Asymmetric organocatalysts

The enantioselective synthesis of organic compounds is one of the key issues to be resolved in the field of synthetic organic chemistry because chiral organic compounds are important as pharmaceutical products, agrochemicals, and fine chemicals. 

Metal-based catalysts have been extensively studied in both academia and industry. 

The award of the Nobel Prize in Chemistry in 2001 to William R. Knowles and Ryoji Noyori for their work on metal-catalyzed enantioselective hydrogenation reactions and to K. Barry Sharpless for his work on catalyzed enantioselective oxidation reactions was a landmark in chiral catalysis studies. Enzymes and biocatalysts have also played a pivotal role as asymmetric catalysts [16]. 

Until fairly recently, primarily transition metal complexes and enzymes were utilized as catalysts for enantioselective synthesis [17]. Nicolaou and Sorensen wrote the following statement in their book published in 1996 [18] In a catalytic asymmetric reaction, a small amount of an enantiomerically pure catalyst, either an enzyme or a synthetic, soluble transition metal complex, is used to produce large quantities of an optically active compound from a precursor that may be chiral or achiral.  

In the past, synthetic organic chemists rarely employed small organic compounds as catalysts, although some of the very first asymmetric catalysts were purely organic molecules. 

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Economic and practical reasons, in addition to green concerns, have meant that many of the first generation of asymmetric organocatalysts have been either natural molecules, such as nomicotine [52] and proline [40], derived directly from the chiral pool (Figure 7.1), or simple derivatives thereof, such as quinine acetate [53] and 5,5-dimethyl thiazolidinium-4-carboxylate (DMTC) [54], which are expected to be either biodegradable or biotransformable, with little impact on the environment. [54]. 

Zhou, L. and Wang, L. (2007) Chiral ionic liquid containing L-proline unit as a highly efficient and recyclable asymmetric organocatalyst for aldol reaction. Chem. Lett., 36 (5), 628-629. 

The use of L-proline, amides derived from it, and related amino acids and small peptides as asymmetric organocatalysts for aldols - and indeed many other reactions mentioned elsewhere in this chapter - expanded hugely in 2006. A review deals with the direct aldol case.96... 

Asymmetric Organocatalysts. Albrecht Berkessel and Harald Groger Copyright 2005 WILEY-VCH Veriag GmbH Co. KGaA, Weinheim ISBN 3-527-30517-3... 

For a recent review on amino acids and peptides as asymmetric organocatalysts see E. R. Jarvo, S. J. Miller, Tetrahedron 2002, 58, 2481-2495. 

Figure 6.2 Structures of asymmetric organocatalysts derived from thiazole.

Total synthesis of marine cyclic guanidine compounds and development of novel guanidine-type asymmetric organocatalysts 03YZ387. 

Asymmetric Organocatalysts, Wiley-VCH Verlag GmbH, Weinheim ... 

Chiral secondary amines such as nonracemic imidazolidin-4-ones have been found to be effective asymmetric organocatalysts in the Diels-Alder cyclization of cyclopentadiene and a,p-unsaturated aldehydes [60]. A tyrosine-derived imidazoli-din-4-one was immobilized on PEG to provide a soluble, polymer-supported catalyst 110. In the presence of 110, Diels-Alder cycloaddition of acrolein 112 to 1,3-cyclohexadiene 111 proceeded smoothly to afford the corresponding cycloadduct 113 with high endo selectivity and enantioselectivity up to 92% ee (Scheme 3.31) [61]. 

Pyrrolidin-2-yltetrazole 204 has been found to be a new, catalytic, and more soluble alternative to proline in a highly selective, organocatalytic route to chiral dihydro-1,2-oxazines <05OL4189> and as an asymmetric organocatalyst for Mannich, nitro-Michael and aldol... 

Proline as an Asymmetric Organocatalyst Iminium-Activation of dienophile... 

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