Chiral amides, asymmetric Michael reactions

Scheme 8.25 Application of a-amino acid amides as chiral auxiliaries for the asymmetric Michael reaction.

Asymmetric Michael reactions in presence of chiral amides. 391... 

Amide and imide enolates. Scheme 5.31 illustrates several examples of asymmetric Michael additions of chiral amide and imide enolates. Yamaguchi [163] investigated the addition of amide lithium enolates to -ethyl crotonate, but found no consistent topicity trend for achiral amides. The three chiral amides tested are illustrated in Scheme 5.31a-c. The highest diastereoselectivity found was with the C2-symmetric amide shown in Scheme 5.3Ic. Evans s imides, as their titanium enolates, afforded the results shown in Scheme 5.31d and e [164,165]. The yields and selectivities for the reaction with acrylates and vinyl ketones are excellent, but the reaction is limited to P-unsubstituted Michael acceptors P-substituted esters and nitriles do not react, and 3-substituted enones add with no selectivity [165]. 

Asymmetric Michael addition reaction represents one of the most extensively explored organoctalytic transformations. Chiral secondary amines such as pyrrolidines have been proved to very effective catalysts for the reactions of Michael donors such as cyclohexanone and aldehydes [31]. Ala-Ala dipeptide 57 [32] was firstly found to be viable catalyst for the reaction of cyclohexanone and nitrosty-rene. Later, some primary amine-amide type catalysts such as 55 [33a], 56 [33b-c] and 58 [33d] have also been indentilied for the same reactions (Scheme 5.16) with slightly lower activity compared with typical chiral pyrrolidine catalysis. 

Since conjugate (Michael) addition and Diels-Alder reactions use a,p-unsat united carbonyl compounds, asymmetric versions of these reactions could use the auxiliaries that we have seen in aldol reactions in the form of 118 and 119. Diels-Alder reactions work very well with these unsaturated amides and also with amides 121 derived from Oppolzer s chiral sultam14 120, prepared simply from camphorsulfonyl chloride. 

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