JPH11514012A - Combinatorial synthesis and analysis of organometallic compounds and catalysts - Google Patents

Abstract

  (57) [Summary] The invention particularly relates to methods for the synthesis, screening and characterization of organometallic compounds and catalysts (eg, homogeneous catalysts). The methods of the present invention allow for the combined synthesis, screening and characterization of libraries of supported and unsupported organometallic compounds and catalysts (eg, homogeneous catalysts). The method of the present invention is applicable to preparing and screening a large number of organometallic compounds that can be used not only as catalysts (eg, homogeneous catalysts), but also as additives and therapeutics.

Description

DETAILED DESCRIPTION OF THE INVENTION             Combinatorial synthesis and analysis of organometallic compounds and catalysts   This invention is part of US Patent Application No. 60 / 016,102, filed July 23, 1996. No. 60 / 028,106 (filed October 9, 1996) US Patent Application No. 60 / 029,255, a continuation-in-part application (filed October 25, 1996) No. 60 / 035,366, filed on Jan. 10, 1997, which is a continuation-in-part of ) Is a continuation-in-part of US Patent Application No. 60 / No. (Attorney Record No. 01670 No. 3-000340) (filed on June 9, 1997). These patents The teachings of the application are incorporated herein by reference.                                Field of the invention   The present invention is particularly directed to the synthesis, screening and characterization of organometallic compounds and catalysts. It relates to a method for characterization. Departure The method of the present invention relates to the combination of a library of supported and unsupported organometallic compounds and catalysts. Combinatorial synthesis, screening, and characterization This is to perform theization. The method of the present invention comprises a catalyst (eg, a homogeneous catalyst) A large number of organometallic compounds that can be used not only as additives, but also as additives and therapeutic agents. It can be applied when making and screening.                                Background of the Invention   Metal complexes stabilized by ancillary ligands (ie, organometallic compounds (organometallic compounds)) are catalysts, additives, stoichiometric reagents (stoichiom etric reagents), monomers, solid precursors, therapeutics, and pharmaceuticals. Ancillary ligand systems contain organic substituents that bind to and associate with the metal center And therefore the shape of the active metal center of the organometallic compound, the electron Gives an opportunity to modify properties and chemical properties.   Certain organometallic compounds include oxidation, reduction, hydrogenation, hydrosylation, , Hydroformylation, polymerization, carbonylation, isomerization, metathesis, carbon-water Element activation, cross-coupling, Friedel-Crafts reaction and Reactions such as alkylation, hydration, dimerization, trimerization, Diels-Alder reaction It becomes a catalyst for the reaction. Organometallic compounds can be used to Prepared by compounding the genus precursor in a suitable solvent at a suitable temperature Can be. The activity and selectivity obtained from the desired organometallic compound depends on the coordination Element shape, selection of metal precursor, reaction conditions (eg, solvent, temperature, time, etc.) and It depends on various factors, including the stability of the desired product. In some cases, The resulting organometallic compound is "activated" by a third component or cocatalyst. Until the catalyst is inactive. In many cases, the third component, the “modifier (modifier) Definer) ”to the active catalyst to improve the performance. High yield of effective catalyst species Effect of cocatalyst, type and amount of modifier, auxiliary ligand, metal The validity of the precursor and the reaction conditions cannot be predicted solely from its principles. Involvement Catalysts found due to lack of theoretical possibilities given many variables It is not surprising that the optimization and tedious and inefficient steps involved.   An important example is the single-sited olefin pol ymerization catalysis). The active site is usually determined by an ancillary ligand. Stabilized ligand-stabilized transition metal alkyl complex  coordinately unsaturated transition metal alkyl complex). Like this Catalysts are often prepared by reacting two components. First The components are stabilized by ancillary ligands and have a relatively low coordination number (typically 3 to 4 ) Transition metal compounds. The second component is known as an activator or cocatalyst Withdrawing an alkylating agent and a negatively charged leaving group ligand from the first component Ion exchange reactants containing soluble Lewis acids, compatible non-coordinating anions Or a combination thereof. Over the past 15 years Metallic catalysts have been discovered, but these discoveries suggest possible catalytic materials Are synthesized individually and then they are screened for catalytic activity. It has taken time-consuming work. New organometallic catalyst synthesized and obtained catalyst To screen for useful properties, Developing an economical, systematic approach can significantly advance the state of the art Will do. Particularly promising methods to simplify the discovery task are ligands and probes. Making a combination library of media and an efficient parallel detection method or Screen compounds in the library for catalytic activity using a rapid sequential detection method Depends on the way you do it.   Combinatorial methods for synthesizing libraries of organic compounds are well known. For example , Pilrung et al., For example, describe a light-dependent spatially addressable synthesis method (lig ht-directed, spatially-addressable synthesis techniques) A method for making arrays of tides and other molecules has been developed (US Pat. No. 5,143,854). No. and PCT WO 90/15070). In addition, Fodor et al. Describe a light-dependent space Automated methods for performing dynamically addressable synthetic methods, photolabile protecting groups, King method and fluorescence intensity data collection method are being developed (Fodor et al., PCT Publication No. WO  92/10092). In addition, recently, Ellman et al. Important organic compounds, benzodiazepines, prostaglandins A set of library of derivatives of carrot and β-turn mimetics Developing combined synthesis (combinatorial synthesis) and screening methods (See U.S. Patent No. 5,288,514).   Using these various combinatorial methods, thousands and millions of different organic Arrays containing elements can be formed (US Pat. No. 805,727). The currently used fixtures for coordinating such libraries Phase synthesis is a step-wise process (ie, building block to form the desired compound). (A method of sequentially coupling the fibers). For example, Pilrung and others The method involves attaching a photoremovable group to the substrate surface and exposing selected areas of the substrate to light. To activate these regions and convert amino acid monomers having photoremovable groups into active regions. And the steps of activation and conjugation are performed with a polymer of desired length and sequence. Polypeptide array on substrate by repeating until peptide is synthesized Are synthesized. This pilling and other methods include joining, masking, unprotecting, joining, etc. It is a sequential and step-by-step process utilized. Biological polymers, biological organic substances (b iological organic molecules) and small organic molecule libraries. They recognize biological rfeceptors (i.e. proteins, DNA, etc.) To screen for the ability to bind and block, Such techniques have been used. Building blocks (ie, monomers, amino acids) Such solid-phase synthesis methods, which in addition include forming the target compound Can be used immediately to prepare a large number of inorganic and organic compounds Absent. In view of semiconductor manufacturing methods, these methods are referred to as "ultra-large-scale immobilized Synthetic method ”(Very Large Scale Immobilized Polymer Synthesis) or“ VLSIP S "technology.   Schultz et al., Combinatorial chemistry method for the first time in the field of materials science (PCT WO / 9611878; The teachings of which are incorporated herein by reference). In particular, Schultz et al. Method for manufacturing and preparing a substrate having an array of various materials in each predetermined area And an apparatus. Usually, a component of the substance is supplied to each predetermined area on the substrate, and At the same time, by reacting the reactants to form various substances, Create a quality array. Using this method by Schultz et al. Numerous substance groups including, intermetallics, alloys, and ceramics binatorially) can be manufactured. Once adjusted, these substances can be It will be possible to screen for useful properties. Field of asymmetric catalysis (Liu) and Ellman (J. Org. Chem. 1995, 60: 7) ) Has developed a solid phase synthesis strategy to synthesize 2-pyrrolidine methanol ligands, Rapid parallel mdethod or serial screening (serai l screening method) using conventional analysis methods Direct evaluation of these ligands for enantioselective addition to aldehyde substrates It was shown that it could be.   From the above, a library of organometallic materials was synthesized, and this library was It is clear that it is necessary to develop methods for screening for gender is there. These methods can greatly accelerate the speed of discovering and optimizing catalytic processes. Let's be. Quite surprisingly, the present invention provides such a method. Things.                                Disclosure of the invention   The present invention provides an array, i.e., a library synthesis and keying of catalysts and organometallic compounds. The present invention relates to a method for performing characterization. More specifically, the method of the invention comprises: A large array of various supported and unsupported ligands, catalysts and organometallic compounds or Combinatorial synthesis, screening and characterization of libraries Is what you do.   Accordingly, the present invention, in one aspect, provides an array of metal-ligand compounds, A method of leaning, (A) synthesizing an array of spatially separated ligands; (B) providing a suitable metal precursor to each element of the ligand array to form a metal-ligand Producing an array of compounds, (C) selectively activating an array of metal-ligand compounds with a suitable cocatalyst; (D) modifying the array of metal-ligand compounds with a third component; (E) Optical imaging, optical spectroscopy, mass spectrometry, chromatography, sound Group consisting of imaging, acoustic spectroscopy, infrared imaging and infrared spectroscopy Using parallel or rapid serial screening methods selected from -Including screening an array of ligand compounds for useful properties Provide the law.   The invention, in another aspect, comprises from 10 to 10⁶Based on different metal-ligand compounds Consists of an array with known locations on the body. In one embodiment, the array comprises 50 It has more than one different metal-ligand compound at each known location on the substrate. Another In some embodiments, the array comprises 100 or more or 500 or more different metal-configurations. Will consist of a ligand compound. In yet another embodiment, the array comprises 1,000 species. 10,000 or more, or 10 or more⁶More than one different metal-ligand compound It has a known position on the substrate.   Other features, objects, and advantages of the invention and preferred embodiments of the invention are set forth in the following details. It will be clear from the simple explanation.                             BRIEF DESCRIPTION OF THE FIGURES   FIGS. 1A and 1B show transition metal-based metallocene catalysts, respectively. ysts) and subsequent transition metals such as zirconium and nickel based catalysts. Here is an example.   2A and 2B show a series of diimine combinations mutated in combination.  ligants) and / or combinations of diamine ligants 2 shows a sequence of solid phase reactions that can be used to perform   3A and 3B show various combination routes for synthesizing various ligands. You.   Figures 4A-4B are made using the combinatorial chemistry format. 2 shows examples of ligand cores that can be produced.   FIG. 5 shows the synthesis of an auxiliary ligand with CN = 1 or 2 and charge = 0 or −1 on a carrier. Here is an example.   FIG. 6 shows a carrier having an auxiliary ligand having CN = 1, 2 or 3, and charge = 0, −1 or −2. The following shows an example of combining.   FIG. 7 shows that the auxiliary ligand represented by [2, 2] is a metal having CN = 2 and charge = −2. An example of synthesis on a carrier together with a complex is shown.   FIG. 8 shows two types of carrier-unsupported auxiliary ligands having CN = 2 and charge = 0, −1 or −2. An example of the synthesis of   FIG. 9 shows CN = 2, charge = −1, and the carrier-unsupported represented as [2, 1]. The synthesis example of an auxiliary ligand is shown.   FIG. 10 shows CN = 2, charge = 0, −1, −2 or −3 and a functional linker (f 1 shows an example of the synthesis of a carrier-unsupported auxiliary ligand having an unctional linker.   FIG. 11 shows a "non-functional" linker with CN = 2, charge = 0, -1 or -2. 1 shows an example of synthesizing a carrier-unsupported auxiliary ligand having a ligand.   FIG. 12 shows a carrier without CN = 2 or 3, and charge = 0, -1, -2, -3 or -4. An example of the synthesis of a supported auxiliary ligand will be described.   FIGS. 13A and 13B show acidic functionalities for R group substituents in an array or library. An example of a synthetic scheme useful for conferring properties is shown.   FIG. 14 consists of 48 diimine ligands, followed by 96 diimine-metallations. The synthesis of a library that converts to a compound library is described.   FIG. 15 shows a sample using a fixed catalyst, a proton sponge, and a reactant-adsorbing reactant. A generalized solution-phase synthesis of imines is shown.   FIG. 16 shows an array of commercially available diketones used to practice the present invention. .   FIG. 17 shows examples of immobilized Lewis acid catalysts and dehydrating reactants.                     DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS                                   table of contents I. Words: Abbreviations and definitions II. Assembly of combinatorial library     A. Overview     B. Carriers and substrates for synthesis     C. Ligand     D. Linker     E. FIG. metal     F. Fixed reactants     G. FIG. Non-coordinating anion (NCA)     H. Design and synthesis of diimine catalyst library III. Screening of combinatorial libraries IV. Example I. Vocabulary: abbreviations and definitions   Abbreviations and generalized chemical formulas used herein have the following meanings. Dienyl; MAO, methylaluminoxane; [Q]⁺[NCA]^-, Reactive cations / Non-coordinating anion compound; EDG, electron donating group; EWG, electron withdrawing group (electro n-withdrawing group); DME, dimethoxyethane; PEG, poly (ethylene glycol) Recall); DEAD, diethyl azodicarboxylate; COD, Clooctadiene; DBU, 1,8-diazabicyclo [5.4.0] undec- 7-ene (1,8-diazabicyclo [5.4.0] undec-7-ene); FMOC, 9-fluoreni Methoxy, HOBT, 1-hydroxybenzotriazole; BTU , O-Benzotriazole-N, N, N ', N'-tetramethyl-uronium- Hexafluorophosphate; DIAD, diisopropylazodicarboxyle To Other abbreviations and chemical formulas used herein are commonly given by those skilled in the art. Has meaning.   catalystA: As used herein, the term “catalyst” increases the rate of a chemical reaction. Or a compound that causes a chemical reaction. The catalyst of the present invention The other is an organometallic compound. Some of the organometallic compounds of the present invention are referred to as "active It becomes catalytically active only after it is "modified". Other organometallic compounds of the invention are , "A catalyst that does not require an activating substance". Have.   Ligand: Organometallic compounds are other atoms conventionally known as "ligands", A central atom or ion surrounded and bound by ions or small molecules It has been formulated as consisting of The ligand is organic (eg, η¹-Aryl , Alkenyl, alkynyl, cyclopentadienyl, CO, alkylidene, cal Ben) or inorganic (eg, Br)^-, Cl^-, OH^-, NO^2-Etc.) It is either charged or neutral. Inorganic or organic moieties in metal compounds The numbers present as ligands are usually indicated by the prefixes di, tri, tetra, etc. complexity If there are multiple organic ligands, prefix bis, tris, tetrakis, etc. Indicated by   As used herein, the term "ancillary ligand" Is different from a "leaving group ligand". Auxiliary ligand Remains associated with the metal center as an integral component catalyst or organic compound. Is what it is. The ancillary ligand depends on the number of coordination sites it occupies and the formal charge. Defined. A leaving group is a ligand that is displaced in a ligand displacement reaction. Detachment The base ligand can be replaced by a component of the auxiliary ligand or activator.   In most cases, assign a charge to the ligand and assign the number of coordination sites occupied by the ligand The format for this is easy and clear. As with many forms of chemistry, these There are instances where allocation can be a symptom of interpretation and debate. This ligand is centered on the metal center It is thought to occupy three or one coordination sites on the metal, depending on the overall symmetry The case of the η5 cyclopentadienyl (Cp) ligand is one such example. metal When the symmetry of a compound is best described as being octahedral Assigns the Cp ligand to occupy three ligand loci (on the face of the octahedron) I can However, the symmetry of the metal compound is tetrahedral, square or triangular. In the best case, the Cp ligand occupies one ligand locus. It is considered to have. For the purposes of the present invention, Cp ligands are metal compounds Let us consider formally above as occupying one coordination locus.   Activator: The activating substance is generally used for synthesizing various catalysts. Activator Quality activates metal centers as a catalyst, for example, activates metal centers Also, in some embodiments, the touch from the source is located at a predetermined area on the substrate. It may be a chemical or energy source that is directed to a medium precursor.   Activator is a chemical reactant that converts a metal compound to an olefin polymerization catalyst In embodiments, the activator typically comprises two broad classes of substances: (1) alkyl (2) ionizing agent.   