Engineering Catalysts for Selective Ester Hydrogenation

• Published in: Organic process research & development 2020-03, Vol.24 (3), p.415-442
• Main Authors: Dub, Pavel A, Batrice, Rami J, Gordon, John C, Scott, Brian L, Minko, Yury, Schmidt, Jurgen G, Williams, Robert F
• Format: Article
• Language: English
• Subjects: base effect; ester hydrogenation; fluoral hemiacetal; homogeneous catalysis; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; mechanism
• ISSN: 1083-6160; 1520-586X
• DOI: 10.1021/acs.oprd.9b00559

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.