Organocatalysis addition

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 ... 

Keywords Aminocatalysis Conjugate addition Cycloaddition Ttninintn ion Organocatalysis... 

In the majority of current theoretical pubhcahons deahng with organocatalysis, Becke s [8a, b] three parameter hybrid functional B3 and the Lee, Yang, and Parr (LYP) correlahon functional [8c] are used in combinahon with standard split valence basis sets (e.g., 6-3IG). In most cases, polarization functions that allow a greater flexibiHty of angle are added (for example, [d,p] means addihonal d-functions for second-row atoms, and additional p-funchons for hydrogen atoms)... 

Tandem intramolecular Michael addition - intramolecular alkylation can lead to cyclopropanes. Matthew J. Gaunt of the University of Cambridge has shown (Angew. Chem. Int. Ed. 2004,43, 2681) that this intramolecular Michael addition also responds to organocatalysis. In this case, the catalyst, a quinine-derived amine, covalently binds to the substrate, then is released at the end of the reaction. 

More recently, MacMillan has introduced the amine catalysts 42 and 45, readily available from L-phenylalanine, methylamine, and acetone or pivalaldehyde, respectively (Schemes 4.15 and 4.16). The broad potential of these materials in enan-tioselective organocatalysis was first proven in Diels-Alder reactions [28] and nitrone cydoadditions [29]. In 1,4-addition of C-nudeophiles MacMillan et al. later showed that Friedel-Crafts reactions of pyrroles with enals can be made highly enantioselective (Scheme 4.15) [30]. 

Other reviews deal with aldol additions of group 1 and 2 enolates,103 direct catalytic asymmetric aldol reactions catalysed by chiral metal complexes,104 the exploitation of multi-point recognition in catalytic asymmetric aldols,105 and recent progress in asymmetric organocatalysis of aldol, Mannich, Michael, and other reactions.106... 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

In this area, Krische and co-workers have developed a family of catalytic transformations based on the use of enones as latent enolates. Nucleophilic activation of the enone is induced via carbometallation, nucleophilic organocatalysis or hydrometallation. The following examples illustrate some aspects of these new catalytic conjugate addition/electrophilic trapping reactions. 

Selected recent developments in the area of asymmetric organocatalysis in our laboratory have been briefly summarized. Enamine catalysis, Brpnsted acid catalysis, and iminium catalysis turn out to be powerful new strategies for organic synthesis. Using Hantzsch ester as the hydride source, highly enantioselective transfer hydrogenantion reactions have been developed. We have also developed an additional new con-... 

Various aspects of organocatalysis with larger molecules are also covered in this book. Possible benefits from immobilization approaches for organic catalysts are pointed out by M. Benaglia. Apart from catalyst recycling or simplified workup procedures, catalyst immobilization can be additionally advantageous in terms of catalyst development and optimization. The use of soluble supports, such as polyethylene glycol, often allows the direct transfer and application of already optimized reaction conditions. 

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