Theoretical Studies on Solvent and Substituent Effects of Cuprate Conjugate Addition

Conjugate addition of lithium diorganocuprate to acrolein, cyclohexenone, and 4,4-dimethylcyclohexenone has been studied in the presence of Me 2 O molecules coordinated on the lithium atoms. Solvation does not change the mechanism of the conjugate addition but increases the activation energy of the C−C bond-forming step through attenuation of the Lewis acidity of the lithium atoms. The substituent on the enone electrophile was found to have considerable influence on the activation energy. Computed activation energy of the conjugate addition of lithium dimethylcuprate to 4,4-dimethylcyclohexenone is Δ E ⧧ = 15.5 kcal/mol, which is close to the experimental data ( E a = 18.2 ± 1.7 kcal/mol). The 12 C/ 13 C kinetic isotope effects were found to be susceptible to substituent effects. The 13 C NMR chemical shift values qualitatively agree with experimental data.