Syntheses Of Guanidine, Guanidinium Salts And Their Applications On Palladium-catalyzed C-C Bond Coupling Reaction

Palladium catalysis has achieved the status of an indispensable tool fororganic synthesis. Among basic types of palladium-catalyzed transformations,the Heck reaction and related chemistry occupy a special place. The reactionpresents one of the simplest ways to obtain variously substituted olefins,dienes, and other unsaturated compounds, many of which are useful as dyes,UV screens, pharmaceuticals, optoelectronic devices etc. The reaction can becatalyzed by palladium complexes with or without phosphine ligands(phosphane assisted vs phosphine-free catalysis). A primary role of phosphineligands is to support palladium in its zero oxidation state in the form of stablespecies. Phosphine ligands are expensive, toxic, and unrecoverable. Inlarge-scale applications on industry, the phosphines might be a more seriouseconomical burden than even palladium itself. Recently, there have been anumber of reports on phosphine-free catalytic systems in relation to thedevelopment of the Heck reaction. However, most of these new ligands are notcommercially available and some are cumbersome to synthesize. Althoughmany immobilized-catalysts have also been explored, the leaching of catalysthas not been resolved in recoverable cycle. The recent development of theionic liquids offered a new method and technology for this reaction. As analternative to volatile, toxic, organic solvents, ILs can serve as an excellentmedium and as a mobile support for Pd catalysts. However, imidazolium saltswere inefficient for aryl bromide or aryl chloride in the absence of phosphineligands at temperatures below 100°C. To avoid catalyst leaching in IL systems,some efforts have been made by introducing functional groups into the ionicliquid which can complex with metal centers. Another way is to introduceimidazolium tags into a metal complex to enhance the solubility of the catalystin ionic liquids. The syntheses of functionalized ionic liquids or ionic metalcomplexes are rather complicated and require multistep procedures. Therefore,finding more simple, efficient, and reusable catalytic systems for thepalladium-catalytic reaction is of importance practically and is still in demand.Guanidines can be categorized as organic superbases owing to theresonance stabilization of their conjugated acids and are therefore expected tocatalyze various types of base-mediated organic reactions and acted as basiccatalyst. Guanidines could also act as ligands towards metals due to theinvolvement of the nitrogen lone pairs. A comparison of the structure ofguanidine with phosphines led us to test the effectiveness of guanidine as aligand in the Heck reaction. Designable structure and easy preparation ofguanidine offer an opportunity for sieving proper ligand in palladium-catalyzed reactions. The positive charge in the guanidinium salts is delocalized over onecarbon and three nitrogen atoms, which gives them a high degree of thermalstability compared to tetraalkylammonium salts. Guanidinium salts exhibitsome particular properties due to the designable alkyl chain, therefore, theycan be use as phase transfer catalyst, Lewis acid and surfactant.Now we concentrate on seeking phosphine-free ligands, in order fordeveloping green chemistry and environmentally benign alternative solvents.A series of tetraalkyl-guanidines, pentaalkyl-guanidines,hexaalkyl-guanidinium halides and corresponding ionic liquids weresynthesized by two routes from dimethylcyanamides or tetraalkylureas. Theutility of these tetraalkyl-guanidines and pentaalkyl-guanidines in Heckreaction and Suzuki reaction confirmed that guanidine-palladium was a highefficient, oxidation resistant, air and water stable catalyst, and this workdeveloped a new method to phosphine-free catalyst system. The reaction inionic liquids avoided the utility of potential toxicity volatile organic solventand could realized the recycle of the solvent and catalyst.Tetraalkylguanidine preparation involved the direct addition of secondaryamines to dimethylcyanamides, then the hexaalkylguanidinium halide (GX)were prepared from tetraalkylguanidine with an alkylating agent in thepresence of an alkaline reagent. 