Substrates in hydroformylations

For symmetric substrates in hydroformylation, the nmi-linear structure of the CBER mechanisms [5W]cber and [3W]cber+uni are visually, diagrammatically and conceptually rather straightforward to follow. When considerations of selectivity are included, be these considerations regio-, chemo- and stereoselective or a combination thereof, issues rapidly become very complex. A question that one may ask is this given a CBER mechanism with simultaneous regio-, chemo- and stereo-... 

Most of the reports on Rh-catalyzed asymmetric hydroformylation are concerned with asymmetric hydroformylation of vinyl aromatics, which are model substrates of interest to the pharmaceutical industry. In 1993 and 1995, reports were published describing the state of the art in hydroformylation with both rhodium and platinum systems.80,81 310 Two reports appeared in 1999 and 2000 on carbonylation and rhodium asymmetric hydroformylation respectively.311,345... 

Scheme 8.5. Hydroformylation of polar substrates in an inverted biphasic SCCO2/H2O system...

However, platinum catalysts have several disadvantages they have low reaction rates, they hydrogenate the substrate and their regioselectivity to the branched aldehyde is low. The selectivity of Pt-diphosphite/SnCl2 systems is also low. When the appropriate diphosphite is used, ee s can be as high as 90% [13]. In the early 90s, several reports were published which described the state of the art in hydroformylation with both rhodium and platinum systems [14-16]. 

This chapter mainly focuses on the latest achievements and recent developments in asymmetric hydroformylation. Since several reviews have been made in the last decade [9,14-16], the chapter discusses the contributions reported between 2000-2005 in particular, although the main diphoshites and phosphine-phosphite rhodium catalytic systems discovered since 1995 are also considered because of their significance in the subject. Particular attention is paid to mechanistic aspects and characterization of intermediates in the case of the hydroformylation of vinyl arenes because this is one of the most important breakthroughs in the area. The application of this catalytic reaction to different type of substrates, in particular dihydrofurans and unsaturated nitriles is the other main subject of this chapter because of their interest in organic synthesis and their industrial relevance. 

The Ruhrchemie/Rhone-Poulenc process is performed annually on a 600,000 metric ton scale (18). In this process, propylene is hydroformylated to form butyraldehyde. While the solubility of propylene in water (200 ppm) is sufficient for catalysis, the technique cannot be extended to longer-chain olefins, such as 1-octene (<3 ppm solubility) (20). Since the reaction occurs in the aqueous phase (21), the hydrophobicity of the substrate is a paramount concern. We overcame these limitations via the addition of a polar organic co-solvent coupled with subsequent phase splitting induced by dissolution of gaseous CO2. This creates the opportunity to run homogeneous reactions with extremely hydrophobic substrates in an organic/aqueous mixture with a water-soluble catalyst. After C02-induced phase separation, the catalyst-rich aqueous phase and the product-rich organic phase can be easily decanted and the aqueous catalyst recycled. 

Alkenes and Dienes. Alkenes exhibit lower reactivity in metal-catalyzed carboxylation than in hydroformylation. The general reactivity pattern of different alkenes, however, is the same terminal linear alkenes are the most reactive substrates. Cycloalkenes are the least reactive, but strained compounds may react under very mild conditions 128... 

The hydroformylation of styrene in triethyl orthoformate is slower than that observed in benzene, but a 98% ee is obtained, since racemization of the product acetal does not occur. Hydrolysis of the acetal to the aldehyde can be accomplished without racemization. A number of other substrates are hydroformylated in the presence of triethyl orthoformate. The reactions are slower, but with all substrates tried except norbomene, enantiomerically pure products can be obtained. 

In this review the synthetic aspects of asymmetric hydroformylation will be discussed first the experimental data relevant to attempt a rationalization of the results will then be considered. The closely related synthesis of optically active aldehydes by hydroformylation of optically active olefinic substrates in the presence of achiral catalysts7,8 and the different asymmetric hydrocarbonylation reactions, such as the synthesis of esters from olefins, carbon monoxide and alcohols in the presence of optically active catalysts9 , are beyond the scope of this review and will not be discussed here. 

As shown in Table 14, starting with the enantioface of an achiral olefin hydro-formylated with an asymmetric catalytic system, a correct prediction of the antipode of a racemic substrate mainly hydroformylated with the same catalytic system has been made in the few cases examined up to now. 

The best optical yields obtained in the hydroformylation are comparable with the highest yield obtained in hydroalkoxycarbonylation using Pd catalysts. In Table 15 the results obtained in hydroformylation with rhodium or platinum catalysts are compared with those obtained in hydroalkoxycarbonylation using identical substrates and identical optically active ligand 9). 

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