CN1267238A - Homogeneous oxidation catalyst using metal complexes - Google Patents

Abstract

The present method provides a method of transferring oxygen to at least one oxidizable site on a target compound. The method includes the steps of selectively oxidizing an oxidizable site on a target compound by reacting in solution: the target compound, a source of oxygen atoms, a source of a Lewis acid, such as a proton, alkali, alkaline earth, rare earth, transition metal or main group metal ion, and a catalyst. The catalyst has general structure (I) wherein Z is preferably N, but may include O and MO is a transition metal-oxo species. The Lewis acid binds to a bidentate secondary site on the Ch1 substituent to form a Lewis acid-catalyst complex.

Description

Use the homogeneous oxidation catalyst of metal complex

The cross reference of related application

Inapplicable

Subsidize the explanation of research about federal government

This work obtains the subsidy (5RO1GM55836) of National Institutes of Health fund.U.S. government enjoys rights and interests more of the present invention.

Background of invention

The present invention relates to the field of oxidation catalyst and catalytic action.More particularly, the present invention relates to be used for olefin oxidation, especially the catalyst field of the enantiomerism selective oxidation of alkene.

Reaction selectivity comprises chemo-selective, regioselectivity and stereoselectivity, all has first-class importance in chemistry and biology.Different functional groups, such as among alcohol, ketone, aldehyde, carboxylic acid and other compound or between the reaction selectivity be referred to as chemo-selective.Regioselectivity refer to a kind of orientation or regional isomer to any other because of the orientation that may produce or disappear in the reformed substrate of reaction or the preferential selectivity of isomers.Stereoselective notion comprises diastereo-isomerism selectivity (have identical connection but selectivity among the diastereoisomer of two kinds of compounds of the non-mirror image that can not overlap is arranged) and enantiomerism selectivity (have identical connection and two kinds of two kinds of compounds of the mirror image that can the overlap selectivity between may enantiomters are arranged).For example, in various medicine production, it has been recognized that catastrophic consequence, promptly a kind of enantiomer has useful character and another kind of enantiomer is harmful to.In order to reach required selectivity degree and type, chemists have adopted a series of chemical reagent of almost containing whole periodic table, collect various chemical elements from all places that can reach.The Several Methods that adopts chiral transition metal to make prochiral olefin produce the enantiomerism selective epoxidation and make the oxidation of prochirality sulfide generation enantiomerism is disclosed in people's such as Jacobsen United States Patent (USP) 5,637,739.

By contrast, nature but utilized in each local environment getable quite a spot of element and under the limited solvent source and the temperature conditions that may reach, utilize these elements to remove to put into practice its exquisite life chemistry.As if design and the interconnecting of unlimited exquisite system of nature by finishing reagent successfully reach its optionally purpose; And by the complexity in this design, nature can utilize the chemical element of minority bringing into play the 26S Proteasome Structure and Function effect in the scope widely, and this is much more extensive for the sphere of action that same purpose is reached than chemists.In this critical difference, the underlying cause is the heavy damage to environment, and this will be attributed to chemistry, and yes is attributed to and lacks suitably thinking or appropriately be concerned about and the industrial chemistry put into practice.By adopting various chemical element to reach aspect the selectivity purpose, chemists can accomplish something in quite simple scope of design.In this process, various biologies can run into unfamiliar thereby usually be poisonous chemical elements.Those preferred reagent of the reactivity interval expansion of hypotoxicity transition elements such as manganese and iron then can be guided produce the whole bag of tricks more even more ideal than existing method environmental protection.

Be devoted to design of the work of sludge proof cheland with the catalyst of the manganese of supporting peroxide activator and iron, " chemical research report " 27 at T.J.Collins, people's such as 279～285 pages (1994) and F.C.Anson " American Chemical Society's meeting will " all has report in 106,4460～4472 pages (1984).A kind of durable especially tetradentate ligands has been done open in " long-lived homogenous oxidation catalyst " literary composition in being entitled as of No. 08/681,237, people's such as T.Collins common unsettled U.S. Patent application series, the disclosure content is now incorporated this paper into as a reference.First stable manganese base is Mn ^VThe exploitation of one oxygenate complex, " American Chemical Society's meeting will " 111 at T.J.Collins, S.W.Gordon-Wylie, 4511～13 pages (1989) and T.J.Collins, R.D.Powell, C.Slebodnick, in " the American Chemical Society's meeting will " 112,899～901 (1990) of E.S.Uffelman report is arranged all; At the complex described in back one piece of article also is stable in water environment.Though above-mentioned 1989 and described big ring four amide ligands of article that are published in " American Chemical Society can will " of people such as nineteen ninety Collins when with the metallic ion coordination of oxidation, be stable, these part-metal complexs and homologue thereof are not highly active oxygen atom transfering reagent.This forms contrast, latter Mn with the system of using dianion porphyrin and two schiff bases (Salen) quadridentate ligands ^VAnd Mn ^IV-oxygenate complex plays a part so-called reactive intermediate in various oxygen atom transfer processes.See also: E.Srinivasan, P.Michaud, J.K.Kochi, " American Chemical Society's meeting will " 108,2309-2320 (1986); J.T.Groves, M.K.Stern, " American Chemical Society's meeting will " 110,8628-8638 (1988); W.Zhang, J.L.Loebach, S.R.Wilson, E.N.Jacobsen, " American Chemical Society's meeting will " 112,2801-2803 (1990).

Summary of the invention

Have reason to believe four previous acid amides Mn ^VThe low activity of-oxygenate complex has higher negative electrical charge and σ-electron donation owing to four amide ligands than porphyrin or double schiff base ligand.The present invention uses a kind of new resistance to oxidation and the transient metal complex of hydrolysis, wherein contains the metal just like iron or manganese one class, and when activated state, it is active that these oxygenate part species shift in the reaction that becomes organic nucleophile at oxygen atom.Importantly, system of the present invention has also used second kind of reaction to strengthen the electrophilicity of oxygenate part.The connection of lewis acid species usually is that the close vicinity in the metal of the tetradentate ligands of modifying-oxygenate part has the increase O-electrophilicity of target and produces effective Metal Substrate O-atom transfer reagent thus with the transmission of positive charge ion form, and is indicated with graphic mode as Fig. 1 of an embodiment that is used for representing catalyst of the present invention.

The invention provides the method that at least one the oxidable active site in a kind of target compound that oxygen atom is transferred to contain a plurality of oxidable active sites gets on, in other words, the method that provides a kind of oxidable active site that makes oxygen atom transfer to prochirality compound species to get on.Term used herein " oxidable " refers to any active site that will accept oxygen atom, for example alkene or alkynyl active site, and the active site that is subjected to the another kind of oxidised form domination that produced by oxidation catalysis system provided by the invention.The relevant situation that contains the compound of a plurality of oxidable active sites will be carried out detailed explanation.The process that the oxidation of prochirality compound species generates chipal compounds is similarly, and different is only to need to exist an oxidable active site and catalyst system must have chirality.Said method comprises the catalyst that adds oxygen atom source, lewis acid species source (the most frequently used is cationic species) and have following structure in the solution that contains the target compound that wherein has a plurality of oxidable active sites: In the formula:

Z is N or O, and at least one and preferably four Z all be the N species;

MO is transition metal-oxygenate species:

Ch ₁Be to be selected from pyridine, pyrimidine, pyrazine, the dicyano pyrazine, single-, two, three or four substituted benzenes, benzimidazole, benzoquinones, bis-imino substituted benzene, indoles, the hat derivative that replaces, cryptand, EDTA derivative, five-membered ring and five-membered ring derivative, derivatives of porphyrin, the phthalocyanine matrix system that metal replaces, two pyridine radicals systems, phenanthroline matrix system and two schiff bases (salen) matrix are;

Ch ₂And Ch ₃Expression links the following unit of structure of adjacent Z atom separately: R in the following formula ₁, R ₂, R ₃And R ₄Be identical or different group paired and accumulation, and each group all is selected from hydrogen, alkyl, aryl, alkenyl, alkynyl, alkaryl, cycloalkyl, cycloalkenyl group, alkoxyl, phenoxy group, halogen, fluoro-alkyl, perfluoroalkyl, fluoroolefins base, perfluoro alkenyl, CH ₂CF ₃, and CF ₃, perhaps R ₁, R ₂, R ₃And R ₄That constitute to replace together or unsubstituted phenyl ring, perhaps R ₁, R ₂Or R ₃, R ₄This two couple's paired R substituting group constitutes cycloalkyl or these groups of cycloalkenyl group together; And

Ch ₄For connecting the unit that is selected from one of following group of adjacent Z atom: R in the formula ₅And R ₆Be identical or different; Cheng Huan's or non-Cheng Huan's, and respectively do for oneself hydrogen, ketone, aldehyde, carboxylic acid, ester, ether, amine, imines, acid amides, nitro, sulfonyl, sulfate radical, phosphoryl, phosphate radical, silicyl, siloxanes, alkyl, aryl, alkenyl, alkynyl, alkaryl, cycloalkyl, cycloalkenyl group, alkoxyl, phenoxy group, halogen, CH ₂CF ₃Or CF ₃, perhaps R ₅, R ₆Right paired R substituting group constitutes cycloalkyl or these groups of cyclenes basic ring together;

And needed oxidable active site produces oxidation in the target compound so that make will to make oxidation time carry out the time of long enough.

