1,2- versus 1,4-Addition to α-donor-cyclopenten-1-ones; a comparison of calculated and experimental data†

Abstract

A series of α-donor-cyclopenten-1-ones, 1 (α-donor; X = H, Cl, Br, OMe, pyrrolidin-1-yl, SPh and SePh) were treated with methyllithium, lithium dimethylcuprate and cyanomethyllithium in tetrahydrofuran at –78 °C. The reactions between 1 and methyllithium gave 1,2-adducts in 28–75% yield. No trace of the corresponding 1,4-adduct was observed. By treatment of 1 with lithium dimethylcuprate only 1,4-addition was obtained in 51–76% yield, except for X = OMe or pyrrolidin-1-yl, which gave no reaction at all. In the reactions between 1 and cyanomethyllithium the 1,2-adducts were the main products (43–60%), but varying amounts of 1,4-adducts (8–30%) were also formed. The products formed have been fully characterized. Net atomic charges obtained by density functional theory (DFT) calculations of the lithiated cations of 1 with X = H, Cl, Br or OMe showed very small differences between the substituted and unsubstituted systems for all X, except for X = OMe. In this case the C² position was positive rather than negative. The C³ position was found to be significantly more negative. The calculated relative energies of the methylated and cyanomethylated 1,2- and 1,4-adducts with X = H, Cl, Br and OMe indicated that the 1,4-adducts were thermodynamically favoured by 8 to 12 kcal mol^–1 for all but one case. In the cyanomethylation of 1 with X = OMe the 1,2-adduct was predicted to be favoured by 12 kcal mol^–1. Thus, the predominance of 1,2-attack in the reactions involving methyllithium and cyanomethyllithium cannot be explained by the relative thermodynamic stabilities of the products.