Regioselectivity in Reactions between Bis(2-benzothiazolyl)ketone and Vinyl Grignard Reagents: C- versus O-alkylation—Part III (original) (raw)
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The Journal of Organic Chemistry, 2010
Radical additions to substituted alkenes are among the most important reactions in radical chemistry. Nonetheless, there is still some controversy in the literature about the factors that affect the rate and regioselectivity in these addition reactions. In this paper, the orientation of (nucleophilic) radical additions to electron-rich, -neutral, and -poor monosubstituted substrates (11 reactions in total) is investigated through the use of chemical concepts and reactivity descriptors. The regioselectivity of the addition of nucleophilic radicals on electron-rich and -neutral alkenes is thermodynamically controlled. An excellent correlation of 94% is found between the differences in activation barriers and in product stabilities (unsubstituted versus substituted site attack). Polar effects at the initial stage of the reaction play a significant role when electron-poor substrates are considered, lowering the extent of regioselectivity toward the unsubstituted sites, as predicted from the stability differences. This is nicely confirmed through an analysis for each of the 11 reactions using the spin-polarized dual descriptor, matching electrophilic and nucleophilic regions.
Tetrahedron, 2002
radical chain reactions of a variety of acyclic and cyclic a-azido ketones with tributyltin hydride have been investigated. The derived N-(tributylstannyl)aminyl radicals normally undergo H-abstraction reaction yielding corresponding amines, and thence symmetrical pyrazines by subsequent self-condensation, in competition with 1,2-H-migration from the a-carbon to nitrogen leading to a-imino ketone decomposition products with loss of the chain-carrying tributyltin radical. The noteworthy occurrence of a quite uncommon radical 1,2hydrogen-atom shift is considered to be largely due to consequent formation of a highly stable, captodative carbon-centred radical. In contrast with our previous N-stannylaminyl radicals produced from a-azido-b-keto esters, the present aminyl congeners give poor amounts (or even none) of nitrogen-inserted amides/lactams, which are envisaged to arise from intramolecular three-membered cyclisation onto the ketone moiety followed by b-scission of the resultant alkoxyl radical. It is inferred that adequate stabilisation of the eventual ring-opened carbon radical be a major factor for the successful outcome of the regiospeci®c nitrogen insertion process. Evidence is also presented that chemoselective attack of tris(trimethylsilyl)silyl radical to the ketone oxygen of an a-azido ketone gives rise to deazidation as a likely consequence of b-elimination of azidyl radical by the ensuing a-silyloxyalkyl radical. X-Ray crystal structure analyses of the bromo ketone 5a, the azido ketone 5b, the caprolactam 22, and the pyrazine 26 have been performed.
The Journal of Physical Chemistry A, 2008
Radicals resulting from one-electron reduction of (N-methylpyridinium-4-yl) methyl esters have been reported to yield (N-methylpyridinium-4-yl)-methyl radical, or N-methyl-γ-picoliniumyl for short, by heterolytic cleavage of carboxylate. This new reaction could provide the foundation for a new structural class of bioreductively-activated, hypoxia-selective antitumor agents. N-methyl-γpicoliniumyl radicals are likely to damage DNA by way of H-abstraction and it is of paramount significance to assess their H-abstraction capabilities. In this context, the benzylic C-H homolyses were studied of toluene (T), γ-picoline (P, 4-methylpyridine), and N-methyl-γ-picolinium (1c, 1,4dimethylpyridinium). With a view to providing capacity for DNA intercalation the properties also were examined of the annulated derivatives 2c (1,4-dimethylquinolinium), 3c (9,10dimethylacridinium), and 4c (1,4-dimethylbenzo[g]quinolinium). The benzylic C-H homolyses were studied with density functional theory (DFT), perturbation theory (up to MP4SDTQ), and configuration interaction methods (QCISD(T), CCSD(T)). While there are many similarities between the results obtained here with DFT and CI theory, a number of significant differences occur and these are shown to be caused by methodological differences in the spin density distributions of the radicals. The quality of the wave functions is established by demonstration of internal consistencies and with reference to a number of observable quantities. The analysis of spin polarization emphasizes the need for a clear distinction between "electron delocalization" and "spin delocalization" in annulated radicals. Aside from their relevance for the rational design of new antitumor drugs, the conceptional insights presented here also will inform the understanding of ferromagnetic materials, of spin-based signaling processes, and of spin topologies in metalloenzymes.
Journal of Physical Chemistry A, 2008
Radicals resulting from one-electron reduction of (N-methylpyridinium-4-yl) methyl esters have been reported to yield (N-methylpyridinium-4-yl)-methyl radical, or N-methyl-γ-picoliniumyl for short, by heterolytic cleavage of carboxylate. This new reaction could provide the foundation for a new structural class of bioreductively-activated, hypoxia-selective antitumor agents. N-methyl-γpicoliniumyl radicals are likely to damage DNA by way of H-abstraction and it is of paramount significance to assess their H-abstraction capabilities. In this context, the benzylic C-H homolyses were studied of toluene (T), γ-picoline (P, 4-methylpyridine), and N-methyl-γ-picolinium (1c, 1,4dimethylpyridinium). With a view to providing capacity for DNA intercalation the properties also were examined of the annulated derivatives 2c (1,4-dimethylquinolinium), 3c (9,10dimethylacridinium), and 4c (1,4-dimethylbenzo[g]quinolinium). The benzylic C-H homolyses were studied with density functional theory (DFT), perturbation theory (up to MP4SDTQ), and configuration interaction methods (QCISD(T), CCSD(T)). While there are many similarities between the results obtained here with DFT and CI theory, a number of significant differences occur and these are shown to be caused by methodological differences in the spin density distributions of the radicals. The quality of the wave functions is established by demonstration of internal consistencies and with reference to a number of observable quantities. The analysis of spin polarization emphasizes the need for a clear distinction between "electron delocalization" and "spin delocalization" in annulated radicals. Aside from their relevance for the rational design of new antitumor drugs, the conceptional insights presented here also will inform the understanding of ferromagnetic materials, of spin-based signaling processes, and of spin topologies in metalloenzymes.
Regioselectivity in free radical bromination of unsymmetrical dimethylated pyridines
During a literature review some curious inconsistencies in the free radical bromination of picolines were noted. To achieve a better understanding of the mechanisms and regioselectivity we reran these reactions, extending our work to unsymmetrical lutidines using N-bromosuccinimide in limiting amount. Characterization of the products was done with GC/MS and H NMR. The regioselectivity of bromination in unsymmetrical dimethylpyridines shows that nitrogen in the ring is deactivating inductively. The competition between 2,3, 2,4, and 2,5 dimethyl pyridine toward bromination results with bromination in the methyl group farthest from the N in the ring. 3,4-Lutidine shows only the 4,4-dibrominated product.
Journal of Organic Chemistry, 1982
Free-radical decomposition of diazonium salts by titanous salts in the presence of olefins conjugated with carbonyl group leads to reductive arylation or arylation and diazo coupling of the radical adduct, depending on the orientation of the aryl radical addition (8 or a). The absolute rate constants of the addition (107-108 M-ls-l at 5 "C) were determined by comparison with the rate of the iodine abstraction by aryl radicals from isopropyl iodide. The obtained data of the addition rates to the position correlate well with the E, steric parameters. The influence of the resonance stabilization of the radical adduct on the reactivity can be significant, but the regioselectivity of the addition is mainly determined by steric effects. The different fate of the a-and 8-radical adducts are discussed on the basis of their different polar character. (5) A. Citterio, F. Minisci, A. Albinati, and S. Bruckner, Tetrahedron Lett., 2909 (1980).