Organometallic compounds

Abstract

The present invention is directed towards the monoarylation of hydrazines. In particular, a process is described herein to selectively add aryls or hetero aryls to hydrazine via a C-N-cross-coupling reaction using special Pd-phos- phine complexes.

Description

[0001] Organometallic Compounds Description The present invention is directed towards novel organometallic palladium complexes and their use in chemical synthesis. In particular, a process is described herein to carry out coupling reactions, like selectively add aryls or hetero aryls to hydrazine via a C-N-cross-coupling reaction, using special Pd-phosphine complexes, such as the monoarylation of hydrazines. Palladium catalysis is used in organic synthetic chemistry to produce a wide variety of compounds. The most prominent palladium-catalyzed reactions include C-C bond-forming reactions and C-heteroatom bond-forming reac- tions, commonly referred to as cross-coupling reactions (EP3845546A). C- N-cross-coupling reactions have already been reported (Ruiz-Castillo, P.; Buchwald, S. L. Applications of Palladium-Catalyzed C–N Cross-Coupling Re- actions. Chem. Rev. 2016, 116 (19), 12564–12649.). E.g., the transition metal-catalyzed monoarylation of ammonia is one of the most attractive syntheses of anilines. However, it is challenging, since the aniline products are more reactive towards a second arylation than ammo- nia is towards the first. Extensive research has led to the development of Pd-, Ni- and Cu-catalyzed protocols that permit the selective synthesis of anilines from ammonia solutions or ammonium salts. For the Pd-catalyzed reactions, bulky, electron-rich ligands are vital to achieve selective mono- arylations (Kim, S.-T.; Kim, S.; Baik, M.-H. How Bulky Ligands Control the Chemoselectivity of Pd-Catalyzed N -Arylation of Ammonia. Chem. Sci. 2020, 11 (4), 1017–1025.). State-of-the-art palladium catalysts such as Buchwald’s Pd[Me3(OMe)XPhos] G3 systems (Surry, D. S.; Buchwald, S. L. Selective Palladium-Catalyzed Arylation of Ammonia: Synthesis of Anilines as Well as Symmetrical and Unsymmetrical Di- and Triarylamines. J. Am. Chem. Soc. 2007, 129 (34), 10354–10355.), Hartwig’s JosiPhos (Shen, Q.; Hartwig, J. F. Palladium-Catalyzed Coupling of Ammonia and Lithium Amide with Aryl Halides. J. Am. Chem. Soc. 2006, 128 (31), 10028–10029.), and Stradiotto’s MorDalPhos (Lundgren, R. J.; Peters, B. D.; Alsabeh, P. G.; Stradiotto, M. A P,N-Ligand for Palladium-Catalyzed Ammonia Arylation: Coupling of Deactivated Aryl Chlorides, Chemoselective Arylations, and Room Temperature Reactions. Angew Chem Int Ed 2010, 49 (24), 4071– 4074) and BippyPhos (Crawford, S. M.; Lavery, C. B.; Stradiotto, M. Bip- pyPhos: A Single Ligand With Unprecedented Scope in the Buchwald–Hart- wig Amination of (Hetero)Aryl Chlorides. Chemistry A European J 2013, 19 (49), 16760–16771) catalyst give high yields at low loadings, moderate temperatures and short reaction times. Compared to the arylation of ammonia, a selective monoarylation of hydra- zine is even harder to achieve. The first arylation activates the ipso-nitrogen for a second arylation due to an increased nucleophilicity. Bulky ligands can overrule this, but the second nitrogen atom of a monoarylated hydrazine is sterically as accessible as hydrazine itself. State-of-the art catalysts for monoarylation of hydrazine such as Stradiotto’s [Pd(cinnamyl)Cl]2 / MorDal- Phos and Hartwig’s Pd[(P(o-tolyl)3] / JosiPhos system (Wang, J. Y.; Choi, K.; Zuend, S. J.; Borate, K.; Shinde, H.; Goetz, R.; Hartwig, J. F. Cross-Cou- pling between Hydrazine and Aryl Halides with Hydroxide Base at Low Load- ings of Palladium by Rate-Determining Deprotonation of Bound Hydrazine. Angew Chem Int Ed 2021, 60 (1), 399–408) require high temperatures, Buchwald’s Pd G1 BrettPhos catalyst an elaborate flow-through protocol (DeAngelis, A.; Wang, D.; Buchwald, S. L. Mild and Rapid Pd-Catalyzed Cross-Coupling with Hydrazine in Continuous Flow: Application to the Syn- thesis of Functionalized Heterocycles. Angew Chem Int Ed 2013, 52 (12), 3434–3437). Several of Buchwald’s new catalysts for C-N-cross coupling are already commercially available (https: / / www.sigmaaldrich.com / DE / de / technical- documents / technical-article / chemistry-and-synthesis / cross-coupling / buch- wald-g6-precatalysts-oxidative-addition-complexes). They have been proven versatile in lots of C-C- or C-N-cross-coupling reactions. However, in particular for the monoarylation of hydrazine still there exists the need in the art to develop even more active and selective catalysts. Hence, it is an object of the present invention to provide a process and a catalyst for the monoarylation of hydrazines which is superior in activity and selectivity to the processes and catalyst known in the prior art for these kind of reactions. These and other object being obvious to those skilled in the art are solved by providing a process for the monoarylation of hydrazines according to claim 1. Further preferred embodiments of the inventive process are men- tioned in dependent claims 2 – 8. In claim 9 a new catalyst for this reaction is described. Claim 9 focusses on a process for producing the catalyst of claim 10. By conducting a process for the selective monoarylation of hydrazine hy- drate or hydrazine salts of the general formular (I) or (II) : NH2NH2[N2H5]W (I) (II) wherein W is a counter anion which comprises the steps of: - providing an organic polar solvent, which does not interact with the reactants added but dissolves the reactants; - adding thereto as a reactant a hydrazine of formula (I) or (II); - adding a catalyst of the general formula (III) or (IV): (III) (IV) wherein R1, R2 are same or different from each other and being linear or branched alkyl; R3, R4, are same or different from each other and being branched or cyclic alkyl; R5, R6, R7 are same or different from each other and being H, linear or branched or cyclic alkyl; R8 is an alkenyl, aryl or aryl alkenyl group; RAand RBare if present independently from each other one or more alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, aralkyl, hydrogen, halogen, heteroaralkyl, alkoxyl, dialkylaminyl, trialkylsilyl; and X is O or S, with O being preferred; Y is an anionic ligand, like halide, tosylate, mesylate, triflate, acetate; Z is a σ-donor ligand, like aryl or heteroaryl; - adding as a further reactant an aryl halide or heteroaryl halide to the reaction mixture; and - adding a base; and - isolating the arylhydrazine from the reaction mixture, the skilled worker is able to solve the problems addressed above. By using the catalysts men- tioned in the process of arylating hydrazines can be performed with an out- standingly high yield. Moreover, the catalysts presented above provide for an extraordinary selectivity in the process of monoarylation hydrazines to an extent which was not foreseeable from the knowledge to date. In a process according to the invention residues R1 and R2 for the ligands can advantageously and independently be selected from the group consist- ing of methyl, ethyl, propyl, iso-propyl, butyl, t-butyl, iso-butyl and sec-bu- tyl . In an even more preferred embodiment R2 is methyl, R1 is methyl, t- butyl or iso-propyl. Most preferably, R1 and R2 are methyl groups. R3, R4 are rather bulky groups which shield the side of the phosphine ligand from any other reaction that can occur. In a preferred embodiment, R3 and R4 are independently from each other tert-butyl, isopropyl, neopentyl, 1- adamantyl, propellane. In a more preferred aspect R3 and R4 are chosen from the group of tert-butyl, or 1-adamantyl. Likewise R5, R6 and R7 are alkyl substituents also. In a preferred embodi- ment, R5, R6 and R7 are independently from each other methyl, ethyl, pro- pyl, isopropyl, butyl, iso-butyl and sec-butyl. In a more preferred aspect R5, R6 and R7 are chosen from the group isopropyl, iso-butyl and sec-butyl. Very preferable, R5, R6 and R7 is isopropyl. R8 can be an aryl, alkenyl or aryl alkenyl moiety. R8 is released from the compound of formula (IV) upon reaction (see scheme 1). In a preferred em- bodiment R8 can be selected from the group consisting of phenyl, ethenyl, naphthyl, allyl, crotyl or 1-tBu-indenyl. Very much preferred is if R8 is phe- nyl ethenyl, naphthyl or vinyl. As will be apparent from the experimental section the position of the residue R8 can be above the attached ring or be- low. The anomers of formula (IV) can be applied in the inventive reaction with equal selectivity and activity. Hence, if a description of a formula (IV) is given this description always encompasses both possible anomers. As mentioned Y is a an anionic ligand, like halide, tosylate, triflate, acetate. A halide like Cl or Br are particularly preferred in this connection. Z is a σ- donor ligand like aryl or heteroaryl for instance, or an alkyl or an alkenyl. Z can also be a bidentate ligand in which one part of the ligand is connected to the Palladium via a σ-donor bond as mentioned before and the other part is connected to the Palladium via a heteroatomic substituent. In a very pre- ferred embodiment this heteroatom is a nitrogen. In an extremely preferred aspect the ligand can comprise a biphenyl structure. In an exemplary but utmostly preferred embodiment of formula (III) an aryl is a substituted or unsubstituted biphenyl moiety. E.g., a catalysts like mentioned in formula (V) can also be used in the present reaction.