As used herein, an "alkylating agent" is, for example, a halide or an alcohol. Non-reactive ligands, such as cooxides, can be used, for example, A reactant that functions by exchanging with a reactive sigma-bonded alkyl group . An example of this type of activation is Cp using methyllithium._Two ^*ScCl to Cp_Two ^*S cMe (where Cp^*= Η_Five-C_FiveMe_Five). In general, activation by alkylation involves a highly coordinated metal center of the catalyst precursor. Run in systems that are saturated and do not require a further reduction in coordination number to function as a catalyst. But this activation mode is not limited to such metal centers .   "Ionizing agent" reduces the coordination number of the transition metal precursor by at least one coordination site Thereby, it functions as an activator to form an ionic product. Ionizing agent There are two types: (1) Lewis acids and (2) ion exchange activators .   "Lewis acids" work by extracting a leaving group from the metal center, Non-coordinating anine (“NCA” consisting of a leaving group ligand and a Lewis acid) Form unsaturated unsaturated transition metal cations. "Ion exchange activators" The compatible non-coordinating anion formed is supplied to the catalyst precursor, Receive a coordinating anion (such as a methyl or halide group). Ion exchange activity The activating substance has the general formula Q⁺NCA^-Where Q⁺Is a reactive cation, N CA^-Is a compatible non-coordinating anion. Lewis acid and ion used in the present invention Exchange activators are soluble, supportable (eg, silica resin-bound) Lewis acids and And both ion-exchange activating substances.   In some cases, activation may be caused by Lewis acids or ion exchange materials. It can be carried out. For example, the catalyst [Cp_TwoZrCH_Three]⁺[B (C₆F_Five)_ThreeCH_Three]^- (Here, [B (C₆F_Five)_ThreeCH_Three] Is "compatible non-coordinating anion" or " Consider two chemical routes to synthesize Use the Lewis acid pathway In this case, the catalyst precursor is [Cp_TwoZr (CH_Three)_Two] And the activator is [B ( C₆F_Five)_Three]. When using the "ion exchange" route, the catalyst precursor is: [Cp_TwoZr (CH_Three)_Two] And the activator is [Ph_ThreeC]⁺[B (C₆F_Five)_ThreeCH_Three ]^-It is. These examples show that all or a portion of the activator is "compatible non-coordinating It indicates that it can be “on” or “counter ion”.   Compatible non-coordinating anions: Compatible non-coordinating anion coordinates to metal cation Or weakly coordinated with metal cations to neutral Lewis acid groups or during catalytic cycling That retain sufficient activity to be displaced by the molecule being converted to Nion. The term "compatible non-coordinating anion" is a term that is safe in the catalyst system of the present invention. When acting as a stabilizing anion, the anionic fragment is transferred to the metal cation Specifically refers to anions that do not form inert neutral products is there.   Organometallic compounds: Classically, one or more metal atoms and one or more carbons of an organic group A compound having a bond with an elemental atom is defined as an "organometallic compound". You. For the purposes of this application, the term “organometallic compound” refers to the presence or absence of a metal-carbon bond. Instead, it encompasses all of the metal compounds stabilized by the auxiliary ligand Is defined as As used herein, “organometallic compound” refers to the first metal Cleaning is distinguished from catalysts by lacking useful levels of catalytic activity. You. However, this definition initially implies that certain classes of reactions (eg, alkene polymerization) ), But has no catalytic activity with respect to other classes of reactions (eg, alkyne polymerization) ) Does not exclude metal compounds identified as having catalytic activity. Absent.   Metallocenes (metallocdens): For example, of zirconium, cobalt or nickel Such a transition metal is at least one substituted or unsubstituted η5-cyclopentadienyl Organometallic compound bound to a thiol group.   Substrate: A material having a rigid or semi-rigid surface. In some embodiments, less substrate At least one surface is substantially flat. In another embodiment, the substrates are physically separated Will be divided into the synthesized areas. Substrate into physically separated composite area Dividing can be, for example, recesses, wells, wells, etched grooves And so on. In yet another embodiment, small beads or pellets are placed on the substrate surface. It may be arranged, for example, in a recess or well on the surface of the substrate or The beads are placed inside or on another area. Separately, small The substrate or pellet itself may be the substrate. A suitable substrate is It can be made of any material that is compatible with the process being sought. Like that Materials include organic and inorganic polymers, quartz, glass, silica, etc., but are not limited to these. It is not specified. The ability to select an appropriate substrate for a given set of conditions is It will be clear to the trader.   Carrier for synthesis: Silica, alumina, resin or controlled pore glass lass, CPG), where the ligand or ligand component is reversible or irreversible Functionalized so that it can bind to A specific example of a carrier for synthesis is Merrifield Tree Includes fat and functionalized silica gel. The carrier for synthesis may be in the “substrate” or “substrate” Can be held on. Here, "carrier for synthesis", "carrier", "bead" And “resin” are used interchangeably.   Predetermined area: The predetermined area is a substrate that can be used to form the selected substance Upper localized addressable area, otherwise "known" area, "reactive" area An area, a "selection" area, or simply an "area". This predetermined area can be any convenient location. Can have any suitable shape, for example, circular, rectangular, oval, wedge, etc. Wear. In addition, the predetermined area may be beads or beads coated with the reactant components of interest. It may be a pellet. In this embodiment, the beads or pellets are beads or pellets. Indicates the history of the pellet (ie, which components were deposited on the beads or pellets) For example, an etched binary barcode can be used to identify It can be identified by una tag. Generally, the predetermined area is about 25 cm^TwoFrom about 10μm^TwoIn You. In a preferred embodiment, the predetermined area, ie, the area where each individual substance is synthesized, is about 1 0cm^TwoLess than. In another preferred embodiment, the predetermined area is 5 cm^TwoLess than In a preferred embodiment, the predetermined area is 1 cm^TwoIs less than. Still another preferred embodiment In the state, the area of the predetermined area is 1 mm^TwoIs less than. In yet another preferred embodiment, , The area is about 10,000μm^TwoIs less than. In yet a further preferred embodiment, the region Is 10 μm^TwoLess than the size.   Linker: As used herein, “linker” or “linker arm” The term intervening between the substrate and the ligand, catalyst or organometallic compound Means A linker is cleavable or non-cleavable.   Metal ionsA: As used herein, the term “metal ion” is for example If a single salt (for example, AlCl_Three, NiCl_TwoEtc.), with organic and inorganic ligands Compound (for example, Gd (NTA)_Two, CuEDTA, etc.) I say. The metal ions used in carrying out the present invention include, for example, main group metal ions. ON (main group metal ions), transition metal ions, lanthanide ions and the like. For example, Ni (COD)_TwoZero-valent metal precursors such as are also included in this definition. II. Combinatorial library assembly A. Overview   The present invention relates to supported and unsupported organometallic compounds and auxiliary ligand-stable catalysts (immediately (Homogeneous catalysts and heterogeneous catalysts) and their combined synthesis , Methods, compositions used for screening and characterization As well as an apparatus. Desirably, the synthesis and scripting of such a library Training in a spatially selective, simultaneous parallel or rapid serial manner Is done. In an embodiment in which library synthesis is performed in parallel, a parallel reactor It is preferred to use Illustrated here are the cores of organometallic compounds and catalysts. This is the first method for preparing and screening a combinatorial library.   The method of the present invention provides for the assembly of a library of organometallic compounds and catalysts. I can. The catalyst of the present invention requires activation by an activating substance, It is of a type that is not needed. The present invention also provides for both supported and unsupported organic A method for synthesizing a metal compound and a catalyst is provided. Library compounds are loaded The compounds are bound to the substrate or need to be Either on the substrate or attached to an intermediate synthesis support within the substrate, depending on is there. The supported library compound is attached to a substrate or a carrier for synthesis, and to the ligand core. Whether it is directly linked through the attached functional group or is itself a ligand core Or via a linker arm which is a side chain of the ligand core. If the library consists of catalysts, the catalysts may be homogeneous, heterogeneous or heterogeneous. They can be assembled into a mixture.   Accordingly, the present invention provides, in one aspect, an array of metal-ligand compounds having the structure Provide a way to manufacture:   (A) A first metal-binding ligand and a second metal-binding ligand are combined in a first region on a substrate. And the second region,   (B) supplying a first metal ion to the first metal binding ligand; Is supplied to the second metal-binding ligand so that the first metal-ligand compound and the second metal- Form a ligand compound.   In this embodiment, the ligand couples these fragments with the fragments of the ligand. Are assembled on a substrate by providing the necessary reactants in stages . Once the ligands are synthesized, the ligands are reacted with metal ions to form metal-ligands. Forms a ligand compound.   The present invention, in another aspect, involves attaching a ligand to a reactive group on a substrate surface. Thus, a method for immobilizing the intact ligand on the substrate is provided. In other words, this In an aspect, the present invention is directed to producing an array of metal-ligand compounds having the following structure: RU:   (A) combining a first metal binding ligand and a second metal binding ligand with a first region of a substrate; Supply to the second area,   (B) the first metal ion as the first metal binding ligand, and the second metal ion as the second metal To provide a binding ligand to form a first metal-ligand compound and a second metal ligand compound. To achieve.   In another embodiment, the metal-ligand compound thus synthesized is referred to as an activator. Let react. Suitable activators are B (C₆F_Five)_ThreeAnd Lewis acids such as MAO And [H (OEt)_Two]⁺[BAr_Four]^-And [H (OEt)_Two]⁺[B (C₆F_Five)_Four]- Una [Q]⁺[NCA]^-Including but not limited to It is not something to be done. In yet another preferred embodiment, the activator is a member of the library. It is independently selected for each compound. In another preferred embodiment, the activated The metal-ligand compound is an olefin polymerization catalyst. In yet another preferred embodiment Is a catalyst that does not require an activating substance.   In yet another aspect, the present invention provides an array of metal-ligand compounds having the structure Here are the methods for manufacturing and screening:   (A) synthesizing an array of spatially separated ligands;   (B) providing a suitable metal precursor to each element of the ligand array to provide a metal- Making an array of ligand compounds,   (C) If necessary, the array of the above-mentioned organometallic compounds is converted to an activating substance (for example, , With a suitable cocatalyst)   (D) if necessary, modifying the array of metal-ligand compounds with a third component And   (E) parallel or rapid serial optical imaging and / or spectroscopy, quality Quantitative analysis, chromatography, acoustic / spectroscopic analysis, infrared imaging Using spectroscopy / analysis of arrays of metal-ligand compounds as described above for useful properties Screening.   Various types of ligands are used in practicing the present invention (see FIGS. 1-13). Want to be). In one preferred embodiment, the ligand is a neutral bidentate ligand.  ligants). In another preferred embodiment, the ligand is a monoanionic bidentate coordination I am a child. In yet another preferred embodiment, the ligand is a chelating diimine ligand (c helating diimine ligands). In yet another preferred embodiment, the ligand is These are salen ligands. Preferred ligands comprise 1, 2, 3, and 4. Each having a coordination number independently selected from the group. These preferred ligands are , 0, -1, -2, -3 and -4. You. Some of the preferred ligands have a charge greater than the coordination number.   The ligand is bonded directly or via a linker group to a substrate or a carrier for synthesis, Apart from this, it is present in the solution. In one preferred embodiment, the ligand is directly synthesized Bound to the carrier. In another alternative preferred embodiment, the ligand is via a linker group. And bound to the carrier for synthesis. In yet another preferred embodiment, the ligand is directly or Is attached to the substrate via a linker group.   Any functional group of the ligand or linker or any component of the ligand or linker is It can be protected to prevent interference with the pulling reaction. This protection is standard Or a variation thereof. Very well-known functional groups Many protection schemes are known to and used by those skilled in the art. You. For example, Green (T) and other "PROTECTIVE GROUPS IN ORGANIC SYNTH ESIS "(Protecting Groups in Organic Synthesis) Second Edition, John Wiley & Sons (John Wi ley and Sons), New York, 1991. For the teaching of this, see Is incorporated here by doing so.   Chemical synthesis process, solid phase synthesis method, solution phase synthesis method or solid phase synthesis method and liquid phase synthesis method Can be performed by a combination of Ligand, metal, activator, counterion , The substrate, the carrier for synthesis, the linker and the additive to the substrate or the carrier for synthesis, Can be changed as part of Lee. The various elements of a library are usually By feeding reactants in parallel to each addressable site, or It is varied by the known "split and pool" combination method. Business Other methods for assembling the combinatorial library are also apparent to the user. Ro U. For example, Thompson, L.A., et al., "Synthesis and Application s of Small Molecule Libraries "(Synthesis and use of small molecule libraries), Ch em. Rev., 1996, 96: 555-600. In addition, within the teaching The contents are incorporated herein by reference.   In the present invention, any number of wide ranges of metal ions are suitable for use. Good fruit In embodiments, the metal ion is a transition metal ion. In another preferred embodiment, the metal The ions are Pd, Ni, Pt, Ir, Rh, Co, Cr, Mo and W ions. is there. When the metal ion is a transition metal ion, in one preferred embodiment, the metal bond The neutral ligand is a neutral bidentate ligand, and the transition metal ion can be substituted in the metal precursor. Stabilized by a functional Lewis base. In another preferred embodiment, the ligand is A monoanionic bidentate ligand in which the transition metal center is a substitutable atom in the metal precursor. It is stabilized by a nonionic leaving group ligand. In yet another preferred embodiment, The ligand is a [2,2] or [2,1] ligand, and each ligand is a main group metal alkyl. Upon contact with the complex, the ligand is in a monoprotic or diprotic form. Especially good Suitable metal alkyl complexes are trialkylaluminum complexes. Particularly suitable one In embodiments, the resulting metal-ligand compound is, for example, a stereoselective coupling Reaction (stereoselective coupling reactions), olefin oligomer formation reaction And organic transfer requiring Lewis acid sites, such as olefin polymerization reactions Useful for animation. In yet another preferred embodiment, the aluminum-ligand The compound is further modified with an ion exchange activator to provide a ligand stable cationic aluminum Produces a nickel compound. Suitable ion exchange activators are [PhNMe_TwoH] [B (C₆F_Five)_Four].   Catalysts prepared using the method of the present invention include oxidation, reduction, hydrogenation, hydrosilation, , Hydrocyanation, polymerization (eg, olefins and acetylene), water gas Conversion reaction, oxo reaction, carboalkoxylation of olefin, carbonylation reaction (Eg, carbonylation reaction of acetylene, alcohol, etc.), decarbonylation, etc. It is useful for catalyzing a wide range of reactions, including: In addition, the reaction It is not limited.   Following the synthesis of a library, as described in detail below, Compounds are screened for useful properties. In one preferred embodiment, useful The property is a property related to the polymerization reaction. In another preferred embodiment, the useful property is Mechanical, optical, physical or morphological properties. Certain preferred embodiments Useful properties include, for example, the lifetime of the metal-ligand compound, under certain reaction conditions. The stability of these compounds in a given reaction, the selectivity of the compounds of the library in a particular reaction, Conversion efficiency of library compounds in a specific reaction or library in a specific reaction Chemical properties, such as the activity of the compound. Libraries are a comprehensive method Can be used to screen for compounds with useful properties . Thus, in one preferred embodiment, screening is performed by scanning mass spectrometry, Luffy, ultraviolet imaging, visible imaging, infrared imaging, electromagnetic imaging , UV spectroscopy, visible spectroscopy, infrared spectroscopy, electromagnetic spectroscopy, acoustic method The method is performed using a method selected from the group consisting of:   In general, for analysis of catalysts and organometallic compounds, each component is quickly checked (character To identify compounds having certain desired properties. You. One example of the use of the present invention is to discover and optimize new catalysts. In one preferred embodiment for synthesizing the catalyst, the components of the combinatorial library are: Activity (ie, turnover), selectivity in converting the reactants to the desired product, Measure properties such as stability during operation over a wide range of substrate concentrations and reaction conditions Analyzed by using high-throughput methods. Spatial selective key Characterization methods include, for example, (i) gas phase product and coagulated phase product And characterization of volatile constituents of (i) identification of cohesive phase products And characterization, (iii) physical properties of the catalytic elements of the library Includes methods that can measure Library of both organometallic compounds and catalysts Measure properties other than catalytic action (eg, binding to target, solubility, hydrophilicity, etc.) To do so, a similar high-throughput method can be used.   