WO1994020510A1 - Catalyseurs homogenes bimetalliques d'hydroformylation, et procedes utilisant ces catalyseurs pour mener des reactions d'hydroformylation - Google Patents

Catalyseurs homogenes bimetalliques d'hydroformylation, et procedes utilisant ces catalyseurs pour mener des reactions d'hydroformylation Download PDF

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WO1994020510A1
WO1994020510A1 PCT/US1994/000262 US9400262W WO9420510A1 WO 1994020510 A1 WO1994020510 A1 WO 1994020510A1 US 9400262 W US9400262 W US 9400262W WO 9420510 A1 WO9420510 A1 WO 9420510A1
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George G. Stanley
Wei-Jun Peng
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Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College
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Definitions

  • This invention relates to novel homogeneous hydroformylation catalysts, and processes for the use of such catalysts in conducting hydroformylation reactions.
  • it relates to novel bimetallic catalyst complexes which selectively convert alkenes to linear aldehydes when a feed constituted of alkenes, hydrogen, and carbon monoxide is reacted in the presence of said catalyst complexes.
  • This invention also relates to asymmetric syntheses in which a prochiral or chiral compound is contacted in the presence of an optically pure metal-ligand complex catalyst, in enantiomeric form, to produce an optically active product.
  • Hydroformylation is an established process used by the chemical industry for converting alkenes to aldehydes, and sometimes alcohols, by reaction with hydrogen and carbon monoxide.
  • a feed stream constituted of alkenes, hydrogen and carbon monoxide is reacted over soluble rhodium- or cobalt-based transition metal catalyst at relatively low temperatures and pressures.
  • Rhodium catalysts the catalysts of choice for hydroformylation reactions, has long been recognized as more active than cobalt for promoting the "oxo" reaction, especially at low temperatures and pressures, even when the catalyst is used in relatively low concentrations.
  • Rhodium catalysts which produce primarily aldehydes, have also provided generally good selectivities in the production of linear aldehydes. Rhodium catalysts, however, require, inter alia, the use of an excess of a phosphine ligand in the reaction to stabilize the catalyst against the formation of decomposition products, and to maintain acceptably high product selectivities.
  • R, R' and R" can be the same or different and each is selected from the group consisting of hydrogen, F, Cl, Br, and I, C, to C ⁇ , alkyl, to C JO alkoxy, to Cg cycloalkyl, C 3 to cycloalkoxy, phenyl, phenyl substituted with F, Cl, Br, and I, phenyl substituted with C, to C JO alkyl, phenyl substituted with G, to cycloalkyl, phenyl substituted with C,to Cjo alkoxy, oxyphenyl, oxyphenyl substituted with C 3 to cycloalkyl, oxyphenyl substituted with F, Cl, Br, and I, oxyphenyl substituted with C 3 to Cg cycloalkoxy;
  • Q and Q' can be the same or different and each is selected from the group consisting of P, As and Sb, and X is an integer ranging from 1 to 5.
  • OBJECTS It is, accordingly, a primary objective of this invention to provide novel catalyst compositions of high activity and selectivity in carrying out hydroformylation reactions.
  • a further, and more specific object is to provide novel homogeneous bimetallic hydroformylation catalyst compositions, particularly rhodium- and ruthenium-based hydroformylation catalyst compositions, and process using these catalysts in conducting hydroformylation reactions to produce products rich in both linear and branched aldehydes; but particularly selective in producing products rich in linear aldehydes.
  • STATEMENT OF INVENTION These objects and others are achieved in accordance with this invention embodying catalyst compositions, and processes using these compositions in conducting hydroformylation reactions, characterized structurally by formula (I) as follows:
  • M and M' can be the same or different and is a Group VDI metal of the Periodic Table of the Elements (E.H. Sargent & Co. Scientific Laboratory Equipment, Copyright 1962), preferably a metal selected from the group consisting of rhodium, ruthenium, cobalt, iron, and palladium, or a Group IB metal, preferably copper
  • X is selected from the group consisting of methylene, substituted methylene CR'R 2 (sometimes referred to herein as CSS where R 1 and R 2 can be the same or different and each consists of a hydrocarbon moiety which can be saturated or unsaturated and which contains up to 20 carbon atoms and is a to C s alkyl (e.g., methyl, ethyl, n-butyl), to C 5 alkyenyl (e.g., vinyl, allyl, 1-butenyl), C, to C 5 alkoxy (e.g., methoxy, ethyoxy, butoxy),
  • the ligands L and V attached to each of the metal atoms, M and M' can be the same or different and can be H, CO, alkenes, alkyls, or other related ligands present either initially in the catalyst precursor or as formed in situ during the hydroformylation reaction.
  • bimetallic hydroformylation catalyst composition embodied by formula (I) can be written in a more simplified form as (IA):
  • the catalyst embodied by formula I or IA is formed by reaction between the polyphosphine ligand characterized by formula II, hereinafter LTTP,
  • LTTP ⁇ R , P-Y-P(R)-X-P(R)-Y-PR' ⁇ (LTTP) (II) as follows: LTTP and two molecules of a metal complex capable of complexing with the LTTP ligand form a generalized bimetallic complex characterized by formula in, as follows:
  • M and M' can be the same or different, L and L' can be the same or different and are ancillary ligands such as hydrogen, halogen, carbonyl, norbomadiene, or the like.
  • the charge on complex m will depend on the oxidation state of the metal centers and the charges and respective numbers of the ligands L and L' designated by w, x, y and z.
  • the values of the numbers w, x, y and z for the ligands L and L' are related to the exact nature of the metal centers and are set to give 14, 16 or 18 electron metal valence electron counts. For example, in the case of:
  • LTTP the ligand represented by formula II, acts as a template for building the bimetallic metal complex and has the ability to both bridge and chelate two metal centers, each of which will lie near the geometric center of the complex in general proximity to one another.
  • LTTP is thus preferably a binucleating tetratertiaryphosphine ligand having a bridging-chelating framework open at its center at which reaction with two metal centers can occur to produce bischelated bimetallic complexes represented by formula HI.
  • a prefered LTTP is one wherein the internal phosphorus atoms are linked through a methylene bridge, Y is an ethyl linkage, R is phenyl or a low molecular weight alkyl, and R' is a low molecular weight alkyl, such as ethyl (Et), as represented by the following structural formulae: rae-eLTTP
  • a tetratertiaryphosphine of this type is chiral at the two internal phosphorus atoms resulting in both racemic (R,R; S,S) and meso (R,S) diastereomers, a potentially desirable feature in promoting potential stereo- and enantio-selective reactions.
  • the catalyst of this invention is highly active and can convert alkenes, notably alpha olefins, via hydroformylation to linear and branched aldehydes at fast rates with remarkably high selectivities ( «30:1 linear to branched). Unlike present commerically used catalysts, there is no need to add excess phosphines to the reaction mixture to maintain the stability of the catalyst. The reason the catalysts of this invention produce a product having a high linea ⁇ branched aldehyde product ratio, it is believed, is due to the geometric configuration of the M 2 (LTTP) moiety. When, for example, an alkene coordinates to Rh 2 H 2 (CO) 2 (LTTP) it can only add to one of the outside axial rhodium coordination sites.
  • LTTP geometric configuration of the M 2
  • Rh 2 LTTP
  • Rh 2 can not attain this geometry because the other half of the complex is present and limits the extent of ligand motion toward trigonal bipyramidal or square pyramidal.
  • Rh(acyl)(CO)(u-LTTP)RhH(CO) a species similar to Rh(acyl)(CO)(u-LTTP)RhH(CO) would be a key intermediate in the catalytic cycle and that this type of system could readily access a "closed-mode" conformation in which an intramolecular hydride transfer could occur.
  • Such a proposed intermediate species is shown below.
  • RhjOL-l P unit essentially acts as a conventional monometallic hydroformylation catalyst until it reaches the acyl intermediate. Then, the rotational flexibility of the LTTP ligand comes into play and bimetallic cooperativity takes place to transfer a hydride to the acyl-bound rhodium. Reductive elimination of aldehyde product, it is believed, will then generate a Rh-Rh bonded complex which can react with Hj to regenerate the starting catalyst.