[0002] (V) wherein U is selected from the group consisting of NH2, NHMe. Here the other residues can take the meaning as mentioned before. Compounds of formula (V) are known to those skilled in the art (US8889857B2). The catalysts (III) (J. Am. Chem. Soc. 2020, 142, 15027−15037, Org. Lett. 2021, 23, 20, 7927–7932) can easily be synthesized according to literature procedures. The catalysts (IV) can be prepared according to the general procedure A mentioned in the experimental section. Other suitable procedures for preparing the catalysts (IV) are, for example, a process for the production of a compound according to claim 9, characterized in that the compound 1,3-Divinyl-1,1,3,3-tetramethyldisilox- anepalladium(0) - Pd2(vs)3is reacted with an allylhalide or naphthyl halide of formula (X)

[0003] wherein R’, R’’, R’’’ are independently of each other selected from the group consisting of H, alkyl, aryl or R’ and R’’ form an ar- omatic or non-aromatic cyclic ring; Y is a halide; and a ligand of formula (VII) R1, R2 are same or different from each other and being linear or branched alkyl; R3, R4, are same or different from each other and being branched or cyclic alkyl; R5, R6, R7 are same or different from each other and being H, linear or branched or cyclic alkyl; RAand RBare if present independently from each other one or more alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, aralkyl, hydrogen, halogen, heteroaralkyl, alkoxyl, dialkylaminyl, trialkylsilyl; X is O or S; are reacted under conditions sufficient to produce the compound of formula (IV). In particular, R’, R’’, R’’’ are independently of each other selected from the group consisting of H, alkyl, aryl, with methyl, ethyl, C3-C8 linear alkyl, phenyl being preferred or R’ and R’’ form an aromatic or non-aromatic cyclic ring; like with 1-methyl naphthaline (1-MeNAP); 2-methyl naphthaline (2- MeNAP); Such reactions are, for example, procedure B, wherein 1,3-Divinyl-1,1,3,3- tetramethyldisiloxanepalladium(0) - Pd2(vs)3, serves as the palladium source (usually as a solution) and is reacted with at least two equivalents of a ligand of formula (VII) for 4 to 8 hours, in particular 3 to 6 hours in a po- lar, aprotic solvent, which can be selected from the group consisting of ke- tones, ethers, esters, in particular acetone, MTBE, THF, ethylacetate. Espe- cially preferred is acetone in this connection. At least two equivalents of a a halide-containing substrate of formula (X), in particular a 1-methyl naph- thaline (1-MeNAP) or 2-methyl naphthaline (2-MeNAP) compound is added and reacted overnight. The reactions are carried out at ambient tempera- ture. To isolate the product, at least about 75% of the solvent is distilled off under reduced pressure. Heptane is added, the mother liquor is removed and the isolated solid can be washed with heptane and dried to obtain the catalyst (IV). In another embodiment, a further suitable procedure for preparing the cata- lysts (IV) is procedure C, wherein a reactor is charged with 1,3-Divinyl- 1,1,3,3-tetramethyldisiloxanepalladium(0) - Pd2(vs)3, (usually as a solu- tion), serving as the palladium source, at least two equivalents of the ligand of formula (VII) and at least two equivalents of a an allylhalide or naphthyl halide of formula (X), in particular a 1-methyl naphthaline (1-MeNAP) or 2- methyl naphthaline (2-MeNAP) compound and a polar, aprotic solvent, which can be selected from the group consisting of ketones, ethers, esters, in partiucular acetone, MTBE, THF, ethylacetate. Especially preferred is ace- tone in this connection. The reaction mixture is stirred overnight and con- centrated under reduced pressure, removing at least about 75% of the solvent. Heptane is added, the mother liquor is removed and the isolated solid can be washed with heptane and dried to obtain the catalyst (IV). For procedures B and C, the number of equivalents given for the ligand of formula (VII) and the organic-halide of formula (X), in particular a 1-methyl naphthaline (1-MeNAP) or 2-methyl naphthaline (2-MeNAP) are based on the amount of the palladium source. Removing of solvent is advantageously accomplished by distillation under reduced pressure. In specific embodi- ments of procedures B and C, removal of the mother liquor can be carried out by sedimentation or centrifugation and decantation or in particular by filtration. The catalysts used for the inventive process are those of formula (III) and (IV) and (V). These catalysts surprisingly provide a selectivity and activity in the present reaction that has been unknown so far. The catalysts are nor- mally used in substoichiometric amounts. Usually, the concentration of these catalysts in the reaction mixture is between 3.3*10-5– 6.7*10-3mol / l, more preferably 1.7*10-4– 6.7*10-3mol / l and most preferably between 3.3*10-3– 6.7*10-3mol / l. In the process of the present invention hydrazine or a hydrazine derivative is selectively arylated via a C-N-cross-coupling reaction. The hydrazines that can be used in this reaction are in principle known to those skilled in the art. The hydrazines can be used in form of the hydrazine as such or as a hydrate or salt thereof. Salts to be used are known to the skilled worker. Versatile salts are those having counter anions selected from the group con- sisting of carboxylates, halides and pseudo halides. Most preferred are ani- ons like OTf-, Cl-, SO42-, OAc-. These compounds are usually used in a con- centration of 0.5 – 2 mol / l, more preferred 0.5 – 1 mol / l and very preferred around 0.67 mol / l. In order to cross-couple the hydrazines or their derivatives with a further reactant an aryl halide has to be added to the reaction mixture. The aryl halide usually is added in concentrations of 0.1 – 3 mol / l, more preferably 0.33 – 2 mol / l and most preferably 0.33 mol / l to the reaction mixture. The ratio of reactants has already been addressed above. The ratio between the hydrazines and the aryl halide as the further reactant can be determined by the skilled person. Usually, the molar ratio ranges between 10:1– 1:1, more preferred 3:1– 1:1 and very preferred 2:1. As an aryl halide for the C-N-cross-coupling reaction any aryl halide or het- eroaryl halide known to the skilled person as being feasible in this reaction can be taken. Normally, the aryl halide consist of an aryl moiety attached to halide. The heteroaryl halide is accordingly. The halide is preferably any of Cl, Br or J. More preferably Br and Cl are addressed here. Most preferably the halide is Cl. The (hetero)aryl moiety can be any (hetero)aryl like e.g. selected from the group consisting of phenyl, naphthyl, pyridyl, pyrazinyl and thienyl. These (hetero)aryls can itself be substituted by further func- tional groups alkoxy, ketone, formyl, ester, ether, amine, silane and borane groups. In particular, electron-withdrawing substituents can be attached to the aryl moiety. Advantageously, these substituents can be those selected from the group consisting of fluorine, cyano, acyl, formyl, nitro, trifluorome- thyl and amide. The inventive process is conducted quite easily. E.g., in a vessel a kind of organic solvents is provided. The organic solvent should be one which does not interact with the reactants nor with the catalyst in order not to inhibit the reaction or to furnish side product production. On the other hand it should be polar enough to dissolve all the reactants and the catalyst to the necessary extent. The skilled workers can choose the solvent according to his needs. Preferably, the solvents are polar aprotic solvents. More prefera- bly, the solvent is selected from ethereal compounds. Most preferable, the organic solvent is selected from the group consisting of THF, dioxane, di- methoxyethane, methyl t-butyl ether, cyclohexyl methyl ether, 2-methyl- tetrahydrofurane. Once the solvent is present, the reactants can be added to the solvent. The sequence of addition is not that critical. Finally, a base needs to be added to the reaction mixture. The base can be selected according to the knowledge of the skilled worker. It should be soluble in the reaction mixture to the necessary extent and be basic enough to deprotonate the Pd-coordinated hydrazine. Preferably, the base is selected from the group consisting of KOH, K2CO3, K3PO4, Cs2CO3,NaOtBu, KOtBu, NaOMe, NaOH. Most preferred are KOH and NaOH In this respect. When all ingredients have been added to the reaction mixture, the mono- arylation happens usually in matter of hours at room temperature. In a pre- ferred embodiment the reaction mixture is allowed to be heated though. More preferably, the process of the invention is conducted at a temperature of 10 °C to 80 °C, even more preferably at 10 – 40 °C and most preferably at 25-30 °C. As a final step the products can be isolated from the reaction mixture ac- cording to the knowledge of those skilled in the art. Preferably, they can be acidified by concentrated hydrochloride acid to generate the hydrochloride salts and purified by two-phase extractions, precipitation and filtration. Al- ternatively, they are not isolated but directly converted into heterocycles by reaction with dicarbonylcompounds or ketones for example. In a further aspect the present invention is directed to a metal complex of formula IV that can be employed,of example, in coupling reactions such as a catalyst for the monoarylation of hydrazines of general formula (IV) wherein R1, R2 are same or different from each other and being linear or branched alkyl; R3, R4, are same or different from each other and being branched or cyclic alkyl; R5, R6, R7 are same or different from each other and being H, linear or branched or cyclic alkyl; R8 is an alkenyl, aryl or aryl alkenyl group; RAand RBare if present independently from each other one or more alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, aralkyl, hydrogen, halogen, heteroaralkyl, alkoxyl, dialkylaminyl, trialkylsilyl; and X is O or S, with O being preferred; Y is a an anionic ligand, like halide, tosylate, mesylate, triflate, acetate. The complexes of formula (VI) can also be employed in organic coupling re- actions. Thus, in an embodiment the Invention also relates to a method for carrying out a coupling reactions comprising the steps of - Providing a reaction mixture comprising at least a substrate, a cou- pling partner and a compound of formula (VI); Reacting the substrate with the coupling partner in the presence of the compound of formula (VI) according to claim 9 to form a coupling product. In an embodiment, the coupling reaction can be a C-C, C-N or a C-O cou- pling reaction. More specifically, the coupling reactions mentioned above are relating to a method for carrying out coupling reactions wherein the coupling reaction is selected from the group consisting of: (i) catalytic hydrofunctionalization reactions of alkynes and alkenes; (ii) catalytic hydroamination reactions of alkynes and alkenes; (iii) catalytic O-H addition reactions on alkynes and alkenes; (iv) catalytic coupling reactions, such as the catalytic amination of aryl fluo- rides, the catalytic N-arylation of aryl fluorides, the catalytic alpha-arylation of carbonyl compounds, the catalytic N-arylation of trifluoroethyl amines or the catalystic N-arylation of amides, in particular benzamides; (v) catalytic Kumada coupling reactions, Murahashi coupling reactions, Negishi coupling reactions or Suzuki coupling reactions, in particular for the preparation of biarylene; (vi) catalytic cross-coupling reactions, in particular C-N and C-O coupling reactions; and / or (vii) catalytic Heck coupling reactions, in particular for the preparation of ar- ylated olefins, and Sonogashira coupling reactions, in particular for the preparation of arylated and alkenylated alkynes. In a further aspect of the present invention the catalyst of formula (IV) can be produced in a process characterized in that a compound of general for- wherein R’, R’’, R’’’ are independently of each other selected from the group consisting of H, alkyl, aryl, with methyl, ethyl, C3-C8 linear alkyl, phenyl being preferred or R’ and R’’ form an aromatic or non-aromatic cyclic ring; like with 1-methyl naphthaline (1-MeNAP); 2-methyl naphthaline (2- MeNAP); Y is a halide; preferably like Cl or Br; and a ligand of formula (VII)

