36293-05-7Relevant articles and documents
P(III)-Assisted Electrochemical Access to Ureas via in situ Generation of Isocyanates from Hydroxamic Acids
Meng, Haiwen,Sun, Kunhui,Xu, Zhimin,Tian, Lifang,Wang, Yahui
supporting information, p. 1768 - 1772 (2021/03/26)
An external oxidant-free protocol for the generation of isocyanates from hydroxamic acids assisted by trivalent phosphine under mild electrochemical conditions was reported. The process started with the anodic oxidation of hydroxamic acids, followed by reacting with phosphine to form corresponding alkoxyphosphoniums and subsequent rearrangement with the release of tri-substituted phosphine oxide as the driving force to give isocyanates, which were trapped by N-based nucleophiles to produce various ureas. This method provides a broadly applicable procedure to access isocyanate intermediates under mild electrochemical conditions.
Metal-free approach for hindered amide-bond formation with hypervalent iodine(iii) reagents: application to hindered peptide synthesis
Lee, Hyo-Jun,Huang, Xiao,Sakaki, Shigeyoshi,Maruoka, Keiji
supporting information, p. 848 - 855 (2021/02/09)
A new bio-inspired approach is reported for amide and peptide synthesis using α-amino esters that possess a potential activating group (PAG) at the ester residue. To activate the ester functionality under mild metal-free conditions, we exploited the facile dearomatization of phenols with hypervalent iodine(iii) reagents. Using a pyridine-hydrogen fluoride complex, highly reactive acyl fluoride intermediates can be successfully generated, thereby allowing for the smooth formation of sterically hindered amides and peptides from bulky amines and α-amino esters, respectively.
Palladium-Catalyzed 2-(Neopentylsulfinyl)aniline Directed C–H Acetoxylation and Alkenylation of Arylacetamides
Barysevich, Maryia V.,Laktsevich-Iskryk, Marharyta V.,Krech, Anastasiya V.,Zhabinskii, Vladimir N.,Khripach, Vladimir A.,Hurski, Alaksiej L.
supporting information, p. 937 - 943 (2020/02/25)
The 2-(neopentylsulfinyl)aniline directing group that promotes rapid palladium-catalyzed C–H acetoxylation and alkenylation of arylacetamides has been developed. The acetoxylation reaches completion within only 40 min at 100 °C and leads to the bis-functionalized products. Alternatively, the reaction can be carried out at room temperature, which is beneficial for sensitive substrates. For the alkenylation, we have developed a protocol in which easily available 1-substituted cyclopropanols were employed as equivalents of vinyl ketones.
Achiral Derivatives of Hydroxamate AR-42 Potently Inhibit Class i HDAC Enzymes and Cancer Cell Proliferation
Tng, Jiahui,Lim, Junxian,Wu, Kai-Chen,Lucke, Andrew J.,Xu, Weijun,Reid, Robert C.,Fairlie, David P.
supporting information, p. 5956 - 5971 (2020/06/05)
AR-42 is an orally active inhibitor of histone deacetylases (HDACs) in clinical trials for multiple myeloma, leukemia, and lymphoma. It has few hydrogen bond donors and acceptors but is a chiral 2-arylbutyrate and potentially prone to racemization. We report achiral AR-42 analogues incorporating a cycloalkyl group linked via a quaternary carbon atom, with up to 40-fold increased potency against human class I HDACs (e.g., JT86, IC50 0.7 nM, HDAC1), 25-fold increased cytotoxicity against five human cancer cell lines, and up to 70-fold less toxicity in normal human cells. JT86 was ninefold more potent than racAR-42 in promoting accumulation of acetylated histone H4 in MM96L melanoma cells. Molecular modeling and structure-activity relationships support binding to HDAC1 with tetrahydropyran acting as a hydrophobic shield from water at the enzyme surface. Such potent inhibitors of class I HDACs may show benefits in diseases (cancers, parasitic infections, inflammatory conditions) where AR-42 is active.
Straightforward formation of carbocations from tertiary carboxylic acids: Via CO release at room temperature
Bartalucci, Niccolò,Pampaloni, Guido,Marchetti, Fabio,Bortoluzzi, Marco,Zacchini, Stefano
supporting information, p. 1574 - 1577 (2019/04/02)
We report an unprecedented mode of reactivity of carboxylic acids. A series of tertiary carboxylic acids, containing at least one phenyl α-substituent, undergo loss of carbon monoxide at room temperature (295 K), by a one pot reaction with 0.5-1 molar equivalents of WCl6 in dichloromethane. A plausible mechanism for the Ph3CCO2H/WCl6 reaction, leading to [CPh3][WOCl5] and Ph3CCl, is proposed on the basis of DFT calculations. The analogous reactions involving CEt(Ph)2CO2H, CMe(Ph)2CO2H and CMe2(Ph)CO2H selectively afforded stable hydrocarbons (alkene or indene, depending on the case), apparently resulting from the rearrangement of elusive tertiary carbocations.