In yet another aspect, the present invention provides a method comprising the steps of:⁶ It consists of an array composed of different metal-ligand compounds. An implementation In one embodiment, the array comprises over 50 different metals at each known location on the substrate. Will consist of a ligand compound. In another embodiment, the array comprises 100 species. It may consist of more than or more than 500 different metal-ligand compounds. Change In another embodiment, the array comprises more than 1,000 species at each known location on the substrate. Or more than 10,000 or 10⁶Distinct metal-ligand combinations beyond species Will consist of things.   Assembling a combinatorial library of organometallic compounds and catalysts Changes in a number of properties of the product itself, the reactions used to prepare the compound, the compound , It is possible to quickly evaluate the influence of a reaction or the like involving. Mutating Examples of characteristics and properties that can be used (here, both are referred to as "parameters") Specifies the ligand core itself and the substituents of the ligand core, the charge of the metal ion and / or Is a counter ion, activator, reaction conditions, solvent, additive, carrier, substrate, linker Including, but not limited to. By using the method of the present invention, Parameters of interest other than those above, whose effects can be investigated Will.   In one preferred embodiment of the present invention, one parameter Mutate only one. In another preferred embodiment, the synthetic compound is a catalyst and comprises various Variations of parameters can be used to carry out a catalytic or desired reaction or group of reactions. Used to identify the optimal species and conditions for   Combinatorial libraries synthesize both organometallic compounds and catalysts. , The optimal metal ion to achieve the desired properties, the charge of the metal ion, the geometry It can be used to specify the chemical shape and / or coordination number. Similarly, The effect of changes in counterions, activators, reaction conditions, solvents and additives Can be used to measure. Library components of interest The properties of, for example, catalyst parameters, solubility, conductivity, hydrophilicity, mechanical properties and General pharmacological parameters (eg, target binding, pharmacokinetic properties, Fabric volume, clearance, etc.).   Specific examples of the types of compounds that can be synthesized and analyzed in combinatorial format are Ni and Pd complexes discovered by Brookhart, Inc. It is. This family of catalysts comprises 4-coordinated Ni²⁺Or Pd²⁺Joined to the center Consists of a 1,2 diimine ligand moiety. These precursors are then converted to Lewis acids, example Lewis acids such as MAO and [H (OEt)_Two]⁺[BAr_Four]^-And [H ( OEt_Two)]⁺[B (C₆F_Five)_Four]^-[Q] such as⁺[NCA]^-Ions in the form of Activated by the exchange reactant to form a polymerization catalyst. The properties of the catalyst (for example, The molecular weight range of the polymer, the statistical properties of polymer branching, etc.) Depends on what you choose. With Combinatorial Library , It is possible to optimize the properties of these components.   Combinatorial libraries also contain organometallic compounds or catalysts on a substrate or carrier. (Silicate, aluminate, polystyrene, etc.) Can be used for The catalyst or organometallic compound is Direct attachment to the body via a functional group on the ligand or via a linker arm Can also be combined. Linker that can be changed throughout the library Parameters are, for example, length, charge, solubility, conformational l lability), including chemical composition. Substituents on these linkers can be varied Therefore, specific combinations of catalysts, linkers, synthesis supports, metals, polymerization conditions, etc. Using a two- or three-dimensional array format or bead carrier. Can be evaluated directly.   For example, compounds such as metal ions, counter ions, types and concentrations of activators, etc. The optimization of the constituents depends on the type of constituents whose effects on the product compounds are being investigated. Achieved by changing the concentration. Specifically, the parameter is a library Parameters throughout the array of addressable locations that make up the available. In addition to the above components, the nature of the substrate is also altered using a combinatorial strategy. Can be obtained.   The effect of changing the properties of each component of the combinatorial library directly or Can be analyzed indirectly. Thus, in one embodiment, the library The structure or properties of the compound itself are examined. In another embodiment, the compound of the library The effect of the object on other molecules or systems is determined. For example, a library of polymerization catalysts When synthesizing a catalyst, the effects of component changes throughout the library are catalyzed. By analyzing the polymer product produced using the library component Can be evaluated. By performing such an analysis, for example, the molecular weight Range, copolymerizability, lifetime, comonomer compatibility, chemical stability, various topologies Determine catalytic properties, including ability to form polymers, molecular weight distribution, and / or microstructure Can be Other means of analyzing combinatorial libraries are available to those of skill in the art. It will be obvious.   Libraries can be made from different materials or have different topological properties. And the effect of the nature of the carrier on the compound as described above. You can find out. In some embodiments, the substrate is also a carrier for synthesis. Is also good. B.Carriers and substrates for synthesis   In one preferred embodiment, the library comprises an array of supported metal-ligand compounds. Consists of i. Generally, when synthesizing a supported organometallic compound or catalyst, the metal The ligand compound is a substrate of an organometallic compound or a substrate for a catalyst or a carrier for synthesis. Directly linked to In another embodiment, the metal-ligand compound is a substrate or a synthetic compound. It is attached to the carrier via a linker arm.   The structure, shape and functional properties of the substrate depend on the nature of the reaction carried out using the substrate. And limited only by size. In some embodiments, the substrate is a porous material. You. In another embodiment, the substrate is a non-porous material. Substrate is substantially flat Or may include a well or a convex portion. Substrates include, for example, holes, needles, valves With integral means for liquid transfer means, such as a pipette or a combination thereof be able to. The substrate has a means for performing the reaction under an inert atmosphere or a controlled atmosphere. You can also. Thus, in one embodiment, the substrate further comprises a cover, The cover has means for replacing the base and its contents with a specific atmosphere. another In embodiments, the substrate is light, sound or ionizing radiation, the substance on or in the substrate. Means for heating or irradiating is applied. In yet another embodiment, the substrate is within the substrate or Comprises means for stirring the substance on the substrate.   In one preferred embodiment, the substrate is a substantially planar substrate having a plurality of recesses or wells. It has an upper surface, and these recesses or wells are formed during the reaction. A large amount of synthesis support can be contained in the well with one or more conversion reactants. It has enough depth to make   The substrate is shaped to allow synthesis and screening of the libraries of the invention. It is composed of any material that can be formed. For materials useful for constructing substrates The only limitation is that the substrate can be adapted to the reaction conditions to which it is exposed. That is something that must be done. Thus, when useful for performing the method of the present invention, Useful substrates include organic and inorganic polymers, metal oxides (eg, silica, alumina ), Mixed metal oxides, metal halides (eg, magnesium chloride), minerals, quartz , Zeolite, Teflon, polyethylene (cross-linked, non-crosslinked, or dendrimeric (Dentrimeric)), polypropylene, copolymer, polypropylene, poly Including but not limited to styrene and ceramics. With other shapes of the substrate The materials from which the substrate is made will be apparent to those skilled in the art. Soluble catalysts are inorganic or organic based Can be adsorbed by the body to form a useful heterogeneous catalyst.   Two-dimensional combinatorial reaction of supported organometallic compounds or catalysts using a carrier for synthesis In one example of the library, the following shapes of the carrier for the synthesis of the substrate are possible. i) porous The carrier is located in the well and the reactants are transferred from the top of the well to the bottom of the well. By flowing through the holes (which may be in the opposite direction of the flow), Ii) the porous carrier is located in the well and the reactants are Inflow / outflow only into the top of or from the wells, iii) non-porous carrier Are located in the wells, allowing the reactants to pass through the holes from the top of the wells to the bottoms of the wells. Flow around the substrate (the flow may be in the opposite direction), iv) the non-porous carrier Reactants are located in the wells and pass through the wells from top to bottom Flow into or out of the well top or only from the well top, or v) The non-porous or porous carrier is not located in the well and the reactants Deposited directly on the substrate surface in an addressable manner.   In embodiments where a ligand or synthesis support is attached to the substrate, the substrate is functionalized to Enables the combination of Ligand by combining each fragment of the ligand on the substrate In embodiments in which is synthesized, the substrate is functionalized so that the first ligand fragment can bind. To In embodiments where no ligand or synthesis support is attached to the substrate, the substrate is functionalized. It may or may not be necessary.   Substrates that can be functionalized are known in the art. For example, functionalizing a glass plate, Oligonucleotide binding can be enabled (eg, Southern rn), Chem. Abstr. 1990, 113: 152979r). Governmentize glass Another method is to use polar silanes containing hydroxyl or amino groups. Brennan, T.M. et al. (U.S. Pat. No. 5,474,796) (The teachings of which are incorporated herein by reference) I have. Organic polymers can also be functionalized. For example, polypropylene , Surface-induced by oxidation with chromic acid, followed by ligands, ligand fragments or Is on a hydroxymethylated or aminomethylated surface with anchors for the synthesis support Can change. Other polymers used to practice the present invention are chloromethyl Surface derivatization by functionalization and subsequent functional group modification, e.g., highly crosslinked Polystyrene-divinylbenzene. Nylon surface Can be derivatized to give rise to an initial surface of the groups.   As with the substrate, the carrier for synthesis may be an organic polymeric or inorganic material, such as Mina, silica, quartz glass, zeolite, Teflon, etc. can be used. It is not limited to these. Depending on the material constituting the carrier for synthesis, the carrier is It can be porous, woven, solid, and It may be flat or bead shaped or any other geometric shape. Carrier for synthesis Is, for example, functionalized polystyrene, polyacrylamide, pore size controlled porous glass (Controlled pore glass) are known in the art. Jones (J ones, J.), "Amino Acid and Peptide Synthesis", "Amino Acid and Peptide Synthesis" , Oxford Science Publications cations), Oxford, 1992; Narang, S., eds. " Synthesis and Application of DNA and RNA "," Synthesis and Application of DNA and RNA, " Academic Press, Inc., New York 1987. These teachings are incorporated herein by reference. Be included. In addition, suitable methods for functionalizing a substrate may be used as a support for synthesis. Suitable for functionalizing the intended material used. Substrate or synthesis support functionalized The ligand or ligand component is then bound to a substrate or carrier for synthesis. C.Ligand   The method of the present invention is widely applicable to all ligands capable of binding metal ions. is there. Achieve ligand combination mutations by solid-phase or solution-phase reactions or multiple reactions can do. Separately, a sequence consisting of a solid phase reaction and a solution phase reaction Can be used in the synthesis of an array of metal binding ligands. Using the method of the present invention The characteristic of a ligand that can be mutated using is that the ligand occupies the metal. The number of possible coordination sites, the charge and electronic effects of the ligand, Including the geometry given to the ligand by the metal, etc. It is not limited. Numerous metal binding ligands are known in the art and Other ligands and ligand parameters that can be mutated using the methods of the invention are: It will be apparent to those skilled in the art. For example, Colman, J.P. et al., "Principles  and Applications of Organotransition Metal Chemistry " Principles and Applications ", University Science Books  Books), California, 1987. Refer to the teaching content. Hereby incorporated by reference.   In one preferred embodiment, the generic approach is as follows: 1) Low coordination numbers (eg For example, metal alkyl complexes of 3 to 5) can be combined in various geometries (eg, triangles, Surface, square quadrangle, square pyramid, pentagon, compound pyramid) Synthesize ligands (eg, auxiliary ligands) to form these libraries 2) forming metal compounds of these libraries, and 3) gold if necessary. Reacting the genus compound library with various activators and / or modifiers; A library of metal compounds can be prepared with various properties and properties (eg, olefin polymerization). Activity, polymerization performance characteristics). In other embodiments, the activation Immobilizing the metal catalyst on a library of supports and / or linkers, Various characteristics (eg, olefin polymerization activity, polymerization performance characteristics) can be examined. You. In a particularly preferred embodiment, the metal ion is a transition metal ion.   In one preferred embodiment, the auxiliary ligand binds to the metal center to reduce the metal center to the low ligand. And does not directly participate in catalytic chemistry. Usually, the coordination number is Less is preferred, but excludes embodiments using larger coordination loci. Not. When the number of coordination loci is 3 or more, the metal-ligand compound It could have a geometric shape.   In another preferred embodiment, the coordination site of the ancillary ligand is 1, 2, 3 or 4; The charge of the child is 0, -1, -2, -3 or -4. Other ancillary ligands are It has more charge than the number of occupied coordination sites. Depending on the ligand, its structural Depending on the nature, the ligand may take more than one coordination number and / or more than one charge . For example, the charge and / or coordination number of the ligand may be determined by the transition metal ion and the transition metal Can be different when bound to different metals such as Wear. Further examples are strongly basic conditions, such as For example, a ligand deprotonated with n-butyllithium and brought into contact with a metal ion becomes more Is different from the same ligand when reacted with metal ions under mild conditions. Different coordination numbers and / or charges.   The ligands, metal-ligand complexes and catalysts which can be used in the process of the invention Examples include, but are not limited to: (1) Cp^*MR2⁺NCA^-(Where M is metal, R is alkyl, NCA is non-arranged) Monoanionic ancillary ligand (e.g., anionic anion) and methyl Mono-Cp system in combination with alumoxane (MAO). (2) For example, a bi-coordinate dianionic auxiliary ligand including a bis-Cp system (US Reference is made to Patents 4,752,597 and 5,470,927, the teachings of which are incorporated by reference. And the heteroatom-based ancillary ligand has a second coordination site. An occupying mono-Cp system (see US Pat. No. 5,064,802, the teachings of which are incorporated herein by reference). Non-Cp bis-amide systems (incorporated herein by reference) (US Pat. Nos. 5,318,935 and 5,495,036. In addition, refer to the teaching And bridged bis-amide ligands and coordination Group IV catalysts stabilized by protons (Organometallics 1995, 14: 3154-3156 and J . Am. Chem. Soc. 1996, 118: 10008-10009, the teachings of which are referenced. Hereby incorporated by reference). (3) For example, Cp (L) CoR⁺X^-And two-coordinate monoanis, including related systems Oh Ancillary ligand. (Reference is made to WO 96/13529, the teachings of which are incorporated by reference. Incorporated here by). (4) For example, Ni²⁺And Pd²⁺Neutral auxiliary ligands in two-coordinates such as the system. For example J. Johnson, et al. Am. Chem. Soc. 1995, 117: 6414-6415 and WO 9 See 6/23010. The teachings are incorporated herein by reference. It is. (5) A neutral auxiliary ligand in the three-coordinated locus. (6) A mono-anionic auxiliary ligand having three coordination sites. (7) Three-coordinate dianionic auxiliary ligand. (8) Trianionic auxiliary ligand. (9) Four-coordinated, neutral, monoanionic and dianionic auxiliary ligands. (10) Auxiliary ligands whose charge is greater than the number of coordination loci occupied by the ligand. (For example, rice See US Patent No. 5,504,049, the teachings of which are incorporated herein by reference. Incorporated in )   One application of the present invention is to use multiple ligands that are components of organometallic compounds or catalysts. Adjustment and screening. Coordination used in practicing the invention The child is a binding domain (bi) of the structural motif groups of the ligand. nding domain), e.g., alkyl, carbene, carbine, cyanide Olefin, ketone, acetylene, allyl, nitrosyl, diazo, dioxo , Disulfur, diseleno, sulfur monoxide, sulfur dioxide, aryl, heterocycle (heterocycle) , Acyl, carbonyl, nitrogen, oxygen, sulfur, phosphine, phosphide, hydride And the like. Other primitives and groups consisting of metal binding domains It is well known in the art and is useful in practicing the present invention. For example, Colman man, J.P.), "PRINCIPLES AND APPLCATIONS OF ORGANOTRANSITION METAL CHE MISTRY "" Principles and Applications of Organic Transition Metal Chemistry ", University Science , (University Science Books), California, 1987. That teaching is incorporated herein by reference.   