Eight-Membered-Ring Lactams - New Scaffolds for Combinatorial Chemistry Prepared by Ring-Expansion of 1,4-Diketones with Primary Amines

Eight‐membered‐ring lactams were prepared by the Bi‐catalyzed reaction of 1,4‐diketones with primary amines. These lactams define a new type of non‐planar molecular scaffold with three points allowing for diversification, which were evaluated as the basis for combinatorial library synthesis. For this reason, reaction conditions were optimized, and the scope and limitations were investigated. After the Bi‐catalyzed reaction, further diversification was achieved by ester saponification and subsequent amide formation with HATU and another primary amine. Representative examples of a model library showed sufficient stability in DMSO and solubility in aqueous buffer, which are mandatory prerequisites due to our in‐house combinatorial chemistry criteria for library production. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)