Homolysis

About: Homolysis is a research topic. Over the lifetime, 4305 publications have been published within this topic receiving 91400 citations.

Catalytic alkylation of remote C–H bonds enabled by proton-coupled electron transfer

Abstract: Despite advances in hydrogen atom transfer (HAT) catalysis, there are currently no molecular HAT catalysts that are capable of homolysing the strong nitrogen-hydrogen (N-H) bonds of N-alkyl amides. The motivation to develop amide homolysis protocols stems from the utility of the resultant amidyl radicals, which are involved in various synthetically useful transformations, including olefin amination and directed carbon-hydrogen (C-H) bond functionalization. In the latter process-a subset of the classical Hofmann-Loffler-Freytag reaction-amidyl radicals remove hydrogen atoms from unactivated aliphatic C-H bonds. Although powerful, these transformations typically require oxidative N-prefunctionalization of the amide starting materials to achieve efficient amidyl generation. Moreover, because these N-activating groups are often incorporated into the final products, these methods are generally not amenable to the direct construction of carbon-carbon (C-C) bonds. Here we report an approach that overcomes these limitations by homolysing the N-H bonds of N-alkyl amides via proton-coupled electron transfer. In this protocol, an excited-state iridium photocatalyst and a weak phosphate base cooperatively serve to remove both a proton and an electron from an amide substrate in a concerted elementary step. The resultant amidyl radical intermediates are shown to promote subsequent C-H abstraction and radical alkylation steps. This C-H alkylation represents a catalytic variant of the Hofmann-Loffler-Freytag reaction, using simple, unfunctionalized amides to direct the formation of new C-C bonds. Given the prevalence of amides in pharmaceuticals and natural products, we anticipate that this method will simplify the synthesis and structural elaboration of amine-containing targets. Moreover, this study demonstrates that concerted proton-coupled electron transfer can enable homolytic activation of common organic functional groups that are energetically inaccessible using traditional HAT-based approaches.

Mechanisms of coenzyme B12-dependent rearrangements.

Abstract: Coenzyme B12 serves as a cofactor in various enzymatic reactions in which a hydrogen atom is interchanged with a substituent on an adjacent carbon atom. Measurement of the dissociation energy of the coenzyme's cobalt-carbon bond and studies of the rearrangement of model free radicals related to those derived from methylmalonyl-coenzyme A suggest that these enzymatic reactions occur through homolytic dissociation of the coenzyme's cobalt-carbon bond, abstraction of a hydrogen atom from the substrate by the coenzyme-derived 5'-deoxyadenosyl radical, and rearrangement of the resulting substrate radical. The only role thus far identified for coenzyme B12 in these reactions--namely, that of a free radical precursor--reflects the weakness, and facile dissociation, of the cobalt-carbon bond.

Selective Generation of Free Radicals from Epoxides Using a Transition-Metal Radical. A Powerful New Tool for Organic Synthesis

Abstract: Bis(cycIopentadienyl)titanium(III) chloride reacts with epoxides by initial C-0 homolysis. The regiochemistry of the opening is determined by the relative stabilities of the radicals. Depending on the reaction partners, these radicals undergo intramolecular (hex-5-enyl cyclization) or intermolecular additions to olefins. The resultant radicals are efficiently scavenged by a second equivalent of Ti(II1) to afford the corresponding Ti(1V) derivative. Treatment of this intermediate with electrophiles such as H+ or halogens provides a route to functionalized cyclopentanes and other useful products. The radical initially formed from an epoxide can also be trapped by H-atom donors such as 1,4- cyclohexadiene or tert-butyl thiol, resulting in an overall reduction of the epoxide. In the absence of a H-atom donor or an olefin, this radical is trapped by Ti(", resulting in a fl-oxido-Ti organometallic species which undergoes facile elimination to give an olefin. The reaction conditions are remarkably mild and are applicable to very sensitive substrates. The considerable utility of epoxides as building blocks for organic synthesis reflects both their ready availability and their ability to undergo selective nucleophilic substitution reactions (eq la) with predictable stereochemistry.' In contrast, the two-

Chemical Kinetics and Combustion Modeling

Abstract: ion of H atoms from fuel or other species by R02 produces alkyl hydroperoxides ROOH that then decompose to produce RO and OH radicals. However, for hydrocarbon fuels more complicated than n-butane, a more rapid process for R02 is isomerization via internal abstraction of H atoms ( 1 94). The general features of this R02 isomerization theory provide the kinetic basis for global reaction schemes for engine knock in internal combustion engines ( 1 96-1 98). The major steps consist schematically of R02 +=t QOOH (internal H atom abstraction) QOOH � QO + OH (0-0 homolysis). At sufficiently low temperatures, molecular oxygen can add further to the QOOH radicals, leading eventually to an overall reaction QOOH + 02 = products + OH + OH. Both alternatives are important since they produce OH radicals through reaction sequences with relatively low energy barriers. ROz isomerization rates are determined primarily by the size of the ringlike intermediate transition state, by the bond energy of the H atom being abstracted internally, and by the equilibrium constant of the R02 addition reaction. For fuels of larger hydrocarbons many isomerizations are possible, and 0-0 homolysis of the QOOH product of the iso­ merization reaction yields a different stable oxygenated species for each isomerization reaction. Thus for n-alkanes, a 1 ,4-H -atom abstraction, followed by 0-0 bond fission, leads to a 3-membered oxygenated ring, an oxiran. Similarly, 1 ,5-processes lead to oxetans, 1 ,6-abstractions produce tetrahydrofurans, and l ,7-abstractions produce tetrahydropyrans. Cur­ rent models generally use activation energies tabulated by Baldwin et al ( 199), but with A factors slightly lower than the 1 0 1 2. 1 S 1 recommended by Baldwin et aI, closer to the value of 1 0 1 1 . 5 S 1 recommended by Benson ( 1 89) for unimolecular reactions involving a cyclic transition state. The isomerization reactions are reversible, and activation energies for the reverse isomerizations are easily computed from the activation energy of the forward (endothermic) reaction and the AH of the reactions ( 1 94). ROz isomerization through internal abstraction of an H atom from a site adjacent to the C-O bond, followed by breakage of the C-O bond, will lead to a conjugate olefin and H02_ Direct abstraction paths leading to the same products have been discussed by Gutman and co-workers (200, 20 1 ), favoring a path proceeding through R02 isomerization. The current work of Wagner et al (20 I) provides some insight into the diffi382 MILLER, KEE & WESTBROOK culties of this reaction, but this is one of the simplest of the R02 iso­ merizations, and there are many more such reactions for which complex analyses are needed to understand fully the detailed reaction rates and mechanisms. Reactions of the product epoxide and other oxygenated species must be included in kinetic models, but very few quantitative studies of H atom abstraction or other reactions for these species have been reported. Current models must estimate both the rates and products for reactions of the epoxides, primarily attributed to H atom abstraction by OH or H02•

Organocatalysis and C-H activation meet radical- and electron-transfer reactions.

Abstract: A radical outlook: Recently published "organocatalytic C-H activation reactions" have now been interpreted as base-promoted homolytic substitutions. The addition of an aryl radical to an arene followed by deprotonation (see above) and electron transfer form part of the chain reaction. Although these new results are not conceptual breakthroughs, they could be experimental breakthroughs because they presage new transformations in radical (anion) chemistry. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.