α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

Klychnikov, Mikhail K.; Pohl, Radek; Cı́sařová, Ivana; Jahn, Ullrich

doi:10.3762/bjoc.17.58

Cited by 7 publications

(6 citation statements)

References 92 publications

(102 reference statements)

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“…Attempts to improve the diastereomeric ratio at this stage by epimerization at C1 under basic conditions using KOtBu in tBuOH failed. [14] Reduction of the amide function to the corresponding aldehyde was accomplished with Red-Al in the presence of KOtBu; [14,15] immediate treatment of the aldehyde mixture with methanolic K 2 CO 3 solution under a nitrogen atmosphere led to complete epimerization to a partly separable 1.1 : 1 mixture of aldehydes (all-S)-11 and (1R,2R,4S)-11 in 90 % yield. The relative configuration of both aldehydes was assigned by NOE experiments (see the Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

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Concise Total Syntheses of (+)‐Brefeldin A, Diastereomers and Analogs and Their Biological Activity

et al. 2023

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Brefeldin A is an important natural product and biochemical tool with cell‐modulating and other diverse biological activities. To explore its chemical space, a generally applicable strategy for total syntheses of naturally occurring (+)‐brefeldin A (BFA), 2‐epi‐BFA, their diastereomers and analogs with varying macrocyclic ring size is reported. The five‐membered ring fragment was constructed by a short three‐step sequence consisting of tandem nucleophilic epoxide opening/Brook rearrangement/radical oxygenation and subsequent thermal radical cyclization based on the persistent radical effect. Further key steps are asymmetric aldehyde vinylation, which enables control of the absolute configuration at the allylic hydroxy group of BFA, cross‐metatheses reactions for attachment of the northern and southern side chains to the cyclopentane unit and final Shiina macrolactonization. The cytotoxic activity of all compounds was determined, and several analogs proved to be similarly active as BFA, providing insight about regions of the skeleton that can be varied or have to be conserved with respect to their biological activities. Fluorescence microscopy revealed that BFA and some non‐natural analogs disassemble the Golgi apparatus in cells with large variation of the disassembly and subsequent reassembly times.

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Section: Resultsmentioning

confidence: 99%

“…Heating α‐(aminoxy) amide 7 in t BuOH in the presence of 10 mol% of TEMPO ( 10 ) at 150 °C for an hour afforded cyclopentanecarboxamide 6 in 84 % yield as an inseparable 4.2 : 3.7 : 2 : 1 mixture. Attempts to improve the diastereomeric ratio at this stage by epimerization at C1 under basic conditions using KO t Bu in t BuOH failed [14] …”

Section: Resultsmentioning

confidence: 99%

Concise Total Syntheses of (+)‐Brefeldin A, Diastereomers and Analogs and Their Biological Activity

et al. 2023

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“…Jahn and co-workers reported a TEMPO-related ATRC of α,γ -dioxygenated amides for the synthesis of γ -lactams. The reaction of α,γ -dioxygenated amides 137 in t -BuOH under the irradiation of microwave at 150 °C for 1 h followed by the treatment with TBAF in THF gave products 138 in good to excellent yields ( Scheme 33 ) [ 59 ]. The proposed reaction mechanism suggests that radicals 139 generated from N -allyl amides 137 undergo a 5- exo cyclization to give radicals 140 which then couple with OTMP radical to form 141 and then products 138 after OTMS deprotection.…”

Section: Second Functionalization With X Via Atom-transfer Radical Cy...mentioning

confidence: 99%

Radical Cyclization-Initiated Difunctionalization Reactions of Alkenes and Alkynes

Zhi,

Ma,

Zhang

2024

Molecules

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Radical reactions are powerful in the synthesis of diverse molecular scaffolds bearing functional groups. In previous review articles, we have presented 1,2-difunctionalizations, remote 1,3-, 1,4-, 1,5-, 1,6- and 1,7-difunctionalizations, and addition followed by cyclization reactions. Presented in this paper is radical cyclization followed by the second functionalization reaction. The second functionalization could be realized by atom transfer reactions, radical or transition metal-assisted coupling reactions, and reactions with neutral molecules, cationic and anionic species.

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“…The group of Jahn applied the radical alkoxyamine isomerization to the synthesis of ent -pregnanolone sulfate . Further, they developed a tandem process that combines a Brook rearrangement with a radical oxygenation to synthesize γ-lactams and introduced a protocol which combines an oxy-Cope rearrangement with alkoxyamine formation. Microwave heating was used for the subsequent alkoxyamine isomerization .…”

Section: Nitroxides In Free-radical Chemistrymentioning

confidence: 99%

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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α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

Cited by 7 publications

References 92 publications

Concise Total Syntheses of (+)‐Brefeldin A, Diastereomers and Analogs and Their Biological Activity

Concise Total Syntheses of (+)‐Brefeldin A, Diastereomers and Analogs and Their Biological Activity

Radical Cyclization-Initiated Difunctionalization Reactions of Alkenes and Alkynes

Organic Synthesis Using Nitroxides

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