[0004] wherein R1, R2 are same or different from each other and being linear or branched alkyl; R3, R4, are same or different from each other and being branched or cyclic alkyl; R5, R6, R7 are same or different from each other and being H, linear or branched or cyclic alkyl; RAand RBare if present independently from each other one or more alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, aralkyl, hydrogen, halogen, heteroaralkyl, alkoxyl, dialkylaminyl, trialkylsilyl; X is O or S, with O being preferred, are reacted under conditions sufficient to produce the respective compound. The condition under which the reaction takes place can be selected accord- ing the viewpoint of the skilled worker. In general the solvents applied can be selected from the group consisting of ketones, ethers, esthers Preferred is acetone, MTBE, THF, ethylacetate. Especially preferred is acetone in this connection. In general, the temperatures applied can range from 10 – 100 °C, more preferably 15 – 50 °C and most preferably at around room temperature. The catalyst of formula (IV) can be isolated according to those skilled in the art. The reaction for forming the catalyst (IV) runs smoothly already under room temperature in a couple of hours, e.g. according to the scheme 1: Scheme 1 Depending on the initial η-allylic Pd-compound (VI) the final catalyst (IV) can have a differing residue R8, like preferably be an alkenyl or an aryl or an aryl alkenyl moiety, like phenyl, ethenyl, naphthyl, allyl, crotyl or 1-tBu- indenyl. Very much preferred is if R8 is phenyl ethenyl, crotyl, naphthyl or vinyl. If a molecule as presented under formula (VI) is used R’, R’’, R’’’ have to be chosen accordingly. E.g., complexes like in scheme 2 have been pre- pared in situ, albeit they were not isolated in pure form so far. Scheme 2 In the process of this invention this catalyst species (IV) shows activities and selectivities for the monoarylation of hydrazines which are paramount. Yields in the region of 99% with nearly no detectable side product could be obtained using these kind of catalysts. A further benefit is that the catalysts are quite easy to produce (e.g. see scheme 1) and manageable so that they are pretty good implementable in a large scale production process. This is all but obvious from the prior art knowledge. It should be clear that all preferred embodiments mentioned for the catalyst of formula (IV) above also are applicable in respect of the process. In par- ticular, as the catalyst of formula (IV) can exist in two anomeric structures both of them are contemplated when looking at a specific structure. "Alkyl" refers to a straight-chain or branched saturated hydrocarbon group. In certain embodiments, the alkyl group may have from 1-20 carbon atoms, in certain embodiments from 1-15 carbon atoms, in certain embodiments, 1-8 carbon atoms. The alkyl group may be unsubstituted. Alternatively, the alkyl group may be substituted. Unless otherwise specified, the alkyl group may be attached at any suitable carbon atom and, if substituted, may be substituted at any suitable atom. Typical alkyl groups include but are not limited to methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl and the like. “Alkenyl” refer to alkyl having one or more double bonds in it. “Aryl alkenyl” refers to an aryl moiety that is at- tached to an alkenyl residue. The term "cycloalkyl" is used to denote a saturated carbocyclic hydrocarbon radical. The cycloalkyl group may have a single ring or multiple condensed rings. In certain embodiments, the cycloalkyl group may have from 3-15 carbon atoms, in certain embodiments, from 3-10 carbon atoms, in certain embodiments, from 3-8 carbon atoms. The cycloalkyl group may be unsub- stituted. Alternatively, the cycloalkyl group may be substituted. Unless other specified, the cycloalkyl group may be attached at any suitable carbon atom and, if substituted, may be substituted at any suitable atom. Typical cycloalkyl groups include but are not limited to cyclopropyl, cyclobutyl, cy- clopentyl, cyclohexyl and the like. "Aryl" refers to an aromatic carbocyclic group. The aryl group may have a single ring or multiple condensed rings. In certain embodiments, the aryl group can have from 6-20 carbon atoms, in certain embodiments from 6-15 carbon atoms, in certain embodiments, 6-12 carbon atoms. The aryl group may be unsubstituted. Alternatively, the aryl group may be substituted. Un- less otherwise specified, the aryl group may be attached at any suitable carbon atom and, if substituted, may be substituted at any suitable atom. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, anthracenyl and the like. "Heteroalkyl" refers to a straight-chain or branched saturated hydrocarbon group wherein one or more carbon atoms are independently replaced with one or more heteroatoms (e.g. nitrogen, oxygen, phosphorus and / or sulfur atoms). The heteroalkyl group may be unsubstituted. Alternatively, the het- eroalkyl group may be substituted. Unless otherwise specified, the heteroal- kyl group may be attached at any suitable atom and, if substituted, may be substituted at any suitable atom. Examples of heteroalkyl groups include but are not limited to ethers, thioethers, primary amines, secondary amines, tertiary amines and the like. "Heterocycloalkyl" refers to a saturated cyclic hydrocarbon group wherein one or more carbon atoms are independently replaced with one or more heteroatoms (e.g. nitrogen, oxygen, phosphorus and / or sulfur atoms). The heterocycloalkyl group may be unsubstituted. Alternatively, the heterocyclo- alkyl group may be substituted. Unless otherwise specified, the heterocyclo- alkyl group may be attached at any suitable atom and, if substituted, may be substituted at any suitable atom. Examples of heterocycloalkyl groups include but are not limited to epoxide, morpholinyl, piperadinyl, piperazinyl, thirranyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, thiazolidinyl, thiomor- pholinyl and the like. "Heteroaryl" refers to an aromatic carbocyclic group wherein one or more carbon atoms are independently replaced with one or more heteroatoms (e.g. nitrogen, oxygen, phosphorus and / or sulfur atoms). The heteroaryl group may be unsubstituted. Alternatively, the heteroaryl group may be substituted. Unless otherwise specified, the heteroaryl group may be at- tached at any suitable atom and, if substituted, may be substituted at any suitable atom. Examples of heteroaryl groups include but are not limited to thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxa- zolyl, isoxazolyl, triazolyl, thiadiazolyl, thiophenyl, oxadiazolyl, pyridinyl, py- rimidyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, indolyl, quinolinyl and the like. "Arylalkyl" refers to an optionally substituted group of the formula aryl-al- kyl-, where aryl and alkyl are as defined above. It should be noted that the possibilities for the residues whether advanta- geous, preferred, or not preferred, mentioned in the present text are also applicable for the residues in the other formulas having same abbreviation for the residues. In a nutshell, it has to be noticed that the process of the invention and the catalysts of formula (IV) have beneficial properties within the field of mono- arylation of hydrazines. The catalysts are easy to produce, the condition un- der which the process runs are mild and the yields and selectivities for the formation of monoarylated products are superb. This is very surprising based on the prior art known to the skilled person.