It will be understood to those of skill in the art that lewis acid comprises cationic, neutral and anionic chemical species.Why adopt " cationic catalyst complex " this term herein, be intended to contain and adopt all these class chemical species as being bonded on the catalyst and changing its active entity, and be not limited only to cationic.

The metal species ion means any lewis acid species, for example ion of proton, alkali metal, alkaline-earth metal, rare earth metal, transition metal or main group metal.

State in the use in the method for optimizing of catalyst, the relative activity of a plurality of oxidable active sites in target compound differs from one another, and the selected cation that joins in the solution wants optionally activated catalyst so that an oxidable active site on the oxidation target compound.Therefore, method of the present invention comprises following some steps: a series of oxidable active site on the identification target compound; Identification has each the oxidable active site in this series active site of different activities successively, and it puts in order is to have the final oxidable active site of that batch that the initial oxidable active site of that batch of the highest relative activity has minimum relative activity to this series active site from the oxidable active site of this series; In this solution, add first kind of cation with activated catalyst, be enough to make first required oxidable active site to produce first kind of cation-catalyst complexes of first activity degree of oxidation thereby generate to have, so just make that second batch of oxidable active site in the oxidable active site of this series has the highest relative activity then in the oxidable active site of the remainder of a series of active sites of target compound.After each available initial oxidable active site is oxidized, just from this solution, chooses wantonly first kind of cation removed.After this, thereby in this solution, add second kind of cation again and generate second kind of cation-catalyst complexes with activated catalyst, the activity degree that this second kind of cation-catalyst complexes has is enough to make the oxidable active site of second batch on the target compound to produce oxidation, and make this oxidation reaction carry out the sufficient time so that make each the second batch of oxidable active site on this target compound all oxidized, so just make that the oxidable active site of next group in a series of oxidable active site on this target compound has the highest relative activity in the oxidable active site of the remainder of this series active site.After oxidation is finished, optional this second kind of cation of removing from this solution.Repeat above-mentioned steps and in this solution, add cation, oxidation reaction is proceeded, the optional then decationizing that from solution, removes, each in succession activity that adds cation-catalyst complex that cation generated in this solution all increases gradually so that make that each the oxidable active site in the oxidable active site of this series is all oxidized successively, be performed until like this each last oxidable active site oxidized till.Inferior active site or a plurality of active site at cation and catalyst generate under the situation of strong chemical bond, just do not require and remove decationizing and cation-catalyst complexes.In addition, also can not make the cation of follow-up adding that catalyst is produced activation if do not need to remove decationizing, it is also just unnecessary to remove decationizing so.

Said method can comprise that also at least one the prochiral oxidable active site that makes on the target compound produces the enantiomerism selective oxidation, and this class target compound may have only an oxidable active site.Catalyst or cation-catalyst complexes used in the enantiomerism selective oxidation comprise the substituting group that makes complex produce asymmetry, like this, when with target compound on the reaction of the oxidable active site of prochirality the time, the generation of the wherein a kind of isomers of cation-catalyst complexes with regard to helping relative other enantiomter, perhaps, had at substrate under the situation of chirality, this complex helps the selection effect in the various diastereo-isomerism variants.Said method is differentiated in the application and can also be worked in dynamics, and in this application, an isomery physical efficiency in the paired enantiomter in the mixture is optionally identified from mixture.

The accompanying drawing summary

The present invention may be better understood with reference to accompanying drawing, comprises title " compound 1 " and [LMn in the accompanying drawing ^V≡ O] ^-, both are as interoperable " term " of Fig. 1 preferred embodiment.

Fig. 1 is that the diagram of catalytic reaction circulation is expressed, and has reason to believe that switching regulator oxidation reaction of the present invention carries out in this manner.

Fig. 2 is the molecular structure of compound 1: the stereo crystal of being drawn that contains non-hydrogen atom is learned structure (ORTEP) figure and is comprised 50% electron density, wherein the Mn atom is positioned at plane top 0.579 and towards the oxygenate atom, the coordination oxygen atom is in the top of manganese symmetrically.Selected part bond distance (): Mn-O (1), 1.549 (3); Mn-N (1), 1.884 (4); Mn-N (2), 1.873 (3); Mn-N (3), 1.881 (3); Mn-N (4), 1.885 (3).

Fig. 3 A and 3B explanation: at A) in, show that the ultraviolet of compound 1 composes (9.71 * 10 ^-5M, the 3m1 sample size), wherein add Li (OSO ₂CF ₃) be dissolved in the five equilibrium liquor sample (beginning addition in 2 μ l, contain 0.06 micromole) of acetonitrile; At B) in, the mol ratio curve after dilution is proofreaied and correct shown.

Fig. 4 represents the infrared spectrogram (thick line) of the compound 1 of infrared spectrum (polyethylene film) figure (fine rule) of compound 1 and lithiumation, and the latter shows at ν (the Mn ≡ relevant with the lithiumation of switch active site ¹⁸O) bands of a spectrum have increased 15cm ^-1Li ⁺Bonding cause the remarkable decline of big ring tetramido-N part electron donation, this decline is compensated by increasing of oxygenate part binding energy again.

Fig. 5 A and 5B represent, at A) in be presented at the rate of change that compound 1 absorbs in 396nm place ultraviolet in the presence of triphenylphosphine and the different switch ions.Normalized observation speed constant: experiment sequence number, cation equivalent number, cation, relative speed ± three time experiment lowest standard deviation: 1. do not have cation, 0,1; 2a, 5, Na ⁺, 2.7 ± 0.1; 3a, 5, Ba ²⁺, 4.8 ± 0.5; 3b, 60, Ba ²⁺, 5.7 ± 0.1; 4a, 5, Mg ²⁺, 7.0 ± 0.4; 4b, 60, Mg ²⁺, 7.2 ± 0.8; 5a, 5, Li ⁺, 13.5 ± 2.0; 6a, 5, Zn ²⁺, 24.5 ± 1; 6b, 60, Zn ²⁺, 24.1 ± 0.8; 5b, 60Li ⁺, 25.0 ± 0.5; 2b, 60, Na ⁺, 506.4 ± 7.0; 7a, 5, Sc ³⁺, 1246.0 ± 206.1; 7b, 60, Sc ³⁺, 1577.6 ± 290.0; At B) in show the amplification of time scale, in order to the fastest oxidation rate of explanation.

Fig. 6 illustrates the synthetic method of part with diagram method.

Fig. 7 reacts with the insertion of diagram method explanation metal such as manganese.

Fig. 8 is chemical species [LMn ^V≡ O] ^{- 1}The wave spectrogram of H NMR.Owing to the low-symmetry that exists pyridine-N and Mn (O) to produce reflects in the RESONANCE ABSORPTION of four methyl resonance cc ' dd ' is observed.

Fig. 9 A and B explanation is at different molar equivalent Na ⁺Condition under be bonded to [LMn ^V≡ O] ^-On Na ⁺The research of ultraviolet spectrum, 0.0 (with long dotted line---expression), 25 (with short dotted line----expression) and 60 (using the most black solid line to represent).The mol ratio curve has indicated two kinds of bonding process and has existed.Wherein a kind of process is Na ⁺Bonding advances switching point and another bonding process is believed and occurred on one of amide oxygen atom.

