Aldehyde (α-Methoxy)allylation via 2-Propanol-Mediated Reductive Coupling: Halide-Dependent Regio- and Enantioselection from 1 of 24 Fluxional Diastereomeric-at-Ruthenium-SEGPHOS Complexes

Halide-dependent regio- and enantioselectivity is observed in methoxyallene-aldehyde reductive couplings mediated by 2-propanol that are catalyzed by the pseudo-diastereomeric-at-metal complexes RuX[η3-(α-MeO)allyl](CO)[(S)-SEGPHOS], where X = Cl vs I. In reactions of the chloride-bound catalyst, for which the CO and chloride ligands adopt a trans-diapical arrangement, equimolar quantities of linear and branched adducts are formed with low levels of enantiomeric enrichment. In reactions of the iodide-bound catalyst, the CO and halide ligands reside in adjacent coordination sites, and complete branched regioselectivity is accompanied by high levels of anti-diastereo- and enantioselectivity. In prior work on isoprene-mediated carbonyl prenylation, the stereochemistries of the chloride- and iodide-bound ruthenium-SEGPHOS catalysts were established by X-ray diffraction and 31P nuclear magnetic resonance spectroscopic analyses of the parent π-allylruthenium complexes, RuX(η3-C3H5)(CO)[(S)-SEGPHOS], where X = Cl vs I. In the present carbonyl (α-methoxy)allylations, calculations of the 24 possible diastereomeric complexes reveal that 4 isomers constitute 93.1% of the resting state, but the kinetic contribution to carbonyl addition is dominated by just the two most stable transition states. These computational data align with experimentally observed diastereo- and enantioselectivities and demonstrate that diastereomeric-at-metal catalysts embody distinct regio- and stereoselectivities, a fact that has broad implications for the field of enantioselective metal catalysis.