38778-78-8Relevant academic research and scientific papers
Redox Property of Enamines
Li, Yao,Wang, Dehong,Zhang, Long,Luo, Sanzhong
, p. 12071 - 12090 (2019/10/11)
Enamines are electron-rich compounds bearing intriguing redox properties. Herein, a series of secondary enamines condensed from primary amine and β-ketocarbonyls were synthesized and their electrochemical oxidation properties were systematically studied by cyclic voltammetry. Furthermore, theoretical calculation of oxidation potentials of enamines, particularly those catalytic intermediates, was also conducted to further broaden the scope investigated. Possible structural factors on oxidation and the nature of the resulted radical cation intermediates were revealed and discussed. Correlation of redox potentials with molecular properties such as highest occupied molecular orbital energies and natural population analysis charge were explored, and there appears no simple linear correlation. On the other hand, a good correlation with Mayr's nucleophilicity parameter N was noted among a range of catalytically relevant enamines. Spin population analysis disclosed that enamine radical cations mainly exhibit the carbon-center free radical feature. Taking experimental and computation data together, a comprehensive picture about the redox property of enamines is presented, which would provide guidance in the development of oxidative enamine catalysis and transformations.
Arynes and Cyclic Alkynes as Synthetic Building Blocks for Stereodefined Quaternary Centers
Picazo, Elias,Anthony, Sarah M.,Giroud, Maude,Simon, Adam,Miller, Margeaux A.,Houk,Garg, Neil K.
supporting information, p. 7605 - 7610 (2018/05/15)
We report a facile method to synthesize stereodefined quaternary centers from reactions of arynes and related strained intermediates using β-ketoester-derived substrates. The conversion of β-ketoesters to chiral enamines is followed by reaction with in situ generated strained arynes or cyclic alkynes. Hydrolytic workup provides the arylated or alkenylated products in enantiomeric excesses as high as 96%. We also describe the one-pot conversion of a β-ketoester substrate to the corresponding enantioenriched α-arylated product. Computations show how chirality is transferred from the N-bound chiral auxiliary to the final products. These are the first theoretical studies of aryne trapping by chiral nucleophiles to set new stereocenters. Our approach provides a solution to the challenging problem of stereoselective β-ketoester arylation/alkenylation, with formation of a quaternary center.
Visible Light Promoted β-C—H Alkylation of β-Ketocarbonyls via a β-Enaminyl Radical Intermediate
Wang, Dehong,Zhang, Long,Luo, Sanzhong
, p. 311 - 320 (2018/02/21)
A 5πe carbonyl activation mode is reported on the basis of photo-induced single-electron-transfer (SET) oxidation of a secondary enamine. The resultant β-enaminyl radical intermediate was trapped by a wide range of Michael acceptors, producing β-alkylation products of β-ketocarbonyls in a highly efficient manner.
Vanadium(IV) acetylacetonate catalyzed stereoselective synthesis of β-enaminoesters and β-enaminones
Laskar, Rajibul A.,Begum, Naznin A.,Hedayetullah Mir, Mohammad,Ali, Shahzad,Khan, Abu T.
, p. 436 - 440 (2013/02/23)
An efficient and stereoselective procedure has been described for the synthesis of a series of β-enaminoesters and β-enaminones by vanadium(IV) acetylacetonate [VO(acac)2] catalyzed reaction of β-ketoesters and 1,3-diketones with both aliphatic and aromatic amines. X-ray crystallographic studies of some representative compounds corroborate two types of structural geometry formed by inter-molecular as well as intra-molecular hydrogen bonds.
A pairwise chemical genetic screen identifies new inhibitors of glucose transport
Ulanovskaya, Olesya A.,Cui, Jiayue,Kron, Stephen J.,Kozmin, Sergey A.
experimental part, p. 222 - 230 (2011/10/08)
Oxidative phosphorylation (OXPHOS) and glycolysis are the two main pathways that control energy metabolism of a cell. The Warburg effect, in which glycolysis remains active even under aerobic conditions, is considered a key driver for cancer cell proliferation, malignancy, metastasis, and therapeutic resistance. To target aerobic glycolysis, we exploited the complementary roles of OXPHOS and glycolysis in ATP synthesis as the basis for a chemical genetic screen, enabling rapid identification of novel small-molecule inhibitors of facilitative glucose transport. Blocking mitochondrial electron transport with antimycin A or leucascandrolide A had little effect on highly glycolytic A549 lung carcinoma cells, but adding known glycolytic inhibitors 2-deoxy-D-glucose, iodoacetate or cytochalasin B, rapidly depleted intracellular ATP, displaying chemical synthetic lethality. Based on this principle, we exposed antimycin A-treated A549 cells to a newly synthesized 955 member diverse scaffold small-molecule library, screening for compounds that rapidly depleted ATP levels. Two compounds potently suppressed ATP synthesis, induced G1 cell-cycle arrest and inhibited lactate production. Pathway analysis revealed that these novel probes inhibited GLUT family of facilitative transmembrane transporters but, unlike cytochalasin B, had no effect on the actin cytoskeleton. Our work illustrated the utility of a pairwise chemical genetic screen for discovery of novel chemical probes, which would be useful not only to study the system-level organization of energy metabolism but could also facilitate development of drugs targeting upregulation of aerobic glycolysis in cancer.
Ca(CF3COO)2: An efficient Lewis acid catalyst for chemo- and regio-selective enamination of β-dicarbonyl compounds
Harrad, Mohamed Anoir,Outtouch, Rachid,Ait Ali, Mustapha,Firdoussi, Larbi El,Karim, Abdallah,Roucoux, Alain
experimental part, p. 442 - 446 (2010/11/21)
A relevant procedure has been developed for the synthesis of β-enaminoesters catalysed by Ca(CF3COO)2. The reaction of β-ketoesters with primary amines was efficiently carried out under solvent-free conditions at room temperature and led to chemo- and regio-selective formations of enamine derivatives in high yields.
Heterocycle Formation through Aza-Annulation: Stereochemically Controlled Syntheses of (+/-)-5-Epitashiromine and (+/-)-Tashiromine
Paulvannan, K.,Stille, John R.
, p. 1613 - 1620 (2007/10/02)
N-alkenylamines, stabilized through conjugation with an electron-withdrawing group, undergo aza-annulation with acryloyl chloride to provide a convergent route for the construction of six-membered nitrogen heterocycles.In addition to enhancing the C-alkylation process of annulation relative to the competing N-acylation process, the electron withdrawing substituent controlled the regioselectivity of alkene formation in both the intermediate enamine and in the unsaturated lactam product.A variety of functional groups, which include -COMe, -COPh, -CO2R, -CONHPh, -CN, -P(O)(OEt)2, and -SO2Ph, were used to determine the effect of the electron-withdrawing substituents upon both the annulation reaction with acryloyl chloride and the subsequent hydrogenation process.When the enamide annulation product was stabilized through conjugation with ester or amide substituents, catalytic hydrogenation of the aza-annulation product resulted in the formation of vicinal stereocenters with high cis selectivity.The utility of this methodology was demonstrated by application of the condensation/aza-annulation/hydrogenation sequence as the key for construction and stereochemical control of the indolizidine ring system of (+/-)-tashiromine.