  • Rh(norb)(depmpe) + is, perhaps, the most analogous monometallic complex to our bimetallic Rh 2 (norb) 2 (LTTP) 2+ system and is a very poor hydroformylation catalyst (see Table A). It has an initial turnover frequency of about 5/hr with a product aldehyde selectivity of only 2:1 linear to branched with large amounts of alkene isomerization observed. Our bimetallic LTTP-based catalyst system is, therefore, at least 70 times faster than this "electronically correct" monometallic analog and markedly more selective and effective as a hydroformylation catalyst system.
  • Rh ⁇ no ⁇ TTP-pr Rh ⁇ no ⁇ TTP-pr * 80 30 30 30 1.9 10.0 4 94
  • Bimetallic model systems have also been prepared which have "spacer" groups replacing the central methylene bridge to probe the importance of having two metal centers present and near one another.
  • Bimetallic rhodium norbomadiene complexes based on p-xylene and pro pylene bridged tetraphosphine ligands (LTTP-p-xyl and LTTP-pr) shown below have been prepared and studied as hydroformylation catalysts.
  • Bimetallic Rh-norbomadiene complexes based on these spaced binucleating tetraphosphine ligands produce very poor hydroformylation catalysts giving results that essentially mirror those seen for the monometallic model systems.
  • the hydroformylation catalytic results for the mono- and bi-metallic complexes discussed here are also summarized in Table A.
  • Molecular modelling studies of the Rh 2 H 2 (CO) 2 (LTTP-p-xylene) and Rh 2 H 2 (CO) 2 (LTTP-pro pyl) catalyst systems clearly indicate that it will be very difficult, if not impossible for the metal centers in these systems to approach one another to do an intramolecular hydride transfer.
  • the presence of the single atom bridge in LTTP which constrains the two square planar rhodium centers to adopt a rotationally flexible face-to-face orientation may well be the key design feature in the Rh 2 (LTTP) complex. This, once again, allows facile intramolecular hydride transfer between the metal centers greatly enhancing the rate and efficency of the hydroformylation reaction.
  • the ethylene-linked terminal phosphines in LTTP simplify the synthetic procedure and gives higher yields of the final tetraphosphine (88-92%) based on Ph(H)PCH 2 P(H)Ph, or 39-43% yields based on the starting PhPH 2 .
  • the presence of the phenyl groups on the central P-CH 2 -P bridge allows more facile crystallizations of bimetallic complexes.
  • the electron-rich alkylated terminal and mostly alkylated internl phosphines coordinate strongly with metal centers and provide a very effective means for inhibiting ligand dissociation and bimetallic fragmentation.
  • the meso and racemic diastereomers of LTTP are both highly reactive binucleating ligands that can bridge and chelate two metal centers, albeit each can form complexes that have different overall geometrical orientations of the phosphines about the two metal centers.
  • the reaction of a metal compound as described by reference to formula HI will produce a large amount of the hydroformylation catalyst composition of the general geometrical configuration described by reference to formula I.
  • the catalyst or catalyst precursor is introduced into the autoclave or reaction vessel dissolved in a liquid medium, or slurried, or otherwise dispersed in a liquid medium to eventually provide a homogeneous reaction phase.
  • Suitable solvents are, e.g., alcohols, ethers, ketones, parafins, cycloparafins, and aromatic hydrocarbons.
  • substituents are carbonyl, carbonyloxy, oxy, hydroxy, alkoxy, phenyl and the like.
  • alpha olefins or olefins unsaturated in the 1-position, include alkenes, alkyl alkenoates, alkenyl alkyl ethers, alkenols, and the like, e.g., ethylene, propene, 1-butene, 1-pentene, 1-hexene, 1-hepene, 1-octene, vinyl acetate, allyl alcohol, and the like.
  • the feed is contacted with the homogeneous catalyst, while carbon monoxide and hydrogen are added, at temperature, pressure and time sufficient to convert the alkene to aldehydes, at high selectivities.
  • the temperature of the reaction ranges from about 50°C to about 150°C, preferably from about 60°C to about 120°C.
  • total pressures range from about 20 pounds per square inch (psi) to about 300 psi, preferably from about 50 psi to about 200 psi.
  • the ratios of H 2 :CO ranges generally from about 10:90 to about 90:10 volume percent, preferably from about 40:60 to 60:40 volume percent.
  • the catalyst is generally employed in the reaction mixture in concentrations ranging from about 10 "5 M to about Iff 2 M (molarity).
  • the catalyst is added to the reaction vessel as a slurry or a solution, the reaction is pressurized and brought to the desired operating temperature.
  • the feed and the carbon monoxide and hydrogen in desired ratios are then introduced into the reaction vessel to commence an operation.
  • Alkene feeds that are liquids at or near room temperature e.g., 1-hexene, 1-octene
  • the process is suited to batchwise operation, or to continuous operation via the use of suitable apparatus.
  • a binucleating tetratertiaiyphosphine ligand (CH-jCHjPEt-*), was prepared by reacting two equivalents of PhPH 2 and one equivalent of CHjClj with KOH in DMF solution to produce Phr ⁇ PCH j pr ⁇ Ph which is isolated.
  • the pressure of the reservoir cylinder was constantly monitored by a pressure transducer.
  • the reservoir pressure and temperature, autoclave temperature, and stir rate data were collected and stored on a Parr 4851 controller and the data transferred periodically to a PC computer for permanent storage and for calculating reaction rates. Analysis of products was performed by GC, NMR and GC/MS measurements.
  • electronrich phosphine ligands generally cause decreases in product selectivities. For these reasons, electron-rich phosphine ligands have proven to be very poor ligands for rhodium hydroformylation catalysts.
  • the bimetallic LTTP-based dirhodium catalyst of this invention has both high activities and very high selectivities giving an initial rate of 370 rurnovers/hr and a linear to branched aldehyde product ratio of at least 30:1. Furthermore, because of the strong rhodium coordinating abilities of this electron-rich LTTP ligand system, an excess of phosphine ligand is not required either for catalyst stability or to enhance linear aldehyde production.
  • Rh j t ⁇ ort j O-TTP 80 30 30 30 1.3 217.5 23
  • Rh ⁇ norb ⁇ TTP Rh ⁇ norb ⁇ TTP
  • Counter anion is BF 4 " for cationic species.
  • Asymmetric synthesis is of importance, for example, in the pharmaceutical industry, since frequently only one optically active isomer (enantiomer) is therapeutically active.
  • An example of such a pharmaceutical product is the non-steroidal anti- inflammatory drug Naproxen.
  • the S enantiomer is a potent anti-arthritic agent, while the R enantiomer is a liver toxin. It is therefore oftentimes desirable to selectively produce one particular enantiomer over its mirror image.
  • asymmetric synthesis desirably affords the ability to control both regioselectivity (branched/normal ratio), e.g., hydroformylation, and stereoselectivity.
  • Various asymmetric synthesis catalysts have been described in the art. For example, Wink, Donald J. et al., Inorg. Chem. 1990, 29, 5006-5008 discloses syntheses of chelating bis(dioxaphospholane) ligands through chlorodioxaphospholane intermediates and the demonstration of catalytic competence of bis(phosphite)rhodium cations.
  • a complex derived from dihydrobenzoin was tested as a precursor in the hydroformylation of olefins and gave a racemic mixture.
  • Catonic rhodium complexes of bis(dioxaphospholane) ligands were tested in the hydrogenation of enamides and gave enantiomeric excesses (ee) on the order of two to ten percent.
  • East Germany patent nos. 275,623 and 280,473 relate to chiral rhodium carbohydrate-phosphinite catalyst production.
  • the catalysts are stated to be useful as stereospecific catalysts for carrying out carbon-carbon bond formation, hydroformylation, hydrosilylation, carbonylation, and hydrogenation reactions to give optically active compounds.
  • Sakai et al., J. Am. Chem. Soc. 1993, 115, 7033-7034 disclose highly enantioselective hydroformylation of olefins catalyzed by new phosphinephosphite-Rh(I) complexes.
  • the search for more effective asymmetric synthesis processes is a constant one in the art. It would be desirable if asymmetric synthesis processes could be provided having good yields of optically active products without the need for optical resolution. It would be further desirable if asymmetric synthesis processes could be provided having the characteristics of high stereoselectivity, high regioselectivity, e.g., hydroformylation, and good reaction rate.
