Enantioselectivity conjugated amides

A useful application of organomagnesium amides is in the enantioselective conjugate addition to enamidomalonate to prepare /3-amino acid derivatives (Scheme 16). The alkylmagnesium amide complexes provided both high yields and high selectivity in the organic transformation. 

Chiral organomagnesium amides form an efficient method to realize enantioselective conjugate addition. Sibi and Asano have reported the Michael addition of cr-bound magnesium reagents derived from bisoxazolines to enamidomalonates (equation 41). The enantioselectivity of the addition is discussed in Section El. This method allows the preparation of chiral -amino acid derivatives. ... 

Mixed aggregates of chiral lithium amide and lithium ester enolate have been employed in the enantioselective conjugate addition on a,/S-unsaturated esters.27 Michael adducts have been obtained in ees up to 76% combining a lithium enolate and a chiral 3-aminopyrrolidine lithium amide. The sense of the induction has been found to be determined by both the relative configuration of the stereogenic centres borne by the amide and the solvent. 

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... 

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, ... 

Using the achiral lithium amide derived from Af-trimethylsilylbenzylamine, an enantioselective conjugate addition followed by alkylation has been realized by Tomioka and coworkers by using the chiral additive 1,2-diphenyl-1,2-dimethoxyethane [149]. Various enantioselective conjugate additions of nitrogen, oxygen, and sulfur nucleophiles under in situ protonation of the intermediate enolate, without trapping with other electrophiles have been described [144]. 

NHC-Cu complexes can also mediate the enantioselective conjugated addition of a PhMejSi- moiety on a,p-unsaturated carbonyl compounds. Hoveyda and co-workers mainly focused their interest on the asymmetric 1,4- and 1,6-additions of silicon residues to ketones and acyclic (thio)esters. Procter developed similar transformations using unsaturated lactones or amides as Michael acceptors. ... 

Pyridine amide, derived from (5)-desmethyl-MAP, induces high enantioselectivity in Cu-catalyzed conjugate addition of Et2Zn to enones (eq 10). ... 

Various other applications are conjugate addition, 4 the ultrasound-promoted perfluoralkylation of SMP enamines, the enantioselective fluorodehydroxylation of SMP 1-yl-sulfur trifluoride, asymmetric telomerization of butadiene, the chiral modification of ruthenium clusters, and the application of SMP amide bases. ... 

Using a chiral auxiliary via an amide or ester leads to asymmetric induction. Aryl aldehydes and conjugated ketones were condensed using proline, leading to modest enantioselectivity. °° Chiral biaryl catalysts have been used with trialkyl-phosphines, giving good enantioselectivity. ° Chiral quinuclidine catalysts lead to... 

---