Decarbonylation of phenylacetic acids by high valent transition metal halides
Bartalucci, Niccolò,Marchetti, Fabio,Zacchini, Stefano,Pampaloni, Guido
, p. 5725 - 5734 (2019/05/10)
Triphenylacetic acid underwent unusual decarbonylation when allowed to react with a series of halides of group 4-6 metals in their highest oxidation state, in dichloromethane at ambient temperature. Thus, the reaction of CPh3COOH with MoCl5, in 1:1 molar ratio, afforded the trityl salt [CPh3][MoOCl4], 1, in 79% yield, while the 1:2 reaction of CPh3COOH with NbF5 afforded [CPh3][NbF6], 2, in 70% yield, NbOF3 being the metal co-product. CPh3COOH reacted with NbCl5, TiF4 and WOCl4 to give mixtures of compounds, however the cation [CPh3]+ was NMR identified in each case. [CPh3][NbCl6], 3, was isolated from NbCl5 and CPh3COCl, prior to being generated from CPh3COOH and PCl5. The reaction of CPh3COOH with TiCl4 was non-selective, and the salt [CPh3][Ti2Cl8(μ-κ2-O2CCPh3)], 4, was obtained in 18% yield. The decarbonylation reactions of CMePh2COCl and CMe2PhCOCl by means of NbCl5 led to the indanes 5a-b, which were isolated in 79-97% yields after hydrolysis of the mixtures and subsequent alumina filtration of the organic phases. The reactions of CH(Ph)2COOH with NbCl5 and WCl6 afforded NbCl4(OOCCHPh2), 6, and CHPh2COCl, respectively, as the prevalent species. CPh2(CH2CH2Br)COOH did not undergo CO release when allowed to interact with WCl6, instead selective intramolecular condensation to C(Ph)2C(O)OCH2CH2, 7, occurred. MeCCCOOH underwent hydrochlorination by WCl6 to give MeC(Cl)CHCOOH, 8, in 72% yield. All the products were fully characterized by elemental analysis, IR and multinuclear NMR spectroscopy. In addition, the solid state structures of 1, 2, 4, 7, and 8 were elucidated by X-ray diffraction.
Chiral 2-Aryl Ferrocene Carboxylic Acids for the Catalytic Asymmetric C(sp3)-H Activation of Thioamides
Sekine, Daichi,Ikeda, Kazuki,Fukagawa, Seiya,Kojima, Masahiro,Yoshino, Tatsuhiko,Matsunaga, Shigeki
supporting information, p. 3970 - 3978 (2019/08/20)
Enantioselective C-H functionalization reactions using trivalent group 9 metals (Co, Rh, Ir) have been investigated mainly on the basis of the development of well-designed chiral cyclopentadienyl (Cp) ligands. Although it has recently been demonstrated th
Chemospecific Cyclizations of α-Carbonyl Sulfoxonium Ylides on Aryls and Heteroaryls
Clare, Daniel,Dobson, Benjamin C.,Inglesby, Phillip A.,A?ssa, Christophe
supporting information, p. 16198 - 16202 (2019/11/03)
The functionalization of aryl and heteroaryls using α-carbonyl sulfoxonium ylides without the help of a directing group has remained so far a neglected area, despite the advantageous safety profile of sulfoxonium ylides. Described herein are the cyclizations of α-carbonyl sulfoxonium ylides onto benzenes, benzofurans and N-p-toluenesulfonyl indoles in the presence of a base in HFIP, whereas pyrroles and N-methyl indoles undergo cyclization in the presence of an iridium catalyst. Significantly, these two sets of conditions are chemospecific for each groups of substrates.
Palladium-catalyzed 2-pyridylmethyl-directed β-C(sp3)–H activation and cyclization of aliphatic amides with gem-dibromoolefins: A rapid access to γ-lactams
Zhou, Danni,Wang, Chunxia,Li, Mingliang,Long, Zheng,Lan, Jingbo
supporting information, p. 191 - 193 (2017/11/17)
The direct Pd-catalyzed β-C(sp3)–H activation and cyclization of aliphatic amides bearing a removable 2-pyridylmethyl directing group with gem-dibromoolefins is described for the first time to construct a variety of γ-lactams. The resulting products with Z- and E-configurations can be easily separated and purified after the reaction, demonstrating the effectiveness and applicability of the method herein developed.
Synthesis, Reactivity, Functionalization, and ADMET Properties of Silicon-Containing Nitrogen Heterocycles
Barraza, Scott J.,Denmark, Scott E.
supporting information, p. 6668 - 6684 (2018/06/12)
Silicon-containing compounds have been largely ignored in drug design and development, despite their potential to improve not only the potency but also the physicochemical and ADMET (absorption, distribution, metabolism, excretion, toxicity) properties of drug-like candidates because of the unique characteristics of silicon. This deficiency is in large part attributable to a lack of general methods for synthesizing diverse organosilicon structures. Accordingly, a new building block strategy has been developed that diverges from traditional approaches to incorporation of silicon into drug candidates. Flexible, multi-gram-scale syntheses of silicon-containing tetrahydroquinoline and tetrahydroisoquinoline building blocks are described, along with methods by which diversely functionalized silicon-containing nitrogen heterocycles can be rapidly built using common reactions optimized to accommodate the properties of silicon. Furthermore, to better clarify the liabilities and advantages of silicon incorporation, select compounds and their carbon analogues were challenged in ADMET-focused biological studies.
