Mechanism Studies of Ir-Catalyzed Asymmetric Hydrogenation of Unsaturated Carboxylic Acids

The Ir-catalyzed asymmetric hydrogenation
of olefins is widely
used for production of value-added bulk and fine chemicals. The iridium
catalysts with chiral spiro phosphine-oxazoline ligands developed
in our group show high activity and high enantioselectivity in the
hydrogenation of olefins bearing a coordinative carboxyl group, such
as α,β-unsaturated carboxylic acids, β,γ-unsaturated
carboxylic acids, and γ,δ-unsaturated carboxylic acids.
Here we conducted detailed mechanistic studies on these Ir-catalyzed
asymmetric hydrogenation reactions by using (E)-2-methyl-3-phenylacrylic
acid as a model substrate. We isolated and characterized several key
intermediates having Ir–H bonds under the real hydrogenation
conditions. Particularly, an Ir­(III) migratory insertion intermediate
was first isolated in an asymmetric hydrogenation reaction promoted
by chiral Ir catalysts. That this intermediate cannot undergo reductive
elimination in the absence of hydrogen strongly supports the involvement
of an Ir­(III)/Ir­(V) cycle in the hydrogenation. On the basis of the
structure of the Ir­(III) intermediate, variable-temperature NMR spectroscopy,
and density functional theory calculations, we elucidated the mechanistic
details of the Ir-catalyzed hydrogenation of unsaturated carboxylic
acids and explained the enantioselectivity of the reactions. These
findings experimentally and computationally elucidate the mechanism
of Ir-catalyzed asymmetric hydrogenation of olefins with a strong
coordinative carboxyl group and will likely inspire further catalyst
design.