Absence of Stereoelectronic Control in Hydrolysis of Cyclic Amidines

Article abstract of DOI:10.1021/ja00279a055

According to Deslongchamps' theory of stereoelectronic control, preferentioal cleavage of a tetrahedral intermediate occurs when there are two lone pairs antiperiplanar to the leaving group.For reasons presented (Perrin and Arrhenius, J.Am.Chem.Soc. 1982, 104, 2839), product studies of hydrolysis of cyclic amidines can test this theory, and initial results supported it.However, those results are ambiguous, owing to a mismatch of leaving abilities.We now find that hydrolysis of three six-membered ring amidines bearing matched leaving groups produces predominantly aminoamide, the product of ring cleavage, and only 3-9percent lactam, as expected from the theory.In contrast, hydrolysis of three five- or seven-membered ring amidines produces substantial (ca. 50percent) lactam.Despite attempts to accomodate these results to the theory, it is concluded that there is no general requirement for two lone pairs antiperiplanar to the leaving group and that stereoelectronic control, even in six-membered ring amidines, contributes less than 2 kcal/mol.