Synthesis of a Stereochemically Diverse Library of Medium-Sized Lactams and Sultams via SNAr Cycloetherification

We have implemented an aldol-based "build/couple/pair" (B/C/P) strategy for the Sinksil of SterreocherniCally. diverse 8-membered lactam and sultam Scaffolds: via SNAr cycloetherification. Each scaffold contains two handles, an amine and aryl bromide, for solid-phase diversification via N-capping and Pd mediated cross coupling. A sparse matrix design strategy that achieves the dual objective of controlling physicochemical properties and selecting diverse library members was implemented. The.production of two 8000-membered libraries is discussed including a full analysis of library purity and property distribution. Library diversity was evaluated in comparison to the Molecular Library Small Molecule Repository (MLSMR) through the use of a multifusion similarity (MFS) map and principal component analysis (PCA).