As described above, a library of ancillary ligands is available in combinatorial chemistry. Produced using the format of A wide range of configurations within the library Child characteristics can be mutated. Characteristics that can be mutated across libraries are: For example, ligand bulk, electronic properties, hydrophobic / hydrophilic, geometric, chirality -, The number of coordination sites of the metal occupied by the ligand, the charge of both the ligand core and its substituents, There is a geometry that the ligand imparts to the metal.   Bidentate, tridentate and tetradentate ligand systems useful in combinatorial synthesis include, for example, Can be constructed from the ligand fragments listed according to their charge.   The synthesis of these ligand libraries utilizes a variety of established organic synthetic methods. Using the combination method (parallel or split pool method) I can. The neutral ligand fragment is an amine (R_ThreeN), phosphine (R_ThreeP), Arsine (R_ThreeAs), stilbin (R_ThreeSb), ether (R_TwoO), thioe Ter (R_TwoS), selenoether (R_TwoSe), telluro ether (R_TwoTe) Ton (R_TwoC = 0), thioketone, imine (R_TwoC = NR), phosphinimine ( R_Three= NR, RP = NR, R_TwoC = PR), pyridine, pyrazole, imidazole , Furan, oxazole, oxazoline, thiophene, thiazole, isoxazo , Isotrazole, arene, nitrile (R-C≡N), isocyanide (R -N≡C), acetylene, and olefins, but are not limited thereto. No.   The monoanionic ligand fragment is an amide (NR_Two), Phosphide (PR_Two), Siri (SiR_Three), Alcido (AsR)_Two), SbR_Two, Alkoxy (OR), thio (SR), selenol (SeR), terol (TeR), siloxy (OSi) R_Three), Cyclopentadienyl (C_FiveR_Five), Boratobenzene (C_ThreeBR₆), Pila Zoyl borate, carboxylate (RCO_Two ^-), Acyl (RCO), amidate, Alkyl, aryl, triflate (R_ThreeCSO_Three ^-), Thiocarboxylates (RC S_Two ^-), Halides, nitrates, etc., but are not limited thereto.   The dianionic ligand fragment is cyclooctatetrenyl (R₈C₈ ^2-), Alkyri Den (R_TwoC), Bolilide (C_FourBR_Five), Imide (RN), phosphide (RP) , Carbides, oxides, sulfides, sulfates, carbonates, etc. It is not specified.   Trianionic ligand fragments include alkylidyne (RC), -P^3-(Phosfi C), -Ar (alcid), and phosphite, but are not limited thereto. Absent.   Multidentate ligands generally involve multiple ligand fragments with one or more pendent R-grooves. ups). Of the above ligand fragment A specific example of a bidentate neutral ligand [2,0] that can be constructed from a list is (Imi Diimine (derived from two imine fragments), (derived from pyridine and imine fragments) ) Pyridyl imine, diamine (derived from two amine fragments), (imine and Imine amines (derived from amines), derived from imines and thioethers ) Imine thioether, imine ether (derived from imine and ether), Imine phosphine (derived from imine and phosphine), (two oxazoly Bisoxazoline (derived from two ethers) and die (derived from two ethers) -Tel, bisphosphinimine (derived from two phosphinimines), ( Diphosphine (derived from two phosphines), derived from phosphine and amine (Derived) phosphine amines. other A bidentate neutral ligand system can also be constructed from the list of neutral ligand fragments described above. Can be.   The bidentate monoanionic ligand [2,1] refers to the neutral ligand fragment as described in the list above. It can be constructed by crosslinking with these monoanionic ligand fragments. Examples include salen and other alkoxyimine ligands (imine and alcohol Xy ligand fragments), amidoamines (derived from amides and amines) Amides) and amide ethers (derived from amides and ethers). However, the present invention is not limited to this. Other bidentate monoanionic ligand systems are similarly constructed. Can be built.   The bidentate dianionic ligand [2,2] comprises two monoanionic ligand fragments or Constructed by combining dianionic and neutral ligand fragments be able to. As a specific example, a dicyclopentadienyl ligand (two cyclo Derived from pentadienyl ligand fragments), cyclopentadienyl amide coordination (Derived from cyclopentadienyl and amide ligand fragments), Midothioether ligand (derived from imide ligand fragment and thioether ligand fragment ), Imidophosphine ligand (imido ligand fragment and phosphine ligand fragment ), Alkoxyamide ligands (alkoxide ligand fragments and amides Derived from ligand fragments), but are not limited thereto. other Bidentate dianionic ligand systems can be similarly constructed.   A bidentate ligand with a charge greater than -2 is a monoanionic ligand fragment, Combine with an anionic or trianionic ligand fragment or Can be constructed by combining functional ligand fragments. For example , Bisimide ligands (derived from two imide ligands), carbine ether There are ligands (derived from carbine and ether ligand fragments).   The tridentate neutral ligand [3,0] consists of three neutral ligand fragments from the list above. It can be constructed by combining them. For example, 2,5 diiminopyri Jill ligand (derived from two imine ligand fragments and one pyridyl ligand fragment ), Triimidazoyl phozphines (central phosphorus atom) Derived from three imidazole ligand fragments attached to Lualkanes (derived from three pyrazole ligands attached to a central carbon atom ), But is not limited to these. Other tridentate neutral ligands (eg [ [3,1], [3,2], [3,3]) can be similarly constructed.   In a preferred embodiment, the coordination numbers (CN) of the auxiliary ligands are each independently 1, 2, 3 Or 4, and the charge of the ligand is independently 0, -1, -2, -3 or -4. is there. The ancillary ligand or ligand fragment need not be negatively charged; Lopyrium (C₇H₇ ⁺Positively charged ligands such as) are also useful in practicing the present invention. Used.   Currently preferred "families" of coordination numbers and charges are: (i) CN = 2, charge (Ii) CN = 2, charge = −1; (iii) CN = 1, charge = −1; (iv) CN = (V) CN = 3, charge = −1; (vi) CN = 1, charge = −2; (vii ) CN = 3, charge = −2; (viii) CN = 2, charge = −3; (ix) CN = 3, charge = − (X) CN = 3, charge = 0; (xi) CN = 4, charge = 0; (xii) CN = 4, charge = -1; (xiii) CN = 4, charge = -2. In another preferred embodiment, the auxiliary ligand Is It has a charge greater than the number of coordination sites occupied by the ligand on the metal ion.   Other suitable examples of the ligand families described herein that are useful in combinatorial synthesis strategies In the embodiment, (1) CN = 2, charge = neutral carrier-supported auxiliary ligand (denoted as [2,0] (2) a carrier-supported auxiliary ligand having CN = 2 and charge = −1 (denoted as [2,1]); 3) CN = 2, charge = -2, auxiliary ligand of metal compound supported on carrier ([2,2] (4) CN = 2, charge = −1, carrier-unsupported auxiliary ligand (denoted as [2,1] ); (5) Carrier-unsupported auxiliary ligand having CN = 2 and charge = -2 (denoted as [2,2]) (6) ancillary coordination with CN = 2, charge = −2, unsupported carrier and functional linker (Noted as [2,2]); (7) CN = 2, charge = −2, unsupported carrier and “non-functional "Auxiliary ligand having a linker (denoted as [2,2]); (8) CN = 3, charge =- 3 is a carrier-unsupported auxiliary ligand (denoted as [3, 3]).   FIG. 3 shows the synthesis of a catalyst precursor using the combination synthesis approach of the present invention. Here are some alternative routes that can be used when doing so. Generally, similar combinatorial chemistries Of other ligand cores that can be made by using the A library could be envisioned. An example is the ligand core shown in FIGS. 4A-G. You.   In one important embodiment of the present invention, an acidic functional group is added to the R group substituent in the library. Position. Acidic functional groups allow catalysts to rapidly incorporate polar functional comonomers Significant effects on the catalytic performance of the polymerization catalyst system, including improving capacity. Bull In late transition metal catalysts, such as the Cookhart catalyst, certain polar functional comonomers Can be used, but the polar functional group coordinates to the metal center in the molecule. In addition, the polymerization rate is greatly reduced (see FIG. 13A). As shown in FIG. 13B When the acidic moiety is properly positioned on the auxiliary ligand, the acidic moiety can coordinate the polar functional group. Polymerizes by competing with the metal center for Speed up. Suitable acidic functional groups include trivalent boron groups, trivalent aluminum groups , Carboxylic acids and sulfuric acids, but are not limited thereto. Acidic sensuality Introducing a group into the R group of the auxiliary ligand system is dependent on all ligand / metal compounds of the present invention. It is a general idea that can be applied to things.   The ligands of the invention, in particular the diimine ligands, may be symmetric or asymmetric. No. Symmetric ligands have two moieties, each derived from the same imine I have. In contrast, asymmetric ligands are derived from non-identical amines. It has two parts. To obtain asymmetric ligands, a number of synthetic routes Can be used. For example, protecting one carbonyl group of a diketone, One carbonyl group is reacted with an amine. Deprotect the protected group Reacting the second carbonyl group with a second amine. Another useful route is , An approximately stoichiometric amount of the primary amine is added, followed by a similar amount of the secondary amine. Add. Other synthetic routes for contrasting and asymmetric ligands will be apparent to those skilled in the art. Will.   The R group, which is a side group of the auxiliary ligand core, has the property that the R group imparts to the organometallic compound. Is selected based on The R group is responsible for the reactivity and stability of the catalyst and organometallic compound. Affects, but does not bind directly and irreversibly to metal centers. Large R group The bulk around the metal center and the ligand-metal compound Child characteristics can be changed. The chiral R group is a ligand-metal compound Can be provided with chirality. Further, using the R group, the ligand-metal It is also possible to adjust the hydrophobicity / hydrophilicity of the compound.   The R groups on the ligand are each independently hydrogen, alkyl, substituted alkyl, aryl, , Substituted aryl, arylalkyl, substituted arylalkyl, acyl, halogen Amino, cyano, nitro, hydroxy, alkoxy, alkylamino, reed Ruamino, silyl, germyl, stannyl, siloxy, phosphino, aryloxy , Aryloxyalkyl, substituted aryloxyalkyl, heteroaryl, substituted Teloaryl, heteroarylalkyl, substituted heteroarylalkyl, heterocycle , Substituted heterocyclic, heterocyclic alkyl, substituted heterocyclic alkyl S-aryl, S-alkyl It is selected from the group consisting of rumercaptan.   As used herein, the term "independently selected" refers to an R group, for example, Indicates that R1, R2, and R3 may be the same or different (for example, R1 Even if 1, R2 and R3 are all substituted alkyl, R1 and R2 are substituted alkyl , R3 may be aryl, etc.). Adjacent R groups combine to form a cyclic structure It may be formed.   Groups named R groups are generally understood as those corresponding to the R group having that name. It has a structure recognized in the world. For purposes of illustration, the R group shown above The representative ones are defined below. These definitions are based on definitions known to those skilled in the art. They are intended to reinforce and illustrate, but not to exclude.   As used herein, the term "alkyl" refers to a branched or unbranched , A saturated or unsaturated, monovalent hydrocarbon group. When the alkyl group is 1-6 If the alkyl has two carbon atoms, the alkyl is said to be "lower alkyl" U. Suitable alkyl groups include, for example, methyl, ethyl, n-propyl, i-propyl , 2-propyl (or allyl), n-butyl, t-butyl, i-butyl (or 2-methylpropyl) and the like. As used herein, the term is Alkyl "is also included.   "Substituted alkyl" refers to one or more functional groups just described, , Aryl, acyl, halogen (ie, alkylhalo, eg, CF_Three), Hide Roxy, amino, alkoxy, alkylamino, acylamino, acyloxy, a Leyloxy, aryloxyalkyl, mercapto, saturated and unsaturated cyclic carbonization It contains hydrogen, heterocycle, and the like. These groups are attached to any carbon in the alkyl moiety. May be combined.   The term "aryl" is used herein to refer to an aromatic substituent, Are substituted or covalently bonded to each other, even if they are a single aromatic ring. Multiple aromatic rings linked to a common group (eg, a methylene or ethylene moiety) You may. A common linking group is a carbonyl as in benzophenone Is also good. The aromatic ring is a substituted or unsubstituted phenyl, naphthyl, biphenyl, diphe Includes nilmethyl and benzophenone.   "Substituted aryl" is used herein to refer to one or more functional groups and includes Functional groups include lower alkyl, acyl, halogen, alkylhalo (eg, CF_Three), Hee Droxy, amino, alkoxy, alkylamino, acylamino, acyloxy, Mercapto, a group fused or covalently bonded to an aromatic ring, Saturated and unsaturated cyclic hydrocarbons linked to the ethylene or ethylene moiety) It is. The linking group is a carbonyl, as in cyclohexyl phenyl ketone. It may be.   The term “acyl” refers to a ketone substituent, —C (O) R, where R is Alkyl or substituted alkyl, aryl or substituted aryl as defined herein Is used to refer to   As used herein, the term "amino" refers to the group -NRR '(wherein , R and R 'are each independently hydrogen, lower alkyl, substituted lower alkyl, Reel, substituted aryl or acyl). Amino group When attached to a metal via an elementary atom, this group is referred to as an "amide" ligand. Will be   The term "alkoxy" is used to refer to the group -OR, where R is alkyl, substituted lower alkyl, aryl, substituted aryl; The kill, aryl and substituted aryl groups are as described herein. As appropriate Alkoxy groups include, for example, methoxy, ethoxy, phenoxy, substituted phenoxy , Benzyloxy, phenethyloxy, t-butoxy and the like.   As used herein, the term "mercapto" means that R and R 'are the same Or different, as described herein, alkyl, aryl, or A portion of the general structure RSR which is a heterocycle is defined.   The term "saturated cyclic hydrocarbon" refers to cyclopropyl, cyclobutyl, cyclo Refers to groups such as pentyl and the like, as well as homologues in the substituents of these structures.   The term "unsaturated cyclic hydrocarbon" refers to cyclopentene, cyclohexene, etc. And monovalent having at least one double bond such as equivalents of these substituents Used to refer to non-aromatic groups of   The term "heteroaryl" as used herein refers to one or more of the aromatic rings Aromatic rings in which the carbon atoms of the above are replaced by heteroatoms such as nitrogen, oxygen or sulfur Means Heteroaryl is a single aromatic ring, multiple aromatic rings, or one or more Refers to a structure which may be one or more aromatic rings bonded to the non-aromatic ring. plural In structures having rings, the rings can be fused to each other, covalently bonded, It can be attached to a common group such as a ren moiety or an ethylene moiety. Common The linking group may be a carbonyl, as in phenylpyridyl ketone . As used herein, the term “heteroaryl” refers to thiophene, pyridine , Isoxazole, phthalimide, pyrazole, indole, furan, etc., or Such rings are defined as benzo-fused and homologous rings.   "Heteroarylalkyl" is a heteroaryl group as defined herein. As such, it refers to a portion of "alkyl" attached through an alkyl group.   "Substituted heteroaryl" is heteroaryl as defined above, When the nucleus is a lower alkyl, acyl, halogen, alkylhalo (eg, CF_Three), Hydro Xy, amino, alkoxy, alkylamino, acylamino, acyloxy, mel It refers to those substituted by one or more substituents such as capto and the like. Thus, thiophene, pyridine, isoxazole, phthalimide, pyrazole, Indole, furan, etc., or a homologue of a benzo-fused product of these rings A teloaromatic ring is defined by the term "substituted heteroaryl".   “Substituted heteroarylalkyl” is the above-mentioned “substituted alkyl” wherein Wherein the alkyl group links the heteroaryl group to the nucleus, as defined in is there.   The term "heterocycle" is used herein to denote from 1-12 carbon atoms and the nitrogen in the ring A ring from 1-4 heteroatoms in the ring selected from phosphorus sulfide or oxygen Or used to describe a monovalent saturated or unsaturated non-aromatic group having multiple fused rings. Used. Heterocycles of this kind, for example tetrahydrofuran, morpholine, piperi Gin, pyrrolidine and the like.   The term "substituted heterocycle" as used herein means that the nucleus of the heterocycle is an alkyl, Sil, halogen, alkylhalo (eg CF_Three), Hydroxy, amino, alcohol One such as xy, alkylamino, acylamino, acyloxy, mercapto, etc. It refers to a part of the “heterocycle” substituted by the above functional groups.   The term "heterocyclic alkyl" refers to an alkyl group, as defined herein, that is Refers to a part of "alkyl" that links a ring group to the nucleus.   The term "substituted heterocyclic alkyl" means that the heterocyclic nucleus is amino, alkoxy, One or more such as alkylamino, acylamino, acyloxy, mercapto, etc. Defines some of the functional groups.   In one preferred embodiment, an array of ligand moieties is synthesized on a substrate. This array is Surlate- or synthetic carrier ligands spatially separated from one another It is a combinatorial array of parts. Any type of ligand described above Although usable in this synthetic strategy, in a preferred embodiment, the array of ligand moieties is neutral Consists of a bidentate or chelating diimine ligand. Following its synthesis, Arrays of ligand moieties are labeled with metal ions (eg, transition element ions, main group metal ions, Lanthanide ion).   