Figure 10 A, B, C and D explanation is at different molar equivalent Zn ²⁺Condition under be bonded to [LMn ^V≡ O] ^-On Zn ²⁺The research of ultraviolet spectrum, 0.0 (with longer dotted line---expression), 0.23 (with short dotted line----expression) and 0.69 (using the most black solid line to represent).

Figure 11 A, B, C and D explanation is at different molar equivalent Mg ²⁺Condition under be bonded to [LMn ^V≡ O] ^-On Mg ²⁺The research of ultraviolet spectrum, the longer dotted line of 0.0 usefulness represents that 0.30 usefulness is represented to represent with the most black solid line of 1.06 usefulness than short dash line.

Figure 12 A and B explanation is at different molar equivalent Ca ²⁺Condition under be bonded to [LMn ^V≡ O] ^-On Ca ²⁺The research of ultraviolet spectrum.

Figure 13 A and B explanation is at different molar equivalent Ba ²⁺Condition under be bonded to [LMn ^V≡ O] ^-On Ba ²⁺The research of ultraviolet spectrum.

Figure 14 A and B explanation is at different molar equivalent Sc ³⁺Condition under be bonded to [LMn ^V≡ O] ^-On Sc ³⁺The research of ultraviolet spectrum.But, Sc ³⁺The behavior of complex bonding show that only equivalent of needs just arrives terminal point.

Figure 15 A～F illustrates usefulness ¹³C-NMR monitors [LMn ^V≡ O] ^-Research with the O atomic reaction activity of tetramethyl-ethylene; Represent the growth in time of carbon product RESONANCE ABSORPTION with from light to dark trajectory gradually.

DESCRIPTION OF THE PREFERRED

The preferred embodiment of used catalyst is to chemistry " greenization " in the inventive method Contribution, the principle of its foundation is that reagent should be made up of the hypotoxicity element. In Green design, Think that those important elements are as described below. Best, said metal is one of hypotoxicity element, Be iron or manganese. The ligand system that supports is preferably biologically normal by carbon, hydrogen, nitrogen, oxygen and other See that element forms. Best, main oxidant is a kind of oxygen that is widespread in nature Change agent, for example one of oxygen or its derivative that is reduced, especially hydrogen peroxide. This inference For advancing ligand design that the case of an important environmental protection, this ligand design purport are provided In avirulence, longevity that peroxide activator and oxygen are provided for the homogeneous oxidizing reaction that haves a wide reach The iron of life and the catalyst of manganese one class.

This class catalyst that can be used for the inventive method of finding has the structure of following general formula:In the formula:

Z is N or O and at least one Z and best four Z are N;

MO is transition metal-oxygenate species;

Ch ₁To be selected from pyridine, pyrimidine, pyrazine, the dicyano pyrazine, single-, two, three or four get For benzene, benzimidazole, benzoquinones, the bis-imino substituted benzene, indoles, the hat derivative of replacement, Cryptand, EDTA derivative, five-membered ring and five-membered ring derivative, derivatives of porphyrin, gold Belong to the phthalocyanine matrix system that replaces, two pyridine radicals systems, phenanthroline matrix system and two schiff bases (salen) Matrix system is according to such as the substituent expression mode of this listed class of this paper Table I;

Ch ₂And Ch₃Expression links the following unit of structure of adjacent Z atom separately:

R in the following formula₁、R ₂、R ₃And R₄Be identical or different group paired and accumulation, and each group is selected from alkyl, aryl, alkenyl, alkynyl, alkaryl, cycloalkyl, cycloalkenyl group, alkoxyl, phenoxy group, halogen, CH₂CF ₃, and CF₃, perhaps R₁、R ₂、R ₃And R₄That consist of to replace together or unsubstituted phenyl ring, perhaps R₁、R ₂Or R₃、R ₄This two couple's paired R Substituting group consists of cycloalkyl or these groups of cycloalkenyl group together; And

Ch ₄For connecting the unit that is selected from one of following group of adjacent Z atom:

R in the formula₅And R₆Identical or different; Cheng Huan's or non-Cheng Huan's, and respectively do for oneself hydrogen, ketone, aldehyde, carboxylic acid, ester, ether, amine, imines, acid amides, nitro, sulfonyl, sulfate radical, phosphoryl, phosphate radical, silicyl, siloxanes, alkyl, aryl, alkenyl, alkynyl, alkaryl, cycloalkyl, cycloalkenyl group, alkoxyl, phenoxy group, halogen, CH₂CF ₃Or CF₃, perhaps R₅、R ₆Right paired R substituting group consists of cycloalkyl or these groups of cyclenes basic ring together.

A preferred embodiment of said catalyst is tetramido part as shown in Figure 1, Be expressed as compound 1 herein. Used catalyst contains the secondary work of bidentate in the methods of the invention The property point, this active site system is made of pyridine nitrogen and adjacent amide oxygen in compound 1. Bonding The electronic action of level ion is to be delivered to Mn (O) part by the perturbation that σ and π combine . This bonding action has strengthened the electron affinity of oxygenate part, has strengthened thus part oxygen The transfer activity of atom. This secondary " switch " effect that is referred to as that is bonded in herein, by This effect arranges secondary reaction with the carrying out of initiation main reaction in time, thereby with acceptable The reactivity that the speed transmission hits and selective.

In the method for the invention, switching process is used to activated compounds 1, so just can Finish easily useful oxidation reaction in the time range. Be bonded to the secondary activity point by control Lewis acid or cation, just can control the relative activity of catalyst. Adopt this technology, As following will carefullyyer state, just can to have a plurality of may oxidation activity points The chemo-selective of the oxidation reaction of required active site and regioselectivity and anti-in the large compound Should order be controlled. In addition, import chirality to required prochirality active site and also can be controlled, By the environment around the synthetic method modified catalyst active site to import asymmetry or to pass through Being coupled to the cationic group of switch brings asymmetry in the cationic catalyst complex into and goes. Can Make it to be conducive to and one of required oxidation active site such as alkene with the size and shape that changes complex Side is than the more preferential contact of opposite side.

Cation part (L)-metal (M)-oxygenate (O)-chemical species { [LM=O]⁺Be used as being similar to the active oxidant in those metal catalytic olefin hydrocarbon oxidation reactions of the present invention, usually carry out in the following manner:

[LM] ⁺+[O]→{[LM＝O] ⁺}+alkene → [LM]⁺+ epoxide (or other oxidation product)

Big ring four acyl ammonia

Stable anion [LM ≡ O] is provided^-Chemical species, for example [LMn^V≡O] ^- These anion Agent is not very active to manganese base chemical species as the O-atom transfer. Change the anion chemistry Species are found to do like this to strengthen manganese so that neutral or cationic chemical species to be provided The catalytic capability of species in oxidation reaction. In a kind of method of the present invention, that bidentate is secondary The ionic bond chalaza joins in the big ring of following formula structureCan regulate electric charge, improve the electron donation of acid amides and change the axial ligand that is bonded to metal Dynamics and thermodynamics. Said [LMn^V≡O] ^-Complex is with the TFMS of representational alkali, alkaline earth or transition-metal cation-[SO₃CF ₃] salt (Triflate) carries out titration. Adopt The ultraviolet/visible light spectrum is followed the tracks of the variation that takes place. Drawing out the mol ratio curve is also resolved In order to be understood as the key process. Fig. 3 uses Li⁺As an example of cation demonstration, wherein K=9.0 * 10⁴～1.2×10 ⁵, pK=4.95～5.08. The mol ratio curve show only exist a kind of Become the key process.

Mn in the ultraviolet spectrum ^VNa is also used in the variation of bands of a spectrum ⁺, Zn ²⁺, Mg ²⁺, Ca ²⁺, Ba ²⁺And Sc ³⁺Monitor.Referring to Fig. 9～14.The cationic catalyst complex of transition-containing metal ion Ru and Rh has prepared and has successfully realized catalytic oxidation.

As shown in Figure 5, in initial tentative reaction, make [LMn ^V≡ O] ^-The switch complex does not exist and exists under the switch ion condition and PPh ₃Reaction is to make Ph ₃P=O.Monitored Mn in the ultraviolet spectrum ^VThe decay of bands of a spectrum.

Result of the test proves that the existence of switch ion has significantly strengthened the transfer activity of O-atom.Can control reaction rate by selecting secondary ion.Successfully making the former muonic catalysis of O-transfer to tetramethyl-ethylene (seeing Figure 15) upward simultaneously again can be by optionally controlling the purpose that secondary ion reach the control reaction rate, and this has proved that oxidation catalyst of the present invention is useful for the oxidation of the various substrates that comprise alkene.

