N-Nosyl Oxaziridines as Terminal Oxidants in Copper(II)-Catalyzed Olefin Oxyaminations

We report that N-4-nosyl-3-phenyloxaziridine is an effective terminal oxidant for copper(II)-catalyzed oxyamination recently developed in our labs. This oxaziridine can be prepared on multi-gram scale and is easily purified by recrystallization. The products of oxyamination using this oxaziridine bear protecting groups that can be readily removed in high yields under mild conditions.     

Electrophilic amination of enolates with oxaziridines: effects of oxaziridine structure and reaction conditions

A range of N-alkoxycarbonyl- and N-carboxamido-oxaziridines has been prepared to test the effects of oxaziridine structure on yields of enolate amination product. Side-products arising from reaction of aldehyde-derived oxaziridines with base were identified, while a ketone-derived oxaziridine afforded moderate yields of amination product with stabilised carbanions.     

IRREVERSIBLE BINDING OF CHLORDIAZEPOXIDE TO HUMAN PLASMA PROTEIN INDUCED BY UV-A RADIATION

Abstract— In view of the phototoxicity of chlordiazepoxide (Librium^®) the kinetics of the reaction in the presence of plasma proteins was studied for chlordiazepoxide upon UV-A irradiation and for its oxaziridine in the dark. Two different methods were used to determine the extent of irreversible binding to protein (up to ∼ 50% was found for both situations). Kinetic data support the conclusion that the formation of oxaziridine from photoexcited chlordiazepoxide is the basic event making chlordiazepoxide phototoxic. The half life of oxaziridine is about 30 min even in the presence of a high concentration of plasma proteins, is in agreement with previous in vivo results, showing covalent binding not only to biomolecules of the UV-A irradiated skin but also to those of inner organs, e.g. liver and kidneys.     

Action des sulfonyloxaziridines sur une imine. Obtention d'une nitrone par transfert regioselectif de l'oxygene sur l'azote

A pyrrolinic imine has been found to react concurrently with the nitrogen or the oxygen of a $\text{N}$-sulfonyl oxaziridine leading to a N-sulfonyl diaziridine and a nitrone respectively. By contrast an oxaziridine is obtained with a peracid. A possible relation between the regioselectivity of the oxygen transfer and the nature of the reagent is outlined.     

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.     

Electrophilic amination of diorganozinc reagents by oxaziridines

Electrophilic amination of organozinc reagents by oxaziridines has been studied. Diorganozinc reagents R₂Zn (R = alkyl or aryl) react with N-Boc oxaziridine to afford N-Boc protected primary amines BocNHR in moderate to good yields. No additives are needed in this reaction, which proceeds at 0 °C. We suggest that the presence of two heteroatoms in oxaziridine allows Lewis base activation of the diorganozinc reagent.     

Radical intermediates in the photorearrangement of 3-hydroxyindolic nitrones

A number of 3-hydroxy substituted indolic nitrones were found to quantitatively photorearrange to (2-benzoylamino)phenyl ketones upon UV-A irradiation. EPR-Spin Trapping experiments suggest that the process, which is believed to proceed via the formation of an oxaziridine, follows a homolytic pathway. Although DFT calculations do not allow to totally exclude alternative routes involving singlet intermediates, they do provide support to the proposed homolytic mechanism, which would be driven by a 1,5-hydrogen transfer subsequent to the oxaziridine ring opening. When this hydrogen transfer was made impossible by methylation of the 3-OH group, a benzoxazine was isolated as the sole reaction product.     

Amination and [2,3]-sigmatropic rearrangement of propargylic sulfides using a ketomalonate-derived oxaziridine: synthesis of N-allenylsulfenimides

Amination of propargylic sulfides with a ketomalonate-derived oxaziridine under metal free conditions gives N-Boc-N-allenylsulfenimides via [2,3]-sigmatropic rearrangement.     

Polarography of heterocyclic compounds

The literature data on the principles of the electrochemical reduction of heteroethylene and heteroparaffin compounds (pyrazoline, diazepine, diaziridine, pyran, pyridazone, aziridine, oxaziridine, and other derivatives), cyclic anhydrides, imides, and hydrazides of acids on a dropping mercury electrode are correlated. In addition, the effect of substituents attached to the heterocyclic ring on the polarographic behavior of heterocycles is analyzed.     

Stereochemistry of the Addition of Lithiated Methyl Phenyl Sulfoxide to Oxaziridines

The stereochemical outcome and diastereoselectivity of the reaction of lithiated methyl phenyl sulfoxide with oxaziridine are reported. The relative stereochemistry of the major diastereomeric products was determined by chemical correlation with the major diastereomeric products from the reaction of lithiated racemic methyl phenyl sulfoxide with nitrones.     

Peracid oxidation of an immonium fluoroborate a new example of oxaziridinium salt.

The second oxaziridinium salt described so far has been prepared by alkylation of an oxaziridine and by oxygenation of an immonium salt. This confirms that this function is indeed accessible, though very reactive.     

Oxaziridines and oxygen transfer. A revised mechanism for the kinetic resolution of 2-n-propyl-3-methyl-3-iso-butyloxaziridine by brucine.

