Probing Substrate Scope with Molecular Volcanoes

Molecular
volcano plots, a tool generally used to identify ideal catalysts for
a given chemical transformation, are employed in an alternative fashion
to examine the substrate scope by revealing the range of substrates
that can be accommodated by a single catalyst. Here the power to rationalize
and better understand the substrate scope is demonstrated through
the evaluation of the energetics of various electrophilic substrates
for a Suzuki cross-coupling reaction. The plots reproduce experimentally
known trends while quantifying the magnitude to which the overall
activity depends on a substrate’s intrinsic electronic and
steric properties and how these energetics are altered by the addition
of substituent groups or changes to the core structure. Overall, the
information revealed by these substrate volcanoes can be used in tandem
with conventional molecular volcano plots to identify general catalyst
design principles for a series of substrates.