Metal-Templated Design: Enantioselective Hydrogen-Bond-Driven Catalysis Requiring Only Parts-per-Million Catalyst Loading

Based on a metal-templated approach
using a rigid and globular
structural scaffold in the form of a bis-cyclometalated octahedral
iridium complex, an exceptionally active hydrogen-bond-mediated asymmetric
catalyst was developed and its mode of action investigated by crystallography,
NMR, computation, kinetic experiments, comparison with a rhodium congener,
and reactions in the presence of competing H-bond donors and acceptors.
Relying exclusively on weak forces, the enantioselective conjugate
reduction of nitroalkenes can be executed at catalyst loadings as
low as 0.004 mol% (40 ppm), representing turnover numbers of up to
20 250. A rate acceleration by the catalyst of 2.5 × 105 was determined. The origin of the catalysis is traced to
an effective stabilization of developing charges in the transition
state by carefully orchestrated hydrogen-bonding and van der Waals
interactions between catalyst and substrates. This study demonstrates
that the proficiency of asymmetric catalysis merely driven by hydrogen-bonding
and van der Waals interactions can rival traditional activation through
direct transition metal coordination of the substrate.