86911-10-6Relevant articles and documents
General C(sp2)-C(sp3) Cross-Electrophile Coupling Reactions Enabled by Overcharge Protection of Homogeneous Electrocatalysts
Hamby, Taylor B.,Sevov, Christo S.,Truesdell, Blaise L.
supporting information, p. 5884 - 5893 (2020/04/10)
Cross-electrophile coupling (XEC) of alkyl and aryl halides promoted by electrochemistry represents an attractive alternative to conventional methods that require stoichiometric quantities of high-energy reductants. Most importantly, electroreduction can readily exceed the reducing potentials of chemical reductants to activate catalysts with improved reactivities and selectivities over conventional systems. This work details the mechanistically-driven development of an electrochemical methodology for XEC that utilizes redox-active shuttles developed by the energy-storage community to protect reactive coupling catalysts from overreduction. The resulting electrocatalytic system is practical, scalable, and broadly applicable to the reductive coupling of a wide range of aryl, heteroaryl, or vinyl bromides with primary or secondary alkyl bromides. The impact of overcharge protection as a strategy for electrosynthetic methodologies is underscored by the dramatic differences in yields from coupling reactions with added redox shuttles (generally >80%) and those without (generally 20%). In addition to excellent yields for a wide range of substrates, reactions protected from overreduction can be performed at high currents and on multigram scales.
Cross-Electrophile Coupling of Vinyl Halides with Alkyl Halides
Johnson, Keywan A.,Biswas, Soumik,Weix, Daniel J.
supporting information, p. 7399 - 7402 (2016/05/24)
An improved method for the reductive coupling of aryl and vinyl bromides with alkyl halides that gave high yields for a variety of substrates at room temperature with a low (2.5 to 0.5 mol %) catalyst loading is presented. Under the optimized conditions, difficult substrates, such as unhindered alkenyl bromides, can be coupled to give the desired olefins with minimal diene formation and good stereoretention. These improved conditions also worked well for aryl bromides. For example, a gram-scale reaction was demonstrated with 0.5 mol % catalyst loading, whereas reactions at 10 mol % catalyst loading completed in as little as 20 minutes. Finally, a low-cost single-component pre-catalyst, (bpy)NiI2 (bpy=2,2′-bipyridine) that is both air- and moisture-stable over a period of months was introduced.
Ni-catalyzed Sonogashira coupling of nonactivated alkyl halides: Orthogonal functionalization of alkyl iodides, bromides, and chlorides
Vechorkin, Oleg,Barmaz, Delphine,Proust, Valerie,Hu, Xile
scheme or table, p. 12078 - 12079 (2010/01/15)
(Chemical Equation Presented) Ni-catalyzed Sonogashira coupling of nonactivated, β-H-containing alkyl halides, including chlorides, is reported. The coupling is tolerant to a wide range of functional groups, including ether, ester, amide, nitrile, keto, h
7-Substituted 5-amino-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as A2A adenosine receptor antagonists: A study on the importance of modifications at the side chain on the activity and solubility
Baraldi,Cacciari,Romagnoli,Spalluto,Monopoli,Ongini,Varani,Borea
, p. 115 - 126 (2007/10/03)
It was demonstrated in the early 1990s that adenosine exerts many physiological functions through the interaction with four different receptors, named A1, A2A, A2B, and A3. In the past few years, our group has been involved in the development of A2A antagonists, which led to the synthesis of SCH 58261 (1), the first potent and selective adenosine A2A antagonist, which has been widely used as a reference compound. In this paper, we present an extended series of pyrazolotriazolopyrimidines synthesized with the aim to investigate the influence of the substitutions on the pyrazole ring. The choice of the substituents was based on their capability to improve water solubility while retaining high affinity and selectivity at the human A2A adenosine receptor subtype. In this series, some structural characteristics that are important for activity, i.e., tricyclic structure, free amino group at 5-position, furan ring, and substituent at 7-position on the pyrazole moiety, have been maintained. We focused our attention on the nature of the phenyl ring substituent to improve water solubility. Following this strategy, we developed new compounds with good affinity and selectivity for A2A adenosine receptors, such as 8d (Ki 0.12 nM; hA1/hA2A ratio = 1025; Rm = 2.8), 8h (Ki 0.22; hA1/hA2A ratio = 9818; Rm = 3.4), 8i (Ki 0.18 nM; hA1/hA2A ratio = 994; Rm = 2.8), 8k (Ki 0.13 nM; hA1/hA2A ratio = 4430; Rm = 3.6), and 14b (Ki 0.19 nM; hA1/hA2A ratio = 2273; Rm = 2.7). All the new synthesized compounds have no significant interaction with either A2B or A3 receptor subtypes. This new series of compounds deeply enlightens some structural requirements to display high affinity and selectivity for the A2A adenosine receptor subtype, although our goal of identifying new compounds with increased water solubility was not completely achieved. On this basis, other strategies will be devised to improve this class of compounds with a profile that appears to be promising for treatment of neurodegenerative disorders, such as Parkinson's disease.
