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 stereogenicityandregio-selectivity in a catalytic process is described. Alternate pseudo-diastereomeric chiral-at-ruthenium complexes of thetype RuX(CO)[& eta;(3)-prenyl][(S)-SEGPHOS]form in a halide-dependent manner and display divergent regio-selectivityin catalytic C-C couplings of isoprene to alcohol proelectrophilesvia hydrogen autotransfer. Whereas the chloride-bound ruthenium-SEGPHOScomplex prefers a trans-relationship between thehalide and carbonyl ligands and delivers products of carbonyl sec-prenylation, the iodide-bound ruthenium-SEGPHOS complexprefers a cis-relationship between the halide andcarbonyl ligands and delivers products of carbonyl tert-prenylation. The chloride- and iodide-bound ruthenium-SEGPHOS complexeswere characterized in solution and solid phase by P-31 NMRand X-ray diffraction. Density functional theory calculations of theiodide-bound catalyst implicate a Curtin-Hammett-type scenarioin which the transition states for aldehyde coordination from an equilibratingmixture of sec- and tert-prenylrutheniumcomplexes are rate- and product-determining. Thus, control of metal-centereddiastereo-selectivity has unlocked the first catalytically enantio-selectiveisoprene-mediated carbonyl tert-prenylations.

Automated summary

The first correlation between metal-centered stereogenicity and regio-selectivity in a catalytic process is described. Alternate pseudo-diastereomeric chiral-at-ruthenium complexes of the type RuX(CO)[& eta;(3)-prenyl][(S)-SEGPHOS] form in a halide-dependent manner and display divergent regio-selectivity in catalytic C-C couplings of isoprene to alcohol proelectrophiles via hydrogen autotransfer. Control of metal-centered diastereo-selectivity has unlocked the first catalytically enantio-selective isoprene-mediated carbonyl tert-prenylations.