Hydroformylation organic synthetic applications

Abstract Recent advances in synthetic aspects of the rhodium-catalyzed hydroformylation of alkenes are reviewed. Emphasis is given to practical improvements, efficient new catalysts for regioselective and enantioselective hydroformylation, and to applications of the reaction in organic synthesis. Furthermore, new developments in directed hydroformylation are covered as well as new approaches toward efficient hydroformylation catalysts employing the concept of self-assembly. 

The aldol reaction is probably one of the most important reactions in organic synthesis. In many industrially important hydroformylation processes selfcondensation of aldehydes is observed. Sometimes this consecutive reaction is favored as in the production of 2-ethyl hexanol. But synthetic applications of tandem hydroformylation/aldol reactions seem to be limited due regiose-lectivity problems of a mixed aldol reaction (Scheme 28). However, various tandem hydroformylation/intramolecular mixed aldol reactions have been described. 

In this chapter we shall review the aqueous hydroformylation of substrates other than simple terminal alkenes. Of course, preparation of butyraldehyde or plasticizer alcohols is also a synthetic application but in the following a few examples are given for application of hydroformylation in reactions of more complex substrates and in synthesis of more elaborate molecules. Most of these chemical transformations could also be effected in one-phase reactions (organic or aqueous), however, the biphasic variants were not inferior in chemistry and offered the advantage of easy catalyst-product separation. 

A chapter written in 1996 covers hydroformylation catalyzed by organometallic complexes in detail,219 whereas a review written 5 years later gives a summary of the advances on hydroformylation with respect to synthetic applications.220 A selection of papers in a special journal issue has been devoted to carbonylation reactions.221 A major area of the research has been the development of fluorous biphasic catalysis and the design of new catalysts for aqueous/organic biphasic catalysis to achieve high activity and regioselectivity of linear or branched aldehyde formation. 

Schmidt AM, Eilbracht P (2004) New Synthetic Applications of Tandem Reactions under Hydroformylation Conditions. In Beller M, Bolm C (eds) Transition Metals for Organic Synthesis Building Blocks and Fine Chemicals. Wiley, Weinheim, p 57... 

This chapter discusses some general aspects of the hydroformylation of alkenes in organic synthesis. It focuses mainly on regio- and stereoselective processes, and analyzes the influence of the substrate and the catalysts. Practical methods which provide high yields and selectivities, and short-cuts compared to classical organic routes will be described. Particular attention will be paid to recent advances that have helped to enlarge the synthetic application of this reaction. Section 6.7 deals with the hydroformylation of alkynes, and such key aspects as hydroformylation in water-gas shift conditions and silylformylation, particularly efficient catalytic systems and the application ofhydroformylation in organic synthesis. 

Thus, considerable effort is necessary to achieve a wide and synthetically useful application of this method. Nevertheless, the first examples of interesting target molecules obtainable via asymmetric hydroformylation have appeared (amino acids, arylpropionic acids)180. Thus, if appropriate catalytic systems and reaction conditions can be found, even industrial applications might be realized within the near future. Thus, asymmetric hydroformylation is considered to be a powerful tool for the preparation of a large number of different chiral products to be used as precursors of several organic compounds endowed with therapeutical activity180. Examples are the essential and non-essential amino acids, 2-arylpropanoic acids, aryloxypropyl-and /1-phenylpropylamines. modified /1-phenylethylamines, pheniramines and others180. 

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