Chiral-at-Ruthenium-SEGPHOS Catalysts Display Diastereomer-Dependent Regioselectivity: Enantioselective Isoprene-Mediated Carbonyl tert -Prenylation via Halide Counterion Effects.

The first correlation between metal-centered stereogenicity and regioselectivity in a catalytic process is described. Alternate pseudo -diastereomeric chiral-at-ruthenium complexes of the type RuX(CO)[η 3 -prenyl][( S )-SEGPHOS] form in a halide-dependent manner and display divergent regioselectivity in catalytic C-C couplings of isoprene to alcohol proelectrophiles via hydrogen autotransfer. Whereas the chloride-bound ruthenium-SEGPHOS complex prefers a trans -relationship between the halide and carbonyl ligands and delivers products of carbonyl sec -prenylation, the iodide-bound ruthenium-SEGPHOS complex prefers a cis -relationship between the halide and carbonyl ligands and delivers products of carbonyl tert -prenylation. The chloride- and iodide-bound ruthenium-SEGPHOS complexes were characterized in solution and solid phase by 31 P NMR and X-ray diffraction. Density functional theory calculations of the iodide-bound catalyst implicate a Curtin-Hammett-type scenario in which the transition states for aldehyde coordination from an equilibrating mixture of sec - and tert -prenylruthenium complexes are rate- and product-determining. Thus, control of metal-centered diastereoselectivity has unlocked the first catalytically enantioselective isoprene-mediated carbonyl tert -prenylations.