Chiral catalyst economy

Using chiral auxiliaries implies that at least one molecule of the auxiliary has to be used for generating one new chiral molecule. Using a chiral catalyst, by contrast, with a turnover number of 1000 means that 1000 new chiral molecules may be generated with the aid of one molecule of the chiral catalyst. Apart from higher chiral economy no covalent attachment is required and the workup is considerably simphfied as only trace amounts of of the catalyst have to be removed. This insight has greatly stimulated the search for chirally catalyzed reactions... 

Recovery and recycling of the chiral auxiliaries and ligands is another important concern in asymmetric synthesis, mainly when they are expensive. Therefore, the cuirent nee plus ultra is the use of chiral inductors in catalytic amounts either as chiral reagents or as ligands of chiral catalysts, that is the practice of "atom economy" as coined by Trost [129], Special emphasis Mil be given to the scope and limitations of this aspect of asymmetric synthesis. 

As compared with stoichiometric asymmetric syntheses, the use of catalytic asymmetric reactions for the syntheses of chiral compounds is a more desirable method in terms of atom economy. In principle, the chemical approach, which uses a small amount of a chiral catalyst, can produce optically active chiral materials in large quantities. In the early days, however, practical access to enantiomerically... 

Asymmetric addition of ketenes to aldehydes is a highly attractive synthetic access to yfi-lactones with perfect atom economy [134, 135]. This reaction can be catalyzed efficiently by using chiral amines as organocatalysts. As early as 1967 Borr-mann et al. described an organocatalytic asymmetric ketene addition to aldehydes [136] chiral tertiary amines, in particular (—)-N,N-dimethyl-a-phenylethylamine or (—)-brucine, were used as catalysts [136]. The resulting lactones were obtained with modest enantioselectivity of up to 44% ee. 

Enantioselective homogeneous hydrogenation catalyzed by chiral transition metal complexes is one of the most well established transformations in asymmetric synthesis [1]. Excellent enantioselectivities have been achieved in the hydrogenation of a wide range of substrates, often with very low catalyst loadings. High reliability, mild reaction conditions, and perfect atom economy are further attractive attributes of this method. In particular complexes based on Ru or Rh have found broad application in industrial processes [1] and the impact of these catalysts has been recognized by the Nobel Prize awarded to Ryoji Noyori and William S. Knowles in 2001 [2]. 

The key to asymmetric hydrogenation is the structure of the chiral ligand. The phosphanes are prepared by a multistep route and are quite expensive, but fortunately one mole of catalyst will make many thousands of moles of product. Even so, the ligand must be made from cheap starting materials. Some economy of scale is achieved by making a ten year supply in a few plant-sized batches. At... 

The high value of catalytically performed reactions as compared to non-catalytic variants is particularly evidenced in the field of enantioselective reactions. Chemists cannot complete enantioselective reactions without certain chiral information in the reacting system. This information is regularly derived from the chiral compounds present in nature, collectively named the chiral pool of the nature. Their availability is often limited, which is not an issue when they are used as catalysts, but causes significant costs of non-catalytic reactions when they are needed in equimolar quantities. The practical value of the catalytic approach to enantioselective processes cannot be overestimated. Asymmetric catalysis characterizes the amplification of chirality one chiral molecule of the catalyst generates an enormous number of chiral molecules of the product in the optically pure form. This results with high chiral economy of catalytically performed enantioselective syntheses. 

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