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Radical Clock (radical + clock)

Distribution by Scientific Domains
Chemistry100%

Selected Abstracts

Cooperative Effects on Radical Recombination in CYP3A4-Catalyzed Oxidation of the Radical Clock ,-Thujone

CHEMBIOCHEM, Issue 4 2009
Yongying Jiang Dr.
Abstract Tick tock: The timing of the ,-thujone radical clock (see scheme) can be specifically altered by an allosteric effector. Progesterone, a well-documented CYP3A4 allosteric effector, was found to increase the yield of the unrearranged, C4-derived product of ,-thujone oxidation at the expense of the combined yields of all the rearranged C4-oxidized metabolites. The results demonstrate that the apparent radical recombination rate in the CYP3A4 hydroxylation of ,-thujone is accelerated by the progesterone hetereotropic cooperativity. [source]

Radical clocks and electron transfer.

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 12 2005
Comparison of crown ether effects on the reactivity of potassium, magnesium towards 1-bromo-2-(3-butenyl)benzene.
Abstract The reaction of the title precursor of the aryl radical clock 1-bromo-2-(3-butenyl)benzene, 1Br, towards potassium and magnesium in THF was studied in the presence and absence of various additives, at ambient and low temperatures. The additives were cis -dicyclohexano-18-crown-6 or tert -butyl alcohol; the first one to render soluble potassium by forming its alkalide, the second to distinguish carbanionic from radical cyclization. The addition of 1Br to a THF stirred suspension of potassium pieces yields remarkably low amounts of products resulting from radical cyclization, in contrast to the amounts reported by Bunnett and Beckwith's group for the reaction in 67% ammonia,33% tert -butyl alcohol medium. The amount of cyclized products obtained with potassium pieces in THF is in the same range as that observed in the reaction of magnesium with 1Br in THF. This similarity allows us to discard the earlier triad hypothesis that we proposed to account for the unexpectedly low amounts of cyclized products of aryl halides radical clocks in Grignard reagent formation. The addition of crown ethers to the THF reaction medium induces contrasting effects for potassium and magnesium. A distinctive increase in the radical cyclization is observed for potassium, whereas the addition of crown inhibits the formation of Grignard reagent more efficiently when the solvent is diethyl ether than when it is THF. The observed effects are explained by putting in perspective the metal reactive dissolution with elementary steps occurring in the vicinity of a cathode. The reaction of potassium pieces or magnesium turnings is comparable to the heterogeneous electron transfer occurring at a cathode whereas the reaction of potassium in the presence of crown ether is comparable to homogeneous conditions of electron transfer obtained in redox catalysis. A discussion of the dianion hypothesis for the Grignard reaction of aryl halides is provided and the importance of considering the reactivity of reactive metal dissolution (or organic corrosion) in the framework of recent progress made in the modelling of electrode reactivity is emphasized. This paper shows that caution should be taken when radical clocks are used to study reactions at the metal,solution interface. More specifically, the non-observation of rearranged products from the radical clock (even for the very rapid ones) under these conditions does not necessary imply that there is no radical intermediate along the dominant reaction channel. This pattern of reactivity strongly contrasts with that usually observed when radical clocks are used in homogeneous media. The leading parameters in the rearranged/unrearranged products ratio seem to be the time that the reactive species (radical anions) created by the first electron transfer spend in the close vicinity of this surface, the rate constant of rearrangement of the radical formed by the cleavage of the radical anion and the redox properties of this radical. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Cooperative Effects on Radical Recombination in CYP3A4-Catalyzed Oxidation of the Radical Clock ,-Thujone

CHEMBIOCHEM, Issue 4 2009
Yongying Jiang Dr.
Abstract Tick tock: The timing of the ,-thujone radical clock (see scheme) can be specifically altered by an allosteric effector. Progesterone, a well-documented CYP3A4 allosteric effector, was found to increase the yield of the unrearranged, C4-derived product of ,-thujone oxidation at the expense of the combined yields of all the rearranged C4-oxidized metabolites. The results demonstrate that the apparent radical recombination rate in the CYP3A4 hydroxylation of ,-thujone is accelerated by the progesterone hetereotropic cooperativity. [source]

Alkyl halides reactions with cathodes or with magnesium.

