- N-Heterocyclic Carbene Catalyzed γ-Dihalomethylenation of Enals by Single-Electron Transfer
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An N-heterocyclic carbene (NHC) catalyzed dihalomethylenation of enals is described. It is a rare example of merging NHC catalysis with single-electron chemistry, a challenging topic with limited previous success. The versatile carbon-centered trihalomethyl radicals have been demonstrated, for the first time, to be compatible with an NHC-bound intermediate, thus leading to efficient and regioselective intermolecular C?C bond formation. The mild process provides straightforward access to unsaturated δ,δ-dihalo esters.
- Yang, Wen,Hu, Weimin,Dong, Xiuqin,Li, Xin,Sun, Jianwei
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- Enantioselective C-H Amination Catalyzed by Nickel Iminyl Complexes Supported by Anionic Bisoxazoline (BOX) Ligands
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The trityl-substituted bisoxazoline (TrHBOX) was prepared as a chiral analogue to a previously reported nickel dipyrrin system capable of ring-closing amination catalysis. Ligand metalation with divalent NiI2(py)4 followed by potassium graphite reduction afforded the monovalent (TrHBOX)Ni(py) (4). Slow addition of 1.4 equiv of a benzene solution of 1-adamantylazide to 4 generated the tetrazido (TrHBOX)Ni(κ2-N4Ad2) (5) and terminal iminyl adduct (TrHBOX)Ni(NAd) (6). Investigation of 6 via single-crystal X-ray crystallography, NMR and EPR spectroscopies, and computations revealed a Ni(II)-iminyl radical formulation, similar to its dipyrrinato congener. Complex 4 exhibits enantioselective intramolecular C-H bond amination to afford N-heterocyclic products from 4-aryl-2-methyl-2-azidopentanes. Catalytic C-H amination occurs under mild conditions (5 mol % catalyst, 60 °C) and provides pyrrolidine products in decent yield (29%-87%) with moderate ee (up to 73%). Substrates with a 3,5-dialkyl substitution on the 4-aryl position maximized the observed enantioselectivity. Kinetic studies to probe the reaction mechanism were conducted using 1H and 19F NMR spectroscopies. A small, intermolecular kinetic isotope effect (1.35 ± 0.03) suggests an H-atom abstraction step with an asymmetric transition state while the reaction rate is measured to be first order in catalyst and zeroth order in substrate concentrations. Enantiospecific deuterium labeling studies show that the enantioselectivity is dictated by both the H-atom abstraction and radical recombination steps due to the comparable rate between radical rotation and C-N bond formation. Furthermore, the competing elements of the two-step reaction where H-removal from the pro-R configuration is preferred while the preferential radical capture occurs with the Si face of the carboradical likely lead to the diminished ee observed, as corroborated by theoretical calculations. Based on these enantio-determining steps, catalytic enantioselective synthesis of 2,5-bis-tertiary pyrrolidines is demonstrated with good yield (50-78%) and moderate ee (up to 79%).
- Dong, Yuyang,Lund, Colton J.,Porter, Gerard J.,Clarke, Ryan M.,Zheng, Shao-Liang,Cundari, Thomas R.,Betley, Theodore A.
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supporting information
p. 817 - 829
(2021/02/03)
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- Two-way homologation of aliphatic aldehydes: Both one-carbon shortening and lengthening via the same intermediate
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Aliphatic aldehydes can be homologated to both one-carbon shorter and one-carbon longer homologous carbonyl compounds through the 2–4 steps of reactions via the same intermediates, β,γ-unsaturated α-nitrosulfones, prepared from the proline-catalyzed sequential reactions of several aliphatic aldehydes with phenylsulfonylnitromethane. While the oxidative cleavage of the key intermediates gave one-carbon less homologous carbonyl compounds, the reduction of the same key intermediates followed by an oxidation produced one-carbon more homologous carbonyl compounds.
- Yoo, Jae Won,Seo, Youngran,Park, Jong Beom,Kim, Young Gyu
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- Efficient C-H Amination Catalysis Using Nickel-Dipyrrin Complexes
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A dipyrrin-supported nickel catalyst (AdFL)Ni(py) (AdFL: 1,9-di(1-adamantyl)-5-perfluorophenyldipyrrin; py: pyridine) displays productive intramolecular C-H bond amination to afford N-heterocyclic products using aliphatic azide substrates. The catalytic amination conditions are mild, requiring 0.1-2 mol% catalyst loading and operational at room temperature. The scope of C-H bond substrates was explored and benzylic, tertiary, secondary, and primary C-H bonds are successfully aminated. The amination chemoselectivity was examined using substrates featuring multiple activatable C-H bonds. Uniformly, the catalyst showcases high chemoselectivity favoring C-H bonds with lower bond dissociation energy as well as a wide range of functional group tolerance (e.g., ethers, halides, thioetheres, esters, etc.). Sequential cyclization of substrates with ester groups could be achieved, providing facile preparation of an indolizidine framework commonly found in a variety of alkaloids. The amination cyclization reaction mechanism was examined employing nuclear magnetic resonance (NMR) spectroscopy to determine the reaction kinetic profile. A large, primary intermolecular kinetic isotope effect (KIE = 31.9 ± 1.0) suggests H-atom abstraction (HAA) is the rate-determining step, indicative of H-atom tunneling being operative. The reaction rate has first order dependence in the catalyst and zeroth order in substrate, consistent with the resting state of the catalyst as the corresponding nickel iminyl radical. The presence of the nickel iminyl was determined by multinuclear NMR spectroscopy observed during catalysis. The activation parameters (ΔH? = 13.4 ± 0.5 kcal/mol; ΔS?= -24.3 ± 1.7 cal/mol·K) were measured using Eyring analysis, implying a highly ordered transition state during the HAA step. The proposed mechanism of rapid iminyl formation, rate-determining HAA, and subsequent radical recombination was corroborated by intramolecular isotope labeling experiments and theoretical calculations.