Referring to Figure 15, for example, selective oxidation method of the present invention can be carried out in the following manner: with oxygenate catalyst [LMn ^V≡ O] ^-With a kind of required alkali, alkaline earth or transition-metal cation source, main group metal ion and a kind of oxygen atom source such as peroxide or oxidant, at room temperature, in the solution that contains solvent and target compound, mix with a plurality of alkene active sites.Reaction is carried out with acceptable speed, can be heated this solution.This reaction meeting produces oxidation reaction at an alkene active site the most active or several active site and any other active site that cation-the catalyst complexes activity will be admitted.

[LMn ^V≡ O] ^-+ switch or cation+alkene or target compound+[O] → at the oxidation product or the epoxide of one or more selected alkene active sites.

A specific reaction is shown among Figure 15.

Make that in order to control reaction the active site that has only an active site or have only those to have certain activity is oxidized, first kind of used cation should be the cation that the sort of generation has lowest activity cation-catalyst complexes.This cation with lowest activity-catalyst complexes that with the cation bonding time, is generated will be only can be to substrate or target compound on the most active alkene active site carry out oxidation.In this manner, by producing active minimum cation-catalyst complexes [LM (O)] from being incorporated into ^-The cation of secondary bonding point of oxygenate-tetramido part begin and be performed until catalytic action till the highest active cation-catalyst complexes, make that to be up to active minimum a series of alkene active sites from activity all oxidized respectively.For containing a plurality of alkene active site a, b, c, d, e, first kind of cationic source that f, the target compound of g etc. will produce the minimum cation-catalyst complexes of activity usually successively joins in the above-mentioned reactant mixture.This cation will be bonded on the secondary bonding point of oxygenate catalyst.It is the oxidation reaction of first alkene active site a that this cation-catalyst complexes will cause on the target compound the highest active alkene active site.Reaction stops immediately, and if necessary, can choose wantonly and remove first kind of cation.Second kind of cationic source of adding and this cation are bonded on the secondary bonding point of oxygenate catalyst in this reactant mixture then, cause the highest alkene active site of activity remaining on the target compound immediately.The i.e. oxidation reaction of second alkene active site b (the highest active site of the former activity that pre-exists is earlier oxidized).Then, if necessary, from this reactant mixture, remove second kind of cation and add the third cation in case with the secondary bonding point bonding of oxygenate catalyst, at this, this catalyst will cause remaining active olefin active site on the target compound, the i.e. oxidation reaction of the 3rd alkene active site c.This process can be proceeded down, makes alkene active site d different on the target compound, e, f, g etc. produce oxidation successively.Adopt certain cation that is subjected to temperature factor control also can obtain a series of different activity.Therefore, cation/catalyst complexes makes active minimum active site produce oxidation under chosen temperature, makes to have only this point just to react.When the rising temperature, can find a certain temperature conditions, two active sites that activity is the highest are compared with other active site and can be produced selective reaction under this temperature, and so on.The above is the example of chemo-selective.Contain in the compound that a kind of alkene inequality by several constitutes or in same compound under the situation of some alkene of being made of respectively several same alkene and several alkene inequality bunch, then one of one of several alkene or several alkene bunch will be bunch more more active than other alkene or alkene.Some difference of activity of each alkene or alkene bunch.Owing to known with the two key various functional groups adjacent or that be linked on this pair key of alkene active site to have different activities, so can accomplish that by control the oxidation reaction that will compare in another functional group the selection of the oxidation reaction in the functional group is more preferential.The oxygenate activity of such catalysts also can be controlled by the way that metal ions M is become another transition metal.For example, the activity of iron active much bigger than manganese in this class catalyst system.For the system that requires mild oxidation, manganese is preferred.

The switch catalyst is useful for introducing asymmetry in the chiral substrates forward.The enantiomerism selectivity relevant with the prochirality active site on the target compound can be controlled by the asymmetry that exists in cation-complex.Oxygen atom branchpoint on the catalyst must be able to touch other oxidable prochirality active site of alkene or target compound.In the oxygenate catalyst, can build up chirality or chirality is brought in this oxygenate catalyst by switch cation and thereon group of connection.Just can control size, shape and the chirality feature of catalyst by the substituting group on the selecting catalyst.Various substituent many variations and these substituent preparation methods are in the people's such as Collins of above citation patent application (incorporating this paper into) and be entitled as the common unsettled U.S. Patent Application Serial 08/681 of " encircling tetramido N-part greatly " people such as S.Gorden-Wylie, all open in 187, the latter's relative section is incorporated this paper into as a reference.Similarly, the position of functional group on the size of target compound and shape and the target compound, especially those functional groups of the most close pair key will controlled catalyst can promptly make the active site of alkene produce oxidation near which end of olefinic double bonds so that oxygen atom is transferred on the alkene.A kind of enantiomter with respect to other enantiomter that perhaps should produce or disappear and preferentially produce or situation about disappearing under, selectivity has also just taken place.Have optionally catalyst of enantiomerism although can buy from the market, the number of times that recycles of best oxidation catalyst only limits to 10～20 times.Have now found that catalyst system of the present invention has the very long life-span, and in the presence of one of oxidation power source, especially oxygen or its reductive derivative, compares with the commercial catalyst, its regeneration times that shows will have more does not know what doubly.

Catalyst system of the present invention also can be transferred to approach that the organic or inorganic substrate gets on to induce chirality from the switch catalyst by making the sulphur compound oxygen atom.For example, a kind of prochirality phosphorus compound can be oxidized on phosphoryl or sulphur, thereby generate the chirality chemical species.

The big ring (compound 1) that pyridine shown in Figure 1 replaces can be taked to synthesize in the above multistep processes of quoting and incorporating big ring four acid amides of disclosed preparation in people's such as S.Gordon-Wylie the co-pending U.S. Patent Application Serial 08/681,187 of this paper into.The parent complex that does not contain pyridine radicals is at T.J.Collins, R.D.Powell, C.Slebodnick, " American Chemical Society can will " 113 of E.S.Uffelman, existing report among the 8419-8425 (1991).

The synthetic of tetradentate ligands generally carries out as follows.The first step is dissolved in amino carboxylic acid, preferred α or β amino carboxylic acid in the carrier solvent and the derivative of a kind of activation in being selected from oxalates and malonate (such as the malonyl chloride under the alkali existence) heats to make intermediate.After finishing optionally two coupling reactions, the intermediate that will contain the diamides dicarboxyl is separated.In second step, in the presence of solvent and coupling agent, in this intermediate, add diamines.This diamines is a kind of diamines that secondary bonding point can be provided, and for example is selected from these diamines that hat derivative, cryptand, EDTA derivative, five-membered ring compounds and five-membered ring derivative as pyridine listed in the Table I, pyrimidine, pyrazine dicyano pyrazine, list or disubstituted benzene, benzimidazole, indoles, replacement, derivatives of porphyrin, the phthalocyanine matrix system of metal-complexing, two pyridine radicals system, coffee are coughed up quinoline matrix system and two schiff bases systems.Coupling agent is phosphorus Halides compound or pivalyl chloride preferably.With the heating of the mixture that makes and make reaction carry out the long enough time, when making solvent, often to reflux 48～72 hours with pyridine to generate big ring four tooth compounds.Usually use stoichiometric reaction reagent.

Substituting group on the amino carboxylic acid, the oxalates of activation or malonate derivative and diamine compounds all can optionally change, and so just can make the four tooth macrocyclic compound that make satisfy the needs of specific final use.Substituent change does not almost have for synthetic method or not influence.

After making macrocyclic ligand, just carry out complexation reaction with it with metal ion, metal ion is the 6th family (Cr, Mo, W), seven races (Mn, Tc, Re), the 8th family (Fe, Ru, Os), the nine degrees of kindred (Co, Rh, Ir), the tenth family (Ni, Pd, Pt) and the transition metal ions of the tenth gang (Cu, Ag, Au) or those metal ions with I, II, III, IV, V, VI, VII or VIII oxidation state in the periodic table of elements preferably.Because the catalyst system that the present invention preferably uses can play abundant oxidation in environment, so avirulent those metals are preferred, manganese and iron ion then are most preferred.

