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.

当前亟需开发用于合成官能化（烯基化和/或手性）伯醇及氟醛半缩醛的高效催化剂与合成工艺。这类化合物是医药、农用化学品、香料等领域的高价值结构砌块。从经济性角度出发，实验室稳定的高砂国际公司（Takasago Int. Corp.）开发的Ru-PNP配合物（更常被称为Ru-MACHO）以及古谢夫（Gusev）的Ru-SNS配合物，无疑是目前从酯与氢气出发制备伯醇的最具吸引力的分子催化剂（Waser M等人，《有机工艺研究与开发》（Org. Proc. Res. Dev.），2018，22，862）。本研究开发了兼具经济竞争力的Ru-SNP(O)z配合物（z=0、1），该类配合物整合了上述两类催化剂的关键结构单元。具体而言，研究发现将SNP杂原子引入配体骨架，对于在动力学控制条件下设计用于氟醛半缩醛合成的高产物选择性催化剂至关重要。基于实验观测与计算分析，本文进一步拓展了当前对酯氢化反应中叔丁醇钾（KO-t-C4H9）催化加速作用的前沿认知。本研究尝试解释为何当碱用量约为底物摩尔量的25%时，催化转化数达到峰值，而当以酮为底物时，该峰值仅出现在碱用量约10 mol%的条件下。