Enantioselective Organocatalysis

The next milestone in the realm of enantioselective organocatalysis was reached by Inoue and coworkers, who elegantly modernized the cyanohydrin reaction, first outlined by Bredig and Fiske in 1912. In these studies, a cyclic histidine-containing dipeptide (4) catalyzed the HCN addition to aromatic aldehydes with high enantioselectivities (97% ee) [Eq. (11.4)] a result that effectively paved the way for the field of peptide-catalyzed nucleophilic addition to aldehydes and imines ... 

This reaction encompasses a number of interesting features (general Brpnsted acid/ Brpnsted base catalysis, bifunctional catalysis, enantioselective organocatalysis, very short hydrogen bonds, similarity to serine protease mechanism, oxyanion hole), and we were able to obtain a complete set of DFT based data for the entire reaction path, from the starting catalyst-substrate complex to the product complex. 

Dalko, P.L (2007) Enantioselective Organocatalysis-Reactions and Experimental Procedures, Wiley-VGH Verlag GmbH, Weinheim, Germany. 

Dalko PI, Moisan L (2001) Enantioselective organocatalysis. Angew Chem Int Ed 40 3726-3748... 

Enders D, Balensiefer T, Niemeier O, Christmann M (2007c) Nucleophilic N-heterocyclic carbenes om asymmetric organocatalysis. In Dalko PI (ed) Enantioselective organocatalysis—reactions and experimental procedures. Wiley-VCII, Weinheim, p 331... 

Gaunt MJ, Johansson CCC, McNally A, Vo NT. Enantioselective organocatalysis. Drug Disc. Today 2007 12 8-27. 

Dalko, P. I., Moisan, L. Enantioselective organocatalysis. Angewandte Chemie, International Edition 2001,40, 3726-3748. 

In 1982, Wynberg and coworkers discovered the cinchona alkaloid catalyzed enantioselective aldol lactonization of ketenes with chloral or trichloroacetone [35], in which the zwitterionic acyl ammonium enolate provides the carbon nucleophile. This work is probably one of the most important early contributions to enantioselective organocatalysis [36], One drawback associated with this process is the severe substrate limitations. The aldehydes should be highly reactive, presumably due to the relatively limited nudeophilicity of ammonium enolates. Nelson and coworkers first addressed the scope and reactivity problems associated with Wynberg s original protocol by combining a cinchona alkaloid derivative (O-trimethylsilylquinine (12) or O-trimethylsilylquinidine (13)) with a metal Lewis acid as a cocatalyst to... 

For recent reviews, see (a) Berkessel, A. and Groger, H. (2005) Asymmetric Organocatalysis From Biomimetic Concepts to Potveiful Methods for Asymmetric Synthesis, Wiley VCH Verlag GmbH, Weinheim (b) Dalko, P.L (ed.) (2007) Enantioselective Organocatalysis Reactions and Experimental Procedures, John Wiley Sons, New York. 

P.I. Dalko (Ed.), Enantioselective Organocatalysis Reactions and experimental procedures, Wiley-VCH, 2007. ISBN-10 3527315225, ISBN-13 978-3527315222. 

Enantioselective organocatalysis (heterocycles as ligands and auxiliary compounds) 01AG(E)3726, 01CRV757. 

Enantioselective Organocatalysis Reactions and Experimental Procedures, ed. P. I. Dalko, Wiley-VCH Verlag GmbH Co. KGaA, 2007. 

---