In another embodiment of the invention, the metal-ligand array or library is Each element of the daughter array contacts the metal ion precursor in the presence of a suitable solvent. In this case, the metal ligand is a neutral bidentate moiety, the metal precursor The quality is stabilized by at least one displaceable neutral Lewis base. Transition Transfer metal ion precursors are particularly preferred. In another preferred embodiment, the ligand moiety is A diimine ligand, wherein the transition metal precursor is selected from Group 10 transition metals. In yet another embodiment, the ligand is a monoanionic bidentate moiety and the transition metal Genus precursors are stabilized by at least one displaceable anionic leaving group ligand Be transformed into   In a preferred embodiment of the present invention, the ligand libraries described herein The catalyst library can be prepared by reacting with a group metal precursor. this Such a catalyst library is used for a stereoselective coupling reaction (here, chiral Louis). Is required), olefin oligomer formation reaction and olefin polymerization reaction Used for various organic transformations that require a Lewis acid moiety, including Is done. Examples of such reactions are the trialkylaluminum [2,2] or [ 2,1] reaction with the ligand library, in which the ligand library Each element is in diprotic or monoprotic form. this The reaction consists of a bidentate ligand bound to a mono- or dialkylaluminum center Generate an organometallic library. Such a library is known as [PhNMe_Two H]⁺[B (C₆F_Five)_Four]^-Reaction using an ion exchange activator such as After further modification, organic coupling reaction, olefin oligomer formation reaction and Ligand-stabilized cations that can act as catalysts for fin polymerization A reactive aluminum reactant can be produced. Such as [2,2] or An example of the [2,1] reaction is shown below in Scheme 1.                                Scheme 1   These compounds are useful, for example, as catalysts for polymerizing organic monomers. You. Organic monomers are ethylene, propylene, butene, isobutylene, hexene , Methyl acrylate, methyl vinyl ether, dienes, etc. It is not specified. The reaction can be carried out in the gas phase or in solution, on a substrate or support for synthesis, or Can be implemented separately. Metal-ligands on substrates or synthesis supports Since the catalytic properties of compounds can be investigated, various substrates or supports for synthesis (eg, (Eg, polystyrene, silica, alumina, etc.) It can be manufactured.   In another preferred embodiment of the invention, two or more elements of the metal-ligand library Is contacted with at least one cocatalyst and at least one monomer To produce a polymer blend. In yet another preferred embodiment of the present invention, a metal- At least two elements of the ligand library span at least one cocatalyst; Olefin, diolefin, acetyl, Polymerizes the len unsaturated monomer.   Another example of a library comprises a diimine ligand of general formula (I): This These libraries are synthesized by solution-phase or solid-phase methods or a combination thereof. can do.   Substituent R¹, R^Two, R^Three, And R^FourShould be selected from the wide range of organic fragments described above Can be. The role of the R group substituent is based on the steric properties, stereochemical properties, and solubility of the ligand system. To modify the electronic properties. The R group can be polar or non-polar, neutral, It can consist of acidic or basic functional groups. Where appropriate, the R groups are as described above, For example, an organic metalloid group such as a silyl or germyl group. R group substituent Has a molecular weight generally in the range of 1 to 10,000 daltons. Molecular weight 10 Polymeric or oligomeric R groups greater than 2,000 can also be made.   The diimine ligand library described above is exposed to many metal precursors to A metal library can be formed. In one method, the ligand library is , A coordinatively unsaturated metal precursor or a weakly bound decarboxylate as shown in Scheme 2 below. Contacting a metal precursor complexed by a leaving ligand.                                Scheme 2 In the formula, L is a neutral Lewis acid base, and n is an integer of 0 or more; Z is an integer of 0 or more; "A" represents the number of L groups moved, a + z = n; M is a metal; X is an anionic ligand such as a halide, hydrocarbyl or hydride; m represents the number of X ligands and is an integer of 0 or more.   A metal catalyst consisting of a noncoordinating anion is converted to a protonated form of a ligand library. It can be synthesized by contacting a metal precursor with a low-valent metal precursor. For example, a transition metal catalyst stabilized with diimine can be prepared in two steps: 1) diimine. The min library is reacted with a non-coordinating anion, Bronsted acid, to produce Step 2) forming an iminium salt library Can be adjusted by a method comprising contacting with a valence metal precursor You. One example of such a method is shown in Scheme 3 below.                                Scheme 3   In some embodiments, the ligands of the present invention may have a pure stereo or positional conformation. However, the ligand is a mixture of isomers. Can also be. Metals suitable for use in the present invention are Cr, Mo, W, Pd, Ni , Pt, Ir, Rh, Co, etc., but are not limited thereto. Departure Activators suitable for use in the disclosed methods are MAO, [H (OHt)_Two]⁺[B Ar_Four]^-Etc., but is not limited thereto. Used in the method of the present invention. Suitable solvents are hexane, CH_TwoCl_Two, Toluene, CHCl_ThreeIncluding However, the present invention is not limited to these.   The method described above may exceed 3, exceed 10, exceed 20, exceed 50, exceed 100 Well, more than 200, more than 500, more than 1,000, more than 10,000 or It can be used to synthesize over 100,000 different compounds. The chemical synthesis process is performed on a substrate or a carrier for synthesis such as pins and beads or in a well. Can be implemented by combining the solid-phase and solution-phase steps You. The method of mutating a ligand is to use a spatially addressable site By dispensing into larel or by known "split and pool" combinations It can be done by the method.   The method of the present invention provides for the length of the binding moiety between the ligand and the substrate or support for synthesis and / or Alternatively, embodiments in which the chemical composition is varied are also included. D.Linker   Combinatorial libraries include organometallic catalysts on a substrate or solid support (eg, , Silica, alumina, polystyrene, etc.) Can be In another embodiment of the invention, a linker group is provided between the substrate and the ligand. And / or between the carrier for synthesis and the ligand and / or between the substrate and the carrier for synthesis. Let A wide range of cleavable and non-cleavable linker groups are known to those of skill in the chemical arts. Used by those skilled in the art, and in the present invention, the ligand and organometallic Can be used to assemble a library. The length and structure of the linker Potential variables that can affect the performance of the catalyst. It can be a factor in measuring. Various linkers suitable for use in the method of the invention of Examples are described in more detail in PCT US94 / 05597, the teachings of which are incorporated by reference. Therefore, it is taken in here. E. FIG.metal   Once formed, the ligand library of the invention is contacted with a metal ion, Organometallic compounds can be produced. These compounds are usually catalysts . Metal ions are in the form of simple salts, mixed salts or organometallic compounds.   When the method of the present invention is used to discover active catalysts, all classes of Metal ions can be used. Extensive gold used in practicing the invention The classes of the group ions are transition metal ions, lanthanide ions, main group metals and activators. Including, but not limited to, nido ions. F.Immobilized reactants   By implementing the present invention, a combination (combinatorial) solution library When made, use one or more immobilized reactants that play different roles It is useful. Thus, for example, immobilized bases, acids, proton sponges, oxidants , Reducing agents, acylation and alkylation catalysts and the like are included in the present invention. Many Such immobilized reactants are known to and used by those of skill in the art. I have. G. FIG.Non-coordinating anion (NCA)   Uncoordinated or weakly coordinated anion in metal center present in catalyst And the reactivity of the catalyst is higher than that of a catalyst in which the anion is coordinated to the metal center. And are known in the art. (See, for example, US Pat. Nos. 5,198,401 and 5,278,1.) 19, 5,502,017 and 5,447,895, the complete developments of these. The indications are incorporated herein by reference. )   High bulk, high stability, non-coordinating with strong cationic metal center, strong Louis Anions that exhibit high acidity and high reactivity are particularly useful in practicing the present invention. In a preferred embodiment, the non-coordinating anion is a boron-containing structure. Another preferred implementation In an embodiment, the non-coordinating anion comprises four aryl structures having one or more electron withdrawing groups. Substituted by a substituent (eg, fluorine) and at least one bulky R group to A tetraarylboron structure that increases the solubility and thermal stability of the metal or catalyst system You. Representative R groups are as described above for the ligand. In a preferred embodiment, R The group is C₁-C₂₀Alkyl or C₁-C₂₀Group 14 metalloy substituted with alkyl (Eg, silicon, germanium, or tin). In carrying out the present invention Other non-coordinating ions used will be apparent to those skilled in the art. H.Design and synthesis of diimine catalyst library   Outline the principles and methods of combining and synthesizing arrays of ligands and organometallic compounds. Solution and solid phase libraries of diimine ligands and organometallic compounds The method of designing and synthesizing the is described.   FIG. 14 illustrates the use of Merrifield resin and the chemical methods described in the Examples section. 6 shows the design of a 96-well ligand and ligand-metal solid phase library used. This The library consists of a diketone precursor bound by Merrifield resin and 4 It consists of 48 diimine ligands derived from 8 substituted anilines. The diketone precursor bound by Merrifield resin is converted to microtiter Add to each of the 96 wells in the microtiter plate. Excessive amount of each Nirin was added to two wells of a microtiter plate and described in the illustrative section. Complete the reaction using the current protocol. Each obtained resin-bonded die Min, combined with Ni and Pd metal ion precursors to form the desired catalyst precursor To manufacture. The catalyst precursor is activated using an appropriate activating substance, and is used in the present invention. Screen for activity and performance using described methods. Wear.   Using the method of the present invention, solution phase diimine ligands and catalyst libraries are also prepared. Can be adjusted. Catalyze the reaction, supply the reactants, by-products and / or Or by using a solid phase reactant that adsorbs unreacted starting material. Liquid phase combinatorial chemistry will be very useful. Diimine A general approach for the parallel synthesis of ligands and corresponding metal compounds This is shown in FIG. 15 and described in section 1.1 of the exemplary section. Substituents on the ligand skeleton (ie, Mutations in R1 and R2) utilize a variety of commercially available 1,2-diketones as illustrated in FIG. Can be achieved by using Condensation of imines in the solution phase, for example, It can be catalyzed by various immobilized Lewis acid catalysts / dehydrating agents (FIG. 17). ). Examples include:                         [PS] -CH_Two-O-TiCl_Three;                         [PS] -CH_Two-O-AlCl_Two;                         [PS] -SO_Two-O-TiCl_Three;                         [PS] -SO_Two-O-AlCl_Two;                         [PS-PEG] -TiCl_Four;                         [PS-PEG] -AlCl_Three;                         [SiO_Two]-(O)_4-n−TiCl_n;as well as                         [SiO_Two]-(O)_3-n−AlCl_n In one embodiment, these catalysts are used as solid phase proton scavengers, [PS] -CH_Two-Pi Use with Peridine.   The selective capture of excess aniline in the presence of diimine can be achieved by various solid-phase reactions. This can be achieved using a reactive material. Examples include:                         [PS] -C (O) Cl + [PS] -CH_Two-Piperidine;                         [PS] -SO_TwoCl + [PS] -CH_Two-Piperidine;                         [PS] -NCO; and                         [PS] −NCS III.Screening of combinatorial libraries   First of all, the success or failure of combinatorial chemistry depends on Whether an assembly (library) of molecular compounds (elements) having elemental compositions can be synthesized And, secondly, to quickly characterize each element to achieve a particular desired property. It depends on whether or not the compound can be obtained. Therefore, one preferred embodiment Now, an array of substances is synthesized on a single substrate. Synthesize arrays of substances on a single substrate Screening of arrays for substances with useful properties Can be performed more easily.   Therefore, following the library synthesis, the library of compounds may be useful features. Screen for gender. Properties that can be screened Electrical, thermomechanical, morphological, optical, magnetic, chemical Including characteristic characteristics. In one preferred embodiment, useful properties are those involved in the polymerization reaction. You. In another preferred embodiment, useful properties include mechanical properties, optical properties, physical properties. Gender or morphological characteristics. In certain preferred embodiments, useful properties include, for example, The lifetime of metal-ligand compounds, the stability of these compounds under specific reaction conditions, Library compound selectivity for a given reaction, Chemistry such as conversion efficiency in the reaction or the activity of library compounds in a particular reaction Characteristic. Other properties that can be screened are shown in Table I below. helpful Any substance found to have properties can subsequently be manufactured on a large scale. Can be. For simplicity, the analytical method of the present invention uses a library of catalytic compounds. A comprehensive example is given by describing the case of use in a computer. like this The use of a library of catalytic compounds is useful for analyzing a library of organometallic compounds. It does not limit the scope of applicable analytical methods.   The properties listed in Table I are well-known and widely used by those skilled in the art. Can be screened using the method and apparatus described in Such a method is , Scanning mass spectrometry, chromatography, ultraviolet imaging, visible imaging, Infrared imaging, electromagnetic imaging, ultraviolet spectroscopy, visible spectroscopy, infrared spectroscopy Including, but not limited to, analysis, electromagnetic spectroscopy, and acoustics. In addition Thus, a scanning system that can be used to screen for the properties listed in Table I is Scanning Raman spectroscopy; scanning NMR spectroscopy; e.g., surface potentiometry, t Tunnel current, nuclear power, acoustic microscopy, shear stress microscopy, ultrafast photoexcitation, electrostatic force Microscopic analysis, tunnel induced photoemission microscopy analysis, magnetic force microscopy analysis, micro Wave field induced surface harmonic generation microscopy analysis, nonlinear ac Tunneling microscope analysis, near-field scanning optical microscope analysis, inelastic electron tunneling Scanning probe spectroscopy, such as optical analysis; optical microscopy at different wavelengths; Optical ellipsometry (for measuring the thickness of multiphase films); Includes, but is not limited to, microscopic analysis; electron (diffraction) microscopic analysis, etc. No.   The currently preferred embodiment uses a scanning sensing system. In one embodiment, , The substrate having the substance array thereon is immobilized and the detector makes an XY motion. This fruit In the embodiment, the base is provided in the closed chamber close to the detection device. Detection device (for example, , RF resonator, SQUID detection device, etc.) m spatial resolution, coupled to an XY positioning table at room temperature heat Attached to rigid rods with low conductivity. Computer controlled location of detector Using a stepping motor (or servomotor) coupled to a positioning device Controlled. In another embodiment, a sensing device is immobilized on a substrate having a substance array thereon. The body performs R-θ movement. In this embodiment, the micrometer and stepping A rotary stage (eg, a spur gear) driven by a gear rack coupled to a motor ) Is placed on the substrate. In each embodiment, the temperature of the detection device and the temperature of the base are, for example, , Can be lowered by helium exchange gas. This scanning system From 600 ° K to 4.2 ° K below (when immersed in liquid helium) Can be operated at temperature.   Using combinatorial chemistry to discover and optimize new catalysts This depends on the activity (ie, turnover), the choice in converting the reactants to the desired product. Characteristics such as stability, stability during operation over a wide range of substrate concentrations and reaction conditions) This is further enhanced by using a high-throughput method in doing so. Spatial selection Alternative characterization methods include, for example, (i) gas phase product and cohesive phase formation Identification and characterization of the volatile components of the product; (ii) Identification and characterization, and (iii) various catalysts in the library Includes methods that allow measurement of physical properties of an element.   High throughput (0.1 to over 1000 library elements per second) ), Position-sensitive (resolution 0.01 to 10 mm) Mass spectrometry and chromatography, ultraviolet, visible, infrared and other electromagnetic imaging and Includes several fundamentally different approaches, including spectroscopy and acoustics You. Methods for measuring catalyst activity and specificity include, for example, direct measurement of product concentration. Or a method of indirectly measuring the heat of reaction. The parallel screening method , A common approach to integrating position-sensitive photon detectors into measurement systems The serial screening method, on the other hand, has a controlled library It relies on scanning or sensing devices / sources relative to each other.   The activity of each compound in the array can be measured in several optical, thermal, and mass spectral It is measured using one or more of the methods. In one example, the reaction is exothermic or endothermic Is a property that localizes the temperature difference in the area adjacent to the compound. By monitoring such temperature changes with infrared imaging technology Active sites in the compound array are identified in parallel. A similar technique is compound array It can also be used when quantifying the stability of each catalyst having in parallel. By measuring the decrease in activity over time for each site in the array, The life of the medium can also be quantified.   