- Desymmetric enantioselective reduction of cyclic 1,3-diketones catalyzed by a recyclable p-chiral phosphinamide organocatalyst
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The P-stereogenic phosphinamides are a structurally novel skeletal class which has not been investigated as chiral organocatalysts. However, chiral cyclic 3-hydroxy ketones are widely used as building blocks in the synthesis of natural products and bioactive compounds. However, general and practical methods for the synthesis of such chiral compounds remain underdeveloped. Herein, we demonstrate that the P-stereogenic phosphinamides are powerful organocatalysts for the desymmetric enantioselective reduction of cyclic 1,3-diketones, providing a useful method for the synthesis of chiral cyclic 3-hydroxy ketones. The protocol displays a broad substrate scope that is amenable to a series of cyclic 2,2-disubstituted five- and six-membered 1,3-diketones. The chiral cyclic 3-hydroxy ketone products bearing an all-carbon chiral quaternary center could be obtained with high enantioselectivities (up to 98% ee) and diastereoselectivities (up to 99:1 dr). Most importantly, the reactions could be practically performed on the gram scale and the catalysts could be reused without compromising the catalytic efficiency. Mechanistic studies revealed that an intermediate formed from P-stereogenic phosphinamide and catecholborane is the real catalytically active species. The results disclosed herein bode well for designing and developing other reactions using P-stereogenic phosphinamides as new organocatalysts.
- Qin, Xu-Long,Li, Ang,Han, Fu-She
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supporting information
p. 2994 - 3002
(2021/03/01)
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- Mild C?F Activation in Perfluorinated Arenes through Photosensitized Insertion of Isonitriles at 350 nm
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Fluorinated compounds have become important in the fields of agrochemical industry, pharmaceutical chemistry and materials sciences. Accordingly, various methods for their preparation have been developed in the past. Fluorinated compounds can be accessed via conjugation with fluorinated building blocks, via C?H fluorination or via selective activation of perfluorinated compounds to give the partially fluorinated congeners. Especially the direct activation of C?F bonds, one of the strongest σ-bonds, still remains challenging and new strategies for C?F activation are desirable. Herein a method for the photochemical activation of aromatic C?F bonds is presented. It is shown that isonitriles selectively insert into aromatic C?F bonds while aliphatic C?F bonds remain unaffected. Mechanistic studies reveal the reaction to proceed via the indirect excitation of the isonitrile to its triplet state by photoexcited acetophenone at 350 nm. Due to the relatively mild light used, the process shows high functional group tolerance and various compounds of the class of benzimidoyl fluorides are accessible from aryl isonitriles and commercially available perfluorinated arenes. (Figure presented.).
- Weidlich, Frauke,Esumi, Naoto,Chen, Dongyang,Mück-Lichtenfeld, Christian,Zysman-Colman, Eli,Studer, Armido
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p. 376 - 383
(2019/11/19)
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- Multicomponent Coupling Reaction of Perfluoroarenes with 1,3-Butadiene and Aryl Grignard Reagents Promoted by an Anionic Ni(II) Complex
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An anionic Ni complex was isolated and its structure determined by X-ray crystallography. With such an anionic complex as a key intermediate, a regio- and stereoselective multicomponent coupling reaction of perfluoroarenes, aryl Grignard reagents, and 1,3-butadiene in a 1:1:2 ratio was achieved, resulting in the formation of 1,6-octadiene derivatives containing two aryl groups, one from the perfluoroarene and the other from the aryl Grignard reagent, at the 3- and 8-positions, respectively.
