Conjugate stoichiometric enantioselective

On the other hand, chiral sulfur-containing but noncoordinating ligands such as sulfonamides have been widely used in the asymmetric Michael reaction. In 1997, Sewald et al. reported the use of a series of chiral sulfonamides depicted in Scheme 2.25 in the Cu-catalysed conjugate addition of ZnEt2 to 2-cyclohexenone. Even the use of a stoichiometric amount of catalyst did not allow the enantioselectivity to be higher than 31% ee. 

TFA) was used in place of TFAA, non-A-protected aziridines were obtained as the products.144 Although the reactions of conjugated trans-olefins show high enantioselectivity, a stoichiometric amount of the nitrido-Mnv species is required. 

Tanaka et al. (152) demonstrated that a chiral copper alkoxide could be used substoichiometrically to deliver MeLi to an enone in conjugate fashion. The precatalyst is formed from amino alcohol 221, MeLi and Cul, Eq. 123a. Under stoichiometric conditions, this catalyst mediates the conjugate addition of MeLi to the macrocyclic enone, affording muscone in 91% ee. Lower enantioselectivity is observed using a substoichiometric amount of 222 (0.5 equiv), affording a 79% yield of muscone in 76% ee, Eq. 123b. These selectivities are attained by portion-wise addition of the substrate and MeLi to the alkoxy-cuprate. This catalyst also exhibits a complex nonlinear effect (78, 153). 

A number of conjugate additions delivering excellent enantioselectivities through the use of organocuprates in the presence of stoichiometric amounts of chiral (non-transferable) ligands are known today [7-9]. 

Many of the copper-mediated transformations summarized in the previous sections of this chapter can also be performed efficiently with catalytic amounts of copper salts or reagents. Indeed, some of the copper-catalyzed reactions have been discovered before the development of stoichiometric organocopper reagents. The focus of the last decade has been put on new copper-catalyzed transformations (e.g., conjugate reductions) and in particular on the discovery of chiral copper catalysts for highly enantioselective 1,4-addition and S -substitution reactions of prochiral substrates. 

Sibi et al. [66] reported the first examples of highly enantioselective conjugate amine additions [67] by use of catalytic amounts of a chiral Lewis acid complex. Addition of 0-benzylhydroxyamine 87 (1.1 equiv.) to the pyrazole-derived crotonamide 86 proceeded smoothly in the presence of stoichiometric amounts of the chiral catalyst prepared from the bis(oxazoline) 50 and MgBr2 OEt2 with high enantiomeric excess (96 % ee) (Sch. 37). This conjugate addition reaction was equally effective with catalytic amounts of the chiral Lewis acid (92 % ee with 30 mol % 88 % ee with 10 mol %). A re face amine addition to the s-cis substrate bound to the chiral complex with tetrahedral- or ds-octahedral arrangements XXXII and XXXni accounts for the product stereochemistry observed (Fig. 7). 

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