Hydroformylation, asymmetric synthesis

Special reactions Haber process, exhaust clean up etc. Hydroformylation of alkenes, methanol carbonylation, asymmetric synthesis etc... 

Optically active aldehydes are important precursors for biologically active compounds, and much effort has been applied to their asymmetric synthesis. Asymmetric hydroformylation has attracted much attention as a potential route to enantiomerically pure aldehyde because this method starts from inexpensive olefins and synthesis gas (CO/H2). Although rhodium-catalyzed hydrogenation has been one of the most important applications of homogeneous catalysis in industry, rhodium-mediated hydroformylation has also been extensively studied as a route to aldehydes. 

The asymmetric hydroformylation of allyl cyanide has recently focused the interest of researchers because the iso-aldehyde derivative can be easily transformed into 2-methyl-4-aminobutanol, a useful building block, for instance for the asymmetric synthesis of tachikinin (58), a novel NK1 receptor agonist developed by Takeda [82], It should be noticed that this aldehyde is not accessible via the hydroformylation of crotononitrile. 

Use of chiral ligands allows asymmetric synthesis of optically active branched aldehydes. In the early 1970s, two groups independently reported the first examples of asymmetric hydroformylation (109). Optical yields of less than 2 % were obtained by using styrene as substrate and a chiral Schiff base-Co or phosphine-Rh complex as catalyst. 

Thus the enantiomeric excesses obtained in the platinum-catalyzed hydroformylation reactions of certain alkenes were achieved at a level (75-85% ee) necessary for facile enrichment to optically pure compounds, presenting an opportunity to establish this reaction as a viable asymmetric synthesis of aldehydes. 

Review R. E. Merrill, Asymmetric synthesis using chiral Phosphine ligands, Reaction Design Corp., Hillside, N.J., 1979. This review covers the literature to mid-1979 (234 references). It discusses mechanisms and applications to asymmetric hydrogenation, hydrosilylation, hydroformylation and alkylation. 

For a good summary of asymmetric hydroformylation of di- and trisubstituted alkenes, see K. Nozaki and I. Ojima, Asymmetric Carbonylations, In Catalytic Asymmetric Synthesis, 2nd ed., I. Ojima, Ed., Wiley-VCH New York, 2000, pp. 429-463. 

This type of enantiomer-differentiating asymmetric synthesis via kinetic resolution of racemic alkcncs during hydroformylation is reported for 3-methyl-l-pentene using optically active bis(A,-a-methylbenzylsalicylaldiminato)cobalt [Co(R -Sal)2] to give low optical yields of the recovered starting material and the hydroformylation product21. 

Terminal alkenes usually give predominantly the linear achiral products. Thus, until now, the hydroformylation method was only of limited value for the asymmetric synthesis of normal open chain aldehydes. 

Enamides can also be used as precursors for the asymmetric synthesis of amino acids via hydroformylation. Thus, asymmetric branched hydroformylation of vinylsuccinimide and vinylphthalimide upon further oxidation leads to, V-protccted amino carboxylic acids such as alanine. Branched products are obtained with high regioselectivities and good to high optical yields of up to 96% (see Table 7)125. 

We describe the extension of this class of bisphosphite catalysts to asymmetric hydroformylation and hydrocyanation of vinylarenes.(3) These enantiose-lective catalytic transformations are employed for the asymmetric synthesis of S-Naproxen, a widely used non-steroidal anti-inflammatory drug (NSAID). Factors which influence regioselectivity and enantioselectivity, as well as characterization of the catalyst resting states, are discussed. 

Selective production of either a linear or branched aldehyde in hydroformylation is quite important in affecting the further utihty of the aldehyde. Linear aldehydes can be converted into linear alcohols useful as detergents, after an aldol reaction followed by hydrogenolysis. Branched aldehydes afford important materials for pharmaceutical use, particularly when asymmetric synthesis of the branched aldehyde can be achieved [57]. 

Solinas M, Gladiali S, Marchetti M (2005) Hydroformylation of aryloxy ethylenes by Rh/BINAPHOS complex - catalyst deactivation path and application to the asymmetric synthesis of 2-aryloxypropanoic acids. J Mol Catal A 226 141-147... 

What has turned out to be an attractive approach to the catalytic asymmetric synthesis is not restricted within hydrogenation. In fact, it has applied to date to most of the catalytic reactions in which an unsaturated substrate is activated by metal complexes they include hydroformylation [4], dimerization or oligomerization [5], cyclopropanation [6], and hydrosilylation [7], of olefins. 

Dendritic catalysis have been used in various chemical reactions, including the Suzuki-Miyaura reaction, Mizoroki-Heck reaction, hydrogenation reaction, carbonylation and hydroformylation reactions, oxidation reaction, polymerization and oligomerization reactions, arylation reaction, alkylation reaction, and asymmetric synthesis [6]. Recently, dendritic catalysts have been reviewed by Astmc et al. [6], In another review article. Reek et al. reviewed the applications of dendrimers as support for recoverable catalysts and reagents [58]. The authors believed that catalytic performance in these systems depends on used dendritic architecture. 

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