- Iwasaki, Takanori,Fukuoka, Asuka,Min, Xin,Yokoyama, Wataru,Kuniyasu, Hitoshi,Kambe, Nobuaki
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supporting information
p. 4868 - 4871
(2016/10/18)
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- Anilinic N-oxides support cytochrome P450-mediated N-dealkylation through hydrogen-atom transfer
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The mechanism of N-dealkylation mediated by cytochrome P450 (P450) has long been studied and argued as either a single electron transfer (SET) or a hydrogen atom transfer (HAT) from the amine to the oxidant of the P450, the reputed iron-oxene. In our study, tertiary anilinic N-oxides were used as oxygen surrogates to directly generate a P450-mediated oxidant that is capable of N-dealkylating the dimethylaniline derived from oxygen donation. These surrogates were employed to probe the generated reactive oxygen species and the subsequent mechanism of N-dealkylation to distinguish between the HAT and SET mechanisms. In addition to the expected N-demethylation of the product aniline, 2,3,4,5,6-pentafluoro-N,N-dimethylaniline N-oxide (PFDMAO) was found to be capable of N-dealkylating both N,N-dimethylaniline (DMA) and N-cyclopropyl-N-methylaniline (CPMA). Rate comparisons of the N-demethylation of DMA supported by PFDMAO show a 27-fold faster rate than when supported by N,N-dimethylaniline N-oxide (DMAO). Whereas intermolecular kinetic isotope effects were masked, intramolecular measurements showed values reflective of those seen previously in DMAO- and the native NADPH/O2-supported systems (2.33 and 2.8 for the N-demethylation of PFDMA and DMA from the PFDMAO system, respectively). PFDMAO-supported N-dealkylation of CPMA led to the ring-intact product N-cyclopropylaniline (CPA), similar to that seen with the native system. The formation of CPA argues against a SET mechanism in favor of a P450-like HAT mechanism. We suggest that the similarity of KIEs, in addition to the formation of the ring-intact CPA, argues for a similar mechanism of Compound I (Cpd I) formation followed by HAT for N-dealkylation by the native and N-oxide-supported systems and demonstrate the ability of the N-oxide-generated oxidant to act as an accurate mimic of the native P450 oxidant.
- Roberts, Kenneth M.,Jones, Jeffery P.
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experimental part
p. 8096 - 8107
(2010/09/11)
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- Reactions of HMPA with hexafluorobenzene, pentafluorochlorobenzene and pentafluorophenol
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Hexamethylphophoramide (HMPA) reacted with hexafluorobenzene and its derivatives with good conversion to give dimethylaminated products and phosphorofluoridates, even in unfavorable reaction stoichiometries. An aromatic nucleophilic mechanism might be inv
- Zhang, Cheng-Pan,Chen, Qing-Yun,Xiao, Ji-Chang
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p. 424 - 428
(2008/12/22)
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- Interaction of N,N-dimethylperfluoroarylamines with nitric and nitrous acids
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N,N-Dimethylpentafluoroaniline enters easily into reactions with a mixture of nitric and sulphuric acids or nitric acid with conversion of the side chain. In the reactions with mixtures of HNO3 and H2SO4, the formation of N-nitroso-N-methyl and N-nitro-N-methylpentafluoroanilines is observed. The ratio of these products was found to depend on the ratio of the acids: the formation of N-nitro-N-methylpentafluoroaniline increases with the quantity of sulphuric acid; N-nitroso-N-methylpentafluoroaniline is obtained when only nitric acid is employed. N,N-Dimethylperfluoro-p-toluidine, N,N-dimethylperfluoro-2,4-xylidine, N,N-dimethylperfluoro-5-aminoindane undergo similar transformations. N-Nitroso derivatives were converted by a mixture of HNO3 and H2SO4, HNO3 or NO2BF4 into the corresponding N-nitro derivatives. Formation of the corresponding N-nitroso-N-methyl derivatives occurs when N,N-dimethylpentafluoroaniline, N,N-dimethylperfluoro-p-toluidine are treated with HNO2.
- Platonov, Vyacheslav E.,Haas, Alois,Schelvis, Meinolf,Lieb, Max,Dvornikova, Kira V.,Osina, Ol'ga I.
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- Condensation of αβ-unsaturated amines with perfluoroarenes
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Condensation of αβ-unsaturated amines (enamines, keten ON-acetals, ynamines) with perfluoroarenes (perfluorobenzene, perfluorotoluene, bromopentafluorobenzene, perfluoropyridine) leads to the formation of ketones, esters, and amines α-substituted by a perfluoroaryl group. In the case of enamines, C-arylation can be followed by intramolecular N-arylation, giving fluorinated tetrahydrocarbazoles which can then be dehydrogenated by chloranil to give fluorinated carbazoles.
- Blazejewski, Jean-Claude,Wakselman, Claude
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p. 2845 - 2850
(2007/10/02)
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