Domino Self-Sensitized Photooxygenation of Conjugated Dienones for the Synthesis of 1,2,4-Trioxanes

Riveira, Martín J.; Martiren, Nadia L.; Mischne, Mirta P.

doi:10.1021/acs.joc.8b03279

Cited by 8 publications

(5 citation statements)

References 50 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The dramatic expansion of medicinal chemistry of organic peroxides was inspired by >100 known peroxide-containing natural products. − The variety of natural examples lessened concerns associated with the perceived peroxide instability and led to research efforts aimed at the development of synthetic approaches to varied classes of cyclic peroxides including 1,2-dioxolanes, − 1,2,4-trioxolanes (ozonides), ,− 1,2-dioxanes, − 1,2,4-trioxanes, − 1,2,4,5-tetraoxanes, − cyclic triperoxides, and tricyclic mono- and bisperoxides. − …”

Section: Introductionmentioning

confidence: 99%

Marriage of Peroxides and Nitrogen Heterocycles: Selective Three-Component Assembly, Peroxide-Preserving Rearrangement, and Stereoelectronic Source of Unusual Stability of Bridged Azaozonides

et al. 2021

View full text Add to dashboard Cite

Stable bridged azaozonides can be selectively assembled via a catalyst-free three-component condensation of 1,5-diketones, hydrogen peroxide, and an NH-group source such as aqueous ammonia or ammonium salts. This procedure is scalable and can produce gram quantities of bicyclic stereochemically rich heterocycles. The new azaozonides are thermally stable and can be stored at room temperature for several months without decomposition and for at least 1 year at −10 °C. The chemical stability of azaozonides was explored for their subsequent selective transformations including the first example of an aminoperoxide rearrangement that preserves the peroxide group. The amino group in aminoperoxides has remarkably low nucleophilicity and does not participate in the usual amine alkylation and acylation reactions. These observations and the 15 pK a units decrease in basicity in comparison with a typical dialkyl amine are attributed to the strong hyperconjugative nN→σ*C–O interaction with the two antiperiplanar C–O bonds. Due to the weakness of the complementary nO→σ*C–N donation from the peroxide oxygens (a consequence of “inverse α-effect”), this interaction depletes electron density from the NH moiety, protects it from oxidation, and makes it similar in properties to an amide.

show abstract

Section: Introductionmentioning

confidence: 99%

Marriage of Peroxides and Nitrogen Heterocycles: Selective Three-Component Assembly, Peroxide-Preserving Rearrangement, and Stereoelectronic Source of Unusual Stability of Bridged Azaozonides

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Very few and specific examples have been described to generate 1 O 2 via self-sensitization under visible light activation. These are mostly related to large polyaromatic compounds such as bilirubin, fullerenes, − or dimethyldihydropyrene derivatives, , while examples of the self-sensitization of smaller molecules remain very limited. − …”

Section: Introductionmentioning

confidence: 99%

Self-Sensitized Photooxidation of Naphthols to Naphthoquinones and the Use of Naphthoquinones as Visible Light Photocatalysts in Batch and Continuous Flow Reactors

et al. 2023

View full text Add to dashboard Cite

Visible light photooxidation of naphthols to produce naphthoquinones, such as the natural product juglone, has been known for decades and has been widely utilized to benchmark the performances of a variety of photocatalytic systems. We discovered that these transformations can occur without the help of a photocatalyst and, even more intriguingly, that the photocatatyst-free process provides higher yields compared to control experiments utilizing state-of-the-art photocatalysts. In addition, we demonstrate that naphthoquinones and their corresponding naphthol precursors can act as alternatives to commonly used organic and organometallic photocatalysts with applications to challenging targets, such as the antimalarial drug artemisinin. This approach was finally transposed in continuous flow reactors where high photocatalyst stability and process efficiency are demonstrated with a 23× improvement in the space-time yield.

show abstract

“…As a result, synthetic approaches have been developed for the synthesis of various classes of cyclic peroxides such as 1,2-dioxanes, − 1,2-dioxolanes, − 1,2,4-trioxanes, − 1,2,4-trioxolanes (ozonides), − bisperoxides, − and triperoxides. , Such peroxides display antiparasitic, ,− anticancer, ,− antifungal, ,, antitubercular, − and antiviral − activities. Synthetic peroxide OZ277 (“arterolane”) is used for the treatment of malaria.…”

Section: Introductionmentioning

confidence: 99%

Inverse α-Effect as the Ariadne’s Thread on the Way to Tricyclic Aminoperoxides: Avoiding Thermodynamic Traps in the Labyrinth of Possibilities

et al. 2022

View full text Add to dashboard Cite

Stable tricyclic aminoperoxides can be selectively assembled via a catalyst-free three-component condensation of β,δ′-triketones, H2O2, and an NH-group source such as aqueous ammonia or ammonium salts. This procedure is scalable and can produce gram quantities of tricyclic heterocycles, containing peroxide, nitrogen, and oxygen cycles in one molecule. Amazingly, such complex tricyclic molecules are selectively formed despite the multitude of alternative reaction routes, via equilibration of peroxide, hemiaminal, monoperoxyacetal, and peroxyhemiaminal functionalities! The reaction is initiated by the “stereoelectronic frustration” of H2O2 and combines elements of thermodynamic and kinetic control with a variety of mono-, bi-, and tricyclic structures evolving under the conditions of thermodynamic control until they reach a kinetic wall created by the inverse α-effect, that is, the stereoelectronic penalty for the formation of peroxycarbenium ions and related transition states. Under these conditions, the reaction stops before reaching the most thermodynamically stable products at a stage where three different heterocycles are assembled and fused at the acyclic precursor frame.

show abstract

Domino Self-Sensitized Photooxygenation of Conjugated Dienones for the Synthesis of 1,2,4-Trioxanes

Cited by 8 publications

References 50 publications

Marriage of Peroxides and Nitrogen Heterocycles: Selective Three-Component Assembly, Peroxide-Preserving Rearrangement, and Stereoelectronic Source of Unusual Stability of Bridged Azaozonides

Marriage of Peroxides and Nitrogen Heterocycles: Selective Three-Component Assembly, Peroxide-Preserving Rearrangement, and Stereoelectronic Source of Unusual Stability of Bridged Azaozonides

Self-Sensitized Photooxidation of Naphthols to Naphthoquinones and the Use of Naphthoquinones as Visible Light Photocatalysts in Batch and Continuous Flow Reactors

Inverse α-Effect as the Ariadne’s Thread on the Way to Tricyclic Aminoperoxides: Avoiding Thermodynamic Traps in the Labyrinth of Possibilities

Contact Info

Product

Resources

About