  • This facet of the present invention relates to asymmetric syntheses in which a prochiral or chiral compound is reacted in the presence of optically pure, metal-ligand complex catalyst, in enantiomeric form, to produce an optically active product.
  • a prochiral or chiral compound is reacted in the presence of optically pure, metal-ligand complex catalyst, in enantiomeric form, to produce an optically active product.
  • the separate SS and RR enantiomers (in substantially pure form) of the racemic form of the general catalyst disclosed in the earlier part of this specification, can effect asymmetric synthesis in various processes with various substrates to produce a specific isomeric material with high enantiomeric excess (ee) and which is optically active.
  • the meso form of this general catalyst is somewhat inactive, notwithstanding the fact that when both the meso and racemic diastereomers of the catalyst are together, there are disclosed to be highly reactive.
  • the processes of this invention are distinctive in that they provide good yields of optically active products having high stereoselectivity, high regioselectivity, and good reaction rate without the need for optical resolution.
  • the processes of this invention stereoselectively produce a chiral center.
  • An advantage of this invention is that optically active products can be synthesized from optically inactive reactants. Another advantage is that yield losses associated with the production of an undesired enantiomer can be substantially reduced.
  • the asymmetric syntheses processes of this invention are useful for the production of numerous optically active organic compounds, e.g., aldehydes, alcohols, ethers, esters, amines, amides, carboxylic acids and the like, which have a wide variety of applications.
  • optically active organic compounds e.g., aldehydes, alcohols, ethers, esters, amines, amides, carboxylic acids and the like, which have a wide variety of applications.
  • the part of the subject invention encompasses the carrying out of any known conventional syntheses in an asymmetric fashion in which the catalyst thereof is replaced by eitiier the SS or RR enantiomers of the racemic form of the optically active metal- ligand complex catalyst as disclosed in the prior art
  • the ligand is symmetrical when referred to as the SS or RR enantiomers of the racemate form of the metal-ligand complex catalyst
  • the term, “optically pure metal- ligand complex catalyst”, “optically pure metal catalyst”, and/or “optically pure catalyst” only refers to the individual SS or RR enantiomers (i.e.
  • Illustrative asymmetric syntheses reactions include, for example, hydroformylation, hydro acylation (intramolecular and intermolecular), hydrocyanation, olefin and ketone hydrosilylation, hydrocarboxylation, hydroamidation, hydroesterification, hydrogenation, hydrogenolysis, aminolysis, alcoholysis, carbonylation, decarbonylation, olefin isomerization, Grignard cross coupling, transfer hydrogenation, olefin hydroboration, olefin cyclopropanation, aldol condensation, allelic alkylation, olefin codimerization, Diels-Alder reactions, and the like.
  • asymmetric syntheses reactions involve the reaction of organic compounds with carbon monoxide, or carbon monoxide and a third reactant, e.g., hydrogen, in the presence of a catalytic amount of an optically active metal-ligand complex catalyst.
  • a third reactant e.g., hydrogen
  • the subject invention relates to asymmetric hydroformylation which involves the use of an optically pure metal-ligand complex catalyst in the production of optically active aldehydes wherein a prochiral or chiral olefinic compound is reacted with carbon monoxide and hydrogen.
  • optically active aldehydes produced correspond to the compounds obtained by the addition of a carbonyl group to an olefinically unsaturated carbon atom in the starting material with simultaneous saturation of the olefinic bond.
  • the processing techniques of this invention may correspond to any of the known processing techniques heretofore employed in conventional asymmetric syntheses reactions including asymmetric hydroformylation reactions.
  • the asymmetric syntheses processes can be conducted in continuous, semi-continuous, or batch fashion and involve a liquid recycle and/or gas recycle operation as desired.
  • the manner or order of addition of the reaction ingredients, catalyst, and solvent are also not critical and may be accomplished in any conventional fashion.
  • the asymmetric syntheses reactions are carried out in a liquid reaction medium that contains a solvent for the optically pure catalyst preferably one in which the reaction ingredients, including catalyst, are substantially soluble.
  • the subject invention encompasses the carrying out of any known conventional syntheses in an asymmetric fashion in which the catalyst thereof is replaced by an optically pure metal-ligand complex catalyst as disclosed herein.
  • Asymmetric intramolecular hydroacylation can be carried out in accordance with conventional procedures known in the art For example, aldehydes containing an olefinic group with three to seven carbons removed can be converted to optically active cyclic ketones under hydroacylation conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • optically active ketones can be prepared by reacting a prochiral olefin and an aldehyde under hydroacylation conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • optically active nitrile compounds can be prepared by reacting a prochiral olefinic compound and hydrogen cyanide under hydrocyanation conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • Asymmetric olefin hydro silylation can be carried out in accordance with conventional procedures known in d e art
  • optically active silyl compounds can be prepared by reacting a prochiral olefin and a silyl compound under hydrosilylation conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • Asymmetric ketone hydrosilylation can be carried out in accordance with conventional procedures known in the art
  • optically active silyl ethers or alcohols can be prepared by reacting a prochiral ketone and a silyl compound under hydrosilylation conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • Asymmetric hydrocarboxylation can be carried out in accordance with conventional procedures known in the art
  • prochiral olefins can be converted to optically active carboxylic acids under hydrocarboxylation conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • optically active amides can be prepared by reacting a prochiral olefin, carbon monoxide, and a primary or secondary amine or ammonia under hydroamidation conditions in the presence of an optically pure metal- ligand complex catalyst described herein.
  • optically active esters can be prepared by reacting a prochiral olefin, carbon monoxide, and an alcohol under hydroesterification conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • Asymmetric olefin hydrogenations and other asymmetric hydrogenations can be carried out in accordance with conventional procedures known in the art.
  • hydrogenation can be used to reduce a carbon-carbon double bond to a single bond.
  • Other double bonds can also be hydro genated, for example, a ketone can be converted to an optically active alcohol under hydrogenation conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • Asymmetric hydrogenolysis can be carried out in accordance with conventional procedures known in the art
  • optically active alcohols can be prepared by reacting an epoxide with hydrogen under hydrogenolysis conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • optically active amines can be prepared by reacting a prochiral olefin with a primary or secondary amine under aminolysis conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • optically active ethers can be prepared by reacting a prochiral olefin with an alcohol under alcoholysis conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • Asymmetric carbonylation can be carried out in accordance with conventional procedures known in the art
  • optically active lactones can be prepared by treatment of allyl alcohols with carbon monoxide under carbonylation conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • Asymmetric decarbonylation can be carried out in accordance with conventional procedures known in the art
  • acyl or aroyl chlorides can be decarbonylated under decarbonylation conditions with retention of configuration in the presence of an optically pure metal-ligand complex catalyst described herein.
  • allelic alcohols can be isomerized under isomerization conditions to produce optically active aldehydes in the presence of an optically pure metal-ligand complex catalyst described herein.
  • Asymmetric Grignard cross coupling can be carried out in accordance with conventional procedures known in the art
  • optically active products can be prepared by reacting a chiral Grignard reagent with an alkyl or aryl halide under Grignard reagent with an alkyl or aryl halide under Grignard cross coupling conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • optically active alcohols can be prepared by reacting a prochiral ketone and an alcohol under transfer hydrogenation conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • Asymmetric olefin hydroboration can be carried out in accordance with conventional procedures known in the art
  • optically active alkyl boranes or alcohols can be prepared by reacting a prochiral olefin and a borane under hydroboration conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • Asymmetric olefin cyclopropanation can be carried out in accordance with conventional procedures known in the art
  • optically active cyclopropanes can be prepared by reacting a prochiral olefin and a diazo compound under cyclopropanation conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • optically active aldols can be prepared by reacting a prochiral ketone or aldehyde and a silyl enol ether under aldol condensation conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • Asymmetric olefin codimerization can be carried out in accordance with conventional procedures known in the art
  • optically active hydrocarbons can be prepared by reacting a prochiral alkene and an alkene under codimerization conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • optically active hydrocarbons can be prepared by reacting a prochiral ketone or aldehyde and an allelic alkylating agent under alkylation conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • optically active olefins can be prepared by reacting a prochiral diene and an olefin under cycloaddition conditions in the presence of an optically pure metal-ligand complex catalyst described herein.
