- Iron-Catalyzed Isopropylation of Electron-Deficient Aryl and Heteroaryl Chlorides
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Traditional methods for the preparation of secondary alkyl-substituted aryl and heteroaryl chlorides challenge both selectivity and functional group tolerance. This contribution describes the use of statistical design of experiments to develop an effective procedure for the preparation of isopropyl-substituted (hetero)arenes with minimal isopropyl to n-propyl isomerization. The reaction tolerates electronically diverse aryl chloride coupling partners, with excellent conversion observed for strongly electron-deficient aromatic rings, such as esters and amides. Electron-rich systems, including methyl- and methoxy-substituted aryl chlorides, were found to be less reactive. Furthermore, the reaction was found to be most successful when heteroaryl chlorides were submitted to the cross-coupling protocol. By mapping substituent effects on reaction selectivity, we were able to show that electron-deficient aryl chlorides are essential for efficient coupling, and use electronic structure calculations to predict the likelihood of successful coupling through the estimation of the electron affinity of each aryl chloride. Moderate isolated yields were achieved with selected aryl chlorides, and moderate to good isolated yields were obtained for all the heteroaryl chlorides coupled. Excellent selectivity was observed when a 2,6-dichloroquinoline was used, allowing mono-substitution on a challenging substrate. (Figure presented.).
- Sanderson, James N.,Dominey, Andrew P.,Percy, Jonathan M.
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p. 1007 - 1017
(2017/03/27)
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- Introducing a new radical trifluoromethylation reagent
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Perfluoro-3-ethyl-2,4-dimethyl-3-pentyl radical (PPFR) is a persistent radical stable at room temperature, but easily decomposes at 90 °C to produce a CF3 radical which is able to react with a variety of aromatic compounds to afford the corresponding trifluoromethyl derivatives, usually as mixtures of regioisomers in good to excellent overall yields.
- Sato, Azusa,Han, Jianlin,Ono, Taizo,Wzorek, Alicja,Ace?a, José Luis,Soloshonok, Vadim A.
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supporting information
p. 5967 - 5970
(2015/03/30)
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- Palladium-catalysed direct cross-coupling of secondary alkyllithium reagents
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Palladium-catalysed cross-coupling of secondary C(sp3) organometallic reagents has been a long-standing challenge in organic synthesis, due to the problems associated with undesired isomerisation or the formation of reduction products. Based on our recently developed catalytic C-C bond formation with organolithium reagents, herein we present a Pd-catalysed cross-coupling of secondary alkyllithium reagents with aryl and alkenyl bromides. The reaction proceeds at room temperature and on short timescales with high selectivity and yields. This methodology is also applicable to hindered aryl bromides, which are a major challenge in the field of metal catalysed cross-coupling reactions.
- Vila, Carlos,Giannerini, Massimo,Hornillos, Valentin,Fananas-Mastral, Martin,Feringa, Ben L.
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p. 1361 - 1367
(2014/03/21)
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- Rearrangement of dimethylcarbene to propene: Study by laser flash photolysis and ab initio molecular orbital theory
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Laser flash photolysis (Nd:YAG laser, 355 nm, 35 mJ, 150 ps) of dimethyldiazirine and dimethyldiazirine-d6 produces dimethylcarbene (DMC) and dimethylcarbene-d6 (DMC-d6), respectively. The carbenes were trapped with pyridine to form ylides which absorb around 364 nm. It was possible to resolve the growth of the ylides as a function of pyridine concentration in Freon-113, α, α,α-trifluoromethylbenzene, and perfluorohexane as a function of temperature. The observed rate constant (k(obs)) of ylide formation was linearly dependent on the concentration of pyridine in all solvents and at all temperatures. From plots of kobs versus [pyridine] it was possible to extract values of k(pyr) (the absolute rate constant of reaction of the carbene with pyridine) and τ, the carbene lifetime in the absence of pyridine, and their associated Arrhenius parameters. In Freon-113 and α, α, α-trifluoromethylbenzene the carbenes decay both by rearrangement and by reaction with solvent. In perfluorohexane the carbene decay appears to be predominantly unimolecular. The experimental results are compared with ab initio molecular orbital calculations. The experimentally determined barrier to disappearance of DMC in perfluorohexane (2.56 ± 0.05 kcal/mol) is much smaller than that calculated (7.4 ± 2 kcal/mol) using ab initio molecular orbital theory. The Arrhenius parameters and isotope effects indicate that the rearrangement of DMC in perfluorohexane has a large component of quantum mechanical tunneling. The activation energy for the disappearance of DMC-d6 in perfluorohexane (5.63 ± 0.03 kcal/mol) is consistent with calculations which indicate that QMT makes only a minor contribution to the deuterated system under the conditions of this study.
- Ford, Francis,Yuzawa, Tetsuro,Platz, Matthew S.,Matzinger, Stephan,Fülscher, Markus
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p. 4430 - 4438
(2007/10/03)
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