Chiral Nitroxide/Copper‐Catalyzed Aerobic Oxidation of Alcohols: Atroposelective Oxidative Desymmetrization

López, Marta Carbó; Chavant, Pierre Y.; Molton, Florian; Royal, Guy; Blandin, Véronique

doi:10.1002/slct.201601993

Cited by 12 publications

(2 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Considering copper-cocatalyzed oxidations, chiral 1,1′-binaphthyl-2,2′-diamine (BINAM) as the Cu ligand provided good selectivity for the preparation of chiral amino alcohols; however, the scope of this transformation was limited to diaryl or acylaryl alcohols. , Further oxidative strategies were developed to resolve axially chiral substrates, and also, atroposelective oxidative desymmetrization was achieved by using chiral Cu complexes. − …”

Section: Oxidation Reactionsmentioning

confidence: 99%

Organic Synthesis Using Nitroxides

Leifert

Studer

2023

Chem. Rev.

View full text Add to dashboard Cite

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.

show abstract

Section: Oxidation Reactionsmentioning

confidence: 99%

Organic Synthesis Using Nitroxides

Leifert

Studer

2023

Chem. Rev.

View full text Add to dashboard Cite

show abstract

“…While nitroxides are outstanding catalysts and reagents for chemical synthesis 12 and even have seen use in enantioselective oxidation of alcohols, 13 their use in atroposelective oxidative kinetic resolution (OKR) and desymmetrization is still in infancy with the work by Blandin being the first example. 14 As part of our longstanding interest in nitroxides, 9 , 15 we recently reported our preliminary findings 16 on chiral nitroxide-copper co-catalyzed aerobic OKR of axially chiral N -aryl-pyrroles ( Scheme 1 b) using readily available (prepared in only five steps) 16 chiral α-hydrogen pre-catalyst 1 (97% ee , see Scheme 2 for the structure). In this full paper, we now report our complete findings on the OKR of biaryl systems and explore the use of this catalyst system in atroposelective desymmetrization reactions as well ( Scheme 1 b)…”

Section: Introductionmentioning

confidence: 99%

Catalytic Atroposelective Aerobic Oxidation Approaches to Axially Chiral Molecules

et al. 2023

View full text Add to dashboard Cite

A copper and chiral nitroxide co-catalyzed aerobic enantioselective oxidation process has been developed that allows access to axially chiral molecules. Two complementary atroposelective approaches, oxidative kinetic resolution (OKR) and desymmetrization, were studied using ambient air as the stoichiometric terminal oxidant. OKR of rac-N-arylpyrrole alcohols and rac-biaryl alcohols affords the optically pure compounds with er up to 3.5:96.5 and 5.5:94.5, respectively. Desymmetrization of prochiral diols provides axially chiral biaryl compounds with er up to 99:1.

show abstract

Multivariate Analysis of Coupled Operando EPR/XANES/EXAFS/UV–Vis/ATR‐IR Spectroscopy: A New Dimension for Mechanistic Studies of Catalytic Gas‐Liquid Phase Reactions

Rabeah

Briois

Adomeit

et al. 2020

Chemistry A European J

View full text Add to dashboard Cite

Operando EPR, XANES/EXAFS, UV‐Vis and ATR‐IR spectroscopic methods have been coupled for the first time in the same experimental setup for investigation of unclear mechanistic aspects of selective aerobic oxidation of benzyl alcohol by a Cu/TEMPO catalytic system (TEMPO=2,2,6,6‐tetramethylpiperidinyloxyl). By multivariate curve resolution with alternating least‐squares fitting (MCR‐ALS) of simultaneously recorded XAS and UV‐Vis data sets, it was found that an initially formed (bpy)(NMI)CuI‐ complex (bpy=2,2′‐bipyridine, NMI=N‐methylimidazole ) is converted to two different CuII species, a mononuclear (bpy)(NMI)(CH3CN)CuII‐OOH species detectable by EPR and ESI‐MS, and an EPR‐silent dinuclear (CH3CN)(bpy)(NMI)CuII(μ‐OH)2⋅CuII (bpy)(NMI) complex. The latter is cleaved in the further course of reaction into (bpy)(NMI)(HOO)CuII‐TEMPO monomers that are also EPR‐silent due to dipolar interaction with bound TEMPO. Both Cu monomers and the Cu dimer are catalytically active in the initial phase of the reaction, yet the dimer is definitely not a major active species nor a resting state since it is irreversibly cleaved in the course of the reaction while catalytic activity is maintained. Gradual formation of non‐reducible CuII leads to slight deactivation at extended reaction times.

show abstract

Chiral Nitroxide/Copper‐Catalyzed Aerobic Oxidation of Alcohols: Atroposelective Oxidative Desymmetrization

Cited by 12 publications

References 81 publications

Organic Synthesis Using Nitroxides

Organic Synthesis Using Nitroxides

Catalytic Atroposelective Aerobic Oxidation Approaches to Axially Chiral Molecules

Multivariate Analysis of Coupled Operando EPR/XANES/EXAFS/UV–Vis/ATR‐IR Spectroscopy: A New Dimension for Mechanistic Studies of Catalytic Gas‐Liquid Phase Reactions

Contact Info

Product

Resources

About