  • Illustrative starting material reactants include, for example, substituted and unsubstituted aldehydes (intramolecular hydroacylation, aldol condensation, allelic alkylation), prochiral olefins (hydroformylation, intermolecular hydroacylation, hydrocyanation, hydrosilylation, hydrocarboxylation, hydroamidation, hydroesterification, aminolysis, alcoholysis, cyclopropanation, hydroboration, Diels-Alder reaction, codimerization), ketones
  • olefin starting material reactants useful in certain of the asymmetric syntheses processes of this invention include tiiose which can be terminally or internally unsaturated and be of straight chain, branched-chain, or cyclic structure.
  • Such olefins can contain from four to forty carbon atoms or greater and may contain one or more ethylenic unsaturated groups. Moreover, such olefins may contain groups or substituents which do not essentially adversely interfere with the asymmetric syntheses process such as carbonyl, carbonyloxy, oxy, hydroxy, oxycarbonyl, halogen, alkoxy, aryl, haloalkyl, and d e like.
  • Illustrative olefinic unsaturated compounds include substituted and unsubstituted alpha olefins, internal olefins, alkyl alkenoates, alkenyl alkanoates, alkenyl alkyl ethers, alkenols, and die like, e.g., 1-butene, 1-pentene, 1-hexene, 1-octene, 1-decene, 1-dodecene, 1-octadecene, 2-butene, isoamylene, 2-pentene, 2-hexene, 3-hexene, 2-heptene, cyclohexene, propylene dinners, propylene trimers, propylene tetramers, 2-ethylhexene, 3-phenyl-l-propene, 1,4-hexadiene, 1,7-octadiene, 3-cyclohexyl- 1-butene, allyl alcohol, hex
  • Illustrative preferred olefinic unsaturated compounds include, for example, p-isobutylstyrene, 2-vinyl-6-methoxynaphthylene, 3-ethenylphenyl phenyl ketone, 4-ethylphenyl-2-thienylketone, 4-ethenyl-2-fluorobiphenyl, 4-(lm,3-dihydro- l-oxo-2H-isoindol-2-yl)styrene, 2-ethyl-5-benzoylthiophene, 3-ethenylphenyl phenyl ether, propenylbenzene, isobutyl-4-propenylbenzene, phenyl vinyl ether, vinyl chloride, and d e like.
  • Suitable olefinic unsaturated compounds useful in certain asymmetric syntheses processes of this invention include substituted aryl ediylenes described in U.S. 4,329,507, incorporated herein by reference in its entirety. Of course, it is understood that mixtures of different olefinic starting materials can be employed, if desired, by d e asymmetric syntheses processes of the subject invention. More preferably, the subject invention is especially useful for the production of optically active aldehydes, by hydroformylating alpha olefins containing from four to forty carbon atoms or greater, as well as starting material mixtures of such alpha olefins and internal olefins. Illustrative prochiral and chiral olefins useful in the processes of this invention include tiiose represented by die formula:
  • R protest R j , R 3 , and « are die same or different (provided Rj is different from Rj and R 3 is different from R and are selected from hydrogen; alkyl; substituted alkyl, said substitution being selected from amino including alkylamino and dialkylamino, such as benzylamino and dibenzylamino, hydroxy, alkoxy, such as methoxy and ethoxy, acyloxy, such as acetoxy, halo, nitro, nitrile, thio, carbonyl, carboxamide, carboxaldehyde, carboxyl, carboxylic ester; aryl including phenyl; substituted aryl including phenyl, said substitution being selected from alkyl, amino including alkylamino and dialkylamino such as benzylamino and dibenzylamino, hydroxy, alkoxy such as methoxy and etiioxy, acyloxy such as acetoxy, halo, nit
  • prochiral and chiral olefins of this definition also include molecules of die above general formula where the R-groups are connected to form ring compounds, e.g., 3-med ⁇ yl-l-cyclohexene, and the like.
  • Illustrative epoxide starting material reactants useful in certain of the asymmetric syntheses processes of this invention, e.g., hydroformylation, include those represented by die formula: R.
  • R s , R ⁇ R 7 , and R g are die same or different (provided R 5 is different from R* and/or R, is different from R 8 ) and are selected from hydrogen, monovalent aliphatic or aromatic groups containing one to about twelve carbon atoms, and divalent aliphatic groups containing four to about six carbon atoms in which any permissible combination of R 5 , Re, R-i, and Riker may be linked together to form a substituted or unsubstituted, carboxylic or heterocyclic ring system such as a monocyclic aromatic or nonaromatic ring system, e.g., cyclohexene oxide.
  • epoxides examples include propylene oxide, 1,2-epoxyoctane, cyclohexene oxide, styrene oxide, and d e like.
  • the catalyst useful in this part of the invention is the optically pure metal-ligand complex catalyst characterized structurally, in general, by formula (I) as follows:
  • M and M' can be die same or different, and each is a Group VIII metal of the Periodic Table of die Elements (E_H. Sargent & Co. Scientific Laboratory Equipment, Copyright 1962) preferably a metal selected from the group consisting of rhodium, rudienium, cobalt, iron, and palladium, or a Group IB metal, preferably copper, X is selected from the group consisting of metiiylene, substituted memylene CR !
  • R 1 and R 2 can be die same or different and each consists of a hydrocarbon moiety which can be saturated or unsaturated and which contains up to twenty carbon atoms and is a C, to C 5 alkyl (e.g., methyl, ediyl, n-butyl), C-.
  • alkyenyl e.g., vinyl, allyl, 1-butenyl
  • C, to C 5 alkoxy e.g., medioxy, ethoxy, butoxy
  • C, to C-a, alcohol e.g., -CH 2 OH, -C ⁇ 2 CH 2 O ⁇
  • C 3 to C 6 cycloalkyl e.g., cyclopropyl, cyclophentyl
  • C 3 to C 6 cycloalkoxy e.g., cyclopropoxy, cyclopentoxy
  • C 10 aryl e.g., phenyl, naphthyl
  • C 6 to C 10 alkaryl e.g., tolyl, xylyl
  • C, 0 aralkyl e.g., benzyl, betaphenylediyl
  • X is methylene, oxygen, NR 3 where R 3 is a hydrocarbon moiety which can be saturated or unsaturated
  • X is methylene
  • Y is an ediyl, propyl, or metasubstituted aryl linkage with hydrogen, F, or methyl substituents, and preferably Y is an ediyl group
  • R is a hydrocarbon moiety which can be saturated or unsaturated and which contains up to twenty carbon atoms and is a C, to C
  • the ligands L and ____.' attached to each of die metal atoms, M and M', can be die same or different and can be H, CO, alkenes, alkyls, or other related ligands present initially in die catalyst precursor.
  • the precursor catalyst in non-isomer form, may be prepared by the disclosure set forth in die earlier part of this specification.
  • the amount of optically pure complex catalyst present in the reaction medium of a given process of tiiis invention need only be that minimum amount necessary to provide d e given metal concentration desired to be employed and which will furnish the basis for at least that catalytic amount of metal necessary to catalyze the particular asymmetric syntheses process desired.
  • metal concentrations in die range of from about 1 ppm to about 10,000 ppm, calculated as free metal, and ligand to metal mole ratios in die catalyst ranging from about 0.5:1 to about 200:1, should be sufficient for most asymmetric syntheses processes.
  • rhodium catalyzed asymmetric hydroformylation processes of this invention it is generally preferred to employ from about 10 to 1000 ppm of rhodium and more preferably from 25 to 750 ppm of rhodium, calculated as free metal.
  • the process conditions employable in the asymmetric processes of this invention are, of course, chosen depending on die particular asymmetric syntheses desired. Such process conditions are well known in the art. All of the asymmetric syntheses processes of this invention can be carried out in accordance witii conventional procedures known in the art. Illustrative reaction conditions for conducting the asymmetric syntheses processes of this invention are described, for example, in Bosnich, B., Asymmetric Catalysis, Martinus Nijhoff Publishers, 1986 and Morrison, James D., Asymmetric Synthesis, Vol. 5, Chiral Catalysis, Academic Press, Inc., 1985, bodi of which are incorporated herein by reference in their entirety.