If prepared metal complex is shifted oxidant with strong oxygen atom subsequently, preferred person is a peroxide, such as mixing such as hydrogen peroxide, tert-butyl peroxide or cumyl peroxides, then generates ligand metal oxygenate complex.Any oxygen atom source all can use.

For the sort of long-lived especially oxidation catalyst when being iron for metal, Ch ₄Have following formula:

In the formula:

Z is and the atom of metal-complexing, is preferably N; When metal complex was in the oxide isolation, X was oxidation resistant functional group; And

R ' and R " be identical or different, and respectively be selected from such class substituting group, promptly such substituting group is inactive, R ' and R " in can form intramolecular strong bond and with R ' and R " the big ring carbon atom of institute's bonding can form strong bond; Such substituting group is sterically hindered and the conformation steric hindrance, and like this, the attenuation by oxygen of this metal complex will be suppressed in the presence of oxide isolation.

X is preferably oxygen or NRs, and its Rs is methyl, phenyl, hydroxyl, oxyl, CF ₃And CH ₂CF ₃R ' and R " preferred separately hydrogen, methyl, halogen, CF ₃And if both become ring, then preferred cycloalkyl such as cyclopenta, cyclobutyl, cyclohexyl or cyclopropyl one class.

In addition, in the time of in being in relatively mild oxidation environment, for example when metal was manganese, R ' and R " can be above to Ch ₄Any group in the defined group or can also be the 9th page and go up to R ₅And R ₆Selected those groups.About having the oxidation catalyst problem of permanent oxidation performance, people such as the T.Collins that quotes in the above are existing detailed descriptionthe in the U.S. Patent Application Serial of submitting in July, 1,996 08/681,237, and this content is incorporated this paper into as a reference.

It is the process of a complexity that manganese inserts in the big ring of compound 1, and its reason is, alkalescence to sprotic condition under, four acid amides master active sites and secondary activity point both are easy to the manganese bonding.Therefore, manganese must be removed it after inserting main active site from secondary activity point.Under the situation of manganese, adopt the operating condition of alkaline aqueous solution just can reach this purpose.Useful synthetic method is undertaken by following embodiment.

Embodiment 1

Under inert gas shielding, with part (425mg, 1.05 * 10 ^-3Mole) be dissolved in dry oxolane (THF, 40ml) in, add two (TMS acid amides) lithium (the 1.0M THF solution of 6.32ml, 6.3 * 10 again ^-3Mole).This mixture is stirred (5 minutes), add acetylacetonate manganese Mn (acac) subsequently ₃(557mg, 1.58 * 10 ^-3Mole) is dissolved in the solution (10ml) of acetonitrile.This reactant mixture was stirred 2 hours, then this solution is placed the inherent air evaporation of a rotary evaporator to doing.Solid residue is dissolved in the low amounts of water and filters to remove solid residue.It is dried that filtrate is evaporated to, again with gained solid Li[LMn ^III] be dissolved in acetone and filter.With excessive TBHP (TBHP) solution (0.586ml, 5.25 * 10 ^-3Mole contains the 90%TBHP of 5% tert-butyl alcohol and 5% water) handle this filtrate.Subsequent reaction is monitored according to the change of color, is become last dark red brown by the bright orange in when beginning.To containing Li[LMn ^V(O)] promptly add excessive tetraphenylphosphonium chloride (2.0g, 5.25 * 10 in the product solution of the lithium salts of the compound 1 of quantitative yield basically ^-3Mole) solution of water-soluble (20ml).By rotary evaporation the solvent volume of this mixture is reduced, thereby obtain [Ph ₄P] water slurry of compound 1.Adopt under the room temperature to [Ph ₄P] method of diffusion pentane steam grows monocrystalline in the ethyl acetate solution of compound 1; Compound 1 anion is carried out x-ray crystal structure measure, it the results are shown in Fig. 2.

(C ₆H ₅) ₄P[compound 1]: C ₄₄H ₄₅MnN ₅O ₅The analytical calculation value of P: C, 65.26; H, 5.60; N, 8.65; P, 3.82.Measured value: C, 65.42; H, 5.67; N, 8.85; P, 3.89. ¹H NMR (chloroform-d ₁): (see figure 8) (C ₆H ₅) ₄P[compound 1] δ 8.58 (m, 1H), 8.10 (m, 1H), 7.47-7.85 (m, 20H), 6.86 (m, 1H), 2.05 (q, 2H, J=7.3Hz), 1.97 (q, 2H, J=7.3Hz), 1.86 (s, 3H), 1.85 (s, 3H), 1.81 (s, 3H), 1.80 (s, 3H), 0.83 (t, eH, J=7.7Hz), 0.55 (t, 3H, J=7.4Hz).ESI-MS (anion): m/z 470.1, [compound 1] ^-1(100%);

Crystal data: monocrystalline is a rhombic system, space group Pbca, a=14.205 (2) , b=19.87 (2) , c=28.341 (4) , V=7999 (9) ³(measuring down) at-100 ℃, Z=8; d _{Calculated value}=1.355gcm ^-3μ=4.24cm ^-1Adopt Mo K α X-ray that Zr-filters and W scan mode to collect 7895 of independent point diffraction sums (2 °＜2 θ＜52.16 °).Adopt SHELXS (G.M.Sheldrick, Acta Cryst., A46, (1990), 467) direct method in the program package solves structure, adopt SHELXL 93[G.M.Sheldrick simultaneously, SHELXL 93, " crystal structure revision program ", University of G ttingen, Germany, 1993] program package, at F ²Carry out the complete matrix least square refinement on the basis.C on the pyridine ring and the differentiation of N are carried out as follows: because do not finding the difference of peak height on the electron density differential chart or be coupled to bond distance's difference between each atom, so these two kinds of atoms all are used as C atom value and revise.(being labeled as N (5) afterwards) demonstrates more obvious asymmetric thermal parameter in the anisotropy correction one of among both.Another (being labeled as C (2)) then is that unique demonstrating may be that atom of H atom site on the electron density differential chart.Because all other hydrogen atoms can both be determined their position clearly on the electron density differential chart, take the temperature factor data again into consideration, so should think to have sufficient foundation for pointing out of these two kinds of atoms.But no matter how they determine, and these two kinds of atoms are still and can exchange.Adopt striding type model and its isotropic temperature factor to be set at 1.2 times of temperature factor of that atom that is connect with them to the correction of hydrogen atom.The methyl hydrogen atom is used as rigid radical correction.Crystal structure is discovered the crystallization water molecule that has fractional value in crystal, and is specified as the NMR spectrum.Correction value to the oxygen atom occupation rate of hydrone is 0.38.Correction converges on R ₁4202 observable reflectance datas (I＞2 σ (I)) are adopted in (based on the F value)=0.0564.

Embodiment group 2

Adopt a series of cations of monovalence, divalence and trivalent and the reversible forming process of secondary complex in acetonitrile of compound 1 monitored by the ultraviolet spectrum.Monoacidic base metal cation series Li ⁺, Na ⁺And K ⁺(making fluoroform sulphonate) shows and becoming the unusual big variation of key properties.Therefore, Li ⁺Become extinction behaviors (Fig. 3) such as key table reveals and mol ratio curve to demonstrate to finishing the Li of lithiation needs 2.5 equivalents ⁺Carry out three times and repeat titration ([compound 1]=0.30,0.27 and 0.14 mM liter ^-1, logK ₂₅°=5.02 ± 0.06).By contrast, Na ⁺The mol ratio curve (Fig. 9) of Cheng Jian has demonstrated two kinds and has become the key process to exist, and its evidence is that first platform is at 8 equivalent Na ⁺In time, begin to occur, and second platform is at 47 equivalent Na ⁺In time, begin to occur.Have reason to believe that first becomes the key behavior is to occur at the bidentate active site, and the behavior of second one-tenth key is to occur on monodentate amide oxygen atom.When adding K ⁺When (up to 60 equivalents), the ultraviolet spectrum does not change.When adding Ba by this way ²⁺In the time of (Figure 13), the non-change that waits extinction takes place in the ultraviolet spectrum, shows that compound 1 anion that has more than 1 can be bonded to Ba ²⁺On; Ba ²⁺Bonding be very strong because its mol ratio curve is presented at Ba when reaching titration end-point ²⁺Equivalent be 1.3.Similarly, Sc ³⁺Bonding demonstrate and non-ly wait the extinction behavior, but only need an equivalent (Figure 14) but reach titration end-point.Unfortunately, the cyclic voltammetric behavior of the system of compound 1 representative is not electrochemical reversible for any switch ion.But, the plane four-coordination Co of compound 1 ^IIIThe cyclic voltammetric of homologue studies show that, but demonstrates electrochemical reversible electronics and shift character for various secondary ions.For example, at excessive Co ^IIIUnder the condition of complex, use Ca ²⁺All can observe the chemical species of double-core, three nuclears and four nuclears.Thus and by the electrospray ionisation mass spectrum result of study that can be observed the multinuclear ion, people can reach a conclusion: the Co of compound 1 ^IIIHomologue is bonded on the switch ion of multi-charge more than once.Compound is bonded to this true Ba of being on the multi-charge switch ion for more than 1 time ²⁺/ compound 1 and Sc ³⁺In the research of the ultraviolet of/compound 1 spectrum bonding not behavior such as extinction such as discoverys grade reasonability foundation consistent with each other is provided.In sum, these results show that bidentate coordination and acid amides-O bonding point both shows significant sensitiveness to the electric charge/ion size ratio of secondary ion or a plurality of ions.

