- Decarboxylative Bromination of Sterically Hindered Carboxylic Acids with Hypervalent Iodine(III) Reagents
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Sterically hindered three-dimensional (3D) alkyl halides are promising precursors for various reactions; however, they are difficult to synthesize via conventional reactions. We present an efficient and practical method for decarboxylative bromination of sterically hindered 3D aliphatic carboxylic acids using commercially available (diacetoxyiodo)benzene and potassium bromide, one of the most stable and cheapest bromine sources in nature. The present method features a metal-free/Br2-free system, mild reaction conditions, one-pot operation under air at room temperature, wide functional group compatibility, and gram-scale synthetic capability. This highly efficient reaction cleanly converts a broad range of carboxylic acids, the most inexpensive and readily available sources of highly strained/naturally occurring/drug-related scaffolds, into the corresponding alkyl bromides in good to high yields.
- Kanazawa, Junichiro,Koyamada, Kenta,Miyamoto, Kazunori,Uchiyama, Masanobu,Watanabe, Ayumi
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supporting information
p. 1328 - 1334
(2020/08/14)
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- Sodium diisopropylamide-mediated dehydrohalogenations: Influence of primary- A nd secondary-shell solvation
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Eliminations of alkyl halides by sodium diisopropylamide (NaDA) in tetrahydrofuran (THF)/hexane or THF/N,N-dimethylethylamine (DMEA) solutions are facile and complementary to analogous reactions of lithium diisopropylamide in THF. Rate studies show a dominance of monomer-based metalations and prevalent secondary-shell solvation effects overlaid on primary-shell effects. 1-Halooctanes exclusively undergo elimination rather than substitution. Rate and isotopic labeling studies on 1-bromooctane reveal an E2-like elimination pathway via trisolvated NaDA monomer. By contrast, 1-chlorooctane is eliminated via disolvated monomer through a carbenoid mechanism. exo-2-Norbornyl chloride and bromide are also eliminated via disolvated monomer; a syn E2 mechanism is inferred for these substrates. The cis- A nd trans-4-tert-butylcyclohexyl bromides show a preference for the elimination of the cis isomer (kcis/ax/ktrans/eq = 10). Rate and isotopic labeling studies are consistent with a trans-diaxial E2 elimination via trisolvated monomer for the cis isomer and a carbenoid mechanism via disolvated monomer for the trans isomer. Vicinal haloethers show substrate-dependent reactivities, affording alkynes and enol ethers. trans-1-Bromo-2-methoxycyclohexane provides enol ether 1-methoxycyclohexene, while trans-1-bromo-2-methoxycyclooctane provides dimeric products consistent with fleeting cycloocta-1,2-diene (cyclic allene), which was fully characterized as two conformers.
- Ma, Yun,Algera, Russell F.,Woltornist, Ryan A.,Collum, David B.
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supporting information
p. 10860 - 10869
(2019/09/30)
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- Catalytic Access to Alkyl Bromides, Chlorides and Iodides via Visible Light-Promoted Decarboxylative Halogenation
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Herein is reported the catalytic, visible light-promoted, decarboxylative halogenation (bromination, chlorination, and iodination) of aliphatic carboxylic acids. This operationally-simple reaction tolerates a range of functional groups, proceeds at room temperature, and is redox neutral. By employing an iridium photocatalyst in concert with a halogen atom source, the use of stoichiometric metals such as silver, mercury, thallium, and lead can be circumvented. This reaction grants access to valuable synthetic building blocks from the large pool of cheap, readily available carboxylic acids.
- Candish, Lisa,Standley, Eric A.,Gómez-Suárez, Adrián,Mukherjee, Satobhisha,Glorius, Frank
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supporting information
p. 9971 - 9974
(2016/07/19)
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- Reductive Chlorination and Bromination of Ketones via Trityl Hydrazones
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A method is presented for the direct transformation of a ketone to the corresponding reduced alkyl chloride or bromide. The process involves the reaction of a ketone trityl hydrazone with tBuOCl to give a diazene which readily collapses to the α-chlorocar
- Reyes, Julius R.,Rawal, Viresh H.
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p. 3077 - 3080
(2016/03/12)
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- Simple, chemoselective hydrogenation with thermodynamic stereocontrol
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Few methods permit the hydrogenation of alkenes to a thermodynamically favored configuration when steric effects dictate the alternative trajectory of hydrogen delivery. Dissolving metal reduction achieves this control, but with extremely low functional group tolerance. Here we demonstrate a catalytic hydrogenation of alkenes that affords the thermodynamic alkane products with remarkably broad functional group compatibility and rapid reaction rates at standard temperature and pressure.
- Iwasaki, Kotaro,Wan, Kanny K.,Oppedisano, Alberto,Crossley, Steven W. M.,Shenvi, Ryan A.
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supporting information
p. 1300 - 1303
(2014/02/14)
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- Diastereofacial selectivity in reactions of substituted cyclohexyl radicals. An experimental and theoretical study
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The diastereofacial selectivity in reactions of a series of alkyl-substituted cyclohexyl radicals has been investigated. In additions of cyclohexyl radicals to alkenes, it has been found that only substituents bound at the olefinic center being attacked by the radical influence the equatorial-axial selectivity. Substituents bound to the radical center or axial substituents β to the radical center lead to increased axial attack. Equatorial β-substituents or axial γ-substituents increase the amount of equatorial attack. The same trends are observed for halogen and hydrogen abstraction reactions; the amount of axial reaction product is usually somewhat higher than in the addition reactions. The stereoselectivities can be explained with steric and torsional effects very similar to those suggested for nucleophilic addition reactions to cyclohexanones. A MM2 force field has been parameterized to gain further insight into the stereochemistry of the reaction.
- Damm,Giese,Hartung,Hasskerl,Houk,Hüter,Zipse
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p. 4067 - 4079
(2007/10/02)
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- MECHANISMS OF FREE-RADICAL REACTIONS. XVII. STEREOSELECTIVITY OF THE FREE-RADICAL ABSTRACTION OF A HALOGEN ATOM FROM 4-tert-BUTYLCYCLOHEXYL HALIDES AND 2-NORBORNYL HALIDES
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The free-radical reduction of cis- and trans-4-tert-butylcyclohexyl halides and also of exo- and endo-2-chloronorbornanes by the trialkyl hydrides of group IVB elements was studied by the method of competing reactions.For the derivatives of cyclohexane the reactivity of the axial C-Hlg bond is 2-4 times higher than the reactivity of the equatorial bond.In the case of halogenonorbornanes the abstraction of the exo-halogen atom takes place at a higher rate.The stereoselectivity of the reaction increases in the transition from the bromides to the chlorides.The nature of the changes in the stereoselectivity with variation in the structure of the reagents and in the nature of the halogen atom agrees well with theories about the torsional interactions arising in the transition state.
- Dneprovskii, A. S.,Pertsikov, B. Z.
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p. 222 - 227
(2007/10/02)
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- New Stereoselective Routes from Alcohols to Secondary Alkyl Bromides with Retention of Configuration
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Secondary alcohols can be converted into the corresponding bromides with high stereoselective retention of configuration; this two-step process proceeds by a double inversion involving the intermediate selenides.
- Sevrin, Mireille,Krief, Alain
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p. 656 - 657
(2007/10/02)
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