  • operating temperatures can range from about -80°C or less to about 500°C or greater and operating pressures can range from about 1 psia or less to about 10,000 psia or greater.
  • the reaction conditions of effecting, for example, the asymmetric hydroformylation process of this invention may be those heretofore conventionally used and may comprise a reaction temperature of from about -25°C or lower to about 200°C and pressures ranging from about 1 to 10,000 psia.
  • asymmetric syntheses process is the hydroformylation of olefinically unsaturated compounds and more preferably olefinic hydrocarbon, witii carbon monoxide and hydrogen to produce optically active aldehydes
  • tiiat the optically active metal-ligand complexes may be employed as catalysts in otiier types of asymmetric syndieses processes to obtain good results.
  • otiier asymmetric syndieses may be performed under their usual conditions, in general it is believed tiiat they may be performed at lower temperatures than normally preferred due to d e optically pure metal-ligand complex catalysts.
  • the total gas pressure of hydrogen, carbon monoxide, and, for example, olefinic unsaturated starting compound of one asymmetric (hydroformylation) process of this invention may range from about 1 to about 10,000 psia. More preferably, however, in the asymmetric hydroformylation of prochiral olefins to produce optically active aldehydes, it is preferred tiiat the process be operated at a total gas pressure of hydrogen, carbon monoxide, and olefinic unsaturated starting compound of less tiian about 1500 psia, and more preferably less than about 1000 psia.
  • the minimum total pressure of the reactants is not particularly critical and is limited predominately only by die amount of reactants necessary to obtain a desired rate of reaction. More specifically, the carbon monoxide partial pressure of the asymmetric hydroformylation process is preferably from about 1 to about 360 psia, and more preferably from about 3 to about 270 psia, while die hydrogen partial pressure is preferably about 15 to about 480 psia and more preferably from about 30 to about 300 psia.
  • the molar ratio of gaseous hydrogen to carbon monoxide may range from about 1:10 to 100:1 or higher, the more preferred hydrogen to carbon monoxide molar ratio being from about 1:1 to about 1:10. Higher molar ratios of carbon monoxide to gaseous hydrogen may generally tend to favor higher branched/normal ratios.
  • the processes of this invention may be conducted at a reaction temperature from about -25°C or lower to about 200°C.
  • the preferred reaction temperature employed in a given process will, of course, be dependent upon die particular starting material and optically pure metal-ligand complex catalyst employed as well as die efficiency desired. Lower reaction temperatures may generally tend to favor higher enantiomeric excesses (ee) and branched normal ratios. For example, asymmetric hydroformylations at reaction temperatures of about 0°C to about 120°C are preferred for all types of olefinic starting materials.
  • alpha-olefins can be effectively hydroformylated at a temperature of from about 0°C to about 90°C while even less reactive olefins than conventional linear alpha-olefins and internal olefins, as well as mixtures of alpha-olefins and internal olefins, are effectively and preferably hydroformylated at a temperature of from about 25°C to about 120°C.
  • the processes are conducted for a period of time sufficient to produce die optically active products. The exact reaction time employed is dependent in part, upon factors such as temperature, nature, and proportion of starting materials, and die like.
  • the reaction time will normally be within the range of from about one-half to about 200 hours or more, and preferably from less than about one to ten hours.
  • the asymmetric syntheses process (for example, asymmetric hydroformylation process) of this invention can be carried out in either the liquid or gaseous state and involve a batch, continuous liquid or gas recycle system, or combination of such systems. A batch system is preferred for conducting die processes of this invention.
  • asymmetric hydroformylation of this invention involves a batch homogeneous catalysis process wherein the hydroformylation is carried out in the presence of any suitable conventional solvent as further outlined herein.
  • suitable organic solvents include, for example, alcohols, alkanes, alkenes, alkynes, ethers, aldehydes, ketones, esters, acids, amides, amines, aromatics, and die like. Any suitable solvent which does not unduly adversely interfere with the intended asymmetric syndieses process can be employed and such solvents may include tiiose heretofore commonly employed in known metal catalyzed processes. Increasing the dielectric constant or polarity of a solvent may generally tend to favor increased reaction rates. Mixtures of one or more different solvents may be employed if desired.
  • the amount of solvent employed is not critical to the subject invention and need only be tiiat amount sufficient to provide die reaction medium with the particular metal concentration desired for a given process.
  • the amount of solvent when employed may range from about five percent by weight up to about ninety-five percent by weight or more, based on d e total weight of the reaction medium.
  • optically active compounds prepared by the processes of this invention include, for example, substituted and unsubstituted alcohols or phenols; amines; amides; ethers or epoxides; esters; carboxylic acids or anhydrides; ketones; olefins; acetylenes; halides or sulfonates; aldehydes; nitrites; and hydrocarbons.
  • Illustrative preferred optically active aldehyde compounds prepared by the asymmetric hydroformylation process of this invention include, for example, S-2-(p- isobutylphenyl)propionaldehyde, S-2-(6-methoxynaphthyl)propionaldehyde, S-2-(3- b ⁇ nzoylphenyl)propionaldehyde, S-2-(p-thenoylphenyl)propionadenhyde, S-2-(3-fluoro-4- phenyl)phenylpropionaldehyde, S-2-[4-(l,3-dihydro-l-oxo-2H-isoindol-2-yl)phenyl]- propionaldehyde, S-2-(2-methylacetaldehyde)-5-benzoylthiophene, and die like.
  • the processes of this invention can provide optically active products having very high enantioselectivity and regioselectivity, e.g., hydroformylation.
  • Enantiomeric excesses (sometimes referred to herein as "ee") of preferably greater than fifty percent, more preferably greater than 75 percent, and most preferably greater than ninety percent can be obtained by die processes of this invention.
  • Branched/normal molar ratios of preferably greater than 5:1, more preferably greater than 10:1, and most preferably greater than 25:1 can be obtained by the processes, e.g., hydroformylation, of this invention.
  • the processes of this invention can also be carried out at highly desirable reaction rates suitable for commercial use.
  • the desired optically active products may be recovered in any conventional manner. Suitable separation techniques include, for example, solvent extraction, crystallization, distillation, vaporization, wiped film evaporation, falling film evaporation, and the like. It may be desired to remove the optically active products from the reaction system as they are formed through the use of trapping agents as described in WO patent 88/08835.
  • optically active products produced by die asymmetric syntheses processes of this invention can undergo further reaction(s) to afford desired derivatives thereof.
  • Such permissible derivatization reactions can be carried out in accordance with conventional procedures known in the art
  • Illustrative derivatization reactions include, for example, esterification, oxidation of alcohols to aldehydes, N-alkylation of amides, addition of aldehydes to amides, nitrile reduction, acylation of ketones by esters, acylation of amines, and the like.
  • illustrative derivatization reactions include, for example, oxidation to carboxylic acids, reduction to alcohols, aldol condensation to alpha, beta-unsaturated compounds, reductive amination to amines, amination to imines, and d e like. This invention is not intended to be limited in any manner by the permissible derivatization reactions.
  • An example of a derivatization reaction involves oxidation of an optically active aldehyde prepared by asymmetric hydroformylation to give the corresponding optically active carboxylic acid.
  • Such oxidation reactions can be carried out by conventional procedures known in the art
  • a number of important pharmaceutical compounds can be prepared by this process including, but not limited to, S-ibuprofen, S-naproxen, S-ketoprofen, S-suprofen, S-flurbiprofen, S-indoprofen, S-tiaprofenic acid, and the like.
  • Illustrative preferred derivatization, i.e. oxidation reactions encompassed within the scope of this invention include, for example, the following reactant/aldehyde intermediate/product combinations:
  • Suitable optically active products prepared by the asymmetric syntheses processes of this invention include by way of example: AL alcohols
  • the processes of this invention can be conducted in a batch or continuous fashion, with recycle of unconsumed starting materials if required.
  • the reaction can be conducted in a single reaction zone or in a plurality of reaction zones, in series, or in parallel, or it may be conducted batchwise or continuously in an elongated tubular zone or series of such zones.
