hour at room temperature.]

[0197] After one hour, the reaction was quenched with a saturated NaCl solution, a drop of the organic phase was rinsed with ethyl acetate through a filter pipette filled with silica gel, and a GC-FID spectrum of the sample was recorded. The product signal was compared with the standard, taking into account a response factor.

[0198] The isolated YPhos-PdX2 complexes (X = Cl, Br, or I) were used as precatalysts. These were compared with other precatalysts. For this purpose, the respective YPhos ligand was used with Pdzdbas-dba, [Pd(allyl)Cl]2, [Pd(cinnamyl)Cl]2, or [Pd(tert-butylindenyl)Cl]2 in a 1:1 ratio.

[0199]

[0200] (1): Addition of 0.5 mol % cyclooctadiene

[0201] Scheme 3: Comparison of different catalysts in the Buchwald-Hartwig amination of 4-chlorotoluene and piperidine.

[0202] Example 10:

[0203] Scheme 4: Comparison of different catalysts in the Buchwald-Hartwig amination of 2-chlorotoluene and n-butylamine; (top) 0.5 mol% loading, comparison of different YPhos ligands and Pd sources;

[0204] Example 11: Comparison of joYPhos with different Pd sources at 0.1 and 0.05 mol%.

[0205] Results without addition of cyclooctadiene

[0206] In our experiments we found that the addition of 1.5-

[0207] Cyclooctadiene in equimolar amounts to the precatalyst ensures better reaction conversions. While in the known allyl, cinnamyl, indenyl or dibenzylideneacetone complexes a diene is present during the reaction, in the

[0208] In the case of the complexes mentioned here, no diene is present in the catalysis. The good coordination properties of 1,5-cyclooctadiene result in better catalytic results. All results below are shown without the addition of 1,5-

[0209] Cyclooctadiene listed. a-Arylation of ketones - General procedure

[0210] In the glove box, a 6 mL vial was filled with the precatalyst (0.01 mmol, 0.01 eq.) and sealed with a septum cap. Another vial in the glove box was filled with potassium tert-butoxide (1.5 mmol, 1.5 eq.), and both vials were removed from the glove box. The base was first dissolved in 4 mL of dry THF, to which 1.1 mmol (1.1 eq.) of cyclohexanone or ethyl phenyl ketone was added, and the mixture was stirred for 30 minutes. Tetradecane (1.0 mmol, 1.0 eq.) and the corresponding haloaryl (1.0 mmol, 1.0 eq.) were added to the mixture in the following order. The solution was transferred to the dry precatalyst in the other vessel and the catalytic reaction was carried out under stirring for 20 hours (cyclohexanone: 60 °C, ethyl phenyl ketone: room temperature).

[0211] After one hour, the reaction was quenched with a saturated NaCl solution, a drop of the organic phase was rinsed with ethyl acetate through a filter pipette filled with silica gel, and a GC-FID spectrum of the sample was recorded. The product signal was compared with the standard, taking into account a response factor.

[0212] Example 12: Reagents: 4-chlorotoluene + cyclohexanone

[0213] &

[0214] L + Pd2dba3- dba 0% 1% 5% 16%

[0215] Implementation at

[0216] Room temperature: L-Pd(allyl)Cl 7% 0% 1% 22%

[0217] L-Pd(cinnamyl)CI 0% 0% 18% 36%

[0218] L-Pd(l-tBu-indenyl)CI 8% 14% 52%

[0219] L-PdCl 24% 3% 18% 50%

[0220] L-HPdCI310% 0% 7% 6%

[0221] Implementation at

[0222] 60 °C:

[0223] L + Pd2dba3- dba 51% 3% 52% 43%

[0224] L-Pd(allyl)Cl 80% 42% 64% 79%

[0225] L-Pd(cinnamyl)CI 56% 3% 63% 68%

[0226] L-Pd(l-tBu-indenyl)CI 69% 50% 56%

[0227] L-PdCl277% 6% 36% 76%

[0228] L-HPdCI353% 4% 25% 11%

[0229] Scheme 5: Comparison of different catalysts in the o-arylation of 4-

[0230] Chlorotoluene and cyclohexanone at room temperature and 60 °C.

[0231] Example 13:

[0232] Scheme 6: Comparison of different catalysts in the o-arylation of 1,3-benzodioxole and ethyl phenyl ketone at room temperature.

[0233] Example 14:

[0234] Note: The addition of 1,5-cyclooctadiene resulted in a deterioration of the results, therefore the addition was omitted.

[0235] Feringa coupling - general implementation

[0236] A 6 ml vial in the glove box was filled with the precatalyst (0.03 mmol, 0.03 eq.) and sealed with a septum cap. The vial was removed from the glove box, and a mixture of haloaryl (1.00 mmol, 1.00 eq.) and tetradecane (1.00 mmol, 1.00 eq.) in 1 ml of dry toluene was added. The organolithium compound (1.2 mmol, diluted with dry toluene to 3.3 ml with a concentration of 0.36 M, 1.2 eq.) was added to the reaction solution via a syringe pump over one hour. The black suspension was quenched with a saturated NaCl solution, a drop of the organic phase was rinsed with ethyl acetate through a filter pipette filled with silica gel, and a GC-FID spectrum of the sample was recorded. The product signal was compared with the standard, taking into account a response factor.