Measurement of the selectivity of catalysts in combinatorial arrays is based on UV / visible / IR imaging. Using soaking and / or spectroscopy, chromatography or mass spectroscopy This is done by: One of the most common methods of the present invention is scanning mass spectrometry. Of the reactants and products adjacent to the catalyst compound in the library It is to measure the relative concentration locally. Such a measurement system is , The binding reactants and / or binding products are vaporized in spatially localized form and Using laser desorption to promote the incorporation of chemicals into the instrument Can be empowered.   Optical methods are used for active and selective characterization. Red Infrared spectroscopy or infrared spectroscopy is performed along the end groups and the polymer chains on the polymer. The relative concentration of the saturated skeleton with the monomer is monitored. In this way, The average molecular weight of the slurry element and the average composition of the copolymer can be estimated. ultraviolet / Visible spectroscopy techniques include, for example, compounds with suitable chromophores (eg, aromatic Group and unsaturated compounds). With another example Benzene is partially oxidized to phenol, resulting in different electron absorption depending on the product. An optical spectrum may result. In this case, benzene is converted to a spectroscopic Is clearly distinguished from phenols as unger prints and therefore has a UV / visible Light analysis can be used to determine the relative amounts of each compound.   Rapid chromatographic analysis of reactants and products as separate substances or mixtures Is used to determine product conversion, product identification, isomer purity, etc. in parallel. Can be used. When conducting the polymerization reaction, the product po The rate of the limmer solution is a measure of the viscosity of the polymer, and thus the molecular weight of the polymer. used. In addition, use mass spectrometry for gas phase characterization Can be.   In addition to the above to screen libraries of compounds for useful properties Those skilled in the art will readily understand that numerous methods and devices may be used. Will be. Such methods and devices are also included within the scope of the present invention.   The present invention relates to the synthesis of supported and unsupported ligand molecules, and the subsequent To an organometallic compound and a catalyst compound. In the following example Describes the synthesis of two representative compounds, diimine and pyridylimine, according to the present invention. The method will be described in detail. Representative Examples Using Both Solution-Phase and Solid-Phase Methods Is shown. The use of these two broad groups of ligands to further illustrate the present invention is described. Is intended to be exemplary and to use the scope of the invention or the method of the invention. Therefore, the range of ligands, organometallic compounds or catalysts that can be assembled was defined. It is not limited. IV. Example   The following examples illustrate various embodiments of the present invention. Example 1 The synthesis of the bis-imine ligand in the solution phase will be described. Example 2 describes the diimine ligand The concept of combination synthesis (combinatorial synthesis) in the solid phase will be described. Implementation Example 3 demonstrates the method of the present invention, in which the synthesis of diimine is carried out on a support, The application to phase synthesis will be described. Example 4 was used in the synthesis of olefins. The utility of the catalyst of the present invention will be described. Both the supported and unsupported catalysts of the present invention are: The ability to polymerize ethylene into poly (ethylene) was evaluated. Hexen The polymerization of higher olefins was also investigated. Example 5 shows the pyridyl imine distribution. The preparation of the ligand and its nickel complex will be described in detail. This catalyst converts hexene and ethylene. Used to polymerize both. Example 6 shows various [2,0] and [2,1] And reaction schemes that can be used to prepare [2,2] ligand libraries explain. Such [2,0], [2,1] and [2,2] ligand libraries Is adjusted from a salen-based skeleton using a solution phase or solid phase method. Can be                                 Example 1   Example 1 describes the use of a combinatorial ligand library library. The solution phase synthesis of the imine ligand component is described in detail. Comprehensive strategy, children An arylbis-imine having both a donating group and an electron-withdrawing group in the aryl moiety Was done. 1.1[(2,4,6Me ₃ PH) DABMe ₂ ] NiBr ₇ via solution phase method Synthesis of     a. Resin-bound Lewis acid catalyst PS-CH_Two-O-TiCl_ThreeSynthesis of   100 mL of anhydrous CH_TwoCl_Two10 g of hydroxymethyl police swollen in water 4.24 g (2.24 mmol) in Tylene (1.12 mmol OH / 1 g resin) TiCl_FourAnd the suspension is added with N_TwoHeat reflux for 1 hour with gentle stirring under did. Resin N_TwoAnd filtered under 5 × 50 mL anhydrous CH_TwoCl_TwoAnd then Dry under high vacuum for 24 hours. Chloride analysis (9.9) 8%) to 0.94 mmol TiCl_Three/ 1 g of resin was obtained.     b. Aniline scavenger PS-SO_TwoSynthesis of Cl   50 mL of anhydrous CH_TwoCl_Two10g PO inside_TwoSO_Two-OH (washed with MeOH And vacuum dried Amberlyst 15 (about 5 mmol OH / 3 g (25 mmol) of SOCl_TwoWas added. This mixture is_Two The mixture was heated under reflux for 18 hours. Resin N_TwoAnd filtered under 5 × 50 mL of anhydrous CH_Two Cl_TwoAnd dried under high vacuum for 24 hours. Chlorine analysis value (16.05%) 4.53 mmol of SO_TwoA loading of 1 g of Cl / resin was obtained.     c. Synthesis of ligand   250 mg (0.24 mmol) of PS-CH_Two-O-TiCl_ThreeAnd 93mg ( 0.25 mmol) PS-CH_Two-5 mL of anhydrous CHCl in piperidine_TwoHanging on To the suspension, 676 mg (0.5 mmol) of 2,4,6-trimethylaniline were added. Was added 8.6 mg (0.1 mmol) of 2,3-butanedione. This mixture Is shaken at room temperature (RT) for 24 hours and then filtered, 2 x 1 mL of anhydrous CH_TwoCl_Two And washed. Analysis by gas chromatography revealed that 2,4,6-trimethyl Luaniline and the product (2,4,6-Me_ThreePh) DABMe_TwoIs about 3: 1 Indicated by ratio.     d. Capture of excess aniline   2,4,6-trimethylaniline and (2,4,6-Me_ThreePh) DABMe_Twoof In a 3: 1 mixture, 111 mg of PS-SO_TwoCl and 185 mg PS-CH_Two− Piperidine was added and the mixture was shaken at room temperature for 12 hours. The resin was filtered and 2x0. 5 mL of anhydrous CH_TwoCl_TwoAnd washed. Evaporate the filtrate to 285 mg (89%) (2,4,6-Me_ThreePH) DABMe_TwoWas obtained as yellow crystals.     e. [(2,4,6-Me_ThreePh) DABMe_Two] NiBr_TwoComplex synthesis   285 mg (0.89 mmol) of (2,4,6-Me_ThreePh) DABMe_TwoAnd 2 74 mg (0.89 mmol) (DME) NiBr_Two5 mL CH_TwoCl_TwoHanging on The suspension was shaken in a sonication bath at room temperature for 24 hours. The solid obtained is filtered Collect 3 x 1 mL anhydrous CH_TwoCl_TwoAnd 456 mg (95%) of [(2 , 4,6-Me_ThreePh) DABMe_Two] To Br_TwoWas obtained as a red powder. 1.2(2,4,6-Me) ₂ DAB (Me) EtPh nickel (II) dibromine Manufacturing                                Scheme 4   (2,4,6-Me)_TwoDAB (Me) EtPh (0.50 g, 1.17 mm Mol) and (DME) NiBr_Two(0.36 g, 1.17 mmol) in 8 mL of dry Dry CH_TwoCl_TwoUnder nitrogen and stirred at room temperature for 8 hours. Red-brown solution obtained And concentrate the residue in CH_TwoCl_TwoRecrystallized from / hexane to give 0.40 g of (2 , 4,6-Me)_TwoDAB (Me) EtPh nickel (II) dibromide 53% In the form of reddish brown crystals. C₃₀H₃₆N_TwoNiBr_TwoTheoretical value of: C 55.88; H 5.62_; N 4.34. Found: C, 55.08; H, 5.55; N, 4.21. 1.3Synthesis in solution phase (spectroscopic analysis model compound)   A compound having all of the structural characteristics of the immobilized compound is used in parallel with the immobilized compound. Produced. Appropriate spectroscopic analysis of similar immobilized compounds with this model compound The parameters could be determined. In addition, these compounds have similar immobilization It has a catalytic activity similar to that represented by the metal-ligand compound. 1.3 (a)(2,4,6-Me) ₂ DAB (Me) Et using benzyl bromide Alkylation                                Scheme 5   (2,4,6-Me)_TwoDAB (Me) Et (2.00 g, 5.99 mmol) ) In a cooled solution (0 ° C.) in 15 ml of dry THF under nitrogen under LDA (4.4). 0 ml, 6.59 mmol, 1.5 M in THF) was added. Stir at 0 ° C for 2 hours After stirring, benzyl bromide (0.86 ml, 7.19 mmol) was added to obtain The solution was stirred at 0 ° C. for 3 hours at room temperature for 10 hours. The reaction mixture is placed on a rotary evaporator (rotov ap) And concentrate the oily residue in 50 ml of Et._TwoDissolved in O, H_TwoO (2x50ml) And washed. Et_TwoO layer is MgSO_FourDry over, filter and concentrate. This crude substance , CH_TwoCl_TwoTogether with a silica gel plug and concentrate again. 54 g of the desired product was obtained in 95% yield as a yellow oil.¹ H NMR 300 MHz, (CDCl_Three) δ7.23-7.28 (m, 3H), 7.19 (d, 2H, J = 6.9 Hz), 6.98 (s, 2H), 6.94 (s, 2H), 2.87 (br s, 4H), 2.64 (q, 2H, J = 7.6 Hz ), 2.37 (s, 3H), 2.35 (s, 3H), 2.14 (s, 6H), 2.06 (s, 6H), 1.12 (t , 3H, J = 7.6 Hz);¹³ C NMR 75 MHz, (CDCl_Three) θ171.97, 169.97, 145.85, 145.56, 141.15, 132.28 , 132.20,128.66,128.28,128.15,125.97,124.37,32.76,31.28,22.24,2 0.67, 18.22, 18.06, 11.24; IR (C = N) @ 1635 cm^-1. 1.3 (b)Benzyl (2,4,6-Me) ₂ DAB (Me) Et (methyl) Hydrolysis                                Scheme 6   10 ml of THF / H_TwoBenzyl (2,4,6-) in O (5: 1 v / v) Me)_TwoDAB (Me) Et (0.20 g, 0.47 mmol) and oxalic acid (0 . (20 g, 2.35 mmol) was heated at 70 ° C. for 8 hours. To room temperature And cool with 30 ml of Et_TwoAfter dilution with O, the organic layer is_TwoCl_Two(2x10m l) and washed with MgSO_FourDry over, filter and concentrate. Gas chromatography When analyzed by GC / MS, the detectable species in the crude reaction mixture were: , 1-phenyl-3,4-hexanedione and 2,4,6-trimethylaniline Was only. The crude mixture was passed through a silica gel plug. Pure 1-phenyl-3,4-hexanedione (89 mg) Was obtained as a colorless oil in> 95% yield.¹H NMR 300 MHz, (CDCl_Three) δ7.20- 7.31 (m, 5H), 3.14 (t, 2H, J = 7.6 Hz) 3.01 (t, 2H, J = 7.4 Hz), 2.75 (Q, 2H, J = 6.7 Hz), 1.07 (t, 3H, J = 6.6 Hz);¹³C NMR 75 MHz, (CDCl_Three) δ199.44, 198.25, 140.19, 128.20, 128.06, 125.94, 37.34, 29.10, 28.67, 6 .53; IR (C = O) @ 1712cm^-1. 1.3 (c)1- (bromomethyl) of (2,4,6-Me) ₂ DAB (Me) Et ) -2-Alkylation with 2-methoxyethane                                Scheme 7   (2,4,6-Me) in 15 ml of dry THF under nitrogen_TwoDAB (Me) To a cooled solution (0 ° C.) of Et (0.50 g, 1.48 mmol) was added LAD (1. 09 ml, 1.65 mmol, 1.5 M in THF) was added. 4 hours at 0 ° C After stirring, 1- (bromoethyl-2-methoxyethane (0.24 ml, 0. 1.79 mmol))_FourNI (0.27 ml g, 0.75 mmol) And the reaction mixture was heated to 50 ° C. and stirred for 10 hours. Cooled to room temperature Afterwards, the reaction mixture was washed with 30 ml of Et._TwoDiluted with O, H_TwoWash with O (3x15ml) , MgSO_FourDry over, filter and concentrate on a rotovap. This crude substance With 20% Et_TwoO / hexane (R_f= 0.45) analyzed by chromatography This gave 0.93 g of the desired product as a yellow oil in 45% yield.¹H N MR 300 MHz, (CDCl_Three) δ6.81 (s, 2H), 3.33 (s, 4H), 3.25-3.32 (m, 2H), 3 .23 (s, 3H), 2.41-2.47 (m, 4H), 2.20 (s, 6H), 1.94 (s, 12H), 1.54- 1.69 (m, 2H), 0.94 (t, 3H, J = 7.5 Hz).¹³C NMR 75 MHz (CDCl_Three) Δ171.97 , 170.35, 145.65, 145.52, 132.15, 128.56, 128.53, 124.36, 71.72, 70.95, 69.48, 58.89, 27.33, 25.51, 22.19, 20.61, 18.06, 11.11 1.3 (d)(2,4,6-Me) ₂ DAB (1 methoxyethoxyethyl) Et Preparation of Hackel (II) dibromide                                Scheme 8   (2,4,6-Me)_TwoDAB (1-methoxyethoxypropoxy) ethane (0.29 g, 0.67 mmol) and (DME) NiBr_Two(0.21 g, 0. 67 mmol) under nitrogen with 6 ml of dry CH_TwoH_TwoAnd stirred at room temperature for 24 hours. Stirred. The reaction mixture was filtered through celite and concentrated to give crude (2,4,6-Me )_TwoDAB (1 methoxyethoxypropyl) ethyl nickel (II) dibromide And this is CH_TwoCl_Two/ Hexane and purified by recrystallization from 0.35 g of Pure product was obtained as red-brown crystals in 80% yield. C₂₈H₄₀N_TwoO_TwoNiBr_TwoTheory of C 51.33; H 6.15; N 4.27. Found: C 52.01; H 6.26 ; N 3.91. 1.3 (e)(2,4,6-Me) ₂ DAB (Me) EtPh palladium (II) Preparation of (Me) Cl                                Scheme 9   (2,4,6-Me)_TwoDAB (Me) EtPh (0.23 g, 0.65 mm Mol) and (COD) PdMeCl (0.17 g, 0.65 mmol) under nitrogen 8ml dry CH_TwoCl_Two  And stirred at room temperature for 8 hours. The obtained orange-red Concentrate the colored solution and remove the residue in CH_TwoCl_Two/0.3 recrystallized from hexane. g of (2,4,6-Me)_TwoDAB (Me) EtPh palladium (II) (Me) Cl was obtained in 80% yield as an orange solid. C₃₁H₃₉N_TwoTheoretical value of PdCl:  C 64.02; H 6.76; N 4.81 Found: C 63.47; H 6.70; N 4.62. 1.4Combinatorial synthesis in solution phase   The formation of bis-imines using a catalyst is based on an aniline containing an electron donating group (X = EDG). In general, it works well for derivatives. However, the electron-withdrawing group (X = EWG) The aniline contained is much less nucleophilic and under standard conditions (Experiment 1 in Table 1) No imine formation is observed. Therefore, typical electron-deficient aniline derivatives (X = 3.5-CF_Three) To initiate the formation of the bis-imine I searched. The overall scheme is shown in Scheme 10. The results are shown in Table 1. You.                               Scheme 10                                 Example 2   Example 2 illustrates the concept of combinatorial synthesis of diimine ligands in the solid phase. less than By the described approach, 1% cross-linked (bromomethyl) polystyrene The alkylation of the imine ligand is performed. Hydrolyze the supported diimine and chemically Pairs used as starting materials for the synthesis of a wide variety of bis-imine ligands A corresponding resin-bound diketone is formed. A similar solution phase reaction was performed in parallel to Completely characterize the solution phase reaction by spectroscopy , Spectroscopic handles (¹H and¹³C NMR, FTI R, Raman IR) to characterize the desired resin-bound compound Helps you to do things. 2.1Combination strategy in solid phase (combinatorial strategy)   This approach is a parametrization of organometallic libraries immobilized on polymer supports. Including synthetic synthesis. The advantage of this approach is that it can significantly reduce excess reactants. Including exposing the reaction to a normalized substrate to efficiently complete the reaction. This will result in excess reactants The quality and / or by-products can then be filtered and thoroughly washed to obtain the desired Is removed from the immobilized substrate. 2.2Preparation of (bromomethyl) polystyrene                               Scheme 11   (Hydroxymethyl) polystyrene (2.50 g, 2.84 mmol, 0.8 0 mmol / g) and triphenylphosphine dibromide (2.40 g, 5.68). Mmol) under nitrogen and 20 ml of dry THF was added. 24 hours at room temperature After stirring, the resin was filtered, THF (3 × 20 ml), DMF (3 × 20 m l), CH_TwoCl_Two(3 × 20 ml), dry under high vacuum, 75 g of (bromomethyl) polystyrene were obtained as a light brown resin. Bromide Of 0.58 mmol / g was calculated based on the analytical value (4.65% Br) of Was done. 2.3(2,4,6-Me) ₂ DAB with (bromomethyl) polystyrene Me) Alkylation of Et                               Scheme 12   (2,4,6-Me) in 15 ml of dry THF under nitrogen_TwoDAB (Me) E t (0.50 g, 1.49 mmol) in a cold solution (0 ° C) with LAD (0.19 g) ml, 1.49 mmol, 1.5 M in THF). Stir at 0 ° C for 2 hours After that, (bromomethyl) polystyrene (1.06 g, 0.75 mmol) was added. The resulting suspension was stirred at 0 ° C. for 3 hours and at room temperature for 10 hours. This resin Was filtered off, THF (2 × 20 ml), H_TwoO (2 × 20 ml), CH_TwoCl_Two(2 x20 ml) and dried under high vacuum to give 0.60 g of the desired light yellow color. A resin was obtained. This resin carrying amount is based on the analysis value of nitrogen (1.07% N). , 0.38 mmol / g. By single bead FTIR, 1635 cm^-1Strong absorption was observed at (C = N). 2.4(2,4,6-Me) ₂ DAB (Me) Et (methyl) polystyrene Hydrolysis                               Scheme 13   17 ml of THF / H_Two(2,4,6-Me) in O (5: 1 v / v)_TwoDA B (Me) Et (methyl) polystyrene (1.0 g, 0.38 mmol) A stirred suspension of uric acid (340 g, 3.80 mmol) was heated at 70 ° C. for 12 hours . Cool to room temperature and add 30 ml Et_TwoAfter dilution with O, the resin is filtered and the filtrate is H_TwoWash with O (2 × 10 ml), MgSO_FourDried over, filtered and concentrated, Chromatography / mass spectrometry and¹> 99% purity by HNR analysis 24 mg of 2,4,6-trimethylaniline was obtained in 98% yield. Beads Dry under high vacuum and dry 850 mg of (2,3-butanedionemethyl) polystyrene was gotten. 1712 cm by single bead FTIR^-1Strong absorption at (C = O) Was observed. 2.5(2,4,6-Me) ₂ DAB with (bromo) PEG polystyrene Me) Alkylation of Et                               Scheme 14   (2,4,6-Me) in 15 ml of dry THF under nitrogen_TwoDAB (Me) LDA (1.63) was added to a cooled solution (0 ° C.) of Et (0.7 g, 2.09 mmol). ml, 2.44 mmol, 1.5 M in THF). Stir at 0 ° C for 4 hours After that, (bromo) PEG polystyrene (2.33 g, 0.70 mmol, 0.1 g) was added. 30 mmol / g) and Bu_FourNI (0.77 g, 2.09 mmol) was added. The reaction mixture was heated to 50 ° C. and stirred for another 8 hours. Then the resin is filtered , THF (3x20ml), H_TwoO (3 × 20 ml), MeOH (3 × 20 ml ). After drying under high vacuum, 2.37 g of (2,4,6-Me )_TwoDAB (Me) Et (bromo) PEG polystyrene was obtained as a yellow resin Was. 0.25 mmol / g loading based on nitrogen analysis (0.71% N) The amount was calculated. Magic Angle Spin (MAS)¹H NMR 400 MHz, (CDCll_Three) δ6 .87 (br s, 2H), 3.51 (br s, 2H), 2.76 (br s, 2H), 2.51 (d, 2H, J = 7. 6 Hz), 2.28 (s, 6H), 2.01 (s, 12H), 1.74 (brs, 2H). 1.03 (t, 3H, J = 6.8 Hz). 2.6Hydrolysis of (2,4,6-Me) ₂ DAB (Me) EtPEG polystyrene Disassembly                               Scheme 15   (2,4,6-Me)_TwoDAB (Me) EtPEG polystyrene (0.50 g , 0.12 mmol, 0.25 mmol / g) and oxalic acid (0.10 g, 1.1 2 mmol) in 20 ml THF / H_TwoDissolved in O (5: 1, v / v) for 8 hours Heat at 70 ° C. with gentle stirring. Cool to room temperature and add 25 ml Et_TwoO After dilution with, the resin was filtered and the filtrate was filtered with H_TwoWash with O (2 × 10 ml) and MgSO_Four Dry over, filter and concentrate to give a quantitative yield of 16 mg of 2,4,6-trimethyl. Aniline was obtained. This 2,4,6-trimethylaniline is used for gas chromatography. Luffy / mass spectrometry and¹NMR analysis indicated a purity of> 99%. Bi Is dried under high vacuum to give 450 mg of 2,3-butanedinone P in beige color. EG resin was obtained. Magic Angle Spin (MAS)¹H 400 MHz, (CDCl_Three) Δ 2.80 (M, 2H), 1.90 (m, 2H), 1.08 (t, 3H, J = 6.8 Hz). 