[0005] Figures: Fig. 1: ESI-MS spectrum of reaction mixture of [Pd(cin- namyl)(tBuBrettPhos)Cl] with 0.01 mmol [Pd(cinnamyl)Cl]2, 2.0 equiv.tBuBrettPhos in 2 mL THF for 30 min at 80 °C. Fig. 2: ESI-MS spectrum of isolated [Pd(allyl)(tBuBrettPhos)Cl] following general procedure A in THF with 0.25 mmol [Pd(allyl)Cl]2. Fig. 3: Comparison of1H NMR spectra of [Pd(1-MeNAP)(tBuBrettPhos)Br](blue),tBuBrettPhos (green), and [Pd(1-MeNAP)Br]2(red). 1H NMR spectrawere recorded at 400 MHz in CD2Cl2 or DMSO-d6 (for [Pd(1-MeNAP)Br]2 due to low solubility in DCM). Fig. 4: Solid state structure of Pd(2-MeNAP)Br-tBuBrettPhos complex. Hy- drogen atoms are omitted for clarity. Red: O, black: C, orange: P, dark green: Br, brown: Pd. The thermal ellipsoids are drawn at the 50% proba- bility level. Disorder of 2-methylnaphthyl group was omitted for clarity. Fig. 5: Solid state structure of Pd(1-MeNAP)Br-tBuBrettPhos complex. Hy- drogen atoms are omitted for clarity. Red: O, black: C, orange: P, dark green: Br, brown: Pd. The thermal ellipsoids are drawn at the 50% proba- bility level.