'Vilsmeier salt' was synthesized fromtetraalkylureas with oxalyl chloride, then reacted with amines to producepentaalkyl -guanidine or hexaalkylguanidine. The syntheses of the guanidinesand guanidinium salts were mild, high yield reactions, and the product are easyto be purified.Guanidinium ionic liquids were synthesized by ionic exchange. Westudied in full the physico-chemical properties of a number of GRILs,involving density, viscosity, polarity, melt point, thermal stability andelectrochemical property, and discovered the relationship of the property andthe structure of the ionic liquids.Guanidine could effectively keep the efficiency of the palladium catalystwhen they were used as ligand in Heck reaction. The high efficient catalyticsystem is suitable for the reaction of aryl bromides and active aryl chlorides,and has toleranted to a broad range of sensitive functional groups. it is one ofthe most efficient phosphine -free catalytic system because the TONs were upto 106 when iodobenzene was used as the substrate. We confirmed the role ofthe guanidine by synthesizing and characterizing the guanidine/palladiumcoordination compound. Guanidine ligand have many advantages to otherphosphine or phosphine-free ligand, such as easy preparation, high activity,and low cost.We also sieved the fine solvents for Heck reaction-hexaalkylguanidiniumionic liquids, and the advantages of using these solvents in Heck reaction wereascribed to 1) Ionic liquids could act as phase-transfer catalyst and increasedpolarity of the solvent, which would stabilize ionic and polar transition statesin the catalytic cycle and could thus lead to an increased overall reaction rate;and 2) Ionic liquids could facilitate oxidative addition and reductiveelimination during a Pd0/PdII catalytic cycle;3) Furthermore, the effect wassometimes attributed to the stabilization of palladium(0) colloids which maybe formed in situ by its extraordinary bulkiness, the size of the Pd particleswas determined by transmission electron microscopy (TEM), and the diameterof most of the Pd particles were in the range of 2– 5nm;4) The catalyticsystem could be reused several times.The basic guanidine-based Br?nsted ionic liquids(GIL2) are efficientreaction media for palladium-catalyzed Heck reaction. The ILs couldeffectively reduce the palladium leaching in catalytic cycle, and playedmultiple roles in the reaction: it could act as a solvent, as a strong base tofacilitate β–hydride elimination, and as a ligand to stabilize activated Pdspecies. To the best of our knowledge, GIL2 is one of the simplest catalystsystems in the Heck reaction by far.Palladium complexes derived from guanidine were very active in theSuzuki cross-coupling of aryl halides including difficult aryl chlorides. Astable and efficient Pd(OAc)2/guanidine catalytic system for Suzuki-Miyauracross-coupling reaction has been developed. In the presence of Pd(OAc)2 andguanidine, coupling of aryl halides with arylboronic acids was carried outsmoothly to afford good to excellent yields and high turnover numbers (TONs)(the maximal TONs were up to 780 000 for the reaction of bromobenzene withphenylboronic acid) using EtOH as the solvent. This new catalytic system wastolerant to a broad range of sensitive functional groups, such as NO2, NH2,CH3CO, COOH groups. This system represents the first guanidine-basedmonopalladium-centered catalyst for the Suzuki reaction at room temperature.Moreover, the Pd(OAc)2/ guanidine /PEG-400(or guanidinium salt solvent)system could be recycled and reused five times without any loss of catalyticactivity for aryl bromides. As a result, this new catalytic system provided aneasy, quick, and convenient procedure for Suzuki reactions.Our research indicated that guanidine/palladium complexe were highlyactive, stable, and green catalysts in both the Heck reaction and Suzukireaction. Guanidinium salt solvents could stabilize the palladium nanoparticlesand the catalyst system could be recycled and reused without losing ofcatalytic activity in both the Heck and Suzuki reaction. The basicguanidine-based Br?nsted ionic liquids could act as solvents, as strong basesand ligands in Heck reaction, this catalytic system could also be recycled andreused without losing of catalytic activity.