[0237] Example 15:

[0238] P 5 P 5 vO

[0239] 73% 95% 74% 89%

[0240] L + Pd2dba3- dba (88%) (81%) (89%) (87%)

[0241] 50% 64% 49% 98%

[0242] L-Pd(allyl)CI (79%) (73%) (83%) (91%) Throughput

[0243] 40% 72% 81% 99% (product share)

[0244] L-Pd(cinnamyl)Cl (82%) (72%) (88%) (92%)

[0245] 42% 92% 93%

[0246] L-Pd(l-tBu-indenyl)CI (78%) (88%) (87%)

[0247] 38% 55% 84% 91%

[0248] L-PdCl2(83%) (69%) (88%) (87%)

[0249] Scheme 7: Comparison of different catalysts in the alkylation of 4-chloroanisole with n-butyllithium.

[0250] Example 16:

[0251]

[0252] Scheme 8: Comparison of different catalysts in the alkylation of 4-chloroanisole with sec-butyllithium.

[0253] Example 17: Kumada coupling - general implementation

[0254] A 6 ml vial in the glove box was filled with the precatalyst (0.03 mmol, 0.03 eq.) and sealed with a septum cap. The vial was removed from the glove box, and a mixture of haloaryl (1.00 mmol, 1.00 eq.) and tetradecane (1.00 mmol, 1.00 eq.) in 1 ml of dry toluene was added to it. The Grignard reagent (1.2 mmol, diluted with dry toluene to 3.3 ml at a concentration of 0.36 M, 1.2 eq.) was added to the reaction solution via a syringe pump over the course of one hour. The black suspension was quenched with a saturated NaCl solution, a drop of the organic phase was rinsed with ethyl acetate through a filter pipette filled with silica gel, and a GC-FID spectrum of the sample was recorded. The product signal was compared with the standard by including a response factor. L+ Pd2dba3- dba >99% >99% 46% 99% 97%

[0255] L-Pd(a I lyl)CI 97% 25% 11% 80% 85%

[0256] L-Pd(cinnamyl)CI 96% 96% 42% 95% >99%

[0257] L-Pd(l-tBu-indenyl)CI >99% >99% 93% 92%

[0258] L-PdCl2>99% >99% 42% 94% 96%

[0259] Scheme 9: Comparison of different catalysts in the alkylation of 4-chlorofluorobenzene with cyclohexylmagnesium chloride. 3 mol% loading, comparison of different YPhos ligands and Pd sources; comparison of keYPhos with different Pd sources at 0.5 mol% loading.

[0260] Example 19:

[0261]

[0262] Scheme 10: Comparison of different catalysts in the alkylation of ethyl 4-chlorobenzoate with / so-propylmagnesium chloride.

Claims

Patent claims 1. A compound of formula I or II Formula I Formula II where X stands for halogen, R1 for alkyl, perfluoroalkyl, aryl or cycloalkyl, each substituted or unsubstituted, cyano, sulfonyl -SO2- R10 with R10 = C1-C5 alkyl, C5-C6 cycloalkyl, C5-C10 aryl, each unsubstituted or substituted with C1 to C4 alkyl or C1 to C4 perfluoroalkyl, silyl -Si(R20R30R40) with R20, R30 and R40, each independently standing for C1-C6 alkyl or C5-C10 aryl, each unsubstituted or substituted with C1 to C4 alkyl, R2 stands for alkyl or cycloalkyl, adamantyl and aryl. R3 stands for alkyl, cycloalkyl and aryl.

2. A compound according to claim 1, wherein X represents chlorine, bromine, iodine or combinations thereof.

3. A compound according to one or more of the preceding claims, wherein R1 represents C1 to C9 alkyl, C4-C8 cycloalkyl, cyano, sulfonyl - SO2-R10 with R10 = C1-C5 alkyl, C5-C6 cycloalkyl, C5-C10 aryl, each unsubstituted or substituted with C1 to C4 alkyl, C1 to C4 alkoxy or C1 to C4 perfluoroalkyl, silyl-Si(R20R30R40) with R20, R30 and R40, each independently representing C1-C6 alkyl or C5-C10 aryl, each unsubstituted or substituted with C1 to C4 alkyl, or R1 representing C5-C10 aryl, which may be substituted once or several times with C1 to C5 alkyl, C1 to C5 alkoxy or C1 to C5 perfluoroalkyl.

4. A compound according to one or more of the preceding claims, wherein R2 represents C1 to C9 alkyl, C4-C8 cycloalkyl, adamantyl or C5-C10 aryl, which may be substituted with C1 to C5 alkyl, C1 to C5 alkoxy or C1 to C5 perfluoroalkyl.

