The mechanism of the enantioselective 1,4-addition of Grignard reagents to alpha,beta-unsaturated carbonyl compounds promoted by copper complexes of chiral ferrocenyl diphosphines is explored through kinetic, spectroscopic, and electrochemical analysis. On the basis of these studies, a structure of the active catalyst is proposed. The roles of the solvent, copper halide, and the Grignard reagent have been examined. Kinetic studies support a reductive elimination as the rate-limiting step in which the chiral catalyst, the substrate, and the Grignard reagent are involved. The thermodynamic activation parameters were determined from the temperature dependence of the reaction rate. The putative active species and the catalytic cycle of the reaction are discussed.

It is no longer necessary to use dialkylzinc reagents to obtain enantioselectivities >95% in the copper-catalyzed asymmetric conjugate addition of organometallic compounds to cyclic enones. We now report how this can be accomplished by using inexpensive and readily available Grignard reagents. Screening of bidentate ligands provided outstanding results with copper complexes of commercially available chiral ferrocenyl-based diphosphines, in particular TaniaPhos and JosiPhos derivatives. These catalysts tolerate a range of Grignard reagents and different cyclic enones as substrates, leading to high regioselectivities and unprecedented enantioselectivities. Moreover, the reactions are successful with moderate catalyst loading (5 mol %) under mild conditions and in the absence of additives.

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