Asymmetric conjugate addition copper complex

Chiral diaminocarbene complexes of copper were used in asymmetric conjugate addition of diethylzinc to Michael acceptors. Achiral copper carbene complexes derived from imidazolium salts were synthesized and characterized for the first time by Arduengo in 1993 [43]. In 2001, Woodward reported the use of such Arduengo-type carbene in copper-catalyzed conjugate addition and showed their strong accelerating effect [44]. The same year, Alex-... 

This work was initiated in 1988 when Villacorta et al.71a reported the asymmetric conjugate addition of a Grignard reagent to 2-cyclohexenone. This study showed that 1,4-adducts with 4-14% ee were obtained in the presence of aminotroponeimine copper complex.713 Enhanced results (74% ee) were obtained by adding HMPA or silyl halides.71b Several other copper complexes were also used for inducing asymmetric conjugate addition reactions. Moderate results were obtained in most cases when THF was used as the solvent and HMPA as the additive. 

To investigate the effect of the substituents in the arenethiolate structure, four differently substituted copper arenethiolates, 25-28, were tested as catalysts, but very low ees were obtained in all cases [34]. The oxazolidine complex 26, developed by Pfaltz et al. [36] and used successfully in asymmetric conjugate addition reactions to cyclic enones, gave a completely racemic product with allylic substrate 20a. 

In the same year, Roland and coworkers described a chiral silver-NHC complex with a tert-butyl substituted backbone for copper-catalyzed addition of Et2Zn to 2-cyclohexanone. However, the addition product was isolated in low enantioselectivity (23% ee) [77]. Later on, Alexakis et al. modified the carbene structure to improve the enantioselectivity (Scheme 3.51) [78]. By using the chiral silver-NHC salt 90 to transmetallate and generate the Cu catalyst, the asymmetric conjugate addition of diethylzinc to 2-cycloheptanone was achieved in good yield (95%) and enantioselectivity (93% ee). 

Chiral Lewis acids derived from complexes between copper(I) chloride with phosphino sulfenyl ferrocenes are efficient catalysts for enantioselective aza-Diels-Alder reaction of A-sulfonyl imines with Danishefsky-type dienes (eq 47), and asymmetric conjugate addition of Grignard reagents to cyclic enones (eq 48).136... 

A new asymmetric urea-copper complex catalyst that is capable of helical chirality inversion has been developed. The enantioselectivity of the asymmetric conjugate addition of diethyl malonate to trans- -nitrostyrene has been found to depend on the helicity of the catalyst. Either enantiomer of the product can be predetermined by selection of the oxidation state of the copper ion. Facile interconversion between the... 

Tanaka reported the synthesis of (/ )-muscone (10) by an enantioselective conjugate addition of chiral alkoxydimethylcuprate, which was prepared from chiral ercdo-3-[(l-methylpyrrol-2-yl)methylamino]-l,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (9), methyllithium, and copper iodide (Scheme 9.7) [16]. In this reaction, convex deviation from a linear correlation was observed when the chiral ligand had a higher enantiopurity. This positive NLE was probably induced by the formation of a reactive homochiral dinuclear copper complex to give (R)-muscone. Rossitter also observed asymmetric amplification in a copper-catalyzed conjugate addition of methyl-... 

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