Stereospecific Cross-Coupling Reactions as a Tool for Three Dimensional Molecular Diversification

PROJECT SUMMARY/ABSTRACT Using enantioenriched organometallic nucleophiles in transition metal-catalyzed carbon-carbon bond-forming reactions, we aim to develop general tools for the rational manipulation of three- dimensional molecular structure. By introducing absolute stereochemistry prior to the formation of a final stereogenic center, and reliably transferring this stereochemistry via stereoretentive or stereoinvertive cross-coupling processes, the rapid preparation of diverse libraries of single- enantiomer drug candidates for use in biological assays will be achievable. The use of enantioenriched secondary alkylboron and alkylstannane nucleophiles will be explored in Pd- and Cu-catalyzed alkyl-aryl and alkyl-alkyl cross-coupling reactions, with particular focus on the derivatization of medicinally relevant organic frameworks and chiral structural motifs that are currently inaccessible but are of biological or pharmaceutical interest.