Amide ligands, conjugate addition

Asymmetric -methylation of a, -enones. Chiral bidendate ligands derived from L-prolinol can be used for asymmetric Michael additions to a, 3-enones with cuprates of the type CH,L CuMgBr (10, 266). The highest optical yield in conjugate addition to chalcone is observed when L is (S)-N-methylprolinol (88% ee). The tridentate chiral ligand 1 is equally effective for asymmetric 3-methylation of chalcone with CH,L CuLi and CuBr the chemical yield is 95%. Reduction of the amide carbonyl group of 1 results in practically total loss of chiral induction. 

The influence of solvent and additives on yield and selectivity has been examined.The conjugate addition of dimethyl cuprate in the presence of a chiral ligand, such as 144, is an example. The use of chiral ligands with Mgl2/l2 and BuaSnl gave conjugate addition products with a,(3-unsaturated amides with... 

Conjugate Addition Reactions. - Two protocols for achieving the enantioselective conjugate addition of an alkyl group to an enone using a cuprate containing a chiral ligand have been reported. In one case the lithium amide (28) was used to prepare an amidocuprate... 

Molander et al, have extended this technology to p-substituted amide borates. This method is complementaiy to known conjugate addition methodology mediated by chiral ligands or chiral hydrogenation methods that produce enantiomeric p-substituted amides. Molander s lab has reported a straightforward chiral synthesis of p-trifluoroborate salts from a,p-unsaturated amides (Scheme 16.14). 

Dual enantioselective control in the Cu-catalysed conjugate addition of dialkylzinc compounds to acyclic and cyclic enones has been realized in the presence of functionalized A -heterocyclic carbene ligands. " For example, a high degree of asymmetric catalysis (up to 96% ee) has been achieved using a (hydroxy amide)-functionalized azolium salt (19). Most likely the selectivity appears because of the facial selection of the enone, which is a result of steric repulsion between the alkyl group on the azolium ring and the alkyl substituent at the / -position of the enone. 

The process involves formation of the conjugate base of the complex by proton loss from an ammonia ligand that remains intact in the complex, this amide ion being reprotonated to regenerate the ammonia in the fast final step where the intermediate reacts with addition... 

Michael additions. Despite tremendous efforts spent in achieving catalytic asymmetric Michael additions, effective additives of wide applicability are still quite rare. Interestingly, a polyamine ligand 29 promotes the addition of ketone enolates. With JV-methoxy-N-methyl amides of a,p-unsaturated acids as acceptors, the addition of lithium fS)-(a-methylbenzyl)benzylamide proceeds in a highly diastereo- and enantioselective manner, ascribable to a six-centered transition state in which the conjugated amide adopts an s-cis conformation, ... 

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