Mechanisms enantioselective conjugate addition

The first prominent catalytic asymmetric addition of an organolithium reagent was realized in the reaction of 1-naphthyllithinmwith l-fluoro-2-naphthy-laldehyde imine in the presence of the chiral diether 1 to afford chiral binaphthyls in over 82% ee (Scheme 2). Merely a catalytic amount of 1 (5 mol %) is required to effect the reaction, in which an enantioselective conjugate addition-elimination mechanism is operative [18]. 

Apart form the aforementioned highly enantioselective hetero-Diels-Alder reactions, that proceed with very low catalyst loadings, the catalytically accessible enolates have also been used for related intramolecular Michael reactions (Philips et al. 2007) and for the desym-metrization of 1,3-diketones yielding cyclopentenes via an intramolecular aldol reaction (Wadamoto et al. 2007). The formation of cyclopentenes, however, presents a special case, so—depending on the stereochemical nature of the enone substrates (s-cis or s-trans) and the stereochemistry of the final products—two different mechanisms are discussed in the literature. Whereas /ran.v-cycl open (cries are proposed to be available upon conjugate addition of a homoenolate to chalcones,... 

Another mechanism for catalysis of conjugate addition is via iminium salts. This reactivity has been exploited for several enantioselective catalysts (see Sect. 6.2). A simple example is provided by the use of pyrrolidine salts [225]. 

Lately, sulfones have become especially important substrates in organocatalysis [87]. First studies on the asymmetric conjugate addition of aldehydes to vinyl sulfones were carried out by Alexakis and Mossd employing as catalyst bipyrrolidine 30 (25 mol%) for the addition of linear and a-branched aldehydes to l,l-bis(benzenesulfonyl)ethylene [88], Large excess of aldehyde (10 equivalents) was required and moderate levels of enantioselection were obtained for linear aldehydes (53-80% ee), while reactions with a-branched nucleophiles led to racemic or very low selectivities (0-12% ee). With respect to the mechanism, the acyclic synclinal model proposed by Seebach and GoUnski [70] involving a trans enamine intermediate was postulated. 

Recently, the mechanism of enantioselective Michael addition of malonic esters and keto esters to cyclic conjugated enones catalyzed by Ru bifunctional complexes 1 was studied in detail. ... 

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