Embodiment group 3

Li during the manganese dentate part of compound 1 system can be composed with IR for the sensitiveness of secondary ion disturbance ⁺Bonding is explained the influence of ν (Mn ≡ O) bands of a spectrum.In order to obtain not have the IR interval of macrocyclic ligand bands of a spectrum.Investigated ¹⁸The manganese dentate of O mark; For preparing this chemical species, with [Et ₄N] [compound 1] and CH ₃CN/H ₂ ¹⁸O (1: 1; 98% ¹⁸O) mixture at room temperature stirred for three weeks together.Belonging to does not respectively have Li ⁺With Li is arranged ⁺The ν of the chemical species of bonding (Mn ≡ O) bands of a spectrum are shown among Fig. 4; The bands of a spectrum of ν (Mn ≡ O) are from belonging to the 939cm of parent complex ^-1Be displaced to and belong to Li ⁺The 954cm of the chemical species of coordination ^-1This orchid moves 15cm ^-1Phenomenon mean Li ⁺The effect of one-tenth key make the remarkable decline of electron donation of big ring four acid amides-N part weaken to some extent, this is owing to enhancing that the oxygenate binding energy increases the electron donation of relevant oxygenate part this decline being compensated.People can infer that the electrophilicity of oxygenate part is also tackled secondary cationic one-tenth key and produced significant enhancement effect.

Embodiment group 4

Even the influence of different switch ion pair reactivities is at first investigated by the evidence that research principle oxidation reaction triphenyl phasphine is oxidized to the triphenyl phasphine oxide.Adopt the compound 1 of an equivalent and the triphenyl phasphine of 100 equivalents, in air and in 15 ℃ acetonitrile, by the reaction of the different switch ions of ultraviolet spectrum monitoring.Different switch ions is to add with the form of fluoroform sulphonate (5 and 60 equivalent); Reaction repeats three times at least.The generation of oxidation product triphenyl phasphine oxide by ¹The interval IR spectrum of H NMR spectrum and ν (P=O) is confirmed.This results are shown in Fig. 5; The relative speed of this reaction is that benchmark carries out normalization with triphenyl phasphine in the speed that does not have to be subjected in the presence of the switch ion parent compound 1 oxidation.As arriving seen in the reaction that is bonded to compound 1 at secondary cation, switch is closely-related with the character of the switch ion that adds to the influence of phosphine oxidation rate.Under the ultraviolet spectrum experimental conditions of non-switch compound 1, it is very slow that triphenyl phasphine is oxidized to the speed of triphenyl phasphine oxide, and reaching reacts completely needs a few kilosecond clocks.In the presence of the different switch ions of 5 equivalents, find with respect to each on-off effect speed of non-on-off effect speed to be successively: Na ⁺=3, Ba ²⁺=5, Mg ²⁺=7, Li ⁺=13, Zn ²⁺=24, Sc ³⁺=1244.Indicate as above institute, find Na in the research of switch ion ⁺Ion is that of giving prominence to has the speed of suitable second number when producing bonding action with compound 1.The relative speed that triphenyl phasphine is had 1 oxidation of compound of different switch character reflects this discovery.Therefore, for Mg ²⁺Or Zn ²⁺, when the switch ion: the ratio of compound 1 finds that the oxidation rate of triphenyl phasphine does not but increase when increase to 60: 1 at 5: 1.When the increase of this ratio to Ba ²⁺Be defined as 1.2 times, Li ⁺Be 2 times, Sc ³⁺When being 1.3 times, the discovery oxidation rate has only small growth.By contrast, Na ⁺: the ratio of compound 1 increased at 60: 1 o'clock from 5: 1, the oxidation rate of phosphine has increased by 169 times.Moreover, add K ⁺(nearly 60 equivalents) can not disturb the oxidation rate of the non-switch compound 1 of parent, and this has strengthened above-mentioned viewpoint, i.e. K ⁺Seem in the concentration range that can be easy to study not can with switch active site bonding.

The increase of oxygenate transfer rate provides real useful properties for above-mentioned slight oxidation signal.We have also studied compound 1 as the reactivity of oxygen atom transfer agent for electron rich alkene-tetramethyl-ethylene.

Embodiment 5

By ¹³The C wave spectrum, under 50 ℃ to [Ph ₄P] compound 1 (1 equivalent), ZnTf ₂, (4.5 equivalent), 2,3-dimethyl-2-butylene (tetramethyl-ethylene, 132 equivalents) and TBHP (90%, 266 equivalent) are dissolved in acetonitrile-d ₃Mixture monitor, till whole alkene have all consumed (48 hours).The observed product of unique energy is 2,3-neohexene-3-alcohol-2 (＞98%); This reaction repeats three times. ¹³C NMR (acetonitrile-d ₃): (seeing Figure 15) 2,3-neohexene-3-alcohol-2: δ 19.5,29.3,73.3,108.7,153.3.Referring to R.W.Murray, W.Kong, S.N.Rajadhyaksha " J.Org.Chem.58,315～321 (1993) ".Referring to Figure 15.

This product solution is also analyzed with GC/MS, and the result has confirmed 2, and 3-neohexene-3-alcohol-2 exists as unique alkene derivative products.The tert-butyl alcohol product that is generated has identical relative abundance with residual TBHP, shows that this is quantitatively property and the selective reaction of a kind of chemistry that is perfectly clear.Obviously, except trace decomposes, the state that the TBHP maintenance that is not used is not consumed, therefore adding alkene again will cause restarting of catalytic oxidation process.Ultraviolet analysis of spectrum to catalytic solution shows, in whole catalytic oxidation process and after this, all exists compound 1 quantitatively.Though ¹³Can detect other product (obviously producing) of trace in the C NMR spectrum by TBHP, but at acetone-d ₆In through the solution of reaction, it contained in the NMR pipe and be statically placed on the testing stand still remain unchanged basically after 9 months; Find after this, wherein contain 2 of identical relative scale, 3-neohexene-3-alcohol-2, the tert-butyl alcohol, TBHP and acetone addition product thereof, these are all at the end established in reaction, do not find other in addition.There is one by ZnTf ₂(1 equivalent), 2,3-dimethyl-2-butylene (30 equivalent) and TBHP (90%, 64 equivalent) are dissolved in acetonitrile-d ₃The control systems that does not contain compound 1 formed of mixture, also use down at 50 ℃ ¹³C NMR monitoring 5 days; Do not observe any variation.When take with temperature rise to 70 ℃ and use tritium for acetonitrile as the measure of solvent when changing reaction condition, what show in Figure 15 belongs to 2,5 identical characteristic peaks of 3-neohexene-3-alcohol-2 have occurred.Therefore, compound 1 provides a kind of gentleness, optionally single-minded and unusual stable oxygen atom transfer catalysis system.

