Vicinal (1,2-disubstituted) functional group motifs are
ubiquitous in structurally complex small molecules that are of
academic and industrial importance, including many widely used
pharmaceutical agents. Many such functional group combinations,
however, remain exceptionally challenging to synthesize. The goal of
research in the Engle lab is to develop a general catalytic platform
for alkene and alkyne difunctionalization to introduce a diverse array
of functional groups at each of the two carbon atoms in a programmable
fashion. Our central hypothesis is that is that Lewis basic directing
groups can be used to: (1) control the regioselectivity of Heck- and
Wacker-type alkene addition, (2) stabilize the resultant alkylmetal
intermediate to allow to allow efficient downstream trapping, and (3)
enhance selectivity for three-component coupling over competitive
two-component coupling. This concept has been used to expand the
synthetic toolkit to include new retrosynthetic disconnections,
including “homo-Michael” addition and β,γ-vicinal
dicarbofunctionalization of alkenyl carbonyl compounds.









Keary Engle (Scripps Research Institute)