Wang Zeming, Li Minhao, Zuo Weiwei
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, P. R. China.
J Am Chem Soc. 2024 Sep 25;146(38):26416-26426. doi: 10.1021/jacs.4c09351. Epub 2024 Sep 16.
The transition metal-catalyzed asymmetric hydrogenation (AH) of ketones to produce enantioenriched alcohols is an important reaction in organic chemistry with applications in the pharmaceutical and agrochemical fields. Using earth-abundant, biorelevant cobalt as the central metal in the catalyst has a high potential to improve sustainability and achieve hydrogenation reactions that are scalable. However, due to the high d-electron count, designing cobalt catalysts that exhibit turnover numbers (TONs, ≥1000) and enantioselectivities (≥90%) sufficient for synthetic utility and practical scalability (≥1 kg scale) remains a challenge. In this work, an efficient catalyst design strategy utilizing an amino(imino)diphosphine Co(II) bromide precatalyst is presented to achieve this goal. The quantitative production of a wide range of secondary chiral alcohols with TONs of up to 150,000 and an enantiomeric excess (e.e.) of up to 99% at a scale of up to 1.35 kg was achieved, indicating that the proposed cobalt catalyst is highly promising for AH and scale-up reactions. A mechanistic study revealed that the synergism of an N-H functionality and a redox-active ligand endows the cobalt catalyst with a high productivity and excellent enantioselectivity.
过渡金属催化的酮不对称氢化（AH）反应生成对映体富集的醇是有机化学中的一个重要反应，在制药和农用化学品领域有应用。使用地球上储量丰富、与生物相关的钴作为催化剂的中心金属，对于提高可持续性以及实现可规模化的氢化反应具有很大潜力。然而，由于钴的d电子数较高，设计出具有足够的周转数（TONs，≥1000）和对映选择性（≥90%）以满足合成实用性和实际可规模化（≥1 kg规模）的钴催化剂仍然是一个挑战。在这项工作中，提出了一种利用氨基（亚氨基）二膦溴化钴（II）预催化剂的高效催化剂设计策略来实现这一目标。在高达1.35 kg的规模下，实现了多种仲手性醇的定量生产，TONs高达150,000，对映体过量（e.e.）高达99%，这表明所提出的钴催化剂在不对称氢化反应和放大反应方面具有很高的前景。机理研究表明，N-H官能团和氧化还原活性配体的协同作用赋予了钴催化剂高活性和优异的对映选择性。