  • the materials of construction employed should be inert to the starting materials during the reaction and the fabrication of the equipment should be able to withstand die reaction temperatures and pressures.
  • Means to introduce and/or adjust the quantity of starting materials or ingredients introduced batchwise or continuously into the reaction zone during the course of the reaction can be conveniently utilized in the processes especially to maintain the desired molar ratio of the starting materials.
  • reaction steps may be effected by die incremental addition of one of the starting materials to the otiier. Also, the reaction steps can be combined by die joint addition of the starting materials to the optically pure metal-ligand complex catalyst. When complete conversion is not desired or not obtainable, the starting materials can be separated from the product and then recycled back into the reaction zone.
  • the processes may be conducted in either glass lined, stainless steel or similar type reaction equipment.
  • the reaction zone may be fitted with one or more internal and/or external heat exchanger(s) in order to control undue temperature fluctuations, or to prevent any possible "runaway" reaction temperatures.
  • d e optically active products of the process of this invention have a wide range of utility that is well known and documented in die prior art, e.g. they are especially useful as pharmaceuticals, flavors, fragrances, agricultural chemicals, and die like.
  • Illustrative therapeutic applications include, for example, non-steroidal anti-inflammatory drugs, ACE inhibitors, beta-blockers, analgesics, bronchodilators, spasmolytics, antihistamines, antibiotics, antitumor agents, and d e like.
  • Achiral molecules or processes which do not include or involve at least one center of asymmetry are symmetrical molecules or processes which do not include or involve at least one center of asymmetry.
  • Prochiral molecules which have the potential to be converted to a chiral product in a particular process.
  • Racemic a 50/50 mixture of two (2) enantiomers of a chiral compound Racemic a 50/50 mixture of two (2) enantiomers of a chiral compound.
  • Stereoisomers compounds which have identical chemical construction, but differ as regards the arrangement of the atoms or groups in space.
  • Enantiomeric a measure of the relative amounts of two (2) Excess (ee) enantiomers present in a product, ee may be calculated by die formula [amount of major enantiomer - amount of minor enantiomer]/[ amount of major enantiomer + amount of minor enantiomer].
  • Optical Activity an indirect measurement of the relative amounts of stereoisomers present in a given product. Chiral compounds have die ability to rotate plane polarized light When one enantiomer is present in excess over the other, the mixture is optically active.
  • Optically Active a mixture of stereoisomers which rotates plane polarized light due to an excess of one of die stereoisomers over the others.
  • (+)-Rh 2 (nbd) 2 (et,ph-P4> SS form of the general formula I compound where nbd is norbomadiene and is for a symmetrical ligand.
  • (+)-Rh 2 (n 3 -allyl) 2 SS form of the general formula I compound where it
  • (etph-P4) is an allyl anion racemic-Rh ⁇ -allyl ⁇ racemate form of the general formula I compound (etph-P4) where it is an allyl anion
  • hydrocarbon is contemplated to include all permissible compounds having at least one hydrogen and one carbon atom.
  • die permissible hydrocarbons include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic organic compounds which can be substituted or unsubstituted.
  • the term "substituted" is contemplated to include all permissible substituents of organic compounds.
  • the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic substituents of organic compounds.
  • Illustrative substituents include, for example, those described hereinabove.
  • the permissible substituents can be one or more and die same or different for appropriate organic compounds.
  • the heteroatoms such as nitrogen may have hydrogen substituents and/or any permissible substituents of organic compounds described herein which satisfy the valencies of the heteroatoms.
  • This invention is not intended to be limited in any manner by the permissible substituents of organic compounds.
  • the following procedures were utilized to prepare the RR and SS enantiomers from the racemic form of the ligands, described in die earlier part of this specification, and also the SS or RR catalyst form, i.e. the optically pure catalyst, herein described.
  • HPLC column 250mm x 20 mm that employs cellulose tris-(3,5- dimemylphenylcarbamate) coated onto 10 um silica gel as a stationary phase.
  • the mobile phase was filtered through a 0.45 um membrane filter and then purged with argon for "20 minutes. Solutions of " 100 mg/ml of the ligand were prepared in d e glovebox and filtered through a 0.45 um membrane filter.
  • a volume of " 500 uL of the ligand solution was injected onto the column.
  • the two enantiomers were resolved with retention times of 13.2 minutes and 14.8 minutes respectively.
  • the first enantiomer is (+)-et,ph-P4, while the second is (-)-et,ph-P4 (determined by polarimetry).
  • the eluted compounds were collected in separate Schlenk flasks under a continuous purge of nitrogen. The flasks were taken into the glovebox where the solvent was removed under reduced pressure. Enantiomeric purity of the ligands was confirmed by NMR and polarimetry.
  • the 150 mL Parr autoclave used is equipped with a packless magnetic drive stirring system and designed to introduce die gas mixture through a dip tube directly into the solution. Turbine type impellers are used to obtain optimum solution/gas mixing. Stir rates of 1000 rpm are typically used.
  • the autoclave is also equipped with a pressure transducer for monitoring the pressure of the autoclave and a thermocouple for determining the temperature of the reaction mixture in the autoclave.
  • (+)-Rh 2 (a_lyl) 2 ((+)-etph-P4)(0.019 g, 0.0253 mmol) was dissolved in 80 ml of acetone in the autoclave in a glove box.
  • the autoclave is closed and removed from the glove box.
  • the autoclave is connected to die high pressure synthesis gas line.
  • the transfer lines and die olefin addition cylinder are evacuated to remove all oxygen.
  • HBF 4 0.16 g of a one percent ether solution, 0.05 mmol
  • 10 ml of acetone is added to the addition cylinder.
  • Syntiiesis gas (1:1 mixture of __ and CO) is introduced into d e autoclave and bubbled through the autoclave to displace the N 2 present.
  • the pressure is adjusted to 45 psi and die stirring begins at 1000 rpm at room temperature for 10 minutes.
  • the pressure inside die addition cylinder is adjusted to 90 psi to force the HBF 4 solution into the autoclave.
  • Begin temperature ramp to 90°C and the pressure inside autoclave is adjusted to 45 psi.
  • the addition cylinder and die transfer lines are reevacuated for 15 minutes.
  • Vinyl acetate (5 ml, 54 mmol, diluted to 10 ml volume with acetone) was added to the addition cylinder and die pressure inside die cylinder is adjusted to 90 psi.
  • die autoclave When die autoclave reaches 90°C, the pressure inside die autoclave is adjusted to 45 psi and the olefin is added. A small aliquot (1 ml) of the reaction solution is then removed for GC analysis (initial sample). The pressure is adjusted to 90 psi and die data logger is turned on. Samples of die reaction solution are typically taken for product analysis at regular intervals throughout the runs that are usually left to run for six to twenty hours.
  • Rate data was obtained by monitoring the decrease in pressure of a 0.3 liter reservoir cylinder tiiat contained approximately 750 psi of H--/CO that was delivered to die autoclave at constant pressure by a two-stage gas regulator.
  • the pressure of the reservoir cylinder was constantly monitored by an electronic pressure transducer.
  • the reservoir pressure and temperature, autoclave temperature, and stir rate data are collected and stored on a Parr 4851 controller and die data transferred at die end of die reaction to a PC computer for permanent storage and for calculating reaction rates.
  • Analysis of products was performed by GC and NMR. Analyses of the product mixtures showed tiiat vinyl acetate was very cleanly hydroformylated to die branched and linear aldehydes in a 4:1 branched to linear ratio.
  • Synthesis gas (1:1 mixture of H ⁇ and CO) is introduced into die autoclave and bubbled through the autoclave to displace the N 2 present.
  • the pressure is adjusted to 45 psi and die stirring begins at 1000 rpm at room temperature for 10 minutes.
  • the pressure inside die addition cylinder is adjusted to 90 psi to force the HBF 4 solution into the autoclave.
  • Begin temperature ramp to 90°C and die pressure inside autoclave is adjusted to 45 psi.
  • the addition cylinder and the transfer lines are reevacuated for 15 minutes.
  • Vinyl propionate (5.319 g, 53 mmol, diluted to 10 ml volume with acetone) was added to die addition cylinder and the pressure inside die cylinder is adjusted to 90 psi.
