65052-48-4Relevant academic research and scientific papers
Development and Molecular Understanding of a Pd-Catalyzed Cyanation of Aryl Boronic Acids Enabled by High-Throughput Experimentation and Data Analysis
De Jesus Silva, Jordan,Bartalucci, Niccolò,Jelier, Benson,Grosslight, Samantha,Gensch, Tobias,Schünemann, Claas,Müller, Bernd,Kamer, Paul C. J.,Copéret, Christophe,Sigman, Matthew S.,Togni, Antonio
, (2021/11/10)
A synthetic method for the palladium-catalyzed cyanation of aryl boronic acids using bench stable and non-toxic N-cyanosuccinimide has been developed. High-throughput experimentation facilitated the screen of 90 different ligands and the resultant statistical data analysis identified that ligand σ-donation, π-acidity and sterics are key drivers that govern yield. Categorization into three ligand groups – monophosphines, bisphosphines and miscellaneous – was performed before the analysis. For the monophosphines, the yield of the reaction increases for strong σ-donating, weak π-accepting ligands, with flexible pendant substituents. For the bisphosphines, the yield predominantly correlates with ligand lability. The applicability of the designed reaction to a wider substrate scope was investigated, showing good functional group tolerance in particular with boronic acids bearing electron-withdrawing substituents. This work outlines the development of a novel reaction, coupled with a fast and efficient workflow to gain understanding of the optimal ligand properties for the design of improved palladium cross-coupling catalysts.
Nickel-Catalyzed Reversible Functional Group Metathesis between Aryl Nitriles and Aryl Thioethers
Delcaillau, Tristan,Boehm, Philip,Morandi, Bill
supporting information, p. 3723 - 3728 (2021/04/07)
We describe a new functional group metathesis between aryl nitriles and aryl thioethers. The catalytic system nickel/dcype is essential to achieve this fully reversible transformation in good to excellent yields. Furthermore, the cyanide- and thiol-free reaction shows high functional group tolerance and great efficiency for the late-stage derivatization of commercial molecules. Finally, synthetic applications demonstrate its versatility and utility in multistep synthesis.
t-BuOK-promoted methylthiolation of aryl fluorides with dimethyldisulfide under transition-metal-free and mild conditions
Huang, Dayun,Wu, Xiangmei
, (2021/03/24)
In the presence of potassium tert-butoxide (t-BuOK), the cross-coupling reaction between aryl fluorides and dimethyldisulfide was developed. A series of aryl methyl sulfides were obtained in moderate to good yields under transition-metal-free and mild conditions.
Pd-Catalyzed Intermolecular Transthiolation of Ar-OTf Using Methyl 3-(Methylthio) Propanoate as a Thiol Surrogate
Pan, Dandan,Xu, Shasha,Tian, Qingqiang,Li, Yahui
supporting information, p. 4616 - 4619 (2021/09/10)
A method for the odorless synthesis of unsymmetrical sulfides via Csp2?O and Csp3?S bond activation is presented. Using methyl 3-(methylthio) propanoate as a MeSH surrogate, a series of substituted aryl methyl sulfides have been obtained in moderate to good yields. This catalytic protocol can also tolerate methyl 3-(methylthio)propionate derivatives to afford the corresponding aryl sulfides.
Copper-Catalyzed Methylthiolation of Aryl Iodides and Bromides with Dimethyl Disulfide in Water
Wang, Ying-Yu,Wu, Xiang-Mei,Yang, Ming-Hua
supporting information, (2020/07/20)
An efficient route to aryl methyl sulfides through the copper-catalyzed coupling reaction of aryl iodides or bromides with dimethyl disulfide in water is described. Electron-donating and electron-withdrawing functional groups in the substrates were tolerated, and the corresponding products were obtained in moderate to good yields.
Lewis Acid–Base Interaction-Controlled ortho-Selective C?H Borylation of Aryl Sulfides
Li, Hong Liang,Kuninobu, Yoichiro,Kanai, Motomu
supporting information, p. 1495 - 1499 (2017/02/05)
An iridium/bipyridine-catalyzed ortho-selective C?H borylation of aryl sulfides was developed. High ortho-selectivity was achieved by a Lewis acid–base interaction between a boryl group of the ligand and a sulfur atom of the substrate. This is the first example of a catalytic and regioselective C?H transformation controlled by a Lewis acid–base interaction between a ligand and a substrate. The C?H borylation reaction could be conducted on a gram scale, and with a bioactive molecule as a substrate, demonstrating its applicability to late-stage regioselective C?H borylation. A bioactive molecule was synthesized from an ortho-borylated product by converting the boryl and methylthio groups of the product.
