Autoassembly of cage structures. 4. Stereochemistry of 2,5-di-tert-butyl-γ-butyrolactone-4-carboxy-s-(α)-phenylethylamide

The diastereoisomeric lactonamides (2a, b), obtained from the dilactone (1) and S-phenylethylamine, have been separated. X-ray crystallography shows that the high-melting isomer (2a) has the R-configuration at the chiral centers C² and C⁴, the enantiomeric conformation of the γ-lactone ring being of the S-type in the twist form, intermediate between envelope²E and semi-chair₃²T. It is shown by molecular mechanics that the minimum steric energy of 2a corresponds to a conformation of the heterocycle close to the envelope form₃E. Examination of van der Waals interactions shows that the calculated structure for 2a is preferred. The reasons for the nonidentity of the forms of the γ-lactone ring of 2a in the crystal and the free state are discussed. The crystal structure of 2a is composed of two geometrically similar independent molecules associated along the axis by weak hydrogen bonds of two types, the energies of which have been estimated from the v_XH values, which are related by the expression v_XH=f(R_X...O), where X=N, O.