598-74-3Relevant articles and documents
One-pot reductive amination of carboxylic acids: a sustainable method for primary amine synthesis
Coeck, Robin,De Vos, Dirk E.
supporting information, p. 5105 - 5114 (2020/08/25)
The reductive amination of carboxylic acids is a very green, efficient and sustainable method for the production of (bio-based) amines. However, with current technology, this reaction requires two to three reaction steps. Here, we report the first (heterogeneous) catalytic system for the one-pot reductive amination of carboxylic acids to amines, with solely H2 and NH3 as the reactants. This reaction can be performed with relatively cheap ruthenium-tungsten bimetallic catalysts in the green and benign solvent cyclopentyl methyl ether (CPME). Selectivities of up to 99% for the primary amine could be achieved at high conversions. Additionally, the catalyst is recyclable and tolerant for common impurities such as water and cations (e.g. sodium carboxylate).
Ruthenium Catalyzed Direct Asymmetric Reductive Amination of Simple Aliphatic Ketones Using Ammonium Iodide and Hydrogen
Ernst, Martin,Ghosh, Tamal,Hashmi, A. Stephen K.,Schaub, Thomas
supporting information, (2020/07/14)
The direct conversion of ketones into chiral primary amines is a key transformation in chemistry. Here, we present a ruthenium catalyzed asymmetric reductive amination (ARA) of purely aliphatic ketones with good yields and moderate enantioselectivity: up to 99 percent yield and 74 percent ee. The strategy involves [Ru(PPh3)3H(CO)Cl] in combination with the ligand (S,S)-f-binaphane as the catalyst, NH4I as the amine source and H2 as the reductant. This is a straightforward and user-friendly process to access industrially relevant chiral aliphatic primary amines. Although the enantioselectivity with this approach is only moderate, to the extent of our knowledge, the maximum ee of 74 percent achieved with this system is the highest reported till now apart from enzyme catalysis for the direct transformation of ketones into chiral aliphatic primary amines.
Rapid and Quantitative Profiling of Substrate Specificity of ω-Transaminases for Ketones
Han, Sang-Woo,Shin, Jong-Shik
, p. 3287 - 3295 (2019/06/21)
ω-Transaminases (ω-TAs) have gained growing attention owing to their capability for asymmetric synthesis of chiral amines from ketones. Reliable high-throughput activity assay of ω-TAs is essential in carrying out extensive substrate profiling and establishing a robust screening platform. Here we report spectrophotometric and colorimetric methods enabling rapid quantitation of ω-TA activities toward ketones in a 96-well microplate format. The assay methods employ benzylamine, a reactive amino donor for ω-TAs, as a cosubstrate and exploit aldehyde dehydrogenase (ALDH) as a reporter enzyme, leading to formation of benzaldehyde detectable by ALDH owing to concomitant NADH generation. Spectrophotometric substrate profiling of two wild-type ω-TAs of opposite stereoselectivity was carried out at 340 nm with 22 ketones, revealing subtle differences in substrate specificities that were consistent with docking simulation results obtained with cognate amines. Colorimetric readout for naked eye detection of the ω-TA activity was also demonstrated by supplementing the assay mixture with color-developing reagents whose color reaction could be quantified at 580 nm. The colorimetric assay was applied to substrate profiling of an engineered ω-TA for 24 ketones, leading to rapid identification of reactive ketones. The ALDH-based assay is expected to be promising for high-throughput screening of enzyme collections and mutant libraries to fish out the best ω-TA candidate as well as to tailor enzyme properties for efficient amination of a target ketone.