Asymmetric Hydroformylation Reaction

The asymmetric reactions discussed in this chapter may be divided into three different types of reaction, as (1) hydrometallation of olefins followed by the C—C bond formation, (2) two C C bond formations on a formally divalent carbon atom, and (3) nucleophilic addition of cyanide or isocyanide anion to a carbonyl or its analogs (Scheme 4.1). For reaction type 1, here described are hydrocarbonyla-tion represented by hydroformylation and hydrocyanation. As for type 2, Pauson-Khand reaction and olefin/CO copolymerization are mentioned. Several nucleophilic additions to aldehydes and imines (or iminiums) are described as type 3. 

In asymmetric reactions in which only one isomer is formed, enantioface discrimination corresponds to asymmetric induction. However, in reactions in which two isomers are formed if both isomers are chiral, as in the hydroformylation of (Z)-2-hexene, the optical purities of the two isomers are in general different and enantioface discrimination does not correspond quantitatively (and sometimes not even quali-... 

A number of metals catalyze the hydroformylation reaction, of which rhodium is by far the most active, Rh >> Co > Ir, Ru > Os > Pt. Platinum and ruthenium are mainly of academic interest, although L2PtCl(SnCl3) complexes with chiral ligands find use in asymmetric alkene hydroformylations.59 In most cases, and certainly in industrial processes, cobalt has now been replaced by rhodium. 

Carbonylation of aromatic olefins also provides an attractive route to profens. The key issues in the hydroformylation reaction (cf. Section 2.1.1 and Scheme 4) are the branched/normal selectivity and the configurational stability of the branched aldehydes. When the Pt -catalyzed asymmetric reaction is performed with triethyl orthoformate, the aldehyde product is immediately removed as... 

Hydroformylation reactions have been one of the most well researched areas of CO2 reaction chemistry. Hydroformylation reactions are necessary for the formulation of complex chemicals. The first complete kinetic study of a hydroformylation reaction was in CO2 and was first published in 1999. Prior to this, most studies had considered the effect of dense CO2 on linear branch ratios or other forms of selectivity. Carbon dioxide has an effect on the selectivity of a variety of hydroformylation reactions and can enhance the rate of reaction Hydroformylation is by its nature regioselective and typically the linear branch or n iso ratio is used as the measure of selectivity. The use of asymmetric catalysts to achieve chiral products has introduced a second degree of selectivity to catalyst design. Advancements in catalyst design, together with solvent selection, are expected to make... 

The historic discovery of Rh complexes of chiral bisphosphites and phosphine-phosphites dramatically raised the enantioselectivities of asymmetric hydrocarbonylation from -50% ee to almost quantitative values in the first half of the 1990s. The successes with Rh catalysts seemed to replace the earfier used Pt catalysts which often suffered from extensive side reactions such as hydrogenation and isomerization, and low selectivity to fso-aldehydes. At this stage, asymmetric hydroformylation has reached the level of enantioselectivity of asymmetric hydrogenation, the most studied asymmetric reaction. 

Two important industrial processes are based on biphasic systems the Shell higher olefin process (SHOP) [3] and the hydroformylation developed by Ruhrchemie/ Rhone Poulenc [4]. Prerequisite was the synthesis of water-soluble ligands, especially water-soluble phosphines. Scheme 1 shows a selection of optically active phosphines for asymmetric reactions under biphasic conditions. 

The effects of bisphosphite ligand structure on regioselectivity and enantio-selectivity in asymmetric styrene hydroformylation are shown in Table 1. Catalytic reactions were preformed at ambient temperature and 130 psi CO/H2. Hydroformylation regioselectivity was determined by GC of the product aldehydes. Enantioselectivity was determined by chiral GC after conversion to the carboxylic acid (eqn 1). The, i -enantiomer of the bisphosphites in Figure 1 all produced the... 

Water-soluble macromolecular metal complexes based on terminally functionalized ethylene oxides and ethylene oxide-propylene oxide block copolymers have been used as catalysts for hydroformylation, hydrogenation, Wacker oxidation of imsaturated compounds, hydroxylation of aromatic compounds, oxidation of saturated and alkylaromatic hydrocarbons, metathesis, Heck reaction, and some asymmetric reactions. 

Macromolecular metal complexes with modified poly(ethylene oxide)s have also been applied as catalysts for asymmetric reactions epoxidation, dihydroxy-lation, hydrogenation, and hydroformylation. 

Stereoselective hydroformylation can be divided into diastereo- and enantioselec-tive (asymmetric) reactions. Enantioselective transformations can be conducted with the assistance of a chiral catalyst. But diastereoselective reactions can also benefit from a chiral catalyst by utilizing Masamuni s principle of matched/mismatched combinations of chiral substrate and chiral catalyst [1]. In this chapter, reference will be made only to ligands originally developed for asymmetric hydroformylation (AHF), but it is clear that they can also be used for diastereoselective transformations. 

Risi and Burke [29, 30] synthesized (+)-patulolide C, which is a macrocyhc compound isolated from a Penicillium urticae mutant via an asymmetric sequential hydroformylation-(intramolecular Wittig olefination) reaction applying... 

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-... 

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... 

In 2000, better results were obtained by Bonnet et al. by using readily available chiral thioureas as new ligands in the asymmetric rhodium-catalysed hydroformylation of styrene. In general, the conversion of styrene and enantioselectivities were modest, but when the reaction was carried out in heptane as the solvent, an enantioselectivity of 41% ee was obtained (Scheme 10.6). 

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