Kh. Shaughnessy et al., A fluorescence-based assay for high-throughput screening of coupling reactions. Application to Heck chemistry, J AM CHEM S, 121(10), 1999, pp. 2123-2132
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.