Engineering Catalysts for Selective Ester Hydrogenation

The development of efficient catalysts and processes for synthesizing functionalized (olefinic and/or chiral) primary alcohols and fluoral hemiacetals is currently needed. These are valuable building blocks for pharmaceuticals, agrochemicals, perfumes, and so forth. From an economic standpoint, bench-stable Takasago Int. Corp.’s Ru-PNP, more commonly known as Ru-MACHO, and Gusev’s Ru-SNS complexes are arguably the most appealing molecular catalysts to access primary alcohols from esters and H₂ (Waser, M. et al. Org. Proc. Res. Dev. 2018, 22, 862). This work introduces economically competitive Ru-SNP­(O)_z complexes (z = 0, 1), which combine key structural elements of both of these catalysts. In particular, the incorporation of SNP heteroatoms into the ligand skeleton was found to be crucial for the design of a more product-selective catalyst in the synthesis of fluoral hemiacetals under kinetically controlled conditions. Based on experimental observations and computational analysis, this paper further extends the current state-of-the-art understanding of the accelerative role of KO-t-C₄H₉ in ester hydrogenation. It attempts to explain why a maximum turnover is seen to occur starting at ∼25 mol % base, in contrast to only ∼10 mol % with ketones as substrates.