2.7(2,4,6-Me) ₂ DAB (Me) Et nickel (II) dibromide Preparation of PEG polystyrene                               Scheme 16   (2,4,6-Me)_TwoDAB (Me) Et PEG polystyrene (0.40 g, 0.10 mmol, 0.25 mmol / g) and (DMe) NiBr_Two(0. 15 g, 0.50 mmol) in 10 ml of dry CH under nitrogen._TwoCl_TwoDissolved in the chamber Stirred at warm for 12 hours. Then, the resin is CH_TwoCl_TwoAnd strong washing with anhydrous acetone And 0.42 g of (2,4,6-Me)_TwoDAB (Me) Et Nickel (II) Dibromide PEG polystyrene was obtained as a dark reddish brown resin. Of this resin The carrying amount was 0.54 mm when calculated from the analysis value of nickel (3.40% Ni). Mol / g, 0.57 mmol / g based on bromine analysis (8.67% Br). Calculated that this indicates some residual nickel (II) on the PEG polystyrene backbone. This indicated that dibromide was coordinated. 2.8(2,4,6-Me) ₂ DAB (Me) Et palladium (II) (Me) Preparation of Cl PEG polystyrene                               Scheme 17   (2,4,6-Me)_TwoDAB (Me) Et PEG polystyrene (0.50 g , 0.12 mmol, 0.25 mmol / g) and (COD) PdMeCl (0. 16 g, 0.63 mmol) in 7 ml of dry CH under nitrogen._TwoCl_TwoDissolve at room temperature For 12 hours. Then, the resin was CH_TwoCl_TwoWash strongly with 0.5 1 g of (2,4,6-Me)_TwoDAB (Me) Et Pd (II) (Me) ClPE G polystyrene was obtained as a red-orange resin. Magic Angle Spin (MA S)¹H NMR 400 MHz, (CDCl_Three) Δ6.97 (br s, 2H), 6.92 (br s, 2H), 2.75 ( br s, 2H), 2.45 (br s, 2H)), 2.32 (s, 3H), 2.30 (s, 3H), 2.24 (s, 6  H), 2.21 (br s, 6H), 1.62 (br s, 2H), 1.03 (br s, 3H), 0.36 (s, 3H) H). 2.9(2,4,6-Me) ₂ DAB (Me) Et palladium (II) (Me) Preparation of Cl PEG polystyrene                               Scheme 18   (2,4,6-Me)_TwoDAB (Me) Et polystyrene (0.30 g, 0. 11 mmol, 0.38 mmol / g) and (COD) PdMeCl (0.15 g , 0.57 mmol) under nitrogen and 8 ml of dry CH_TwoCl_TwoWas dissolved. After stirring for 10 hours, the resin was washed with CH_TwoCl_TwoStrong wash with, dry under high vacuum, 0.32 g of (2,4,6-Me)_TwoDAB (Me) Et palladium (II) (M e) Cl polystyrene was obtained as a red-orange resin. This resin Is 0.32 mm based on the analytical value of palladium (4.15% Pd). Mol / g, 0.39 mmol / g based on chlorine analysis (3.39% Cl) It was calculated.   Example 2 uses the solid phase combination method (solid phase combinatorial method) of the present invention. 1 shows the synthesis of a representative diimine ligand. The diimine of Example 2 was synthesized except on a carrier. And then coupled to a carrier for further modification. Attached to the carrier Following the hydrolysis of the diimine, the dike used to produce further diimine Tons are generated.                                 Example 3   Example 3 describes the method of the present invention for the solid-phase synthesis of a diimine ligand synthesized on a carrier. Here is an example of application. 3.1 Bis-imine formation on solid phase                               Scheme 19   2,3 butanedione (methyl) polystyrene (0.10 g, 0. 08 mmol) dry CH_TwoCl_Two3,5-bis (trifluoromethyl) Le) aniline (0.25 ml, 1.60 mmol) and TiCl_Four (0.80 ml, 0.80 mmol, CH_TwoCl_Two1.0M). mixture The material was stirred at room temperature for 24 hours, the resin was filtered and CH_TwoCl_Two(3 × 10 ml), M MeOH (3 × 10 ml), H_TwoWash vigorously with O (3 × 10 ml) and under high vacuum Drying yielded 0.11 g of the desired resin. The amount of this resin carried is determined by nitrogen analysis. It was calculated to be 0.43 mmol / g based on the value (0.43% N).   Example 3 demonstrates that diimines can be formed directly on resins functionalized with diketones. It is for explanation.                                 Example 4   Example 4 shows that the catalyst of the invention can be used for the polymerization of olefins. Departure Both light and unsupported catalysts polymerize ethylene into poly (ethylene) It was discussed what could be done. The weight of higher olefins such as hexene The case was also considered. 4.1Polymerization of ethylene                               Scheme 20   The above resin-bound nickel (II) dibromide complex (0.16 g, 0.03 mmol Was suspended in 10 ml of dry toluene, and MAO was added thereto (2.00 m). 1,300.0 mmol, 10% by weight in toluene). Resin immediately turns dark blue It changed color. After stirring for one hour, ethylene gas was bubbled through the suspension for one minute. The reaction vessel was sealed at 5 PSI. The internal thermocouple generates 2 degrees of heat at 29 ° C. It was measured to occur over a period of 0 minutes. After stirring for another 1.5 hours, Slowly return to room temperature, filter viscous solution and remove beads with toluene (3 × 10 ml) And washed. The filtrate was concentrated and then quenched with MeOH to give a white rubbery (Po I) Ethylene was formed immediately. This material was filtered and dried to give 1.60 g of (Poly) ethylene was obtained. Dry the beads under high vacuum and remove the polystyrene beads. Yielded 1.60 g of material, corresponding to a 10-fold increase in weight.   Except for washing the MAO-activated catalyst with toluene (3 × 10 ml) The same procedure was followed. After filtering off the excess MAO and before introducing ethylene Dissolve in 10 ml of toluene. The same product as in the above procedure was obtained. This wash The dissolved resin was dissolved in 10 ml of hexane instead of toluene. Similarly, the amount of (poly) ethylene on the beads was as small as 0.26 g.   The above examples demonstrate that the supported catalyst of the present invention can catalyze the polymerization of olefins. Showed that you can. 4.2[2-Ph) PMI (2,6- (Pr) ₂ Ph] using NiBr ₂ / MAO Ethylene polymerization   6 mg (0.01 mmol) of [2-Ph) PMI in anhydrous degassed toluene 2,6- (Pr)_TwoPh)] NiBr_TwoTo a suspension of 3.3 mL (5 mL) in toluene. (Mmol) of 10% MAO and the resulting green solution was stirred at room temperature for 1 hour. Was. The solution was then flushed with ethylene and placed under 10 psi of ethylene. For 2 hours. To the reaction mixture was added 4M HCl (50 mL) and Et._TwoO (100 mL), the layers were separated, and the organic layer was dried over MgSO 4._FourDried on. rotation Removal of volatile components in the evaporator yielded 1.3 g of polymer material. 4.3(2,4,6-Me) ₂ DAB (1-methoxyethoxypropyl) Et Ethylene polymerization using nickel (II) dibromide                               Scheme 21   (2,4,6-Me)_TwoDAB (1-methoxyethoxypropyl) ethyl nick Kel (II) dibromide (0.02 g, 0.03 mmol) was added to 15 ml of dry toluene. Suspended in ene and added MAO (2.00 ml, 300.0 mmol, toluene 10% by weight). The solution turned dark blue over 1 hour. Stir for 1 hour After that, ethylene gas was bubbled through the suspension for 1 minute, and then the reaction vessel was And sealed. The internal thermocouple generates 23 ° C heat for 45 minutes. Was measured. After stirring for another 1.5 hours, the temperature gradually returns to room temperature and The liquid was quenched with MeOH followed by 5N HCl. Filtration of precipitated polyethylene After collecting and drying under high vacuum, 1.38 g of polyethylene were obtained. Was. 4.4(2,4,6-Me) ₂ DAB (Me) EtPh nickel (II) dibro Polymerization of ethylene using amide                               Scheme 22   (2,4,6-Me)_TwoDAB (Me) EtPh nickel (II) dibromide ( (0.02 g, 0.03 mmol) in 15 ml of dry toluene. (2.00 ml, 9.33 mmol, 10% by weight in toluene). The solution is It turned deep blue over 1 hour. After stirring for 1 hour, Was bubbled through for 1 minute and the reaction vessel was sealed at 5 psi. With the internal thermocouple, An exotherm of 19 ° C. was measured over 45 minutes. Another 1.5 o'clock After stirring for a while, the temperature gradually returned to room temperature and the solution was washed with MeOH followed by 5N H 2. Quenched with Cl. When the precipitated polyethylene was collected by filtration, After drying, 2.10 g of polyethylene was obtained.   In the above examples, the supported and unsupported catalysts of the present invention are used for the olefin polymerization reaction. Show that you can. 4.5(2,4,6-Me) ₂ DAB (Me) Et nickel (II) dibromide Polymerization of ethylene using PEG polystyrene                               Scheme 23   The above resin-bound nickel (II) dibromide resin (0.20 g, 0.02 mmol (0.10 mmol / g) was suspended in 20 ml of dry toluene, and MAO was added. (2.00 ml, 300.0 mmol, 10% by weight in toluene). Resin is straight The color changed to dark blue soon. After stirring for 1 hour, the suspension was passed through ethylene gas for 1 minute. The reaction vessel was sealed at 5 psi while bubbling air through. For the internal thermocouple, An exotherm was measured over 45 minutes. Stir for another 1.5 hours Later, the temperature gradually returned to room temperature, the solution was filtered, and the beads were washed with toluene (3 × 10 m Washed in l). Dry the beads under high vacuum to increase the mass by a factor of 3 compared to polystyrene beads. 0.67 g of material corresponding to were obtained. No polyethylene can be obtained from the filtrate. won. 4.6(2,4,6-Me) ₂ DAB (Me) Et palladium (II) (Me) Polymerization of ethylene using ClPEG polystyrene                               Scheme 24   The above resin-bound palladium (II) (Me) Cl resin (0.20 g, 0.02 Remol, 0.10 mmol / g) in 20 ml of dry CH._TwoCl_TwoSuspended in NaB (Ar ')_FourF was added (18 mg, 0.02 mmol). Resin for 1 hour And the suspension was bubbled with ethylene gas for 1 minute. Reaction vessel Was sealed at 5 psi. No exotherm was observed throughout the course of the reaction. Further 1. After stirring for 5 hours, the solution was filtered and the beads were washed with toluene (3 × 10 ml). Was. Dry the beads under high vacuum, corresponding to a 20% weight gain of polystyrene beads 0.25 g of material was obtained. No polyethylene was obtained from the filtrate. 4.7(2,4,6-Me) ₂ DAB (Me) Et palladium (II) (Me) Polymerization of ethylene using Cl polystyrene                               Scheme 25   The above resin-bound palladium (II) (Me) Cl resin (0.10 g, 0.03 Remol, 0.32 mmol / g) in 25 ml of dry CH._TwoCl_TwoSuspended in NaB (Ar ')_FourF was added (30 mg, 0.03 mmol). Tree for one hour The fat turned brownish red and ethylene gas was bubbled through the suspension for 1 minute. Reaction vessel Was sealed at 5 psi. Throughout the course of the reaction, a temperature of 23 ° C was observed. Was. After stirring for an additional 1.5 hours, the solution was filtered and the beads were washed with toluene (3 × 10 ml). Dry the beads under high vacuum to obtain 100 0.25 g of material corresponding to a% weight gain was obtained. From the filtrate, 2.28 g of po The ethylene was obtained as a colorless rubber. Gel filtration chromatography (Torue Mn = 18,518; Mw = 31,811; M_w/ M_n=  1.72. 4.8(2,4,6-Me) ₂ DAB (Me) Et palladium (II) (Me) Polymerization of ethylene using Cl                               Scheme 26   (2,4,6-Me)_TwoDAB (Me) Et palladium (II) (Me) Cl ( 0.02 g, 0.03 mmol) in 25 ml of dry CH_TwoCl_TwoSuspended in NaB (Ar ')_FourF was added (30 mg, 0.03 mmol). Dissolve for 1 hour The liquid turned brown-red and ethylene gas was bubbled through the suspension for 1 minute. 5p reaction vessel sealed in si. An exotherm of 28 ° C. was observed throughout the course of the reaction. Further 2. After stirring for 5 hours, the solution was filtered through celite. From the filtrate, 3.50 g Was obtained as a colorless rubber. Gel filtration chromatography (g (Ruen, 23 ° C, polystyrene standard): W_n= 21,016; M_w = 31,471; M_w/ M_n=  1.50. 4.9[2-Ph) PMI (2,6- (Pr) ₂ Ph] using NiBr ₂ / MAO Hexene polymerization   6 mg of [2-Ph) PMI (2,6- (Pr) in 1 mL of anhydrous degassed toluene_Two Ph)] NiBr_Two(0.01 mmol) of suspension in 3.3 mL (5 mmol) ) Was added, and the resulting green solution was stirred at room temperature for 1 hour. Stirred. Next, 8.4 g (100 mmol) of hexene was added to the solution, and the solution was dissolved. Liquid to N_TwoStirred under for 24 hours. The reaction mixture was added with 4M HCl (50 mL) Et_TwoO (100 mL) was added, the layers were separated and the organic layer was dried over MgSO_FourDried on . Removal of volatile components on a rotary evaporator yielded 3.9 g (46%) of polymer material. Was.                                 Example 5   Example 5 details the preparation of the pyridylimine ligand and its nickel complex. This Was used for the polymerization of both hexene and ethylene. Pyridylimine nickel The synthesis route of the complex is shown in Scheme 27.                               Scheme 27 5.1Preparation of 2-acetyl-6-bromopyridine   20 mL anhydrous Et_Two3.00 g (12.7) of 2,6-dibromopyridine in O Mmol) in 1.6 M n-BuL in cyclohexane. 8.0 mL (12.8 mmol) of i was added dropwise over 30 minutes. − After stirring at 78 ° C. for 3 hours, 8.2 mL (88 mmol) of N, N-dimethyl Ruacetamide was added dropwise and the solution was stirred at -78 ° C for 1 hour. Add to room temperature Heat up, Et_TwoO (100 mL) and saturated NH_FourAdd an aqueous solution of Cl (50 mL) Was isolated. Organic layer_TwoSO_FourDried on a rotary evaporator to remove volatile components Was. The yellow solid obtained was recrystallized from hexane and 1.8 g (71%) of 2 -Acetyl-6-bromopyridine was obtained as colorless crystals.¹ H NMR (CDCl_Three): Δ 2.81 (s, 3H); 7.67-7.77 (m, 2 H); 8.22 (dd, J = 6. 8, 1.6 Hz, 1H). Mass spec: m / e 200. 5.2Preparation of 2-acetyl-6-phenylpyridine   200 mg (1.0 mmol) of 2-acetyl in 10 mL of degassed toluene -6-bromopyridine and 23 mg (0.02 mmol) of (Ph_ThreeP)_FourWith Pd A Schlenk tube filled with the solution was charged with 8 mL of degassed H 2 O / MeOH (4: 1). 150 mg (1.2 mmol) of phenylboronic acid and 270 mg (2.5 mmol) Na)_TwoCO_ThreeWas added. The two-phase mixture is stirred for 1 Heated to 80 ° C for hours. Cool to room temperature and Et_TwoO (50 mL) Was isolated. Organic layer_TwoSO_FourDried on a rotary evaporator to remove volatile components Was. The oil obtained is 10-50% CH_TwoCl_Two/ Silica on silica with hexane Chromatographically treated, 176 mg (89%) of 2-acetyl-6-phenyl Pyridine was obtained as a white powder.¹H NMR (CDCl_Three): Δ 2.84 (s, 3H); 7.43 -7.62 (m, 3H); 7.91-8.08 (m, 3H); 8.18 (d, J = 6.6 Hz, 2H). Mass spectrometry Value: m / e 197. 5.32-acetyl-6-phenylpyridine 2,6-di (isopropyl) fe Preparation of Nilimine [(2-Ph) PMI (2,6- (Pr) ₂ Ph]]   197 mg (mmol) of 2-acetyl-6-phenylamine in 5 mL of anhydrous MeOH Phenylpyridine and 266 mg (1.5 mmol) of 2,6-diisopropylani 0.1M H in phosphorus and MeOH_TwoSO_FourWas heated at 50 ° C. for 12 hours . The volatile components were removed on a rotary evaporator and the crude material was removed from 5% EtOAc / hex. Chromatographed on silica together with the eluate, 287 mg (80%) (2-Ph) PMI (2,6- (Pr)_TwoPh) was obtained as a yellow solid .¹H NMR (CDCl_Three): Δ 1.17 (ddd, J = 4.6, 1.7, 0.7 Hz, 12H); 2.23 (d.J = 2.5 Hz, 3H); 2.73 (dq, J = 6.8, 2.5 Hz); 7.10-7.25 (m, 3H); 7.60-7. 75 (m, 2H); 7.90-8.06 (m, 2H); 8.33-8.40 (m, 1H). Mass spec value: m / e 35 6. 5.4Preparation of [(2-Ph) PMI (2,6- (Pr) ₂ Ph)] NiBr ₂   Anhydrous CH_TwoCl_TwoOf 71 mg (0.2 mmol) of (2-Ph) PMI (2 , 6- (Pr)_TwoPh) and 62 mg (0.2 mmol) of (dimethoxyethane) The suspension of nickel (II) bromide is_TwoFor 48 hours at room temperature. Volatilization The volatile components were removed on a rotary evaporator, and the solid content was washed several times with hexane to give 101 mg ( 88%) of 1 [(2-Ph) PMI (2,6- (Pr)_TwoPh)] NiBr_TwoBut, Obtained as an orange powder.   In the above examples, pyridyl imine can be prepared by the method of the present invention. Shows that these imines can be used in the polymerization of olefins. did. An analog of the solid phase of the above catalyst is shown in Scheme 13 (insert) above. Prepared using the starting materials used.                                 Example 6   This example describes various [2,0], [2,1], [2,2] ligand libraries. 2 shows a reaction scheme that can be used to adjust the pH. Such [2,0], [ [2,1] and [2,2] ligand libraries¹And R^TwoIs the above-mentioned Jimin Libra Solution using the synthetic methods outlined in Scheme 14 defined in the Lee chapter. It can be adjusted from the basic salen system using a liquid or solid phase method.                               Scheme 28   Scheme 28 describes the chemistry involved in both the solution and solid phase methods. You. When this chemistry is performed via solid-phase chemistry, the skeleton becomes Combined with child.   The [2,0] ligand library is substituted or oxidative as described above for the diimine system. Can be converted to an organometallic library by using the addition method . [2,1] Ligand libraries can be prepared using oxidative addition or metathesis reactions. It can be converted to an organometallic library. Hetero to low valence metal precursors Oxidative addition of atom-proton to form hydride or hydrocarbyl ligand-metal compound Forming a product is an effective way to generate a reactive organometallic library. You. Metathesis reaction is also performed from [2,1] ligand library to organometallic library. It is useful for making Bronsted acid library described above Is This library can extract acidic protons on the [2,1] ligand Metal reactants containing leaving group ligands (such as main group alkyls such as trimethylaluminum) To be used directly for metathesis reactions. Wear. Separately, the [2,1] ligand library is deprotonated and updated. Metal salt library capable of performing a metathesis reaction by being reacted with a metal compound Can also be formed. Other mechanisms that cause loss of tin or silyl by-products A thethesis reaction is also conceivable.   Diamide-based organometallic libraries are oxidative additions or membranes similar to those described above. It can be prepared from a diamino ligand library using a thesis reaction. Diamino The ligand library was prepared using the synthesis described in FIGS. 2B, 7 and 11. Can be adjusted.   The tetradentate [4,0] ligand is a [2,0] ligand, as described in Scheme 15. It can be manufactured by combining two ligands. Such union An example of such an arrangement is shown in the figure below. The [4,0] ligand-metal library is [4,0] Ligand similar to that described for construction of [2,0] bis-imine libraries It can be made by contacting a suitable transition metal precursor in a similar manner. it can.                               Scheme 29   It should be understood that the above description is illustrative and not restrictive. It is. Many embodiments will be apparent to those of skill in the art upon reading the above description. Therefore The scope of the invention is not defined by reference to the above description, but instead , Refer to the appended claims for their full scope of equivalents Should be determined. Disclosure of articles and literature in all, including patent applications and publications Is hereby incorporated by reference for all purposes.

