Electrochemical deamination of alkoxyamine lactams

Romero‐Ibañez, Julio; Cruz-Gregorio, Enrique; Cruz‐Gregorio, Silvano; Quintero, Leticia; Bernès, Syl­vain; González-Perea, Mario; Sartillo‐Piscil, Fernando

doi:10.1016/j.tetlet.2020.152279

Cited by 4 publications

(5 citation statements)

References 22 publications

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“…Products of Nitroxide-Mediated Homolytic Aromatic Substitution a, 1378,1379,1383 a Dashed lines mark formed bonds; C marks the carbon to which the nitroxide was connected in the staring material; HAS = homolytic aromatic substitution; HWE = Horner−Wadsworth−Emmons reaction. were also developed, and methylation of carboxylic acids 1400 as well as substitution of the aminoxy moiety in alkoxyamines with water as nucleophile 1401 were disclosed. Another method to liberate nitroxides from methoxyamines uses mCPBA as the oxidant.…”

Section: Reactions Of Alkoxyaminesmentioning

confidence: 99%

“…This method was also applied to sugar derivatives, and excellent yields could be obtainedalso in the formation of disaccharides . Electrochemical processes were also developed, and methylation of carboxylic acids as well as substitution of the aminoxy moiety in alkoxyamines with water as nucleophile were disclosed.…”

Section: Nitroxides In Free-radical Chemistrymentioning

confidence: 99%

“…Indoline Synthesis via Homolytic Aromatic Substitution with a Nitroxide as an Oxidant 1377 Scheme 92. Products of Nitroxide-Mediated Homolytic Aromatic Substitution a, 1378,1379,1383 were also developed, and methylation of carboxylic acids 1400 as well as substitution of the aminoxy moiety in alkoxyamines with water as nucleophile 1401 were disclosed. Another method to liberate nitroxides from methoxyamines uses mCPBA as the oxidant.…”

Section: Reactions Of Alkoxyaminesmentioning

confidence: 99%

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Organic Synthesis Using Nitroxides

Leifert

Studer

2023

Chem. Rev.

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Nitroxides, also known as nitroxyl radicals, are long-lived or stable radicals with the general structure R 1 R 2 N−O • . The spin distribution over the nitroxide N and O atoms contributes to the thermodynamic stability of these radicals. The presence of bulky N-substituents R 1 and R 2 prevents nitroxide radical dimerization, ensuring their kinetic stability. Despite their reactivity toward various transient C radicals, some nitroxides can be easily stored under air at room temperature. Furthermore, nitroxides can be oxidized to oxoammonium salts (R 1 R 2 N�O + ) or reduced to anions (R 1 R 2 N−O − ), enabling them to act as valuable oxidants or reductants depending on their oxidation state. Therefore, they exhibit interesting reactivity across all three oxidation states. Due to these fascinating properties, nitroxides find extensive applications in diverse fields such as biochemistry, medicinal chemistry, materials science, and organic synthesis. This review focuses on the versatile applications of nitroxides in organic synthesis. For their use in other important fields, we will refer to several review articles. The introductory part provides a brief overview of the history of nitroxide chemistry. Subsequently, the key methods for preparing nitroxides are discussed, followed by an examination of their structural diversity and physical properties. The main portion of this review is dedicated to oxidation reactions, wherein parent nitroxides or their corresponding oxoammonium salts serve as active species. It will be demonstrated that various functional groups (such as alcohols, amines, enolates, and alkanes among others) can be efficiently oxidized. These oxidations can be carried out using nitroxides as catalysts in combination with various stoichiometric terminal oxidants. By reducing nitroxides to their corresponding anions, they become effective reducing reagents with intriguing applications in organic synthesis. Nitroxides possess the ability to selectively react with transient radicals, making them useful for terminating radical cascade reactions by forming alkoxyamines. Depending on their structure, alkoxyamines exhibit weak C−O bonds, allowing for the thermal generation of C radicals through reversible C−O bond cleavage. Such thermally generated C radicals can participate in various radical transformations, as discussed toward the end of this review. Furthermore, the application of this strategy in natural product synthesis will be presented.

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Section: Reactions Of Alkoxyaminesmentioning

confidence: 99%

Section: Nitroxides In Free-radical Chemistrymentioning

confidence: 99%

Section: Reactions Of Alkoxyaminesmentioning

confidence: 99%

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Organic Synthesis Using Nitroxides

Leifert

Studer

2023

Chem. Rev.

