Laser Flash Photolysis Studies of Alkoxyl Radical Kinetics Using 4-Nitrobenzenesulfenate Esters as Radical Precursors

Horner, John H.; Choi, Seung-Yong; Newcomb, Martin

doi:10.1021/ol006469g

Cited by 44 publications

(25 citation statements)

References 33 publications

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“…This chemistry could be fast (intramolecular) and might separate the radical in terms of physical proximity from the iron atom. The cumyloxy radical from cumene hydroperoxide could react directly with the enzyme or undergo Scheme 3 -scission to afford the methyl radical (32). In either case, free radical chemistry (abstraction) would be expected.…”

Section: Discussionmentioning

confidence: 99%

Secondary Alkyl Hydroperoxides as Inhibitors and Alternate Substrates for Lipoxygenase

et al. 2007

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Lipoxygenase plays a central role in polyunsaturated fatty acid metabolism, inaugurating the biosynthesis of eicosanoids in animals and phytooxylipins in plants. Redox cycling of the non-heme iron cofactor represents a critical element of the catalytic mechanism. Paradoxically, the isolated enzyme contains Fe(II), but the catalytically active form contains Fe(III), and the natural oxidant for the iron is the hydroperoxide product of the catalyzed reaction. Controlling the redox state of lipoxygenase iron with small molecules, inhibitors or activators, could be a means to modulate the activity of the enzyme. The effects of secondary alkyl hydroperoxides and the corresponding alcohols on soybean lipoxygenase-1 reaction rates were investigated and found to be very different. Secondary alcohols were noncompetitive or linear mixed inhibitors with inhibition constants in the millimolar concentration range, with more hydrophobic compounds producing lower values. Secondary alkyl hydroperoxides were inhibitors of lipoxygenase-1 primarily at high substrate concentration. They were more effective inhibitors than the alcohols, with dissociation constants in the micromolar concentration range. The hydroperoxides bearing longer alkyl substituents were the more effective inhibitors. Oxidation of the iron in lipoxygenase-1 by 2-hydroperoxyalkanes was evident in electron paramagnetic resonance (EPR) measurements, but the enzyme was neither activated nor was it inactivated. Instead there was evidence for an entirely different reaction catalyzed by the enzyme, a homolytic dehydration of the hydroperoxide to produce the corresponding carbonyl compound.

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Section: Discussionmentioning

confidence: 99%

Secondary Alkyl Hydroperoxides as Inhibitors and Alternate Substrates for Lipoxygenase

et al. 2007

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“…vs the 1,4 or 1,6 variants. 31 Rare exceptions 17 to this rule are cases where C5 lacks a H atom, or when adjacent C-H bonds are significantly weaker (e.g., benzylic, tertiary, αoxy), or when geometry precludes 1,5-HAT. Otherwise, selective 1,5-HAT of an initiating radical typically offers access to a δ carbon radical, exclusively.…”

Section: Syn Thesismentioning

confidence: 99%

Remote C–H Functionalization via Selective Hydrogen Atom Transfer

2018

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The selective functionalization of remote C-H bonds via intramolecular hydrogen atom transfer (HAT) is transformative for organic synthesis. This radical-mediated strategy provides access to novel reactivity that is complementary to closed-shell pathways. As modern methods for mild generation of radicals are continually developed, inherent selectivity paradigms of HAT mechanisms offer unparalleled opportunities for developing new strategies for C-H functionalization. This review outlines the history, recent advances, and mechanistic underpinnings of intramolecular HAT as a guide to addressing ongoing challenges in this arena.

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“…The range obtained for k SR Ic (0.4e1.5Â10 8 s À1 ) indicates that the 1,5-H-shift in tert-alkoxyl radical Ic, in spite of its steric encroachment near oxygen, is not slower than 1,5-H-shift in the 1-pentoxyl radical (k SR ¼2.7Â10 7 s À1 at 20 C). 40,41 Yields of alcohol 3c between 23 and 36% show that an effective H-atom donor exists in reaction mixtures used for mechanistic experiments starting from 1c (Table 2). Since benzylic radicals, for example, II, abstract a Br-atom from BrCCl 3 much faster than an H-atom from any known reductant, the issue of radical reduction is restricted to alkoxyl radical Ic.…”

Section: Homolytic Substitutionmentioning

confidence: 99%