asymmetric catalysis · copper · homogeneous catalysis · Michael additionCopper-catalyzed asymmetric conjugate addition reactions of organometallic reagents to Michael acceptors have been an important research topic for two decades. New procedures developed by careful tuning of the reaction conditions, the organometallic reagent, and the chiral ligand provide the conjugate adducts with very high enantioselectivities.[1] This brief overview of copper-catalyzed asymmetric conjugate addition reactions highlights some of the most important recent contributions.Copper-catalyzed enantioselective conjugate addition reactions were first studied with Grignard reagents.[2] With chiral ferrocene ligands, such as taniaphos [3] or josiphos, [4] EtMgBr underwent Michael addition to unsaturated esters, such as 1 a and 1 b. In the presence of the regioisomeric copper-ligand complex 2 a (0.5 mol %) or 2 b (1.5 mol %), the expected adducts 3 a and 3 b were formed in 99 % yield with 93 and 96 % ee, respectively (Scheme 1).[5] Interestingly, the use of (S)-Tol-binap (4) in combination with CuI (1 mol %) enables stereoselective addition reactions to E-and Z-unsaturated esters to be carried out. For example, (E)-5 and (Z)-5 were converted into the two enantiomeric Michael adducts 6 and ent-6 in 93 and 94 % ee, respectively. [6] No isomerization of the sensitive unsaturated ester (Z)-5 was observed during the reaction.This methodology could be used directly for the addition of MeMgBr to the a,b-unsaturated ester 7 in the presence of (S)-Tol-binap (4) and CuI. The conjugate adduct 8 was formed in 68 % yield with 96 % ee (Scheme 2). By using an iterative reaction sequence, it was possible to synthesize both anti-9 (obtained with (R)-binap) and syn-9 (obtained with (S)-binap) with d.r. > 95:5. Remarkably, the stereoselectivity of the addition is not affected by the stereogenic center already present in the substrate. Further iterations provided a straightforward route to the marine natural product siphonarienal (10).[7] When (R,S)-josiphos [4] is used as the chiral ligand, the addition of MeMgBr proceeds most efficiently with unsaturated thioesters, rather than methyl esters, as substrates. Thus, the Michael adduct 12 was formed in 92 % yield with 96 % ee from 11. Compound 12 was converted readily in two steps into the chiral unsaturated thioester 13 (81 %), which was transformed in a further asymmetric conjugate addition step into either syn-14 or anti-14 with d.r. ! 95:5, depending on the configuration of the josiphos catalyst. This iterative method was applied to the synthesis of the insect pheromone (À)-lardolure (15). [8] To extend the scope of the 1,4-addition of organomagnesium reagents, [9] a new modular phosphine-phosphite ligand 16 was prepared from inexpensive 2-tert-butylphenol (17) and taddol. [10,11] This type of ligand enables the conjugate addition of a broad range of Grignard reagents to 2-cyclohexenone. The use of a nonpolar, weakly coordinating ether, such as 2-methyltetrahydrofuran, [12] as the solvent proved essentia...