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“…This synthetic alternative allows the access to a wide diversity of 3-hydroxy lactams 57a-i under ecofriendly fashion and also opens up new avenues for electrochemical functionalization of 3-alkoxyamine lactams with different nucleophiles (Scheme 12). 36…”

Section: Electrochemical Deamination Of 3-alkoxyamine Lactamsmentioning

confidence: 99%

Transition-Metal-Free Functionalization of Saturated and Unsaturated Amines to Bioactive Alkaloids Mediated by Sodium Chlorite

Romero‐Ibañez¹,

Fuentes²,

Sartillo‐Piscil³

2020

Synlett

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New approaches to the synthesis of alkaloids through the straightforward functionalization of C(sp3)–H and C(sp2)=C(sp2) bonds of simple five and six-membered ring N-heterocycles are highlighted. The direct functionalization of preexisting N-heterocycles to advanced alkaloids intermediates is a chemical operation that commonly requires the intervention of transition or precious metals. Regardless the inherent unwanted waste production, the high economical cost of many transition metal catalysts limits their use globally. Here, we account our efforts directed toward the synthesis of bioactive alkaloids under an economic and ecological fashion by using NaClO2 as the key activating or oxidizing reagent that substitutes the use of transition metal catalysts. While undesired metal wastes are collected during the extraction process of a transition metal catalyzed reaction, innocuous NaCl is the commonly product waste when NaClO2 is employed in our chemical transformations. Beginning with the synthesis of 2,3-epoxyamides from allyl amines, we concluded with the functionalization of multiple and remote C(sp3)-H and C(sp3)–C(sp3) bonds in piperidine rings that enabled the preparation of important bioactive alkaloids. For the latter functionalization, a precise amount of co-oxidant reagent (NaOCl) and radical 2,2,6,6-tetramethylpiperidinyloxy (TEMPO) were needed.

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“…3 In this regard, during the last six years our research group has developed, from simple saturated tertiary cyclic amines and under transition-metal-free conditions, a series of C-H oxidation reactions of cyclic amines to bioactive alkaloids or advanced alkaloid intermediates. 4 These strategies are grounded on a selective and dual C(sp 3 )-H functionalization of tertiary piperidines and pyrrolidines mediated by TEMPO and sodium oxychloride reagents (Na-ClO 2 and NaClO). 5 The proposed reaction mechanism states that the first C-H oxidation is initiated by the interaction of the oxoammonium cation A (formed by oxidation of TEMPO radical C-H Bond Functionalization of Heterocy-J.…”

mentioning

confidence: 99%

On the Reaction Mechanism of the Selective C(sp3)–H Functionalization of N-Benzylpiperidines Mediated by TEMPO Oxoammonium Cation

et al. 2023

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The selective and dual C(sp3)−H oxidation of N-heterocycles to their corresponding 3-alkoxyamino lactams mediated by TEMPO oxoammonium cation (TEMPO+) is turning into a convenient non-metallic strategy for the rapid functionalization of piperidines and pyrrolidines to bioactive alkaloids. Mechanistic proposal suggests that TEMPO+ prefers to oxidize endocyclic C−H bond of either N-substituted-piperidines or pyrrolidines to their corresponding endocyclic iminium intermediates, which are transformed into enamine intermediates, and then trapped by oxoammonium cation. Although the product formation seems to be in concordance with this mechanistic rationale, neither experimental evidence nor theoretical calculations have been reported. Accordingly, the current investigation provides computational findings explaining that the origin of the selective C−H oxidation is attributed to an unprecedented C−H… interaction between two hydrogen atoms of TEMPO+ with the aromatic ring of piperidine benzyl group. To prove the existence of the enamine intermediate, we developed an unprecedented transition-metal-free tetra C−H oxidation of two N-benzyl-4-methylenepiperidines. Accordingly, the existence of the elusive enamine intermediate was attained by generating a transitory dienamine intermediate, which is trapped by TEMPO+ and NaClO2 to their corresponding 4-(alkoxyaminomethyl)-3,4-epoxy-2-piperidone

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Electrochemical deamination of alkoxyamine lactams

Cited by 4 publications

References 22 publications

Organic Synthesis Using Nitroxides

Organic Synthesis Using Nitroxides

Transition-Metal-Free Functionalization of Saturated and Unsaturated Amines to Bioactive Alkaloids Mediated by Sodium Chlorite

On the Reaction Mechanism of the Selective C(sp3)–H Functionalization of N-Benzylpiperidines Mediated by TEMPO Oxoammonium Cation

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