Ir-Catalyzed Atroposelective Desymmetrization of Heterobiaryls: Hydroarylation of Vinyl Ethers and Bicycloalkenes

A highly
regio-, diastereo-, and enantioselective, scalable Ir-catalyzed hydroarylation
of electron-rich acyclic and tensioned cyclic olefins with heterobiaryls
is described. The reaction of acyclic vinyl ethers, dihydrofuran,
and norbornenes with a variety of aryl isoquinoline, quinazoline,
and picoline derivatives takes place with simultaneous installation
of central and axial chirality, reaching complete branched/linear
or exo/endo ratios and excellent diastereo- and enantiomeric excesses
when in situ formed [IrI/Tol-SDP] or [IrI/Tol-BINAP]
complexes are used as the catalysts. Deuterium labeling experiments
and a comprehensive computational study suggest that, despite fast
double bond migratory insertion into Ir–H, the reaction proceeds
through a modified Chalk–Harrod mechanism, starting with selectivity-determining
insertion into Ir–CAryl. The regioselectivity is
controlled by the electron-donating alkoxy group, whereas diastereo-
and enantioselectivity have a complex origin, which depend on the
relative orientation of the alkoxy group and the establishment of
adequate π–π interactions between the biaryl and
the phosphine.