63035-45-0Relevant academic research and scientific papers
Coupling N-H Deprotonation, C-H Activation, and Oxidation: Metal-Free C(sp3)-H Aminations with Unprotected Anilines
Evoniuk, Christopher J.,Gomes, Gabriel Dos Passos,Hill, Sean P.,Fujita, Satoshi,Hanson, Kenneth,Alabugin, Igor V.
supporting information, p. 16210 - 16221 (2017/11/22)
An intramolecular oxidative C(sp3)-H amination from unprotected anilines and C(sp3)-H bonds readily occurs under mild conditions using t-BuOK, molecular oxygen and N,N-dimethylformamide (DMF). Success of this process, which requires mildly acidic N-H bonds and an activated C(sp3)-H bond (BDE 85 kcal/mol), stems from synergy between basic, radical, and oxidizing species working together to promote a coordinated sequence of deprotonation: H atom transfer and oxidation that forges a new C-N bond. This process is applicable for the synthesis of a wide variety of N-heterocycles, ranging from small molecules to extended aromatics without the need for transition metals or strong oxidants. Computational results reveal the mechanistic details and energy landscape for the sequence of individual steps that comprise this reaction cascade. The importance of base in this process stems from the much greater acidity of transition state and product for the 2c,3e C-N bond formation relative to the reactant. In this scenario, selective deprotonation provides the driving force for the process.
Development of Tetrachlorophthalimides as Liver X Receptor β (LXRβ)-Selective Agonists
Nomura, Sayaka,Endo-Umeda, Kaori,Makishima, Makoto,Hashimoto, Yuichi,Ishikawa, Minoru
, p. 2347 - 2360 (2016/10/25)
Liver X receptor (LXR) agonists are candidates for the treatment of atherosclerosis via induction of ABCA1 (ATP-binding cassette A1) gene expression, which contributes to reverse cholesterol transport (RCT) and to cholesterol efflux from the liver and intestine. However, LXR agonists also induce genes involved in lipogenesis, such as SREBP-1c (sterol regulatory binding element protein 1c) and FAS (fatty acid synthase), thereby causing an undesirable increase in plasma and hepatic triglyceride (TG) levels. Recent studies indicate that LXRα contributes to lipogenesis in liver, and selective LXRβ activation improves RCT in mice. Therefore, LXRβ-selective agonists are promising candidates to improve atherosclerosis without increasing plasma or hepatic TG levels. However, the ligand-binding domains in the two LXR isoforms α/β share high sequence identity, and few LXR ligands show subtype selectivity. In this study we identified a tetrachlorophthalimide analogue as an LXRβ-selective agonist. Structural development led to (E)-4,5,6,7-tetrachloro-2-(2-styrylphenyl)isoindoline-1,3-dione (24 a), which shows potent and selective LXRβ agonistic activity in reporter gene assays. In binding assays, compound 24 a bound to LXRβ preferentially over LXRα. It also induced the expression of ABCA1 mRNA but not SREBP-1c mRNA in cells. Compound 24 a appears to be a promising lead compound for therapeutic agents to treat atherosclerosis without the side effects induced by LXRα/β dual agonists.
Double C-H amination by consecutive SET oxidations
Evoniuk, Christopher J.,Hill, Sean P.,Hanson, Kenneth,Alabugin, Igor V.
supporting information, p. 7138 - 7141 (2016/06/09)
A new method for intramolecular C-H oxidative amination is based on a FeCl3-mediated oxidative reaction of anilines with activated sp3 C-H bonds. The amino group plays multiple roles in the reaction cascade: (1) as the activating group in single-electron-transfer (SET) oxidation process, (2) as a directing group in benzylic/allylic C-H activation at a remote position, and (3) internal nucleophile trapping reactive intermediates formed from the C-H activation steps. These multielectron oxidation reactions proceed with catalytic amounts of Fe(iii) and inexpensive reagents.
