Producing specific secondary alcohols via ketone catalysis

Jing Wu et al. have synthesized enantiomerically pure secondary alcohols under mild reaction conditions. The stereospecific alcohols, formed by the hydrosilylation of prochiral ketones, are intermediates in the manufacturing of industrial compounds and pharmaceuticals. Previous methods for creating the alcohols have been hampered by the high cost of metal catalysts, low substrate-to-catalyst ratios, and rigorous production conditions. In previous work, the authors developed a system using the atropisomeric dipyridylphosphine ligand P-Phos [2,2 ,6,6 -tetramethoxy-4,4 bis-(diphenylphosphino)-3,3 bipyridine] and its analogs for ruthenium-catalyzed hydrogenation of a broad scope of simple ketones. In the present study, the authors employed the Xyl-P-Phos analog and demonstrated that, in a nitrogen atmosphere, it served as an effective catalyst for the hydrosilylation of acetophenone in the presence of CuF2. Other copper(I) and copper(II) salts showed diminished reactivities. When the reactions were carried out in air atmosphere and at moderately low temperatures ( 20°C), they could produce levels of enantioselectivities for metaand parasubstituted acetophenones of up to 97% and achieve high activities with substrate ligand ratios of 50,000– 100,000. The authors employed their catalyst system in a wide array of asymmetric diaryl ketones without the addition of organic or inorganic bases and found similar selectivities, representing an important advancement in the field.