Iron catalyzed asymmetric hydrogenation of ketones

Chiral molecules, such as alcohols, are vital for the manufacturing of fine chemicals, pharmaceuticals, agrochemicals, fragrances, and novel materials. These molecules need to be produced in high yield and high optical purity and preferentially catalytically. Among all the asymmetric catalytic reactions, asymmetric hydrogenation with H2 (AH) is the most widely used in the industry. With few exceptions, these AH processes use catalysts based on the three critical metals, rhodium, ruthenium, and iridium. Herein we describe a simple, industrially viable iron catalyst that allows for the AH of ketones, a process currently dominated by ruthenium and rhodium catalysts. By combining a chiral, 22-membered macrocyclic ligand with the cheap, readily available Fe3(CO)12, a wide variety of ketones have been hydrogenated under 50 bar H2 at 45-65 °C, affording highly valuable chiral alcohols with enantioselectivities approaching or surpassing those obtained with the noble metal catalysts. In contrast to AH by most noble metal catalysts, the iron-catalyzed hydrogenation appears to be heterogeneous.