Direct Observation of Diastereomeric α‑C-Bound Enolates during Enantioselective α‑Arylations: Synthesis, Characterization, and Reactivity of Arylpalladium Fluorooxindole Complexes

The
Pd-catalyzed asymmetric α-arylation of carbonyl compounds
is a valuable strategy to form benzylic stereocenters. However, the
origin of the stereoselectivity of these reactions is poorly understood,
and little is known about the reactivity of the putative diastereomeric
arylpalladium enolate intermediates. To this end, we report the synthesis
and characterization of a series of diphosphine-ligated arylpalladium
fluoroenolate complexes, including complexes bearing a metal-bound,
stereogenic carbon and an enantioenriched chiral diphosphine ligand.
These complexes reductively eliminate to form chiral α-aryl-α-fluorooxindoles
with enantioselectivities and rates that are relevant to those of
the catalytic process with SEGPHOS as the ancillary ligand. Kinetic
studies showed that the rate of reductive elimination is slightly
slower than the rate of epimerization of the intermediate, causing
the reductive elimination step to impart the greatest influence on
the enantioselectivity. DFT calculations of these processes are consistent
with these experimental rates and suggest that the minor diastereomer
forms the major enantiomer of the product. The rates of reductive
elimination from complexes containing a variety of electronically
varied aryl ligands revealed the unusual trend that complexes bearing
more electron-rich aryl ligands react faster than those bearing more
electron-poor aryl ligands. Noncovalent Interaction (NCI) and Natural
Bond Orbital (NBO) analyses of the transition-state structures for
reductive elimination from the SEGPHOS-ligated complexes revealed
key donor–acceptor interactions between the Pd center and the
fluoroenolate fragment. These interactions stabilize the pathway
to the major product enantiomer more strongly than they stabilize
that to the minor enantiomer.