Thereby the enzyme of playing the part of nature designer role is usually made accurate arrangement to multiple reaction and is reached target selection on time and space.Although modern chemistry has accumulated rich knowledge to how spatially arranging reaction so that reach selectivity, arrange multiple reaction carefully in time so that the domination selectivity but is a brand-new research field.Various variations on activity, spatial orientation and the size that the above-mentioned oxidation catalyst of employing this paper is provided, can design a kind of ligand system for order and the reactivity point of organizing an above oxidation reaction, thereby reach the active and purpose optionally of goal response.Ligand system of the present invention has the character of significant anti-oxidant decomposition, thereby very long-life and reusable catalyst is provided.The synthetic method for preparing many different compounds 1 had been carried out selected, making can be according to a series of two amines of two-step method from list in Table I and method (having incorporated this paper into as a reference) the preparation part that proposes according to people such as Gorden-Wylie, and its improvements are to substitute those two amines described in the Gorden-Wylie synthetic method with listed two amines in the Table I.Importantly to recognize; the method that is provided clearly will be to the needed transition metal of the environmental protection range expansion of the manganese reactivity that may reach for example; simultaneously owing to allow people to improve the slow oxygen atom transfer agent reactivity of other kind carefully; or more generally; the reactivity of the compound 1 that raising designs to obtain oxidation catalyst such as combining for the reaction with more than one and the reaction reagent of mutation one class thereof, thereby the target of reactivity might be come true in the greenization of chemistry.People might utilize new method of the present invention to go to finish and use the necessary whole tasks of the catalytic elements current element that does not meet environmental protection requirement that is using of replacement that meet environmental protection requirement.Arranging the exploration of multiple reaction is the reactivity problem of difficult treatment in time, such as for the green reagent, the especially oxidant that are difficult to obtain that obtain other kind and for reaching problems such as enantiomerism selectivity in the oxidation reaction and chemo-selective, provide huge hope, and these problems have proved a kind of resistance that the exploration that lacks great ambition is explored.

Table I azepine aryl substitute

Parent complex (pyridine-) pyridine-

Pyrimidine-pyrazine-dicyano pyrazine-simple aromatics substitute

Q ₁=NH ₂, RNH, R ₂N, CO ₂H, SO ₃H, OH, SH

Q ₁=NH ₂, RNH, R ₂N, CO ₂H, SO ₃H, OH, SHQ ₂=NH ₂, RNH, R ₂N, CO ₂H, SO ₃H, OH, other switch substituting group of SH

Benzimidazole-indoles-

The continuous hat derivative that replaces of Table I

Q ₁=NH, NR, O or S Q ₁=NH, NR, O or S

Q ₂=NH, NR, O or S Q ₂=NH, NR, O or S

Q ₃=NH, NR, O or S Q ₃=NH, NR, O or S

Q ₄=NH, NR, O or S

The phendioxin 2-hat-4-that the benzo that replaces-9-hat-3-replaces

Q ₁=NH, NR, O or SQ ₂=NH, NR, O or SQ ₃=NH, NR, O or SQ ₄=NH, NR, O or SQ ₅=NH, NR, O or S

The phendioxin 5-hat-5-that replaces

Q ₁=NH, NR, O or SQ ₂=NH, NR, O or SQ ₃=NH, NR, O or SQ ₄=NH, NR, O or SQ ₅=NH, NR, O or SQ ₆=NH, NR, O or S

The phendioxin 8-hat-6-that replaces

Table I continues other cryptand Q ₁=NH, NR, O or SQ ₂=NH, NR, O or SQ ₃=NH, NR, O or SQ ₄=NH, NR, O or S

Q ₁=NH, NR, O or SQ ₂=NH, NR, O or SQ ₃=NH, NR, O or SQ ₄=NH, NR, O or S

Q ₁=NH, NR, O or S Q ₁=NH, NR, O or SQ ₂=NH, NR, O or S Q ₂=NH, NR, O or SQ ₃=NH, NR, O or S Q ₃=NH, NR, O or SQ ₄=NH, NR, O or S Q ₄=NH, NR, O or S

Table I continues the EDTA derivative Ethylenediamine tetra-acetic acid-

The tetraazacyclododecane tetradecane tetraacethyl-

Table I continues five-membered ring

Q=NH (pyrroles-), S (thiophene-), O (furans-), CH ₂(cyclopentadiene-), RCH (cyclopentadienyl group of replacement-, R=alkyl, aryl)

R ₁=H, alkyl, aryl, alkenyl, halogen

R ₂=H, alkyl, aryl, alkenyl, halogen five-membered ring derivative M=V, Cr, Mn, Fe, Co, Ni, Ru, Os, Rh for example can obtain ferrocene/ferrocene switch derivative R for M=Fe ₁=H, alkyl, aryl, alkenyl, halogen R ₅=H, alkyl, aryl, alkenyl, halogen R ₂=H, alkyl, aryl, alkenyl, halogen R ₆=H, alkyl, aryl, alkenyl, halogen R ₃=H, alkyl, aryl, alkenyl, halogen R ₇=H, alkyl, aryl, alkenyl, halogen R ₄=H, alkyl, aryl, alkenyl, halogen R ₈=H, alkyl, aryl, alkenyl, halogen

Table I continues the porphyryl switch

The oxidation state of metal-complexing, free porphyrin alkali or metal-complexing porphyrin by porphyrin changes, the change of metalloporphyrin axial coordination and optical means etc., can finish on-off action.

Table I continues phthalocyanine base switch

The axial coordination of the metal-complexing by free phthalocyanine alkali, the change of metal-complexing phthalocyanine oxidation state, metal phthalocyanine complex and optical means etc. can be finished on-off action.

The continuous two pyridine radicals systems of Table I

The continuous coffee of Table I is coughed up quinoline matrix system

The continuous two Schiff base switch body of Table I are

Claims (33)

1. the method at least one the oxidable active site on the target compound that oxygen is transferred to contain a plurality of oxidable active sites, this method comprises:

Thereby make the oxidable active site on the target compound that contains a plurality of oxidable active sites produce selective oxidation reaction by following compounds is reacted in solution:

Said target compound;

A kind of oxygen atom source;

A kind of Louis's acid source; And

The catalyst that a kind of structure is following In the formula:

Z is N or O, and at least one Z is N;

MO is transition metal-oxygenate species;

Ch ₁Be to be selected from pyridine, pyrimidine, pyrazine, the dicyano pyrazine, single-, two, three or four substituted benzenes, benzimidazole, benzoquinones, bis-imino substituted benzene, indoles, the hat derivative that replaces, cryptand, EDTA derivative, five-membered ring and five-membered ring derivative, derivatives of porphyrin, the phthalocyanine matrix system that metal replaces, two pyridine radicals systems, phenanthroline matrix system and two schiff bases (salen) matrix are;

Ch ₂And Ch ₃Expression links the following unit of structure of adjacent Z atom separately: R in the following formula ₁, R ₂, R ₃And R ₄Be identical or different group paired and accumulation, and each group all is selected from alkyl, aryl, alkenyl, alkynyl, alkaryl, cycloalkyl, cycloalkenyl group, alkoxyl, phenoxy group, halogen, haloalkyl, whole haloalkyl, CH ₂CF ₃, and CF ₃, perhaps R ₁, R ₂, R ₃And R ₄That constitute to replace together or unsubstituted phenyl ring, perhaps R ₁, R ₂Or R ₃, R ₄This two couple's paired R substituting group constitutes cycloalkyl or these groups of cycloalkenyl group together; And

Ch ₄For connecting the unit that is selected from one of following group of adjacent Z atom: R in the formula ₅And R ₆Be identical or different; Cheng Huan's or non-Cheng Huan's, and respectively do for oneself hydrogen, ketone, aldehyde, carboxylic acid, ester, ether, amine, imines, acid amides, nitro, sulfonyl, sulfate radical, phosphoryl, phosphate radical, silicyl, siloxanes, alkyl, aryl, alkenyl, alkynyl, alkaryl, cycloalkyl, cycloalkenyl group, alkoxyl, phenoxy group, halogen, CH ₂CF ₃Or CF ₃, perhaps R ₅, R ₆Right paired R substituting group constitutes cycloalkyl or these groups of cyclenes basic ring together; The R of wherein substituent selection and non-Cheng Huan ₅, R ₆Identical; And make said reaction carry out the long enough time so that make at least one the oxidable active site on the target compound produce oxidation.

2. the described method of claim 1, wherein said lewis acid is selected from proton, the ion of alkali metal, alkaline-earth metal, rare earth or transition metal or main group metal.

3. the method for claim 1, the relative activity of wherein said a plurality of oxidable active sites on target compound differs from one another, and the approach that selected lewis acid can be by generating cation-catalyst complexes optionally activated catalyst so that make an oxidable active site on the target compound produce oxidation.