The mechanism of kinetic resolution of an oxaziridine by brucine is re-examined. Contrary to a currently accepted report, two oxaziridines re-investigated do not transfer oxygen to the tertiary amine, brucine.     

Asymmetric sulfoxidation using [(3,3-Dimethoxycamphoryl)sulfonyl]oxaziridine

[(3,3-Dimethoxycamphoryl)sulfonyl]oxaziridine oxidizes sulfides to sulfoxides cleanly and efficiently in up to 98% ee.     

Heteroatom transfer to alkenes by N-protected-oxaziridines: new reaction pathways and products

N-Alkoxycarbonyl- and N-carboxamido-oxaziridines are shown to react with aromatic alkenes to give epoxide, aziridine or hydro-oxidation products, in ratios depending on the oxaziridine structure. Chiral oxaziridines can effect epoxidation and hydro-oxidation with promising levels of asymmetric induction.     

Quinazolines and 1,4-benzodiazepines. XLVI. Photochemistry of nitrones and oxaziridines

The cyclic nitrones 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5a ) and 1,3-dihydro-7-methylthio-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5b ) are photoisomerized to readily isolable oxaziridines, 7-chloro-4,5-epoxy-5-phenyl-1,3,4–5-tetrahydro-2H-1,4-benzodiazepin-2-one ( 6a ) and 4,5-epoxy-5-phenyl-1,3,4,5-tetrahydro-7-methylthio-2H-1,4-benzo-diazepin-2-one ( 6b ). Oxaziridine 6b upon further irradiation gave ring expansion and ring contraction products, 4,6-dihydro-2-phenyl-9-methylthio-5H-1,3,6-benzoxadiazocin-5-one ( 7b ) and 4-benzoyl-3,4-dihydro-6-methylthioquinoxalin-2(1H)-one ( 8b ) respectively. The ring contraction product, 4-benzoyl-6-chloro-3,4-dihydroquinoxalin-2(1H)-one ( 8a ), was obtained from irradiation of oxaziridine 6a .     

Optically pure N-hydroxy-O-triisopropylsilyl-alpha-L-amino acid methyl esters from AlCl3-assisted ring opening of chiral oxaziridines by nitrogen containing nucleophiles

[reaction: see text] This article reports a straightforward and unprecedented process of AlCl3-assisted oxaziridine ring opening by nitrogen containing nucleophiles, in a totally anhydrous milieu. Under these conditions, nucleophiles exclusively attack the carbon atom of the three-membered heterocycles, obtained from methyl esters of natural alpha-amino acids, generating N-hydroxy-alpha-L-amino acid methyl esters. No nitrones, amides, or other side products, either from unwanted rearrangements or due to the attack of the nucleophile on the N atom of the oxaziridine systems, are formed. The hydroxylamine compounds are recovered in excellent yields, after their site-specific conversion into the corresponding O-triisopropylsilyl derivatives, by exposure to triisopropylsilyl triflate in the presence of 1H-imidazole. Derivatization, performed immediately after the recovery of the N-hydroxylated precursors, allows the chiral integrity of the asymmetric alpha-carbon atoms in the amino acid methyl esters to be retained. It also protects the obtained compounds from frame degradation by disproportionation. N-Hydroxy-O-triisopropylsilyl-alpha-L-amino acid methyl esters are important intermediates in the study of natural alpha-L-amino acid metabolic pathways and are ideal candidates as starting materials in the synthesis of biologically, pharmacologically, and nutritionally important N-hydroxy peptides.     

Asymmetric synthesis of the ab-ring of aklavinone

A formal synthesis of the AB-ring of aklavinone 3 was achieved via the asymmetric synthesis of diol 8 prepared in three steps from tetralone 5. The crucial step involved the asymmetric hydroxylation of 5 in ≥ 95% ee using (camphorylsulfonyl)oxaziridine derivative (+)-4b.     

A mechanistic study of oxygen atom transfer from N-sulfonyloxaziridine to enolates

Enolate additions to chiral N-sulfonyloxaziridines providing enantiomerically enriched α-hydroxy carbonyl compounds is a reaction of importance, yet a clear understanding of the factors governing stereoinduction in these transformations remains ambiguous. This is despite, previous computational studies, one by Bach et al. employing truncated model systems exploring oxygen atom transfer to an unsubstituted lithium enolate and another by our own group. In clarifying this reactivity we report here a computational study examining oxygen atom transfer from 1-S-(+)-(10-camphorsulfonyl)oxaziridine, viz., archetypal Davis chiral oxaziridine to substituted Li, Na, K enolates offering improved mechanistic understanding. From this investigation, a revised model is offered revealing the metal cation, chelation effects and sterics as decisive stereocontrolling factors in enolate additions to chiral N-sulfonyloxaziridines affording enantiomerically enriched α-hydroxy carbonyl compounds.     

Synthesis of new 3,5-diarylisoxazolidines by cycloaddition of oxaziridines and alkenes

This article reports a novel process of cycloaddition of C-aryloxaziridines with a variety of alkenes to afford stable, five-membered heterocycles 13–24. The steric hindrance of the tert-butyl group on the nitrogen atom of the oxaziridine is responsible for the high stereoselectivity of the cycloaddition reaction.