- Betley, Theodore A.,Clarke, Ryan M.,Dong, Yuyang,Porter, Gerard J.
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supporting information
p. 10996 - 11005
(2020/07/08)
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- A metal-free desulfurizing radical reductive C-C coupling of thiols and alkenes
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An intermolecular reductive C-C coupling of electrophilic alkyl radicals and alkenes has been developed. Thiols were used as both hydrogen-donating reagents and alkyl radical precursors in the presence of triethyl phosphite and radical initiator. A wide range of alkenes, including styrenes, and aliphatic olefins were well tolerated in this transformation. Mechanistic studies indicated that a phosphite promoted radical desulfurization of thiols to access electrophilic alkyl radicals and a radical chain propagation process may be involved in this transformation.
- Qin, Qixue,Wang, Weijing,Zhang, Cheng,Song, Song,Jiao, Ning
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supporting information
p. 10583 - 10586
(2019/09/06)
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- Reductive C-C Coupling by Desulfurizing Gold-Catalyzed Photoreactions
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[Au2(μ-dppm)2]Cl2-mediated photocatalysis reactions are usually initiated by ultraviolet A (UVA) light; herein, an unreported system using blue light-emitting diodes (LEDs) as excitation light source was found. The red shift of the absorption wavelength originates from the combination of [Au2(μ-dppm)2]Cl2 and ligand (Ph3P or mercaptan). On the basis of this finding, a gold-catalyzed reductive desulfurizing C-C coupling of electrophilic radicals and styrenes mediated by blue LEDs is presented, a coupling which cannot be efficiently accessed by previously reported methods. This mild and highly efficient C-C bond formation strategy uses mercaptans both as electron-deficient alkyl radical precursor as well as the hydrogen source. Two examples of amino acids have also been modified by using this strategy. Moreover, this methodology could be applied in polymer synthesis. Gram-scale synthesis and mechanistic insights into this transformation are also presented.
- Zhang, Lumin,Si, Xiaojia,Yang, Yangyang,Witzel, Sina,Sekine, Kohei,Rudolph, Matthias,Rominger, Frank,Hashmi, A. Stephen K.
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p. 6118 - 6123
(2019/07/03)
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- In search of open-chain 1,3-stereocontrol
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Methylation of methyl 4-phenylpentanoate 25 gives the diastereoisomers methyl (2RS,4SR)-2-methyl-4-phenylpentanoate 26 and methyl (2RS,4RS)- 2-methyl-4-phenylpentanoate 27 in a ratio of 44:56. The aldehydes 3-dimethyl(phenyl)silylbutanal 28, 3-dimethyl(ph
- Barbero, Asun,Blakemore, David C.,Fleming, Ian,Wesley, Robert N.
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p. 1329 - 1352
(2007/10/03)
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- A New Approach to Aromatic Substitution - para-Specific Alkylation of Acetophenone by Alkyl Radicals in Strongly Acidic Media
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Acetophenone in 25percent oleum is substituted by various alkyl radicals specifically in the para-position.The radicals used include cyclohexyl, 3-chloro-1-methylpropyl, 3-bromo-1-methylpropyl, 4-chloro-1-methylbutyl, 4-bromo-1-methylbutyl, 5-bromo-1-methylpentyl, 5-acetoxy-1-methylpentyl, 3-carboxy-1-methylpropyl, 4-carboxy-1-methylbutyl and 5-carboxy-1-methylpentyl.They were all generated by hydrogen atom abstraction at the radical position by dimethylaminium radicals, generated in turn from protonated dimethylchloramine and ferrous sulphate.Yields were generally poor to moderate but utilised simple conditions and cheap reagents.
- Din, Laily Bin,Meth-Cohn, Otto,Walshe, Nigel D. A.
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p. 781 - 786
(2007/10/02)
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- Rate and Regioselectivity of Hydrogenolysis of Some Phenyl-Substituted Cyclopropanes
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Several phenyl-substituted cyclopropane derivatives were investigated regarding rate and regiochemistry of their hydrogenolysis.The following reactivity sequence has been established: 1 2 4 7 9.Substituent effects are discussed and compared to those reported for monoactivated cyclopropanes.
- Brueckner, Christiane,Reissig, Hans-Ulrich
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p. 627 - 630
(2007/10/02)
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