Hydroformylation.asymmetric

Asymmetric Hydroformylation.—A-Vinylimides [e.g., (10)] have been hydro-formylated in up to 41 % e.e. with excellent selectivities to the desired branched isomers in the presence of [RhH(CO)(PPh3)3] + L2 [La=chiral biphosphine, e.g. (-)-diop or (Ic)]. In contrast, linear disubstituted iV-vinylimides or -amides [e.g., (11)] reacted sluggishly and (12), although reactive, gave 1% e.e. Asymmetric hydrocarboxylation of these substrates in the presence of [PdClg-(PPhs)2]+La produced a-amido esters in 1% e.e.  

Sheludyakov, V. A. Golodov, and D. V. Sokol skii, Dokl. Akad. Nauk. SSSR, 

Hetorogenized Catalysts.—Reaction of [Ru(NH3)60H] + with a Faujasite-type zeolite gives a supported Ru complex, which effects hydroformylation of ethylene the catalytic species may be ruthenium clusters that are trapped in the zeolite cages. The effect of reaction conditions upon the selectivity of the hydroformylation of methyl methacrylate with [RhH(CO)(PPh3)3] or its polymer-anchored analogue has been investigated and hydroformylation of hex-l-ene and cyclo-octa-1,5-diene has been carried out with cobalt, rhodium, and platinum-tin complexes anchored to an ion-exchange resin via quaternary amino-phosphines.  

Asymmetric hydroformylation allows the conversion of olefins into optically active aldehydes in a single step. From the point of view of synthesis of optically active pharmaceutical intermediates and fine chemicals, this reaction is of considerable interest. As shown by reactions 5.4.1 and 5.4.2, hydroformylations of 1,2- and 1,1-disubsti-tuted alkenes can lead to the formation of four possible stereoisomers. To be useful, asymmetric hydroformylation must therefore be both regio- and enantioselective. 

Considerable progress has been made toward the development of catalytic asymmetric hydroformylation reactions. The most successful catalytic systems involve chelating phosphorous ligands in combination with Rh-based precatalysts. Structures of the two most effective chiral ligands are shown by 5.48 and 5.49. 

The regio- and enantioselectivities in asymmetric hydroformylation reactions depend both on the structure of the alkene and the chiral ligand, and no single ligand performs equally well for all alkenes. 

The ligand (R,S)-BINAPHOS, 5.48, is very effective for mono- and 1,1-disubstituted alkenes. Thus, as shown by reaction 5.4.3, a catalytic system based on RhfCOl Cacac) and 5.48 hydroformylates styrene with high regio- and enantioselectivity. However, for 1,2-disubstituted alkenes, the ligand 5.49 gives much better results. 

In this chapter we will concentrate on the asymmetric hydroformylation of vinyl aromatics, which are model substrates of interest to the pharmaceutical industry [ 1]. In 1993 and 1995 some reports were published which described the state of the art in hydroformylation with both rhodium and platinum systems [2, 3]. A report about carbonylation appeared in 1999 [4]. 

Highly enantioselective hydroformylation catalyzed by chiral metal complexes has been obtained with oidy a few catalytic systems. Many chiral phosphorus ligands have been used in Pt(II) and Rh(I) systems in the asymmetric hydroformylation of styrene. The first highly enantioselective examples of asymmetric hydroformylation of styrene were reported by Consiglio et al. in 1991 and used Pt-Sn systems [5, 6]. They achieved an ee of 86%. Platinum catalysts have several disadvantages they have low reaction rates, they hydrogenate the substrate and their regioselectivity to the 

Modified Rh systems show considerable activity in the hydroformylation of styrene to the branched aldehydes. Chiral diphosphine rhodium complexes that lead to high activity and high regioselectivity in branched aldehyde have been studied. These systems do not provide high enantioselectivity [2, 3]. Stanley reported that a tetraphosphine hgand can be used to form a bimetallic complex [8] and provide ee s up to 85% using vinyl esters. 

The catalyst discovered by Takaya et al. using (R,S) BINAPHOS, a phosphine-phosphite hgand of Ci symmetry [14] has provided ee s as high as 96% as well as total conversions and high regioselectivities. The origin of the stereodifferentiation in rhodium catalyzed hydroformylation has been discussed in theoretical reports [15, 16]. 

