Catalytic asymmetric Payne oxidation under the catalysis of P-spiro chiral triaminoiminophosphorane: application to the synthesis of N-sulfonyl oxaziridines

The studies on the development of a highly enantioselective oxidation of N-sulfonyl imines with hydrogen peroxide–trichloroacetonitrile system utilizing P-spiro chiral triaminoiminophosphoranes as an organic base catalyst are detailed. This method is general and scalable, and exhibits unique chemoselectivity, providing a practical stereoselective route to structurally diverse N-sulfonyl oxaziridines. The mechanistic investigations reveal that the reaction proceeds through the Payne-type oxidation pathway. The synthetic utility of the optically active N-sulfonyl oxaziridines as versatile organic oxidants and chiral building blocks is also demonstrated.     

Recent applications of N-sulfonyloxaziridines (Davis oxaziridines) in organic synthesis

N-Sulfonyloxaziridines are the most commonly used oxaziridines in organic synthesis. Most applications of these stable, commercially available reagents involve the stereo- and regioselective oxidation of nucleophiles which have found many applications in the synthesis of architecturally complex molecules. In addition, these oxaziridines have been used in cycloaddition reactions (oxyamination), epoxidation of alkenes, silyl enol ethers and enamines, as well as C-H oxidation and amination reactions. The object of this review is to highlight recent applications of N-sulfonyloxaziridines in organic synthesis.     

Synthesis and reactivity of two new trichloromethyl substituted dihydroisoquinoline-derived oxaziridines

N-Alkyl oxaziridines may be used as reagents for the oxidation of sulfides in acid-promoted reactions. This article reports on a simple and efficient synthesis of two new trichloromethyl substituted dihydroisoquinoline oxaziridines, a new family of organic oxidizing agents. Their oxygen transfer capability with respect to sulfides as model substrates and in the absence of acid is investigated.     

Copper-catalyzed oxaziridine-mediated oxidation of C-h bonds

The highly regio- and chemoselective oxidation of activated C-H bonds has been observed via copper-catalyzed reactions of oxaziridines. The oxidation proceeded with a variety of substrates, primarily comprising allylic and benzylic examples, as well as one example of an otherwise unactivated tertiary C-H bond. The mechanism of the reaction is proposed to involve single-electron transfer to the oxaziridines to generate a copper-bound radical anion, followed by hydrogen atom abstraction and collapse to products, with regeneration of the catalyst by a final single-electron transfer event. The involvement of allylic radical intermediates was supported by a radical-trapping experiment with TEMPO.     

Enantio- and Diastereoselective Oxidation of N-Alkylimines Using Chiral α-Bromonitriles and Hydrogen Peroxide System

Chiral α-bromonitriles were prepared with good chemical and optical yields starting from natural α-amino acids by dehydrating the corresponding α-bromoamides with thionyl chloride. The combined system α-bromonitriles/hydrogen peroxide was examined for the enantio- and diastereoselective oxidation of N-alkylimines in basic media at room temperature. The oxidation of N-tertiobutylarylimines leads to optically active oxaziridines with moderate enantiomeric excess. However, the oxidation of (S)-1-phenylethylarylimines affords the corresponding oxaziridines with good diasteromeric excess up to 97/3 as proved by gaseous-phase chromatography.     

Enantioselective N-heterocyclic carbene catalyzed formal [3+2] cycloaddition using α-aroyloxyaldehydes and oxaziridines

An enantioselective N-heterocyclic carbene catalysed formal [3+2] cycloaddition has been developed for the synthesis of oxazolindin-4-one products. The reaction of oxaziridines and α-aroyloxyaldehydes under N-heterocyclic carbene catalysis provides the formal cycloaddition products with excellent control of the diastereo- and enantioselectivity (12 examples, up to >95:5 dr, >99:1 er). A matched-mismatched effect between the enantiomer of the catalyst and oxaziridine was identified, and preliminary mechanistic studies have allowed the proposal of a model to explain these observations.     

Iron catalyzed asymmetric oxyamination of olefins

The regioselective and enantioselective oxyamination of alkenes with N-sulfonyl oxaziridines is catalyzed by a novel iron(II) bis(oxazoline) complex. This process affords oxazolidine products that can be easily manipulated to yield highly enantioenriched free amino alcohols. The regioselectivity of this process is complementary to that obtained from the analogous copper(II)-catalyzed reaction. Thus, both regioisomers of enantioenriched 1,2-aminoalcohols can be obtained using oxaziridine-mediated oxyamination reactions, and the overall sense of regiochemistry can be controlled using the appropriate choice of inexpensive first-row transition metal catalyst.     