4. the method for claim 3, this method also comprises following steps:

A series of oxidable active site on the identification target compound, arrange by active size sequence, generally begin from the oxidable active site of this series one group has the most oxidable active site of high relative activity and arranges that last group has till the oxidable active site of minimum relative activity to the oxidable active site of this series; And

(a) the first kind of cation that adds activated catalyst in solution be so that generate the first cation-catalyst complexes with first reactivity, and first reactivity of this first cation-catalyst complexes is enough to make that first group of oxidable active site has precedence over other oxidable active site and be subjected to selective oxidation in the target compound;

(b) make oxidation reaction carry out one sufficiently long period so that make each the initial oxidable active site on the target compound all be subjected to oxidation, thereby make second group of oxidable active site in the oxidable active site of series in the oxidable active site of the remainder of this series active site, have the highest relative reactivity;

(c) randomly from this solution, remove first kind of cation;

(d) add second kind of cation in this solution, the cation-catalyst complexes with second reactivity that is produced is enough to second group of oxidable active site of optionally oxidation;

(e) make oxidation reaction carry out that second group of oxidable active site is subjected to oxidation on one section target compound of chien shih when sufficiently long, thus make in a series of oxidable active site on the target compound arbitrary next organize oxidable active site and in the oxidable active site of the remainder of this series active site, have the highest relative reactivity;

(f) randomly from this solution, remove second kind of cation;

(g) by in solution, adding selected cationic step successively, to each the oxidable active site repeating step (d)～(f) in succession in a series of oxidable active site on the target compound, make oxidation reaction carry out and under adding, from this solution, remove before a kind of selected cation before a kind of cation, all have the reactivity that increases gradually and make the oxidable active site of respectively organizing in a series of oxidable active sites be subjected to oxidation successively thereby each adds cation in this solution in succession, till last oxidable active site is oxidized.

5. the described method of claim 4, wherein said oxidable active site group comprises an oxidable active site.

6. the described method of claim 4, wherein said oxidable active site group comprises more than one oxidable active site.

7. the described method of claim 1, wherein said target compound has the oxidable active site of prochirality of at least one, and said lewis acid catalyst complex has, and chirality is feasible to produce catalytic action to the enantiomerism selective oxidation of said at least one oxidable active site.

8. the described method of claim 7, wherein said oxidable active site is the compound that contains prochirality phosphorus.

9. the described method of claim 1, wherein said oxidable active site is an alkene.

10. the described method of claim 7, wherein said oxidable active site is an alkynes.

11. the described method of claim 7, wherein the transition metal of said catalyst is a manganese.

12. the described method of claim 7, wherein the transition metal of said catalyst is an iron.

13. those transition metal that the described method of claim 7, wherein said transition metal are selected from the 6th in the periodic table of elements, seven, eight, nine, ten and ten gangs or have I, II, III, IV, V, VI, VII or VIII oxidation state.

14. the described method of claim 1, wherein said oxidable active site is an alkynes.

15. the described method of claim 1, wherein said oxidable active site is an alkene.

16. the described method of claim 1, wherein the transition metal of said catalyst is a manganese.

17. the described method of claim 1, wherein the transition metal of said catalyst is an iron.

18. those transition metal that the described method of claim 1, wherein said transition metal are selected from the 6th in the periodic table of elements, seven, eight, nine, ten and ten gangs or have I, II, III, IV, V, VI, VII or VIII oxidation state.

19. the described method of claim 1, wherein said lewis acid is selected from the atom of group of the lanthanides.

20. the described method of claim 1, wherein said lewis acid is selected from the atom of actinium series.

21. the described method of claim 1, wherein said cation is selected from Li ⁺, Na ⁺, Zn ²⁺, Mg ²⁺, Ca ²⁺, Ba ²⁺, Sc ³⁺, Rh ³⁺And Ru ²⁺

22. the described method of claim 1, the metal in wherein said metal-oxygenate chemical species is an iron, and Ch ₄Be

In the formula:

Z is and the atom of metal-complexing, is preferably N; When metal complex was in the oxide isolation, X was oxidation resistant functional group; And

R ' and R " be identical or different, and respectively be selected from such class substituting group, promptly such substituting group is inactive, R ' and R " in can form intramolecular strong bond and with R ' and R " the big ring carbon atom of institute's bonding can form strong bond; Such substituting group is sterically hindered and the conformation steric hindrance, and like this, the attenuation by oxygen of this metal complex will be suppressed in the presence of oxide isolation.

23. the described method of claim 22, R wherein ₅And R ₆Respectively be selected from hydrogen, halogen, methyl, CF ₃And if the words of Cheng Huan are for being selected from cyclobutyl, cyclopenta, cyclopropyl or cyclohexyl.

24. one kind makes oxygen transfer to method on the oxidable active site on the target compound, this method comprises

Thereby make the oxidable active site on the target compound with the oxidable active site of prochirality optionally produce oxidation by following compounds is reacted in solution:

Target compound;

A kind of oxygen atom source;

A kind of Louis's acid source; And

A kind of and lewis acid forms the catalyst of complex, and said complex has chirality, and said catalyst has following structure

In the formula:

Z is N or O, and at least one Z is N;

MO is transition metal-oxygenate species;

Ch ₁Be to be selected from pyridine, pyrimidine, pyrazine, the dicyano pyrazine, single-, two, three or four substituted benzenes, benzimidazole, benzoquinones, bis-imino substituted benzene, indoles, the hat derivative that replaces, cryptand, EDTA derivative, five-membered ring and five-membered ring derivative, derivatives of porphyrin, the phthalocyanine matrix system that metal replaces, two pyridine radicals systems, phenanthroline matrix system and two schiff bases (salen) matrix are;

Ch ₂And Ch ₃Expression links the following unit of structure of adjacent Z atom separately:

R in the following formula ₁, R ₂, R ₃And R ₄Be identical or different group paired and accumulation, and each group all is selected from alkyl, aryl, alkenyl, alkynyl, alkaryl, cycloalkyl, cycloalkenyl group, alkoxyl, phenoxy group, halogen, haloalkyl, whole haloalkyl, CH ₂CF ₃, and CF ₃, perhaps R ₁, R ₂, R ₃And R ₄That constitute to replace together or unsubstituted phenyl ring, perhaps R ₁, R ₂Or R ₃, R ₄This two couple's paired R substituting group constitutes cycloalkyl or these groups of cycloalkenyl group together; And

Ch ₄For connecting the unit that is selected from one of following group of adjacent Z atom:

R in the formula ₅And R ₆Be identical or different; Cheng Huan's or non-Cheng Huan's, and respectively do for oneself hydrogen, ketone, aldehyde, carboxylic acid, ester, ether, amine, imines, acid amides, nitro, sulfonyl, sulfate radical, phosphoryl, phosphate radical, silicyl, siloxanes, alkyl, aryl, alkenyl, alkynyl, alkaryl, cycloalkyl, cycloalkenyl group, alkoxyl, phenoxy group, halogen, haloalkyl, whole haloalkyl, CH ₂CF ₃Or CF ₃, perhaps R ₅, R ₆Right paired R substituting group constitutes cycloalkyl or these groups of cyclenes basic ring together; And

Lewis acid-catalyst complexes wherein produces catalytic action to the enantiomerism selective oxidation of the said oxidable active site of target compound.

25. the described method of claim 24, lewis acid wherein is selected from proton, the ion of alkali metal, alkaline-earth metal, rare earth or transition metal.

26. the described method of claim 24, wherein said oxidable active site is an alkene.

27. the described method of claim 24, wherein said oxidable active site is an alkynes.

28. the described method of claim 24, wherein said oxidable active site is phosphorous compound.

29. the described method of claim 24, wherein the transition metal of said catalyst is a manganese.

30. the described method of claim 24, wherein the transition metal of said catalyst is an iron.

31. those transition metal that the described method of claim 24, the transition metal in wherein said metal-oxygenate species are selected from the 6th in the periodic table of elements, seven, eight, nine, ten and ten gangs or have I, II, III, IV, V, VI, VII or VIII oxidation state.

32. the described method of claim 24, wherein said lewis acid is selected from the group of the lanthanides atom.

33. the described method of claim 24, wherein said lewis acid is selected from the actinium series atom.

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