Atropisomeric Properties of 7-, 8-, and 9-Membered-Ring Dibenzolactams: Conformation, Thermal Stability, and Chemical Reactivity

The atropisomeric enantiomers of 7-, 8-, and 9-membered-ring dibenzolactams were separated by using chiral HPLC, and their stereochemistries were clarified by using X-ray crystallographic analysis. The atropisomers showed high stereochemical stability with the 8-membered ring being the most stable. In 7- and 8-membered dibenzolactams, highly stereoselective C7-methylation proceeded from the lower side of the ring to provide the products with a C7-methyl group in the pseudoaxial orientation, which converted to thermodynamically more stable isomers with the pseudoequatorial C7-methyl group. In 9-membered dibenzolactam, C7-methylation occurred from the opposite (upper) side of the ring to provide a thermodynamically stable product with the pseudoequatorial C7-methyl group.采用手性高效液相色谱（chiral HPLC）分离了7元、8元及9元环二苯并内酰胺的阻转异构对映异构体，并通过X射线晶体衍射分析明确了其立体化学构型。该类阻转异构体展现出较高的立体化学稳定性，其中8元环体系的稳定性最为突出。在7元及8元环二苯并内酰胺中，高立体选择性的C7位甲基化反应沿环的下方一侧进行，所得产物的C7位甲基呈假直立取向，该产物可转化为热力学更稳定的异构体，其C7位甲基为假平伏取向。在9元环二苯并内酰胺中，C7位甲基化反应沿环的另一侧（上方）进行，最终得到热力学稳定的产物，其C7位甲基为假平伏取向。