5. A compound according to one or more of the preceding claims, wherein R3 represents C1-C12 alkyl, adamantyl, C4-C8 cycloalkyl and C5-C10 aryl, which may be substituted with C1 to C5 alkyl, C1 to C5 alkoxy or 6. A compound according to one or more of the preceding claims, wherein R1 is selected from methyl, ethyl, propyl, isopropyl, n-butyl, n-butyl, n-butyl, tert-butyl. -Butyl, n-pentyl, n-pentyl (amyl), 2-pentyl (sec-pentyl), 3-pentyl, 2-methylbutyl, 3-methylbutyl ( / so-pentyl or iso-amyl), 3-methylbut-2-yl, 2-methylbut-2-yl, 2,2-dimethylpropyl (neopentyl), n-hexyl, trifluoromethyl, cyclobutyl, cyclopentyl, cyclohexyl, menthyl, phenyl, o-toluyl, naphtyl, o-methoxyphenyl, o-ethoxyphenyl, di-(o-methoxy)phenyl, p-trifluoromethylphenyl, trimethylsilyl, triisopropylsilyl, tri-tert-butylsilyl, cyano, methylsulfonyl, toluylsulfonyl and trifluoromethylsulfonyl.

7. A compound according to one or more of the preceding claims, wherein R2 is selected from methyl, ethyl, propyl, isopropyl, n-butyl, se-butyl, tert-butyl, n-pentyl, n-pentyl (amyl), 2-pentyl (sec-pentyl), 3-pentyl, 2-methylbutyl, 3-methylbutyl (se-pentyl or iso-amyl), 3-methylbut-2-yl, 2-methylbut-2-yl, 2,2-dimethylpropyl (neopentyl), n-hexyl, trifluoromethyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-adamantyl, 2-adamantyl, phenyl, o-, m-, or p-methylphenyl, naphthyl.

8. A compound according to one or more of the preceding claims, wherein R.3 is selected from methyl, ethyl, propyl, isopropyl, n-butyl, se-butyl, tert-butyl, n-pentyl, n-pentyl (amyl), 2-pentyl (sec-pentyl), 3-pentyl, 2-methylbutyl, 3-methylbutyl (se-pentyl or iso-amyl), 3-methylbut-2-yl, 2-methylbut-2-yl, 2,2-dimethylpropyl (neopentyl), n-hexyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl.

9. A compound according to one or more of the preceding claims, wherein R.2 represents C1 to C9 alkyl or C4-C8 cycloalkyl and R.3 represents C1 to C12 alkyl or C4-C8 cycloalkyl, in particular wherein R2 and R3 are C4-C8 cycloalkyl.

10. A compound according to claim 9, wherein R2 and R3 are cyclohexyl or wherein R2 is isopropyl or tert-butyl and R3 is cyclohexyl.

11. A compound according to one or more of the preceding claims, wherein R1 is selected from the group consisting of methyl, phenyl, o-tolyl and o-methoxyphenyl.

12. A method for producing compounds according to one or more of claims 1 to 11 of formula I, wherein a ligand of type R1-C-(P(R2)2)(P(R3)3), wherein R1, R2 and R3 are defined in the preceding claims, is reacted with a palladium compound of type PdX2 or L n (PdX2), where X is a halogen as defined above, L is a neutral electron donor ligand and n = 1 or 2.

13. A method for producing compounds according to one or more of claims 1 to 11 of formula II, wherein a ligand of type R1-CH-(P(R2)2)(P(R3)3)(X), wherein R1, R2 and R3 are defined in the preceding claims, is reacted with a palladium compound of type H2PdX4, PdX2 or L n (PdX2), where X as above defines halogen, L is a neutral electron-donating ligand, and n = 1 or 2.

14. Method for carrying out a coupling reaction, comprising the following steps - Providing a reaction mixture containing at least one substrate, one coupling partner and one metal complex according to one of claims 1 to 11; and - Reacting the substrate with the coupling partner in the presence of the metal complex or its derivative to form a coupling product.

15. Method for carrying out a coupling reaction comprising the following steps - Providing a metal complex according to a method according to at least one of claims 12 to 13; - Providing a reaction mixture containing at least one substrate, one coupling partner, and the metal complex; and - Reacting the substrate with the coupling partner in the presence of the metal complex or its derivative to form a coupling product.

16. A method according to one or more of claims 14 to 15, wherein the coupling reaction can be selected from the group consisting of (i) catalytic hydrofunctionalization reactions of alkynes and alkenes; (ii) catalytic hydroamination reactions of alkynes and alkenes; (iii) catalytic OH addition reactions on alkynes and alkenes; (iv) catalytic coupling reactions; (v) catalytic Kumada coupling reactions, Murahashi coupling reactions, Negishi coupling reactions or Suzuki coupling reactions, in particular for the production of biaryls; (vi) catalytic cross-coupling reactions, in particular CN and C- O-coupling reactions; and / or (vii) catalytic Heck coupling reactions, especially for the preparation of arylated olefins, and Sonogashira coupling reactions, especially for the preparation of arylated and alkenylated alkynes.

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