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 12 2006
Grignard reagent studied with radical clocks.
Abstract In the mechanism of reaction of Grignard reagent formation for alkyl halides (RX), it is generally assumed that the alkyl radical, formed by the electron transfer from the metal to this halide, reacts rapidly with the paramagnetic MgX, species. The previous comparisons of aryl halides reactivity toward magnesium and their reactivity toward a cathode strongly suggested that MgX, species are not, for the aryl halides, compulsory to rationalise the observed facts. The aryl radicals formed by electron transfer from the metal to the aryl halide would undergo a rapid second electron transfer to yield carbanions transformed into RMgX by reaction with MgX2. In contrast, for the alkyl halides, the reduction of the rapidly formed alkyl radicals into carbanions has seldom been discussed as a possible fate for these radicals, the main discussed fates being dimerisation, disproportionation, hydrogen abstraction from the solvent, rearrangement or coupling with MgX, radicals. Two main differences distinguish the reactivity of alkyl halides from their aryl halides counterpart. First, the radical anions of aryl halides may have a given lifetime whereas electron transfer to alkyl halides is concerted with the cleavage of the molecule. Second, the aryl radicals display far stronger oxidising properties than the alkyl radicals. The counterpart of this property is that aryl carbanions display weaker reducing properties than the alkyl ones. In this report, putting in perspective Grignard reaction and the experimental results obtained with identical radical clocks in electrochemistry, we tentatively provide an answer to the question raised in the title. The comparison of electrochemical patterns of reactivity of selected alkyl halides and the evolutions of yields in the preparation of Grignard reagent suggest a new explanation for the lower yields generally observed when alkyl iodides are the starting substrates. It involves an autocatalytic reaction where carbanionic species formed from the alkyl radicals and diffusing away from the metal surface, transfer one electron to the alkyl halide; the result would be the creation of two radicals leading to an increased amount of by-products. If the carbanionic mechanism were to be retained for the formation of alkyl Grignard reagent one would have to admit that the magnesium surface behaves as a cathode displaying high current densities reminiscent of microelectrodes. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Radical clocks and electron transfer.

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 12 2005
Comparison of crown ether effects on the reactivity of potassium, magnesium towards 1-bromo-2-(3-butenyl)benzene.
Abstract The reaction of the title precursor of the aryl radical clock 1-bromo-2-(3-butenyl)benzene, 1Br, towards potassium and magnesium in THF was studied in the presence and absence of various additives, at ambient and low temperatures. The additives were cis -dicyclohexano-18-crown-6 or tert -butyl alcohol; the first one to render soluble potassium by forming its alkalide, the second to distinguish carbanionic from radical cyclization. The addition of 1Br to a THF stirred suspension of potassium pieces yields remarkably low amounts of products resulting from radical cyclization, in contrast to the amounts reported by Bunnett and Beckwith's group for the reaction in 67% ammonia,33% tert -butyl alcohol medium. The amount of cyclized products obtained with potassium pieces in THF is in the same range as that observed in the reaction of magnesium with 1Br in THF. This similarity allows us to discard the earlier triad hypothesis that we proposed to account for the unexpectedly low amounts of cyclized products of aryl halides radical clocks in Grignard reagent formation. The addition of crown ethers to the THF reaction medium induces contrasting effects for potassium and magnesium. A distinctive increase in the radical cyclization is observed for potassium, whereas the addition of crown inhibits the formation of Grignard reagent more efficiently when the solvent is diethyl ether than when it is THF. The observed effects are explained by putting in perspective the metal reactive dissolution with elementary steps occurring in the vicinity of a cathode. The reaction of potassium pieces or magnesium turnings is comparable to the heterogeneous electron transfer occurring at a cathode whereas the reaction of potassium in the presence of crown ether is comparable to homogeneous conditions of electron transfer obtained in redox catalysis. A discussion of the dianion hypothesis for the Grignard reaction of aryl halides is provided and the importance of considering the reactivity of reactive metal dissolution (or organic corrosion) in the framework of recent progress made in the modelling of electrode reactivity is emphasized. This paper shows that caution should be taken when radical clocks are used to study reactions at the metal,solution interface. More specifically, the non-observation of rearranged products from the radical clock (even for the very rapid ones) under these conditions does not necessary imply that there is no radical intermediate along the dominant reaction channel. This pattern of reactivity strongly contrasts with that usually observed when radical clocks are used in homogeneous media. The leading parameters in the rearranged/unrearranged products ratio seem to be the time that the reactive species (radical anions) created by the first electron transfer spend in the close vicinity of this surface, the rate constant of rearrangement of the radical formed by the cleavage of the radical anion and the redox properties of this radical. Copyright © 2005 John Wiley & Sons, Ltd. [source]