[0006] Experimental report: I. General All reactions were performed in oven-dried glassware containing a Teflon- coated stirring bar and dry septum under nitrogen atmosphere. Optimization reactions were monitored by19F NMR analysis using 1, 4-difluorobenzene as internal standard. Characterization of the compounds was done by: and31P NMR spectra were recorded on an Avance-III-300or Avance-III-400 spectrometer at 25 °C if not stated otherwise.19F NMRspectra were recorded on Spinsolve Benchtop NMR (MAGRITEK) spectrome- ters at 25 °C. All values of the chemical shift are in ppm regarding the δ- scale. To display multiplicities and signal forms correctly the following ab- breviations were used: s = singlet, d = doublet, t=triplet, q = quartet, spt = septet, m = multiplet, dd = doublet of doublet, dq = doublet of quartet, dspt= doublet of septet, br = broad signal. Column chromatography was performed on a CombiFlash Companion (Isco) and a Pure C-815 Flash (Büchi) using Reveleris packed columns (12 g or 40 g). Mass spectrometric data (EI) were acquired on a GC-MS Agilent 5977B MSD. Mass spectra (ESI) of Pd complexes were recorded via direct injection using acetonitrile / water (0.1% formic acid) as eluent. Samples were prepared by dissolving the com- plex in acetonitrile (ca. 1 mg / mL) and filtration through a PTFE syringe fil- ter. The evaluation and calculation of MS spectra were performed with the MassLynx software HRMS analyses were acquired using a GC-MS system consisting of an Agilent 7250 GC / Q-TOF, in which ionization was achieved by EI. Infrared spectra were recorded on Bruker Vertex 70 Spectrometer with Universal ATR Sampling Accessory. Melting points were measured on a Mettler Toledo MP70. Elemental analysis was performed on a varioMICRO CHNS. Commercial substrates were used as received unless otherwise stated. Am- monium triflate was washed with ether, dried in vacuo, and stored in the glovebox. Solvents were purchased (puriss p.A.) from commercial suppliers and dried by standard procedures (Armarego, W. L. F.; Chai, C. L. L. Purifi- cation of Laboratory Chemicals, 5th ed.; Butterworth-Heinemann: Amster- dam; Boston, 2003). All solvents and liquid reactants were degassed by Ar-gonpurge prior to use. [Pd(1-MeNAP)Br]2as well as other Pd sources weredonated by Umicore (EP4267591A). KOH pellets were imported into a glove- box and pulverized into a fine powder with a mortar and pestle. [N2H5][OTf] was synthesized by previously reported procedure (Mock, M. T.; Chen, S.; O’Hagan, M.; Rousseau, R.; Dougherty, W. G.; Kassel, W. S.; Bullock, R. M. Dinitrogen Reduction by a Chromium(0) Complex Supported by a 16-Mem- bered Phosphorus Macrocycle. J. Am. Chem. Soc. 2013, 135 (31), 11493– 11496). II. Production of the catalysts tested General preparation of Pd pre-catalysts – Procedure A Catalysts of formula (IV) [Pd(MeNAP)Br]2(EP4267591A) (0.125 or 0.25 mmol) and ligand (2.0 equiv.) were weighed in an oven-dry vial. After addition of 5 or 10 mL THF or acetone, the reaction mixture was stirred at room temperature overnight. 90% of the solvent was evaporated and 5 or 10 mL pentane was added. The mixture was stored at -20 °C over night to crystallize the product. The mother liquor was decanted and the remaining solid was washed with pen- tane (3x5mL) and dried under high vacuum to afford the Pd complex. Catalysts of formula (III) and (V): The catalysts are commercially available under https: / / www.sigmaal- drich.com / DE / en / technical-documents / technical-article / chemistry-and-syn- thesis / cross-coupling / buchwald-g6-precatalysts-oxidative-addition-com- plexes or can be prepared as mentioned in: King, R.; Senecal, T. D.; Shu, W.; Buchwald, S. L. A General, Practical Palladium-Catalyzed Cyanation of (Hetero)Aryl Chlorides and Bromides. Angew. Chem. Int. Ed. 2013, 52 (38), 10035–10039. III. Results on generation of Pd catalysts 2-di-tert-butylphosphino(2',4',6'-triisopropyl-3,6-dimethoxy-4'- (naphthalen-1-ylmethyl)-[1,1'-biphenyl])bromo- palladium(II) [Pd(1-MeNAP)(tBuBrettPhos)Br] ^ ^ Following general procedure A with [Pd(1-MeNAP)Br]2(81.9 mg, 0.125mmol) and tBuBrettPhos (122 mg, 0.25 mmol) in acetone, the title com-pound was obtained as yellow solid (169 mg, 0.208 mmol, 83%).1H NMR (400 MHz, CD2Cl2): δ = 8.61 - 8.59 (m, 1 H), 7.80 - 7.70 (m, 2 H), 7.44 - 7.36 (m, 4 H), 6.93 - 6.87 (m, 2 H), 5.04 (s, 1 H), 5.03 (s, 1 H), 4.21 (s, 2 H), 3.80 (s, 3 H), 3.66 (s, 3 H), 1.93 (sept., J = 6.8 Hz, 1 H),1.86 - 1.76 (m, 2 H), 1.49 (d, J = 14.9 Hz, 18 H), 1.03 (d, J = 6.9 Hz, 6 H),0.92 (d, J = 6.6 Hz, 6 H), 0.84 (d, J = 6.7 Hz, 6 H) ppm.13C NMR (75 MHz, CD2Cl2): δ = 155.7 (d, J = 2.8 Hz), 151.2 (d, J = 22.9 Hz), 140.0 (d, J = 22.9 Hz), 136.3, 134.5 (d, J = 6.0 Hz), 134.3 (d, J = 4.5 Hz), 133.8 (d, J = 15.5 Hz), 129.3, 128.4 (d, J = 3.0 Hz), 127.2, 126.0, 125.6, 125.4, 113.9 (d, J = 1.7 Hz), 112.3 (d, J = 18.1 Hz), 111.4 (d, J = 3.9 Hz), 92.3 (d, J = 9.2 Hz), 55.0 (d, J = 3.0 Hz), 54.8, 54.5, 50.6 (d, J = 8.3 Hz), 43.8 (d, J = 9.1 Hz), 38.4 (d, J = 7.2 Hz), 32.2, 32.1 (d, J = 7.7 Hz), 31.9, 31.0, 25.4, 23.4, 17.8 ppm.31P NMR (162 MHz, CD2Cl2): δ = 94.3, 84.3 ppm. MS (ESI-TOF): m / z (%) = 772.38 (2), 731.22 (100). EA: Calc. for C42H58O2PBrPd: C, 62.11%; H, 7.20%; N, 0.00%; Found: C, 62.01%; H, 6.84%; N, 0.00%. Procedure B: The same compound as above was prepared with this procedure B, which also serves as general procedure. A round-bottomed flask was charged with 1,3-Divinyl-1,1,3,3-tetramethyldisiloxanepalladium(0) - Pd2(vs)3, as a vssolution with ~10% Pd,(9.35 g, 4.22 mmol), Acetone (40 mL)andtBuBrettPhos (4.14 g, 8.44 mmol, 2 eq.). The reaction mixture was stirred at room temperature for 6 hours before 1-Br-Methylnaphthalene (2g, 8.44 mmol, 2 eq.) and Acetone (10 mL) were added. The reaction mixture was stirred at room temperature overnight and afterwards concentrated to ap- prox. 10 mL under reduced pressure at 35 °C. n-Heptanes (50 mL) were added to the concentrate to precipitate [Pd(1-MeNAP)(tBuBrettPhos)Br]. The mother liquor was filtered off, the isolated solid was washed with n- Heptanes (4x15 mL) and dried under vacuum to afford [Pd(1- MeNAP)(tBuBrettPhos)Br] as a dark-orange solid (5.68 g, 6.99 mmol, 83%). The analytical data of the product obtained are in agreement to those of the product obtained above for the product of procedure A. Procedure C: The same compound as above was prepared with this procedure C, which also serves as general procedure. A round-bottomed flask was subsequently charged with Pd2(vs)3(9.35 g, 4.22 mmol), Acetone (50 mL),tBuBrettPhos(4.14 g, 8.44 mmol, 2 eq.) and1-Br-Methylnaphthalene (2g, 8.44 mmol, 2eq.). The reaction mixture was stirred at room temperature overnight and afterwards concentrated to approx. 10 mL under reduced pressure at 35 °C. n-Heptanes (50 mL) were added to the concentrate to precipitate [Pd(1- MeNAP)(tBuBrettPhos)Br]. The mother liquor was filtered off, the isolated solid was washed with n-Heptanes (4x15 mL) and dried under vacuum toafford [Pd(1-MeNAP)(tBuBrettPhos)Br] as a dark-orange solid(5.58 g, 6.99mmol, 81%).1H NMR (600 MHz, C6D6): δ = 9.22 (d, 1 H), 7.74 (d, 1 H), 7.67 (d, 1 H), 7.63 (t, 1 H), 7.45 (d, 1 H), 7.35 (q, 2 H), 6,32 (d, 1 H), 6.26 (dd, 1 H), 5.22 (d, 2 H), 4.69 (s, 2 H), 3.09 (d, 6 H), 2.14 (sept., 1 H), 1.85 (sept., 2 H), 1.59 (d, 18 H), 1.01 (t, 12 H), 0.85 (d, 6 H). 6.0 Hz), 18.9 ppm. 31P NMR (162 MHz, CD2Cl2): δ = 85.2 ppm. MS (ESI-TOF): m / z (%) = 772.42 (13), 731.29 (100), 590.14(1), 485.24 (2). 