51698-53-4Relevant articles and documents
Enantioselective Nickel-Catalyzed Hydrocyanation using Chiral Phosphine-Phosphite Ligands: Recent Improvements and Insights
Falk, Anna,Cavalieri, Alberto,Nichol, Gary S.,Vogt, Dieter,Schmalz, Hans-Günther
, p. 3317 - 3320 (2015)
The asymmetric hydrocyanation of vinylarenes was investigated using hydrogen cyanide (HCN) in the presence of 5 mol% of a catalyst prepared from a phenol-derived chiral phosphine-phosphite ligand and bis(cyclooctadiene)nickel [Ni(cod)2]. The reactions were performed in tetrahydrofuran (THF) at room temperature to give exclusively the branched nitriles with superior enantioselectivities of 88-99% ee for vinylarenes and 74-94% ee for vinylheteroarenes, respectively. Using styrene as a model substrate it was shown that the catalyst loading could be decreased to 0.42 mol% without any loss of selectivity (88% ee). The structure of the pre-catalyst, i.e., a tetrahedral Ni(0)(P,P-chelate)(cod) complex, was proven by X-ray and NMR analysis. Additional insight into the reaction course was gained by monitoring the hydrocyanation of styrene-d8 by means of 2D NMR spectroscopy.
Discovery of Conformationally Restricted Human Glutaminyl Cyclase Inhibitors as Potent Anti-Alzheimer's Agents by Structure-Based Design
Hoang, Van-Hai,Ngo, Van T.H.,Cui, Minghua,Manh, Nguyen Van,Tran, Phuong-Thao,Ann, Jihyae,Ha, Hee-Jin,Kim, Hee,Choi, Kwanghyun,Kim, Young-Ho,Chang, Hyerim,MacAlino, Stephani Joy Y.,Lee, Jiyoun,Choi, Sun
, p. 8011 - 8027 (2019/10/11)
Alzheimer's disease (AD) is an incurable, progressive neurodegenerative disease whose pathogenesis cannot be defined by one single element but consists of various factors; thus, there is a call for alternative approaches to tackle the multifaceted aspects of AD. Among the potential alternative targets, we aim to focus on glutaminyl cyclase (QC), which reduces the toxic pyroform of β-amyloid in the brains of AD patients. On the basis of a putative active conformation of the prototype inhibitor 1, a series of N-substituted thiourea, urea, and α-substituted amide derivatives were developed. The structure-activity relationship analyses indicated that conformationally restrained inhibitors demonstrated much improved QC inhibition in vitro compared to nonrestricted analogues, and several selected compounds demonstrated desirable therapeutic activity in an AD mouse model. The conformational analysis of a representative inhibitor indicated that the inhibitor appeared to maintain the Z-E conformation at the active site, as it is critical for its potent activity.
Facile Ruthenium(II)-Catalyzed α-Alkylation of Arylmethyl Nitriles Using Alcohols Enabled by Metal-Ligand Cooperation
Thiyagarajan, Subramanian,Gunanathan, Chidambaram
, p. 5483 - 5490 (2017/08/17)
A facile ruthenium(II)-catalyzed α-alkylation of arylmethyl nitriles using alcohols is reported. The ruthenium pincer catalyst serves as an efficient catalyst for this atom-economical transformation that undergoes alkylation via borrowing hydrogen pathways, producing water as the only byproduct. Arylmethyl nitriles containing different substituents can be effectively alkylated using diverse primary alcohols. Notably, using ethanol and methanol as alkylating reagents, challenging ethylation and methylation of arylmethyl nitriles were performed. Secondary alcohols do not undergo alkylation reactions. Thus, phenylacetonitrile was chemoselectively alkylated using primary alcohols in the presence of secondary alcohols. Diols provided a mixture of products. When deuterium-labeled alcohol was used, the expected deuterium transposition occurred, providing both α-alkylation and α-deuteration of arylmethyl nitriles. Consumption of nitrile was monitored by GC, which indicated the involvement of first-order kinetics. Plausible mechanistic pathways are suggested on the basis of experimental evidence. The ruthenium catalyst reacts with base and generates an unsaturated intermediate, which further reacts with both nitriles and alcohols. While nitrile is transformed to enamine via [2 + 2] cycloaddition, alcohol is oxidized to aldehyde. The metal bound enamine adduct reacts with aldehyde via Michael addition, resulting in an ene-imine adduct, which perhaps undergoes direct hydrogenation by a Ru dihydride intermediate, produced from alcohol oxidation. However, in situ monitoring of the reaction mixture confirmed the presence of unsaturated vinyl nitrile in the reaction mixture in minor amounts (10%), indicating the possible dissociation of ene-imine adduct during the catalysis, which may further be hydrogenated to provide the α-alkylated nitriles. Overall, the efficient α-alkylation of nitriles using alcohols can be attributed to the amine-amide metal-ligand cooperation that is operative in the ruthenium pincer catalyst, which enables all of the catalytic intermediates to remain in the +2 oxidation state throughout the catalytic cycle.
Copper-Catalyzed Cyanation of N-Tosylhydrazones with Thiocyanate Salt as the "cN" Source
Huang, Yubing,Yu, Yue,Zhu, Zhongzhi,Zhu, Chuanle,Cen, Jinghe,Li, Xianwei,Wu, Wanqing,Jiang, Huanfeng
, p. 7621 - 7627 (2017/07/26)
A novel protocol for the synthesis of α-aryl nitriles has been successfully achieved via a copper-catalyzed cyanation of N-tosylhydrazones employing thiocyanate as the source of cyanide. The features of this method include a convenient operation, readily available substrates, low-toxicity thiocyanate salts, and a broad substrate scope.