2 Rhodium systems with chiral diphosphite ligands 

A modified 14 with perfluoralkylphenyl groups increased the selectivity up to 96%.280 Both high enantioselectivity (91%) and high regioselectivity (98.8%) were achieved under mild conditions with a new chiral diphosphite ligand derived from D-(+)-glucose.281 

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Considerable advances in asymmetric hydroformylation, a process which, among other things, provides a potential route to enantiomericaHy pure biologically active compounds, have occurred. Of particular interest are preparations of nonsteroidal antiinflammatory (NSAI) pharmaceuticals such as Naproxen (8) and Ibuprofen (9), where the represents a chiral center. 

Styrene, a-ethyl-asymmetric hydroformylation catalysts, platinum complexes, 6, 266 asymmetric hydrogenation catalysts, rhodium complexes, 6, 250 Styrene, a-methyl-asymmetric carbonylation catalysis by palladium complexes, 6, 293 carbonylation... 

Hydroformylation has been extensively studied since it produces optically active aldehydes which could be important precursors for pharmaceutical and fine chemical compounds. Thus, asymmetric hydroformylation of styrene (Scheme 27) is a model reaction for the synthesis of ibuprofen or naproxen. Phosphorus ligands were used for this reaction with excellent results, espe-... 

Some chiral mono-, acyl- and di-thioureas have been used as ligand for the Rh-catalysed asymmetric hydroformylation of styrene. Although thiourea ligands form inactive systems with [Rh(COD)Cl]2 as the catalyst precursor, in standard conditions (40 °C, 40 bar CO -l- H2 1/1), the cationic Rh complex [Rh(COD)2]Bp4 combined with monothioureas as the ligand showed moderate to good activity (Scheme 29) [114]. 

In 1999, Casado et al. developed heterotetranuclear complexes (TiRh3) depicted in Scheme 10.3 with bridging sullido ligands combined with P-donor ligands. These complexes were further tested as catalysts for the asymmetric hydroformylation reaction of styrene. In this process, [CpTi((/i3-S)3 Rh(tfbb 3] was efficiently active under mild conditions (10 bar, CO/H2 = 1 atm, 353 K). In order to explore the effect of the added phosphorus ligand and the possibilities of this system for the asymmetric hydroformylation of styrene, achiral diphosphines such as dppe (l,2-bis(diphenylphosphine)ethane) and... 

The discovery of the bisphospholane scaffold as a new privileged structure for asymmetric induction in alkene hydroformylation has triggered research for new and improved bisphospholane-type ligands. In this context (k,k)-Ph-bpc has been identified as an excellent ligand for asymmetric hydroformylation, which gives state-of-the-art regio- and enantioselectivities... 

The major problem remains control of regioselectivity in favor of the branched regioisomer. While aryl alkenes as well as heteroatom-substituted alkenes favor the chiral branched isomer, for aliphatic alkenes such an intrinsic element of regiocontrol is not available. As a matter of fact branched-selective and asymmetric hydroformylation of aliphatic alkenes stands as an unsolved problem. In this respect regio- and enantioselective hydroformy-... 

The asymmetric hydroformylation of a 1,3-diene has been recently used in the course of a total synthesis of the antifungal natural product ambruticin. The retrosynthesis as well as the hydroformylation key step are depicted in Scheme 25 [75]. 

Although significant progress in the field of asymmetric hydroformylation has been made, it is limited to a rather narrow substrate scope. An alternative approach to a stereoselective hydroformylation might employ substrate control of a chiral alkenic starting material. Of particular use... 

Platinum complexes with chiral phosphorus ligands have been extensively used in asymmetric hydroformylation. In most cases, styrene has been used as the substrate to evaluate the efficiency of the catalyst systems. In addition, styrere was of interest as a model intermediate in the synthesis of arylpropionic acids, a family of anti-inflammatory drugs.308,309 Until 1993 the best enantio-selectivities in asymmetric hydroformylation were provided by platinum complexes, although the activities and regioselectivities were, in many cases, far from the obtained for rhodium catalysts. A report on asymmetric carbonylation was published in 1993.310 Two reviews dedicated to asymmetric hydroformylation, which appeared in 1995, include the most important studies and results on platinum-catalogued asymmetric hydroformylation.80,81 A report appeared in 1999 about hydrocarbonylation of carbon-carbon double bonds catalyzed by Ptn complexes, including a proposal for a mechanism for this process.311... 