Normal,abnormal and pseudo-abnormal reaction pathways for the imine-peroxyacid reaction

Steric and mesomeric effects have a marked influence upon the formation of oxaziridine (normal pathway) or nitrone (abnormal pathway) products from the imine-peroxyacid reaction; n.m.r. studies of the thermal isomerization of oxaziridines to nitrones provide evidence of a pseudo-abnormal oxidation pathway.     

Asymmetric Isothiourea‐Catalysed Formal [3+2] Cycloadditions of Ammonium Enolates with Oxaziridines

A highly enantioselective Lewis base‐catalysed formal [3+2] cycloaddition of ammonium enolates and oxaziridines to give stereodefined oxazolidin‐4‐ones in high yield is described. Employing an enantioenriched oxaziridine in this process leads to a matched/mis‐matched effect with the isothiourea catalyst and allowed the synthesis of either syn‐ or anti‐stereodefined oxazolidin‐4‐ones in high d.r., yield and ee. Additionally, the oxazolidin‐4‐one products have been derivatised to afford functionalised enantioenriched building blocks.     

Activation of oxaziridines by lewis acids: application in enantioselective sulfoxidation

The preparation of new and easily accessible chiral N-alkyloxaziridines for asymmetric sulfides oxidation was investigated. Most significantly, we report here that inert N-alkyloxaziridines can be activated by Lewis acids to achieve a fast, selective, and efficient oxygen atom transfer to sulfides. Asymmetric sulfoxidation by three new chiral oxaziridines (two of them were structurally characterized by X-ray analysis) afforded enantioselectivities ranging from 22% to 63% ee with the simplest aryl alkyl sulfides.     

Deacylative Carbon-Carbon Bond Cleavage of Ketone Equivalents: Applications to Radical Carbon-Carbon Bond Formation Reactions

This article describes the synthetic application of ketone-derived oxaziridines as alkyl radical precursors in copper-catalyzed Carbon-Carbon bond formation reactions. Experimental and computational studies indicate a free radical mechanism, where alkyl radicals are efficiently generated via cleavage of a Carbon-Carbon bond of oxaziridines. Acyclic and unstrained cyclic oxaziridines are applicable to the present radical process, allowing for the generation of various alkyl radicals with good functional group compatibility.     

Photolyse d'oxazirannes: VI—Détermination par RMN du proton des configurations et conformations privilégiées d'oxazirannes à jonction spirannique

The structures of imines and oxaziridines derived from 2-methyl and 2,6-dimethyl cyclohexanone have been determined by ¹H n.m.r. spectroscopy. The preferred conformation of all the oxaziridines we examined was found to have the nitrogen atom in equatorial position.     

Chiral liquid chromatography separation and chiroptical properties of the enantiomers of dimethyl alpha-hydroxyfarnesylphosphonate,a precursor of a farnesyl protein transferase inhibitor

The HPLC enantiomeric separation of racemic and non-racemic samples of dimethyl alpha-hydroxyfarnesylphosphonate (1) was accomplished using Chiralcel OD as chiral stationary phase. Single enantiomers were isolated by semipreparative HPLC and their CD spectra and optical rotations were measured. The method ascertains enantiomeric excess of 1, obtained by oxidation of dimethylfarnesylphosphonate with enantiopure oxaziridines, avoiding converting the enantiomers to diastereomers by the use of a chiral auxiliary. Stability of the solutions of 1 is strongly dependent on the nature of the solvent.     

Stereochemistry of the oxidation of imines derived from substituted cyclohexanones: axial vs equatorial attack and evidence for delivery by an adjacent hydroxyl group

A set of conformationally biased imines derived from substituted cyclohexanones and benzylamine or diphenylmethylamine, respectively, were oxidized to the corresponding oxaziridines. The structures of the oxaziridines were determined via NMR comparison of two series of differently N-substituted oxaziridines. Thus, those compounds having an axially disposed nitrogen substituent displayed an upfield-shifted axial proton in a 1,3-relationship to the oxaziridine nitrogen in the N-diphenylmethyl series relative to the N-benzyl compounds. Analysis of the products obtained from these reactions suggests that (1) adjacent hydroxyl groups favor syn oxidant addition and (2) imines containing adjacent methoxy groups preferentially undergo attack anti to the resident alkoxy substituent.     