2-diadamantylphosphino(2',4',6'-triisopropyl-3,6-dimethoxy-4'-(na- phthalen-1-ylmethyl)-[1,1'-biphenyl])bromo- palladium(II) [Pd(1- MeNAP)(AdBrettPhos)Br] ^ ^ Following general procedure A with [Pd(1-MeNAP)Br]2(81.9 mg, 0.125mmol) and AdBrettPhos (169 mg, 0.25 mmol) in acetone, the title com-pound was obtained as yellow solid (195 mg, 0.201 mmol, 81%).1H NMR (400 MHz, CD2Cl2): δ = 8.58 – 8.55 (m, 1 H), 7.81 - 7.71 (m, 2 H), 7.46 - 7.33 (m, 4 H), 6.90 (d, J = 1.2 Hz, 2 H), 5.06 (s, 1 H), 5.04 (s, 1 H), 4.22 (s, 2 H), 3.84 (s, 3 H), 3.65 (s, 3 H), 2.29 (br. s, 12 H), 2.01 (br. s, 6 H), 1.85 - 1.71 (m, 15 H,), 1.03 (d, J = 6.9 Hz, 6 H), 0.93 – 0.91 (m, 12 H) ppm.13C NMR (75 MHz, CD2Cl2): δ = 155.7 (d, J = 2.2 Hz), 151.2 (d, J = 23.4 Hz), 140.5 (d, J = 23.8 Hz), 136.3, 134.4 (d, J = 1.5 Hz), 134.3, 132.6 (d, J = 13.8 Hz), 129.4, 128.4 (d, J = 6.0 Hz),, 127.2, 126.0, 125.7, 125.3, 113.6 (d, J = 1.7 Hz), 112.3 (d, J = 21.1 Hz), 111.1 (d, J = 3.3 Hz), 92.2 (d, J = 8.8 Hz), 55.0 (d, J = 3.3 Hz), 54.8, 50.7 (d, J = 8.3 Hz), 43.7, 43.5 (d, J = 5.3 Hz), 42.3 (d, J = 3.8 Hz), 37.2 (d, J = 1.1 Hz), 32.0 (d, J = 18.1 Hz), 29.9 (d, J = 9.1 Hz), 25.4, 23.6, 17.8 ppm.31P NMR (162 MHz, CD2Cl2): δ = 100.3, 86.2 ppm. MS (ESI-TOF): m / z (%)= 887.51 (32).EA: Calc. for C54H70O2PBrPd: C, 66.97%; H, 7.29%; N, 0.00%; Found: C, 67.09%; H, 6.94%; N, 0.00%. 2-diadamantylphosphino(2',4',6'-triisopropyl-3,6-dimethoxy-4'-(na- phthalen-2-ylmethyl)-[1,1'-biphenyl])bromo- palladium(II) [Pd(2- MeNAP)(AdBrettPhos)Br] ^ 29.8 (d, J = 9.1 Hz), 24.4 (d, J = 6.0 Hz), 19.0 ppm. 31P NMR (162 MHz, CD2Cl2): δ = 86.4 ppm. MS (ESI-TOF): m / z (%) = 928.44 (22), 887.44 (100), 827.22 (7), 746.41 (2) 641.35 (11). IV. General procedure for the arylation of hydrazinium triflate An oven-dried vial was charged with [Pd(1-MeNAP)(tBuBrettPhos)Br] (8.1 mg, 0.01 mmol, 1.0 mol%) and aryl chloride (1.0 mmol, 1.0 equiv., if solid), then KOH (253 mg, 4.5 mmol, 4.5 equiv.), [N2H5][OTf] (364 mg, 2.0 mmol, 2.0 equiv.), aryl chloride (1.0 mmol, 1.0 equiv., if liquid) and 3 mL 1,4-Dioxane were added in the glovebox and the vial was closed with a sep- tum cap. The resulting mixture was stirred at 25 °C for 16 h. Afterwards, acetylacetone (929 µL, 9 mmol, 9.0 equiv) was added to the reaction and the mixture was stirred at 100 °C for 6 h. The reaction was then cooled to room temperature, diluted with EtOAc (30 mL), and washed with saturated NaHCO3(30 mL), water (30 mL) and brine (30 mL). The organic phase was dried over MgSO4and purified by flash column chromatography (SiO2, cy- clohexane / ethyl acetate) to yield the products. Alternatively, the reaction mixture was diluted with diethyl ether after the reaction time of 16 h, and washed with saturated Na2CO3(30 mL), water (30 mL) and brine (30 mL). And then the organic layer was separated and acidified to pH＝3-4 by add- ing 37% HCl. The precipitate was filtered, washed with diethyl ether and dried under the vacuum to afford the corresponding aryl hydrazine hydro- chloride salts. V. Isolating and X-ray of the crystals of catalyst (IV) Single crystals of Pd(2-MeNAP)Br-tBuBrettPhos were grown by slow diffusion of n-hexane into a saturated solution of the complex in toluene. A crystal was taken up in perfluorinated oil and mounted onto a fiber loop on a Rigaku Oxford diffraction XtaLAB SuperNova diffractometer equipped with an Atlas CCD detector. The crystal was kept at 110.00(10) K during data collection. The obtained diffraction data was analyzed using CrysAlisPro software package. Using Olex2, the structure was solved with the ShelXT structure solution program using Intrinsic Phasing and refined with the ShelXL refinement package using Least Squares minimization (O. V. Dolo- manov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard, H. Puschmann, J. Appl. Crystallogr. 2009, 42, 339–341; G. M. Sheldrick, Acta Crystallogr. Sect. Found. Adv. 2015, 71, 3–8; G. M. Sheldrick, Acta Crystallogr. Sect. C Struct. Chem. 2015, 71, 3–8; P. Van Der Sluis, A. L. Spek, Acta Crystallogr A Found Crystallogr 1990, 46, 194–201). Crystal data and structure refinement for Pd(2-MeNAP)Br-tBuBrettPhos complex: Identification code paf1947b_auto_a.cif Empirical formula C37.33 H51.56 Br0.89 O1.78 P0.89 Pd0.89 Formula weight 721.92 Temperature 110(2) K Wavelength ^ 1.54184 Å (Cu K^) Crystal system monoclinic Space group C 2 / c (no.15) Unit cell dimensions a = 21.0683(3) Å ^= 90° b = 11.5672(2) Å ^= 91.5110(10)° c = 31.8109(5) Å ^ = 90° Volume 7749.7(2) Å3Z 9 Density ^(calculated) 1.392 g / cm3Absorption coefficient µ 5.709 mm-1F(000) 3376 Crystal size 0.344 x 0.136 x 0.098 mm3Theta range for data collection 2.779 to 76.405° Index ranges -24 <= h <= 26, -7 <= k< = 14, -39 <= l< = 38 Reflections collected 25989 Independent reflections 7566 [Rint = 0.0280, Rsigma = 0.0260] Completeness to theta = 67.684° 99.3 % Absorption correction multi-scan Max. and min. transmission 1.00000 and 0.44247 Refinement method full-matrix least-squares on F2Data / restraints / parameters 7566 / 0 / 457 Goodness-of-fit on F21.038 Final R indices [I > 2 ^(I)] R1 = 0.0308, wR2 = 0.0767 R indices (all data) R1 = 0.0331, wR2 = 0.0779 Extinction coefficient n / a Largest diff. peak and hole 1.311 and -0.786 e-Å-3and Single crystals of Pd(1-MeNAP)Br-tBuBrettPhos were grown by slow diffusion of n-hexane into a saturated solution of the complex in toluene. A crystal was taken up in perfluorinated oil and mounted onto a fiber loop on a Rigaku Oxford diffraction XtaLAB SuperNova diffractometer equipped with an Atlas CCD detector. The crystal was kept at 110.00(10) K during data collection. The obtained diffraction data was analyzed using CrysAlisPro software package. Using Olex2, the structure was solved with the ShelXT structure solution program using Intrinsic Phasing and refined with the ShelXL refinement package using Least Squares minimization (O. V. Dolo- manov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard, H. Puschmann, J. Appl. Crystallogr. 2009, 42, 339–341; G. M. Sheldrick, Acta Crystallogr. Sect. Found. Adv. 2015, 71, 3–8; G. M. Sheldrick, Acta Crystallogr. Sect. C Struct. Chem. 2015, 71, 3–8; P. Van Der Sluis, A. L. Spek, Acta Crystallogr A Found Crystallogr 1990, 46, 194–201). Crystal data and structure refinement for Pd(1-MeNAP)Br-tBuBrettPhos complex. Identification code xub2255_auto_a.cif Empirical formula C33.60 H46.40 Br0.80 O1.60 P0.80 Pd0.80 Formula weight 649.73 Temperature 110(2) K Wavelength ^ 1.54184 Å (Cu K^) Crystal system monoclinic Space group P 21 / c (no.14) Unit cell dimensions a = 13.5515(2) Å ^= 90° b = 12.38630(10) Å ^= 97.4060(10)° c = 22.8312(3) Å ^ = 90° Volume 3800.31(8) Å3Z 5 Density ^(calculated) 1.419 g / cm3 Absorption coefficient µ 5.821 mm-1F(000) 1688 Crystal size 0.240 x 0.204 x 0.131 mm3Theta range for data collection 3.289 to 77.056° Index ranges -16 <= h <= 17, -15 <= k< = 6, -27 <= l< = 28 Reflections collected 27573 Independent reflections 7616 [Rint = 0.0425, Rsigma = 0.0370] Completeness to theta = 67.684° 100 % Absorption correction multi-scan Max. and min. transmission 1.00000 and 0.55798 Refinement method full-matrix least-squares on F2Data / restraints / parameters 7616 / 0 / 438 Goodness-of-fit on F21.043 Final R indices [I > 2 ^(I)] R1 = 0.0298, wR2 = 0.0747 R indices (all data) R1 = 0.0326, wR2 = 0.0763 Extinction coefficient n / a Largest diff. peak and hole 0.651 and -0.802 e-Å-3VI. Results on hydrazine coupling of aryl chloride Conditions: 1.0 mmol 1a, 1.0 mol% [Pd], 1.0 mol% ligand, 1.5 equiv. KOH, 1.5 mL dioxane, 25 °C, 16 h.19F NMR yields with 1,4-difluorobenzene as internal standard.a[Pd] / ligand=1:1.5b4.5 equiv. KOH, 3 mL dioxane Additional Screening Results entry [N2H4] 11a^[%] 11b^[%] 11c^[%] 1N2H4H2O95 <1 <12b^ [N2H5][OAc] 82 " 33b^[N2H5][Cl] 95 " <14b^ [N2H5][Br] 34 " "5b^[N2H5] 93 " " 1 / 2[SO4] 6b^ [N2H5][OTf] 96 " "7bc^[N2H5][OTf] 98 " " aConditions: 1.0 mmol 10a, 2.0 equiv. [N2H4], 1.0 mol% [Pd(1-MeNAP)(tBuBrettPhos)Br],3.0 equiv. KOH, 1.5 mL Dioxane, 25 °C, 16 h.b4.5 equiv. KOH.C3 mL Dioxane. Yieldsdetermined by19F NMR using 1,4-difluorobenzene as internal standard. VII. Results on cross coupling reactions 1. Arylation of benzamide [Pd(1-MeNAP)(tBuBrettPhos)Br] (4.1 mg, 1 mol%) and benzamide (0.60 mmol) K3PO4(0.70 mmol) were treated with a solution of 4-chloroanisole (0.50 mmol, 1 equiv.), n-hexadecane (20 µL, internal standard) in tert-buta- nol (2 mL). The reaction mixture was stirred at room temperature for 16 hours and was then quenched with NH₄Cl (0.5 mL). The mixture was then diluted with 3 mL of ethyl acetate. A 0.5 mL aliquot of the organic phase was diluted with 3 mL of ethyl acetate and washed with 3 mL of NH₄Cl, filtered through MgSO₄ and celite, and analyzed by GC (GC analyses were carried out using an HP-5 capillary column (Phenyl methyl si- loxane, 30 m × 320 × 0.25, 100 / 2.3-30-300 / 3) using the following condi- tions: Carrier gas: N2; Initial Temperature: 60 °C; Final Temperature: 300 °C; Rate: 30 °C·min−1 ; Hold Time: 8 min; Column Flow: 1.0 mL min−1 ; Detector: FID, Temperature FID: 330 °C). Based on the calculated response factors vs hexadecane (0.69 for 3a, 0.59 for 1a), a 88% yield at 90% conversion was detected. The identity of the product was confirmed by GC-MS (Mass spectrometric data were acquired on a GC-MS Agilent 5977B MSD). 2. Arylation of trifluoroethyl amine [Pd(1-MeNAP)(tBuBrettPhos)Br] (4.1 mg, 2 mol%), NaOtBu (29.4 mg, 0.30 mmol) and a stock solution containing 4-chloroanisole (0.250 mmol, 1 equiv.), trifluoroethylamine (0.50 mmol), and n-hexadecane (20 µL, internal standard) in dioxane (2 mL) were combined under inert conditions in a 20 mL crimp cap vial equipped with magnetic stir bar. The reaction mixture was stirred at room temperature for 16 hours, quenched with (0.5 mL) of NH₄Cl and diluted with 3 mL of ethyl acetate. A 0.5 mL aliquot was transferred to a new vial containing 3 mL of ethyl acetate and 3 mL of NH₄Cl. After filtration through MgSO₄ and Celite, a 0.5 mL portion investigated by GC (GC analyses were carried out using an HP-5 capillary column (Phenyl methyl siloxane, 30 m × 320 × 0.25, 100 / 2.3-30-300 / 3) using the following conditions: Carrier gas: N2; Initial Temperature: 60 °C; Final Temperature: 300 °C; Rate: 30 °C·min−1 ; Hold Time: 8 min; Column Flow: 1.0 mL min−1 ; Detector: FID, Temperature FID: 330 °C). Based on the calculated response factors vs hexadecane (0.49 for 3a, 0.59 for 1a), a 99% yield at >99% conversion was detected. The identity of the product was confirmed by GC-MS (see GCMS spectra 1) (Mass spectrometric data were acquired on a GC-MS Agilent 5977B MSD). 3. Amination of aryl fluorides [Pd(1-MeNAP)(tBuBrettPhos)Br] (5.1 mg, 2.50 mol%), LiHMDS (129 mg, 0.75 mmol) and a stock solution containing 4-fluoroanisole (0.250 mmol, 1 equiv.), aniline (0.50 mmol), and n-hexadecane (20 µL, internal standard) in toluene (2 mL) were combined under inert conditions in a 20 mL crimp cap vial equipped with magnetic stir bar. The reaction mixture was stirred at 60 °C for 16 hours, quenched with 0.5 mL of NH₄Cl and diluted with 3 mL of ethyl acetate. A 0.5 mL aliquot was transferred to a new vial containing 3 mL of ethyl acetate and 3 mL of NH₄Cl. After filtration through MgSO₄ and Celite, a 0.5 mL portion investi- gated by gas chromatography (GCA). Based on the calculated response factors vs hexadecane, 64% yield at 70% conversion was detected. Discussion of the results: When using [Pd(1-MeNAP)(tBuBrettPhos)Br] cat- alyst, significant conversion was achieved even under mild conditions, with the reaction temperature lowered to 60^°C substantially lower than the con- ditions reported for similar challenging electron-rich aryl chlorides such as 4-chloroanisole. At this low temperature, LiHMDS can be employed without causing side reactions. These results clearly demonstrate that the MeNAP complex bearing a standard ligand exhibits markedly superior catalytic ac- tivity compared to current mainstream catalytic systems. 4. Alpha-arylation of carbonyl compounds a) Arylation of tert-Butylacetate with 4-fluoroanisole [Pd(1-MeNAP)(tBuBrettPhos)Br] (2.04 mg, 1 mol%), LiHMDS (129 mg, 0.75 mmol) and a stock solution containing 4-fluoroanisole (0.250 mmol, 1 equiv.), tert-Butylacetate (0.50 mmol), and n-hexadecane (20 µL, internal standard) in toluene (2 mL) were combined under inert conditions in a 20 mL crimp cap vial equipped with magnetic stir bar. The reaction mixture was stirred at 30 °C for 12 hours, quenched with 0.5 mL of NH₄Cl and diluted with 3 mL of ethyl acetate. A 0.5 mL ali- quot was transferred to a new vial containing 3 mL of ethyl acetate and 3 mL of NH₄Cl. After filtration through MgSO₄ and Celite, a 0.5 mL portion investigated by gas chromatography (GCC). Based on the cal- culated response factors vs hexadecane, 61% yield at 85% conversion was detected (seen GCC). [Pd(1-MeNAP)(tBuBrettPhos)Br] (2.04 mg, 1 mol%), LiHMDS (129 mg, 0.75 mmol) and a stock solution containing 4-fluoroanisole (0.250 mmol, 1 equiv.), N,N-Diethylacetamide (0.50 mmol), and n- hexadecane (20 µL, internal standard) in toluene (2 mL) were com- bined under inert conditions in a 20 mL crimp cap vial equipped with magnetic stir bar. The reaction mixture was stirred at 30 °C for 12 hours, quenched with 0.5 mL of NH₄Cl and diluted with 3 mL of ethyl acetate. A 0.5 mL aliquot was transferred to a new vial containing 3 mL of ethyl acetate and 3 mL of NH₄Cl. After filtration through MgSO₄ and Celite, a 0.5 mL portion investigated by gas chromatography (GCA). Based on the calculated response factors vs hexadecane, 53% yield at 60% conversion was detected (seen GCC). c) Arylation of acetophenone with 4-fluoroanisole [Pd(1-MeNAP)(tBuBrettPhos)Br] (2.04 mg, 1 mol%), LiHMDS (129 mg, 0.75 mmol) and a stock solution containing 4-fluoroanisole (0.250 mmol, 1 equiv.), acetophenon (0.50 mmol), and n-hexadecane (20 µL, internal standard) in toluene (2 mL) were combined under inert condi- tions in a 20 mL crimp cap vial equipped with magnetic stir bar. The reaction mixture was stirred at 30 °C for 12 hours, quenched with 0.5 mL of NH₄Cl and diluted with 3 mL of ethyl acetate. A 0.5 mL aliquot was transferred to a new vial containing 3 mL of ethyl acetate and 3 mL of NH₄Cl. After filtration through MgSO₄ and Celite, a 0.5 mL por- tion investigated by GCA. Based on the calculated response factors vs hexadecane, 80% yield at 85% conversion was detected (seen GCC). Discussion of the results: The α-arylation of carbonyl compounds, such as esters and protected amino acids, remains a significant challenge in Pd-cata- lyzed cross-coupling reactions due to the intrinsically low nucleophilicity of the α-carbon adjacent to the carbonyl group. This reduced nucleophilicity stems from the strong electron-withdrawing effect of the carbonyl moiety, which stabilizes the α-position via resonance, thereby decreasing its reactivity compared to typical amines. This work addresses these limitations by employing α-MeNAP-based Pd precatalysts that demonstrate superior catalytic activity at significantly milder temperatures, often near room temperature (30 °C), thereby enabling more efficient and selective α-arylation of carbonyl compounds under gentler con- ditions. In direct comparison, the one component catalyst [Pd(1- MeNAP)(tBuBrettPhos)Br], gave a high yield within 12 hours at 30 °C. It is the first example of coupling of non-activated aryl fluorides with carbonyl compounds and serves as a further example demonstrating the advantages of this catalyst system.

