Copper catalysed 1,4-addition of organozinc reagents to α,β-unsaturated carbonyl compounds: a mechanistic investigation

A mechanistic study of the 1,4-addition of diethylzinc to 2-cyclohexenone catalysed by copper complexes of the Schiff base ligand H2L1 was performed. The kinetic law of this system was determined and the nature of the different copper complexes involved in the reaction was investigated. The experimental results indicate a first-order dependence of the reaction rate on 2-cyclohexenone concentration, a zero-order on diethylzinc concentration, and a first-order dependence with respect to the concentration of a 1:1.2 mixture of Cu(OTf)2 and H2L1. A sharp change in the kinetics of the reaction was observed at catalyst concentrations higher than 9 mM, indicating the possible formation of catalytically inactive species. An aggregate copper complex, with the molecular formula [(CuL1)2 · Cu(OTf)2](TfOH)1/3 (1), is formed upon mixing Cu(OTf)2 and ligand H2L1 in toluene. Complex 1 is reduced in situ to a catalytically active copper(I) species by addition of 12 equivalents of Et2Zn. This species is able to perform the conjugate addition to 2-cyclohexenone under stoichiometric conditions and resumes its catalytic activity in the presence of 2-cyclohexenone and Et2Zn.