A fluorescence-based assay for high-throughput screening of coupling reactions. Application to Heck chemistry

A new fluorescence-based assay for high-throughput screening of reactions t hat couple two organic molecules is described. The assay involves reaction of one substrate containing a tethered fluorophore with a second molecule t hat is attached to a solid support. A successful coupling process is signal ed by fluorescence of the solid support, which can be isolated by either si mple centrifugation or filtration. To evaluate this assay in the context of a catalytic process under intense current study, we searched for improved, readily available phosphines for Heck chemistry. An acrylate containing a tethered coumarin was reacted with an aryl halide supported on a cross-link ed polystyrene resin. Comparison of the results from our fluorescence-based assay with results from serial GC analysis showed that the fluorescence-ba sed assay accurately selected the most active ligands for the Heck coupling of aryl bromides and chlorides. Two ligands chosen by the assay, tri (tert -butyl)phosphine and di(tert-butylphosphino)ferrocene, were found to be the most active systems to date for the olefination of unactivated aryl bromid es, and di(tert-butylphosphino)ferrocene is the most efficient ligand for o lefination of unactivated aryl chlorides.