Claims

Claims 1. Process for the selective monoarylation of hydrazine hydrate or hydra- zine salts of the general formular (I) or (II) : NH2NH2[N2H5]W (I) (II) wherein W is a counter anion which comprises the steps of: - providing an organic polar solvent, which does not interact with the reactants added but dissolves the reactants; - adding thereto as a reactant a hydrazine of formula (I) or (II); - adding a catalyst of the general formula (III) or (IV):wherein R1, R2 are same or different from each other and being linear or branched alkyl; R3, R4, are same or different from each other and being branched or cyclic alkyl; R5, R6, R7 are same or different from each other and being H, linear or branched or cyclic alkyl; R8 is an alkenyl, aryl or aryl alkenyl group; RAand RBare if present independently from each other one or more alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, aralkyl, hydrogen,halogen, heteroaralkyl, alkoxyl, dialkylaminyl, trialkylsilyl; and X is O or S, with O being preferred; Y is an anionic ligand; Z is a σ-donor ligand; - adding as a further reactant an aryl halide or heteroaryl halide to the reaction mixture; and - adding a base; and - isolating the arylhydrazine from the reaction mixture.

2. Process according to claim 1, wherein R1 is methyl, ethyl, propyl, iso- propyl, butyl, iso-butyl and sec-butyl, R2 is methyl, ethyl, propyl, iso- propyl, butyl, iso-butyl and sec-butyl, R3 is tert-butyl, isopropyl or 1- adamantyl, propellane, R4 is tert-butyl, isopropyl or 1-adamantyl, pro- pellane; R5 is methyl, ethyl, propyl, isopropyl, butyl, iso-butyl and sec- butyl, R6 methyl, ethyl, propyl, isopropyl, butyl, iso-butyl and sec-bu- tyl, R7 is methyl, ethyl, propyl, isopropyl, butyl, iso-butyl and sec-bu- tyl .

3. Process according to one of claims 1 – 2, wherein the aryl halide is se- lected from the group consisting of phenyl, naphthyl, pyridyl, pyrazinyl and thienyl.

4. Process according to one of claims 1 – 3, wherein the organic solvent is selected from the group consisting of THF, dioxane, DME, CPME, 2- MeTHF.

5. Process according to one of claims 1 – 4, wherein the base is selected from the group consisting of KOH, K2CO3, K3PO4, Cs2CO3,NaOtBu, KOtBu, NaOMe, NaOH.

6. Process according to one of claims 1 – 5, wherein the process is con- ducted at a temperature of 10°C to 80°C.

7. Process according to one of claims 1 – 6, wherein the arylhydrazine is isolated by acidified by concentrated hydrochloride acid to generatethe hydrochloride salts and purified by two-phase extractions, precipi- tation and filtration.

8. Process according to one of claims 1 - 7, wherein Z is a bidentate lig- and in which one part of the ligand is connected to the Palladium via a σ-donor bond as mentioned before and the other part is connected to the Palladium via a heteroatomic substituent.

9. Catalyst of general formula (IV)wherein R1, R2 are same or different from each other and being linear or branched alkyl; R3, R4, are same or different from each other and being branched or cyclic alkyl; R5, R6, R7 are same or different from each other and being H, linear or branched or cyclic alkyl; R8 is an alkenyl, aryl or aryl alkenyl group; RAand RBare if present independently from each other one or more alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, aralkyl, hydrogen, halo- gen, heteroaralkyl, alkoxyl, dialkylaminyl, trialkylsilyl; and X is O or S, with O being preferred; Y is a an anionic ligand.

10. A process for the production of a compound according to claim 9, characterized in that the compound 1,3-Divinyl-1,1,3,3-tetramethyldisiloxanepalladium(0) - Pd2(vs)3is reacted with an al- lylhalide or naphthyl halide of formula (X)wherein R’, R’’, R’’’ are independently of each other selected from the group consisting of H, alkyl, aryl or R’ and R’’ form an aromatic or non-aromatic cyclic ring; Y is a halide; and a ligand of formula (VII)wherein R1, R2 are same or different from each other and being linear or branched alkyl; R3, R4, are same or different from each other and being branched or cyclic alkyl; R5, R6, R7 are same or different from each other and being H, linear or branched or cyclic alkyl; RAand RBare if present independently from each other one or more alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, aralkyl, hydrogen, halogen, heteroaralkyl, alkoxyl, dialkylaminyl, trialkylsilyl; X is O or S;are reacted under conditions sufficient to produce the compound of claim 9.Process of claim 10, wherein the reaction is a one-pot reaction.

11. The process of claim 10, wherein the allylhalide or naphthyl halide of formula (X) is a 1-methyl naphthaline (1-MeNAP) or 2-methyl naph- thaline (2-MeNAP) compound.

12. A method for carrying out a coupling reactions comprising the steps of - Providing a reaction mixture comprising at least a substrate, a cou- pling partner and a compound of formula (VI) according to claim 9; - Reacting the substrate with the coupling partner in the presence of the compound of formula (VI) according to claim 9 to form a cou- pling product.

13. The method of claim 12, the coupling reaction being a C-C, C-N or a C- O coupling reaction.

14. The method of any of claims 12 to 13, wherein the coupling reaction is selected from the group consisting of: (i) catalytic hydrofunctionalization reactions of alkynes and alkenes; (ii) catalytic hydroamination reactions of alkynes and alkenes; (iii) catalytic O-H addition reactions on alkynes and alkenes; (iv) catalytic coupling reactions, such as the catalytic amination of aryl fluorides, the catalytic N-arylation of aryl fluorides, the catalytic alpha- arylation of carbonyl compounds, the catalytic N-arylation of trifluoro- ethyl amines or the catalystic N-arylation of amides, in particular ben- zamides; (v) catalytic Kumada coupling reactions, Murahashi coupling reactions, Negishi coupling reactions or Suzuki coupling reactions, in particular for the preparation of biarylene;(vi) catalytic cross-coupling reactions, in particular C-N and C-O cou- pling reactions; and / or (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.

15. Process for the production of a compound according to claim 9, characterized in that a compound of general formula (VI)wherein R’, R’’, R’’’ are independently of each other selected from the group consisting of H, alkyl, aryl or R’ and R’’ form an aromatic or non- aromatic cyclic ring; Y is a halide; and a ligand of formula (VII)wherein R1, R2 are same or different from each other and being linear or branched alkyl; R3, R4, are same or different from each other and being branched or cyclic alkyl; R5, R6, R7 are same or different from each other and being H, linear or branched or cyclic alkyl; RAand RBare if present independently from each other one or more alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, aralkyl, hydrogen, halogen, heteroaralkyl, alkoxyl, dialkylaminyl, trialkylsilyl; X is O or S; are reacted under conditions sufficient to produce the compound of claim 9.

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