  • die autoclave When die autoclave reaches 90°C, the pressure inside die autoclave is adjusted to 45 psi and die olefin is added. A small aliquot (1 ml) of the reaction solution is then removed for GC analysis (initial sample). The pressure is adjusted to 90 psi and die data logger is turned on. Samples of the reaction solution are typically taken for product analysis at regular intervals throughout the runs that are usually left to run for 6 to 20 hours.
  • a catalyst solution is prepared as in Example 4 except tiiat it contains para-isobutyl styrene. This solution is charged to a 100 ml rector and is charged to a pressure of 67 psi with hydrogen gas and to 200 psi with CO. The rate of the reaction is determined by monitoring the drop in pressure as die synthesis gas is consumed. Reaction rate is approximately 0.1 g-mole/liter/hour. When the rate has slowed due to consumption of the styrene starting material, the reaction mixture is removed from die reactor under a nitrogen atmosphere. A portion of the reaction mixture is analyzed by gas chromatography to determine product composition. An isomer ratio of 66:1 (2-(4-isobutyl)phenyl-propionaldehyde:3-(4- isobutyl)phenyl-propionaldehyde) is observed.
  • Three ml of the solution is diluted in 50 ml acetone and is treated with 0.3 g potassium permanganate and 0.32 g magnesium sulfate to effect oxidation of the product aldehydes to tiieir respective acids.
  • the mixture is stirred at room temperature for 30 minutes after which time the solvent is removed under reduced pressure.
  • the residue is extracted 3 times with 50 ml of hot water.
  • the three aqueous solutions are then combined, filtered, and washed with 50 ml chloroform.
  • the aqueous layer is then acidified with HC1 to a pH of 2.0 and then is extracted with 50 ml of chloroform.
  • a catalyst solution is prepared as in Example 4 except that it contains 5 g methoxyvinylnaphthalene and 24.5 g acetone. This solution is charged to a 100 ml reactor and is charged to a pressure of 40 psi witii hydrogen gas and 200 psi with CO. The rate of die reaction is determined by monitoring die drop in pressure as synthesis gas is consumed. Reaction rate is approximately 0.1 g-mole/liter/hour. When the rate has slowed due to consumption of the styrene starting material, the reaction mixture is removed from die reactor under a nitrogen atmosphere.
  • reaction mixture A portion of the reaction mixture is analyzed by GC to determine product composition. An isomer ratio of 80:1 (2-(6-methoxy)-naphthylpropionaldehyde:3-(6- methoxy)naphti ⁇ yl-propionaldehyde) is observed.
  • Three ml of the solution is diluted in 50 ml acetone and is treated with 0.3 g potassium permanganat and 0.32 g magnesium sulfate to effect oxidation of the product aldehydes to tiieir respective acids.
  • the mixture is stirred at room temperature for 30 minutes, after which time the solvent is removed under reduced pressure.
  • the residue is extracted three times with 50 ml of hot water.
  • the three aqueous solutions are then combined, filtered, and washed witii 50 ml chloroform.
  • the aqueous layer is then acidified witii HC1 to a pH of 2.0 and dien is extracted widi 50 ml of chloroform.
  • the chloroform is removed in vacuo and die resulting residue dissolved in 0.5 ml toluene.
  • Example 4 Asymmetric Hydrosilylation of Acetophenone
  • the catalyst (0.020 g) of Example 4 is charged to a 50 ml Schlenk flask under nitrogen. Tetrahydrofuran (THF) (5.0 ml) is added to dissolve die catalyst 0.58 ml of acetophenone and 0.93 ml of diphenylsilane are added to die flask via syringe. The solution is stirred under nitrogen for 18 hours. The solution is treated with 10 ml of 10% hydrochloric acid and is extracted two times with 10 ml of diethyl ether.
  • THF Tetrahydrofuran
  • Example 4 Asymmetric Hydrocyanation of Styrene
  • the catalyst (0.15 g) of Example 4 is charged to a 50 ml Schlenk flask under nitrogen.
  • Deoxygenated THF (10 ml) is added, and die solution is stirred for 30 minutes.
  • 2.0 ml of styrene and 2.00 ml of acetone cyanohydrin are added to the flask via syringe.
  • the solution is stirred for 24 hours at 25°C.
  • Example 4 The catalyst (0.046 g) of Example 4 is charged to a 50 ml Schlenk flask under nitrogen. Deoxygenated THF (5.0 ml) is added, and die solution is stirred under nitrogen for 30 minutes. 0.500 g of norbomene and 1.00 ml of acetone cyanohydrin are added to the flask via syringe. The solution is refluxed under nitrogen for five hours.
  • This reaction mixture is analyzed by GC on a Chiraldex B-PH column which can separate the two enantiomers of the resulting 2-norbornane carbonitrile. Only a single regioisomer of 2-norbornane carbonitrile is observed by this analysis. This analysis indicates a 75:25 ratio of the enantiomers for an ee (enantiomeric excess) of 50%.
  • Example 4 The catalyst (0.173 g) of Example 4 is charged to a 50 ml Schlenk flask under nitrogen. Deoxygenated THF (10 ml) is added and the solution is stitred for 30 minutes. 2.0 ml of styrene and 2.00 ml of acetone cyanohydrin are added to die flask via syringe. The solution is stitred for 24 hours at 25°C.
  • This reaction mixture is analyzed by gas chromatography on a Chiraldex B-PH column which can separate the two enantiomers of the resulting sec-phenylethyl alcohol. This analysis indicates a 60:40 ratio of die S and R enantiomers for an ee (enantiomeric excess) of 20%.
  • EXAMPLE 13 Asymmetric Hydrogenation of Itaconic Acid
  • a catalyst solution is prepared as in Example 4 except acetone is replaced witii 10 ml of tetrahydrofuran.
  • the solution is charged to a 100 ml reactor and is heated to 35°C.
  • the reactor is pressurized to 100 psi with hydrogen and is stirred for 15 minutes.
  • the reactor is vented, and a solution of 0.50 g of itaconic acid and 5 ml of tetrahydrofuran is added to the reactor.
  • the reactor is pressurized witii 1000 psi of hydrogen and stirred for two hours.
  • reaction mixture is analyzed by GC on a Chiraldex B-PH column which can separate the two enantiomers of the resulting 2-methylsuccinate. This analysis indicates a 60:40 ratio of the enantiomers for an ee (enantiomeric excess) of 20%.
  • EXAMPLE 14 Asymmetric Hydroboration of Styrene
  • the catalyst (0.050 g) of Example 4, excluding acetone, is charged to a 50 ml Schlenk flask under nitrogen.
  • Distilled 1,2-dimed ⁇ oxyed ⁇ ane (2.0 ml) is added to die flask.
  • 0.23 ml of styrene and 0.23 ml of catecholborane are added to die flask via syringe.
  • the solution is stirred under nitrogen for two hours.
  • the solution is treated witii 4 ml of metiianol, 4.8 ml of 3.0 mol/liter sodium hydroxide solution and 0.52 ml of 30% hydrogen peroxide.
  • the solution is stirred for three hours and is extracted with 10 ml of diethyl ether. A portion of this solution is analyzed by GC to determine product composition. An isomer ratio of 3:1 (sec-phenethyl alcohol:2-phenylethanol) is observed. A second portion of this solution is analyzed by GC on a Chiraldex B-PH column which can separate the two enantiomers of the resulting sec-phenethyl alcohol. This analysis indicates a 61:39 ratio of the S and R enantiomers for an ee (enantiomeric excess) of 22%.
  • EXAMPLE 15 Asymmetric Cyclopropanation of Styrene
  • the catalyst (0.085 g) of Example 4 is charged to a 25 ml Schlenk flask under nitrogen.
  • Toluene (5.0 ml) is added to the flask under nitrogen.
  • 0.10 ml of triethylamine is added to die flask via syringe, and die solution is stirred under nitrogen for 15 minutes.
  • 5.0 ml of styrene is added by syringe followed by 0.250 ml of ethyldiazoacetate. The solution is stirred under nitrogen for two hours.
