Nucleophilic character of alkyl radicals—VII

Minisci, Francesco; Mondelli, R.; Gardini, G. P.; Porta, Ombretta

doi:10.1016/0040-4020(72)80077-2

Cited by 67 publications

(16 citation statements)

References 22 publications

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“…Interestingly, the regioselectivity is orthogonal to that observed for the Friedel-Crafts reaction, thus increasing the appeal of such transformations. Traditionally, carboxylic acids 5 and halides 6 have been employed as radical precursors, but more recently the toolbox has been expanded to include alcohols, 7 boronic acids, 8 sulfinate salts, 9 alkenes, 10 and alkyltrifluoroborates. 11 However, in most of the previous contributions, high temperatures, (sub)stoichiometric amounts of expensive metal salts, an excess of the radical precursor, and strong oxidants or expensive photocatalysts 7,11a,12 are required to achieve good yields.…”

Section: Introductionmentioning

confidence: 99%

Late-Stage C–H Alkylation of Heterocycles and 1,4-Quinones via Oxidative Homolysis of 1,4-Dihydropyridines

et al. 2017

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Under oxidative conditions, 1,4-dihydropyridines (DHPs) undergo a homolytic cleavage, forming exclusively a Csp3-centered radical that can engage in the C-H alkylation of heterocyclic bases and 1,4-quinones. DHPs are readily prepared from aldehydes, and, considering that aldehydes normally require harsh reaction conditions to take part in such transformations, with mixtures of alkylated and acylated products often being obtained, this net decarbonylative alkylation approach becomes particularly useful. The present method takes place under mild reaction conditions and requires only persulfate as a stoichiometric oxidant, making the procedure suitable for the late-stage C-H alkylation of complex molecules. Notably, structurally complex pharmaceutical agents could be functionalized or prepared with this protocol, such as the anti-malarial Atovaquone and anti-theilerial Parvaquone, thus evidencing its applicability. Mechanistic studies revealed a likely radical chain process via the formation of a dearomatized intermediate and provided a deeper understanding of the factors governing the reactivity of these radical forebears.

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Section: Introductionmentioning

confidence: 99%

Late-Stage C–H Alkylation of Heterocycles and 1,4-Quinones via Oxidative Homolysis of 1,4-Dihydropyridines

et al. 2017

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“…For the decarboxylative alkylation, N -[(cyclohexylcarbonyl)oxy]phthalimide ( 1 ) and isoquinoline ( 2 ) were used as test substrates during the investigations of the reaction conditions. Trifluoroacetic acid was added to lower the LUMO coefficient of the heterocycle through protonation, thus facilitating the nucleophilic attack of the nucleophilic alkyl radical [ 10 , 11 , 12 ]. First, the catalytic activity of different photoredox catalysts under irradiation with LEDs was tested.…”

Section: Resultsmentioning

confidence: 99%

“…A particularly interesting option for the late-stage modification of heteroaromatic systems lies in their reaction with free radicals which can be generated under conditions tolerating a wide variety of functional groups [ 10 ]. Minisci and coworkers used the oxidative decarboxylation of carboxylic acids for the radical functionalization of a wide variety of heteroarenes [ 11 , 12 ]. The radical generation was effected by electron transfer from carboxylate ions to Ag 2+ ions generated in situ from Ag + through the action of peroxydisulfate as the terminal oxidant.…”

Section: Introductionmentioning

confidence: 99%

A Visible Light-Driven Minisci-Type Reaction with N-Hydroxyphthalimide Esters

2018

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A visible light-promoted protocol for the redox-neutral coupling of N-hydroxyphthalimide esters with different N-heterocyclic compounds is described. The reaction proceeds through an alkyl radical intermediate generated by reductive decarboxylation of N-hydroxyphthalimide esters. In contrast to the original Minisci protocol, polyalkylation can largely be avoided. Mechanistic investigations revealed a radical chain mechanism which in some cases can proceed even if no photocatalyst is added. This valuable and functional group-tolerant reaction produces substituted heterocycles in moderate to excellent yield. The use of inexpensive starting materials and LEDs as the light source are key features of this C–C bond formation.

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“…tion of 2, however, are similar in those of 1, and the t-butyl radical gives only mono-subtitution products whereas isopropyl and ethyl radicals gave disubstitution products 9. In the reaction of 2, those two radicals are less nucleophilic [7] and more regiospecific to attack the electron deficient C-7 position. On the other hand, t-butyl radical is more nucleophilic and attacks also the C-6 position in minor extent.…”

Section: Nov-dec 1986mentioning

confidence: 99%

Reaction of pyrazine‐2,3‐dicarbonitrile and 1,3‐dimethyllumazine with alkyl radicals

Tada

Ito

Ohshima

1986

Journal of Heterocyclic Chem

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Pyrazine‐2,3‐dicarbonitrile (1) reacts with alkyl radicals to give mono‐ 3 and di‐alkylated pyrazine‐2,3‐dicarbonitriles 4. Similarly 1,3‐dimethyllumazine (2) reacts with alkyl radicals to give 7‐alkyl‐1,3‐dimethyllumazines 8 as the major product. The reactivity of alkyl radicals decreases in the order tertiary, secondary, and primary, and 1 is more reactive than 2 in those radical substitution reactions.

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Nucleophilic character of alkyl radicals—VII

Cited by 67 publications

References 22 publications

Late-Stage C–H Alkylation of Heterocycles and 1,4-Quinones via Oxidative Homolysis of 1,4-Dihydropyridines

Late-Stage C–H Alkylation of Heterocycles and 1,4-Quinones via Oxidative Homolysis of 1,4-Dihydropyridines

A Visible Light-Driven Minisci-Type Reaction with N-Hydroxyphthalimide Esters

Reaction of pyrazine‐2,3‐dicarbonitrile and 1,3‐dimethyllumazine with alkyl radicals

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