Enones, asymmetric catalysis reactions

For these and similar reactions recently a variety of Lewis acidic aluminium, rare earth metals, and titanium alkoxides have been applied. Alkoxides have the additional advantage that they can be made as enantiomers using asymmetric alcohols which opens the possibility of asymmetric catalysis. Examples of asymmetric alcohols are bis-naphtols, menthol, tartaric acid derivatives [28], Other reactions comprise activation of aldehydes towards a large number of nucleophiles, addition of nucleophiles to enones, ketones, etc. 

The asymmetric epoxidation of enones with polyleucine as catalyst is called the Julia-Colonna epoxidation [27]. Although the reaction was originally performed in a triphasic solvent system [27], phase-transfer catalysis [28] or nonaqueous conditions [29] were found to increase the reaction rates considerably. The reaction can be applied to dienones, thus affording vinylepoxides with high regio- and enantio-selectivity (Scheme 9.7a) [29]. 

Phase-transfer catalysis has been widely been used for asymmetric epoxidation of enones [100]. This catalytic reaction was pioneered by Wynberg et al., who used mainly the chiral and pseudo-enantiomeric quaternary ammonium salts 66 and 67, derived from the cinchona alkaloids quinine and quinidine, respectively [101-105],... 

Do not suppose that the regioselectivity problem is now trivial. In a study mainly aimed at achieving asymmetric reactions, Braun34 showed just how narrow is the gap between 1,2 and 1,4 addition. The silyl enol ether 101, easily made from the enantiomerically pure ester 100, gave mainly (>95 5) direct (1,2) addition to a simple enone under the usual conditions (TiCl4 catalysis) for Michael addition. 

Reaction with alkaline peroxide (or hypochlorite) and a chiral catalyst allows the asymmetric epoxidation of enones. Excellent asymmetric induction has been achieved using metal-chiral ligand complexes, such as those derived from lanthanides and (/ )- or (5)-BlNOL. Alternatively, phase-transfer catalysis using ammonium salt derivatives of Cinchona alkaloids, or the use of polyanuno acid... 

Some other very important events in the historic development of asymmetric organocatalysis appeared between 1980 and the late 1990s, such as the development of the enantioselective alkylation of enolates using cinchona-alkaloid-based quaternary ammonium salts under phase-transfer conditions or the use of chiral Bronsted acids by Inoue or Jacobsen for the asymmetric hydro-cyanation of aldehydes and imines respectively. These initial reports acted as the launching point for a very rich chemistry that was extensively developed in the following years, such as the enantioselective catalysis by H-bonding activation or the asymmetric phase-transfer catalysis. The same would apply to the development of enantioselective versions of the Morita-Baylis-Hillman reaction,to the use of polyamino acids for the epoxidation of enones, also known as the Julia epoxidation or to the chemistry by Denmark in the phosphor-amide-catalyzed aldol reaction. ... 

The initial spark for proline catalysis was provided independently and simultaneously by two groups in 1971. Hajos and Parrish on the one hand (Scheme 5.1), and Eder, Sauer and Wiechert (Scheme 5.2) on the other developed an asymmetric aldol cyclisation of triketones such as 1 to bicyclic allq l ketones 2. In the former report, (S)-proline was applied at 3 mol%, a low organocatalyst loading, even to date. The quantitative cyclisation reaction was completed in the reasonable time of 20 h, and provided the product in 93.4% ee. Dehydration to enone 3 completed the synthesis of a valuable building block in steroid chemistry. 

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