Scale-up Studies in Asymmetric Transfer Hydrogenation

Catalytic asymmetric transfer hydrogenation is an efficient method for producing optically active alcohols and amines. Analysis of launched and development pharmaceuticals show that these types of chiral centers occur most frequently, so this technology is proving particularly valuable. The chapter will describe the background, development, and application of asymmetric transfer hydrogenation, with particular emphasis on Avecia s proprietary CATHy catalysts. 

Asymmetric Catalysis on Industrial Scale Challenges, Approaches and Solutions Edited by H. U. Blaser, E. Schmidt 

Copyright 2004 Wiley-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-30631-5 

Noyori was subsequently able to show that triethylamine salts of formic acid (TEAF) could be used to reduce ketones to alcohols and imines to amines with high enantioselectivities [4]. The byproduct of this reaction is carbon dioxide gas and this prevents the possibility of the reverse reaction. Strangely, aminoalcohol ligands are poor in this reaction, whilst unsymmetrical 1,2-diamines have proven very effective. A particularly effective ligand is mono-N-tosyl-l,2-diphenylethylene-diamine. 

The CATHy catalysts, like their ruthenium analogues are also active in the reduction of ketones and imines using the formate system [5], Wills has published on the reduction of ketones [9], and Baker on the reduction of imines [6], The development of this process for large-scale use has proven more complex and this will be described elsewhere in this chapter. 

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Blacker, J. and Martin, J. Scale-up Studies in Asymmetric Transfer Hydrogenation in Asymmetric Catalysis on Industrial Scale, Blaser, H.U. and Schmidt, E. (Eds). Wiley-VCH New York, 2004, 201-216. 

Blacker J, Martin J (2004) Scale up studies in asymmetric transfer hydrogenation. In Blaser HU, Schmidt E (eds) Asymmetric catalysis on an industrial scale challenges. Approaches and solutions. Wiley, New York, p 201... 

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