Metal-Free, DTBP-Mediated Methylthiolation of Arylboronic Acids with Dimethyldisulfide
Wu, Xiang-Mei,Lou, Jia-Ming,Yan, Guo-Bing
supporting information, p. 2269 - 2273 (2016/10/30)
An efficient method for the C-S bond formation via the coupling reaction of arylboronic acids with dimethyldisulfide has been developed under the metal-free conditions. This novel protocol provides an attractive route for the synthesis of aryl methyl sulf
Transnitrilation from Dimethylmalononitrile to Aryl Grignard and Lithium Reagents: A Practical Method for Aryl Nitrile Synthesis
Reeves, Jonathan T.,Malapit, Christian A.,Buono, Frederic G.,Sidhu, Kanwar P.,Marsini, Maurice A.,Sader, C. Avery,Fandrick, Keith R.,Busacca, Carl A.,Senanayake, Chris H.
supporting information, p. 9481 - 9488 (2015/08/11)
An electrophilic cyanation of aryl Grignard or lithium reagents, generated in situ from the corresponding aryl bromides or iodides, by a transnitrilation with dimethylmalononitrile (DMMN) was developed. DMMN is a commercially available, bench-stable solid. The transnitrilation with DMMN avoids the use of toxic reagents and transition metals and occurs under mild reaction conditions, even for extremely sterically hindered substrates. The transnitrilation of aryllithium species generated by directed ortho-lithiation enabled a net C-H cyanation. The intermediacy of a Thorpe-type imine adduct in the reaction was supported by isolation of the corresponding ketone from the quenched reaction. Computational studies supported the energetic favorability of retro-Thorpe fragmentation of the imine adduct. (Chemical Equation Presented).
An investigation by means of correlation analysis into the mechanisms of oxidation of aryl methyl sulfides and sulfoxides by dimethyldioxirane in various solvents
Hanson, Peter,Hendrickx, Ramon A.A.J.,Smith, John R. Lindsay
, p. XX745-761 (2008/09/17)
Relative rate constants have been measured for the oxidation of aryl methyl sulfides and sulfoxides by dimethyldioxirane in acetone, in mixtures of acetone with aprotic co-solvents of both higher and lower relative permittivity, and in aqueous acetone mixtures. Correlation analyses of the effects of substituents in the different solvents show that, with one exception, reactions take place via a single step mechanism in which the formation of the new SO bond and the elimination of acetone occur concertedly. The exception was oxidation of the sulfides in aqueous acetone containing the highest proportion of water of those studied (20% v/v). Here, the behaviour of the reaction is consistent with a two-step mechanism in which the oxidant reversibly attacks the sulfide to form an open-chain sulfonium betaine that subsequently fragments to sulfoxide and acetone. There is no evidence for the participation of an intermediate dioxathietane as has been found in the case of sulfide oxidations by (trifluoromethyl)methyldioxirane in CH2Cl2 and similar aprotic solvents. It is not justified to generalise a mechanism involving a betaine, with or without a derived dioxathietane, to the reactions of dimethyldioxirane in acetone. This journal is The Royal Society of Chemistry.
Acridone-based inhibitors of inosine 5′-monophosphate dehydrogenase: Discovery and SAR leading to the identification of N-(2-(6-(4-ethylpiperazin-1- yl)pyridin-3-yl)propan-2-yl)-2-fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide (BMS-566419)
Watterson, Scott H.,Chen, Ping,Zhao, Yufen,Gu, Henry H.,Dhar, T. G. Murali,Xiao, Zili,Ballentine, Shelley K.,Shen, Zhongqi,Fleener, Catherine A.,Rouleau, Katherine A.,Obermeier, Mary,Yang, Zheng,McIntyre, Kim W.,Shuster, David J.,Witmer, Mark,Dambach, Donna,Chao, Sam,Mathur, Arvind,Chen, Bang-Chi,Barrish, Joel C.,Robl, Jeffrey A.,Townsend, Robert,Iwanowicz, Edwin J.
, p. 3730 - 3742 (2008/02/12)
Inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosine nucleotides, catalyzes the irreversible nicotinamide-adenine dinucleotide dependent oxidation of inosine-5′- monophosphate to xanthosine-5′-monophosphate. Mycophenolate Mofetil (MMF), a prodrug of mycophenolic acid, has clinical utility for the treatment of transplant rejection based on its inhibition of IMPDH. The overall clinical benefit of MMF is limited by what is generally believed to be compound-based, dose-limiting gastrointestinal (GI) toxicity that is related to its specific pharmacokinetic characteristics. Thus, development of an IMPDH inhibitor with a novel structure and a different pharmacokinetic profile may reduce the likelihood of GI toxicity and allow for increased efficacy. This article will detail the discovery and SAR leading to a novel and potent acridone-based IMPDH inhibitor 4m and its efficacy and GI tolerability when administered orally in a rat adjuvant arthritis model.