The cA-PtCl2(diphosphine)/SnCl2 constitutes the system mostly used in catalyzed hydroformylation of alkenes and many diphosphines have been tested. In the 1980s, Stille and co-workers reported on the preparation of platinum complexes with chiral diphosphines related to BPPM (82) and (83) and their activity in asymmetric hydroformylation of a variety of prochiral alkenes.312-314 Although the branched/normal ratios were low (0.5), ees in the range 70-80% were achieved in the hydroformylation of styrene and related substrates. When the hydroformylation of styrene, 2-ethenyl-6-methoxynaphthalene, and vinyl acetate with [(-)-BPPM]PtCl2-SnCl2 were carried out in the presence of triethyl orthoformate, enantiomerically pure acetals were obtained. 

Platinum(II) complexes with diphosphines based on DIOP (85),315-321 CHIRAPHOS (86),316,320 and bdpp (87)322-325 backbones have been prepared to be used, in the presence of SnCl2, as catalyst precursors in asymmetric hydroformylation of styrene and other alkenes. 

MeOBIPHEP is the atropisomeric diphosphine 2,2,-bis(diphenylphosphino)-6,6 -dimethoxy-l,-l -biphenyl (100), has been synthesized. In the presence of SnCl2, this species is an efficient catalyst for the asymmetric hydroformylation of styrene. Asymmetric inductions are higher than those attainable using the system [PtCl2 (i )-(+)-BINAP ]/SnCl2, where BINAP is 2,2 -bis(di-phenylphosphino)-l,l,-binaphthyl. The influence of CO and H2 partial pressures on the catalytic activity of the (99)/SnCl2 system has also been studied.328 Complexes [PtMeCl(P-P)][(101), P-P = (5)-6,6,-(dimethoxybiphenyl)-2,2,-diylbis(diphenylphosphine) ((5)-MOBIPH) (102),... 

Several types of chiral diphosphite ligand have been synthesized and tested in Pt-catalyzed asymmetric hydroformylation.338-341... 

Diastereomeric diphosphites (107)-(110) were prepared by the reaction of enantiomerically pure 2,2 -dihydroxy-5,5, 6,6, 7,7, 8,8 -octahydro-l,l -binaphthyl or 2,2 -dihydroxy-l,l -binaphthyl with chlorophosphites. The structure of R-bis-(4R,6R)-(l 07) was determined by XRD. The diphosphites were tested in the Pt- and Rh-catalyzed asymmetric hydroformylation of styrene. 

Homochiral pyridyl, bipyridyl, and phosphino derivatives of 2,2-dimethyl-1,3-dioxolane (113)-(115) were prepared from T-(+)-tartrate. These compounds were assessed in metal-catalyzed asymmetric hydroformylation of styrene enantioselectivity was generally low.342... 

Chiral bis-(binaphthophosphole) (bis(BNP)) ligands have been used in the asymmetric hydroformylation of styrene. In solution, the free diphospholes display fluxional behavior. Consistent with their structure, the reaction of the bis(BNP) compounds with platinum(II) derivatives gives either cis chelate mononuclear complexes or trans phosphorus-bridged polynuclear derivatives. Coordination to platinum enhances the conformational stability of bis(BNP)s and diastereomeric complexes can be detected in solution. In the presence of SnCl2, the platinum complexes give rise to catalysts that exhibit remarkable activity in the hydroformylation of styrene. Under optimum conditions, reaction takes place with high branched selectivity (80-85%) and moderate enantio-selectivity (up to 45% ee). 

CHIRAPHOS (86), bdpp (87), DIOP (85), deguphos (117), and related chiral diphosphines have been used as ligands in asymmetric hydroformylation of styrene and related substrates.255 347-349... 

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