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.

Grant Number: 5R01GM131079-07
NIH Institute/Center: NIH
Principal Investigator: Mark Biscoe