  • reaction mixture A portion of the reaction mixture is analyzed by GC to determine product composition. An isomer ratio of 2.1:1 (transxis) is observed for die product cyclopropanes. A second portion of this solution is analyzed by gas chromatography on a Chiraldex B-PH column which can separate the two enantiomers of the resulting cis-ethyl- 2-phenylcyclopropanecarboxylate. This analysis indicates a 63:37 ratio of the cis cyclopropane enantiomers for an ee (enantiomeric excess) of 26%.
  • Example 4 The catalyst (0.050 g) of Example 4 is charged to a 50 ml Schlenk flask under nitrogen. Toluene (5.0 ml) is added to die flask. 0.55 ml of styrene and 0.55 ml of trichlorosilane are added to the solution via syringe, and die solution is stirred under nitrogen for 24 hours. A portion of the reaction mixture is analyzed by GC to determine die product composition. Only a single regioisomer, 2-trichlorosilylethylbenzene, is observed.
  • reaction mixture is concentrated to an oil under vacuum and is dissolved in 5.0 ml of absolute ethanol. 1.0 ml of triethylamine is added to the solution. This solution is analyzed by GC on a Chiraldex B-PH column which can separate the two enantiomers of the resulting 2-triethoxysilylethylbenzene- This analysis indicates a 65:35 ratio of the enantiomers for an ee (enantiomeric excess) of 26%.
  • Example 4 The catalyst (0.050 g) of Example 4 is charged to a 50 ml Schlenk flask under nitrogen. Dichloromethane (2.0 ml) is added to die flask under nitrogen. 0.20 ml of benzaldehyde and 0.40 ml of methyl trimethylsilyl dimetiiylketene acetal is added to the flask via syringe. The solution is stirred under nitrogen for 18 hours. The solution is treated witii 10 ml of 10% hydrochloric acid and is extracted two times with 10 ml of diethyl ether.
  • EXAMPLE 18 Asymmetric Hydroformylation of Vinyl Benzoate (+)-Rh 2 (allyl) 2 (et,ph-P4)(0.020 g, 0.0266 mmol) was dissolved in 70 ml of acetone in the autoclave in a glovebox. The autoclave is closed and removed from the glovebox. The autoclave is connected to die high pressure synthesis gas line. The transfer lines and die olefin addition cylinder are evacuated to remove all oxygen. HBF 4 (0.816 g of a 1% ether solution, 0.05 mmol) in 10 ml of acetone is added to die addition cylinder.
  • Synthesis gas (1:1 mixture of H 2 and CO) is introduced into the autoclave and bubbled through the autoclave to displace die N 2 present.
  • the pressure is adjusted to 45 psi and die stirring begins at 1000 rpm at room temperature for 10 minutes.
  • the pressure inside die addition cylinder is adjusted to 90 psi to force the HBF 4 solution into the autoclave.
  • Begin temperature ramp to 90°C and die pressure inside autoclave is adjusted to 45 psi.
  • the addition cylinder and die transfer lines are reevacuated for 15 minutes.
  • Vinyl benzoate (7.900 g, 53.3 mmol, diluted to 10 mL volume with acetone) was added to die addition cylinder and die pressure inside the cylinder is adjusted to 90 psi.
  • the pressure inside die autoclave is adjusted to 45 psi and die olefin is added.
  • a small aliquot (1 ml) of the reaction solution is then removed for GC analysis (initial sample).
  • the pressure is adjusted to 90 psi and die data logger is turned on. Samples of the reaction solution are typically taken for product analysis at regular intervals throughout the runs that are usually left to run for 6 to 24 hours.

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Abstract

L'invention concerne de nouveaux catalyseurs homogènes bimétalliques d'hydroformylation et des procédés utilisant ces catalyseurs pour convertir dans des conditions douces des alcènes, en particulier des alpha-oléfines, en produits riches en aldéhydes, en particulier en un produit présentant un rapport élevé entre aldéhydes linéaires et aldéhydes ramifiées. Les catalyseurs peuvent être produits à partir d'un ligand de binucléation qui est une tétraphosphine tertiaire capable d'une forte liaison de coordination avec deux centres métalliques pour les tenir globalement proches l'un de l'autre. On produit des précurseurs des catalyseurs bimétalliques, qui, par réaction avec l'oxyde de carbone et l'hydrogène, forment un système catalyseur bimétallique actif pour les réactions d'hydroformylation. Cette invention concerne également une synthèse asymétrique dans laquelle un composé prochiral ou chiral est mis en contact, en présence d'un catalyseur qui est un complexe optiquement pur métal-ligand, sous la forme d'un énantiomère, pour fournir un produit optiquement actif.
PCT/US1994/000262 1993-03-09 1994-01-07 Catalyseurs homogenes bimetalliques d'hydroformylation, et procedes utilisant ces catalyseurs pour mener des reactions d'hydroformylation WO1994020510A1 (fr)

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EP94907166A EP0673381A4 (fr) 1993-03-09 1994-01-07 Catalyseurs homogenes bimetalliques d'hydroformylation, et procedes utilisant ces catalyseurs pour mener des reactions d'hydroformylation.
AU60847/94A AU6084794A (en) 1993-03-09 1994-01-07 Homogeneous bimetallic hydroformylation catalysts and processes utilizing these catalysts for conducting hydroformylation reactions

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6756411B2 (en) 1995-06-29 2004-06-29 Sasol Technology (Proprietary) Limited Process for producing oxygenated products
EP2516373B1 (fr) 2009-12-22 2016-09-21 Dow Technology Investments LLC Réglage du rapport aldéhyde normal:aldéhyde iso dans un procédé d'hydroformylation à ligand mixte
WO2019237090A1 (fr) * 2018-06-08 2019-12-12 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Compositions de catalyseur d'hydroformylation et leurs méthodes d'utilisation

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US3939188A (en) * 1972-03-24 1976-02-17 Exxon Research And Engineering Company Preparation of zerovalent phosphine substituted rhodium compounds and their use in the selective carbonylation of olefins
US4987242A (en) * 1988-10-28 1991-01-22 Jagmohan Khanna Hydrogenation catalyst useful in the production of alpha-6-deoxytetracyclines
US5200539A (en) * 1990-08-27 1993-04-06 Louisiana State University Board Of Supervisors, A Governing Body Of Louisiana State University Agricultural And Mechanical College Homogeneous bimetallic hydroformylation catalysts, and processes utilizing these catalysts for conducting hydroformylation reactions

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Publication number Priority date Publication date Assignee Title
US3939188A (en) * 1972-03-24 1976-02-17 Exxon Research And Engineering Company Preparation of zerovalent phosphine substituted rhodium compounds and their use in the selective carbonylation of olefins
US4987242A (en) * 1988-10-28 1991-01-22 Jagmohan Khanna Hydrogenation catalyst useful in the production of alpha-6-deoxytetracyclines
US5200539A (en) * 1990-08-27 1993-04-06 Louisiana State University Board Of Supervisors, A Governing Body Of Louisiana State University Agricultural And Mechanical College Homogeneous bimetallic hydroformylation catalysts, and processes utilizing these catalysts for conducting hydroformylation reactions

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Inorganic Chemistry, Volume 2,8, No. 10, issued October 1989, S.A. LANEMAN et al., "Synthesis of a Binucleating Tetratetiary Phosphine Ligand System and the Structural Characterization of both Meso and Racemic Diasteremers of N12C(eLTTP) (eLTTP= (E+2PCH2CH2)(PH)PCH2P(PH)(CH2CH2PET2))", see page 1872. *
See also references of EP0673381A4 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6756411B2 (en) 1995-06-29 2004-06-29 Sasol Technology (Proprietary) Limited Process for producing oxygenated products
EP2516373B1 (fr) 2009-12-22 2016-09-21 Dow Technology Investments LLC Réglage du rapport aldéhyde normal:aldéhyde iso dans un procédé d'hydroformylation à ligand mixte
EP2516373B2 (fr) † 2009-12-22 2020-08-12 Dow Technology Investments LLC Réglage du rapport aldéhyde normal:aldéhyde iso dans un procédé d'hydroformylation à ligand mixte
WO2019237090A1 (fr) * 2018-06-08 2019-12-12 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Compositions de catalyseur d'hydroformylation et leurs méthodes d'utilisation

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