Conjugate acid structure for oxaziridines bearing primary and secondary 2-alky 1 groups

The protonation of five representative oxaziridines is reported for inert solvents (deuterio-chloroform or carbon tetrachloride) where conjugate acid formation may be effected by the addition of about 20% (v/v) TFA. Comparison of the ¹H nmr chemical shifts for neutral and conjugate acid forms suggests that oxaziridines usually undergo protonation on the N-atom under these conditions. For one compound studied, 2-ethyl-3-p-nitrophenyloxaziridine, there is a possibility that protonation occurs on the alternative O-atom. The relevance of these findings to the mechanism of the acid-catalysed hydrolysis of oxaziridines is discussed.     

Kinetic study of oxidation of N‐(α‐methylbenzylidene) anilines by dimethyldioxirane

A kinetic study of the oxidation of substituted N‐(α‐methylbenzylidene) anilines by dimethyldioxirane was investigated using a UV/VIS spectrophotometer. Oxaziridines and nitrones were formed as intermediates, and in the excess of dimethyldioxirane corresponding carbonyl compounds, nitrosobenzene or nitrobenzene, were formed quantitatively. The kinetic data were used in the equation for the formation of oxaziridines and nitrones as an intermediate and further oxidation to the corresponding acetophenones and nitrosobenzene. Hammett ρ values were determined for compounds p‐substituted on the aromatic ring attached to the carbon atom of the imino group, and it was found that these substituents have very little effect on the oxidation reaction. © 2007 Wiley Periodicals, Inc. Int J Chem Kinet 39: 492–497, 2007     

Efficient nitrogen transfer from aldehyde-derived N-acyloxaziridines

The effect of solvent polarity on the reaction of 3-aryl-N-carboxamido- and 3-aryl-N-alkoxycarbonyl oxaziridines has been studied and an efficient procedure for high yielding sulfimidation developed by use of polar solvents. The first examples of asymmetric sulfimidation using novel chiral oxaziridines have been carried out with low diastereoselectivity (up to 30% de).     

Action de l'eau oxygénée et de l'acide p-nitroperbenzoïque sur des imines,des oxazirannes et des nitrones cycliques stéroïdiques dérivés de la conanine

Hydrogen peroxide and a peracid react with pyrrolidinic imines, oxaziridines and nitrones of the steroïdal series, to give α-hydroxylated nitrones, α-peroxyimines, hydroxylactones or hydroxamic acids. Analogies and differences between reactivities of both oxidants are shown. Thus, a peracid oxidizes a nitrone as well as an oxaziridine, whereas hydrogen peroxide which oxidizes a nitrone, by contrast, deoxygenates an oxaziridine. Differences appear also, depending on the structure of the intermediates formed which carry either hydroperoxide or perester groups. The presence of a better leaving group in the latter case may modify the course of reactions effected on a α-hydroxylated nitrone or imine. Furthermore the acylation of an aldonitrone facilitates its oxidation and leads with a peracid to an O-acylhydroxamic acid protected from further oxidation.     

Chemoselective and enantioselective oxidation of indoles employing aspartyl peptide catalysts

Catalytic enantioselective indole oxidation is a process of particular relevance to the chemistry of complex alkaloids, as it has been implicated in their biosynthesis. In the context of synthetic methodology, catalytic enantioselective indole oxidation allows a rapid and biomimetic entry into several classes of alkaloid natural products. Despite this potentially high utility in the total synthesis, reports of catalytic enantioselective indole oxidation remain sparse. Here we report a highly chemoselective catalytic system for the indole oxidation that delivers 3-hydroxy-indolenines with good chemical yields and moderate to high levels of enantio- and diastereoselectivity (up to 95:5 er and up to 92:8 dr). These results represent, to our knowledge, the most selective values yet reported in the literature for catalytic asymmetric indole oxidation. Furthermore, the utility of enantioenriched hydroxy-indolenines in stereospecific rearrangements is demonstrated.     

Oxaziridine-mediated catalytic hydroxylation of unactivated 3 degrees C-H bonds using hydrogen peroxide

The design, structural characterization, and evaluation of a unique class of 1,2,3-benzoxathiazine-based oxaziridines as potent O-atom transfer agents for catalytic C-H hydroxylation and alkene epoxidation are described. Turnover of this reaction is made possible by employing a diaryl diselenide cocatalyst and urea.H2O2 as the terminal oxidant. Oxidation of saturated hydrocarbons is strongly biased toward 3 degrees C-H bonds even in systems possessing a significantly greater number of methylene groups. In addition, the benzoxathiazine catalyst is effective for epoxidation of terminal and electron-deficient olefins. Collectively, these findings represent an important first step toward the advancement of general methodology for selective C-H oxidation.