────────────────────────────────────────────────── ─── Continuation of front page    (31) Priority claim number 60 / 029,255 (32) Priority Date October 25, 1996 (33) Priority country United States (US) (31) Priority claim number 60 / 035,366 (32) Priority date January 10, 1997 (33) Priority country United States (US) (81) Designated countries EP (AT, BE, CH, DE, DK, ES, FI, FR, GB, GR, IE, IT, L U, MC, NL, PT, SE), OA (BF, BJ, CF) , CG, CI, CM, GA, GN, ML, MR, NE, SN, TD, TG), AP (GH, KE, LS, MW, S D, SZ, UG, ZW), UA (AM, AZ, BY, KG) , KZ, MD, RU, TJ, TM), AL, AM, AT , AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CU, CZ, DE, DK, EE, ES, F I, GB, GE, GH, HU, IL, IS, JP, KE , KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MD, MG, MK, MN, MW, M X, NO, NZ, PL, PT, RO, RU, SD, SE , SG, SI, SK, SL, TJ, TM, TR, TT, UA, UG, US, UZ, VN, YU, ZW (72) Inventor Goldwasser, Icy             United States, California             94025, Menlo Park, 435 Encina             Le Avenue, Apartment Sea (72) Inventors Bussy, Thomas             United States, California             94025, Menlo Park, 462 Raven             Zwood (72) Inventor Turner, Howard             United States, California             95008, Campbell, 2948 Massy             coat (72) Inventors Ban Beek, Johannes A. M.             United States, California             94043, Mountain View, 75 tee             Rera Court (72) Inventor Murphy, Vince             United States, California             95014, Cupertino, 20800 Homes             Ted Road # 11 F (72) Inventors Powers, Timothy             United States, California             94595, Walnut Creek, 111 A             Dams Ranch Road

Claims (1)

[Claims] 1. (A) synthesizing a first metal-binding ligand and a second metal-binding ligand in a first region and a second region on a substrate; and (b) synthesizing a first metal ion with the first metal-binding ligand. Supplying a second metal ion to the second metal binding ligand to form a first metal-ligand compound and a second metal-ligand compound. A method for producing an array of ligand compounds. 2. And (c) activating the first metal-ligand compound using a first activating substance and activating the second metal-ligand compound using a second activating substance. The method according to claim 1. 3. The step (a) includes: (i) combining a first component of the first metal binding ligand and a first component of the second metal binding ligand in a first region and a second region on the base; (Ii) synthesizing a second component of the first metal binding ligand and a second component of the second metal binding ligand in the first region and the second region on the substrate. The method of claim 1 comprising: 4. 3. The method according to claim 2, wherein said first activating metal-ligand compound and said second activating metal-ligand compound are organometallic compounds. 5. 3. The method according to claim 2, wherein said first activating metal-ligand compound and said second activating metal-ligand compound are homogeneous catalysts. 6. The method according to claim 5, wherein the homogeneous catalyst is a polymerization catalyst. 7. 3. The method according to claim 2, wherein said first activating metal-ligand compound and said second activating metal-ligand compound are heterogeneous catalysts. 8. The method of claim 1, wherein said first metal-ligand compound and said second metal-ligand compound are metallocene compounds. 9. The method of claim 1, wherein said first metal-ligand compound and said second metal-ligand compound are catalysts without an activator. 10. 10. The method according to claim 9, wherein the catalyst without the activating substance is a homogeneous catalyst. 11. 10. The method according to claim 9, wherein the catalyst without activator is a heterogeneous catalyst. 12. The method according to claim 1, wherein the first metal binding ligand and the second metal binding ligand are neutral bidentate ligands. 13. 2. The method according to claim 1, wherein the first metal binding ligand and the second metal binding ligand are monoanionic bidentate ligands. 14． The method according to claim 1, wherein the first metal binding ligand and the second metal binding ligand are chelating diamine ligands. 15. 15. The method according to claim 14, wherein the chelating diamine ligand is a 1,2-diamine ligand. 16. The method according to claim 1, wherein the first metal binding ligand and the second metal binding ligand are salen ligands. 17． The method according to claim 1, wherein the first metal binding ligand and the second metal binding ligand are auxiliary ligands. 18. 2. The method of claim 1, wherein the first metal binding ligand and the second metal binding ligand have a coordination number (CN) independently selected from the group consisting of 1, 2, and 3. Method. 19. The first metal-binding ligand and the second metal-binding ligand have a charge independently selected from the group consisting of 0, -1, -2, -3 and -4. The method described in the section. 20. The first metal binding ligand and the second metal binding ligand are (i) CN = 2, charge = −2, (ii) CN = 2, charge = −1, and (iii) CN = 1. , Charge = -1, (iv) CN = 2, charge = neutral, (v) CN = 3, charge = -1, (vi) CN = 1, charge = -2, (Vii) CN = 3, charge And (viii) CN = 2, charge = −3, (ix) CN = 3, charge = −3, each having a coordination number (CN) and a charge independently selected from the group consisting of: 2. The method according to claim 1. 21. The method of claim 1, wherein the first metal binding ligand and the second metal binding ligand are auxiliary ligands each having a charge greater than the coordination number. 22. The method according to claim 1, wherein the first metal ion and the second metal ion are each a transition metal ion. 23. The first metal binding ligand and the second metal binding ligand are neutral bidentate ligands, and each of the transition metal ions is stabilized by a neutral Lewis acid having substitution activity. 23. The method of claim 22, wherein 24. 23. The first metal-binding ligand and the second metal-binding ligand are chelating diamine ligands, and each of the transition metal ions is a Group 10 transition metal. The method described in. 25. The first metal-binding ligand and the second metal-binding ligand are monoanionic bidentate ligands, and each of the transition metal ions is a substituted anionic leaving group ligand having a substitution activity. 23. The method of claim 22, wherein the method is stabilized by: 26. The first activator and the second activator are MAO, [Q] ⁺ [NCA] ⁻ , [H (OEt ₂ )] ⁺ [BAr ₄ ] ⁻ and [H (OEt ₂ )] ⁺ [B ( C ₆ F _{5) 4]} ^- the method according to claim 2 which is selected independently from the group consisting of. 27. 3. The method of claim 2, wherein said first and second activators are each independently selected and become a counterion after activation. 28. The method of claim 1, wherein the first and second metal ions are independently selected from the group consisting of Pd, Ni, Pt, Ir, Rh, Cr, Mo, W, and Co. 29. The method according to claim 1, wherein the first metal-binding ligand and the second metal-binding ligand are supported. 30. 30. The method of claim 29, wherein said first and second metal binding ligands are directly bonded to said substrate. 31. 30. The method according to claim 29, wherein the first metal binding ligand and the second metal binding ligand are bound to the substrate via a first linker group and a second linker group. 32. 30. The method according to claim 29, wherein the first and second metal binding ligands are bound to a first and second synthesis support on the substrate. 33. 33. The method according to claim 32, wherein the first metal binding ligand and the second metal binding ligand are directly bonded to the first synthesis support and the second synthesis support. 34. The first metal-binding ligand and the second metal-binding ligand are bonded to the first and second synthesis carriers via a first linker group and a second linker group, respectively. 33. The method of claim 32. 35. The method of claim 1, wherein the first metal binding ligand and the second metal binding ligand are unsupported. 36. The method of claim 1, further comprising the step of screening said array of metal-ligand compounds for useful properties. 37. 37. The method of claim 36, wherein said useful property is a polymerization property. 38. 37. The method of claim 36, wherein said useful property is a mechanical property. 39. 37. The method according to claim 36, wherein said useful property is an optical property. 40. 37. The method of claim 36, wherein said useful property is a physical property. 41. 37. The method of claim 36, wherein said useful property is a morphological property. 42. 37. The method of claim 36, wherein said useful property is the lifetime of said metal-ligand compound. 43. 37. The method of claim 36, wherein said useful property is the stability of said metal-ligand compound with respect to particular reaction conditions. 44. 37. The method of claim 36, wherein said useful property is the selectivity of said metal-ligand compound for a particular reaction. 45. 37. The method of claim 36, wherein said useful property is the conversion efficiency of said metal-ligand compound for a particular reaction. 46. 37. The method of claim 36, wherein the useful property is the activity of the metal-ligand compound on a particular reaction. 47. Said substrate comprising: (i) a porous or non-porous substrate wherein said sample chamber is filled with a reactant gas at a pressure P and wherein each of said catalysts is selectively activated; and (ii) a reactant at a pressure P. 2. The method of claim 1, wherein the gas is introduced into the lower pressure region through the supported catalyst and the substrate, and wherein each of the catalysts has a shape selected from the group consisting of a selectively activated porous substrate. The described method. 48. Supplying the components of the homogeneous catalyst to the synthesis support material contained in the substrate, wherein the synthesis support material and the substrate are contained in (i) a well, the components being passed through a hole in the bottom of the well; A porous or non-porous synthetic carrier material flowing to the top or from the top of the well; (ii) a porous material contained within the well, with components flowing into the top of the well or exiting from the top of the well. Or a non-porous synthetic carrier material and (iii) a porous or non-porous carrier which acts as both said synthetic carrier material and said substrate and whose components are deposited directly on the surface of said substrate. The method of claim 1 having a selected shape. 49. (I) screening the arrays simultaneously, (ii) screening the arrays sequentially, (iii) positioning a detector away from the arrays, screening the arrays, and then screening a portion of the arrays. 37. The method of claim 36, wherein said array is screened in a manner selected from the group consisting of screening the array in an intervalwise manner in which the detection device is repositioned to perform. 50. Uses a technique selected from the group consisting of scanning mass spectrometry, chromatography, ultraviolet imaging, visible imaging, infrared imaging, electromagnetic imaging, ultraviolet spectroscopy, visible spectroscopy, infrared spectroscopy, electromagnetic spectroscopy, and acoustic analysis 37. The method of claim 36 wherein said utility is screened for. 51. The metal - each ligand compounds, the method according to claim 1, wherein synthesized in an area of less than 25 cm ^2. 52. The metal - each ligand compounds, the method according to claim 1, wherein synthesized in an area of less than 10 cm ^2. 53. The metal - each ligand compounds, the method according to claim 1, wherein synthesized in an area of less than 1 cm ^2. 54. The metal - each ligand compounds, the method according to claim 1, wherein synthesized in an area of less than 1 mm ^2. 55. The method of claim 1, wherein each of said metal-ligand compounds is synthesized to an area of less than 10,000 μm ² . 56. The method of claim 1 wherein each of said metal-ligand compounds is synthesized to an area of less than 1,000 μm ² . 57. ^2. The method of claim 1, wherein each of said metal-ligand compounds is performed on an area of less than 100 [mu] m < ² >. 58. The method of claim 1, wherein each of said metal-ligand compounds is performed on an area of less than 1 μm ² . 59. The method of claim 1, wherein at least ten different metal-ligand compounds are synthesized on the substrate. 60. The method of claim 1, wherein at least 20 different metal-ligand compounds are synthesized on the substrate. 61. The method of claim 1, wherein at least 50 different metal-ligand compounds are synthesized on said substrate. 62. The method of claim 1, wherein at least 100 different metal-ligand compounds are synthesized on said substrate. 63. The method of claim 1, wherein at least 200 different metal-ligand compounds are synthesized on the substrate. 64. The method of claim 1 wherein at least 500 different metal-ligand compounds are synthesized on said substrate. 65. The method of claim 1 wherein at least 1,000 different metal-ligand compounds are synthesized on said substrate. 66. The method of claim 1 wherein at least 10,000 different metal-ligand compounds are synthesized on said substrate. 67. The method of claim 1 wherein at least 10 ⁶ different metal-ligand compounds are synthesized on said substrate. 68. The first metal-binding ligand and the second metal-binding ligand are [2,2] or [2,1] ligands, and each of the metal-binding ligands is the first metal-binding ligand. The metal-ligand compound and the second metal-ligand compound are each contacted with a main metal alkyl complex in a monoprotonic or diprotonic form, according to claim 1. Method. 69. 69. The method according to claim 68, wherein said main group metal alkyl complex is a trialkylaluminum complex. 70. 69. The method of claim 68, wherein said metal-ligand compound is useful for organic transformation reactions requiring a Lewis acid moiety. 71. 71. The method of claim 70, wherein said organic transformation reaction is selected from the group consisting of a stereoselective coupling reaction, an olefin oligomer formation reaction, and an olefin polymerization reaction. 72. 69. The array of claim 68, wherein the array of metal-ligand compounds is further modified by reaction with an ion exchange activator to produce an array of ligand-stabilized cationic aluminum reactants. the method of. 73. The method according to claim 72, wherein the ion exchange activating substance is [PhNMe ₂ H] [B (C ₆ F ₅ ) ₄ ]. 74. 73. The method of claim 72, wherein the ligand-stabilized cationic aluminum reactant can be used as a catalyst for a reaction selected from the group consisting of an organic coupling reaction, an olefin oligomer formation reaction, and an olefin polymerization reaction. Method. 75. The method of claim 1, wherein the first metal-ligand compound and the second metal-ligand compound are provided to the substrate by using a liquid dispensing method in combination with a masking method. 76. A process for producing a polymer blend comprising the step of contacting at least two metal-ligand compounds prepared according to the process of claim 1 with a cocatalyst and a monomer. 77. A process for polymerizing olefins, diolefins and acetylenically unsaturated monomers, comprising contacting at least one metal-ligand compound prepared according to the process of claim 1 with a cocatalyst and a support. 78. (A) supplying a first metal binding ligand and a second metal binding ligand to a first region and a second region on a substrate; and (b) supplying a first metal ion to the first metal binding ligand. Supplying a second metal ion to the second metal binding ligand to form a first metal-ligand compound and a second metal-ligand compound. A method for producing an array of ligand compounds. 79. (A) synthesizing an array of spatially separated ligands; and (b) providing an appropriate metal precursor to each element of the ligand array to produce an array of metal-ligand compounds. (C) if necessary, activating the metal-ligand compound array with a suitable cocatalyst; and (d) optionally, converting the metal-ligand compound array to a third component. (E) a parallel or rapid serial screening method selected from the group consisting of optical imaging, optical spectroscopy, mass spectrometry, chromatography, acoustic imaging, acoustic spectroscopy, infrared imaging and infrared spectroscopy. A method of making and screening an array of metal-ligand compounds comprising using said array of metal-ligand compounds for useful properties. 80. An array of at least 10 different metal-ligand compounds provided at known locations on a substrate. 81. 81. The array of claim 80, wherein the array comprises more than 20 different metal-ligand compounds at known locations on the substrate. 82. 81. The array of claim 80, wherein the array comprises more than 50 different metal-ligand compounds at known locations on the substrate. 83. 81. The array of claim 80, wherein the array comprises more than 100 different metal-ligand compounds at known locations on the substrate. 84. 81. The array of claim 80, wherein the array comprises more than 200 different metal-ligand compounds at known locations on the substrate. 85. 81. The array of claim 80, wherein the array comprises more than 500 different metal-ligand compounds at known locations on the substrate. 86. 81. The array of claim 80, wherein the array comprises more than 1,000 different metal-ligand compounds at known locations on the substrate. 87. 81. The array of claim 80, wherein the array comprises more than 10,000 different metal-ligand compounds at known locations on the substrate. 88. Said array, said at known locations on the substrate, different metals above ¹⁰⁶ - array according to the 80th paragraph claims containing a ligand compound. 89. 80. The method of claim 80, wherein each of the metal-ligand compounds of the array has similar functionality, thereby allowing the metal-ligand compounds of the array to be compared for selected properties. An array according to clause.