Chiral Oxaziridines Research Articles

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.

N-Sulfonyl α-imino ester-derived chiral oxaziridines: catalytic asymmetric synthesis and application as a modular chiral organic oxidant.

A novel class of chiral N-sulfonyl oxaziridines is introduced for use as structurally modifiable chiral oxidants. These oxaziridines are readily prepared from N-sulfonyl α-imino esters in a highly enantioenriched form by oxidation with hydrogen peroxide using l-isoleucine-derived triaminoiminophosphorane as a catalyst. The distinct advantage of their structural modularity is demonstrated through the identification of an optimal oxaziridine that exhibits high reactivity and enantiospecificity in the asymmetric oxidation of a silyl enol ether and N-sulfonyl allylic and homoallylic amines.

Photochemical Rearrangement of Chiral Oxaziridines in Continuous Flow: Application Toward the Scale-Up of a Chiral Bicyclic Lactam

A method for synthesizing chiral lactams from chiral oxaziridines in continuous flow is described. The oxaziridines are readily available from cyclic ketones. Photolysis of the oxaziridines using the Booker-Milburn flow system provides conversion to the chiral lactams in good yield and short residence times. Application of this chemistry toward the synthesis of a chiral bicyclic lactam is described.

ChemInform Abstract: The Practical Preparation of Chiral N‐Sulfonyl Oxaziridines via Catalytic Asymmetric Payne Oxidation.

AbstractAromatic and aliphatic N‐sulfonyl imines are converted to N‐sulfonyl oxaziridines with excellent enantioselectivities.

Corrigendum: Fluorescent Mimetics of CMP-Neu5Ac Are Highly Potent, Cell-Permeable Polarization Probes of Eukaryotic and Bacterial Sialyltransferases and Inhibit Cellular Sialylation

In this Communication, reference compound 1-Ac and intermediate 5-p were used. While both compounds were reported initially in reference 12b as cited, the detailed experimental protocols and spectroscopic data were published subsequently in reference 12c, which has to be added. The application of chiral oxaziridines for the stereoselective oxidation of phosphonates was published originally in reference 15a as cited. The method has been applied to allyl phosphonates in another reference 15b, which has to be added. References 12 and 15 should read as follows:

ChemInform Abstract: Synthesis of Optically Active Trifluoromethyl Substituted Diaziridines and Oxaziridines.

(E)-Trifluoromethyl imines were considered as ideal substrates to be transformed into the corresponding diaziridines by a direct amination reaction with nosyloxycarbamates. The diastereoselective induction was strongly controlled by the N-substituent. Similar results were obtained in the epoxidation reactions performed on the same substrates using m-CPBA as oxidant. Starting from enantiopure imines chiral diaziridines or oxaziridines were obtained with very high enantiopurity.

ChemInform Abstract: Asymmetric Synthesis of Chiral Phosphorus Compounds by Destructive- Selective Oxidation of P(III) Compounds by Means of Chiral Oxaziridines.

ChemInform Abstract: Asymmetric Synthesis of Chiral Phosphorus Compounds by Destructive- Selective Oxidation of P(III) Compounds by Means of Chiral Oxaziridines.

3+2]-Cycloaddition Reaction between Chiral Oxaziridines and Nitriles: Enantioselective Synthesis of 2,3-Dihydro-1,2,4-oxadiazoles

Enantiomerically pure 2,3-dihydro-1,2,4-oxadiazoles were synthesized by a cycloaddition reaction between chiral oxaziridines and nitriles. Assignment of absolute configurations was made by X-ray diffraction analysis, NOESY spectra, and theoretical calculations.

ChemInform Abstract: A Highly Enantioselective Benzothiepine Synthesis.

A highly enantioselective synthesis of benzothiepine 1a has been accomplished via an enantioenriched sulfoxide intermediate obtained by asymmetric oxidation with a chiral oxaziridine in 89:11 er. The key step is a thermodynamically controlled asymmetric cyclization reaction that produces two new stereogenic centers. The (4R,5R) isomer 1a was obtained in 98:2 er.

DITOX derived α-sulfinyl carbanion as nucleophile in conjugate addition reactions to pyrrolo[2,1-a]isoquinolones

The synthesis of DITOX, both in racemic and enantioenriched forms, was accomplished via sulfur oxidation of 1,3-dithiane or 2-acyl-1,3-dithiane derivatives, using chiral oxaziridines for the asymmetric process. The conjugate addition reaction of the α-sulfinyl carbanion derived from DITOX, prepared by deprotonation using the mixture of bases NaHMDS/n-BuLi, to the bicyclic γ-lactam unit of C-10b substituted dihydropyrrolo[2,1-a]isoquinolones led diastereoselectively to the corresponding trans isomer.

Asymmetric synthesis of modafinil and its derivatives by enantioselective oxidation of thioethers: comparison of various methods including synthesis in ionic liquids

The oxidation of 2-(benzhydrylthio)acetic acid and its derivatives was performed with various catalytic and stoichiometric enantioselective reagents, the best results being obtained with stoichiometric chiral oxaziridine 5. The use of [bmim][PF 6] as a solvent with 5 gave slightly higher yields and, in the case of the model compound thioanisole, a reversal of the enantioselectivity.

Optically Pure N‐Hydroxy‐O‐triisopropylsilyl‐α‐L‐amino Acid Methyl Esters from AlCl3‐Assisted Ring Opening of Chiral Oxaziridines by Nitrogen Containing Nucleophiles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Heteroatom Transfer to Alkenes by N‐Protected‐oxaziridines: New Reaction Pathways and Products.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric Synthesis of α‐Sulfinylphosphonates in the Thiolane Series.

AbstractFor Abstract see ChemInform Abstract in Full Text.

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.

Asymmetric synthesis of α-sulfinylphosphonates in the thiolane series

A series of enantiomerically enriched 2-phosphonothiolane sulfoxides were obtained by diastereoselective S-oxidation combined with kinetic resolution using a chiral oxaziridine. Enantioselective oxidation of the corresponding 2-phosphono-2,3-didehydrothiolanes with the same oxidizing agent led to the corresponding sulfoxides with ee up to 98%.

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.

Efficient Nitrogen Transfer from Aldehyde‐Derived N‐Acyloxaziridines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

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).

A highly enantioselective benzothiepine synthesis

A highly enantioselective synthesis of benzothiepine 1a has been accomplished via an enantioenriched sulfoxide intermediate obtained by asymmetric oxidation with a chiral oxaziridine in 89:11 er. The key step is a thermodynamically controlled asymmetric cyclization reaction that produces two new stereogenic centers. The (4R,5R) isomer 1a was obtained in 98:2 er.